Non-Scarring Alopecias

• Chapter organization: non-cicatricial (non-scarring) alopecias reviewed first, then cicatricial (scarring) alopecias, then structural hair shaft abnormalities.
• Chapter 68 reviews hair follicle structure/function and hair cycle regulation.
• Table 69.1 outlines the clinical evaluation of alopecia; Figs. 69.1 and 69.2 depict a clinical approach and diagnostic tests.
• Choice of trichoscopy, histopathology, hair shaft analysis, and blood tests is guided by the differential diagnosis.

Historical information

• Increased hair shedding vs. only reduction in hair density (latter points to hair follicle miniaturization).
• Shedding vs. hair breakage.
• Expected hair length (identifies "hair that never grows").
• Coexisting scalp symptoms (scaling, pruritus, burning, trichodynia [pain and/or paresthesias], tenderness).
• Duration, including age of onset.
• Persistent vs. intermittent with recurrent episodes.
• Possible triggering factors (postpartum, medications/supplements, preceding high fever/severe illness, malnutrition, flare of systemic disease e.g. lupus, significant emotional stress).
• Review of systems for underlying systemic disease (e.g. thyroid dysfunction).
• Family history of alopecia.

Physical examination

• Diffuse vs. patchy or patterned alopecia.
• Cicatricial vs. non-cicatricial alopecia.
• Length and structure of hairs.
• Scalp changes (scaling, erythema, pustules, tenderness, drainage, scarring).

Diagnostic procedures

• Gentle hair pull test.
• Trichoscopy.
• Hair card test.
• Light microscopy of cut hair shafts (± polarized light microscopy).
• Trichogram (if telogen effluvium or loose anagen hair syndrome suspected).
• Fungal culture and/or Wood's lamp exam; bacterial culture.
• Trichoscopy-guided biopsy for histopathology.
• Biopsy for direct immunofluorescence (DIF) (discoid lupus vs. lichen planopilaris, mucous membrane pemphigoid).
• Blood tests (e.g. DHEA-S, free testosterone, TSH).

Treatment considerations

• Previous therapies, including duration and correct use.
• Psychological burden and QoL impact.
• Comorbidities/current medications (drug–drug interactions) or supplements (biotin interferes with avidin-based lab assays).
• Expectations (halting progression, preventing relapse, degree of regrowth).
• Commitment to long-term therapy.
• In women of childbearing age: discuss pregnancy plans and contraindicated medications.

• Gentle hair pull test — hair not washed for 24 hours; assesses telogen hairs.
• Trichogram (unit area trichogram) — plucking hairs from predefined areas; determines anagen:telogen ratio.
• Trichoscopy (handheld dermatoscope) — visualization of hair shafts, follicular openings, interfollicular skin (10×).
• Trichoscopy (digital dermatoscope) — higher magnification; photography and measurements (e.g. hair density); easier to perform.
• Hair card test — visualization of hair ends (newly growing vs. broken hairs distinguished).
• Cut hairs (light microscopy) — assessment for hair shaft abnormalities associated with fragility.
• Additional investigations: fungal culture, Wood's lamp examination, scalp biopsy, polarized light microscopy of scalp hairs, blood tests.

• Non-cicatricial alopecia
• Diffuse (majority of scalp): telogen effluvium (most common); less common — anagen effluvium, diffuse alopecia areata, female androgenetic alopecia (FAGA), hair shaft abnormalities, other (e.g. Sézary syndrome, ichthyosis).
• Patterned: FAGA (Christmas tree pattern), traction alopecia*, male AGA (bitemporal), hyperandrogenism in women.
• Circumscribed: CCCA (early stages), alopecia areata (ophiasis), pressure (postoperative) alopecia, alopecia areata (limited patch), tinea capitis, trichotillomania, secondary syphilis, pressure (postoperative) alopecia*.
• *if chronic/severe, can become scarring.
• Cicatricial alopecia
• Inflammatory: circumscribed/patchy — CCCA, lichen planopilaris (LPP), discoid lupus erythematosus (DLE), folliculitis decalvans, dissecting cellulitis, acne keloidalis, sarcoidosis, pseudopelade of Brocq.
• Non-inflammatory (end-stage cicatricial alopecia): radiation-induced, aplasia cutis congenita, organoid nevi.
• Fibrosing alopecia in a pattern distribution — patterned (occasionally more diffuse).
• Persistent chemotherapy-induced alopecia — diffuse.
• Frontal fibrosing alopecia, CCCA, acne keloidalis — patterned (widened part line(s): frontal/temporal, vertex/midline, occipital, posterolateral).

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• Synonyms: Male pattern hair loss (MPHL), female pattern hair loss (FPHL), female androgenetic alopecia (FAGA).
• Key features:
• DHT is a key hormone in pathogenesis.
• Conversion of terminal scalp hairs into miniaturized vellus hairs.
• Treatment: oral 5α-reductase inhibitors, topical minoxidil, low-dose oral minoxidil.

Introduction

• Androgen-dependent disorder; both prevalence and severity increase with age.
• Up to 80% of men and 50% of women have evidence of AGA during their lifetime.
• FAGA and male AGA share pathogenetic, histopathologic, trichoscopic features but differ in distribution.
• Onset can occur during adolescence; pediatric AGA is rare.

Pathogenesis

• Genetic factors: polygenic basis in men (GWAS-supported). Androgen receptor gene polymorphisms significant in men, not women.
• WNT10A — expressed in follicular bulge during anagen; WNT signaling critical for follicle development; loss-of-function mutations cause ectodermal dysplasias.
• APCDD1 — encodes a WNT signaling inhibitor, implicated in AGA.
• FAGA associated with polymorphisms in CYP19A1 (aromatase, converts C19 androgens to C18 estrogens) and ESR2 (estrogen receptor 2).
• Hormonal factors: DHT triggers hair follicle miniaturization.
• 5α-reductase (types I, II, III) converts testosterone to DHT.
• DHT may not directly miniaturize follicles but co-mediates hair sheath thickening, perifollicular fibrosis, and sometimes calcification — restricting follicle growth space/oxygen/nutrient supply.
• 5α-reductase activity and DHT levels increased in balding vs. non-balding scalp skin.
• Decreasing DHT levels (skin and blood) associated with reversal of miniaturization in men.
• Most patients (men and women) have normal circulating testosterone; systemic hyperandrogenism signs unusual — AGA is a local androgen-driven process.

Clinical features

• Most common presentation: progressive non-synchronized hair miniaturization → vellus hairs (short, thin, hypopigmented, nearly invisible) → "terminal hair loss" with retention of vellus hairs; prolonged disease → follicular dropout.
• Men: progressive recession of frontotemporal hairline + diffuse crown thinning (see Ch. 157).
• Women: frontal hairline usually preserved; hair loss favors mid-scalp/frontal region → "Christmas tree" pattern; central part-line widening indicates FAGA severity.
• Occasionally men develop female pattern and vice versa.
• Increased hair shedding may precede clinical thinning.
• Grading scales:
• Hamilton and Norwood scales — male AGA.
• Ludwig grading system — female AGA; 3 major grades.
• Sinclair scale — FAGA; 5 stages:
• Stage 1 – normal.
• Stage 2 – widening of central part line.
• Stage 3 – widening of part line with translucency of hairs at its border.
• Stage 4 – development of bald area anteriorly along part line.
• Stage 5 – advanced hair loss.

Diagnosis

• Men: usually clinical, straightforward.
• Women: additional evaluation with trichoscopy helpful — heterogeneity of hair shaft thickness, predominance of follicular units with only one terminal hair (both due to non-synchronized miniaturization), sparse yellow dots (empty follicles with sebum/keratotic material).
• No routine screening labs in absence of hyperandrogenism signs (authors' practice); some experts order DHEA-S, total/free testosterone routinely in women.
• Increased risk of metabolic syndrome, cardiovascular disease, prostate cancer in men with AGA — consider longitudinal evaluation.
• Scalp biopsy helpful in confusing presentations; requires appreciation of follicular unit structure at different levels; histopathologic findings in Table 69.3, illustrated Fig. 69.9A,C,D.

Differential diagnosis

• In men: usually straightforward unless coincident with alopecia areata or telogen effluvium.
• FAGA may coincide with superimposed telogen effluvium.
• Early-onset or severe patterned hair loss in women → suggest pathologic hyperandrogenism; screen total/free testosterone, DHEA-S, 17-hydroxyprogesterone (see Ch. 70).
• Senile (senescent) alopecia — age-related, more synchronized miniaturization than AGA; shares some clinical/trichoscopic features but does NOT respond to antiandrogen therapies.

Treatment

• Topical minoxidil 2% and 5% — FDA-approved for men and women.
• Minoxidil-induced hair growth often causes telogen hair shedding and paradoxical worsening ~3–6 weeks after starting treatment; resolves with continued use.
• Low-dose oral minoxidil — off-label but well documented; dose range 0.625–2.5 mg/day in women, 0.625–5 mg/day in men.
• Side effects: facial hypertrichosis, periorbital edema, lightheadedness, other potential cardiovascular effects (see Ch. 157).
• Oral finasteride (type II 5α-reductase inhibitor):
• Approved for men at 1 mg/day; halts hair loss in 90% of men, partial regrowth in ~65%; continued use needed to sustain effects.
• Not FDA-approved for women, but efficacy/safety documented at 2.5–5 mg/day.
• Possible teratogenicity (indirect evidence); DHT required for male genitalia development → adequate contraception required in women of childbearing age.
• Side effects: reversible loss of libido, reduced ejaculate volume, erectile dysfunction (~2% of men); post-finasteride syndrome (long-lasting sexual dysfunction) reported, incidence unknown.
• Finasteride 5 mg/day (BPH dose) reduces overall prostatic carcinoma incidence in elderly men but increases risk of high-grade prostatic carcinoma diagnosis at that higher dose; uncertain if overdiagnosis or true increased metastasis/mortality risk.
• Finasteride 1 mg/day lowers serum PSA — adjust measured PSA upward by 40%–50% for prostate cancer screening purposes.
• Oral dutasteride — more potent (inhibits 5α-reductase types I and II); not FDA-approved for AGA; efficacy documented at 0.5 mg/week to 0.5 mg/day.
• Meta-analysis of oral therapies for male AGA: dutasteride 0.5 mg/day most effective, then finasteride 5 mg/day, then minoxidil 5 mg/day.
• Effectiveness of finasteride/dutasteride decreases with age.
• Intralesional/topical dutasteride under investigation; topical 0.01% dutasteride solution + microneedling shows improvement.
• Topical 0.5% finasteride spray solution showed significant improvement in hair counts in RCT.
• Additional less rigorously evidenced therapies for FAGA: spironolactone, cyproterone acetate plus ethinyl estradiol, alfatradiol (17α-estradiol).
• Low-level light therapy and platelet-rich plasma reviewed in Ch. 157.
• Hair transplantation — mainstay, combined with medical therapy for optimal results (see Ch. 157).

• Ludwig grading system — 1–3 grades — female AGA.
• Hamilton and Norwood classifications — I–VIII and I–VII — male AGA.
• Sinclair scale — 5 stages — FAGA.
• Severity of Alopecia Tool (SALT) — 0–100 — alopecia areata.
• Alopecia Areata Severity Index (AASI) — 0–250 — alopecia areata.
• Alopecia Areata Predictive Score (AAPS) — 6-point scale (−4 to +2), trichoscopy-based — alopecia areata.
• Points added for upright regrowing hairs and pigtail hairs (positive signs); points subtracted for exclamation hairs, tapered hairs, broken hairs, black dots (negative signs).
• Score of 1 or 2 = associated with treatment response; scores of −1, −2, −3, −4 = unlikely response.
• Lichen Planopilaris Activity Index (LPPAI) — 0–10 — based on symptoms (30%), signs (scale, erythema; 30%), anagen pull test (25%), spreading (15%).
• Frontal Fibrosing Alopecia Severity Score (FFASS) — 0–25 — based on cm of hairline recession, loss of eyebrows, perifollicular inflammation, symptoms (pruritus, pain).
• Lee classification — 9 grades — dissecting cellulitis; based on presence/absence of intercommunicating sinus tracts and scarring plus number of involved regions.
• Melo classification — 3 grades, trichoscopy-based — dissecting cellulitis.
• Additional scoring systems: Ebling and Rook 5-stage classification, Savin's pictorial grading (9), Olsen's classification (3) for FAGA, alopecia barbae severity score (ALBAS; 0–100) for alopecia areata.

• Healthy hairs — uniform in color/shape; follicular units contain 1–4 hairs (average 2.3).
• Exclamation point hair — alopecia areata, trichotillomania, chemotherapy-induced alopecia.
• Comma hairs — tinea capitis.
• Broken hair — trichotillomania, tinea capitis, alopecia areata.
• Yellow dots — alopecia areata and androgenetic alopecia.
• Black dots — alopecia areata, tinea capitis, trichotillomania, anagen effluvium.
• Perifollicular pustule — folliculitis decalvans.
• Hair tufts (>5 hairs/follicular unit, "tufted folliculitis") — folliculitis decalvans.
• Perifollicular scaling — lichen planopilaris, folliculitis decalvans, frontal fibrosing alopecia.
• Seropurulent exudate — dissecting cellulitis and tinea capitis.
• Thick arborizing/tortuous vessels — systemic lupus erythematosus.
• Upright regrowing hair — healthy regrowth; zigzag hairs seen in tinea capitis.

Androgenetic alopecia

• Normal total number of hair follicles when counted in superficial dermis.
• Decreased number of hair follicles when counted at dermal–subcutaneous fat junction ("miniaturization").
• No significant inflammation.
• Increased fibrous "streamers" below miniaturized hairs.
• Slightly increased telogen count.
• Uninvolved scalp (e.g. occiput) appears normal.

Telogen effluvium

• Normal total number of hairs; normal number of terminal (large) hairs.
• Increase in telogen count to >20% (>15% suggestive); telogen count seldom exceeds 50%; >80% is inconsistent with telogen effluvium.
• Absence of inflammation and scarring.

Alopecia areata

• Early/progressive ("acute"/"subacute"): normal total hairs; peribulbar mononuclear infiltrate (± occasional eosinophils) predominantly affecting terminal anagen/catagen bulbs; occasional exocytosis into bulbar epithelium; degenerative matrix changes; increased terminal catagen/telogen hairs; increased miniaturized hairs; trichomalacia and marked narrowing of hair shafts; pigment casts.
• Longstanding/stable ("chronic"): majority of hairs in catagen/telogen; diffuse miniaturization; numerous miniaturized, "arrested," rapidly cycling nanogen hairs; mild peribulbar mononuclear infiltrate around nanogen hairs with anagen-like/catagen-like bulbs.

Trichotillomania

• Follicles normal size; total number of hairs (terminal and vellus) normal.
• Incomplete, disrupted follicular anatomy.
• Increased number of terminal catagen and/or telogen hairs.
• Trichomalacia and pigment casts; no significant inflammation.

Pressure(-induced) alopecia

• Early: vascular thrombosis and inflammation within dermis/superficial fat.
• Necrosis of epidermis and eccrine coils when severe.
• Synchronized conversion of most/all terminal follicles to catagen/telogen (without miniaturization).
• Pigment casts, incontinent pigment within collapsed root sheaths, trichomalacia (but NOT distorted follicular anatomy).

Traction alopecia

• Early/progressive: increased telogen/catagen follicles; occasional trichomalacia; no significant inflammation; over time drop-out of terminal hairs with retention of miniaturized hairs.
• Late: markedly reduced total terminal hairs; residual vellus follicles; distinct connective tissue columns replace follicles ("blank spaces"/follicular scars); sebaceous glands with arrector pili muscles persist even where hair-producing epithelium lost; no significant perifollicular inflammation.

Psoriasiform alopecia

• Psoriasiform epidermal changes may/may not be present.
• Marked increase in catagen/telogen % with hair miniaturization.
• Occasional miniaturized follicle with peribulbar chronic inflammation; plasma cells rare/absent.
• Marked atrophy of sebaceous glands.

TNF inhibitor-induced psoriasiform alopecia

• Psoriasiform dermatitis often present.
• Increase in catagen/telogen hairs and miniaturization, similar to alopecia areata.
• Some peribulbar/superficial perivascular inflammation, often with eosinophils and plasma cells.

Lichen planopilaris

• Perifollicular band-like lymphoid infiltrate obscuring follicular epithelium–dermis interface; vacuolar interface alteration and hypergranulosis within affected infundibula (sometimes colloid/Civatte bodies).
• Inflammation predominantly affects upper follicle (infundibulum and isthmus).
• Occasional interfollicular epidermal LP changes.
• Reduced/absent sebaceous glands.
• Over time, perifollicular fibrosis prominent; lymphocytic infiltrate "backs away" from follicle.
• Artifactual cleft between epithelium and stroma ("floating" epithelium) = Max-Joseph spaces.
• End-stages: follicular "tufting".
• "Naked" hair shaft fragments in giant cells.
• DIF: colloid bodies (usually IgM) adjacent to follicular epithelium; linear "shaggy" band of fibrinogen when epidermis involved.

Central centrifugal cicatricial alopecia (CCCA)

• Premature desquamation of the inner root sheath in subisthmic area.
• Eccentric epithelial atrophy (thinning) in subisthmic area.
• Concentric lamellar fibroplasia (onion skin-like fibrosis) of affected follicles.
• Variably dense lymphocytic perifollicular inflammation, primarily at upper isthmus/lower infundibulum.
• Occasional fusion of infundibula (polytrichia).
• Advanced: total destruction of follicular epithelium with retained hair shaft fragments and granulomatous inflammation.
• Pustular lesions ("folliculitis decalvans" pattern): intrafollicular and perifollicular infiltrates rich in neutrophils and lymphocytes.

Discoid lupus erythematosus

• Vacuolar interface alteration of epidermis and follicular epithelium (epidermis may be spared).
• Interface change in follicles usually vacuolar rather than lichenoid (less inflammation).
• Reduced sebaceous glands.
• Follicular (and/or epidermal) BMZ thickening in late stages.
• Chronic inflammation with lymphocytes (often plasma cells) of eccrine glands and arrector pili.
• Perineurial lymphoid infiltrate may be seen.
• Increased dermal mucin.
• "Naked" hair shaft fragments in giant cells.
• DIF: granular deposits of IgG and C3 (less commonly IgM/IgA) at DEJ and/or follicular epithelium–dermis junction.

Folliculitis decalvans

• Pustular neutrophilic folliculitis rich in lymphocytes and plasma cells.
• Early: perifollicular inflammation with mixed, predominantly neutrophilic infiltrate; follicular neutrophilic abscesses.
• Rupture of hair follicles with partly granulomatous inflammation.
• "Naked" hair shaft fragments within giant cells.
• Gram-positive cocci often present.
• Late: perifollicular scarring with "tufting" and interfollicular dermal scarring.

Acne keloidalis

• Perifollicular chronic inflammation (lymphocytic/plasmacytic), most intense at isthmus and lower infundibulum.
• Lamellar fibroplasia, most marked at isthmus.
• Loss of sebaceous glands.
• Total follicular destruction in advanced disease.

Dissecting cellulitis

• Moderately dense perifollicular lymphocytic inflammation affecting lower half of dermis, extending into subcutaneous fat (early).
• Numerous intact, seemingly undamaged follicles in upper dermis with intact sebaceous glands.
• Increased % catagen/telogen hairs.
• Lymphocyte-dominant infiltrate initially → neutrophils become more numerous in longstanding, fluctuant lesions.
• Vascular proliferation accompanies infiltrate; deep dermis/subcutaneous fat show granulation tissue histology.
• Chronic abscesses eventually become lined with squamous epithelium; true sinus tracts form.
• When inflammation subsides: dense fibrosis of dermis and superficial fat with loss of follicles.

"End-stage" cicatricial alopecia

• Decreased total number of hairs, especially terminal hairs.
• Loss of sebaceous glands in zones of follicular loss.
• Residual "naked" hair shafts within histiocytic giant cells surrounded by mild granulomatous inflammation.
• Follicular streamers (stelae) without overlying follicles.
• Cylindrical columns of connective tissue at sites of former follicles.
• Trichomalacia is characterized by pleated or twisted hair shafts within follicular infundibula.

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• Key features:
• Increased shedding of otherwise normal telogen hairs in response to an external or internal trigger (e.g. medication, high fever, malnutrition, systemic disease, significant emotional stress).
• A chronic form with no identifiable precipitating factor is observed in some women.
• Lab evaluation directed by history, physical exam, trichoscopy, and trichogram.

Introduction

• Scalp hair grows longer than body hair due to longer anagen phase.
• Human hair cycling is asynchronous (unlike molting mammals) — fairly uniform density maintained at all times.
• Normal scalp: ~100,000 hair follicles; ~90% in anagen (lasts 2–4 years); catagen 0.5–1% of follicles; telogen 10% of follicles (lasts ~3 months) → exogen → shed.
• Daily shedding: ~50–200 hairs.
• Most common disturbance: shortened anagen phase.

Pathogenesis

• External/internal factors trigger simultaneous transition of many follicles from anagen to telogen → hair shedding → clinically apparent hair loss at conclusion of telogen (usually 3 months after inciting cause).
• Triggers: pregnancy, medications, high fever, malnutrition, systemic diseases (e.g. lupus), significant emotional stress, inflammatory scalp disorders.
• Systemic infections: ~25% of SARS-CoV-2 infected individuals experienced telogen effluvium within following 2 months.
• Severity depends on drug, dosage, and patient susceptibility.
• Significant number of women have chronic telogen effluvium with no identifiable trigger.

Clinical features and diagnosis

• Thinning/loss of terminal hairs across entire scalp, may involve other hairy body regions.
• Trichogram: increased % telogen hairs, >20% diagnostic.
• Trichoscopy: often diagnosis of exclusion; increased % of follicular units with only one hair is most characteristic feature; multiple short upright regrowing hairs seen during regrowth phase.
• Past events (illness/pregnancy) → complete regrowth expected; ongoing issue (e.g. hypothyroidism) needs to be addressed first.
• Chronic telogen effluvium can continue for years/decades, usually does NOT lead to baldness.
• If trigger unclear after history/exam: assess thyroid function, CBC, metabolic panel, ESR, serum ferritin.
• Serum ferritin should be at least 40 ng/dl; relationship of reduced iron stores to hair loss still uncertain.
• Persistent cases (>6 months): repeat trichoscopy; consider trichoscopy-guided biopsy from vertex to exclude early AGA; ratio of terminal to vellus hairs at isthmus level distinguishes from AGA. Coexistence of TE and AGA common.

Triggers of Telogen Effluvium

• Shedding of the newborn (physiologic).
• Pregnancy.
• High fever.
• Severe infection (bacterial, viral) or illness.
• Endocrinopathy (hyperthyroidism, hypothyroidism).
• Nutritional deficiencies (malnutrition, malabsorption, weight reduction diets, fad diets, post-bariatric surgery).
• Chronic systemic disease (AIDS, SLE).
• Major surgical procedure (general anesthesia).
• Acute or chronic blood loss, iron deficiency.
• Medications:
• Discontinuation of oral contraceptives.
• Endocrine therapies (e.g. selective estrogen receptor modulators).
• Retinoids (acitretin, isotretinoin) and vitamin A excess.
• Anticoagulants (especially heparin).
• Antithyroid drugs (propylthiouracil, methimazole).
• Lithium.
• Anticonvulsants (phenytoin, valproic acid, carbamazepine).
• Interferon-α-2b.
• β-blockers (propranolol, metoprolol, timolol).
• Immunosuppressive drugs (methotrexate, azathioprine).
• NSAIDs (ibuprofen, ketoprofen).
• Levodopa.
• Allopurinol.
• Exposure to heavy metals (e.g. cadmium)* — *also causes anagen effluvium.
• Severe, prolonged psychological stress.
• Inflammatory scalp disorders (severe seborrheic dermatitis, psoriasis, allergic contact dermatitis).
• Also a chronic form of telogen effluvium with no attributable cause or illness.

Treatment

• Correct underlying disorders or discontinue/substitute offending medications — otherwise no well-documented treatment.
• Iron replacement if serum ferritin <40 ng/dl (recommended by many hair experts after determining etiology).
• Topical or low-dose oral minoxidil as off-label, nonspecific hair growth-promoting agent; platelet-rich plasma injections also used.

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• Develops from abrupt, simultaneous inhibition of mitotic activity of follicular matrix cells.
• Anagen follicles with highest mitotic activity most affected; those with less mitotic activity enter telogen phase (unaffected).
• Loss of actively growing anagen hairs within days to weeks.
• Chemotherapy is the most common cause.
• Other causes: thallium, other heavy metals (arsenic, lead, bismuth), ionizing radiation, severe nutritional deficiencies.
• Systemic medications used for skin disease as rare cause: methotrexate, azathioprine, retinoids.
• May be related to other hair disorders, e.g. alopecia areata.

Diagnosis

• History and clinical appearance; abrupt loss of up to 90% of hair shafts is distinct finding.
• Trichoscopy: multiple black dots, terminal hairs with proximal thinning, exclamation point hairs.
• Patients receiving taxanes and anthracyclines can develop persistent chemotherapy-induced alopecia, which may improve with topical or low-dose oral minoxidil.

Treatment

• Discontinuation/avoidance of causative factor.
• Scalp cooling during chemotherapy (cold caps/cooling systems) shows benefit in up to 50% of patients, depending on regimen.
• Used primarily in breast cancer patients rather than hematologic malignancies (theoretical reduction in chemotherapy efficacy).

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• Key features:
• Autoimmune disease characterized by chronic or episodic non-cicatricial hair loss.
• Presents with hairless patches, most commonly on scalp; may result in total hair loss.
• Typical trichoscopic features: exclamation point hairs, black dots, yellow dots.
• Long-standing disease associated with follicular dropout and may become irreversible.

Introduction

• Autoimmune disease; genetic factors play a role in susceptibility.
• Chronic relapsing course; scalp and beard most common sites.
• Prevalence: ~0.1%–0.2%; lifetime risk ~2%.

Pathogenesis

• Complex, involving immune, genetic, environmental factors.
• Autoimmune T-cell mediated disease with predominant Th1/IFN-γ response → stimulation of CD8+NKG2D+ effector T cells.
• These infiltrate affected follicles → upregulation of MHC and loss of hair follicle immune privilege.
• IL-15 upregulated in diseased follicles → activates IFN-γ-producing CD8+NKG2D+ cytotoxic T cells → positive feedback loop with additional IL-15 production → continued autoimmune attack, transition from anagen to catagen.
• IFN-γ and IL-15 depend on JAK-STAT signaling pathway for activation/proliferation of autoreactive T cells → explains therapeutic response to JAK inhibitors.
• Follicular stem cells not usually targeted → allows future regrowth via spontaneous remission or effective treatment.
• Environmental factors implicated: viral infections, vaccines, medications, stress.
• Genetics: polygenic disease; GWAS confirm association with HLA genes — HLA-DQB1*03 allele is important susceptibility marker.
• Strong association with genes in ULBP gene cluster (chromosome 6q25), encoding activating ligands of NKG2D receptor.
• Increased risk of other autoimmune diseases (thyroid disease, rheumatoid arthritis) — shared inherited autoimmune pathway.
• Susceptibility loci shared with other autoimmune diseases: CTLA-4, IL-2/IL-21, IL-2RA.
• PTPN22 (encodes lymphoid protein tyrosine phosphatase suppressing T cell proliferation) and IL-1 cluster genes (IL-1RA) associated with severe forms.

Clinical features

• Round or oval patches of non-scarring hair loss (patchy alopecia areata).
• Alopecia totalis — loss of all scalp hair.
• Alopecia universalis — loss of all scalp and body hair.
• Ophiasis — band-like pattern along periphery of temporal and occipital scalp.
• Alopecia of beard, eyebrows, other hair-bearing sites.
• Reticular variant — recurrent patchy disease with concurrent hair loss in one area and spontaneous regrowth in another.
• Sisaipho (ophiasis inversus) — unusual variant sparing temporal and occipital areas.
• Diffuse variant — rare; widespread thinning or primarily vertex; non-pigmented hairs may remain unaffected → appears as rapid graying.
• Hair loss generally reversible; late-stage disease characterized by progressive follicular drop-out.
• Prognosis worsens when disease persists >5 years; hair loss can become irreversible if it persists >10 years — but irreversibility should not be assumed nor be a contraindication to a therapeutic trial.
• AAPS used to estimate probability of hair regrowth based on trichoscopy findings.
• Nail involvement, especially in severe disease: most common is nail pitting (grid-like pattern). Other changes: trachyonychia (sandpaper-like roughness from excessive longitudinal ridging), brittle nails, onycholysis, koilonychia, rarely onychomadesis.

Trichoscopic findings (three most common)

1. Exclamation point hairs — proximal hair shaft thinning from arrested mitotic activity in germinal matrix.
2. Black dots — residual dark hair shaft visible in follicular opening when exclamation point hairs break off.
3. Yellow dots — empty follicles filled with keratotic material and sebum (may be subtle in prepubescent children).

• Tapered hairs — very long exclamation point hairs; indicate moderate disease activity.
• Pigtail (circle) and upright regrowing hairs — indicate hair regrowth.

Comorbidities and associated disorders

• Most common immune-mediated associated disorders: thyroid dysfunction (OR 4.4), atopy (OR 2.4), SLE (OR 3.5).
• Reported comorbidities: metabolic syndrome, depression, anxiety.
• Down syndrome — increased incidence of alopecia areata.
• Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) — alopecia areata occurs in ~1/3 of patients.
• Some families with vitamin D-dependent rickets type II also develop alopecia areata.
• Satoyoshi syndrome — multisystem disorder; severe alopecia areata is the major criterion; intermittent painful muscle spasms, diarrhea, and antinuclear antibodies are minor criteria (2 of 3 required for diagnosis).
• Gut dysbiosis observed in a small study of patients with alopecia areata.

Differential diagnosis

• Tinea capitis, trichotillomania, temporal triangular alopecia, traction alopecia, secondary syphilis, loose anagen syndrome, pressure-related alopecia, aplasia cutis, "burnt-out" cicatricial alopecia.
• Diffuse variant may initially be confused with telogen effluvium and AGA.
• History/exam (including trichoscopy) usually sufficient; scalp biopsy useful for less distinctive presentations (histopathology in Table 69.3).

Treatment

• Multiple off-label topical, intralesional, and systemic therapies; approach depends on age, disease extent, patient expectations.
• FDA-approved oral JAK inhibitors: baricitinib (severe alopecia areata in adults), ritlecitinib (extensive hair loss, age ≥12 years).
• Most experts view SALT score >20 as indication for systemic therapy.

Topical and intralesional

• First-line: ultrapotent (class I) topical corticosteroid.
• Additional options: calcineurin inhibitors, minoxidil, anthralin, and (especially for eyebrows) prostaglandin analogues (bimatoprost, latanoprost) and topical JAK inhibitors.
• Children with severe disease: contact immunotherapy (diphenylcyclopropenone [diphencyprone], squaric acid dibutyl ester) before systemic therapy.
• Avoid concurrent systemic immunosuppressants during contact immunotherapy (blunts desired inflammatory response).
• Solitary patch: intralesional triamcinolone acetonide 2.5–5 mg/ml every 3–4 weeks; ~0.1 ml injected mid-to-deep dermis, injection sites 1 cm apart; max dose per session in average adult: 10–20 mg.

Systemic

• Adults/adolescents with severe disease: prednisone/prednisolone, JAK inhibitors, cyclosporine.
• Pulse corticosteroids (children and adults): dexamethasone 0.1 mg/kg twice weekly, prednisolone 200 mg weekly, prednisolone 5 mg/kg (up to 300 mg) monthly.
• Daily corticosteroids for rapidly progressive disease: initial prednisolone 0.4–0.6 mg/kg/day with gradual taper over at least 12 weeks, possible transition to pulse regimen.
• Steroid-sparing/monotherapy: cyclosporine 3–5 mg/kg/day or methotrexate 15–20 mg weekly (younger patients: target dose ~0.4 mg/kg/week).
• Limited data: mycophenolate mofetil, azathioprine, dapsone, sulfasalazine, IL-17 inhibitors, apremilast, dupilumab (latter successful in concomitant atopic dermatitis).
• Oral JAK inhibitors: baricitinib and ritlecitinib (FDA-approved), also tofacitinib and deuruxolitinib — effective but maintenance therapy needed to avoid relapse.
• Topical JAK inhibitors (2% tofacitinib, 1.5% ruxolitinib) — less effective than oral counterparts.
• JAK inhibitor use in children off-label; max daily dose 0.625 mg (<20 kg) to 1.25 mg (20–40 kg).
• Low-dose oral minoxidil as supplemental therapy regardless of preferred treatment.

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• Key features:
• Body-focused repetitive behavior disorder characterized by hair pulling.
• Varying lengths of hair typically seen within areas of alopecia.
• Most specific trichoscopic features: coiled hairs, flame hairs, v-sign.
• Related disorder: trichotemnomania (hairs compulsively cut or shaved).

Pathogenesis

• Classified by American Psychiatric Association as one of the "obsessive–compulsive and related disorders" (see Ch. 7 for clinical criteria).
• Heterogeneous group — mild habit to impulse-control disorder, personality disorder, or intellectual disability.
• Many patients who pull their hair do not fulfill psychiatric diagnostic criteria.

Clinical features

• Usually scalp hair plucked → patchy or full alopecia.
• May also pluck eyebrows, eyelashes, extremities, pubic region.
• Irregularly shaped patches, erosions, crusts, hairs of varying lengths.
• Diagnosis supported by shaving small involved area → normal, dense regrowth (very short hairs usually not plucked).
• Seven trichoscopy features with highest specificity: hook hairs; coiled hairs; v-sign (two hairs broken at same level in one follicle); hair powder; flame hairs (semi-transparent, wavy, cone-shaped residues); tulip hairs (short hairs with tulip flower-like ends); trichoptilosis.
• Broken hairs and black dots are common but nonspecific.
• Histopathologic findings outlined in Table 69.3.

Treatment

• No specific approach established as effective in any large controlled study.
• Hypnosis, behavioral modification therapy, insight-oriented psychotherapy, pharmacologic therapy tried — success rates low.
• Habit reversal training often used first-line non-pharmacologic treatment.
• Pharmacologic options: N-acetylcysteine, clomipramine, olanzapine.
• Preschool children: hair pulling often resolves with no treatment.

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• Develops after prolonged immobilization (lengthy surgical procedure, ICU hospitalization).
• Typically supine patient with head fixed on operating table/bed → alopecia on occiput.
• Theoretically due to locally reduced microcirculation from pressure.
• Complete regrowth usually occurs; cases of permanent (cicatricial) hair loss reported.
• Nonspecific trichoscopy findings.
• Halo scalp ring — analogous condition in newborns; self-resolving occipital band of alopecia; believed due to pressure from maternal cervix during labor.

• Synonym: congenital triangular alopecia.
• Hairless patch in temporal region (unilateral or bilateral); may be present at birth or appear during first decade of life.
• Usually triangular shape ("lancet" points superiorly); oval and other shapes seen.
• Trichoscopy: very thin and vellus hairs within entire patch.
• Usually permanent.

• Results from repetitive, prolonged tension on scalp hairs.
• Develops from cornrows, braids, dreadlocks, ponytails, chignons; also hair extensions, turbans.
• Hair loss accentuated in areas of greatest tension; most commonly frontal and temporal areas.
• Advanced disease: "fringe sign" — thin strip of retained hairs in original frontotemporal hairline, separated from current hair-bearing margin by a 1–3 cm hairless band.
• Permanent follicle damage and irreversible hair loss possible in late-stage disease.
• Histopathologic findings in Table 69.3.
• Trichoscopy: reflects mechanical tension without chaotic arrangement typical of trichotillomania.
• Flambeau sign — perifollicular linear white tracks parallel to emerging terminal hair (characteristic finding).
• Vellus hairs present in frontal area — differentiates from frontal fibrosing alopecia.
• Hair casts and broken hairs — additional but nonspecific.

Treatment

• Major intervention: switch to looser hairstyle, less tension; avoid tight cornrows, heavy sewn-in extensions.
• Hair regrowth: topical or low-dose oral minoxidil.
• Topical or intralesional corticosteroids; antibiotics (topical clindamycin, oral doxycycline) may have some efficacy.
• Late-stage irreversible disease: hair restoration (see Ch. 157).

• Unknown etiology; associated with local lymphatic dilatation and edematous thickening of subcutis and dermis.
• Soft, "spongy" scalp with depression when pressed with finger.
• With hair loss: termed lipedematous alopecia.
• Hairs usually sparse and short (~1–2 cm).
• Trichoscopy: multiple thin and vellus hairs, linear erythema with fine arborizing vessels.
• Primary pathologic finding: approximate doubling of scalp thickness from expansion of subcutaneous fat layer.
• Prominent alopecia histopathology: thickened adipose layer, replacement of follicles with fibrous tracts without discernible inflammation.
• Case reports: partial regrowth with topical clobetasol, intralesional triamcinolone, or mycophenolate mofetil.

• Most common form: circumscribed, non-cicatricial, within psoriatic plaques; hair loss in tufts as thick scales shed.
• Clinically apparent psoriatic alopecia rare, but decreased hair density frequently seen histologically in scalp psoriasis (with increased telogen hair follicles).
• Rapid development of severe psoriatic alopecia described as paradoxical phenomenon with TNF inhibitors (e.g. infliximab, adalimumab) despite otherwise successful psoriasis treatment.
• Rarely leads to cicatricial alopecia.
• Trichoscopy of psoriatic cicatricial alopecia: milky-red areas with no follicular openings (dots), plus vascular abnormalities typical for psoriasis (regularly distributed red dots or lace-like structures in linear arrangement, bushy or glomerular structures).

• Primary syphilis: hair loss does not occur unless chancre located on scalp.
• Secondary syphilis: most typical presentation is "moth-eaten" pattern with multiple, small, ill-defined hairless patches primarily in parieto-occipital region; may also affect eyebrows, beard, other hair-bearing sites; diffuse scalp alopecia (as in TE) less common.
• Lues maligna: hair loss within nodulo-ulcerative lesions that heal with scarring → secondary cicatricial alopecia.
• Tertiary syphilis: hair loss may occur within cutaneous gummas.

• Common presenting sign of SLE; can accompany a disease flare.
• Criterion in both SLICC and EULAR/ACR criteria for SLE.
• Three clinical forms:

1. Diffuse hair loss resembling typical telogen effluvium.
2. Focal hair loss resembling alopecia areata.
3. "Lupus hairs" — short, brittle, fragile hair shafts (also seen in other autoimmune connective tissue diseases).

• Trichoscopy: thick, arborizing/tortuous interfollicular vessels; decreased hair density and shaft diameter; hair shaft hypopigmentation; randomly distributed wavy hair shafts ("lupus hairs").

• Rare autosomal recessive disorder.
• Multiple, widely distributed milia-like papules plus complete absence of hair noted within a few months of birth.
• Patients have hair at birth; once shed, not replaced.
• Non-cicatricial but non-reversible; due to mutations in the hairless gene (HR), which encodes a transcriptional corepressor of multiple nuclear receptors and Notch target genes.
• Histology: replacement of middle and lower portions of hair follicle by keratinizing cysts.

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• Alopecia can occur at any hair-bearing site, though the scalp is the chapter's primary focus.
• Eyebrows and/or eyelashes (madarosis) — may be observed in alopecia areata, trichotillomania, frontal fibrosing alopecia.
• Hypotrichosis of lateral third of eyebrows — may be a clue to hypothyroidism or due to chronic rubbing/scratching.
• Beard hair loss — common finding in alopecia areata.
• Loss of body hair — can develop in alopecia universalis; occasionally in anagen effluvium.
• Non-scarring alopecia of axillae and groin — characteristic finding in Graham Little–Piccardi–Lasseur syndrome.
• Symmetric patches of alopecia on anterolateral shins and thighs — etiology unknown; more obvious in men.

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• Alopecia QOL scores comparable to psoriasis/atopic dermatitis; distress often disproportionate to objective severity; patients often feel trivialised.

• Onset/duration: rapid (alopecia areata, acute TE) vs gradual ill-defined (FPHL, most scarring alopecias).
• Patchy vs diffuse. Scalp area affected: vertex/top = pattern hair loss; hairline = FFA/ophiasis AA; vertex+frontal extension = FD/PB; occipital/nape = DC/AKN.
• Quantity of shedding (shedding score); symptoms — itch (LPP, CDLE, less FFA), pain/crusting/pustules (FD, DC), trichodynia, hair breakage (traction, hair shaft disorders), textural change.
• Hair loss beyond scalp (facial, limb) often unrecognised by patients (especially women).
• Atopy → AA association; severe acne conglobata/HS → DC; mucocutaneous LP → LPP; sudden shedding → enquire illness/surgery/weight loss/new medications/stress in prior 2–3 months; family history (first-degree AA relative → 10-fold risk increase); autoimmune (especially thyroid) disease.

• Whole-scalp exam, good lighting, illuminated magnifier/dermatoscope; global visual assessment; partings to assess density; hairline examination; trichoscopy mandatory ****.
• Hair pull tests: easy removal of short broken (exclamation mark) hairs = AA; TTM hairs don't pull out; ~50 hairs gripped for shedding assessment, multiple sites; pull test affected by recent washing/brushing — negative pull doesn't exclude TE.
• Examine face/body for AA/FFA; excess body hair in females → androgen excess.
• Diagnostic algorithm provided ****.

• FBC, ferritin, TFTs routinely; ANA if CDLE suspected; androgen screen in select FPHL cases (teens/20s, menstrual irregularity, other androgen signs, severe/Hamilton-Norwood pattern loss).
• Bacterial swabs for pustules; mycology for scale/hairs (tinea capitis can mimic DC).
• Trichograms rarely performed now; phototrichogram = research tool (anagen:telogen ratio via 2 photos 2–3 days apart).
• Light microscopy for hair shaft disorders (≥50 hairs, cut not plucked, except loose anagen syndrome); polarising filters for tiger tail pattern (TTD); pili trianguli et canaliculi needs scanning EM.
• Histology: distinguishes scarring/non-scarring, lymphocytic vs neutrophilic; identifies follicular miniaturisation, unsuspected AA/LE, sarcoidosis, secondary syphilis, lymphoma, metastases.
• Biopsy technique: two 4 mm punches, oriented with hair growth direction, into subcutaneous fat **; scarring alopecia — from active edge, one vertical + one horizontal section ; non-scarring — both horizontal, affected + control area (vertex vs occiput) **; transverse 4mm biopsy shows up to 30–40 follicles.

• Photography (standardised lighting/background/head position); measurements (patches, hairline in FFA); severity scores: SALT (AA), Ludwig, Sinclair, FPHL-SI (FPHL), Hamilton-Norwood (MPHL), FFASI, FFASS (FFA), LPPAI (LPP), central scalp alopecia photographic scale (CCCA), M-TAS (traction alopecia), CLASI (CDLE), Sinclair hair shedding scale (TE/pattern hair loss).

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• Common chronic inflammatory non-scarring hair loss, T-cell-mediated autoimmune; severity ranges from patches (usually spontaneous recovery) to complete alopecia (poor regrowth prognosis); nails may be affected.
• Attributed to Celsus (~25 BC–AD 50): "areae" — "alopecia" and "ophiasis". Term "alopecia areata" first used by Sauvages, 1763. Robert Willan described as "porrigo decalvans" (Bateman's 1819 atlas). Detailed account by Hebra and Kaposi. Autoimmune hypothesis first suggested by Rothman (discussion of Van Scott paper).

• Mayo Clinic (Olmsted County, 1975–1989): incidence 0.20/1000 person-years, lifetime risk 1.7%; extension (1990–2009): 0.21/1000, 2.1%.
• UK primary care study (>4 million people, 2009–2018): incidence 0.26/1000 person-years.
• Any age; most before 40, peak onset 25–29.
• Similar frequency both sexes (US); slightly greater in females (UK).
• All ethnic groups; more common in black/Hispanic nurses (US self-report study); 3-fold greater incidence in Asian ethnicity (UK study).

• Autoimmune disease: significant associations with vitiligo, thyroid disease, lupus erythematosus, psoriasis, rheumatoid arthritis (4334 AA patients vs >700,000 controls, Chu et al.). Type 1 diabetes not increased in patients but increased in relatives (possible protective effect). Coeliac disease association suggested in small series, not confirmed in larger studies.
• Atopic disease (especially atopic dermatitis) more common, associated with earlier onset/more severe hair loss; Korean study — atopic dermatitis more common in early-onset AA, thyroid disease most common in late-onset.
• Down syndrome: AA in 6% (60/1000) and 8.9% (19/214) of institutionalised populations in two studies.
• APS-1 (AIRE gene mutation, chromosome 21q22): Addison disease, hypoparathyroidism, chronic mucocutaneous candidiasis; AA in ~50% of cases.
• QOL impairment common (not universal — 57% reduced QOL in one study); bullying in 23% of children; increased depression/anxiety prevalence, bidirectional relationship; association between depression and circulating IL-17E/IL-22.

• Pathology: perifollicular/intrafollicular inflammatory infiltrate concentrated around hair bulb ** — mainly CD4+ activated T lymphocytes, macrophages, Langerhans cells, NK marker+ cells; minimal infiltrate at isthmus (explains no follicle destruction). Increased MHC I/II and ICAM-1 expression. Normal follicle numbers in bald patches/universalis; follicles smaller, don't develop beyond anagen 3/4 while disease active **.
• Autoimmune evidence: increased other autoimmune diseases; increased organ-specific autoantibodies (HF antibodies don't bind HFs in vivo, significance unclear); T-lymphocyte-infiltrated hair bulbs; animal models — CD4+/CD8+ depletion → regrowth; human alopecic skin regrows hair when transplanted onto immunodeficient mice; T cells from AA scalps + HF homogenates induce AA pathology when injected into autologous scalp grafts on immunodeficient mice (T-cell mediated, not serum); shared genetic associations with autoimmune diseases, particularly MHC genes.
• Candidate autoantigens: trichohyalin and tyrosinase-related protein 2 epitopes.
• Immune privilege collapse: NK/CD8+ cell invasion, pro-inflammatory cytokines (IFN-γ) → IL-15/IL-15Rα release by follicular keratinocytes → sustains CD8+ autoreactivity.
• Alopecia areata as a "reaction pattern": NK cells/"unconventional" T cells may trigger collapse in autoantigen-independent manner (Gilhar humanised mouse model — NKG2D+/CD56+ PBMCs induce AA pathology).
• Th2 activity also implicated (consistent with atopy association).

• Positive family history 10–20% of cases (may be underestimate); more common with onset <30 years; lifetime risk in children of proband ~6%.
• Twin concordance: monozygotic 55%/42%, dizygotic 0%/10%.
• Strongest MHC associations: HLA-DQB10301, HLA-DRB11104; GWAS confirmed HLA-DR association; genes controlling Treg activation/proliferation; strong ULBP cluster association (NKG2D receptor ligands). Shared risk loci with Graves disease, IBD, coeliac disease, vitiligo, RA, SLE, psoriasis.

• Infection theory has long history; emotional stress/traumatic life events reported 4–85% (uncontrolled series) — inconsistent controlled study results.
• Dust mite allergy proposed role in early-onset AA; seasonal relapse after allergic rhinitis reported.
• Vitamin D deficiency more frequent in AA (cross-sectional studies) but large prospective study found no association with incidence (deficiency may be consequence not cause); no vitamin D supplementation trials.
• Zinc, iron, folate deficiencies linked but evidence conflicting/small studies.

• Characteristic: circumscribed, hairless, smooth patch, normal/slightly reddened skin **; exclamation mark hairs (short, easily extractable, broken) at margins during active phase **; strongly positive hair pull at margins = active disease.
• Unpredictable course; may regrow within months or coalesce/progress to alopecia totalis or alopecia universalis; regrowth initially fine/non-pigmented, usually normalises.
• Scalp usually first site; beard patches conspicuous in dark-haired men **; eyebrows/eyelashes may be only site affected; ophiasis = extension along back of scalp **.
• Trichoscopy: yellow dots (6–100%), short vellus hairs (34–100%), black dots/cadaverised hairs (0–84%), broken hairs (0–71%), exclamation mark hairs (12–71%) ****. Yellow dots (follicular infundibula filled with keratin) predominate in chronic disease; black dots in actively progressing disease.
• In grey-haired patients: AA preferentially affects pigmented hair, sparing white hair — explains "going white overnight" accounts; regrowth may show hypopigmentation initially, usually recovers (concurrent vitiligo consideration if persistently non-pigmented) ****.
• Nail involvement: 7–66% reported frequency; fine stippled pitting **** most typical; also trachyonychia, atrophic dystrophy, red lunula spotting, longitudinal splitting.

• Diffuse alopecia areata: acute onset, large shedding increase, diffuse (not necessarily uniform) density reduction; strongly positive pull test; "acute diffuse and total alopecia" — rapidly progressive, young adult women, usually recovers spontaneously within 6 months, good prognosis, mostly East Asian reports.
• Alopecia areata incognita (Rebora, 1987): adult women, rapid increase in shedding resembling acute TE, no rarefaction unless persists, small proportion (1–2%) develop patches; strongly positive pull with telogen roots; histology shows follicular miniaturisation and increased telogen; status uncertain; yellow dots consistent but also seen in FPHL.

• Children: tinea capitis (scalp inflammation, scaling), trichotillomania (asymmetric/artificial shapes, firmly anchored broken hairs); early scarring alopecia; secondary syphilis, lupus erythematosus; alopecia totalis/universalis in infancy → consider genetic atrichia (HR or VDR gene mutations).

• Patchy, alopecia totalis, alopecia universalis; SALT (Severity of Alopecia Tool) most widely used ****; DLQI for QOL.

• Does not destroy follicles; regrowth potential retained, possibly lifelong; 34–50% recover within 1 year (secondary/tertiary referral data), almost all experience >1 episode; 14–25% progress to totalis/universalis, full recovery from these <10%. Japan study: 80% spontaneous remission within 1 year in patients with few circumscribed patches. Less favourable with childhood onset and ophiasis.

• Usually clinical diagnosis; biopsy if diagnostic uncertainty (diffuse alopecia, possible early scarring); selective tests: fungal culture, LE serology, vitamin D, FBC/iron studies, syphilis serology; screening for other autoimmune disease not routinely recommended except thyroid.

• No treatment alters disease course; counselling paramount, assess psychosocial impact.
• Limited patchy AA: potent topical steroid (e.g. clobetasol) ≥3 months; folliculitis/atrophy risk; ineffective in totalis/universalis unless occluded (5/28 patients sustained regrowth with clobetasol + plastic film occlusion, common folliculitis).
• Intralesional steroid most effective local treatment — complete regrowth in 63% at 4 months (one study), 82% >50% regrowth at 12 weeks (another); triamcinolone acetonide 5–10 mg/mL most used (2.5 mg/mL as effective in one comparison); total dose limit ~20 mg; local atrophy common (recovers); not suitable for rapidly progressive/totalis/universalis; lower concentrations (2.5–5 mg/mL) for eyebrow/beard.
• Dithranol (anthralin) — irritant dermatitis induction, recent series show benefit; limiting factors: sore scalp, discoloration, staining.
• Topical minoxidil — poor efficacy evidence.
• Extensive/rapidly progressive AA: systemic steroids controversial (very unlikely response in totalis/universalis); short courses for exacerbations; various protocols, no clear superiority.
• Extensive patchy/totalis/universalis: Contact immunotherapy (since early 1980s) — most effective/documented treatment; DPCP (diphenylcyclopropenone) most used allergen (also dinitrochlorobenzene, squaric acid dibutylester). Analysis of 45 studies/2227 patients: 56% patchy, 29% totalis/universalis had major regrowth; adverse prognostic factors: SALT>50, atopy, nail involvement, disease duration >1 year; relapse ~half (lower with maintenance 38% vs 49% without). Children: response rates 33%, 32% (two series); third study <10% sustained benefit. Common: occipital/cervical lymphadenopathy; severe dermatitis; uncommon: urticaria, vitiligo, pigmentary changes.
• Systemic immunosuppressants (ciclosporin, azathioprine, methotrexate) used in severe AA — ciclosporin more effective/lower relapse combined with steroids; methotrexate most widely used, insufficient evidence alone but some benefit with corticosteroids.
• JAK inhibitors: ruxolitinib, tofacitinib promote regrowth; baricitinib phase III trials (1200 patients, SALT≥50) — at 36 weeks 36–39% achieved SALT≤20 with 4mg daily, 23% SALT≤10; authorised in USA 2022 for severe AA; side effects minor (URI most common); continued treatment needed to maintain response.
• PRP: RCT more effective than intralesional steroid in limited patchy disease with more lasting remission; not sustained benefit in severe (>50%) AA.
• Phototherapy: UVB and PDT ineffective; PUVA slightly stronger evidence (no controlled trials).
• Laser: 308nm excimer laser, ~50% patches respond, arduous regimens (twice weekly ×12 weeks).
• Children: limited options (topical steroids, minoxidil, anthralin); parents need support for very young children; older children face bullying.
• Nail disease: intralesional steroid improvement (relapses); oral tofacitinib good response reports even without hair growth; may remit spontaneously in children.
• Non-medical: wigs/hairpieces/bandanas for women; men often shave heads; semipermanent tattooing for eyebrows.

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Synonym: congenital triangular alopecia. First described by Sabouraud, 1905.

• Congenital, likely mosaic disease with para-dominant inheritance; associations: Down syndrome, phakomatosis pigmentovascularis.
• Presents age 3–6 years, often unnoticed at birth; triangular (base to anterior hairline), oval, or lancet-shaped; unilateral (>80%) or bilateral ****; fine vellus hairs only, may have terminal hair "islands"; asymptomatic, unchanged over time.
• Differential: alopecia areata (TTA lacks yellow dots, exclamation mark/broken hairs).
• Histology: normal vellus hairs/density, no terminal hairs.
• Management: topical minoxidil (needs ongoing treatment); surgical excision or hair transplantation.

Synonym: papular atrichia. MIM: 209500.

• Rare autosomal recessive, HR gene (chromosome 8p21) mutation — zinc finger transcription factor; dysregulated hair cycle, immature HF structures, keratin-filled follicular cysts. First hair cycle normal; dermal papilla-bulge signalling perturbed after → catagen follicles can't re-enter anagen.
• Born with full hair, shed within months, not replaced — complete irreversible alopecia indistinguishable from alopecia universalis; papular lesions later in childhood, may regress leaving pitted scars.
• Box 87.1 diagnostic criteria (4/5 major required): permanent complete absence of scalp hair by first months of life; smooth whitish/milia-like papules face/scalp/arms/elbows/thighs/knees; follicular cysts replacing mature HF structures on histology; HR gene mutation; clinical/molecular exclusion of VDDR type 2a. Minor: consanguinity, absent secondary body hair, normal growth/development, lack of treatment response.
• Genetic testing gold standard; histology shows replacement of proximal 2/3 of HFs with vertically orientated epithelial structures, follicular remnants, variable keratin-filled cysts.
• No treatment.

Synonym: vitamin D-resistant rickets. MIM: 277440.

• VDR gene mutations, chromosome 12q12-q14; target-organ vitamin D resistance; phenotype variable depending on mutation/residual receptor activity.
• Alopecia develops within first 2 years in ~2/3 of cases; complete alopecia, indistinguishable from APL/alopecia universalis; papular lesions also seen; untreated: bone pain/deformity, muscle weakness, hypotonia, recurrent infections, growth retardation.
• Biochemistry: hypocalcaemia, hypophosphataemia, raised alkaline phosphatase, secondary hyperparathyroidism; biopsy shows thinned/hypoplastic HFs, no inflammation.
• Management: high-dose oral/IV calcium for bone/mineral abnormalities; no effective alopecia treatment.

Synonym: peroneal alopecia. First described 1920.

• Non-scarring lower leg alopecia; middle-aged/older men; estimated prevalence up to 35%; rarely described in literature.
• Cause unclear; friction from clothing/leg crossing suggested; frictional alopecia from tight socks with clear demarcation described; other associations: male pattern hair loss, hypothyroidism, peripheral vascular disease.
• Symmetrical circumscribed smooth patches, peroneal nerve distribution, may spread to thighs.
• Differential: alopecia areata (clinical/dermoscopy features, regrowth history differentiate).
• Biopsy: lack of HFs only. No treatment shown effective; reduce friction, exclude associations; reassurance.

• Sebaceous naevus (organoid naevus, Chapter 73): childhood hairless patch, linear configuration, yellowish/thickened.
• Aplasia cutis: localised absence of skin at birth, usually scalp vertex, may be ulcerated or scarred at birth; usually isolated, can be part of malformation syndromes.
• Sutural alopecia: patches over cranial sutures in Hallermann-Streiff syndrome (Chapter 66).

• Scalp electrodes, infusions, forceps delivery (neonatal trauma) — distinguish from aplasia cutis; scalp/brain surgery, embolisation can cause scarring (e.g. occipital ischaemic necrosis post-meningioma embolisation).

Synonym: postoperative alopecia. First described by Abel and Lewis (8 women, gynaecological surgery).

• Any prolonged immobility/pressure (tight headbands, mask straps).
• Pathophysiology: localised ischaemic injury/hypoxia.
• Circumscribed hair loss at pressure points, occiput commonest; swelling/tenderness/exudation/crusting/ulceration initially; usually temporary, regrows within 4 months; permanent alopecia possible with longer surgery duration.
• Dermoscopy: redness, black dots, broken hairs, thin residual hairs (resembles AA but no yellow dots/tapered hairs).
• Histology: thrombosis, hair bulb necrosis, variable inflammation; virtually all catagen/telogen hairs; trichomalacia, pigment casts, increased apoptosis.
• Management: prevention (positioning, cushioning, repositioning); topical steroid/minoxidil role undetermined.

• First described in Greenlandic women, 1907. South African study: 17.1% of schoolgirls, 31.7% adult women.
• Sustained mechanical HF damage, mainly terminal hairs; "biphasic" — reversible early, permanent if sustained; highly curled hair more susceptible.
• Patterns follow hairstyle: temporal (tight ponytails), cornrow/braid loss ****, occipital (chignon/bun), marginal (Sikh male hair twisting), tight scarves.
• Features: reduced hair density, preferential terminal hair loss with vellus preservation, "fringe sign" (retained terminal hairs at furthest tension point); "tenting", folliculitis, hair casts suggest ongoing traction; trichoscopy: broken/vellus hairs, hair casts, fibrotic white dots/lost ostia (chronic/scarring), tulip hairs, Flambeau sign.
• risk categories: High (frequent tight buns/ponytails, weaves/braids/extensions on relaxed hair, tight braids/cornrows/dreadlocks, painful/tenting styles); Moderate (looser braids/cornrows/dreadlocks, weaves/extensions on natural hair, wigs with cotton/nylon cap, permanent waving); Low (loose ponytails/buns, wigs with satin cap, natural hair).
• Cicatricial marginal alopecia: marginal hair loss resembling AA without clear traction history — likely end-stage chronic traction variant.
• Differential: FFA can present with hairline recession and "pseudo-fringe".
• Histology: early — increased telogen, trichomalacia; late — follicular drop-out with sebaceous gland preservation, deep fibrous tracts, follicular plugging, pigment casts, ORS tears, perifollicular haemorrhage.
• Management: M-TAS score for monitoring; prevention/education primary; early reversible — potent topical/intralesional steroid + antibiotics if inflamed, topical/oral minoxidil; established (follicle loss) — permanent, hair transplant/scalp reduction only options.

Synonym: hair pulling disorder. First described by Hallopeau, 1889.

• Compulsive hair pulling; related: trichoteiromania (rubbing), trichodaganomania (biting), trichotemnomania (cutting); lifetime prevalence 1–3%.
• Two forms: (1) infants/young children — habit like thumb sucking/nail biting, slightly more boys, usually resolves; (2) adolescents/adults — predominantly female, associated psychological/behavioural stress, coexisting depression/anxiety, shame → social avoidance.
• DSM-5 classification — obsessive-compulsive spectrum disorder, grouped with OCD, BDD, nail biting disorder, skin picking disorder, tic disorders, eating disorders.
• Box 87.3 DSM-5 criteria: recurrent hair pulling causing loss; repeated attempts to decrease/stop; clinically significant distress/impairment; not attributable to another medical condition; not better explained by another mental disorder.
• Young children: gradual/unconscious, one frontoparietal region typically, bizarre/angular pattern, twisted/broken hairs at various distances. Older patients: coarse stubble area, asymmetrical/extensive, scalp margins typically spared, hair not lost completely (unlike AA), remaining hairs short/broken/anchored, normal-appearing scalp ****. Two types: "automatic" (unaware) vs "focused" (specific hairs targeted as "not right").
• Other sites: eyelashes, eyebrows, beard, mons pubis, perianal region; repetitive rituals (eating/biting hair); rare complication trichobezoar — abdominal pain, vomiting, bowel obstruction requiring surgery.
• Differential: ringworm, AA (in TTM hair not completely lost, broken hairs firmly anchored unlike exclamation mark hairs); AA/TTM coexistence reported; genetic hair fragility disorders excluded by microscopy.
• Investigations: hair shaft microscopy shows differing lengths, broken/tapered hairs; trichoscopy features — broken hairs of differing lengths, black dots, longitudinal split hairs, irregular coiled hairs, "hair powder", "flame hairs", "tulip hair", "V sign"; yellow dots uncommon (helps differentiate from AA).
• Histology: increased catagen/telogen, empty canals; severe — follicular plugging, matrix clefts, epithelium-sheath separation, haemorrhage, pigment casts; trichomalacia ****.
• Management: relationship building crucial; young children — distraction techniques, paediatric psychology; adolescents/adults can be intractable — psychiatric/psychology referral. Meta-analysis: CBT with habit reversal training superior to drug treatment (3 components: awareness training, response training, social support). Pharmacological (if CBT fails/comorbid psychiatric condition/lacks insight): clomipramine, olanzapine, N-acetylcysteine effective vs placebo in RCTs; SSRIs not convincingly beneficial. Electronic awareness devices in development. Confrontational approach unsuccessful (like dermatitis artefacta).

• Three types: (1) alopecia localised to plaques; (2) generalised TE with erythrodermic/generalised pustular psoriasis; (3) scarring psoriatic alopecia (rare).
• Sebaceous gland dysfunction (cytokine dysregulation, atrophy) suggested underlying mechanism; scarring form cause unclear (coincidence, direct HF destruction, genetic variant, scratching/secondary infection).
• Hair loss confined to plaques, regrows when plaques resolve; rare scarring cases in longstanding severe disease.
• Histology: typical psoriasis interfollicular changes, reduced sebaceous glands, increased catagen/telogen, follicular miniaturisation, variable perifollicular inflammation, infundibular dilatation; scarring form shows HF fibrosis, follicular infundibular inflammation.
• Management: standard scalp psoriasis regimens (Chapter 35).

• Paradoxical reaction (with psoriasis, vitiligo, patchy alopecia) to anti-TNF; shows both psoriasiform and AA features; LPP also reported. Large Korean database study (>11,000 cases) found no significantly increased AA risk overall.
• TNF-α regulates plasmacytoid dendritic cell maturation (secrete IFN-α); TNF inhibition → increased pDC numbers → paradoxically increased IFN-α → psoriasiform changes/hair loss.
• Diagnostic criteria: recent anti-TNF initiation; no prior psoriasis (or flare) before starting anti-TNF; alopecic scalp plaque(s); red scaly/pustular lesions on scalp/elsewhere. More common in female patients, RA/Crohn disease.
• Histology similar to psoriatic alopecia; eosinophils, plasma cells, AA-like peribulbar infiltrate suggest this diagnosis.
• Management: topical anti-inflammatory, methotrexate, ciclosporin may allow continued anti-TNF; stop if severe (switching anti-TNF generally unhelpful); no clear resolution difference between continuing/discontinuing therapy.

• Both regrowth of coexisting AA and new-onset AA-like patches reported.
• Anti-IL-4/IL-13, downregulates Th2 pathways; may improve AA by reducing IL-4-induced inflammation/Th2 impact on Tregs; new-onset lesions may reflect reduced Th2 promoting Th1/Th17 imbalance.
• Regrowth more in women/longstanding eczema/multiple atopic comorbidities; new hair loss predominantly male, fewer comorbidities; typical AA patches or AA-like with redness/scaling.
• Dupilumab-induced AA may be reversible with standard therapy without discontinuation.

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• Tinea capitis (Chapter 32); Infestations (Chapter 34).

• Alopecia in 2.9–7% of secondary syphilis, may be presenting feature; moth-eaten appearance typical, may be diffuse (mimics TE); other secondary syphilis features usually present but hair loss may be only sign.
• Trichoscopy: reduced density, yellow dots, broken hairs, increased vellus hairs; pigtail/zig-zag hairs.
• Histology: increased catagen/telogen, peribulbar lymphocytic infiltrate (like AA) but absence of eosinophils + presence of plasma cells differentiate. Serpiginous nodulo-squamous syphilide (tertiary) may affect scalp; syphilitic gumma causes scarring alopecia.

• Diffuse hair loss common, associated with lower CD4 counts (marker of progression); sudden greying, hair straightening in black patients (independent of nutrition).
• Antiretroviral-induced alopecia: protease inhibitors (indinavir), NRTIs (lamivudine); median onset 2.5 months, resolves with regimen change.
• AA onset reported with new HIV infection; remission of chronic alopecia universalis after HIV diagnosis also observed.
• Eyelash trichomegaly reported, usually advanced disease, regresses with ART.
• Various folliculitis forms: acneform, staphylococcal, eosinophilic pustular (Chapter 31).

• VZV reactivation (shingles); HF involvement predominantly bulge/infundibulum; scalp involvement: dermatomal VZV folliculitis, AA-like lesions, rarely scarring alopecia; AA-VZV association reported (Chapter 25).

• Mycobacterium leprae; scalp relatively immune (higher temperature) — eyebrow/body hair loss occurs in lepromatous leprosy; scalp involvement mild when it occurs (Chapter 28).

• Caused by trichodysplasia-associated polyomavirus (TSPyV); mainly immunosuppressed (solid-organ transplant), also HIV, lupus; likely primary infection not reactivation.
• Small skin-coloured follicular papules with central keratin spines (spicules), alopecia; nose/central face most common; eyebrow loss common ****.
• Histology: dilated HF, keratin plugging, absent hair shaft, aberrant IRS keratinisation with viral inclusions positive for polyomavirus on immunohistochemistry ****; TSPyV PCR confirms diagnosis.
• Treatment: reduced immunosuppression, 3% topical cidofovir, systemic valganciclovir, physical extraction of spicules, oral leflunomide.

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Synonym: telogen defluvium. Term coined by Kligman, 1961.

• Non-specific reaction pattern (any triggering insult); increased telogen proportion, hair shedding, reduced density.
• Pathophysiology: hair cycle synchronisation lost in early childhood (unlike infancy moult waves); normal daily shedding often ~100 hairs (up to). Estimates: scalp-plucked data — 86% anagen, 1% catagen, 13% telogen; horizontal biopsy data — 93% anagen, 7% telogen; ~100,000 scalp hairs → ~7000 telogen at any time → ~70 hairs/day shed (telogen ~100 days). Perceived shedding threshold poorly defined; introspection may increase detection.
• Headington's 5 functional types:

1. Immediate anagen release — commonest; premature anagen→telogen transition, shedding ~3 months later (physiological stress, medications); resolves when trigger removed.
2. Delayed anagen release — prolonged anagen, reduced telogen proportion; rebalancing → shedding 3 months later; underlies postpartum TE and post-OCP cessation.
3. Short anagen syndrome — shortened anagen, more telogen daily; can't grow hair past certain length; every 50% anagen reduction doubles telogen hair numbers; key component of AGA miniaturisation.
4. Immediate telogen release — premature exogen (teloptosis); telogen follicles may remain empty (kenogen) for weeks; minoxidil precipitates this (explains 4–6 week shedding increase); also retinoids, excessive UV, seborrhoeic dermatitis; modulation of proteolytic activity central to exogen control.
5. Delayed telogen release — anagen restarts after prolonged telogen; seen with synchronous seasonal coats; may occur seasonally in humans.

• Rebora's alternative classification: premature teloptosis; collective teloptosis (combines delayed anagen/telogen release); premature entry into telogen phase. Additional "autoimmune (inflammatory) TE" — excessive shedding + marked trichodynia, strong autoimmune associations (high thyroid peroxidase antibodies), responds to topical corticosteroids; relationship with diffuse AA needs clarification.
• Biological factors: oxidative stress, mast cell degranulation/neurogenic inflammation, catagen-inducing pro-inflammatory cytokines.

Clinical features

• Acute TE: 3 months after trigger (febrile illness e.g. SARS-CoV-2, surgical trauma, starvation, haemorrhage) **. Daily loss <100 to >1000 hairs; never causes total baldness; spontaneous regrowth 3–6 months if trigger not repeated; ~1/3** cases no identifiable trigger. "Three Bs" (break-up, bankruptcy, bereavement, J. Shapiro) — everyday stresses insufficient.
• Chronic diffuse telogen hair loss: >6 months, idiopathic (primary chronic TE) or secondary; must fit chronological relationship with resolution/recurrence.
• Clinical assessment: history for triggers/medications; "bag sign" (patient brings evidence of daily shed) ****; exclude AGA/AA.
• Trichodynia: unpleasant scalp symptoms (paraesthesia, pain, burning, itch) with hair loss; more frequent in TE than AGA/controls, positively associated with higher depression scores; may correlate with scalp telangiectasia, more common in women; possibly linked to low B12; pathogenesis: neurogenic inflammation/mast cell degranulation, substance P central role.
• Objective assessment techniques:

1. Hair pull test — abnormal if >10% removed (recent study of 182 people suggests normal ≤2 hairs/pull); TE = removed throughout scalp, AGA = predominantly vertex; significant interobserver variation; negative test doesn't exclude TE.
2. Trichogram/hair microscopy — >25% telogen hairs in acute TE ****; atypical telogen hairs (tail/remnant sheath) prominent; suprabulbar shaft thinning also seen.
3. Phototrichogram — research tool.
4. 60-second hair count — shampoo 3 days, comb over sheet on day 4 for 60s, 3 consecutive days.
5. Modified wash test (MWT) — abstain 5 days, shampoo, collect/count shed hairs, divide <3cm (vellus) vs >3cm (terminal); interpretation table for AGA/TE/both/normal.
6. Visual hair shedding scales (Sinclair scale) — bundles of 10/50/100/200/400/750 hairs; ≥400/750 abnormal ****.
7. Scalp biopsy.

Clinical variants

• Drug-induced TE: starts 6–12 weeks after treatment start; commonest mechanism immediate telogen release; also stopping anagen-promoting drugs (OCP/minoxidil) or exogen-triggering drugs (retinoids); confirm chronology, discontinue ≥3 months.
• Postpartum TE (telogen gravidarum): 2–3 months post-childbirth, oestrogen-mediated anagen prolongation/synchronisation; most common after first pregnancy, occurs in ~20% of women; delivery stress/autoimmune sequelae (postpartum thyroiditis) also proposed.
• Seasonal hair shedding: study (n=823) — max telogen levels summer (July), smaller spring peak (April), lowest in winter; evolutionary throwback (thicker winter coat), controlled by photoperiod/neuroendocrine signalling/UV.
• Cronkhite-Canada syndrome: rare — GI polyposis, diarrhoea, protein-losing enteropathy, weight loss + diffuse hair loss; non-inflammatory anagen-telogen conversion early event, follicular miniaturisation also reported; AA-like features described recently.

Differential: early AGA shedding can be diffuse/episodic mimicking TE; AA incognita causes diffuse thinning (hair colour transition sign helps differentiate); biopsy may be needed.

Investigations

• Box 87.4 screening bloods: FBC, ferritin/iron studies/ESR, TFTs, renal/liver function, calcium/vitamin D, zinc, B12/folate, ± connective tissue screen, ± syphilis serology, ± hormone profile.
• Ferritin: sensitive marker but complex — 39% of women below lowest male value despite no biological reason; ferritin >70 μg/L needed for 99% confidence of adequate bone marrow iron; acute phase reactant (check ESR too). Conflicting studies (some show lower ferritin in TE, others not). Rushton studies: increased ferritin/reduced shedding with iron + L-lysine (1000–1500mg daily). Recommendation: maintain ferritin >70 μg/L with diet/supplementation.
• Zinc: cofactor for skin homeostasis enzymes; acrodermatitis enteropathica/acquired deficiency (parenteral nutrition) → severe TE ****; some association evidence for isolated low levels.
• Other: low B12, biotin deficiency, low vitamin D associated.
• Scalp biopsy (horizontal sectioning) if needed — normal follicular units, normal terminal:vellus ratio, increased telogen %.

Management

• Expectant management for acute TE with obvious cause; shedding ceases 3–6 months, full recovery ~6 more months; address underlying cause; topical steroids if trichodynia (risk of side effects); topical/oral minoxidil may help chronic (not acute) TE; novel: olfactory receptor (OR2AT4) topical solution, arrector pili muscle constrictor topical.

• Idiopathic, sometimes self-limiting, predominantly middle-aged women; trigger obscure; often only noticed by individual; process >6 months but hair density maintained.
• Pathophysiology: reduction in variance of anagen duration (narrower spread) — contrasts with AGA's anagen shortening; hypotheses: age-related effects, perimenopausal oestrogen fluctuations affecting clock genes; associated with VDR gene polymorphisms and heavy metal exposure; female squirrel monkey potential animal model.
• Almost exclusively women 4th–6th decades (one long-haired man reported); sudden-onset increased shedding persisting ≥6 months, often on background of high hair density/ability to grow long hair when younger ****; no visible central parting widening; mild temporal recession sometimes; trichoscopy normal, no HF miniaturisation on biopsy.
• Differential: FPHL (early AGA can present with episodic shedding); psychogenic pseudo-effluvium (body dysmorphic disorder — preoccupation without objective alopecia evidence).
• Investigations: diagnosis of exclusion; biopsy often required (Whiting: biopsy itself is "therapeutic" — reassurance); horizontal sectioning shows terminal:vellus ratio maintained (9T:1V) but slightly higher telogen rate (89% anagen, 11% telogen); higher Sinclair grades (3–5) correlate strongly with AGA on biopsy (allowing clinical diagnosis alone); natural history poorly characterised (one longitudinal study only).
• Management: explanation important; no treatment necessary (doesn't cause baldness); antiandrogens have little effect; topical/oral minoxidil reduces shedding and may improve trichodynia.

Terminology: AGA = male balding/MPHL in most men — genetically determined, requires androgens + age. Preference for non-aetiological term "female pattern hair loss (FPHL)" in women as androgen/genetic role less conclusive.

Epidemiology

• MPHL: nearly all white men develop some frontal temple recession by teens; progresses to bald scalp in 50–60% by age 70; 15–20% show no balding beyond temporal recession even in old age. Balding less common in Asian men (wide variation) — Thailand/Singapore rates close to white European men; Japanese men balding starts ~1 decade later, prevalence ~30% lower per decade group; Korean men 20–40% lower than white (40–70 age group, gap narrows with age); Chinese study: 41.4% of men >70 had AGA; Korean/Chinese studies show "female" pattern hair loss preserved frontal hairline in 11.1%/3.7% of men respectively ****.
• FPHL: UK/USA studies — 3–6% women <30, 29–42% ≥70 **; multiracial Brazilian study (350 women, 20–75 years, Fitzpatrick I-VI): ~10% at 20-29 rising to 70%** at 65-75 (no white/darker skin difference, likely reflects Sinclair grade 2/trichoscopy-based criteria); Asian women lower/later onset (nearly 25% Korean women >70 show hair loss); no African women prevalence data published.

Pathophysiology — Male AGA

• Endocrine factors: James Hamilton — men castrated before puberty don't bald unless given testosterone. DHT (5α-reduced metabolite) primarily drives hair loss; 3 isoforms of 5α-reductase (SRD5A1, -A2, -A3); type 2 restricted to prostate/epididymis/certain skin HFs.
• Type 2 5α-reductase deficiency (pseudohermaphroditism) — normal testosterone, low DHT, pubic/axillary hair grows but no balding/scanty body/beard hair. 5α-reductase inhibitor prevented balding in macaques. Finasteride (type 2 inhibitor) RCTs — prevents/slows progression in most men, some regrowth in ~2/3 — confirms partial reversibility (contrary to Hamilton's eunuch conclusions).
• Circulating androgen studies mixed — some show no difference (total T/DHT) vs controls, others raised free testosterone/DHT:T ratio in early-onset balding; some men resemble PCOS hormonal profile ("male equivalent of PCOS" proposed).
• Other implicated hormones: prolactin, melatonin, parathyroid hormone, insulin-like growth factor.
• Prostaglandins: elevated prostaglandin D2 synthase mRNA/protein in bald vs haired scalp; PGD2 inhibited hair growth in explants/mice; K14-Ptgs2 transgenic mice (elevated PGD2) developed alopecia/miniaturisation via GPR44 receptor.
• Heritable factors: twin concordance monozygotic 80–90%; high frequency of balding in bald men's fathers (32/54=59.3% vs 1/65 sons of non-bald controls, OR 5.5, 95%CI 1.26-23.99 in young men with bald father, falling with age); non-balding trend opposite (OR 3.2 in ≥70). Highly polygenic (>600 loci now linked). First: AR gene (X chromosome); strongest association region between AR and EDA2R. Meta-analysis of 8 GWAS: 63 loci explaining ~39% of phenotypic variance (6 X-chromosome, 57 autosomal); larger GWAS (>70,000 men): 71 loci explaining ~38% risk, SNP-based heritability (h²SNP) 94% (matches twin studies — risk almost entirely genetic). Candidate genes: SRD5A2, FGF5, IRF4, DKK2; pathways — androgen metabolism/signalling, melatonin signalling, adipogenesis, Wnt signalling. Genetic overlap with height, lifespan, cancer risk, neurodegenerative disorders.

Pathophysiology — FPHL

• Less clear aetiology; may be multifactorial trait rather than single entity.
• Androgens' role less clear; hair loss reported before Hamilton's male observations in women with androgen-secreting tumours. Cohort studies: pattern hair loss in 22%/23% of PCOS patients (USA/China) vs hirsutism in 70%/58%. Azziz et al.: hair loss in only 4% of >800 hyperandrogenic women (75% hirsute) — near population frequency. Isolated FPHL reported without androgens (complete androgen insensitivity, severe hypoandrogenism/17α-hydroxylase deficiency).
• Studies noting elevated androgens/androgen-excess features more common with hair loss: Futterweit — 38.5% of 109 hair loss women had androgen excess evidence; Vexiau — abnormal hormone profiles in 67% hair-loss-only, 84% hair loss+hirsute women; polycystic ovary US evidence in 67% vs 27% control (89 women); other studies failed to find raised androgens.
• Antiandrogen quality of evidence poor: RCT finasteride 1mg postmenopausal — no benefit at 1 year; uncontrolled higher-dose series showed improvement; minoxidil vs cyproterone acetate (CPA) 1-year trial — minoxidil improved, CPA group deteriorated overall (subgroup with menstrual irregularities on CPA improved slightly).
• Paradoxically, testosterone implants for androgen deficiency improved scalp hair growth (with hirsutism side effect); androgen decline from 4th decade parallels density/diameter decline with age — anabolic (not virilising) effect proposed.
• Thyroid deficiency link to hair loss under-researched — some evidence hypothyroidism increases shedding, reversible with replacement.
• Oestrogen protective evidence: increasing FPHL post-menopause, anagen prolongation in pregnancy, hair loss with tamoxifen/aromatase inhibitors; lower oestrogen:androgen ratios in premenopausal FPHL (small study); but no clear oestrogen supplement effect, inhibitory in other species.
• Iron/vitamin D controversial; no controlled iron supplementation trials; one study — antiandrogen response only with ferritin >40 μg/L.
• Heritable factors: Osborn 1916 single-gene model (B/b alleles) — men BB/Bb bald, only BB women bald; Smith/Wells found increased balding in male relatives of hair-loss women; Küster/Happle proposed polygenic threshold model. Twin study: strong heritability for greying and frontotemporal recession, none for diffuse top-of-scalp thinning (subjects ≥59 years). No FPHL GWAS yet; weak ESR2 (oestrogen receptor) associations in 2 studies; German/UK study — weak AR/EDA2R association in UK early-onset cohort only, no association with other 11 male-AGA loci.

Pathology (both sexes)

• Hair cycle dynamics: anagen duration reduced (years → months/weeks); telogen-to-exogen time unchanged (2-3 months) but kenogen lengthened → more "empty" follicles.
• Miniaturisation: HFs shrink to produce smaller/thinner fibres; differs from true vellus (no prior terminal growth history); cross-sectional area constant within an anagen cycle — miniaturisation occurs between cycles; may occur rapidly (single cycle, disputed) or stepwise; FPHL histopathology shows progressive follicle count reduction with severity (follicles eventually deleted, not just miniaturised); Whiting found lower total follicle count in balding vs non-balding men (cross-sectional but supported by longitudinal phototrichogram data showing miniaturised hairs disappear).
• Stelae/fibrous tracts/streamers — dermal remnants marking former terminal follicle position; Arao-Perkins bodies (elastic fibre clumps) in stelae, like ladder rungs with progressive anagen shortening.
• Follicular units: FPHL diffuse thinning = reduction in terminal hairs per unit (not whole-unit miniaturisation); baldness only when all hairs in a unit miniaturise — early/common event in men, late/less common in women. FPHL generally less severe, later, diffuse rather than bald spot.
• Inflammation: Whiting — inflammation in 70% male AGA biopsies vs 40% non-balding controls; moderate lymphohistiocytic in ~1/3 AGA vs 10% controls; infiltrate mainly lymphocytes/histiocytes (± eosinophils/mast cells/neutrophils), mainly upper follicle, may be associated with perifollicular fibrosis; also seen in FPHL; role in pathogenesis proposed (Jaworsky et al.) but unproven, anti-inflammatory treatment doesn't conspicuously reverse it.
• Arrector degeneration: 8-biopsy study — arrector pili degeneration/fat replacement observed, speculated linked to stem/progenitor cell depletion.
• Histopathology: reduced terminal HFs, increased miniaturised HFs with angiofibrotic streamers, variable increased telogen/catagen, mild-moderate perifollicular lymphohistiocytic infiltrate ± concentric perifollicular collagen **. Best seen horizontally; miniaturised follicle = diameter less than IRS thickness (Whiting); terminal:vellus ratio changes from ≥7:1 to ≤2:1** in both male AGA and FPHL. Solar degenerative changes as protective hair coverage lost.

Clinical features

• MPHL: patterned — frontotemporal recession + vertex loss; hairs shorter, may become finer; complete loss possible except lateral/posterior margins (which may also thin in elderly). Hamilton classification, revised by Norwood — still widely used. Small proportion show diffuse crown/frontal loss with retained hairline (female-pattern-like). Diffuse unpatterned alopecia — uncommon, diffuse global reduction affecting sides/back too (donor site involved — unsuitable for transplant).
• FPHL: gradual thinning over years, any age from puberty; may pre-date obvious density reduction with shedding/volume loss; widening central parting, diffuse frontal/mid-scalp reduction; "Christmas-tree pattern" (Olsen) — frontal accentuation; frontal hairline typically retained (minor postpubertal temporal recession common regardless of diffuse loss); more global reduction (parietal/occipital) unlike male AGA. Ludwig 3-grade classification; Sinclair 5-grade classification more sensitive, largely replaced Ludwig (grade 1 = normal density, grade 5 = most severe) **. Hair pull test may be normal (unlike TE) but increased in active loss. Trichoscopy: differing density mid-frontal vs occipital scalp; 2-3 terminal hairs/ostium occipitally vs 1 (sometimes 2) mid-frontally; hair diameter diversity** increased in early FPHL (Bhamla: 75% sensitivity, 62% specificity, low diversity better at ruling out than high at ruling in).
• Children/adolescents: rare, youngest reported case age 6; usually "female" pattern (Christmas-tree pattern) in both sexes prepubertally; adolescents show female pattern more too, but most males eventually typical male pattern; seborrhoeic dermatitis/acne prominent, hyperandrogenism signs important in teenage girls; strong family history typical (Tosti et al: postadrenarche DHEA-S levels without puberty signs — possibly adrenarche androgens trigger in genetically susceptible children, or non-androgen-driven mechanism).
• Senescent alopecia (Kligman concept): diffuse thinning >50 years, no family history; modest telogen increase, follicle size reduction but not to miniaturised extent, uncommon inflammation. Whiting disputed on histological grounds (most elderly hair loss is androgen-dependent). Karnik: differing gene expression profiles support senescent alopecia as separate entity.

Differential diagnosis

• Men: rarely difficult; consider other diffuse causes if rapid progression. FPHL differential: chronic TE, FAPD. Women with skin of colour: CCCA. Chronic TE women: chronic diffuse shedding without parting widening, ponytail volume loss up to 1/3, mild bitemporal recession; scalp biopsy: pattern hair loss in ~60%, chronic TE in ~40%. CCCA: localised vertex thinning, lost follicular openings, more localised than FPHL. Rare: diffuse AA, SLE.

Complications and co-morbidities

• Increased coronary heart disease risk with vertex balding but not frontal (RR 1.18-1.44), increases with earlier/more severe onset.
• Prostate cancer association with vertex balding (meta-analyses RR 1.18-1.24), not other patterns.
• Metabolic syndrome increased in balding men (some studies, not Korean large study); increased in FPHL women (correlates with severity in Korean study); Birch: FPHL + hirsutism women had raised BMI vs controls, non-hirsute FPHL women did not.

Investigations

• Men: usually unnecessary. Women: careful history/exam; consider hyperandrogenism if male-pattern (especially vertex balding); other features — hirsutism, acne, menstrual disturbance, subfertility, acanthosis nigricans. Androgen Excess and PCOS Society recommended bloods: total/free testosterone, iron studies, thyroid profile, vitamin D, zinc, prolactin. Scalp biopsy rarely needed but useful for early FPHL vs chronic TE; FAPD needs biopsy for scarring.

Management

• Balding is biologically normal, psychologically significant nonetheless; body dysmorphic disorder consideration important (treatment unlikely successful in this group). Women report worse QOL impact than men (society regards female hair loss as more abnormal); distress correlates with self-perception more than objective severity.
• Cosmetic: hair stylist help, camouflage fibres/scalp dye, scalp tattooing, wigs/prostheses (interwoven wigs need periodic adjustment).
• Male medical treatment: only minoxidil and finasteride licensed.
• Minoxidil (2%/5% topical solution, 5% foam, BD): mean hair count increase ~8% (2%), 10–12% (5%); global photography improvement ~60% (5%) vs 40% (2%) vs 23% placebo; response peaks 16 weeks; sustained to 5 years if maintained; lost within 4–6 months of stopping; promotes kenogen follicle anagen entry, does not reverse miniaturisation. Side effects: local irritation (more with 5%); rare allergic reactions to minoxidil/propylene glycol.
• Finasteride 1mg daily: reduces serum/scalp DHT by up to 70%; prevents/slows progression in most men, ~2/3 improve; peaks ~12 months; effect via anagen prolongation, minimal miniaturisation reversal; small increase in sexual dysfunction (resolves on stopping in most); some report persistent side effects (see post-finasteride syndrome).
• Dutasteride: inhibits type 1+2, greater DHT suppression; meta-analysis shows greater hair growth than finasteride; similar side effect profile; licensed for balding only in Japan/South Korea (elsewhere for BPH).
• Female medical treatment:
• Topical minoxidil (2% BD, 5% foam OD): trials show 15-33% vs 9-14% vehicle hair count increase; hair weight increase 42.5% vs 1.9%; ~40% appear non-responders; 5% vs 2% lotion 48-week trial: 18% vs 14% vs 7% placebo increase in non-vellus counts. Side effects: unsightly deposits, scalp irritation (may cause temporary shedding increase — warn patients), facial hypertrichosis (higher concentrations), transient shedding at 2-8 weeks (don't stop treatment).
• Oral minoxidil: increasingly favoured; failed in AA in 1980s; Sinclair 2018 pilot (oral minoxidil + spironolactone) suggested efficacy/safety; RCT — oral 1mg daily = topical 5% solution efficacy; large study (1404 patients): most common side effect hypertrichosis (14 withdrawals); systemic effects: lightheadedness 1.7%, fluid retention 1.3%, tachycardia 0.9%, headache 0.4%, periorbital oedema 0.3%, insomnia 0.2% (29 discontinuations, 1.2%); no life-threatening effects.
• Antiandrogens: cyproterone acetate vs minoxidil RCT — minoxidil group improved, CPA group worsened overall (subgroup with menstrual irregularities on CPA slightly improved). Spironolactone open series (80 women, 1 year, 200mg daily or CPA): 44% improved. Flutamide 250mg daily RCT (Italy, 48 hyperandrogenic women) — modest improvement vs CPA/finasteride (unblinded, crude assessment). Bicalutamide safer alternative. Finasteride ineffective in RCT (postmenopausal, 1mg); uncontrolled series show improvement (higher doses 2.5mg — 62% improved one study); meta-analysis (9 studies) — doesn't increase density but may improve clinical evaluation, higher doses (2.5-5mg) more effective.
• Antiandrogen problems: continued treatment needed; avoid pregnancy (feminising male fetus); CPA side effects (weight gain, fatigue, low libido, mastodynia, nausea, headache, depression), hepatotoxicity risk (flutamide, high-dose CPA); spironolactone breast soreness/menstrual irregularity (probably safest); finasteride well tolerated, consider in postmenopausal/infertile women.
• Iron: controversial; open trial — ferritin >40 μg/L group improved with CPA, <40 μg/L group did not; check ferritin, supplement if <40 μg/L (won't halt/reverse alone but may improve response to specific treatments).
• Transgender patients: transgender women — oestradiol/spironolactone titration may promote hair growth; transgender men — pattern hair loss can worsen with masculinising hormones, 5α-reductase inhibitors helpful; standard minoxidil/surgery also applicable.
• PRP: increased density in male AGA (multiple studies); less clear in women; meta-analysis (7 RCTs) — significant increased density vs placebo (pooled mean +30 hairs/cm², wide CI, heterogeneity); monthly ×3 then maintenance typical.
• Low-level laser light therapy (LLLT): systematic review/network meta-analysis ranked as most effective non-surgical intervention vs finasteride/dutasteride/topical minoxidil/PRP/placebo (low/very low evidence quality); combining with minoxidil more effective than monotherapy.

Chemotherapy-induced alopecia (CIA)

• Occurs in up to 65% of regimens; 47% rate it most traumatic aspect, 8% reject chemotherapy because of it; risk factors: specific agent/protocol ****, combination therapy, route, patient factors (performance status, nutrition, age, pre-existing hair disorders).
• CTCAE v5.0 grading: grade 0 (none), grade 1 (<50%, not obvious, no wig needed), grade 2 (>50%, apparent, wig needed).
• Pathophysiology: hair matrix in anagen bulb highly metabolically active/vulnerable; bulge stem cells relatively resistant (allow regrowth). Murine model (cyclophosphamide) — 2 dystrophy types: dystrophic anagen (lower dose, primary recovery in same anagen phase then secondary recovery via new cycle); dystrophic telogen (severe insult, skip primary recovery, go directly catagen/telogen → secondary recovery, shorter regrowth pathway). In humans — prominent anagen effluvium but also increased telogen on serial trichograms (HF response depends on cycle stage at insult; TE response occurs in late-stage anagen HF).
• Hair shedding within 1-3 weeks, complete within 1-2 months; rapid/diffuse/extensive; trichoscopy: black dots, broken hairs; Pohl-Pinkus constriction (like Beau lines) in remaining hairs; most marked in high-friction areas; usually temporary, recovers within months; regrowth colour/shape changes (curly/straight) described.
• Management: psychological preparation, wigs. Scalp cooling — vasoconstriction reduces drug uptake, suppresses metabolic activity; variable results, good efficacy in some; requires additional time, discomfort, unavailable in all centres, contraindicated in some haematological malignancies; scalp metastasis risk concern probably unfounded. Topical minoxidil NOT effective at prevention but may hasten recovery (small trial). Eyebrow/eyelash loss common — topical bimatoprost 0.03% restores eyelashes rapidly post-chemotherapy (length, thickness, pigmentation).

Persistent chemotherapy-induced alopecia (pCIA)

• Definition: absent/incomplete regrowth 6 months beyond chemotherapy completion; associated with bone marrow transplant conditioning and taxane regimens for breast cancer; higher doses increase risk. UK survey: persisting hair loss >6 months in 23.3% docetaxel vs 10.1% paclitaxel breast cancer patients (P<0.01).
• Pathophysiology unclear — likely HF stem cell damage inhibiting regeneration; reduced-function ABCB1 gene mutation (p-glycoprotein efflux pump) = genetic risk factor.
• Non-scarring diffuse alopecia or FPHL-like (clinically/histologically) ****; trichoscopy: variable HS diameter, increased vellus, predominantly single hairs/ostia; rarely inflammatory scarring alopecia.
• Investigations: exclude reversible TE causes; scalp biopsy (horizontal+vertical) — reduced density, decreased terminal:vellus ratio, end-stage fibrous streamers.
• Management: prevention — scalp cooling dramatically reduces risk; topical/oral minoxidil may improve density; antiandrogen therapy sometimes tried (caution in hormone-sensitive cancers, liaise with oncology). Eyelash regrowth improved with bimatoprost even if delayed up to 6 months.

Therapies for cancer that can cause hair loss

• Endocrine therapies: 70% breast cancers hormone-receptor positive; antioestrogens (tamoxifen), aromatase inhibitors (anastrazole, letrazole), GnRH agonists (leuprolide) used 5-10 years; hormone therapy-induced alopecia (HTIA) in 4.4% (RR 12.88, 95%CI 7.46-22.24); FPHL-mimicking diffuse alopecia, mean onset 16.8 months; loss of oestrogen's anagen-promoting effect + androgen-dominant shift proposed.
• EGFR/MAP kinase inhibitors: cutaneous reactions 75–90%; itchy papular/pustular reaction face/chest/back, weeks 1; better classified as folliculitis (no comedones/distal follicular inflammation); rarely FD-like scarring alopecia; trichomegaly (eyelash) in up to 10%. Rash correlates with antitumour effect — continue treatment where possible; emollients/sun protection; topical corticosteroids, oral tetracyclines, sometimes isotretinoin for significant symptoms; trim eyelashes regularly.
• Tyrosine kinase inhibitors: hair/skin depigmentation via c-kit modulation of tyrosinase; treatment pause → repigmentation in same fibre → striped hair appearance.
• Immune checkpoint inhibitors: immune-related toxicities include vitiligo/poliosis, alopecia areata, LPP — may suggest good therapeutic response; onset can be delayed months.
• Hedgehog pathway inhibitors (vismodegib, sonidegib) for BCC (pathway abnormal in >90% of BCCs): diffuse alopecia (scalp+body) in 46–66% across studies of vismodegib; pretreatment assessment recommended; treatments — topical minoxidil, bimatoprost, sometimes antiandrogens; dose adjustment if severe.

Post-radiotherapy alopecia

• HF stem cells relatively radiation-sensitive (unlike chemo resistance); head/neck radiotherapy can cause persistent alopecia; patterns — localised (treatment field) or diffuse (whole brain irradiation); may accompany radiation dermatitis. Regrows usually 2-4 months; persistent radiation-induced alopecia ("total loss/incomplete regrowth 6 months post-completion") more with higher doses/combined chemotherapy. Management: topical steroids for dermatitis, minoxidil for growth stimulation, cosmetic camouflage, surgical correction for localised patches.

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• Originally oral antihypertensive; 2% lotion licensed 1988 UK/USA. Well tolerated; side effects: local irritation, facial hypertrichosis, headaches, rare dizziness/palpitations; avoid pregnancy/lactation; foam is propylene glycol-free (less irritating than lotion); caution on face (contact dermatitis risk).
• Effects: anagen prolongation, telogen shortening, kenogen stimulation; density returns to baseline within 6 months of stopping — long-term strategy.
• Mode of action: vasodilator; opens ATP-sensitive K channels; induces VEGF/HIF-1α; promotes prostaglandin synthesis (PGE2/PGE2R) influencing Wnt/β-catenin in dermal papilla.
• Converted to active minoxidil sulphate by SULT1A1 in follicle ORS — enzyme activity variability explains differential response; aspirin/salicylate decreases sulphotransferase activity, reducing efficacy. Direct minoxidil sulphate application gaining popularity (penetration/stability issues).

• Doses 0.25-5mg daily; "5 Cs": convenience, cosmesis, cost savings, co-therapy, compliance (+ 6th "C" — complicated, for when topical fails/not tolerated).
• Converted by liver/platelet sulphotransferase; higher follicular accumulation, lower SULT1A1 activation threshold vs topical route.
• Dosing: women start 0.5mg daily, increase by 0.25mg every 3 months to max 2.5mg daily; men start 2.5mg daily (hypertrichosis better tolerated), increase by 1.25mg every 3 months to max 5mg daily.
• Large cohort (1404 patients): only 1.7% discontinued for side effects; main issues — body/facial hypertrichosis, low BP symptoms, fluid retention, tachycardia; reflex tachycardia day 1, BP effects within first week, hypertrichosis takes 3 months; routine lab monitoring not generally needed; baseline ECG not required <5mg/day without cardiac/renal history.

• Latanoprost, bimatoprost (F2α analogues); stimulate eyelash growth (observed with intraocular glaucoma treatment); licensed cosmetic bimatoprost (Latisse®) for eyelash hypotrichosis (FDA, USA).
• Bimatoprost 0.03% or latanoprost 0.005% applied nightly to upper eyelid margin (± eyebrows); side effects: irritation, skin hyperpigmentation; avoid eye contact (reduces intraocular pressure, permanent iris discoloration risk); mechanism: anagen promotion via vasodilatation + mitogenic effect.

• Autologous concentrated platelets from centrifuged blood; used orthopaedics/dentistry/dermatology (wound healing, skin rejuvenation, hair growth); no standardised isolation technique, kits achieve 300–700% platelet enrichment.
• Injected into scalp; uncomfortable but minor side effects (pain, swelling, bruising, headache), postop infection rare; efficacy wanes after >4 months — typically monthly ×3 then 3-monthly maintenance.
• Mode of action: activated platelets release VEGF, EGF, IGF-1, FGF, PDGF, TGF-β — decrease apoptosis, initiate Wnt/β-catenin in dermal papilla, increase vasculature.

• Electric pens/microrollers — controlled tissue injury/microchannels; weekly-monthly; aim = pinpoint bleeding, mild redness; side effects: pain, localised infection; rationale = wound healing response (platelet/epidermal growth factors, VEGF, enhanced drug delivery).

• Cold/red laser, 650-900nm; "photobiomodulation"; used in wound healing, nerve regeneration, pain, increasingly hair regeneration.
• Mechanism unknown — photochemical reactions, transcription factor induction, cell signalling activation, increased mitochondrial energy, promotes anagen prolongation.
• Devices: hoods, caps, combs; 15-30 minutes 3-4×/week recommended for mild-moderate loss; side effects rare (scalp discomfort, urticaria, acne, dryness, eye damage risk).

• Adipose-derived stem cells; abdominal fat removed, enzymatically degraded, centrifuged, injected into scalp; expensive, unsubstantiated permanent-solution claims — caution advised pending long-term data; main side effects bruising/oedema.

• Combined OCP suppresses gonadotrophins/ovulation; POP increases uterine mucus. Concern: progestogens may exacerbate androgen-sensitive conditions (AGA, hirsutism). Some progestogens increase SHBG (reduces free androgen), some directly block androgen receptor. androgen index: antiandrogen progestogens (dienogest, cyproterone acetate, normogestrol, drospirenone); lower androgenic (desogestrel, gestodene, norgestimate); moderate-high androgenic (norethisterone, levonorgestrel/norgestrel).

• Off-licence for AGA/hirsutism; caution in premenopausal women (fetal feminisation risk — avoid pregnancy); breast/ovarian cancer risk unclear.
• Spironolactone: potassium-sparing diuretic; competitively binds androgen receptor, weakly inhibits androgen biosynthesis; side effects — menstrual irregularities, postmenopausal bleeding, breast tenderness, fatigue, elevated potassium/slight BP reduction (rarely significant without renal impairment; routine renal monitoring not needed <50 years with normal function); large cohort study (1.3 million women ≥55, 8.4 million patient-years) — no increased breast cancer incidence.
• Cyproterone acetate: synthetic progestogen, blocks AR, inhibits gonadotropin secretion, suppresses cutaneous 5α-reductase; premenopausal 50-100mg/day first 10 days of cycle; postmenopausal continuous (e.g. 50mg daily); side effects dose-dependent (weight gain, fatigue, low libido, breast tenderness, nausea, headache, depression); strong dose-effect with increased intracranial meningioma risk (middle skull base).
• Flutamide/bicalutamide: non-steroidal pure antiandrogens, inhibit androgen binding; flutamide no antigonadotrophic effect (serum androgens can rise); bicalutamide doesn't cross blood-brain barrier; rare fatal hepatotoxicity with high-dose flutamide limits use; bicalutamide better safety profile, doses 25-50mg daily, regular LFT monitoring recommended.
• 5α-reductase inhibitors: block testosterone→DHT; associated with increased depression, type 2 diabetes, gynaecomastia; suicide/erectile dysfunction less clearly associated; finasteride not associated with increased male breast cancer (female risk unknown).
• Finasteride 1mg daily (Propecia®) licensed for MPHL — reduces scalp DHT 64%, serum DHT 68%; reduces serum PSA by 50% (double measured value to correct); no effect on spermatogenesis/semen, no partner-exposure precaution needed.
• Dutasteride: dual type 1+2 inhibitor, greater potency; usual dose 0.5mg daily (lower regimens e.g. 0.5mg weekly used in some conditions); sexual side effects more common than finasteride, dose-related; longer half-life → slower side effect reversal.
• Post-finasteride syndrome (PFS): persistent/new symptoms despite stopping — sexual (libido loss, erectile dysfunction, genital numbness, ejaculation problems), psychological (suicidal thoughts, anxiety/depression, irritability, sleep problems), cognitive (concentration/memory, confidence loss), physical (muscle cramps, fatigue, gynaecomastia, dry skin). Postmarketing reports prompted labelling changes; PFS Foundation exists. Mechanism unclear — reduced brain neurosteroid synthesis, impaired testosterone synthesis increasing oestrogen/reducing DHT effects (normally reverts on stopping); data poor quality/uncontrolled/bias-prone; nocebo effects well documented; women show extremely low prevalence with no persistence — PFS currently described only in men. Identify pre-existing depression/sexual dysfunction before starting (increased risk); counsel all patients about persistence risk.

• Hair transplantation mainstream for MPHL/FPHL, selected scarring alopecias; can treat eyebrows/beard; occipital "safe donor area" (resistant to miniaturisation) used; strip technique or follicular unit extraction (FUE); up to 5000 follicular units/session; transplanted hairs shed then regrow at 3-4 months; full results 6-12 months.
• Patient selection factors: adequate donor area (occipital, or beard/body for burns scars); age (not usually <25 years — unpredictable progression); site affected (frontal more effective than vertex, which progresses); underlying process progression (donor dominance in AGA vs PCA where transplants remain vulnerable to disease process).
• **** Strip vs FUE: Strip — most grafts/session, no head shaving; disadvantages linear occipital scar, higher wound issue risk. FUE — less visible scarring, usable for beard/body donation, finer hair harvesting, less pain/downtime; disadvantages — fewer grafts/session, higher graft transection rate, shaved donor area.
• Complications: wound infection, bleeding, facial swelling; postoperative "shock loss" (anagen effluvium) possible either technique.
• Small-medium stable alopecia patches may be surgically excised ± scalp expanders/flaps.

Shampoos

• Cleansing agent, average hair surface area 4-8m²; detergent + foaming agents, conditioners, thickeners/opacifiers/pearlescents, stabilising agents (sequestering, preservatives, pH buffers, UV filters), perfume/colour, active ingredients (tar, zinc pyrithione, panthenol, hydrolysed protein).
• 5 detergent categories: anionic, cationic, amphoteric, non-ionic, natural surfactants (saponins).
• Dry shampoos: lipid-absorbing powder, no detergent.
• Safety: extensively tested for eye irritancy; allergic contact dermatitis possible (fragrances, preservatives).
• Washing frequency doesn't affect alopecia course; delayed washing → more telogen hairs dislodged when washed (misleading impression washing causes loss).

Conditioners

• Restore manageability/glossiness/softness lost from sebum removal; components: organic acids (pH ~5), fatty compounds (triglycerides, waxes, phospholipids, ceramides), vitamins (D-panthenol), protein hydrolysates (temporary shaft repair/thickening), cationic detergents (increase cuticle adherence/shine), silicone derivatives, cationic polymers (film formation).
• Forms: instant (rinse-off), 2-in-1, deep conditioners (up to 30 min under heat), leave-on (film-forming polymers); "co-washing" (conditioner as shampoo substitute) for very dry/damaged hair.
• Natural oils/butters (coconut, tea tree, argan, jojoba, shea) may impart shine but can be comedogenic/irritating; little evidence of shaft strength improvement.

Temporary hair styling

• Wet hair stretched/dried under tension forms new ionic/hydrogen bonds; lasts until next wash; products (gels, foams, waxes) vary in physical properties for different applications.

Permanent hair styling

• Disulphide bonds broken/reformed via chemicals — hazardous, best done by experienced practitioners.
• Permanent waving: reducing lotion (thioglycolate, pH~9) cleaves disulphide bonds → shaped around curlers → oxidising neutralising solution (hydrogen peroxide-based) reforms bonds.
• Permanent straightening (relaxing): same principle, mechanical straightening with comb; applied to new growth every 6-8 weeks; lye relaxers (sodium/potassium hydroxide, pH 13-14: base [stronger, needs scalp protection] or no-base); no-lye relaxers (guanidine hydroxide + calcium hydroxide, or lithium hydroxide) — less irritating but can leave mineral deposits causing dryness/brittleness. Hot combing (thermal straightening) — older method with petroleum jelly/liquid paraffin heat transfer. Chemical relaxing previously used by ~80% of African American women 20 years ago; increasing shift to natural hairstyles recently.

Hair colouring

• Ancient practice (Egyptians, Romans — bleached blond fashion).
• Dye types: temporary, semipermanent, permanent; small molecules penetrate best.
• ~50–80% of adult women, 10% of men >40 use hair dyes; main adverse effect = allergic contact dermatitis to PPD (para-phenylenediamine) — 1.5% of European population estimated allergic, 4–6% of patch-tested populations. IARC: occupational hair dye exposure "probably carcinogenic," personal use "not classifiable" (inconclusive epidemiology). Large US study (>100,000 women): no significant solid cancer risk increase overall with permanent dyes; slightly increased BCC risk; higher cumulative exposure positively associated with hormone-receptor-negative breast cancer and ovarian cancer; increased Hodgkin lymphoma only in naturally dark-haired women; higher BCC risk in naturally light-haired women. Genetic susceptibility (arylamine activation/detoxification genes) may modify individual risk.
• Excluding bleach — non-oxidation dyes (temporary, semipermanent/direct — plant-based, metallic salts) vs oxidation dyes (permanent — diamines including PPD, aminophenols, phenols/naphthols).
• Plant-based: henna (Lawsonia inermis) — reddish-brown on dark hair, orange on white/blond; generally safe (rare contact allergy/type I hypersensitivity); G6PD deficiency children risk life-threatening haemolysis with topical henna. Black henna (red henna + PPD) for temporary tattoos — sensitisation risk. Chamomile (apigenin) yellow tint. Indigo mixing gives chestnut-black range.
• Metallic dyes (lead/silver salts): progressive darkening especially grey hair, dull leaden colour, damages shaft, non-removable colour.
• Temporary colourants: azo derivatives, triphenylmethane basic dyes, azine derivatives, indoamines/indophenols; lasts until next wash.
• Semipermanent (direct) colourants: fade with repeated shampooing (normally 6 washes, some up to 12); small intrinsically coloured molecules; types — nitro dyes, solvent-assisted dyes, anion-cation complexes, self-oxidising dyes, cationic/basic dyes, reactive dyes.
• Permanent colourants: most used type; roots recoloured ~every 6 weeks; PPDs/aminophenols (colourless primary intermediates) oxidised by hydrogen peroxide → quinone mono/diimine → penetrate cortex; couplers (m-diamines, m-aminophenols, polyphenols) react to form permanent colour; alkaline pH (9-10, ammonia); hydrogen peroxide causes structural hair damage. UK law: hairdressers legally required patch test before application (Health and Safety at Work Act 1974); consumer allergy alert test 48h before use identifies >90% of allergic individuals; if PPD-allergic, avoid cross-reactive agents (sulphonamides, some local anaesthetics — benzocaine, procaine).
• Hair bleaching: oxidises melanin; brown easier to bleach than red; hydrogen peroxide solutions 3/6/9% (10/20/30 volume) + ammonia; terminated with acid pH shampoo/rinse; can cause dryness/fragility; some bleaching occurs with prolonged sun exposure.

• Wigs: NHS prescriptions available (variably by UK region); synthetic (prestyled, cheaper, heat-damaged, 3-6 month lifespan) vs human hair (natural look, styleable, more expensive, ~1 year lifespan with care); specialist wigs for complete hair loss (Supplex, Dermalite); vacuum wigs; newer heat-resistant synthetic and blended wigs; fitted by specialist wig salon, adjustable straps ± tapes/glues/clips; various cap types (wefted, hand-tied, net, lace front, monofilament, silicone suction); partial wigs for smaller areas.
• Hair systems (mesh integration/Intralace systems™): partial wigs integrating own remaining hair, fixed to scalp; expensive, regular maintenance, not universally suitable.
• Extensions/clip-ins: add length/volume; limited benefit for top-of-scalp alopecia (no coverage there); wefted panels or individual attachment (tape, glue, beads); clip-ins self-attachable.

• Coloured fibres/sprays specifically for alopecia; also products for grey roots/dry shampoo purposes; helpful for small alopecia areas/thinning. Make-up (eyebrow pencils, eyeshadows, eyeliners, false lashes) for eyebrow/lash loss.
• Tattooing: cosmetic tattooing (permanent make-up)/microblading for eyebrow/lash loss (lasts 2-3 years, topping up every 18 months); scalp tattooing/micropigmentation useful for short dark hair in men and thinning in FPHL women (fades, repeated every few years).

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• Take patients with hair growth disorders seriously and provide emotional support
• Classify the hair disorder by the patient's history and clinical pattern
• Exclude or confirm common hair growth disorders by clinical assessment and diagnostic tools
• Find the right treatment for the confirmed diagnosis
• Dispel misconceptions about treatment options and results; educate the patient

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• Hair is enormously important for social communication and sexual attraction
• Alopecia, structural hair shaft defects or excessive body hair → diminished well-being and self-esteem, depressive moods, social withdrawal
• Definitions given in eTable 88-0.1 (online edition)
• Effluvium = the process of hair shedding; alopecia = the final result
• Both terms are nonspecific; they give no etiologic information
• Alopecias are grouped into:
• Diffuse, patterned and focal hair loss
• Scarring (cicatricial) vs nonscarring
• Scarring alopecia: permanent destruction of follicular stem cell structure → loss of hair-producing capacity
• Nonscarring alopecia: follicle not ultimately destroyed; regrowth follows periods of shedding
• In both, hair loss may be diffuse over the whole scalp or circumscribed (few, more or less demarcated areas)
• Alopecia from improper or missing follicle development (rare inherited):
• Focal, e.g. aplasia cutis congenita (Chapter 107)
• Diffuse, e.g. ectodermal dysplasia (Chapter 142)
• Structural hair shaft defects:
• Acquired: increased hair breakage, usually from grooming practices; reversible once triggers stop
• Inherited: with or without increased breakage; cannot be cured but tend to improve with age

• See Chapter 86

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• Additional diagnostic procedures in online Table 88-1.1
• Data from Olsen EA (J Am Acad Dermatol 2003)

• Critical for the initial differential diagnosis and for the patient relationship
• Ask about duration and pattern: present at birth, gradual from a certain age, or rapid onset?
• Present at birth → points to a genetic disorder
• More common in children: tinea capitis, alopecia areata, trichotillomania
• Rapid-onset hirsutism → think androgen-secreting tumor
• Gradual fronto-parietal thinning → fits androgenetic alopecia (AGA)
• Is the hair shedding or thinning? Coming out "by the root" or breaking off?
• Also ask about: family history, current and past medications, pregnancy, menses, menopause, thyroid function, diet, past and present health, surgeries, accidents, physical or emotional stress, hair care practices

• First assess the overall pattern: density, distribution, focal vs global
• Note scaling, erythema, erosions, crust, pustules, and presence or absence of follicular ostia
• Examine the nails: alopecia areata, lichen planopilaris (LPP) and ectodermal dysplasia can affect finger and toe nails
• Excess body hair is often shaved or epilated → extent of unwanted terminal hair assessed by patient self-assessment with images (see Hirsutism)

• Qualitative ancillary test of ongoing activity of hair loss
• Grasp approximately 50–60 hairs and tug from proximal to distal
• Removal of 6 hairs = positive (active shedding)
• Also positive if 3 hairs can be pulled out in several different areas of the scalp
• Examine proximal ends against a white background (dark hair) or black background (light hair)
• Blunt tip → hair breakage
• Tapered tip → regrowth or miniaturized hairs
• Light microscopy of proximal ends: broken (blunt) ends vs club hairs (telogen)

• Necessary, particularly to confirm scarring alopecia
• Also consider for the differential of TE, diffuse alopecia areata and AGA
• Consensus meeting on cicatricial alopecia, February 2001 recommendations:
• Biopsy 1: one 4-mm punch including subcutaneous tissue from a clinically active area, processed for horizontal sections, stained with H&E
• Elastin (acid alcoholic orcein), mucin, and PAS stains may add information
• Biopsy 2: second 4-mm punch from a clinically active area, cut vertically into two equal halves
• One half → transversely cut routine histologic sections
• Other half → direct immunofluorescence (DIF)
• Nonscarring alopecia: usually one biopsy from the affected area suffices; preferably horizontal sections

• Simple quantification of hair loss: proportion of anagen vs catagen and telogen hairs
• Preparation:
• No hair washing for 3–4 days before the test
• Avoid perms, dyes, straightening for at least 6 weeks before
• Technique: about 25–50 hairs grasped with a needle holder close to the scalp and plucked sharply in the direction of hair growth
• Proximal ends placed on a glass slide in a drop of water under a cover slip
• Alternative: 1% dimethylcinnamaldehyde in 0.5 N HCl → stains anagen hairs red (protein-bound citrulline in the inner root sheath)
• Roots examined by light microscopy at 100× magnification
• Interpretation:
• 10%–20% telogen = normal (anagen percentage slightly higher in women and children than men)
• Telogen count >35% → highly suspicious for TE
• Repeated trichograms follow the condition and measure treatment results
• Tinea capitis: plucked hairs examined for spores, mounted in 5% KOH and gently heated

• A. Telogen club hairs: cornified, depigmented, rounded-up bulb without attached root sheath
• B. Loose anagen hair (by hair pull): ruffled cuticle, no attached root sheath
• Anagen hairs recognized by pigmented, somewhat distorted, malleable bulb
• Anagen hairs should NOT normally be found in a hair pull in patients with alopecia areata
• C. Normal anagen hair obtained by hair pluck (for comparison)
• D. Newly growing anagen hair: tapered distal tip (vs blunt distal end of cut/trimmed or intrinsically broken hairs)

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• Most common form of human hair loss
• Nonscarring, under the influence of androgens (dihydrotestosterone, DHT); androgen susceptibility of follicles is important
• Reduced terminal hair density in a typical pattern in both genders; terminal → vellus-like hair conversion; increased telogen hairs (during active shedding)
• Gender-specific classifications with clinical overlap: Norwood–Hamilton (men), Ludwig (women)
• FDA-approved options: topical minoxidil 2% (women) and 5% (men), oral finasteride 1 mg daily (men), hair restoration surgery, low laser light

• AGA / pattern hair loss: by far the most common hair loss in men and women
• Male pattern hair loss (MPHL) (male AGA, male balding): androgen-dependent, genetically determined trait
• Female pattern hair loss (FPHL) (female AGA): believed to be the same entity
• Androgen requirement less clear-cut than in men; distribution generally different
• In both sexes: progressive decline in anagen duration, increase in telogen duration, miniaturization of scalp follicles

Men

• Prevalence estimates vary widely; most men develop some hairline recession in their lifetime
• Progression to at least type III in about 50% of men and women beyond 40 years
• Risk depends on family history in the father, mother, or maternal grandfather
• Men whose father had hair loss were twice as likely to have hair loss
• Ethnic variation:
• 4 times less frequent in men of African ancestry
• About 3 times less frequent in Korean men
• About 1.5 times less frequent in men from China, Japan or Thailand

Women

• FPHL less common than MPHL but shows similar age-related increase in frequency and severity
• Can start as early as the prepubertal period in both men and women
• About 40% of Caucasian women have some FPHL by age 70
• FPHL seems less frequent in Asian women

• Underlying causes not yet determined
• MPHL: combination of androgen hyperactivity, genetic predisposition to androgen sensitivity, and an androgen-independent genetic predisposition
• FPHL: may have a more complex etiology; androgen action plus genetic sensitivity still seems dominant in most cases
• Large pigmented terminal hairs gradually replaced by fine, nearly invisible, colorless vellus hairs, progressively with each cycle
• Scalp hair cycle:
• Anagen (growth): approximately 2–6 years
• Catagen: short, 2–3 weeks; represents the termination of anagen
• Telogen: hair does not grow; shed after about 12 weeks
• Transition to catagen → decreased anagen-maintaining cytokines in the follicle
• MPHL and FPHL: progressive decrease in anagen duration with each cycle → shorter, thinner hairs
• Interval between late telogen shedding (exogen) and new anagen increases → more empty follicles → apparent reduced density

• Usually not difficult to identify in a classic pattern
• Hamilton scale (1951): first grading scale for MPHL, types I to VIII
• Type I: prepubertal scalp, terminal hair on forehead and all over scalp
• Types II and III: gradual frontal, mostly M-shaped recession
• Types IV, V, VI: additional gradual vertex thinning
• Types VII and VIII: confluence of balding areas; hair only around the back and sides
• Norwood modification (1975): added variants IIIa, IVa, Va (more prominent receding of the middle portion of the frontal hairline) and type III vertex (loss mainly in the tonsure area, frontotemporal recession never exceeding type III)
• Fig. 88-4 stages shown: I, II, IIa, III, IIIa, III vertex, IV, IVa, V, Va, VI, VII
• Ludwig classification (1977): women; diffuse crown loss with persistence of the frontal hairline
• Olsen (1994): women may show increasing loss towards the front, frontal accentuation or "Christmas tree pattern"
• Pattern hair loss in women: male pattern (Hamilton), diffuse (Ludwig), frontal accentuation (Olsen); characteristic widened hair part
• Women can show a male pattern, and men a more female pattern
• Scalp exam plus history usually allow a definitive diagnosis
• Standardized global scalp photography (especially of the part): qualitative assessment of progression and therapy control
• Pull test and trichogram: information on ongoing activity
• Videodermoscopy and phototrichogram: therapy control
• Diagnosis harder if loss is diffuse or coexists with TE, diffuse alopecia areata or mild cicatricial alopecia
• Scalp biopsy gives a definitive diagnosis: histology, number of terminal vs vellus hairs per area, number of anagen vs telogen hairs
• Laboratory (women):
• Ferritin and TSH recommended to rule out an underlying TE
• Extensive androgen workup NOT recommended for a routine visit
• Women with irregular periods and/or other signs of androgen excess: check at least free and total testosterone and DHEA-S
• Best timing: morning, on one of the days of the menstrual cycle; must be off the pill for at least one cycle

• Early vertex balding correlated with increased risk of coronary heart disease and insulin resistance, especially in young men with hypertension, obesity, dyslipidemia
• Early vertex balding also correlated with increased risk of prostate cancer

• Telogen effluvium
• Diffuse alopecia areata
• Trichotillomania
• Secondary syphilis

• AGA is progressive: hair density decreases approximately 6% of hair fibers per year
• Increased shedding can occur periodically; extent depends on genetic predisposition
• Two pharmaceutical treatments approved for men: oral finasteride and topical minoxidil

Minoxidil

• Biologic response modifier; halts AGA in many patients and regrows hair to a certain extent
• Piperidinopyrimidine derivative; caused hypertrichosis when given orally as an antihypertensive
• Now used as 2% and 5% topical lotion or foam
• Mechanism not fully understood:
• Possible direct effect on follicle cells; mitogenic on epidermal cells → prolonged survival and increased proliferation of follicles in vitro
• Converted to minoxidil sulfate, a potassium channel agonist → increased K+ permeability → impaired calcium entry into cells → decreased epidermal growth factors → enhanced hair growth
• Efficacy:
• Increased hair counts probably reflect reversal of miniaturized hairs into thicker terminal hairs
• Studied on the vertex, but also works on the frontal scalp, especially if hairs are not completely miniaturized
• Moderate to dense regrowth in up to 30%–45% of patients
• Increased shedding in the first 4–6 weeks in some patients → a positive sign (anagen induction with earlier "molting" of telogen hairs); educate patients to improve compliance
• Side effects:
• Contact dermatitis in 6.5%
• Facial hypertrichosis in 3%–5% of women
• Most patients have irritation from propylene glycol, not true minoxidil allergy → use 2% lotion (less propylene glycol), vehicles with butylene glycol, or the foam
• To discriminate the culprit: patch test or repeated open application test on the volar forearm
• Systemic absorption minimal; serum levels too low for hemodynamic effects in normotensive or hypertensive patients
• <1 in 1,000 may get tachycardia and decreased blood pressure
• Patients with hypotension or heart problems: use with cardiologist approval
• Cardiac effects from earlier studies not definitely linked to minoxidil; may reflect increased CAD in subsets of men with AGA
• Use:
• Solution twice daily: 1 mL or 25 drops bid; also 5% foam
• After shampooing, hair and scalp at least towel-dry
• Must stay on scalp at least 4 hours before the next shampoo
• Lifelong treatment; takes 4–6 months to start working; maximum effect after 1 year

Finasteride

• Synthetic azo-steroid; used for AGA in men since 1997
• Potent, highly sensitive selective 5α-reductase type 2 inhibitor; binds irreversibly to isoenzyme 2; blocks testosterone → DHT
• Pharmacologic half-life about 8 hours
• 1 mg daily reduces scalp DHT by 64% and serum DHT by 68%
• Nonlinear dose–response: higher doses do NOT give significantly greater DHT suppression or clinical benefit
• Efficacy:
• Significant hair count increase in vertex and frontal AGA at 6 and 12 months (placebo-controlled)
• Stabilizes hair loss in 80% (vertex) and 70% (frontal)
• Mild to moderate regrowth: 61% vertex, 37% frontal
• After 24 months: 66% had some vertex regrowth (approximately 10%–25% of previously lost hair)
• Most show no further loss; only a few continue to lose hair
• Use beyond 2 years does NOT promote further regrowth; density stabilizes with retention of new hair
• If successful, continue indefinitely: balding resumes once treatment stops
• Side effects (<2% of patients):
• Decreased libido 1.8% vs 1.3% placebo
• Erectile dysfunction 1.3% vs 0.7% placebo
• Decreased ejaculate volume 0.8% vs 0.4% placebo
• Does NOT affect spermatogenesis or semen production in men aged 19–41 years
• Effect on prostate volume and PSA in younger men small and reversible after stopping
• Decreases PSA by 50% in older men → take a baseline PSA in men over 40; advise the family doctor to double the PSA value while on finasteride
• Long-term effects of 1 mg daily unknown
• 7-year placebo-controlled study, 9,060 men ≥55 years, 5 mg/day: finasteride prevents or delays prostate cancer, but slightly higher risk of high-grade prostate cancer
• Not approved for women; efficacy in FPHL controversial
• Multicenter double-blind RCT, 1 mg/day in postmenopausal women with FPHL: no difference in anagen:telogen ratio or terminal:miniaturized hair ratio
• Camacho et al: regrowth with 2.5 mg/day in 41 women with FPHL and SAHA (seborrhea, acne, hirsutism, alopecia)

Dutasteride

• Inhibitor of type I and II 5α-reductase
• Approved at 0.5 mg daily for symptomatic BPH
• Some studies show great efficacy in MPHL and FPHL
• NOT FDA approved for AGA; more safety data needed

Cyproterone Acetate (CPA)

• Antiandrogen; synthetic derivative of 17-hydroxyprogesterone
• AR antagonist with weak progestational and glucocorticoid activity
• Also inhibits 21-hydroxylase (reducing aldosterone) and, to a lesser extent, 3β-hydroxysteroid dehydrogenase (both needed for cortisol synthesis)
• Available in Europe, Canada and South America; usually combined with ethinyl estradiol as a birth control pill
• Not FDA approved for AGA
• Suggested FPHL regimens:
• 100 mg CPA daily on days 5–15 + 50 μg ethinyl estradiol on days 5–25, or
• 50 mg CPA daily on days 1–10 + 35 μg ethinyl estradiol on days 1–21
• 12-month RCT, 66 women: 33 used topical minoxidil 2% + combined OC vs 33 on CPA 52 mg daily + ethinyl estradiol 35 μg for 20 days of the cycle → CPA combination gave greater hair density in women with hyperandrogenism
• Side effects: irregular menses, weight gain, breast tenderness, loss of libido, depression, nausea
• Use in men obsolete unless a gender change is desired

Spironolactone

• Synthetic 17-lactone; renal competitive aldosterone antagonist with mild antiandrogenic effect (blocks AR, preventing DHT interaction)
• Maximum androgen suppression after 4–12 months; 200 mg daily required
• May have a preventive effect in FPHL and may reduce shedding in women without hyperandrogenism
• Not FDA approved for FPHL; as an antiandrogen, should not be used in men
• Main side effect: menstrual irregularities → mitigated by decreasing dose to 50–75 mg/day and adding OCs, or after 2–3 months of therapy
• Contraindications: renal insufficiency, hyperkalemia, pregnancy, abnormal uterine bleeding, genetic predisposition to breast cancer

17α- and 17β-Estradiol

• Topical 17α- or 17β-estradiol commercially available in Europe for FPHL
• Studies: increased anagen and decreased telogen rates vs placebo
• Pathways of 17α-estradiol-induced regrowth unknown
• Niiyama et al: 17α-estradiol diminishes DHT formed by follicles incubated with testosterone, while increasing weaker steroids
• Follicles in women with FPHL express more aromatase than male follicles
• Under 17α-estradiol, increased conversion of testosterone → 17β-estradiol and androstenedione → estrone in occipital follicles → may explain benefit
• Women on aromatase inhibitors develop FPHL more rapidly
• Another theory: systemic induction of SHBG → less free, bioavailable testosterone
• Absorbed through scalp → consider systemic side effects; cannot be used in men

Low-Level Light Therapy

• Many devices sold without prescription; manufacturers often "guarantee" regrowth
• Only FDA-approved low-fluence laser device: HairMax LaserComb (Lexington International, Boca Raton, FL; FDA approval as a medical device)
• Paradoxical hair growth seen during laser hair removal at relatively low fluences; mechanism unknown
• One theory: increased dermal papilla blood flow
• Appears safe; more studies needed on mechanism and efficacy

Hair Restoration Surgery

• Most successful and permanent treatment for AGA in suitable candidates
• Includes hair transplantation (HT) and, in skillful hands, scalp-reduction surgery
• Suitable HT candidates: reasonable expectations, adequate donor supply, no contraindications to surgery
• Most dramatic cosmetic change: Hamilton–Norwood VI and VII, and anterior accentuation (subtypes IIIa and IVa, "Christmas tree pattern")
• Larger numbers of smaller grafts per session → very natural results
• Advisable to place small grafts between pre-existing hairs to account for future loss
• Rational donor use (strip harvesting or FU extraction) allows several sessions with progressive loss
• Based on donor dominance: androgen-independent follicles retain their properties when moved to androgen-dependent areas
• Donor supply limited by strip area (size of the "safe zone", scalp elasticity) and donor hair density
• Outpatient procedure; up to 10 hours depending mainly on number of grafts
• Tumescent anesthesia for donor and recipient areas, sometimes with nerve blocks
• Strip harvesting: most commonly used; fast removal of large numbers of hairs, leaves a fine line scar (minimized by special harvesting and closure)
• Strip dissected under magnification into follicular units (FUs), "families" of hairs growing together in one connective tissue sheath
• Recipient sites prepared with small needles or spears sized to the graft
• Follicular unit extraction (FUE): individual FUs harvested with very small blunt punches
• More time consuming but avoids a long occipital scar
• Indicated for patients wanting a very short hairstyle

Wigs and Hairpieces

• For patients not candidates for surgery, women with extensive loss, and/or those unsatisfied with medical therapy
• Excellent cosmetic results, especially custom made
• Reluctance easier to overcome if the piece blends with existing hair and is comfortable
• Women tend to be less reluctant, especially if exposing her natural hairline

Treatment Algorithm for Male Pattern Hair Loss

• Norwood–Hamilton stage III–V:
• Oral finasteride and/or topical minoxidil solution and/or low-fluence laser light for 1 year
• Improvement or stabilization?
• Yes → continue medical therapy indefinitely
• No → hair transplantation ± scalp reduction
• Norwood–Hamilton stage Va, VI, VII:
• Hair transplantation ± scalp reduction and/or finasteride, topical minoxidil, low-fluence laser light, hairpiece
• (Flowchart reconstructed from column-scrambled text)

Treatment Algorithm for Female Pattern Hair Loss

• (Source caption misprinted as "male pattern hair loss"; content is female)
• Ludwig stage I–II:
• Topical minoxidil solution for 1 year (+ endocrine workup)
• Improvement or stabilization?
• Yes → continue topical minoxidil indefinitely
• No → hairpiece and/or antiandrogens/finasteride, low-fluence laser light
• Ludwig stage III:
• Occipital donor area adequate?
• Yes → hair transplantation and/or antiandrogens/finasteride, low-fluence laser light, hairpiece
• No → hairpiece and/or antiandrogens/finasteride, low-fluence laser light
• (Flowchart reconstructed from column-scrambled text; exact placement of the endocrine workup box is uncertain)

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Hypotrichosis Simplex

• Progressive global loss of scalp hair starting in childhood
• Autosomal dominant; both sexes equally
• Eyebrows and body hair unaffected
• Pathogenesis not fully understood; in two families, a defect in the corneodesmosin gene (adhesion protein) (35-year-old woman)

Reduced or Absent Hair Growth Associated with Ectodermal Dysplasia

• Failure of normal in utero follicle development → reduced or absent follicles
• Often with ectodermal defects; most often abnormalities of bones, CNS, teeth or eyes (Chapter 142)
• Most common: hypohidrotic ectodermal dysplasia → sparse hair, abnormal teeth, reduced or absent sweating
• Mutation in the ectodysplasin signaling pathway (involved in early embryonic follicle formation)

Atrichia with Papular Lesions

• Autosomal dominant per source (presents in infancy)
• Hair usually present at birth; alopecia develops within the first year
• Papular follicular cysts appear several years after alopecia
• Mutations in the hairless gene or the vitamin D receptor gene
• Follicle formation in utero normal; massive apoptosis in the bulb during the first catagen → dermal papilla separates from follicle base → failure to re-enter anagen → follicular epithelium becomes cystic
• Universal hair loss in the first month of life: differential is atrichia with papular lesions vs alopecia areata universalis
• Familial universal alopecia → gene testing and genetic counseling

Short Anagen Syndrome

• Poorly understood presentation of short, fine hair in children
• Hair fails to grow long because of a shortened anagen
• Hair density and shafts appear normal
• May improve after puberty
• Autosomal dominant or sporadic

Loose Anagen Syndrome

• Easy, painless epilation of anagen hair; hair appears to grow slowly
• Density normal or reduced; some children have demarcated areas of incomplete alopecia
• Typical patient: 2–5 years old, more often girls, hair most often light blond
• Tends to improve without treatment with age
• Diagnosis by microscopy of gently pulled hair: 80%–100% anagen hairs with ruffled cuticle and no inner root sheath
• Hair loss can cycle; a gentle pull may not yield enough → parent collects at home for later microscopy
• Familial, sporadic, or associated with Noonan syndrome or hypohidrotic ectodermal dysplasia (source: "hyperplasia"); also seen with HIV
• Differential: hair shaft abnormalities, alopecia areata, trichotillomania

Epidemiology

• Second most common cause of hair loss in women after FPHL
• Nonpatterned increased shedding of terminal hairs diffusely over the entire scalp; apparent thinning in severe cases
• Both genders, but more females complain
• Can copresent with AGA, particularly early-onset → complicates diagnosis and treatment
• Differs from AGA: not androgen-sensitive, not inherited, no terminal-to-vellus transition → no decrease in matrix cell volume or hair shaft diameter
• Related to external causes; often reversed when the stimulus is removed

Acute Telogen Effluvium at a Glance

• Nonscarring alopecia
• Sudden conversion of large numbers of anagen hairs to telogen → diffuse shedding
• Seen after severe illness, surgery, nutritional deficiency, iron deficiency, childbirth, medications, and thyroid disease
• Reversible once the initiating factor is eliminated

Etiology and Pathogenesis

• Best described as a premature shift of hairs from anagen into catagen and telogen
• Variants: anagen may be prolonged, or telogen shortened or prolonged; the type depends on the stimulus
• Main clinical difference: latency of onset after the stimulus
• Postpartum hair loss: generally 2 or 3 months postpartum (some longer)
• Mechanism: delayed anagen → catagen/telogen transition → simultaneous shedding of large numbers of terminal hairs
• Regrows, but may show changes in texture, color, curliness, and may not reach previous length
• Pregnancy (parturition or abortion) may in some cases produce permanent changes in anagen length
• Other triggers usually involve premature termination of anagen:
• Oral contraceptives: transient TE 2–3 months after discontinuing or changing; delayed onset distinguishes it from drug-induced anagen effluvium (AE)
• 1970s "crash" diets: TE about 3 months after starting, depending on severity of weight loss; sudden deprivation of amino acids and other dietary factors; regrowth after stopping
• Surgery, psychological trauma, febrile illness
• Drugs: temporary hair loss usually, but not necessarily, of the AE type; time course and severity may make TE appropriate
• TE-producing agents: cimetidine, enalapril, captopril, imiquimod, metoprolol, propranolol, lithium, L-dopa, trimethadione, bromocriptine
• Etretinate and isotretinoin: more of the AE type, as is hair loss sometimes after renal dialysis (possibly with hypervitaminosis A)
• Environmental contamination/poisoning (selenium, arsenic, thallium, mercury, lead): AE-like rapid onset, probably via cytotoxicity

Clinical Findings (Acute TE)

• Fairly sudden onset of massive shedding
• Normal anagen/telogen ratio of 90:10 can switch to 70:10 (as printed; likely 70:30)
• "Bag sign": women bring bags of collected hair
• >300 telogen hairs can be shed per day
• Scalp may show reduced density, especially temporal
• Pull test usually positive (3 or more hairs from different parts of the scalp)
• Trichogram/phototrichogram quantifies telogen hairs
• Scalp biopsy helps distinguish from diffuse alopecia areata or AGA

Causes of Telogen Effluvium

• (Drug list ends at colchicine in the extracted text; it may be truncated)

Chronic Telogen Effluvium (CTE)

• Etiology and pathogenesis:
• First proposed in 1996 to separate the abrupt-onset, short-acting TE (exogenous triggers or parturition) from a more durable condition not clearly related to an external event
• Chronic malnutrition → CTE (as crash diets → acute TE); protein deficiency is the likely mechanism
• Less clear: zinc or biotin deficiency
• Iron deficiency (low serum ferritin, anemia): controversial trigger
• Hypothyroidism also associated
• Clinical findings:
• Most common in women
• Ongoing massive shedding or recurrent episodes
• Rule of thumb: diffuse shedding lasting >6 months after a trigger or after withdrawal of a suspected drug = CTE
• Density normal or reduced; regrowing tapered new anagen hairs usually found
• Pull test moderately positive
• Trichogram/phototrichogram confirms and quantifies
• Scalp biopsy very helpful for confirmation and distinction from other alopecias
• Because FPHL/MPHL and alopecia areata may copresent, assay serum iron and thyroid hormones to exclude treatable causes

Acute Telogen Effluvium Differential Diagnosis

• Androgenetic alopecia
• Diffuse alopecia areata
• Trichotillomania
• Anagen effluvium
• Secondary syphilis

Prognosis and Clinical Course

• Both acute and chronic TE usually resolve once triggers are eliminated; in CTE triggers may be hard to identify
• Women are often most concerned about complete baldness → reassure: TE does NOT lead to complete baldness
• Hair likely regrows around 6 months after removing the trigger
• Shedding may persist for a few weeks or months after the trigger is gone

Treatment

• Removal of the cause is the major goal
• Iron supplementation if ferritin <70 ng/mL
• Borderline hypothyroidism can be hard to identify
• Suspect in women with hair loss plus depression, lack of energy, mental fatigue, cold intolerance, weight gain and/or constipation
• TSH may fluctuate but is usually elevated, with normal or reduced thyroid hormone
• Suspected thyroid dysfunction → follow closely with an endocrinologist
• Topical 2% or 5% minoxidil, 1 mL twice daily: helpful especially with prolonged loss of unknown trigger or drug-related loss when the drug cannot be stopped

• Disturbance of hair follicle matrix cells; anagen interrupted
• Hair falls out 7–14 days after the initiating event, without entering catagen or telogen
• Two types:
• Dystrophic AE: caused by chemotherapy, radiation, toxins or alopecia areata
• Bulbs (from pull test or trichogram) show a tapered tip with weakened shaft broken shortly above the bulb ("dystrophic hair")
• Immediate anagen release:
• Chemotherapy quickly causes severe loss, even total baldness; rapid onset indicates immediate anagen release
• Easy release of anagen hairs on gentle pulling; anagen hair has a broom-shaped, pigmented bulb
• Agents: vincristine, vinblastine, methotrexate, doxorubicin, fluorouracil
• Normal-appearing anagen hair with inner and outer root sheath can be found to some extent in every AE, but especially in bullous dermatoses of the scalp with sub- or intraepidermal blisters
• Hair usually regrows after around 120 days once the trigger is removed
• Incomplete recovery after multiagent chemotherapy reported
• Advise patients about scalp prostheses and other head coverings

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• Nonscarring hair disorder
• Both genders equally; any age, but higher incidence at younger age
• Most common form of hair loss in children
• Well-demarcated round or oval bald spots on the scalp or other body sites
• 5% develop loss of entire scalp hair (alopecia areata totalis); 1% develop alopecia areata universalis (loss of all body hair)
• Nail changes: pitting or sandpaper nails
• Thought to be autoimmune, with a possible hereditary component
• Usually without associated disorders, but can coexist with Hashimoto thyroiditis or vitiligo

Epidemiology

• About 0.2% of the world population affected at any time; lifetime risk 1.7%
• Common cause of abrupt-onset hair loss, but less frequent than AGA or TE
• Sexes equally affected; any age, higher incidence when younger
• Most common alopecia in children
• Familial occurrence around 15%; expression varies among family members
• 5% progress to alopecia totalis, 1% to alopecia universalis at some point

Etiology and Pathogenesis

• Chronic, organ-specific autoimmune disease mediated by autoreactive CD8+ T cells; affects hair follicles and sometimes nails
• Inappropriate immune response to hair follicle-associated antigens
• Collapse of the anagen hair bulb immune privilege, probably induced by interferon-γ, may be key
• Melanogenesis-associated autoantigens, normally sequestered by functional immune privilege, may be a key target
• Positive family history in 10% up to 42%; much higher in early-onset disease
• Many patients report major emotional stress before onset
• GWAS: several loci with genes controlling innate and acquired immunity, and genes expressed in the hair follicle
• Histology: T-cell infiltrate in and around bulbs of anagen follicles ("swarm of bees")
• Classic infiltrate may be missing in subacute or chronic forms
• Consider AA whenever high percentages of telogen or miniaturized hairs are present, even without peribulbar inflammation

Clinical Findings

• Acute onset
• Oval or round, well-circumscribed bald patches with a smooth surface in a diffuse distribution
• Alopecia totalis: loss of entire scalp hair; sudden or following partial alopecia
• Alopecia universalis: loss of all body hair; sudden or after long-standing partial alopecia
• Partial alopecia may affect other body areas
• Hallmarks:
• "Black dots" (cadaver hairs, point noir): hairs breaking before reaching the skin surface
• Exclamation point hairs: blunt distal end, tapering proximally; appear when broken hairs (black dots) are pushed out of the follicle
• Initial patch most often on the scalp, but any hair-bearing site
• Usually asymptomatic; some have mild itching and erythema
• Less commonly diffuse generalized pattern resembling AGA or TE
• Acute stage: gentle pull at the periphery of bald areas yields >10 hairs
• Nail involvement common: pitting, sandpaper-like appearance
• Associations: cataracts, thyroid disease, vitiligo, atopic dermatitis, psoriasis, IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome), Cronkhite–Canada syndrome, Down syndrome
• Diagnosis: patch shape and appearance, exclamation point hairs, nail changes; usually obvious
• Family history and/or associated diseases support the diagnosis when in doubt
• Scalp biopsy: generalized miniaturization, marked increase in catagen and telogen follicles
• Acute phase: peribulbar lymphocytic infiltrate ("swarm of bees"); sometimes mast cells, plasma cells, eosinophils
• Thyroid function tests should be performed

Nonscarring Focal Hair Loss Differential Diagnosis

• Temporal triangular alopecia
• Tinea capitis
• Early scarring alopecia
• Trichotillomania
• Secondary syphilis (alopecia areolaris)
• Androgenetic alopecia
• Telogen effluvium
• Anagen effluvium

Complications

• Relapsing course and progression to totalis or universalis are dreaded complications
• Missing scalp/facial hair, including nasal hair, eyelashes, eyebrows → more sunburn, skin cancer, nasopharyngeal and ophthalmologic inflammation
• Not life threatening, but appearance change → reduced well-being and self-esteem, severe depression, social withdrawal

Prognosis and Clinical Course

• Very variable, irregular relapsing course
• About 25% have a solitary episode
• Spontaneous regrowth common; different body areas regrow independently
• About 60% have at least partial regrowth by 1 year, often followed by repeated episodes
• About 40% of relapses within the first year, but many relapse after 5 years
• Hair may regrow white, later returning to natural color
• Poor prognosis:
• Involvement of the occiput and/or hairline (ophiasis pattern when sweeping around the scalp periphery)
• Chronic relapsing course
• Nail changes
• Onset in childhood
• Progression to totalis also higher with hair loss on the trunk and extremities

Treatment

• Very little evidence-based data; recommendations mainly from case series and clinical experience
• All treatments palliative: control the current episode, do NOT cure
• Published guidelines exist; algorithm by age and scalp involvement

Treatment Algorithm for Alopecia Areata

• (Copyright Jerry Shapiro, Vera Price and Harvey Lui; flowchart reconstructed from column-scrambled text)
• Age <10 years:
• Minoxidil 5% solution ± short-contact anthralin or topical corticosteroid
• Age >10 years: decide by extent of scalp involvement
• <50% involvement: intralesional corticosteroids ± minoxidil 5% solution ± short-contact anthralin ± topical corticosteroid
• >50% involvement: topical immunotherapy (DPCP / SADBE / DNCB)
• Good response → continue topical immunotherapy prn
• Poor response → minoxidil 5% solution ± short-contact anthralin or topical corticosteroid, or PUVA
• Scalp prostheses should be considered with >50% scalp involvement

Conservative Management

• High spontaneous remission rate, especially with short history and limited scalp involvement
• In totalis and universalis, treatments have a high failure rate
• After discussing risks and benefits, "no treatment" may be legitimate

Topical Corticosteroids

• Superpotent (class I) and potent (class II) widely used
• Efficacy proven for class I under occlusion and class II combined with minoxidil

Intralesional Corticosteroids

• Triamcinolone acetonide or triamcinolone hexacetonide
• First-line therapy for adults with <50% scalp involvement
• Triamcinolone acetonide 2.5–10 mg/mL
• Repeated every 4 to 6 weeks; total per session 15–40 mg
• Initial response often after 4–8 weeks
• Scalp indentation at injection sites from nonpermanent atrophy of subcutaneous fat
• Permanent atrophy if the same area is injected repeatedly over months and years
• No regrowth after 4 months → consider other options
• Used on scalp, eyebrows and beard; can be combined with topicals

Systemic Corticosteroids

• Effective, but regrown hair frequently falls out when stopped
• Controversial; mainly short-term for rapidly advancing loss
• Not routine: do not alter long-term prognosis; side effects striae, acne, obesity, cataracts, hypertension
• Doses:
• Prednisone 20–40 mg daily, tapered to 5 mg daily over a few weeks
• Pulse regimens: oral prednisolone 100–300 mg or IV methylprednisolone 250 mg

Topical Minoxidil

• Some evidence of clinically acceptable regrowth with 5% solution
• Better results combined with class II topical corticosteroids or anthralin
• Little efficacy in totalis and universalis

Anthralin

• Irritant with possible nonspecific immunomodulating effect; mainly a psoriasis drug (Chapter 18)
• Cosmetically acceptable improvement in 20% to 25% of patchy AA
• 0.2%–1.0% cream or ointment, applied daily to affected areas:
• 20–30 minutes for the first 2 weeks
• Then 45 minutes daily for 2 weeks
• Up to a maximum of 1 hour daily; some tolerate overnight therapy
• New growth usually seen after 2–3 months
• Good safety profile → can be used in children
• Side effects: irritation, scaling, folliculitis, regional lymphadenopathy
• Not suitable for eyebrows and beard
• Avoid the eyes; protect treated skin from UV
• Brown discoloration of skin and staining of clothes/linen
• Rinse with cool or lukewarm water (hot water increases staining of tiles and bathtub)

Topical Immunotherapy

• Not FDA approved, but seems the most effective option with the best safety profile for chronic severe AA
• Mechanism not fully understood:
• Decreased peribulbar CD4+/CD8+ ratio
• Shift of T lymphocytes from perifollicular to interfollicular areas and dermis
• Goal: create a contact dermatitis
• Most common sensitizers: diphenylcyclopropenone (DPCP) and squaric acid dibutyl ester (SADBE)
• Compounded in acetone, stored in opaque bottles (photodegradation)
• Protocol:
• Sensitize with a small amount of 2% solution on a small scalp area or other site (often the arm) 1 week before treatment
• Then apply weekly to the scalp starting at 0.0001%
• No washing for 48 h; protect from UV
• Increase concentration weekly until mild erythema and mild itching; continue at that concentration
• Highest concentration 2%
• Success 17%–75%; lowest in totalis and universalis
• Side effects: lymphadenopathy in 100%, severe contact eczema, skin discoloration including vitiliginous patches and hyperpigmentation on scalp and elsewhere
• Greater caution in atopic dermatitis and dark skin types

Photo(chemo)therapy

• UVB useful in some patients
• Oral and topical PUVA: may affect T-cell function and antigen presentation; may inhibit the local attack by depleting Langerhans cells
• Very high relapse rate, especially after tapering
• Long-term UV promotes all skin cancers, including melanoma → only in exceptional cases

Cyclosporine

• Systemic 4–6 mg/kg/day beneficial in some patients
• Side effects: elevated transaminases and cholesterol, headaches, dysesthesia, fatigue, diarrhea, gingival hyperplasia, flushing, myalgias
• Can combine with low-dose oral prednisone; may be considered with severe atopic dermatitis plus AA
• Side effects and high recurrence after discontinuation → relatively impractical

Camouflage, Wigs, and Hairpieces

• Extensive scalp AA (progressive despite treatment, or during treatment) can be camouflaged with wigs
• Women with eyebrow AA: consider permanent makeup
• Provide psychological support; support groups (National Alopecia Areata Foundation, www.naaf.org) helpful for patients and relatives

• Nonscarring, noninflammatory
• One or more roughly triangular, oval, or lancet-shaped patches in the fronto-temporal area
• A few terminal or vellus-like hairs often at the periphery; scalp normal
• Usually asymptomatic; hair elsewhere of normal density
• Unilateral 80%, bitemporal 20%
• A strip of normal-density hair between the patch and the forehead
• Present at birth or first appears before school age
• Reported in Asian and Caucasian patients; no sex predilection
• Unresponsive to medical treatment; hair transplantation or excision reasonable
• Often misdiagnosed as alopecia areata

• Hair loss common in secondary or tertiary syphilis
• Classic: irregular patchy loss scattered across the scalp, "moth eaten"
• Eyebrows may be shed; patchy loss in the beard or other hair-bearing areas
• Can be very difficult to distinguish from alopecia areata
• Histology: plasma cells, lack of peribulbar eosinophils, abundant lymphocytes in the isthmus
• Essential syphilitic alopecia: no other cutaneous sign of secondary syphilis; diffuse shedding resembling TE

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• Diverse group of scalp disorders causing permanent hair loss
• Primary cicatricial alopecia: idiopathic inflammatory diseases with a folliculocentric inflammatory process that ultimately destroys the follicle
• Secondary cicatricial alopecia: from almost any cutaneous inflammatory process of the scalp or physical trauma injuring skin and appendages
• All scarring alopecias: clinically loss of follicular ostia; pathologically replacement of follicles with fibrous tissue
• Psychosocially distressing; medico-surgically challenging

• Occurs in a heterogeneous group of hair disorders with a wide variety of causes
• Inflammation → permanent destruction of follicular stem cell structure → replacement with fibrous tissue
• Can be primary or secondary
• Differential in each case: alopecia areata, another form of cicatricial alopecia, temporal triangular alopecia, trichotillomania, secondary syphilis (alopecia areolaris)
• Hair loss ends in permanent alopecia
• No evidence-based treatment available

Epidemiology

• Inflammatory cicatricial alopecias are rare

Etiology and Pathogenesis

• Mechanisms of follicle stem cell destruction not completely understood; no cure
• Inflammatory infiltrate affects the upper, permanent portion of the follicle: infundibulum and below it the isthmus
• Isthmus houses pluripotent hair stem cells in the bulge region, where the arrector pili muscle attaches to the outer root sheath
• Bulge stem cells renew the upper follicle and sebaceous glands, and restore the lower cyclical follicle at the onset of each new anagen
• Damage to the bulge and sebaceous gland in the isthmus → incomplete hair cycle, possibly with chronic follicular inflammation and foreign body reaction → scarring hair loss
• Working classification by scalp biopsy pathology, North American Hair Research Society (NAHRS), 2001

Forms of Primary Cicatricial Alopecia

• Source: Olsen EA et al, NAHRS-sponsored Workshop on Cicatricial Alopecia, Duke University Medical Center, February 10–11, 2001 (J Am Acad Dermatol 2003)

Clinical Findings

• Usually affects the central and parietal scalp first, then other sites
• Isolated patches with atrophy and lack of follicular ostia, plus inflammatory changes: diffuse or perifollicular erythema, follicular hyperkeratosis, pigment changes, tufting, pustules
• Clinical inflammation may be absent, with inflammation only histologically in the deep dermis and subcutis
• 10× dermatoscope with and without polarized light: presence/absence of follicular ostia, perifollicular erythema, follicular hyperkeratosis
• Crucial: whole-scalp exam, detailed history, biopsies of an active lesion
• Itching or pain approximate disease activity but may be absent
• Indirect symptoms help, e.g. sun sensitivity → DLE
• Scalp biopsy required to confirm (as described under Biopsy)
• Keratosis follicularis spinulosa decalvans: cicatricial alopecia with follicular plugging; see Chapter 87 and online

Chronic Cutaneous Lupus Erythematosus (Discoid Lupus Erythematosus, DLE)

• See also Chapter 155
• DLE together with LPP: most common cause of inflammatory cicatricial alopecia
• Women > men; adults > children; first onset typically 20–40 years
• SLE develops in 26%–31% of children and about 5%–10% of adults with DLE
• Higher incidence of concurrent alopecia areata
• Associated with verruciform xanthoma and papulonodular dermal mucinosis
• Clinical presentation:
• One or more erythematous, atrophic, alopecic patches
• Follicular hyperkeratosis, hyperpigmentation, hypopigmentation, telangiectasia
• Hyperpigmentation frequently in the center of the lesion
• Active lesions sensitive or pruritic; may worsen after UV
• Pathology:
• Early active lesions: lymphocyte-mediated interface dermatitis, vacuolar degeneration of the basal layer, necrotic keratinocytes, thickened basement membrane, destruction of sebaceous glands
• Elastic fibers frequently destroyed throughout the reticular dermis
• Infiltrate mainly in the upper follicle, but also deeper follicle, interfollicular epidermis, and around periadnexal vessels
• DIF: linear granular IgG and C3 at the DEJ; also IgM, C1q, rarely IgA
• Management and treatment:
• Hydroxychloroquine 200–400 mg daily (adults) or 4–6 mg/kg (children): highly effective
• Baseline ophthalmologic exam and CBC required
• Bridge therapy: oral prednisone 1 mg/kg tapered over the first 8 weeks in adults with rapidly progressive disease
• Limited or slowly progressive DLE: intralesional triamcinolone acetonide 10 mg/cc every 4–6 weeks, alone or with oral therapy
• With or without topical class I or II corticosteroids
• Topical corticosteroids alone effective in milder DLE
• Oral acitretin and isotretinoin: some efficacy
• Mycophenolate mofetil, methotrexate, azathioprine only if the above fail
• Multimodal aggressive therapy in rapidly progressive DLE may reverse early alopecic patches and save follicles

Lichen Planopilaris (LPP)

• Follicular variant of lichen planus; with DLE, most common cause of primary cicatricial alopecia
• Subtypes: classic LPP, frontal fibrosing alopecia (FFA), Graham–Little syndrome
• Classic LPP: onset around the fifth decade; women > men
• Extracranial lichen planus in up to 28%
• FFA: predominantly postmenopausal women
• Graham–Little–Piccardi–Lassueur syndrome: very rare, mainly adult women
• LPP of the scalp, noncicatricial alopecia of eyebrows, axilla and groin, and keratosis pilaris
• Lichenoid drug eruptions can present as LPP
• Most common drugs: gold, antimalarials, captopril
• Actinic lichenoid drug eruption (sun-exposed sites only): quinine, thiazide diuretics
• Clinical presentations:
• Classic LPP: starts at the crown and vertex; perifollicular erythema and follicular hyperkeratosis
• Patches smaller, irregular, interconnected → reticulated pattern compared with DLE; overlap with DLE frequent
• Itching, burning, scalp sensitivity
• FFA: frontal, band-like or circumferential scarring alopecia
• Sometimes a few hairs spared in the original frontal hairline
• Follicular hyperkeratosis and perifollicular erythema in a band along the frontal hairline
• Eyebrow alopecia frequent
• Graham–Little syndrome: classic LPP on the scalp, nonscarring alopecia of axillae, pubic area, eyebrows, and keratosis pilaris of trunk and extremities
• Pathology (all three subgroups similar):
• Lymphocytic infiltrate and interface dermatitis in and around the upper permanent follicle
• Unlike DLE: vascular plexus NOT inflamed, mucin absent
• DIF: globular cytoid deposits of IgM (rarely IgA, IgG or C3) in the dermis around the infundibulum
• Management and treatment:
• First line for moderately active classic LPP: intralesional triamcinolone acetonide 10 mg/cc every 4–6 weeks, or combined with topical class I or II corticosteroids
• Oral therapy literature limited; cyclosporine, retinoids, antimalarials, griseofulvin help in rapidly progressive LPP
• Oral corticosteroids as bridge in the first weeks for very active cases
• FFA: lower-dose intralesional triamcinolone (2.5–5 mg/cc), or topical minoxidil or tacrolimus; no effective treatment reported yet
• Graham–Little: managed like classic LPP

Classic Pseudopelade of Brocq (PPB)

• Idiopathic lymphocytic primary cicatricial alopecia, mainly of the scalp
• Second most common cause of primary cicatricial alopecia (as stated in source)
• Most often women aged 30–50 years
• Clinical presentation:
• Vertex and occipital scalp
• Small flesh-toned alopecic patches with irregular margins: "footprints in the snow"
• May present as a noninflammatory centrifugally spreading patch → possibly a variant of CCCA in Caucasians
• Follicular hyperkeratosis and perifollicular/diffuse erythema mostly absent
• May overlap clinically with LPP
• Pathology:
• Early: sparse to moderate lymphocytic infiltrate around the infundibulum with complete destruction of sebaceous glands
• Late: follicles completely replaced by fibrous tracts
• Unlike DLE and LPP: interface dermatitis usually absent; elastic fibers preserved and thickened
• Management and treatment:
• First choice: intralesional triamcinolone acetonide 10 mg/cc every 4–6 weeks plus topical corticosteroids
• Hydroxychloroquine, oral prednisone, isotretinoin: some effectiveness

Central Centrifugal Cicatricial Alopecia (CCCA)

• Lymphocytic primary cicatricial alopecia, mainly in women of color
• Unclear contribution of chemical processing, heat, traction, or other trauma
• Rarely in Caucasians (sometimes called "central elliptical pseudopelade") and African-American men
• Debated whether CCCA is a variant of PPB (clinical and histologic similarities)
• Clinical presentation:
• Skin-colored patch of scarring alopecia on the crown, gradually spreading centrifugally to the parietal areas
• Perifollicular hyperpigmentation and polytrichia may be present
• Itching, tenderness, "pins and needles" sensations
• Pathology: limited studies; similar to PPB
• Management and treatment:
• Topical corticosteroids and tetracycline effective in active progressive cases
• Some recommend switching to more natural, less traumatizing hair care
• Wigs and hairpieces frequently used for camouflage

Alopecia Mucinosa (AM)

• Indurated, well-demarcated erythematous or skin-colored patches of scarring or nonscarring alopecia
• May have diffuse hair loss and eyebrow alopecia
• Some cases: grouped follicular papules, follicular cysts, follicular hyperkeratosis
• Early lesions: mucin in the outer root sheath; advanced: entire pilosebaceous unit replaced by pools of mucin
• Strictly NOT a primary cicatricial alopecia: follicle not replaced by a true scar
• Idiopathic or with cutaneous T-cell lymphoma / mycosis fungoides
• Cell atypia and monoclonal T-cell populations can occur in both the idiopathic and the lymphoma-associated forms
• Management and treatment:
• Complete workup to exclude mycosis fungoides and Sézary syndrome (its advanced endpoint)
• Effective: oral corticosteroids, minocycline, isotretinoin
• Variable outcomes: topical and intralesional corticosteroids, dapsone, indomethacin, light therapy

Folliculitis Decalvans (FD)

• About 11% of all primary cicatricial alopecia cases
• Young and middle-aged adults, slight male preference
• Suspected factors: Staphylococcus aureus infection, hypersensitivity to "superantigens", defective host cell-mediated immunity
• Clinical presentation:
• Often starts at the vertex: erythematous alopecic patches, follicular pustules, follicular hyperkeratosis
• Tufted folliculitis typical (also in other cicatricial alopecias): multiple hairs (5–15) from one dilated follicular orifice
• Older lesions may lack pustules but scarring may continue
• Possible overlap with acne keloidalis: some AKN patients develop progressive FD-like scarring elsewhere on the scalp
• Pain, itching, burning
• Pathology:
• Early: keratin aggregation in the infundibulum with numerous intraluminal neutrophils; intra- and perifollicular neutrophilic infiltrate
• Sebaceous glands destroyed early
• Advanced: neutrophils, lymphocytes, plasma cells extending into the dermis; frequent hair shaft granulomas with foreign-body giant cells
• End stage: follicular and interstitial dermal fibrosis, hypertrophic scarring
• Management and treatment:
• Generally difficult; activity may persist many years
• Bacterial cultures with sensitivities recommended
• Eradicate S. aureus with minocycline, erythromycin, cephalosporins, sulfamethoxazole-trimethoprim
• Relapse often after stopping → may need low-dose antibiotics for many years
• Rifampin + clindamycin: good response but more side effects
• Oral fusidic acid alone or combined: effective in some
• Combine oral therapy with topical antibiotics (mupirocin, 1.5% fusidic acid, 2% erythromycin) and antibacterial cleansers
• Intralesional triamcinolone acetonide 10 mg/cc every 4–6 weeks reduces inflammation, itching, burning, pain
• Intranasal S. aureus eradication with topical antibacterials useful

Dissecting Folliculitis (DF)

• Also dissecting cellulitis or perifolliculitis capitis abscedens et suffodiens of Hoffman
• Related to acne conglobata and hidradenitis suppurativa → follicular occlusion triad
• Mainly young men 18–40 years; African-American men more often than Caucasian
• Pathogenesis may include follicular occlusion, seborrhea, androgens, secondary bacterial overgrowth, and abnormal host response to bacterial antigens
• Clinical presentation:
• Fluctuating nodules, abscesses, sinuses with spontaneous pus discharge; erythematous follicular papules and pustules
• Initial lesions mostly vertex and occipital scalp
• Multifocal lesions form an intercommunicating ridge; pressing one region discharges seropurulent exudate elsewhere
• Pruritic and tender
• Chronic relapsing course → cicatricial alopecia, possibly with hypertrophic or keloidal scars
• Pathology:
• Early: intra- and perifollicular neutrophilic infiltrate with follicular occlusion
• Advanced: interconnecting sinus tracts lined by squamous epithelium, follicular perforation, perifollicular and deep dermal abscesses
• Management and treatment:
• Multimodal: systemic antibiotics (minocycline, tetracycline, cloxacillin, erythromycin, cephalosporin, clindamycin), intralesional corticosteroids, oral prednisolone
• Antibiotic benefit likely anti-inflammatory rather than antibacterial
• Isotretinoin 0.5–1 mg/kg/d: prolonged remission
• Exceptional for extreme refractory cases: incision and drainage of painful nodules, marsupialization with curettage, complete scalp extirpation with skin grafting

Acne Keloidalis Nuchae (AKN)

• Mainly African-American men aged 14 to 25
• Idiopathic primary cicatricial alopecia; may be triggered by trauma (shirt collars) or infection (Demodex or bacteria)
• Clinically: skin-colored follicular papules, pustules, plaques, and keloid-like scarred lesions on the occipital scalp
• Histology: acute inflammation with neutrophilic or lymphocytic infiltrate and chronic granulomatous inflammation around the isthmus and lower infundibulum
• Treatment usually difficult and protracted:
• First choice: monthly intralesional triamcinolone acetonide (10–40 mg/mL) alone or with topical 2% clindamycin or oral tetracyclines
• Mild cases: class I or II topical steroids ± topical antibiotics
• Cryotherapy and laser therapy: some success
• Surgical excision of extensive keloidal lesions only for refractory, extensive, symptomatic cases

Acne Necrotica (Varioliformis)

• Very rare, chronic; mainly adults
• Frontal and parietal scalp and seborrheic areas of the face
• Umbilicated, pruritic or painful papules with central necrosis
• Leaves varioliform (smallpox-like) scars
• Histology: suppurative, necrotic, infundibular folliculitis with lymphocytic or mixed infiltrate
• Treatment: oral antibiotics, isotretinoin, intralesional or topical corticosteroids; excision of larger scarred areas

Erosive Pustular Dermatosis

• Uncommon; mainly elderly women
• Lesion: suppurative, necrotic, erosive papule or plaque
• Histology: early nonspecific; older lesions extensive chronic mixed dermal infiltrate, later dermal fibrosis
• Treatment: class I or II topical steroids ± topical antibiotics, systemic antibiotics, oral isotretinoin

• Alopecia areata
• Secondary cicatricial alopecia
• Temporal triangular alopecia
• Trichotillomania
• Secondary syphilis (alopecia areolaris)

• Once the follicle is destroyed and replaced by fibrous tissue, no hope for regrowth
• Medical therapy may fail; inflammation may continue → disfiguring permanent alopecia

• Main goal: stop the inflammation and further progression
• Extensive loss and/or treatment failure → camouflage, hairpieces, wigs
• Women with extensive crown/vertex LPP benefit greatly from a well-designed hairpiece, especially if the frontal hairline is preserved; more comfortable than a full wig
• Hair restoration surgery (HT, scalp reduction) for burnt-out cicatricial alopecia
• No disease activity for at least 1 year without therapy
• Warn about limited graft survival and recurrence, apparently higher in neutrophilic primary cicatricial alopecia

• Etiology and pathogenesis:
• Permanent loss from scalp conditions not related to the follicle; the primary event develops outside the FU → incidental follicle destruction
• Causes: congenital defects, trauma, inflammatory conditions, infections, neoplasms, rarely drugs
• Permanent chronic traction alopecia and surgical scars also count
• Clinical findings:
• Thorough history crucial
• Early diagnosis may rest on specific clinical/histologic features of the underlying disorder
• Follicular orifices lost; histology shows extensive scarring with fibrosis, loss of elastic fibers and adnexal structures
• Differential diagnosis:
• Primary cicatricial alopecia
• Alopecia areata
• Temporal triangular alopecia
• Trichotillomania
• Secondary syphilis (alopecia areolaris)
• Prognosis: depends on the underlying disease; once scar forms and adnexa are destroyed, no regrowth
• Treatment: specific for active conditions; in localized end-stage lesions, hair restoration surgery is the mainstay

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• Acute or chronic mechanical insult → reversible or irreversible alopecia
• Three types: (1) acute trauma, (2) prolonged traction, (3) pressure

• Usually fine streaks of hair loss in the injured area; contusion or destruction of wound borders → irregular, large patches
• After scalp surgery, especially extensive scalp reduction or large donor strip harvesting, if too much tension at closure
• Usually reversible, but can be permanent
• Traumatic birth-induced alopecia infrequent: extractor marks, tears, contusions, or resulting infections
• Aplasia cutis congenita: consider in the differential of cicatricial alopecia at birth

• Prolonged traction → transient loss or, if continued, follicular atrophy → cicatricial alopecia
• Causes: tight ponytails, braids, heavy dreadlocks, extensive use of rollers
• Marginal traction alopecia more common in African-American women (braiding, weaving; ethnic differences in hair fragility and styling)
• Patchy frontal/temporal traction alopecia in Sikh boys (tight "topknot")
• Cicatricial traction alopecia: HT if the patient stops injurious hairstyles and has sufficient donor hair

• Greek: tricho = hair, tillo = pull, mania = excessive excitement
• Traumatic alopecia from an irresistible compulsion to pull out, twist or break one's own hair
• Relatively common; estimated incidence 1 million Americans
• Two forms:
• Infantile / early-onset: starts in early childhood, typically short duration, may resolve spontaneously or with simple interventions
• Analogous to habits like thumb sucking
• Boys more often affected
• Around or after puberty: more chronic, sign of more severe psychopathology
• Classified as an impulse control disorder
• Women far more often affected
• Clinical: single or multiple asymmetric, occasionally geometric patches on scalp or other areas
• NOT smoothly bald (unlike AA): short or bristly anagen hairs
• Telogen hairs plucked easily; anagen hairs plucked, twisted, broken at various lengths
• Regrowing anagen hair must reach a certain length before it can be plucked again
• Differential: alopecia areata, tinea capitis
• Scalp biopsy diagnostic if in doubt: increased catagen hairs, trichomalacia, pigment casts in the follicular canal
• Therapy: education of patient and/or parents; in late-onset cases, treat the underlying psychopathology
• Patients who deny self-infliction usually refuse psychiatric/psychological referral → treatment difficult

• After a patient was unconscious and immobile for some time
• Presumably ischemia from body weight pressure on a scalp area
• Ischemic injury may cause permanent hair loss

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• Structural defects of the hair shaft; inherited or acquired
• Inherited forms may cause increased breakage or unruly scalp hair

Trichorrhexis Nodosa

• Inherited or acquired
• Breach in the cuticle → separation and fraying of cortical fibers → node-like swelling → fracture with a splayed paintbrush or fan-like end
• Congenital: at birth or in the first months
• Rarely with teeth and nail defects or hyperkeratosis
• Metabolic associations: argininosuccinic aciduria (Chapter 131), Menkes syndrome, trichothiodystrophy
• Acquired form much more common:
• Proximal: more common in African-American women, usually after repeated chemical or hot-comb straightening
• Distal: mostly from excessive brushing, teasing, or chemicals (bleaching, permanent waves)
• Advise avoiding harsh chemical or physical styling
• Proximal form may take months to a year to resolve even after stopping the hair care

Trichoschisis and Trichothiodystrophy

• Trichoschisis: clean transverse fracture at a site of focal cuticle absence
• Usually, but not specifically, a marker for sulfur-deficient hair in trichothiodystrophy (Chapter 139)
• Scalp hair, eyelashes, eyebrows short and brittle
• Hair cysteine content <one-half normal, mainly from a major reduction and altered composition of ultrahigh-sulfur matrix proteins
• Polarized light: "tiger tail" pattern of alternating light and dark bands (from variable sulfur content)
• Confocal and scanning electron microscopy detect various structural abnormalities → hair excessively prone to breakage and weathering
• Diagnostic: sulfur and amino acid analysis of hair
• Identifies a group of autosomal recessive disorders with neuroectodermal abnormalities

Trichoclasis

• Common "greenstick" fracture of the hair shaft
• Transverse fracture splinted partly or completely by intact cuticle
• Cuticle, cortex and sulfur content normal
• No specific underlying disease; occurs in normal hair or with pili torti

Pili Torti and Menkes Syndrome

• Pili torti: shafts flattened and twisted on their axis, usually 180° (range 90°–360°), at multiple irregular intervals along an otherwise straight shaft
• Not a specific abnormality; seen in many syndromes and with other shaft disorders
• Inheritance mostly autosomal dominant; also autosomal recessive or sporadic
• Clinically: patchy alopecia with coarse stubble or longer broken hairs
• Hair fragility usually improves after puberty
• Menkes kinky hair syndrome (steely hair syndrome, trichopoliodystrophy):
• Pili torti combined with trichorrhexis nodosa, trichoclasis, trichoptilosis
• X-linked recessive multisystem disease beginning in infancy
• Depigmented hair, skin hypopigmentation, mental retardation, neurologic impairment from cerebral and cerebellar degeneration, plus bone and connective tissue degeneration
• Defective copper transport with intracellular copper accumulation → functional deficiency of copper-dependent enzymes
• Most patients die by age 3 years
• Copper uptake is normal → copper supplementation ineffective, but copper-histidine given immediately postpartum may prevent or ameliorate severe neurodegeneration
• Diagnostic: low serum copper and ceruloplasmin levels

Trichorrhexis Invaginata ("Bamboo Hair") and Netherton Syndrome

• Diagnostic marker for Netherton syndrome; may also occur sporadically or with other shaft abnormalities
• Netherton syndrome: autosomal recessive; triad of atopic diathesis, ichthyosiform skin changes, trichorrhexis invaginata (Chapter 49)
• Primary defect: abnormal keratinization in the keratogenous zone → intussusception of the hard, fully keratinized distal shaft into the soft, incompletely keratinized proximal shaft
• Typical "ball-and-socket" deformity
• After fracture: golf tee-shaped distal end
• Affected short brittle hairs may be scattered over the scalp → sampling errors
• Therapy: retinoids and phototherapy may be considered; often improves with age

Monilethrix

• Extremely short, brittle, fragile, beaded hairs emerging from hyperkeratotic follicular orifices
• Elliptical nodes 0.7–1 mm apart, with tapered nonmedullated constrictions (internodes)
• Internodes are the predetermined breaking points; often show longitudinal ridges
• Mostly autosomal dominant with variable expression; rarely autosomal recessive
• AD form: mutations in one of three type II hair keratin genes: KHb1 (KRT81), KHb3 (KRT83), KHb6 (KRT86)
• AR form: desmoglein 4 (DSG4)
• Mildest cases localized to the occiput or nape
• May occur alone or with keratosis pilaris, nail and teeth abnormalities, syndactyly, cataracts, physical retardation
• Retinoids and topical minoxidil may help; often improves spontaneously with age

Localized Autosomal Recessive Hypotrichosis

• Rare autosomal recessive; localized sparse broken hair of scalp and eyebrows
• Mutation in desmoglein 4 (DSG4)
• Unlike monilethrix, no beading

Uncombable Hair Syndrome

• Also spun glass hair or pili trianguli et canaliculi
• Autosomal dominant or sporadic
• Rigid shafts with triangular or kidney bean-shaped cross section; also irregular forms (flattened, heart-shaped, longitudinal grooves)
• Hair dry, coarse, usually blond to light brown, spangled appearance
• Frizzy, unruly, kinky, unmanageable from infancy; grows in multiple directions, cannot be combed flat
• Males and females equally
• Most often first in early childhood, but can develop as late as age 12 years
• Polarized light: homogeneous band on one edge (shadow cast by the pili canaliculi)
• No definitive therapy; may improve over time untreated

Wooly Hair

• Rare congenital structural anomaly; extreme kinkiness of scalp hair in Caucasians
• At birth or in the first months
• Curls average diameter only 0.5 cm, lying closely together → hard to comb; hairs may be more fragile
• Growth rate usually normal, but anagen may be truncated → hair does not grow long
• Shaft: elliptical cross section, axial rotation, kinked
• Forms:
• Wooly hair nevus: circumscribed
• Whole-scalp forms: autosomal dominant wooly hair (hereditary wooly hair) and the much rarer autosomal recessive (familial wooly hair)
• AR form can be syndromic with palmoplantar hyperkeratosis and heart anomalies
• No treatment; avoid harsh physical and chemical cosmetic treatments
• Most pronounced in childhood; often less severe in adulthood

Marie–Unna Hypotrichosis

• Autosomal dominant
• Sparse or absent hair at birth; variable coarse, wiry growth in childhood (scalp and eyebrows)
• Later scalp loss in a pattern resembling AGA, with scattered thick hairs in balding areas
• Body hair sparse or absent
• Males and females equally
• Light and electron microscopy: irregular twisting, longitudinal ridging, cuticle peeling
• Diffuse follicular hyperkeratosis and facial milia-like lesions may be present
• Mutations in the upstream untranslated open reading frame of the hairless gene, mapping to chromosome 8p21
• No known treatment

Pili Annulati

• Ringed hairs; autosomal dominant or sporadic; no increased breakage
• Present at birth or develops in infancy
• Alternating light and dark bands from air-filled cavities in the cortex
• Ringing clinically visible only in blond or light brown hair
• Gene locus: chromosome 12q24
• No treatment necessary; gentle hair care

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• Excessive terminal hair growth in a male distribution in women
• Ferriman–Gallwey score of 8 or more
• Distinguish from hypertrichosis: generalized excess hair, hereditary or medication-induced, in men and women
• Nonsexual pattern; not caused by androgen excess (though hyperandrogenism may aggravate it)

• Terminal body hair in women in a male distribution
• Ferriman–Gallwey score ≥8 = hirsute
• Mild to moderate hirsutism with regular menses → most likely idiopathic hirsutism; hormone testing not necessary
• Hormone testing necessary with moderate to severe hirsutism and in all hirsute women with irregular menses or signs of virilization
• Therapy should always include direct hair removal, with or without medical therapy

• About 5% of women of childbearing age have mild to severe hirsutism (Ferriman–Gallwey ≥8)

• Before puberty: body hair is vellus (small, straight, fair); sebaceous glands small
• At puberty, rising androgens convert vellus follicles in specific areas into terminal follicles (larger, curlier, darker)
• Terminal body (sexual) hair entirely androgen dependent, especially testosterone
• Beard hair requires higher androgen levels than pubic and axillary hair
• Elsewhere (e.g. forehead, cheeks): androgens greatly enlarge sebaceous glands while hair stays vellus
• Hirsutism = interaction of androgen level and follicle sensitivity
• "Idiopathic hirsutism": hirsutism without evidence of androgen excess
• Most women with a twofold or greater androgen elevation have some hirsutism; others instead show a "hirsutism equivalent": acne vulgaris, seborrhea, pattern alopecia, hidradenitis suppurativa, hyperhidrosis
• Androgen excess relates to increased bioactive free testosterone
• Total testosterone = albumin-bound + SHBG-bound testosterone
• Hirsute women commonly have relatively low SHBG → more bioactive testosterone → free testosterone may be elevated with normal total testosterone
• SHBG suppressed by hyperinsulinemia of insulin resistance and by androgen excess itself
• SHBG also low in hypothyroidism; rarely congenitally absent

• 9 body areas, each scored 1 to 4:
• Upper lip, chin, chest, abdomen, pelvis, upper arms, thighs, upper back, lower back
• (Figure is a scoring diagram; area labels and 1–4 grading recovered, the drawings were not)

• Scoring difficult because most women use hair removal
• Useful: patient self-rates hair growth with images in the Ferriman–Gallwey areas (upper lip, chin and cheeks, chest, abdomen, pubic area and lower abdomen, arms, legs, upper back, lower back, buttocks)

• Mild hirsutism (Ferriman–Gallwey 8–15), regular menses, no risk factors → reasonable not to test (very high likelihood of idiopathic hirsutism)
• Moderate or severe (score >15), or features suggesting an underlying disorder → rule out androgen excess
• Onset or progression of hirsutism, or virilization (clitoromegaly, increasing muscularity) → concern for androgen-secreting neoplasm
• Most androgenic drugs are NOT detected by testosterone assays → history is key
• Drugs: anabolic or androgenic steroids; risk higher in athletes, or with endometriosis or sexual dysfunction
• Valproic acid is unique in raising plasma testosterone
• PCOS is a frequent cause → look for anovulation (menstrual irregularity), obesity, metabolic syndrome, insulin resistance (acanthosis nigricans, family history of type 2 diabetes)
• With risk factors like menstrual irregularity, even normal degrees of focal hirsutism usually reflect androgen excess
• Other endocrinopathies:
• Cushing syndrome: truncal obesity, moon facies, buffalo hump, purple striae, proximal muscle weakness
• Virilizing congenital adrenal hyperplasia or PCOS: history of premature pubic hair or acne
• Hyperprolactinemia: galactorrhea
• Acromegaly: coarsening facial features, hand or foot enlargement

• Androgen-secreting tumors
• Adrenal: adenoma; adenocarcinoma (rare); ectopic ACTH-secreting tumor (rare)
• Ovarian: gonadal stromal tumor; thecoma; lipoid tumor
• Functional androgen excess
• Adrenal enzyme deficiencies (congenital adrenal hyperplasia): early-onset 21-hydroxylase deficiency; late-onset 21-hydroxylase deficiency; 11β-hydroxylase deficiency; 3β-ol dehydrogenase deficiency
• Cushing syndrome
• Polycystic ovarian disease (with or without adrenal contribution)
• Hyperthecosis
• "Idiopathic" hirsutism
• Medication/drug use
• Source: Hughes CL, Hirsutism, in Disorders of Hair Growth (Olsen EA, ed), 1994, Table 14-2

• Once androgen excess is confirmed:
• Pregnancy test (if amenorrhea)
• Pelvic ultrasonography (suspected ovarian neoplasm or PCOS)
• DHEA-S and early-morning 17-hydroxyprogesterone (suspected CAH or adrenal neoplasm)
• Prolactin
• May include thyroid function, adrenocortical function, IGF-I
• Dexamethasone suppression testing typically starts further workup to find the androgen source
• Not suppressible → consider Cushing syndrome, neoplasm, PCOS
• Suppressible → ACTH stimulation test for CAH
• Suspected undetected neoplasm → imaging, e.g. abdominal CT for adrenal neoplasm

• Hirsutism tends to worsen with age
• Underlying hyperandrogenemic disorders must be ruled out

• Goals: remove existing terminal hair and prevent further vellus-to-terminal transformation
• Direct hair removal for all hirsute women; moderate to severe hirsutism and androgen excess → add medical therapy
• Nonpermanent hair removal:
• Shaving, depilatories (last 12 hours to a few days)
• Waxing, threading, sugaring (last up to 4 weeks)
• Permanent hair removal:
• Electrolysis (for white and blond hair)
• Photoepilation (intense pulsed light or laser): several sessions at 4–6-week intervals, because only anagen follicles with dark bulbs are destroyed
• Topical eflornithine: slows the hair cycle; combinable with every hair removal technique
• First-line medical therapy: oral contraceptives, possibly with antiandrogens
• Glucocorticoids: for nonclassic CAH with suboptimal response to or intolerance of OCs/antiandrogens, or seeking ovulation induction
• GnRH agonists: severe hyperandrogenemia (e.g. ovarian hyperthecosis) with suboptimal response to OCs and antiandrogens

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• Androgen-independent generalized increased hair growth on the body; hair terminal or lanugo
• Acquired or inherited
• Congenital hypertrichosis lanuginosa:
• Generalized overgrowth of silvery blonde to gray lanugo hair at birth or early childhood
• Rare; thought autosomal dominant with variable expressivity
• Most have anomalous dental eruption
• Lanugo may persist, increase or decrease with age
• Ambras syndrome (hypertrichosis universalis congenita):
• Autosomal dominant
• Much longer, thicker hair over the entire body, accentuated on the face, ears and shoulders
• May have facial dysmorphism and dental anomalies
• X-linked dominant congenital generalized hypertrichosis: described in a five-generation family; accentuated on the face and upper body
• Gingival fibromatosis (autosomal dominant or recessive):
• Frequent hypertrichosis, mostly face, eyebrows, limbs, upper back
• May be associated with seizures and oligophrenia
• Hypertrichosis may be delayed until puberty, while gingival fibromatosis usually appears with eruption of the primary teeth

Clinical Features: rapid complete hair loss in one/more round-oval patches, typically 1-5cm, usually scalp, bearded area, eyebrows, eyelashes (less frequently other hairy areas)

• Early course may spare gray hair (white hairs rarely affected); sudden hair whitening may represent widespread alopecia areata in salt-and-pepper-hair patient
• ~10% of patients (especially long-standing/extensive cases) develop uniform nail pits (transverse/longitudinal lines); onychomadesis, red/spotted lunulae less often; dermoscopy typically shows diffuse round/polycyclic perifollicular yellow dots
• Alopecia totalis = complete scalp hair loss; alopecia universalis = complete all-body hair loss; ophiasis = confluent temporal/occipital scalp loss; sisaipho = entire scalp except that area
• Rarely diffuse pattern mimicking pattern alopecia; clues: periodic regrowth history, nail pitting, tapered fractures/"exclamation point" hairs
• Alopecia areata = anagen effluvium (inflammatory hair matrix insult → shaft tapering, anagen hair fracture); as hair miniaturizes/converts anagen-to-telogen, remaining lower hair portion rises above scalp level → exclamation point hair
• Higher-than-usual incidence of atopic dermatitis, Down syndrome, lichen planus, autoimmune diseases (SLE, thyroiditis, diabetes, myasthenia gravis, vitiligo) — but most cases occur without associated disease; routine screening of little value unless prompted by signs/symptoms
• Migratory poliosis of scalp may be forme fruste — migrating circular white-hair patches, never lose hair (histology resembles alopecia areata)

Etiologic Factors: oligoclonal/autoreactive T lymphocytes in peribulbar infiltrate; many respond to immunomodulating drugs

• Nude-mice SCID grafting model: affected scalp skin loses infiltrating lymphocytes and regrows hair; injecting T lymphocytes with scalp homogenate reproduces alopecia; follicular melanocytes can substitute for scalp homogenate (evidence follicular melanocytes = target for activated T cells) — supported by white hair rarely affected, regrowing hair often depigmented
• Early hair loss phase mediated by type 1 cytokines (IL-2, IFN-γ, TNF-α)
• ~25% have positive family history; twin case reports; "early-onset, severe, familial clustering" subset has significant HLA-DR4/DR11/DQ7 association; "later-onset, milder, better-prognosis" subset has lower familial rate, lacks these HLAs
• Familial alopecia areata + hereditary thrombocytopenia related to chromosome 17 gene mutations described; PTPN22 R620W variant associated with various autoimmune disorders including alopecia areata (early onset, widespread hair loss, positive family history)

Histology: early — lymphoid infiltrate in peribulbar area of anagen/early catagen follicles; eosinophils may be present; lymphocyte-mediated bulb damage → melanin pigment incontinence in surrounding stroma

• Many catagen hairs + pigment casts in follicular canal can cause histologic confusion with trichotillomania; follicles eventually miniaturize (small dystrophic anagen hairs high in dermis, persistent lymphocytic peribulbar infiltrate)
• Fibrous tract remnants beneath miniaturized bulbs may contain lymphoid cells, eosinophils, melanin pigment; over time lymphocytes disappear (focal eosinophils/pigment remain), finally only focal melanin pigment remains
• Every alopecia areata histologic feature may be seen in syphilis

Differential Diagnosis: sharply circumscribed patch + exclamation point hairs + no scarring = indicative; consider tinea capitis, androgenetic alopecia, early LE, syphilis, congenital triangular alopecia, alopecia neoplastica, trichotillomania

• Southwest Asia endemic areas: Pheidole ants shear hair shafts overnight, causing round patches closely mimicking alopecia areata

Treatment: highly variable natural course — some patches regrow in weeks untreated (anecdotal success reports must account for high spontaneous recovery rate)

• Intralesional corticosteroid injections = treatment of choice for localized cosmetically-conspicuous patches (frontal hairline, eyebrow); triamcinolone 2-5mg/mL intradermal or superficial subcutaneous; large volumes/higher concentrations increase atrophy risk; injection under pressure or small-bore syringe increases retinal artery embolization risk
• Topical corticosteroids and topical JAK inhibitors less effective but useful for children; pulsed oral corticosteroids for rapidly progressing/widespread disease (long-term treatment often needed to maintain growth — weigh risks/benefits)
• 66-patient study: monthly methylprednisolone (500mg/day x3 days, or 5mg/kg BID x3 days for children) — >60% widespread patchy alopecia responded; half of alopecia totalis responded; quarter of universalis responded; ophiasis didn't respond; predictors of response: disease duration ≤6 months, onset age <10, multifocal disease
• Oral JAK inhibitors show excellent response in many; low-dose methotrexate option for JAK contraindications; phosphodiesterase 4 inhibitors and platelet-rich plasma roles unclear
• Contact sensitization induction (squaric acid dibutyl ester, DNCB, diphencyprone) useful in refractory cases; anthralin no added benefit; topical/oral PUVA option for refractory/widespread lesions
• Topical minoxidil combined or single-agent; sulfasalazine up to 1.5g TID used; cyclosporine useful for initial remittive therapy
• Psoriasis biologics = mixed/disappointing results (alopecia areata has developed during biologic therapy for other conditions); eosinophils often noted in infiltrate — tocilizumab reported effective
• 308nm xenon chloride excimer laser (300-2300 mJ/cm²/session) regrowth after 11-12 sessions over 9-11 weeks; periocular pigmentation/iris darkening with travoprost/bimatoprost/latanoprost for eyelash disease (mixed results); botanicals (peony glucosides, glycyrrhizin) show some promise
• Tremendous psychological stress — education, cosmetic alternatives (wigs), innovative therapy research all important; National Alopecia Areata Foundation (www.naaf.org) resource

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• Excessive normal telogen club hair shedding, most often 3-5 months after premature anagen-to-telogen conversion induced by surgery, parturition, fever, drugs, dieting, or traction
• Local early telogen conversion patches induced by papulosquamous scalp diseases; alternatively follicles may remain in prolonged anagen (pregnancy) — delivery releases many follicles simultaneously into telogen, shedding 3-5 months later
• Telogen prolongation during pregnancy → initial hair loss wave soon after delivery or heralding early pregnancy termination
• Anagen phase shortening occurs in pattern (androgenetic) alopecia and chronic telogen effluvium — greater telogen proportion at any time = chronic increased telogen shed
• Topical minoxidil may cause telogen effluvium (premature telogen termination needed to initiate anagen in responding follicles → early telogen release, brief effluvium)
• Whatever cause: each hair has visible depigmented club-shaped bulb, lacks sheath

Assessment: slow pull test (minimal discomfort) — >4-6 club hairs abnormal (influenced by recent shampooing: 2-3 hairs abnormal on freshly-shampooed scalp, combing, effluvium phase)

• Trichogram (50 hairs plucked with Kelly clamp+rubber drains) gives anagen/telogen ratio but hair pull/combing/trichoscopy preferred by patients
• Dr. Jeffrey Miller's 1-minute combing technique: comb 1 minute before shampooing x3 consecutive days, vertex-to-anterior-hairline; normal range 10-15 lost hairs, >50 = common in telogen effluvium; serial counts monitor progress

Causes/Workup: may relate to protein/nutrient deprivation; assess diet, iron saturation/ferritin (iron may just be overall nutritional status marker); supplement identified deficiencies, encourage varied diet

• Investigate blood loss sources (menstrual, GI); hypothyroidism, allergic contact dermatitis to hair dyes, renal dialysis with secondary hypervitaminosis A also associated; many drugs cause drug-induced telogen effluvium
• Postnatal infant telogen effluvium: birth to 4 months age, usually regrows by 6 months; chronic telogen effluvium may relate to anagen phase shortening, may respond to 5% minoxidil solution
• Trichodynia common in telogen effluvium and pattern hair loss; may coexist with depression, obsessive personality disorder, or anxiety signs

Histology: 4mm punch biopsy normally shows 25-50 hairs on transverse sectioning; >12-15% terminal follicles in telogen = significant anagen-to-telogen shift

• Pattern (androgenetic) alopecia: miniaturization, variable hair shaft diameter, increased telogen proportion; traction alopecia/trichotillosis: increased catagen+telogen hairs (pigment casts, empty anagen follicles, trichomalacia, catagen hairs distinguish from simple telogen effluvium)

Treatment: usually no specific therapy needed — hair loss stops spontaneously within months, regrows; drug-induced responds to discontinuation; good prognosis if specific cause pinpointed

• Address papulosquamous scalp disorders; determine iron/thyroid status; balanced diet encouraged, targeted nutritional supplementation possibly beneficial
• Avoid high-dose biotin (interferes with thyroid/cardiac enzyme lab assays); mouse model shows sonic stress can induce catagen conversion (potential future study tool)

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• Usually hair shaft fracture related to alopecia areata, syphilis, chemotherapy, or heavy metal ingestion; trichograms show tapered fractures; only anagen hairs affected (10% telogen scalp hairs have no matrix, unaffected)
• Scalp cooling can reduce chemotherapy hair loss; topical minoxidil shortens baldness period by average 50 days
• Loose anagen syndrome (Price, 1989): anagen hairs pulled from scalp with little effort; mostly blond girls, usually improves with age; related to hair cuticle defect (cuticle folds back like rumpled sock instead of anchoring firmly, allowing shaft extraction)
• Woolly hair can associate with loose anagen syndrome; keratin mutation E337K in K6HF identified in 3/9 studied families; colobomas also associated
• Anagen hairs easily extracted from active LE and lichen planopilaris areas (usually lack root sheath normally surrounding plucked anagen hair); anagen effluvium also described in pemphigus lesions

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Male-Pattern Baldness: shows in teens/20s/early 30s, gradual loss chiefly vertex/frontotemporal; may begin any time post-puberty; "whisker hair" or acquired progressive hair kinking may be first sign

• Several patterns (including female-patterned hair loss in men) but most common = biparietal recession + vertex hair loss; rate varies individually
• Follicles produce finer/lighter hairs each cycle until terminal hairs replaced by vellus; hair shaft diameter varies significantly during process; parietal/occipital areas usually permanently spared from miniaturization — most suitable hair transplant donor sites
• Early-onset male-pattern alopecia related to androgen receptor gene, closely related to PCOS in women; polygenic inheritance arguments: high prevalence, gaussian population distribution, increased risk with more affected relatives, greater risk with severely- vs. mildly-affected relative, greater import of affected mother than father
• Dependent on adequate androgen stimulation, related to androgen receptor gene; eunuchs castrated before/during adolescence don't bald (androgen therapy can induce it); balding scalp shows increased 5α-reduction of testosterone → increased dihydrotestosterone; congenital 5α-reductase deficiency (type 2 isoenzyme lacking) → no baldness
• Progressive anagen phase shortening as hair shaft diameter decreases (hairs narrow AND shorten); higher telogen proportion in affected area → greater telogen shed
• Histologically decrease in anagen, increase in telogen follicles present; follicular miniaturization and shaft diameter variability noted (particularly evident in transverse sections)
• Below miniaturized/telogen follicle level: vascular/fibromucinous fibrous tract remnant present (numerous in cross section); many mast cells in fibrous tract remnant (inflammatory cells absent)
• Sebaceous glands may be enlarged, hair thinning may associate with solar elastosis; sparse lymphoid inflammation with spongiosis common at follicular infundibulum/hair bulge level
• Miniaturized human follicles grafted onto immunodeficient mice regenerate quickly, as well or better than terminal follicles from same individual — suggests even advanced pattern alopecia may be reversible
• Partial reversal noted after chemotherapy or methotrexate psoriasis treatment; stem cell therapy research ongoing (potential platelet-rich plasma regrowth basis)
• Men with Kennedy disease (spinal/bulbar muscular atrophy, X-linked, androgen receptor gene CAG repeat expansion) have decreased pattern alopecia incidence

Treatment (Male): minoxidil promotes dermal papilla cell survival, prolongs anagen, enlarges shaft diameter/length; available OTC as solution/foam, better results with oral minoxidil (up to 5mg/day men; 1.25mg/day women to minimize facial hypertrichosis risk)

• 5α-reductase inhibitors (finasteride, dutasteride) increase apical scalp growth, rarely improve temple patterning; prostate cancer prevention trial (different dosage form) showed decreased cancer incidence but higher average Gleason score in cancers that occurred (possibly only lower-grade cancers prevented); impotence and depression also reported
• Other promising treatments: fluridil (topical antiandrogen suppressing human androgen receptor), topical adenosine, hormone-enriched topical cell culture medium
• Hair transplantation (occipital-area micrografts to anterior scalp) can satisfactorily recreate hairlines with excellent cosmetic results; platelet-rich plasma and microneedling roles being defined

Female-Pattern Alopecia (Androgenetic Alopecia in Women): diffuse hair loss throughout apical scalp, part wider anteriorly, typically frontal hairline sparing (subset shows "male" temporal recession pattern — should prompt virilization evaluation)

• Address cultural haircare practices and supplement use; large biotin doses interfere with lab assays, little benefit evidence
• Both sexes with pattern alopecia have higher 5α-reductase and androgen receptor levels in frontal vs. occipital follicles; hierarchy of androgen sensitivity within follicular units evidenced
• Other androgen excess evidence (hirsutism, menstrual irregularities, acne) or sudden onset → evaluate as for hirsutism; oral minoxidil and oral antiandrogens (spironolactone, cyproterone acetate) used (spironolactone <100mg/day less effective)
• Finasteride/dutasteride contraindicated in women who may become pregnant; hair transplantation, wigs, interwoven hair for cosmetic results
• Pilot study: topical melatonin appeared to prolong anagen phase, may be beneficial; telogen effluvium may worsen preexisting pattern alopecia — address reversible causes (seborrheic dermatitis, nutrient deficiency, thyroid disease)
• Platelet-rich plasma/microneedling role being defined (as in men); low-level (especially red spectrum) light has supporting evidence in both sexes

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• Compulsive hair plucking from scalp/brows/eyelashes; irregular alopecia patches with varying hair lengths; rough scalp texture from short broken-off hair remnants
• Mostly girls <10 years (boys/adults also engage); some patients report exquisite localized follicular pain/itch relieved only by plucking
• Ask "how" (not "if") hair removal is done; if unrevealing, shave 3cm² area — resulting hairs too short to pluck, normal regrowth in "skin window" within 3 weeks confirms diagnosis
• Biopsy (especially horizontal) may show empty anagen follicles, catagen hairs, pigment casts in infundibulum, trichomalacia, hemorrhage; alopecia areata shares many features — search for peribulbar lymphocytes/inflammatory cells in fibrous tract remnants to differentiate
• Usually OCD manifestation, may associate with depression/anxiety; may include trichophagia (compulsive plucked-hair swallowing) → gastric bezoar (Rapunzel syndrome)
• Treatment: behavior modification, psychotherapy, N-acetylcysteine, psychopharmacologic medication for compulsive disorders (attend to psychiatric comorbidities); valproic acid, quetiapine, naltrexone reported effective for some; bimatoprost for eyelash involvement (may darken light eyes)

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• Alopecia syphilitica: typical moth-eaten occipital scalp appearance, or generalized thinning, or alopecia-areata-resembling; eyebrows/eyelashes/body hair may be involved; may be first syphilis sign; histology mimics alopecia areata
• Follicular mucinosis (alopecia mucinosa): most often scalp/beard, boggy red plaque or hypopigmented patch with hair loss; comedo-like lesions may exude mucin when expressed
• Biopsy: mucin deposition in outer root sheath/sebaceous glands, stains as hyaluronic acid (not epithelial sialomucin); primary cases (no underlying disease) usually localized head/neck lesions in young people (may show clonality even without clinical progression)
• Secondary type associated with MF-type CTCL or chronic inflammatory skin disease; MF-associated lesions generally widespread/chronic in older patients; intralesional steroids and phototherapy reported useful
• Vascular/neurologic alopecia: most often lower extremities, seen with diabetes/atherosclerosis; meralgia paresthetica may cause outer-thigh anesthetic-area alopecia
• Endocrinologic alopecia: hypothyroidism → coarse, dry, brittle, sparse hair (telogen proportion 3-7x normal 10%); hyperthyroidism → extremely fine, sparse hair
• Congenital alopecia: total/partial loss or lack of initial growth, usually with other ectodermal defects (nails, teeth, bone); light sparse slow-growing hair
• Hypotrichosis of the scalp: group of monogenetic conditions, sparse hair in school-age patients progressing to near-total alopecia by 20s; generalized scalp, no accompanying findings; histology shows increased telogen hairs; mutations in lanosterol synthetase, APCDDD1, desmoglein 4, CDSN, KRT74, EPS8L3, RPL21, KRT71 genes
• Congenital triangular alopecia and aplasia cutis congenita = congenital localized hair disorder examples; hidrotic ectodermal dysplasia = diffuse hair abnormality with dental/nail changes
• Short anagen syndrome: reduced hair length, lifelong low-grade shedding; persistent alopecia after repeated chemotherapy may represent stem cell exhaustion
• Lipedematous alopecia: scalp thickening resembling thick cotton batting; hair normal or shortened/sparse; biopsy shows increased subcutaneous fat thickness + variable lymphoid inflammation; similar appearance from lupus-associated scalp mucinosis

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• Rare AR disorder, early-onset atrichia followed by papular eruption within first years of life; linked to chromosome 8p21, mutations in "hairless gene"

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• Anagen Phase: Active growth phase; lasts 2 to 6 years; 85 to 90% of scalp hair follicles.
• Catagen Phase: Brief involutional/apoptotic transition phase; lasts 2 to 3 weeks; <1% of hair follicles.
• Telogen Phase: Resting phase prior to shedding; lasts 3 months; 10 to 15% of hair follicles.
• Normal Daily Hair Shedding: 50 to 100 hairs/day.

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Androgenetic Alopecia (AGA / Pattern Hair Loss)

• Pathophysiology: Genetically determined sensitivity of hair follicles to Dihydrotestosterone (DHT) (produced by 5α-reductase conversion of testosterone) → progressive Follicular Miniaturization (terminal hairs convert to fine vellus hairs).
• Clinical Patterns:
• Male Pattern: Hamilton-Norwood classification (bitemporal recession and vertex thinning).
• Female Pattern: Ludwig classification (diffuse central crown thinning with preservation of frontal hairline).
• Pharmacotherapy:
• Topical Minoxidil 5%: Vasodilator; prolongs anagen phase; indicated for men and women.
• Oral Finasteride (1 mg daily): Selective Type II 5α-Reductase Inhibitor; decreases serum/scalp DHT by >60%; indicated for men (CONTRAINDICATED in women of childbearing potential).
• Alternatives: Oral Spironolactone (women), Oral Dutasteride (dual 5α-reductase inhibitor).

Alopecia Areata (AA)

• Pathophysiology: Autoimmune T-cell-mediated attack (CD4+/CD8+) on the hair follicle bulb resulting from loss of hair follicle immune privilege.
• Clinical Presentation: Smooth, circumscribed, non-scarring patches of hair loss on scalp or beard.
• Pathognomonic Dermoscopy Sign: "Exclamation Mark Hairs" (short broken hairs tapering proximally near scalp surface) at active patch margins.
• Severe Variants: Alopecia Totalis (100% loss of scalp hair); Alopecia Universalis (100% loss of all scalp and body hair).
• Pharmacotherapy:
• Localized Disease: Intralesional Triamcinolone Acetonide (5 mg/mL injected intradermally every 4–6 weeks); high-potency topical steroids.
• Severe / Extensive Disease: Oral JAK Inhibitors: Baricitinib (Olumiant) or Ritlecitinib (Litfulo) (FDA-approved systemic therapy for severe AA).

Telogen Effluvium (TE)

• Pathophysiology: Premature shift of a large percentage (>30%) of anagen growing hairs into the telogen resting phase triggered by a major acute metabolic stressor.
• Timing: Hair shedding begins 2 to 4 months AFTER the triggering event.
• Common Triggers: High fever / severe infection (COVID-19), Childbirth (Telogen Gravidarum), Major surgery, Severe psychological trauma, Rapid weight loss / crash dieting, Thyroid dysfunction, Iron deficiency.
• Diagnostic Test: Hair Pull Test POSITIVE (>6 telogen hairs easily extracted per pull). Self-limiting; complete regrow occurs within 6 to 12 months.

Anagen Effluvium

• Sudden, massive shedding of active anagen hairs occurring days to weeks after systemic chemotherapy or radiation therapy; caused by acute mitotic arrest of hair matrix cells.

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