Psoriasis — Clinical Variants

• Chronic, immune-mediated disorder from a polygenic predisposition + environmental triggers (trauma, infections, medications, psychological stress)
• Pathophysiology involves T cell classes interacting with DCs and innate immune cells (neutrophils, keratinocytes)
• Susceptibility genes point to innate + adaptive immune systems AND altered epidermal differentiation
• Classic lesion: sharply demarcated, scaly, erythematous plaques; occasionally sterile pustules
• Most common sites: scalp, elbows, knees → then nails, hands, feet, trunk (including intergluteal fold)
• Histology: acanthosis with elongated rete ridges, hypogranulosis, hyper-/parakeratosis, dilated vessels, perivascular lymphocytic infiltrate with neutrophils singly or in aggregates
• Psoriatic arthritis = major systemic association; classic presentation = asymmetric oligoarthritis of small joints of hands/feet; other comorbidities: depression, metabolic syndrome, cardiovascular disease
• Treatment: topical (limited disease) → phototherapy/MTX/cyclosporine/biologics (moderate-severe)

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• Robert Willan (1809) — first accurate description
• Hebra (1841) — definitively separated psoriasis from leprosy
• Heinrich Koebner (1879) — described plaques developing at sites of injury
• WHO 2014 resolution: recognized psoriasis as "chronic, noncommunicable, painful, disfiguring and disabling disease for which there is no cure"

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A. General

• Chronic plaque psoriasis (psoriasis vulgaris) = most common variant
• Less often: erythrodermic (near-total BSA) or guttate (numerous small disseminated papules)
• Type I (HLA-Cw6+): earlier onset, more widespread, frequent recurrences vs Type II
• Lesion size: pinpoint to >20 cm; outline circular, oval, or polycyclic
• Woronoff's ring = pale blanching ring surrounding lesions
• Auspitz sign = pinpoint bleeding when scale removed → reflects elongated dermal papillary vessels + thinned suprapapillary epidermis
• Involution starts centrally → annular lesions
• Pinpoint papules around plaques + active edge with intense erythema = unstable phase

B. Chronic Plaque Psoriasis

• Sites of predilection: scalp, elbows, knees, lumbosacral area, hands, feet
• Genitalia involved in up to 45%
• ~15% have remissions lasting ≥5 years
• PASI: scored across 4 body regions (head, trunk, upper limbs, lower limbs) × erythema/induration/scaling (0–4 each) × area involvement (0–6) × region-specific correction factors (head 0.1, trunk 0.3, upper limbs 0.2, lower limbs 0.4); RANGE 0–72
• Other severity tools: Palmoplantar Psoriasis PGA, Psoriasis Scalp Severity Index, Nail Psoriasis Severity Index, Static PGA of Genitalia

C. Guttate Psoriasis

• More common in children/adolescents; often preceded by upper respiratory infection
• >half have elevated ASO, anti-DNase B, or streptozyme titer

D. Erythrodermic Psoriasis

• Generalized erythema/scaling; onset gradual or acute
• Clues: previous plaques in classic locations, characteristic nail changes, CENTRAL FACIAL SPARING

E. CARD14-Associated Papulosquamous Eruption

• Features of BOTH psoriasis and pityriasis rubra pilaris
• Early onset, prominent cheeks/chin/ears, family history of psoriasis/PRP, minimal response to conventional therapy, improves with ustekinumab
• Mechanism: NF-κB upregulation → ↑IL-8/CCL20 → DC IL-23 → T cell IL-17/IL-22

F. Pustular Disease

Generalized pustular psoriasis — neutrophil-dominant; triggers: pregnancy, rapid corticosteroid taper, hypocalcemia, infections

• Related autoinflammatory genotypes: DIRA (IL-1 receptor antagonist deficiency), DITRA (IL-36 receptor antagonist deficiency)
• Four phenotypic patterns:

1. von Zumbusch — abrupt generalized erythema + pustulation, painful, fever, feels ill; resolves over days with extensive scaling
2. Annular — annular erythema/scaling with pustules at the advancing edge, centrifugal expansion, central healing
3. Exanthematic — acute small pustules, appear/disappear over days, usually follows infection or drugs (e.g. lithium); overlaps with AGEP; no systemic symptoms
4. "Localized" — pustules within/at edge of existing plaques (unstable phase, or after irritants like tars/anthralin)

Pustulosis of the palms and soles

• Sterile pustules + yellow-brown macules on palmoplantar surfaces; course CHRONIC and LOCALIZED (unlike GPP)
• Triggers: focal infection, stress; smoking may aggravate
• Associated with SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis)
• Can be a paradoxical reaction to TNF inhibitors

Acrodermatitis continua of Hallopeau

• Rare; pustules on distal fingers (occasionally toes); nail bed pustules → nail plate shedding
• Can be accompanied by annulus migrans of the tongue

G. Special Locations

• Scalp: discrete lesions (vs poorly defined seborrheic dermatitis); extends to face periphery, retroauricular, posterior neck; pityriasis amiantacea (asbestos-like scale on hair shafts) — psoriasis is the MOST COMMON cause, though also seen in seborrheic dermatitis, infected AD, tinea capitis
• Flexural ("inverse") psoriasis: shiny, pink-red, sharply demarcated, thin plaques with LESS scale; central fissure common; sites: retroauricular fold, intergluteal cleft, inguinal crease, axilla, inframammary; can be triggered by dermatophyte, candidal, or bacterial infection
• Oral mucosa: annulus migrans (migratory annular erythema with white scale) on the tongue (resembles geographic tongue) — seen with acrodermatitis continua and GPP
• Nail psoriasis: reported in 10%–80%; fingernails > toenails; Dutch survey: 79% had nail involvement, 52% pain, 14% major daily life restriction; nail involvement predicts increased risk of psoriatic arthritis
• Pits = matrix involvement (proximal)
• Leukonychia/loss of transparency = mid-matrix
• Oil drop/salmon patch = nail bed involvement (leukocyte exocytosis)
• Splinter hemorrhages = increased capillary fragility
• Subungual hyperkeratosis + distal onycholysis = distal nail bed parakeratosis

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• ILVEN: linear psoriasiform lesions along lines of Blaschko; distinct from linear psoriasis but a subset shows CARD14 mosaicism
• Reactive arthritis: urethritis + arthritis + ocular findings + oral ulcers + psoriasiform skin lesions
• Uncommon in children; more common in MEN
• Chlamydia trachomatis major cause; also shigellosis
• Eye: conjunctivitis common; also iritis, uveitis with glaucoma, keratitis
• Cutaneous lesions in ~5%: soles, extensor legs, penis, dorsal hands/fingers, nails, scalp
• Keratoderma blennorrhagicum = thick yellow scale, often pustular, on soles
• Balanitis circinata = psoriatic plaques on the penis
• Strong HLA-B27 association; can be severe in HIV-infected patients
• Sneddon–Wilkinson disease (subcorneal pustular dermatosis): annular/polycyclic lesions starting in flexures; very superficial (SUBCORNEAL) sterile pustules; gravity-dependent fluid layering (clear above, pus below); cyclic course; associated with IgA paraproteinemia; responds to dapsone; must exclude IgA pemphigus (subcorneal pustular dermatosis type) via immunofluorescence

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• SCC in situ (Bowen disease, erythroplasia of Queyrat) — consider for single/limited treatment-resistant plaques
• Mycosis fungoides — clues: wrinkling (epidermal atrophy), progression to infiltrated plaques
• Dermatomyositis — can mimic scalp/elbow/knee/hand involvement
• Hypertrophic lichen planus — shin plaques; violaceous lesions elsewhere + mucosal involvement favor LP
• Keratotic eczema of palms/soles — sharp margination favors psoriasis
• Rupioid psoriasis (pronounced hyperkeratosis) → consider concomitant hypothyroidism
• Erythroderma differential: Sézary syndrome, pityriasis rubra pilaris, drug reactions
• Guttate psoriasis differential: small plaque parapsoriasis, pityriasis lichenoides chronica, secondary syphilis, pityriasis rosea, tinea corporis (if annular/limited), pemphigus foliaceus (if upper trunk predominant)
• Flexural/intertrigo differential: seborrheic dermatitis, contact dermatitis, candidiasis, tinea incognito, erythrasma, extramammary Paget disease; in infants, consider Langerhans cell histiocytosis
• Pustular differential: AGEP (histologically similar; eosinophils favor AGEP); DIRA/DITRA; for annular pustular psoriasis — Sneddon-Wilkinson and other subcorneal pustule causes

Differential Diagnosis of Subcorneal/Intraepidermal Neutrophilic Pustules

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A. Progression Through Lesion Stages

Initial lesion (pinhead papule): NOT yet diagnostic — superficial perivascular lymphs/histiocytes, papillary edema, dilated capillaries; mild acanthosis, NO parakeratosis; mast cell degranulation constant in guttate lesions; neutrophils NOT yet present

Active lesion (fully developed guttate or expanding plaque edge): DIAGNOSTIC

• Increased, tortuous papillary capillaries; mixed perivascular infiltrate (lymphs, histiocytes, neutrophils)
• Acanthotic epidermis with focal neutrophil/lymphocyte accumulation; granular layer absent; parakeratosis
• Spongiform pustule of Kogoj = neutrophil accumulation in a spongiotic focus
• Microabscess of Munro = neutrophils/remnants in stratum corneum with surrounding parakeratosis
• Both are PATHOGNOMONIC for psoriasis AND AGEP

Stable lesion: elongated tortuous capillaries in club-shaped dermal papillae with only a thin suprapapillary plate — explains the Auspitz sign

• Modest perivascular infiltrate (lymphs, histiocytes); lesion is heterogeneous ("hot spots" vs "cold spots")
• Squared-off, elongated rete ridges with basal coalescence; parakeratosis, absent granular layer

B. Pustular Psoriasis Histology

• Neutrophil accumulation is predominant; acanthotic epidermis
• Exaggerated spongiform pustules of Kogoj and microabscesses of Munro

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• Psoriasis comprises a family of common, immune-mediated, and often genetically determined, inflammatory skin diseases, recognised by its distinctive clinical appearances, and associated with diseases in other organs, in particular psoriatic arthritis. A fundamental classification into plaque forms of the disease and pustular forms, which may co-exist. Chronic plaque psoriasis (psoriasis vulgaris) = the commoner form and characterised by red, scaly, sharply demarcated plaques of variable extent and severity. Pustular psoriasis characterised by sterile pustule presence and is distinct from psoriasis vulgaris in its genetic susceptibility, pathogenesis, clinical features, and treatment response.
• Pending a full aetiological and molecular classification, Box 35.1 provides a provisional working classification.
• This chapter divided into three sections: plaque psoriasis, pustular psoriasis, and psoriatic arthritis.

• Clinical forms of psoriasis (based on morphology or natural history): Plaque psoriasis (psoriasis vulgaris); Acute guttate psoriasis; "Unstable" psoriasis; Erythrodermic psoriasis; Pustular psoriasis; Atypical forms of psoriasis
• Other specified forms of psoriasis (based on age or precipitants): Linear and segmental psoriasis; Psoriasis in childhood and old age; Photoaggravated psoriasis; Drug-induced or exacerbated psoriasis; HIV-induced or exacerbated psoriasis
• Psoriasis affecting specific sites: Scalp psoriasis; Follicular psoriasis; Seborrhoeic psoriasis (sebopsoriasis); Flexural psoriasis (inverse psoriasis); Genital psoriasis; Non-pustular palmoplantar psoriasis; Nail psoriasis; Mucosal lesions; Ocular lesions

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Early changes

• Vasodilatation, papillary oedema, and leukocyte infiltration appear to precede epidermal changes in early developing lesions. Compact hyperkeratosis, disappearance of the granular layer, and epidermal hyperplasia follow. Mitotic figures in keratinocytes and leukocytic infiltration in spongiotic foci seen in the epidermis' lower half. Scattered parakeratosis mounds set in a predominantly orthokeratotic stratum corneum appear, with or without neutrophils (intraepidermal spongiform pustule of Kogoj). Epidermal hyperplasia with rete ridges of even length and prominently dilated, tortuous papillary capillaries associated with mixed mononuclear and neutrophil infiltrates seen.

Changes in fully developed plaques

• Parakeratosis associated with focal orthokeratosis, near absence of the granular layer, hyperplasia with rete ridge elongation, and supra-papillary epidermal thinning. The rete ridges often clubbed, branched, or fused at their bases, with mononuclear leukocyte infiltrates in the epidermis' lower half. Neutrophils may sometimes be seen in the stratum corneum (Munro microabscesses). Dilated, tortuous, papillary blood vessels almost touch the undersurface of the thinning supra-papillary epidermis and are surrounded by a mixed mononuclear and neutrophil infiltrate, as well as extravasated erythrocytes. Epidermal invasion with leukocytes takes place particularly in the supra-papillary region. Necrotic keratinocytes may be seen in the upper and mid epidermis.

History

• Pruritus often the dominant symptom and, although not as severe as in atopic eczema, experienced by the majority of patients and contributes to impairment in quality of life, partly through disturbed sleep. Skin tightness and burning frequent in unstable, erythrodermic, or pustular psoriasis, and pain may be experienced in areas of fissure formation, particularly in palmoplantar or flexural disease. Shedding of scale can be a significant symptom, for instance in scalp psoriasis, and contributes to feelings of embarrassment. The disease's impact and its symptoms on patients' relationships, activities, and occupation can be severe, and its assessment may be assisted by patient completed questionnaires.
• The first psoriasis manifestation may develop at any age, and in general those with earlier onset disease more likely to have a psoriasis family history. The disease course including the frequency of relapses and remissions varies greatly between individuals. Exacerbating factors should be enquired after and responses to previous treatments noted. Important to ask concerning involvement by psoriasis of specific sites that may not be volunteered by the patient, for instance the ano-genital region. A detailed medical history should be taken including an enquiry into symptoms of common co-morbidities, particularly of articular symptoms.

Presentation

• Chronic plaque psoriasis = the most common psoriasis type, accounting for about 80-90% of all cases. Presents as a papulo-squamous rash, and diagnosis based on individual lesions' characteristics and their skin distribution. Typical lesions: red scaly plaques, remarkably well demarcated from unaffected skin, with sharply delineated edges. Plaques may be encircled by a clear peripheral zone, the halo or ring of Woronoff. There may be any number of lesions or only a single one. When multiple, lesions usually monomorphic and distributed relatively symmetrically over the scalp, trunk, and extensor limb surfaces. Vary in diameter from one to several centimetres and oval or irregular in shape. Large plaques may form by coalescence of smaller plaques and commonly seen on the legs and sacral region. Involuting lesions may clear from the centre initially, producing annular or arcuate shapes. Postinflammatory hyperpigmentation or hypopigmentation common, particularly in patients with skin of colour. Linear and geometric configurations may arise at trauma sites as an isomorphic (Koebner) phenomenon.
• Most psoriasis lesions surmounted by silvery white scales, which vary considerably in thickness. Scaling amount may be minimal in partially treated disease, and in the flexures. When scaling not evident it can often be induced by light scratching, a useful sign in diagnostically uncertain lesions. Successive removal of scales usually reveals an underlying smooth, glossy red membrane with small bleeding points where the thin supra-papillary epidermis has been torn off (Auspitz sign). The epidermal thickening characteristic of the psoriasis process causes the lesions to be raised from the adjoining skin and easily palpable. Evidence that untreated plaque thickness varies between patients but is relatively constant in an individual and may predict treatment response. These diagnostic features may not all be present at the same time or in every case and are sometimes obscured or evanescent. The variety of morphologies of chronic plaque psoriasis has led some authors to attempt a sub-classification according to phenotype and to speculate it may in fact be several distinct disease entities.

Psoriasis affecting specific sites

Scalp psoriasis

• The scalp = one of the most common areas affected by plaque psoriasis and often the site first affected. The whole scalp may be diffusely involved or multiple discrete plaques of varying size may be seen. Very thick plaques can develop, especially at the occiput. Plaques tend to be restricted to hair-bearing areas, extending a short distance beyond the hairline and around the ears. Hair growth rate normal, and common scalp psoriasis not a frequent alopecia cause, although it may occur. Erythrodermic psoriasis may be associated with severe hair loss, as may vigorous local treatment. A morphological entity consisting of plaques of asbestos-like scaling, firmly adherent to the scalp and associated hair, has been termed pityriasis (tinea) amiantacea. Most common in children and young adults, and best regarded as a non-specific reaction pattern, which may be seen in other scaling scalp conditions. May be an early manifestation occurring before the other psoriasis signs. Hair loss, sometimes cicatricial, may be seen in pityriasis amiantacea.

Follicular psoriasis

• Psoriasis affecting hair follicles on the trunk and limbs — follicular psoriasis — may occur as an isolated phenomenon, or in association with plaque psoriasis. The lesions smaller than typical guttate psoriasis lesions and may be either grouped or diffuse. In children may be confused with pityriasis rubra pilaris (PRP).

Seborrhoeic psoriasis (sebopsoriasis)

• Plaques of thin, sharply demarcated erythema with variable scale may occur in the typical seborrhoeic dermatitis distribution, involving paranasal areas, external ears, medial eyebrows, hairline, pre-sternal, and inter-scapular chest wall. These may occur in individuals with plaque psoriasis elsewhere. When it arises as an isolated phenomenon, difficult to distinguish from seborrhoeic dermatitis, and may represent a koebnerisation of psoriasis within this entity. Face involvement other than in a seborrhoeic distribution uncommon in adults, and when it occurs often an indication of widespread psoriasis elsewhere on the skin.

Flexural psoriasis (inverse psoriasis)

• Psoriasis involving the inguinal creases, axillae, submammary folds, gluteal cleft, umbilicus, and other body folds more common in older adults and associated with obesity. Flexural involvement often seen in individuals with plaque psoriasis elsewhere on the skin. Less frequently, lesions confined to flexural sites, and sometimes referred to as inverse psoriasis. Inverse psoriasis may occur as a primary disorder or as a Koebner phenomenon on top of infective or seborrhoeic intertriginous dermatoses. Failure to respond to antibacterial or antifungal preparations should arouse suspicion.
• Flexural plaques are thin, scaling greatly reduced or absent, and a confident diagnosis may therefore be difficult. The surface has a glazed hue and fissuring at the depth of the skin fold common, especially in the gluteal cleft. The lesion edges usually well defined, unless secondary infection or medicament dermatitis, both quite common events, have occurred. Napkin area involvement (psoriatic napkin eruption) may be the first psoriasis presentation in infancy.

Genital psoriasis

• Genital skin can be considered a flexural skin type, and there are similarities between psoriasis as it affects flexural and genital sites. Genital skin often involved in individuals with inverse psoriasis, less frequently in those with plaque psoriasis and may be the only psoriasis manifestation. Has been shown to cause particular problems with sexual function.
• Skin of the scrotum and penile shaft may be affected by psoriasis, but the glans penis = the most frequently affected part. In circumcised men, lesions on the glans similar in appearance to plaques at other sites. In the uncircumcised, the plaques may lack scale but the colour and well-defined edge usually distinctive. Where confirmatory signs elsewhere absent, a diagnostic biopsy may be necessary as it may resemble erythroplasia or plasma cell balanitis.
• Patients with vulval involvement often complain of marked pruritus. The most common vulval presentation: a symmetrical, red, non-scaly, well-demarcated thin plaque affecting the labia majora. Psoriasis among the commoner chronic vulvitis causes in children, and among adults should be considered in the differential diagnosis of chronic erythematous vulvitis without vaginitis.

Non-pustular palmoplantar psoriasis

• On the palms and soles, psoriasis may present as typical scaly patches on which a fine silvery scale can be evoked by scratching, as less well-defined plaques resembling lichen simplex or hyperkeratotic eczema. Mixed forms occasionally occur. Often difficult to distinguish between psoriasis and eczema, with which it may sometimes appear to alternate. A sharply defined edge at the wrist, forearm, or palm and vesiculation absence are helpful. On the dorsal surface, the knuckles frequently show a dull-red skin thickening. Elsewhere on the hands and feet, psoriasis retains its typical character. There may be a relationship to trauma or occupational irritants.

Nail psoriasis

• The nails grow more quickly in psoriasis patients. Nail dystrophy may be seen in association with all psoriasis types or occasionally as an isolated feature. Its incidence estimates vary considerably. Minor involvement degrees (e.g. pitting) difficult to define clinically but nail unit abnormalities have been detected by ultrasonography in up to 73% of plaque psoriasis patients. On clinical examination, nail changes present in about 40% of cases at any point in time and lifetime prevalence is 80-90%. Nail psoriasis characterised by hyperkeratosis of the nail matrix and often the nail plate. In one reported case series, parakeratosis present in 78% of cases and unlike plaque psoriasis hypergranulosis is a common feature. Neutrophilic infiltration of the nail bed present in 63% of patients.
• Nail psoriasis associated with more extensive psoriasis, longer disease duration, family history of psoriasis, and the presence of psoriatic arthritis. In one German study, psoriatic arthritis was present in more than twice as many psoriasis patients with nail disease.
• Psoriasis may affect any part of the nail unit, including the nail matrix, nail bed, and hyponychium. Nail matrix disease presents with pits, ridges, and grooves of the nail plate. Pitting = the most frequent fingernail change seen, individual pits being uniform in size at about 1mm diameter and sometimes arranged longitudinally. Nail bed disease can be seen as subungual "oil drops" that are highly specific for psoriasis. Nail bed disease also causes subungual hyperkeratosis, splinter haemorrhages, and distal onycholysis. Can be difficult to distinguish clinically between toenail bed psoriasis and onychomycosis, which quite often coexists.

Mucosal lesions

• Whether psoriasis affects the oral mucosa is a matter of controversy. True mucosal involvement appears rare. Geographic tongue (benign migratory glossitis) and fissured tongue both more frequent among psoriasis patients than healthy controls. The association of both psoriasis and geographic tongue with HLA-C\*06:02 provides further evidence that the two disorders are related, but whether geographic tongue is an oral manifestation of psoriasis per se remains to be established.

Ocular lesions

• Psoriasis may affect ocular structures directly, or by associated immunological phenomena. Direct involvement of the eyelids or eyelid margins may cause blepharitis and its consequences, which are the most frequent ocular psoriasis complications. A chronic non-specific conjunctivitis has also been reported to be common in psoriasis, and xerosis may also be seen. Keratitis rare. Uveitis = an important immunologically mediated complication and has been found to be associated with more extensive psoriasis. More strongly associated with psoriatic arthritis.

Clinical variants (based on morphology or natural history)

Acute guttate psoriasis

• Describes the sudden onset of a shower of small lesions (Latin plural Guttae meaning drops), appearing diffusely over the body. Should be distinguished from small plaque psoriasis and follicular psoriasis, which follow a more chronic course. In one series, 12% of all affected psoriasis patients had experienced acute guttate psoriasis. More common in children and young adults in whom it may be the first psoriasis presentation. Frequently follows several weeks after pharyngitis caused by group A streptococci, serological evidence for which can be found in about 60% of individuals. A guttate flare may also occur in adults with plaque psoriasis and in this context more common in patients whose psoriasis had its onset in childhood.
• In the early stages of acute guttate psoriasis there may be little scaling. Lesions from 2 or 3mm to 1cm diameter, round or slightly oval. Scattered more or less evenly over the body, particularly on the trunk and proximal limb part, rarely on the soles but not infrequently on the face, ears, and scalp. Lesions on the face often sparse, difficult to see, and disappear quickly. Although guttate lesions normally profuse, occasionally no more than half a dozen present on the body, and in the early stages the colour not specific. Diagnosis made chiefly from the scaling's nature, the general distribution, and evidence for preceding infection. Lesions usually resolve over about 3 months. A significant minority of patients with acute guttate psoriasis subsequently develop plaque psoriasis.

"Unstable" psoriasis (syn. active psoriasis, eruptive inflammatory psoriasis)

• In contrast to plaque psoriasis lesions, which are static for prolonged periods, in some individuals and in some disease phases there's more marked activity in the form of plaque enlargement that can become more intensely red, and the development of many new smaller plaques. Patients may complain of more pain or pruritus within the plaques. The Koebner phenomenon thought to be more frequent in this disease phase. The immediate outcome unpredictable; the lesions may return to the inactive state, or progress to localised pustulation or erythrodermic psoriasis. Patients may develop unstable phases repeatedly, settling back again into the stable disease forms. Recognised precipitants include withdrawal of systemic or potent topical corticosteroids, treatment with irritants such as tar or dithranol, acute infection, and severe emotional distress. Serum levels of IL-17 and the IL-1 receptor antagonist higher in patients during the disease's unstable phase.

Erythrodermic psoriasis

• In which most or all of the body surface affected by psoriasis, uncommon, occurring in 1-2% of patients. Psoriasis has been found to be the underlying cause in about 25% of erythroderma cases. Erythroderma in psoriasis may be chronic, due to the gradual extension of plaque psoriasis, or acute as part of the spectrum of "unstable" psoriasis. In the chronic form, the individual may be systemically well, the clinical characteristics of psoriasis are retained, and there are usually some areas of uninvolved skin. Mild topical treatments well tolerated, and overall prognosis good.
• The acute form often precipitated by environmental or therapeutic triggers including systemic illness, alcohol excess, antimalarials, irritating topical treatments, ultraviolet radiation, or by withdrawal of systemic treatments including corticosteroids, ciclosporin, methotrexate, or TNF inhibitors. The patient may be febrile and systemically ill. Dependent oedema common. Itching often severe. The entire skin may be affected and psoriasis's clinical characteristics often lost. There may be clinical overlap with generalised pustular psoriasis. Untreated, the course is prolonged, relapses frequent, and there's appreciable mortality. Complications are those of skin failure, including sepsis, hypothermia or hyperthermia, hypoalbuminaemia, anaemia, dehydration, and high output cardiac failure.

Pustular psoriasis

• See later.

Atypical forms of psoriasis

• In a disease as common and variable as psoriasis, atypical forms are frequent. Many unusual localisations have been recorded, including digital and interdigital forms. Verrucous lesions particularly affect the legs. Rupioid, elephantine, and ostraceous psoriasis are terms sometimes used to describe plaques associated with gross hyperkeratosis. Rupioid psoriasis refers to limpet-like cone-shaped lesions. The term elephantine psoriasis might be used to describe unusual but very persistent, thickly scaled, large plaques that sometimes occur on the back, limbs, hips, or elsewhere. Ostraceous psoriasis, an infrequently used term, refers to a ring-like hyperkeratotic lesion with a concave surface, resembling an oyster shell.

Other specified forms of psoriasis (based on age, precipitants)

Linear and segmental psoriasis

• True linear or segmental psoriasis, in which lesions unilateral or Blaschko-linear, extremely rare. Called isolated linear psoriasis when it occurs alone, or superimposed linear psoriasis when, as occurs more frequently, it arises in association with non-segmental plaque psoriasis. The segmental lesions tend to arise at a young age, and often more severe and treatment refractory than the associated non-segmental disease. Segmental manifestations thought to represent genetic mosaicism arising by postzygotic loss of heterozygosity or a postzygotic new mutation at a psoriasis susceptibility locus.
• This phenomenon shouldn't be confused with inflammatory linear verrucous epidermal naevus, or a Koebner response of psoriasis on verrucous epidermal naevus of the non-inflammatory type or at the site of prior herpes zoster.

Psoriasis in childhood and old age

• Psoriasis common in children with a cumulative prevalence up to 18 years of 0.71%. Congenital psoriasis very rare. In some series girls outnumber boys. Psoriasis in children significantly associated with several co-morbidities including obesity and diabetes. No evidence that psoriasis onset in childhood predicts severe disease in adult life.
• All the clinical variants of psoriasis described in adults recognised in childhood but with a different frequency according to the age group. Establishing the diagnosis in infancy can be challenging because of limited involvement or an atypical appearance. The napkin area frequently the first site affected; under age 2 years, napkin psoriasis with or without disseminated lesions = the most frequent form, presenting with well-defined erythema devoid of scale. At this site, psoriasis must be differentiated from irritant contact dermatitis and seborrhoeic dermatitis. Napkin seborrhoeic dermatitis = a particular diagnostic problem as a significant proportion of affected children develop plaque psoriasis in adulthood.
• Guttate psoriasis more frequent in children than adults, particularly under age 12 years. In older children, plaque psoriasis = the most frequent presentation, and the face and anogenital sites appear to be affected more frequently than in adults. The disease often first appears in the scalp, where it may present as pityriasis amiantacea. Apart from the common forms, several other psoriasis patterns occur in childhood. Interdigital tinea uncommon in children and a toe cleft intertrigo may be psoriatic. Other flexural forms also occur. The disease may mimic chronic blepharitis, usually unilaterally, with a small psoriasis plaque on one eyelid extending to the lid margin, or on the cheek at the angle of the mouth. Erythrodermic and pustular psoriasis variants rare in childhood. Pustular psoriasis may be the first psoriasis presentation and tends to follow a benign course. Although localised pustular psoriasis extremely rare in children, parakeratosis pustulosa (an indolent and recurrent scaling pustular acrodermatitis, sometimes around the nail of only one digit) often proves to be psoriatic. Psoriatic arthritis relatively uncommon in childhood.
• In older age groups, psoriasis that starts for the first time after age 65 years tends to be less extensive than early-onset disease. Less often a psoriasis family history. Plaque psoriasis with prominent scalp involvement = the commonest phenotype. Inverse psoriasis and erythrodermic psoriasis may be more common than in early-onset disease, whereas guttate and generalised pustular psoriasis rare.

Drug-induced or exacerbated psoriasis

• See later.

Photoaggravated psoriasis

• See later.

HIV-induced or exacerbated psoriasis

• The association between severe psoriasis, psoriatic arthritis, and HIV infection well recognised. Psoriasis may be the first HIV infection presentation, as may the deterioration in previously stable disease. Plaque psoriasis = the most frequent phenotype, with a predilection for the scalp and palmoplantar skin. Sebopsoriasis, rupioid psoriasis, and erythrodermic psoriasis also common, as are mixed patterns. Psoriasis tends to be more prevalent in the later stages of HIV-related immunodysfunction, but may occur earlier. The mechanisms of psoriasis worsening in HIV infection unclear and represents a paradox, given that T cells are the major HIV target. Suggested explanations include HIV-induced reduction in regulatory T cells, an increased number of memory CD8+ T cells, effects of HIV on dendritic cell populations, HIV proteins acting as superantigens, or shared genetic variants between psoriasis and HIV responder status. One suggestion: HIV affects peripheral blood Th cells and affects to a lesser degree cutaneous resident memory T cells which are pathogenic in psoriasis. Psoriasis tends to improve with a reduced viral load, especially on treatment with antiretroviral therapy.

• The clinical characteristics already described usually sufficient to enable the diagnosis to be made, but doubt may arise in atypical cases, in particular sites, and when psoriasis is complicated by or alternates with other diseases. The diseases that need to be distinguished from psoriasis vary depending on the clinical variant of psoriasis and the site affected.
• In seborrhoeic dermatitis, the lesions lighter in colour, less well defined, and covered with a dull or branny scale. Eczema at times develops a psoriasiform appearance, especially on the legs. Hyperkeratotic eczema of the palms = a common misdiagnosis cause. Colour, scratch-evoked scaling, and well-defined margins suggestive of psoriasis, and nail changes may be diagnostic. Lichen planus can give rise to difficulty when the two diseases coexist, especially when present as hypertrophic lesions on the legs, as penile lesions, and on the palms. The violaceous colour, Wickham's striae, and oral changes presence usually decisive. Chronic hand or foot eczema can be difficult to differentiate from palmar or plantar psoriasis, and exudate or microvesicles presence should be sought to support the former diagnosis. Lichen simplex can resemble psoriasis closely, particularly on the scalp and near the elbow. The intensified skin markings, rather ill-defined edge, and marked itching characteristic, and the elbow point tends to be avoided. Pityriasis lichenoides chronica can closely resemble guttate psoriasis, but the lesions usually less evenly scattered, have a brownish red or orange-brown colour, and capped by a "mica-like" scale. Candidiasis shows a glistening deep red colour suggestive of psoriasis, particularly in the flexures, but scaling tends to be confined to the edge, and small satellite pustules and papules usually evident outside the main area. Tinea cruris has a well-defined, often polycyclic edge, but Trichophyton rubrum infections, especially of the palm, may cause difficulty. If corticosteroids have been applied, scaling may be absent and the diagnosis must be made by mycological examination of skin scrapings.
• Less common causes of confusion: PRP and secondary syphilis. The resemblance to PRP may be close, especially in the erythrodermic phase. In PRP dark red follicular lesions apparent, and the acquired palmar and plantar keratoderma has a yellow-orange tinge. The psoriasiform syphilis lesions may cause difficulty to the inexperienced; condylomas, mucosal lesions, and other disease signs usually found, if sought. Porokeratosis of Mibelli on the palms and soles, patches of Bowen and Paget disease, and penile erythroplasia may resemble psoriasis, but the lesions often solitary. Mycosis fungoides can clinically also appear similar to psoriasis. In atypical psoriasis that doesn't respond to conventional therapy, this diagnosis should be considered and appropriate investigations performed. The coexistence of two inflammatory diseases should also be considered — for example, allergic contact dermatitis in the context of psoriasis.

Diseases distinguished from psoriasis by clinical variant and site

• Chronic plaque psoriasis: Lichen simplex; Discoid eczema; Lichen planus; Secondary syphilis; Bowen disease; Cutaneous lupus.
• Guttate psoriasis: Pityriasis rosea; Lichen planus; Pityriasis lichenoides chronica.
• Flexural psoriasis: Seborrhoeic dermatitis; Candidiasis; Tinea cruris; Bacterial intertrigo; Allergic contact dermatitis; Tinea corporis; Langerhans cell histiocytosis.
• Erythrodermic psoriasis: Drug induced; Eczema; Cutaneous T-cell lymphoma/Sézary syndrome; Pityriasis rubra pilaris; Hailey-Hailey disease; Mycosis fungoides.

• Aspects of psoriasis severity include the extent and severity of the inflammation at a particular time point, cumulative psoriasis activity over time, the involvement of areas of skin that may cause specific problems (for instance, face, hands, or genital skin), the presence or absence of co-morbid conditions, the disease's impact on an individual's quality of life, and the affected skin's responsiveness to treatments. Psoriasis varies in its severity between patients, and over time. Instruments to measure various elements of psoriasis severity have been developed for research, including drug development, and for clinical practice, including treatment selection and determining the response to treatment.
• The Psoriasis Area and Severity Index (PASI) has been widely used in clinical trials and adopted in clinical practice, and its use in a specialist setting as both a severity score and an outcome measure has been endorsed in several European clinical practice guidelines and systematic literature reviews. The PASI initially developed in 1978 as an outcome measure in a clinical trial of etretinate in psoriasis and has since been partially validated. Affected body surface area (BSA) estimated for the head and neck, trunk, upper limbs, and buttocks separately with a correction factor to allow for the differing surface areas of these four regions. Erythema, scaling, and induration graded in each region and a combined score ranging from 0 to 72 calculated as in Table 35.3. PASI not appropriate in psoriasis forms other than plaque disease, e.g. guttate or pustular psoriasis, when a record of percentage BSA affected may be preferred. PASI has been criticised as non-linear with a low response distribution, resulting in a lack of sensitivity to change in milder psoriasis, and because it's complicated to calculate. The static Physician Global Assessment (sPGA) may be more appropriate in a non-specialist environment. This is an assessment of the average erythema, scaling, and induration of all psoriasis lesions on a 5-, 6-, or 7-point rating ranging from "clear" to "very severe," without affected BSA assessment. Although not well standardised, straightforward to use and easy to understand.

PASI calculation

• Graded per region (Head, Upper limbs, Trunk, Lower limbs): Thickness (0-4), Scaling (0-4), Erythema (0-4), × Area (0-6):
• Head: (thickness + scaling + erythema) × 0.1 = A
• Upper limbs: (thickness + scaling + erythema) × 0.2 = B
• Trunk: (thickness + scaling + erythema) × 0.3 = C
• Lower limbs: (thickness + scaling + erythema) × 0.4 = D
• PASI = A + B + C + D
• Severity grading: 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe.
• Area grading: 0 = no involvement; 1 = 0-<10%; 2 = 10-<30%; 3 = 30-<50%; 4 = 50-<70%; 5 = 70-<90%; 6 = 90-<100%. (Axillae = upper limb; Neck/buttocks = trunk; Genito-femoral = lower limb)

• The disease's impact on the individual can be measured using health-related quality of life (HRQoL) instruments. The most frequently used HRQoL measure has been the skin-specific tool the Dermatology Life Quality Index (DLQI), which is simple to administer, validated, and useful in clinical trials and in clinical practice. This 10-point questionnaire generates a score from 0 to 30, and scores of greater than 10 have been shown to reflect a very large effect on a patient's life. The DLQI has been criticised for being influenced by the patient's age and gender, and as being relatively insensitive to the effects of psoriasis on mood, stress, sleep, fatigue, and addictive behaviours. More recently developed scores include Skindex-17, and in clinical trials, generic quality of life instruments such as the 36-item Short Form Health Survey (SF-36) and EQ-5D also often used. Quality of life scores (e.g. DLQI) correlate only moderately with psoriasis severity scores (e.g. PASI), because they measure different disease aspects. Psoriasis on the face, hands, or genitals may have a disproportionate effect on quality of life resulting in a high HRQoL score with a relatively low PASI. Alternatively, a mismatch between a low PASI and significantly impaired HRQoL score can suggest co-morbid depression, and psychological support should be considered under these circumstances.
• Psoriasis severity is continuously distributed and, although attempts have been made to categorise psoriasis as mild, moderate, or severe, the thresholds arbitrary and not standardised. Severe psoriasis has been variously defined as a PASI >12, as a PASI ≥10 with a DLQI ≥10, or a score of 10 or more in either the PASI or DLQI or BSA >10%. A recent consensus statement from the International Psoriasis Council rejected the notion of mild, moderate, or severe psoriasis, in favour of a classification into two groups, candidates for topical treatment or candidates for systemic treatment, the latter group characterised by either an affected BSA of ≥10%, or the involvement of high impact sites, or topical treatment failure.

• In many instances, plaque psoriasis persistent, changing little over years. In other individuals, the disease less stable with considerable variation in the extent and degree of inflammation, sometimes in relation to environmental triggers such as infections, alcohol consumption, emotional distress, or climate. A deterioration in the symptoms and extent of psoriasis in the winter months common, with a tendency for it to be milder in the autumn.
• In the few longitudinal studies reported, spontaneous remission occurs in between a third and a half of patients, and has been described for as long as 54 years. The cause of these spontaneous remissions unknown. Psoriasis can be maintained in prolonged remission using systemic or biological treatment, but untreated, relapse is the rule. The time to relapse after treatment varies enormously between individuals and between therapeutic modalities.
• Acute guttate attacks carry a better prognosis than those of a slower onset and have longer remissions after treatment. Few studies have assessed the long-term prognosis for first episodes of guttate psoriasis. In one study, only 5 of 15 patients followed up 10 years after an initial guttate psoriasis episode had developed plaque disease. At the other extreme, erythrodermic and pustular forms carry appreciable mortality and arthropathic forms considerable morbidity. Severe plaque psoriasis shortens life expectancy by an average of 4-6 years.

• Psoriasis diagnosis usually apparent on clinical examination and there's no reliable diagnostic test. A biopsy of lesional skin may occasionally be helpful in atypical cases to exclude other pathologies. No constantly present laboratory abnormality in uncomplicated psoriasis. High sensitivity C-reactive protein may be mildly elevated, with higher levels seen in psoriatic arthritis and especially in generalised pustular psoriasis. Identifying biomarkers in the skin or peripheral blood of disease severity, natural history, co-morbidity risk, and treatment response = a focus of research in stratified medicine. Screening for known co-morbidities should also be undertaken which will include assessments for psoriatic arthritis, metabolic syndrome, and depression. Investigations appropriate for initiating or monitoring systemic and biological treatments may be required.

• Pustular psoriasis is a group of rare diseases characterised by primary, sterile pustules on variably erythematous skin. A clinically diverse range of pustular phenotypes recognised. Useful to separate these clinical entities into generalised pustular psoriasis (GPP) and localised pustular psoriasis. GPP usually acute, often associated with systemic symptoms and may be life threatening. Localised pustular psoriasis usually chronic, mainly effects acral skin, and comprises palmoplantar pustulosis (PPP) and acrodermatitis of Hallopeau (ACH). European consensus classification criteria and disease definitions have been published.
• Pustular psoriasis is distinct from chronic plaque psoriasis in clinical presentation, genetics, immunology, and response to treatment. Its place within the family of psoriatic disease is being refined as the molecular genetic basis of these diseases is further resolved. Although pustular psoriasis and plaque psoriasis vulgaris co-exist more frequently than expected by chance, many patients with pustular psoriasis don't have plaque psoriasis. However, there are phases of pustular psoriasis that can be difficult to distinguish clinically from unstable plaque psoriasis. Also, pustules, more readily seen by dermoscopy, may be provoked within plaques of psoriasis vulgaris in the unstable phase of the disease. Although this has sometimes been referred to confusingly as "localised GPP," this is better considered "plaque psoriasis with pustules" ("psoriasis cum pustulatione") rather than a form of pustular psoriasis per se.
• Unlike chronic plaque psoriasis, pustular psoriasis isn't associated with HLA-C\*06:02. Recent molecular genetic studies have revealed mutations in IL36RN in a significant minority of patients with GPP and to a lesser extent in localised pustular psoriasis. IL36RN mutations haven't been identified in patients with chronic plaque psoriasis.

Consensus definitions for the diagnosis of pustular psoriasis

• Generalised pustular psoriasis: Primary, sterile, macroscopically visible pustules on non-acral skin (excludes cases where pustulation is restricted to psoriatic plaques). Sub-classifiers: Relapsing or persistent; ± systemic inflammation; ± psoriasis vulgaris.
• Palmoplantar pustulosis: Primary, persistent, sterile, macroscopically visible pustules on palms and/or soles ± psoriasis vulgaris.
• Acrodermatitis of Hallopeau: Primary, persistent, sterile, macroscopically visible pustules affecting the nail apparatus ± psoriasis vulgaris.

• GPP = a rare disease defined by the presence of primary, sterile, macroscopically visible pustules on non-acral skin. Often relapsing and remitting, with acute flares of cutaneous inflammation with systemic symptoms. Less frequent chronic persistent forms occur. There's a relationship between these entities and chronic plaque psoriasis, in that some patients may have phases of plaque psoriasis before or after GPP, but in many GPP occurs as the sole phenotype without plaque psoriasis at any time.
• GPP heterogeneous in its age at onset, genetics, phenotype, precipitants, severity, and natural history. Several overlapping clinical subgroups recognised.

Acute generalised pustular psoriasis (von Zumbusch)

• This relapsing and remitting GPP pattern is named after Leo von Zumbusch, who described a brother and sister who experienced repeated waves of acute erythema and pustulation over many years, sometimes provoked by topical treatment. This is the most acute and severe GPP form and is clinically and genetically heterogeneous. May occur as the sole phenotype or arise following chronic plaque psoriasis, acrodermatitis continua of Hallopeau, or palmoplantar pustulosis. Japanese diagnostic criteria require each of the following four features for a definitive diagnosis:

1. Systemic symptoms such as fever and fatigue
2. Multiple sterile pustules that sometimes merge to form lakes of pus
3. Kogoj's spongiform pustules on skin biopsy
4. Repeated recurrence

• The eruption may be ushered in by a sensation of burning in the skin, which becomes dry and tender. These warning signs — not always present — followed by an abrupt onset of high fever and severe malaise. Pre-existing lesions become fiery and develop pinpoint pustules. Sheets of erythema and pustulation spread to involve previously unaffected skin, the flexures and genital regions being particularly involved. Any configuration or variety of pustular exanthem may occur, for instance isolated pustules, lakes of pus, circinate lesions, plaques of erythema with pustular collarettes, or a generalised erythroderma. Waves of pustulation may succeed each other, subsiding into exfoliation of the dried pustules. The nails may become thickened or separated by subungual lakes of pus. The buccal mucosa and tongue may be involved, the lesions on the latter being clinically and histologically indistinguishable from geographic tongue.
• In the acute phase, the affected individual may be systemically unwell. Hypovolaemia and oligaemia can cause acute kidney injury. Hypoalbuminaemia in the acute episode may be profound and associated with hypocalcaemia. The absorption of orally administered therapeutic drugs may also be impaired. Abnormalities of liver enzymes common, occurring in up to a half of patients during the acute episode. Cholestatic jaundice has been reported as a consequence of neutrophilic cholangitis. Acute respiratory distress syndrome (psoriasis-associated aseptic pneumonitis) rare but possibly underreported. Presents with rapidly deteriorating dyspnoea and hypoxia in the absence of infection. If acute GPP lasts more than a few days, telogen effluvium may follow 2-3 months after the height of the illness. Amyloidosis is a rare late complication of repeated flares.
• GPP may manifest only in pregnancy when it has been referred to as impetigo herpetiformis. This is a very rare entity, first described by Hebra in 1872, 37 years before the report of GPP by von Zumbusch, and the relationship between these diseases has generated controversy subsequently. Recent molecular genetic studies support the view that impetigo herpetiformis represents GPP triggered by or occurring in pregnancy. Onset usually in the last trimester of pregnancy, but may be earlier, and has been recorded in the first month of pregnancy and in the first day of the puerperium. The disease tends to persist until the child is born, and occasionally long afterwards. The eruption often starts in the inguino-genital region and other flexures, spreading centrifugally, with minute pustules arising on an acutely inflamed skin area. Constitutional disturbance characteristically severe, and death may occur due to cardiac or renal failure. The more severe and longstanding the disease, the greater the risks of placental insufficiency leading to stillbirth, or neonatal death. Characteristically, the disease recurs in subsequent pregnancies. Recurrence has been described in up to nine successive pregnancies, and on subsequent use of oral contraceptives.

Subacute annular generalised pustular psoriasis

• Annular and other patterned lesions may be seen in acute GPP (von Zumbusch) but are more characteristic of the rarer subacute or chronic forms in which lesions are persistent, and without the severe flares of acute GPP. Lesions begin as discrete erythema areas, which become raised and oedematous. Pustules appear peripherally on the crest of the advancing edge, become desiccated, and leave a trailing fringe of scale as the lesion slowly advances. Generally no systemic symptoms.
• Subacute annular GPP = the most common GPP presentation in infancy and early childhood. Although GPP can begin at any age in childhood, in over 25% of cases onset has been in the first year of life. The disease may begin in the first few weeks of life and two congenital GPP cases have been described. In at least one third of infantile cases, a history of an eruption diagnosed as seborrhoeic dermatitis, napkin dermatitis, or sudden-onset napkin psoriasis is obtained. GPP may be localised to flexural areas, for instance the neck, for long periods.
• Some authors have separated a related pattern, well described by Lapière, as recurrent circinate erythematous psoriasis. As with subcorneal pustular dermatosis of Sneddon and Wilkinson, the relation to GPP isn't universally accepted, and these conditions specifically excluded in Japanese diagnostic criteria for GPP, while being accepted in European classification criteria.
• Linear forms of pustular psoriasis are occasionally observed within the context of more generalised pustulosis.

• The intense inflammation of GPP characterised by infiltration of masses of neutrophils. Discrete collections of neutrophils in the oedematous stratum spinosum case the characteristic spongiform pustule of Kogoj. There may be acanthosis with elongation of rete ridges. The stratum corneum becomes parakeratotic and subcorneal pustules shed as epidermal turnover is accelerated. Similar features seen in subacute as in acute patterns but in a less intense form.

• An extensive differential diagnosis of GPP, comprising eruptions that cause widespread non-follicular pustules. In acute GPP, the presence of fever, leukocytosis, and elevated inflammatory markers may lead to a mistaken diagnosis of systemic infection, sometimes leading to a counterproductive discontinuation of necessary immunosuppressive treatment. The differentiation of acute GPP from unstable psoriasis with secondary pustulation (psoriasis cum pustulatione) can be challenging, especially in those with both GPP and plaque psoriasis and requires careful consideration of all available clinical information, including the history, morphology, systemic symptoms, laboratory parameters (peripheral white cell count and acute phase reactants), and genetics. AGEP can also be a difficult differential diagnosis, occurring as an acute, spontaneously healing reaction to drugs, usually antimicrobials. There's an overlap in the immunopathogenesis of GPP and AGEP, but the pustulation usually resolves more rapidly in the latter. A skin biopsy may contribute features that assist in the distinction.
• Slow centrifugal spread of subacute annular GPP may mimic erythema annulare centrifugum. Pemphigus foliaceus and IgA pemphigus can mimic subacute GPP, but histological and immunofluorescence testing will distinguish between them. Occasionally, the bowel bypass syndrome, Sweet syndrome, and Behçet syndrome cause difficulties. Extensive impetigo, tinea, or candidiasis in the immunosuppressed should be remembered.

• GPP's severity varies greatly between patients and over time. Disease activity at a given time point has been categorised as mild, moderate, or severe based upon the extent of erythema, oedema, and pustulation, fever, and laboratory abnormalities (leukocytosis, elevated inflammatory markers, and albumin). Modifications of PGA (GPPGA) and PASI (GPPASI) in which the scaling subscore is replaced by a pustule severity have been validated and used in clinical trials.

• Acute GPP typically characterised by flares and remissions. Flare frequency and duration varies from patient to patient, and they may be provoked by a known trigger or be spontaneous. Flares tend to last days or weeks without treatment, in one large series ranging from 7 to 60 days with a mean of 16 days. In between flares, there may be more limited GPP areas, the skin may be clear, or there may be plaque psoriasis. Mortality rates directly attributable to GPP or its associated treatment of 2-16% have been reported. The prognosis better when there's a clear trigger, exemplified by acute GPP of pregnancy. GPP developing from acrodermatitis continua of Hallopeau seems to have the worst prognosis. The prognosis good for subacute annular GPP and, consequently, for GPP in infants and children.

• In the acute phase, inflammation activity reflected in elevated C-reactive protein and erythrocyte sedimentation rate levels. There may be an absolute lymphopenia at the onset of generalised pustular psoriasis followed by a polymorphonuclear leukocytosis with a left shift. Liver enzymes, renal function, albumin, and calcium levels should be monitored. A skin biopsy may be useful to demonstrate characteristic histological features and exclude other diagnoses.

• Palmoplantar pustulosis (PPP) is a chronic condition in which multiple sterile pustules occur on the palms and/or soles, often with associated erythema and scaling. The disease persistent, and very resistant to treatment. The relationship between PPP and plaque psoriasis controversial. The two diseases occur together more frequently than expected by chance but more usually PPP occurs in isolation. This, and the absence of the genetic associations characteristic of chronic plaque psoriasis, indicate that PPP represents a distinct entity within the family of psoriatic skin diseases. Synonyms/inclusions: Chronic palmoplantar pustular psoriasis; Pustulosis palmaris et plantaris; Persistent palmoplantar pustulosis.

History

• Itching is variable; more often the patient complains of burning discomfort or pain in the lesions. Pain on standing or walking, especially when there's fissuring, and limitation of hand function have a detrimental effect on patient normal functioning and quality of life.

Presentation

• The disease presents as a pustular eruption either diffusely or within well-defined plaques. The disease may be limited to the palms, or to the soles, or both may be affected. On the hands, the thenar eminence = the most common site. Less commonly, the hypothenar eminence or the central palm or the distal palm involved. On the feet, the instep, the medial or lateral border of the foot at the level of the instep, or the sides or back of the heel involved. Less frequently, the distal sole or the whole sole implicated. Digital lesions less common although associated subungual pustulation is sometimes seen. A striking symmetry of the lesions on the hands or feet common, but sometimes a solitary lesion persists for months before others appear.
• The affected area dusky red and scaly, and fissures may develop. Removal of scale (e.g. by treatment) leaves a glazed dull red surface. Within this plaque, numerous pustules present, usually 2-5mm diameter. In early disease, dermoscopy can help to identify vesicles, or vesico-pustules within plaques, the lesions arising at the top of dermatoglyphic ridges. Fresh pustules yellow; older ones yellow-brown or dark brown as the pustule dries. Normally, pustules in all evolution stages are seen. Eventually, the desiccated pustule is exfoliated. Plaques of psoriasis may be present elsewhere on the body in a minority of patients and may be mild and atypical.
• Pustular bacterid (of Andrews) was a term first used to describe an acute monomorphic eruption of sterile pustules occurring on the hands and feet. Whether it's a distinct entity or merely an acute PPP variant unclear.

• An infiltrate of inflammatory cells including T lymphocytes, dendritic cells, eosinophils, and mast cells in the dermis. Early lesions are vesicles in the absence of spongiosis, that develop into pustules containing mononuclear cells and neutrophils as they become more superficial. Early vesicles appear to arise in or near epidermal sweat ducts, around which are increased Langerhans cell numbers.

• Palmoplantar plaque psoriasis can be difficult to exclude in phases of PPP when pustules absent, for instance on treatment. Tinea and eczema common differential diagnoses. Tinea usually asymmetrical or unilateral and the toe clefts may be involved. Microscopy and culture or PCR will confirm the diagnosis. Secondary infection of eczema may be pustular but is more painful, and Gram stains and culture of pustule contents will establish the diagnosis. Allergic contact dermatitis caused by rubber in footwear shouldn't cause diagnostic difficulties: typically, the insteps spared. The chronic acropustulosis seen in black infants doesn't occur in adults.

• The impact of palmoplantar skin involvement on physical functioning and quality of life is disproportionate to the relatively small area affected. In clinical trials, the PPPASI or fresh pustule counts have been used to measure disease severity.

• The course usually prolonged. Slow spread or extension may be refractory to all treatment. Sometimes spontaneous remission does occur but is more often temporary than permanent. In one cohort of 59 patients, only nine had a remission for more than a year.

• The diagnosis can usually be made clinically. Skin scrapings for mycological examination may be needed, and occasionally bacterial swabs or patch testing may be indicated.

• Acrodermatitis continua of Hallopeau (ACH) is a rare chronic sterile pustular eruption initially affecting the nail units of the fingers or toes, from where it slowly extends proximally. May evolve into GPP. Synonyms/inclusions: Acropustulosis; Pustular acrodermatitis; Acrodermatitis perstans; Dermatitis repens.

• The relationship between ACH and psoriasis in general and with GPP in particular has been debated since the entity was first recognised by Hallopeau in 1890. Patients with ACH may have additional plaque psoriasis and GPP.

History and presentation

• The first lesion starts on a finger or thumb more often than on a toe. Usually unilateral and remains restricted to one or a limited number of digits. The skin over the distal phalanx becomes red and scaly, and pustules develop. The nail folds and nail bed may be involved, leading to nail dystrophy. The lesion's proximal edge bordered by a fringe of undermined epidermis, irregular, often sodden, and sometimes preceded by a line of vesiculo-pustules. Removal of scale or desiccation of pustules may leave a brighter red, glazed, very sore and painful digit. Slow proximal extension is the rule but this may take several years. Eventually, other digits may be involved. The nail plate may be completely destroyed. Bone changes can occur with osteolysis of the tuft of the distal phalanx. The digit's free end may become wasted and tapered, mimicking scleroderma.

• The features are similar to those of GPP. In the epidermis, there are numerous subcorneal neutrophilic pustules and spongiform pustules with hypergranulosis and parakeratotic hyperkeratosis. A lymphocytic infiltrate in the dermis, which in chronic disease may become atrophic.

• The distribution of lesions in ACH is distinctive, as is the local destruction of soft tissue, nail apparatus, and sometimes the terminal digit. In the earlier stages, staphylococcal infection, pulp infection, herpetic whitlow, tinea, or contact dermatitis may be suspected. Candidiasis only likely to be a problem in the immunocompromised. Parakeratosis pustulosa should be considered in children.

• The usual course prolonged. Slow spread or extension may be refractory to all treatment. Sometimes spontaneous remission does occur but is more often temporary than permanent.

• The diagnosis can usually be made clinically. Swabs for bacterial culture should be taken.

• Worldwide occurrence: affects 2%–3% of Americans; prevalence ranges from 0.1% to 3% in various populations
• A chronic disorder with polygenic predisposition combined with triggering environmental factors such as trauma, infection, or medication
• Erythematous scaly papules and plaques; pustular and erythrodermic eruptions occur
• Most common sites of involvement: scalp, elbows, knees, hands, feet, trunk, and nails
• Psoriatic arthritis occurs in 10%–25% of patients; pustular and erythrodermic forms may be associated with fever
• Pathology characterized by:
• Uniform elongation of rete ridges
• Dilated blood vessels
• Thinning of the suprapapillary plate
• Intermittent parakeratosis
• Epidermal and perivascular dermal infiltrates of lymphocytes, with neutrophils occasionally in aggregates in the epidermis

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History

• Useful to determine:
• Age at onset
• Family history (younger onset + positive family history → more widespread and recurrent disease)
• Prior course: major differences between "acute" and "chronic" disease
• Chronic: lesions persist unchanged for months or years
• Acute: sudden outbreak within days
• Great variability in relapses (weekly/monthly vs. only occasional)
• Frequently relapsing patients → more severe disease with rapidly enlarging lesions → require more rigorous treatment
• Certain medications may worsen psoriasis
• Inquire about joint complaints: onset before 4th decade and/or warm swollen joints → suspect psoriatic arthritis

Cutaneous Lesions

• Classic lesion: well-demarcated, raised, red plaque with white scaly surface
• Size varies from pinpoint papules to large plaques
• Under scale: glossy homogeneous erythema
• Bleeding points appear when scale removed → traumatizing dilated capillaries = Auspitz sign
• Symmetric eruption (symmetry helpful for diagnosis); unilateral involvement can occur
• Koebner phenomenon (isomorphic response):
• Traumatic induction of psoriasis on non-lesional skin
• Occurs more frequently during flares
• All-or-none phenomenon
• Usually occurs 7–14 days after injury
• Approximately 25% of patients have trauma-related Koebner phenomenon at some point
• Lifetime prevalence estimates up to 76% when including infection, stress, drug reactions
• Not specific for psoriasis

Clinical Patterns of Skin Presentation

Psoriasis Vulgaris (Chronic Stationary / Plaque-Type Psoriasis)

• Most common form: ~90% of patients
• Red, scaly, symmetrically distributed plaques
• Characteristically on extensor aspects of extremities (elbows, knees)
• Also: scalp, lower lumbosacral, buttocks, genitalia, umbilicus, intergluteal cleft
• Constant production of large amounts of scale
• Subtypes:
• Psoriasis geographica: lesions confluence forming land-map-like borders
• Psoriasis gyrata: circinate extension from confluence of several plaques
• Annular psoriasis: partial central clearing → ring-like lesions → portends good prognosis
• Rupioid psoriasis: cone or limpet-shaped lesions
• Ostraceous psoriasis: ring-like hyperkeratotic concave lesion resembling oyster shell
• Elephantine psoriasis: thickly scaling large plaques, usually on lower extremities
• Woronoff ring: hypopigmented ring surrounding psoriatic lesions (usually associated with treatment — UV or topical corticosteroids)
• May result from inhibition of prostaglandin synthesis

Guttate (Eruptive) Psoriasis

• From Latin gutta (= "a drop")
• Small papules (0.5–1.5 cm diameter) over upper trunk and proximal extremities
• Typically early age / young adults
• Strongest association with HLA-Cw6
• Streptococcal throat infection frequently precedes or is concomitant with onset/flare
• Antibiotic treatment has not been shown to be beneficial or shorten disease course
• Patients with chronic plaque psoriasis may also develop guttate lesions

Small Plaque Psoriasis

• Resembles guttate clinically but distinguished by:
• Onset in older patients
• Chronicity
• Somewhat larger lesions (typically 1–2 cm), thicker and scalier
• Said to be common adult-onset presentation in Korea and other Asian countries

Inverse (Flexural) Psoriasis

• Localized in major skin folds: axillae, genito-crural region, neck
• Scaling minimal or absent
• Glossy sharply demarcated erythema in areas of skin-to-skin contact
• Sweating impaired in affected areas

Erythrodermic Psoriasis

• Generalized form affecting all body sites (face, hands, feet, nails, trunk, extremities)
• Erythema is most prominent feature
• Superficial scaling (not thick adherent white scale)
• Complications:
• Excessive heat loss due to generalized vasodilatation → hypothermia
• Shivering to raise body temperature
• Hypohidrotic skin (sweat duct occlusion) → risk of hyperthermia in warm climates
• Lower extremity edema (vasodilatation + protein loss)
• High-output cardiac failure
• Impaired hepatic and renal function
• Two forms:

1. Chronic plaque psoriasis worsening to involve most/all skin → relatively responsive to therapy
2. Sudden generalized erythroderma (or from nontolerated external treatment, e.g., UVB, anthralin → generalized Koebner reaction)

• Generalized pustular psoriasis may revert to erythroderma with diminished pustule formation

Pustular Psoriasis

• Clinical variants:
• Generalized pustular psoriasis (von Zumbusch type)
• Annular pustular psoriasis
• Impetigo herpetiformis
• Localized variants: pustulosis palmaris et plantaris; acrodermatitis continua of Hallopeau
• In children: can be complicated by sterile, lytic lesions of bones → can be manifestation of SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis)

Generalized Pustular Psoriasis (von Zumbusch)

• Distinctive acute variant; usually preceded by other forms of the disease
• Characterized by:
• Fever lasting several days
• Sudden generalized eruption of sterile pustules 2–3 mm diameter
• Disseminated over trunk, extremities, nail beds, palms, soles
• Pustules arise on highly erythematous skin (first as patches → confluent)
• Disease occurs in waves of fevers and pustules
• Prolonged disease → fingertip atrophy
• Erythema can become confluent → erythroderma
• Provoking agents: infections, irritating topical treatment (Koebner), withdrawal of oral corticosteroids
• Associated with prominent systemic signs; life-threatening complications:
• Hypocalcemia
• Bacterial superinfection
• Sepsis
• Dehydration
• Acute respiratory distress syndrome (reported)
• Treatment: etretinate, methotrexate, cyclosporine, infliximab, or oral corticosteroids
• IL36RN gene mutations: recessive loss-of-function mutations encoding IL-36 receptor antagonist (IL-36ra) identified in generalized pustular psoriasis
• IL-36ra is anti-inflammatory cytokine inhibiting IL-36α, IL-36β, IL-36γ

Exanthematic Pustular Psoriasis

• Tends to occur after viral infection
• Widespread pustules with generalized plaque psoriasis
• No constitutional symptoms (unlike von Zumbusch)
• Tends not to recur
• Overlap with acute generalized exanthematous pustulosis (drug eruption)

Annular Pustular Psoriasis

• Rare variant; presents in annular or circinate form
• Pustules on ring-like erythema (may resemble erythema annulare centrifugum)
• Identical lesions found in impetigo herpetiformis (some define as variant of pustular psoriasis in pregnancy)
• Onset usually early in third trimester; persists until delivery
• Develops earlier in subsequent pregnancies
• Often associated with hypocalcemia
• Usually no personal or family history of psoriasis

Localized Pustular Psoriasis Variants

• Pustulosis palmaris et plantaris and acrodermatitis continua (of Hallopeau) discussed in Chapter 21

Sebopsoriasis

• Common clinical entity
• Erythematous plaques with greasy scales in seborrheic areas:
• Scalp, glabella, nasolabial folds, perioral, presternal, intertriginous areas
• Difficult to distinguish from seborrheic dermatitis without typical psoriasis findings elsewhere
• May represent modification of seborrheic dermatitis by genetic background of psoriasis
• Relatively resistant to treatment
• Antifungal agents may be useful (etiologic role of Pityrosporum unproven)

Napkin Psoriasis

• Begins between ages 3 and 6 months
• First appears in diaper area as confluent red area
• Few days later: small red papules on trunk (may involve limbs)
• Papules have typical white scales of psoriasis
• Face may be involved
• Responds readily to treatment; tends to disappear after age 1 year

Linear Psoriasis

• Very rare form
• Presents as linear lesion most commonly on limbs; may be limited to dermatome on trunk
• May be an underlying nevus (possibly ILVEN — inflammatory linear verrucous epidermal nevus)
• Existence of linear psoriasis distinct from ILVEN is controversial

Related Physical Findings

Nail Changes in Psoriasis

• Found in up to 40% of patients
• Rare in absence of skin disease elsewhere
• Increases with age, duration/extent of disease, and presence of psoriatic arthritis

Nail Changes in Psoriasis

• Nail pitting: one of commonest features; fingers > toes; pits 0.5–2.0 mm; due to defective keratinization in proximal nail matrix
• Onychodystrophy: leukonychia, crumbling nail, red spots in lunula
• Stronger association with psoriatic arthritis than other nail changes
• Oil spots / salmon patches: translucent yellow-red discolorations beneath nail plate (psoriasiform hyperplasia + parakeratosis + microvascular changes + trapped neutrophils in nail bed)
• Considered nearly specific for psoriasis (unlike pitting, also seen in alopecia areata)
• Splinter hemorrhages: from capillary bleeding under thin suprapapillary plate
• Subungual hyperkeratosis: often accompanied by onycholysis (distal nail plate separation)
• Anonychia: total loss of nail plate; rarely in pustulosis palmaris et plantaris; can be seen in other forms of pustular psoriasis

Geographic Tongue

• Also known as benign migratory glossitis or glossitis areata migrans
• Idiopathic inflammatory disorder with local loss of filiform papillae
• Asymptomatic erythematous patches with serpiginous borders (map-like)
• Migratory nature
• Postulated to be oral variant of psoriasis (histologic features: acanthosis, clubbing of rete ridges, focal parakeratosis, neutrophilic infiltrate)
• Prevalence increased in psoriatic patients
• Relatively common condition; seen in many nonpsoriatic individuals

Psoriatic Arthritis

• Extracutaneous manifestation seen in up to 40% of patients
• Strong genetic component; several overlapping subtypes (discussed in Chapter 19)

Laboratory Tests

• Histopathologic examination rarely necessary for diagnosis; helpful in difficult cases
• Early pustular psoriasis: epidermis usually only slightly acanthotic; psoriasiform hyperplasia in older/persistent lesions
• Neutrophils migrate from dilated upper dermal vessels → aggregate beneath stratum corneum and upper Malpighian layer → spongiform pustules of Kogoj
• Other lab abnormalities (not specific, not in all patients):
• Severe psoriasis vulgaris, generalized pustular, erythroderma: negative nitrogen balance → decreased serum albumin
• Altered lipid profiles (even at onset):
• 15% higher HDL levels
• Cholesterol–triglyceride ratio for VLDL 19% higher
• Plasma apolipoprotein-A1 11% higher
• Serum uric acid elevated in up to 50% of patients (correlates with extent/activity)
• Increased risk of gouty arthritis
• Normalizes after therapy
• Markers of systemic inflammation increased: CRP, α2-macroglobulin, ESR (rare in uncomplicated chronic plaque psoriasis)
• Increased serum IgA levels and IgA immune complexes
• Secondary amyloidosis (carries poor prognosis)

Special Tests

• Immunostaining, FACS, T-cell receptor gene rearrangements: important for research; generally not required for diagnosis or management

Differential Diagnosis

Psoriasis Vulgaris — Most Likely

• Discoid/nummular eczema
• Cutaneous T-cell lymphoma (CTCL)
• Tinea corporis

Psoriasis Vulgaris — Consider

• Pityriasis rubra pilaris
• Seborrheic dermatitis
• Subacute cutaneous lupus erythematosus
• Erythrokeratoderma (keratoderma variabilis / progressive symmetric erythrokeratoderma)
• Inflammatory linear verrucous epidermal nevus
• Hypertrophic lichen planus
• Lichen simplex chronicus
• Contact dermatitis
• Chronic cutaneous lupus erythematosus / discoid lupus erythematosus
• Hailey–Hailey disease (flexural)
• Intertrigo (flexural)
• Candida infection (flexural)

Psoriasis Vulgaris — Always Rule Out

• Bowen's disease / squamous cell carcinoma in situ
• Extramammary Paget's disease

Guttate — Most Likely

• Pityriasis rosea
• Pityriasis lichenoides chronica
• Lichen planus

Guttate — Consider

• Small plaque parapsoriasis
• PLEVA
• Lichen planus
• Drug eruption

Guttate — Always Rule Out

• Secondary syphilis

Erythrodermic — Most Likely

• Drug-induced erythroderma
• Eczema
• CTCL / Sézary syndrome
• Pityriasis rubra pilaris

Pustular — Most Likely

• Impetigo
• Superficial candidiasis
• Reactive arthritis syndrome
• Superficial folliculitis

Pustular — Consider

• Pemphigus foliaceus
• IgA pemphigus
• Sneddon–Wilkinson disease (subcorneal pustular dermatosis)
• Migratory necrolytic erythema
• Transient neonatal pustular melanosis
• Acropustulosis of infancy
• Acute generalized exanthematous pustulosis

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• There is no known prevention for psoriasis.

• Common, chronic, recurrent inflammatory disease: circumscribed, erythematous, dry, scaling plaques, usually silvery white lamellar scale. Symmetric; predilection: scalp, nails, extensor limb surfaces, umbilical region, sacrum.
• Usually slow onset; may be exanthematous with sudden guttate (droplike) lesions. Itching/burning may be severe.
• Early lesions: small erythematous macules, dry silvery scale from onset → enlarge by peripheral extension/coalescence. Micaceous scale (peels in layers), looser peripherally, adherent centrally. Removal → bleeding points (Auspitz sign).
• Descriptive terms: guttata (water-drop size), follicularis (tiny scaly lesions at follicular orifices), figurata/annulata/gyrata (curved patterns from central involution), discoidea (solid patches, no central involution), rupioides (crusted, syphilitic rupia-like), ostracea (thick lamellar scale like oyster shell).
• Chronic plaque psoriasis = stable trunk/extremity lesions. Inverse psoriasis = intertriginous predominance. Pustular variants: chronic (palms/soles) or eruptive (severe toxicity, hypocalcemia).
• Nails: distal onycholysis; random pitting (proximal matrix parakeratosis); oil spots (yellow subungual parakeratosis, distal matrix); salmon patches (nail bed psoriasis). Thick subungual hyperkeratosis may resemble onychomycosis.

• Overlaps with seborrheic dermatitis: face, under breasts, scalp, flexures, axillae — moist, erythematous, yellow greasy scale rather than dry micaceous. Sebopsoriasis/seborrhiasis.

• Selectively/exclusively folds/flexures: ears, axillae, groin, inframammary folds, navel, intergluteal crease, penis, lips, web spaces; may also involve scalp/nails.

• Diaper area, infants ages 2-8 months; brightly erythematous, sharply demarcated. Clears with topical therapy but may reappear in adulthood.

• 2-5 mm water-drop lesions, abrupt eruption after acute infection (e.g., streptococcal pharyngitis); mostly age <30.
• Responds rapidly to erythemogenic-dose broad-band UVB (suberythemogenic doses have little impact — one of few forms where broad-band has advantage over NB UVB). MED testing recommended.
• Recurrence may relate to pharyngeal streptococcal carriage (patient or contact) — dicloxacillin 250mg QID ×10 days + rifampin 600mg/day may clear chronic carriage.

• Typically patients with existing plaque psoriasis/psoriatic arthritis. Sudden onset — lakes of pus periungually, palms, plaque edges; flexural erythema precedes generalization → generalized erythema + more pustules. Pruritus/burning. Mucous membrane lesions common (red scaly lips, superficial tongue/mouth ulcerations, geographic/fissured tongue).
• Frequently ill: fever, erythroderma, hypocalcemia, cachexia. ARDS reported with pustular/erythrodermic psoriasis. Other complications: pneumonia, CHF, hepatitis.
• Provoked by systemic corticosteroid withdrawal; also observed as presenting sign of Cushing disease. Other implicated drugs: iodides, coal tar, terbinafine, minocycline, hydroxychloroquine, acetazolamide, salicylates. Strong familial psoriasis history usual. Can occur in infants/children without drug trigger, or as episodic event punctuating localized acral pustular psoriasis.
• Treatment: acitretin often effective; IL-36 biologic therapy, anakinra, canakinumab may be needed; isotretinoin sometimes effective; cyclosporine, methotrexate, other biologics as alternatives; dapsone 50-100 mg/day effective in some cases.

• Acral erythematous plaques studded with pustules; nail beds heavily involved — fingernails float on pus lakes → anonychia. Hyperkeratosis → fingertips increasingly painful, taper to keratotic points. Occasional generalized pustular flares. (See Dermatitis Repens below.)

• Term for pustular psoriasis of pregnancy. Flexural erythema with pustules → generalized pustular flare + increasing toxicity. Systemic retinoids inappropriate (pregnancy). Many respond only to delivery — early delivery strongly considered once safe for infant. Alternatively prednisone 1 mg/kg/day (also aids neonatal lung maturity). Cyclosporine also used.

• Generalized erythroderma (see Exfoliative Dermatitis section below).

• Unpredictable — usually begins scalp/elbows, may remain localized for years; chronic disease may be limited to fingernails. Sacral involvement may be confused with candidiasis/tinea.
• Isomorphic response (Koebner phenomenon): typical lesions at sites of trivial injury (scratches, incisions, burns), after viral exanthema/pityriasis rosea, or if severely burned during phototherapy (reducing light dose resolves the flare and clears plaques).
• Woronoff ring: concentric blanching at periphery of healing plaque — often first sign of phototherapy response.
• Palms/soles: may be exclusively affected, chronic, extremely treatment-resistant.
• Hepatitis C association with psoriasis and psoriatic arthritis — full hepatitis panel before hepatotoxic drugs (methotrexate); IFN treatment of hepatitis can exacerbate/induce psoriasis. Anti-TNF-α promising even with chronic HCV; etanercept improves liver manifestations.

• All psoriasis is histologically pustular. Spongiform intraepidermal pustules + Munro microabscesses in stratum corneum.
• Early guttate: focal parakeratosis with "seagull" outline, neutrophils immediately above (sampling error may miss). Plaque psoriasis: numerous neutrophilic foci at multiple stratum corneum levels atop parakeratosis foci, alternating with orthokeratotic zones (rhythmic pattern). Focal granular layer absence corresponds to parakeratosis foci.
• Well-developed plaques: regular acanthosis, long bulbous rete ridges, thinning over dermal papillae, dilated papillary capillaries — correlates with Auspitz sign. Spongiosis scant except around neutrophil collections.
• Pustular psoriasis, geographic tongue, Reiter syndrome: larger spongiform pustules, little acanthosis in grossly pustular lesions. Reiter: massively thickened stratum corneum with prominent neutrophil foci above parakeratosis alternating with orthokeratosis.
• Acral lesions: often nondiagnostic, prominent spongiosis → differential of psoriasis vs chronic psoriasiform spongiotic dermatitis; neutrophil foci with serum may mimic impetiginized crusting.
• DIF: intense stratum corneum autofluorescence with all antibodies/complement/fibrin, independent of fluorescent label (also seen in H&E, unstained frozen sections) — also noted in psoriasiform candidiasis.
• Distinguished from dermatitis by: paucity of edema, relative absence of spongiosis, tortuous capillary loops, neutrophils above parakeratosis foci.
• Psoriasiform syphilis: long slender rete ridges, vacuolar interface dermatitis, endothelial-swollen "no-lumen" vessels, plasma cells (absent in ~1/3 of biopsies but other features still suggestive).
• Mycosis fungoides psoriasiform lesions: epidermotropism of large, dark, angulated lymphocytes with little spongiosis; papillary dermal fibrosis; asymmetric superficial perivascular infiltrate favoring epidermal side ("bare underbelly sign").

• DM, LE, seborrheic dermatitis, pityriasis rosea, lichen planus, eczema, psoriasiform syphilid.
• Distribution: psoriasis on extensor elbows/knees/scalp; DM shares this distribution; LE generally lacks extensor involvement. DM: heliotrope sign, atrophy, poikiloderma, nailfold changes. DLE: follicular hyperkeratosis (carpet tack sign).
• Seborrheic dermatitis: eyebrows, nasolabial angle, ears, sternal region, flexures; greasy yellowish scale vs dry white shiny psoriatic scale; Auspitz sign absent in seborrheic dermatitis.
• Pityriasis rosea: upper arms/trunk/thighs, weeks duration, oval lesions along skin tension lines, crinkling + collarette scale, herald patch.
• Lichen planus: flexor wrists/ankles, pronounced violaceous color (marked hyperpigmentation in darker skin); nails longitudinally ridged/thickened (not pitted); pterygium characteristic.
• Hand eczema: psoriasis more sharply marginated but can be indistinguishable.
• Psoriasiform syphilid: infiltrated copper-colored papules, figurate pattern; serologic tests positive (prozone reactions possible — dilute serum); generalized lymphadenopathy, mucous patches.

• Chronic hand/foot inflammatory disease, usually stable on extremities, rare generalized pustular flares. Begins distally on a digit (nail bed pustule or paronychia); extension via fresh pustules with hyperkeratosis/crusting. Unilateral initially, asymmetric throughout. Nails become dystrophic/float on pus; anonychia common in chronic cases. "Dermatitis repens" for more indolent distal finger involvement.
• Mucous membrane involvement possible even with localized skin disease: painful circular white tongue plaques with inflammatory areolae, fibrinous membrane; fissured/geographic tongue.
• Histology: acute stage intraepithelial spongiform pustules identical to psoriasis; later hyperkeratosis with parakeratosis or atrophy.
• Treatment: topical corticosteroids, calcipotriene, dapsone, sulfapyridine, methotrexate, PUVA, acitretin, cyclosporine, topical mechlorethamine, anti-TNF agents, anakinra. Note: anti-TNF agents have also triggered similar eruptions.

• Bilateral, symmetric; thenar/hypothenar eminences or central palms/soles. Erythematous areas with pinhead pustules → enlarge/coalesce into pus lakes → denuded areas/crusts/hyperkeratosis.
• Strongly associated with thyroid disorders and cigarette smoking. Lithium and other psoriasis-aggravating drugs can induce it.
• SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) — Kahn's designation. History: 1968 Kato — first case, bilateral clavicular osteomyelitis + palmoplantar pustulosis; 1974 Sonozaki — persistent PPP + sternoclavicular hyperostosis.
• Features: PPP + acneiform eruption + sternoclavicular/sternomanubrial/costochondral joint pain/swelling; shoulder/neck/back pain, motion limitation. Brachial plexus neuropathy, subclavian vein occlusion possible. Lumbar spine/sacroiliac usually spared. Chronic multifocal osteomyelitis (children) = pediatric variant. May coexist with Behçet disease features. Knees/spine/ankles may be involved; ivory vertebrae described.
• Treatment resistant. Topical steroids, retinoids, calcipotriene, macrolactams = some benefit. Acitretin 1 mg/kg/day = generally extremely effective (faster rebound than etretinate). Also: apremilast, dapsone, colchicine, tofacitinib, cyclosporine, hydroxyurea, alitretinoin, cefcapene pivoxil HCl (3rd-gen cephalosporin), leflunomide, MMF. Oral 8-MOP + high-intensity UVA or soak PUVA; grenz ray = prolonged remissions in some. SAPHO chronic osteomyelitis may respond to bisphosphonates.

• First described by George Andrews. Symmetric, grouped, vesicular/pustular palm/sole eruption with exacerbations/remissions. Andrews considered discovery/elimination of a remote infection focus crucial to diagnosis.
• Pustules primary; tiny hemorrhagic puncta intermingled. Coalescing → honeycomb epidermal structure. Begins midpalm/sole, spreads outward; no web space involvement (unlike tinea pedis).
• Fully developed: complete, symmetric palm/sole coverage. During flares: leukocytosis 12,000-19,000/mm³, 65-80% neutrophils. Scaling in evolved lesions (adherent, tough, dry); pustule/vesicle crops during exacerbations, severe itching, tenderness possible. Regarded by many as infection-triggered psoriasis variant.

• Common (incidence 10-78% reported); older patients, active exacerbations, enthesitis, psoriatic arthritis more likely to show nail abnormalities
• Nail plate pits (most common), less often furrows/Beau lines, crumbling plate, leukonychia (rough/smooth surface); splinter hemorrhages in nail bed, reddish bed discoloration, horny masses
• Hyponychium: subungual hyperkeratosis, oil spots, yellowish-green discoloration in onycholysis area; may closely simulate onychomycosis
• Nail disease severity may correlate with skin/joint disease severity; pustular psoriasis may cause onycholysis with nail bed/perionychial pus lakes; rarely anonychia results
• Other papulosquamous diseases affect nails similarly (except nail pitting, psoriasis-specific); Reiter disease, pityriasis rubra pilaris, Sézary syndrome, acrokeratosis paraneoplastica produce hypertrophic nails with subungual hyperkeratosis
• Treatment depends on cutaneous/nail involvement degree (see Ch. 10); successful systemic psoriasis treatment usually improves/clears nails — methotrexate, PUVA, cyclosporine, biologics, acitretin effective; secukinumab specifically trial-supported for nail psoriasis
• Local therapies limited: intralesional triamcinolone 3-5mg/mL via 30-gauge needle frequently helpful (digital nerve block facilitates); lasers, phototherapy, PDT other procedural options
• Topical 5-FU to proximal nailfold effective (avoid free nail edge — distal onycholysis risk); topical cyclosporine, tacrolimus, tazarotene 0.1% gel also helpful; topical calcipotriol improves ~50% of localized pustular nail psoriasis (maintenance after systemic retinoid success)

• Definition: Chronic, polygenic, systemic inflammatory dermatosis driven by the IL-23 / IL-17 cytokine axis.
• Pathophysiology: Dendritic cells secrete IL-23 → activates Th17/Tc17 cells → release of IL-17A, IL-17F, IL-22, TNF-α → hyperproliferation of keratinocytes. Epidermal transit time reduced from normal 28 days to 3 to 4 days. Susceptibility gene: PSORS1 (HLA-Cw6 allele).
• Key Clinical Diagnostic Signs:
• Auspitz Sign: Pinpoint bleeding after lifting silvery-white scale (rupture of capillaries in dermal papillae).
• Koebner Phenomenon: Development of new psoriasis plaques along lines of skin trauma.
• Woronoff Ring: Pale blanching ring surrounding resolving psoriasis plaque.

Histopathology of Psoriasis

• Regular acanthosis with uniform elongation of rete ridges ("test tubes in a rack").
• Hyperkeratosis with Parakeratosis (retained nuclei in stratum corneum).
• Loss of stratum granulosum.
• Munro Microabscesses: Neutrophil collections in stratum corneum.
• Kogoj Spongiform Pustules: Neutrophil collections in upper spinous layer.
• Thinning of suprapapillary plates with dilated tortuous capillaries in dermal papillae.

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• Most common subtype (80–90%); sharply demarcated erythematous plaques with thick, silvery-white micaceous scale on extensor knees, elbows, scalp, presacral region.

• Multiple small, drop-like (1–10 mm) papules over trunk and limbs.
• Classic Trigger: Group A Beta-Hemolytic Streptococcal pharyngitis (tonsillitis); elevated ASO titer. High rate of spontaneous clearance or evolution to chronic plaque psoriasis.

• Smooth, red, shiny, glazed plaques WITHOUT SCALE located in body folds (axillae, groin, inframammary, gluteal cleft).

• Generalized Pustular Psoriasis (Von Zumbusch): Life-threatening acute eruption of sterile pustules on fiery red skin, fever, leukocytosis, hypocalcemia. Triggered by rapid withdrawal of oral systemic corticosteroids!
• Palmoplantar Pustulosis: Sterile yellow pustules on scaly palmar/plantar plaques; strongly linked to cigarette smoking.

• Generalized erythema affecting > 90% Body Surface Area. High risk of hypothermia, high-output heart failure, hypoalbuminemia, sepsis.

• Pitting (proximal matrix damage), Oil Drop / Salmon Patch Sign (yellow-brown bed discoloration), subungual hyperkeratosis, onycholysis, splinter hemorrhages. Present in up to 80% of psoriatic arthritis patients.