Cutaneous Photosensitivity Diseases

• All skin phototypes react to sunlight because skin contains chromophores (molecules) that absorb UVR or visible light.
• Absorbed energy is re-emitted harmlessly OR diverted to drive thermochemical reactions → molecular/cellular/tissue/clinical changes.
• Changes are either repaired or become permanent.
• Nucleic acids are the most ubiquitous chromophores and can initiate UVR-induced changes.
• Opsin-3 in melanocytes may act as a sensor for visible light — appears to be a negative regulator of melanin production.
• Photodermatoses result from either:
• Abnormal tissue responses following absorption of photons by endogenous molecules, OR
• Expected responses to absorption by porphyrins or photosensitizing drugs/chemicals.

• Immunologically mediated:
• Polymorphous light eruption (PMLE)
• Actinic prurigo
• Hydroa vacciniforme
• Chronic actinic dermatitis (CAD)
• Solar urticaria
• Defective DNA repair and chromosomal instability disorders
• Photoaggravated dermatoses
• Chemical- and drug-induced photosensitivity
• Exogenous: ingested or externally applied drugs/chemicals
• Endogenous: cutaneous porphyrias, pellagra, Smith–Lemli–Opitz syndrome

• Worldwide, PMLE is the most common photodermatosis.
• Photoaggravated dermatoses, drug-induced photosensitivity, and CAD are also commonly observed, depending on population.
• Solar urticaria is relatively uncommon.
• All have a significant negative effect on quality of life.

• Onset within hours of sun exposure, pink-red edematous papules/papulovesicles/plaques primarily on extensor forearms/dorsal hands/neck, mildly pruritic, lesions last days to a few weeks → PMLE.
• Onset within hours, non-pruritic, lesions last weeks to months → Cutaneous lupus erythematosus (check ANA, anti-Ro, anti-La).
• Onset within minutes, lesions resemble hives, primarily upper chest/outer arms, pruritus > burning/pain, lesions last < 24 hours → Solar urticaria.
• Pain > pruritus, primarily on dorsal hands → Erythropoietic protoporphyria (EPP).
• Eczematous eruption, primarily in sun-exposed areas + review topical medications/sunscreens → Photoallergic contact dermatitis.
• Eczematous eruption + review systemic drugs → Photoallergic drug eruption.
• Eczematous eruption + underlying dermatosis history (e.g. atopic dermatitis) → Photoaggravated dermatosis.
• Initially sharp cut-off at clothing lines, profound lichenification, chronic duration → Chronic actinic dermatitis.
• Resembles sunburn + review systemic drugs → Phototoxic drug reaction to systemic medication.
• Resembles sunburn + review topical medications/chemicals → Phototoxic contact dermatitis to topical medication or chemical.
• Sun sensitivity history but no visible eruption at exam is characteristic for PMLE and solar urticaria.

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Key features

• Phototoxicity: exaggerated sunburn-like reaction, usually medication-caused.
• Photoallergy: eczematous lesions, most commonly related to topical photoallergens.
• Cutaneous porphyrias: example of phototoxicity induced by endogenous agents.
• Management: identification/avoidance of offending agent + photoprotection.

Introduction and history

• Divided into phototoxicity and photoallergy.
• Phototoxicity: direct tissue/cellular injury following UVR-induced activation of phototoxic agent; theoretically inducible in any individual.
• Photoallergy: DTH response — sensitization phase, incubation period of 7–10 days (after first exposure), then clinical elicitation reaction on subsequent challenge; only immunologically sensitized individuals affected.
• Phototoxic agents used as medications since as early as 4000 BCE (Mesopotamia, later India/Egypt): plant-derived psoralens for leukoderma.
• 1913: Meyer-Betz demonstrated hematoporphyrin-induced phototoxicity on himself.
• Current PUVA method introduced in the 1970s.
• Photoallergy first recognized in 1939 based on classic sulfanilamide study by Epstein.

Epidemiology

• Exact prevalences unknown; frequency in photodermatology referral centers: 3%–16% for phototoxicity, 1%–8% for photoallergy.
• Both more common in White vs Black individuals.

Pathogenesis

• Phototoxicity: generation of free oxygen radicals, superoxide anions, hydroxyl radicals, singlet oxygen → cytotoxic tissue effects.
• Other mechanisms: stable photoproducts (e.g. chlorpromazine, tetracyclines), photoadducts (e.g. psoralens), recruitment of inflammatory mediators (e.g. porphyrins, demeclocycline).
• Photoallergy pathogenesis identical to allergic contact dermatitis, except requires UVR to induce photoallergen formation.

Clinical features — Phototoxicity

• Develops within hours of cutaneous/systemic exposure to phototoxic agent + appropriate UVR.
• Action spectrum for vast majority of agents falls within UVA.
• Erythema, edema, burning/stinging; vesicles/bullae in severe cases.
• Oral medication reactions resemble exaggerated sunburn; resolve with desquamation and hyperpigmentation once agent/UVR avoided.
• Other manifestations:
• Pseudoporphyria — frequently caused by NSAIDs, especially naproxen.
• Photo-onycholysis — reported with tetracyclines and psoralens.
• Slate-gray hyperpigmentation — reported with amiodarone, tricyclic antidepressants, diltiazem.
• Lichenoid eruptions — seen with quinine and quinidine.
• Burning/pain sensations — amiodarone.
• Systematic review of oral agent phototoxicity: strongest evidence for vemurafenib, NSAIDs, antibiotics (fluoroquinolones and tetracyclines).
• 5-FU, methotrexate, retinoids associated with photosensitivity reactions, but not typical phototoxicity/photoallergy.
• 5-FU: UVR exacerbates inflammation at AK sites.
• Methotrexate: causes "recall" of prior UVR-induced erythema; phototesting normal; mechanism unclear.
• Isotretinoin/acitretin/topical tretinoin: phototesting usually normal; propensity for UVR erythema likely due to retinoid-induced stratum corneum thinning.
• Phytophotodermatitis: linear streaks of erythema ~1 day after contact with furocoumarin-containing plants + subsequent UVA exposure; linear postinflammatory hyperpigmentation classic.
• Plants: yarrow, parsley, celery, lime, fig.
• Common in vegetable harvesters, bartenders mixing drinks outdoors.
• Roofers/road workers: phototoxicity from tar + UVA.
• St John's wort (Hypericum perforatum): contains hypericin (phototoxic agent).
• Voriconazole: prophylactic antifungal in immunocompromised hosts; causes phototoxic reactions, actinic cheilitis, lentigines, increased risk of large hypertrophic actinic keratoses, aggressive cutaneous SCC, and cutaneous melanoma. Alternative: posaconazole (not associated with phototoxicity).
• Vemurafenib (selective BRAF inhibitor): phototoxic with action spectrum in UVA range.

Common Phototoxic Agents

• Antiarrhythmics: amiodarone, quinidine.
• Anti-fibrotic agents: pirfenidone.
• Calcium channel blockers: diltiazem.
• Diuretics: furosemide, thiazides.
• NSAIDs: nabumetone, naproxen, piroxicam.
• Phenothiazines: chlorpromazine, prochlorperazine.
• Photodynamic therapy agents: aminolevulinic acid, methyl aminolevulinate.
• Psoralens (oral or topical): 5-methoxypsoralen, 8-methoxypsoralen, 4,5′,8-trimethylpsoralen.
• Quinolones: ciprofloxacin, lomefloxacin, nalidixic acid, sparfloxacin.
• St. John's wort: hypericin.
• Sulfonamides: sulfonylureas.
• Tar (topical).
• Targeted therapies: BRAF inhibitors (e.g. vemurafenib), anti-CCR4 antibody (mogamulizumab), EGFR inhibitors, avapritinib, enzalutamide.
• Tetracyclines: doxycycline, demeclocycline.
• Triazole antifungals: voriconazole.

Common Photoallergic Agents

• Topical agents:
• Sunscreens (active UV absorbers): oxybenzone (benzophenone-3), octocrylene.
• Fragrances: 6-methylcoumarin, musk ambrette, sandalwood oil.
• Antimicrobial agents: bithionol, chlorhexidine, fenticlor, hexachlorophene.
• NSAIDs: diclofenac, etofenamate (outside US), ketoprofen.
• Phenothiazines: chlorpromazine, promethazine.
• Systemic agents:
• Antiarrhythmics: quinidine.
• Antimalarials: quinine.
• Antifungals: griseofulvin.
• Antimicrobials: quinolones (e.g. enoxacin, lomefloxacin), sulfonamides.
• NSAIDs: ketoprofen, piroxicam* (*often positive patch test to thimerosal).

Clinical features — Photoallergy

• In previously sensitized individuals: exposure to photoallergens + sunlight → pruritic eczematous eruption.
• More severe: vesicles and bullae (less common than in phototoxic reactions).
• Phototoxic reactions usually resemble sunburns; photoallergic often resemble allergic contact dermatitis, but morphology alone may not always distinguish.
• UK/US: sunscreen agents (especially benzophenone-3/oxybenzone) most common cause of photoallergy — but overall prevalence among sunscreen users very low.
• Europe: topical NSAIDs, especially ketoprofen and etofenamate, most common cause.
• Confirmed by photopatch testing: duplicate sets of photoallergens on patient's back, only one set irradiated with UVA; interpretation shown in Fig. 87.19.

Commonly Employed Photopatch Test Series (selected concentrations)

• Sunscreen ingredients:
• Ethylhexyl methoxycinnamate (octinoxate) — 7.5% pet (NA) / 10% pet (Europe)
• Benzophenone-4 (sulisobenzone) — 2% pet
• PABA — 10% pet
• Ethylhexyl dimethyl PABA (padimate O) — 10% pet
• Benzophenone-3 (oxybenzone) — 10% pet
• Ethylhexyl salicylate (octisalate) — 5% pet
• Butyl methoxydibenzoyl methane (avobenzone) — 5% pet (NA) / 10% pet (Europe)
• Homosalate — 5% pet
• Methyl anthranilate — 5% pet
• Benzophenone-8 — 10% pet
• Ensulizole — 10% pet
• 4-methyl-benzylidene camphor (enzacamene) — 10% pet
• Octocrylene — 10% pet
• Isoamyl p-methoxycinnamate — 10% pet
• Bemotrizinol (Tinosorb S) — 10% pet
• Drometrizole trisiloxane (Mexoryl XL) — 10% pet
• Uvinul A Plus — 10% pet
• Ethylhexyl triazone — 10% pet
• Bisoctrizole (Tinosorb M) — 10% pet
• Iscotrizinol (Uvasorb HEB) — 10% pet
• Terephthalylidene dicamphor sulfonic acid — 10% aq
• Microbicides: dichlorophene 1% pet, triclosan 2% pet, hexachlorophene 1% pet, chlorhexidine diacetate 0.5% aq, 3,4,5-tribromosalicylanilide 1% pet, bithionol 1% pet, fentichlor 1% pet.
• Anti-psychotics: promethazine hydrochloride 0.1% pet.
• NSAIDs: ketoprofen 5% pet (NA)/1% pet (Europe), etofenamate 2% pet, piroxicam 1% pet, benzydamine hydrochloride 2% pet.
• Fragrances: musk ambrette 1% pet, lichen acid mix 0.3% pet.
• Plants: sesquiterpene lactone mix 0.1% pet.
• Miscellaneous: sandalwood oil 2% pet, thiourea 0.1% pet.
• A petrolatum (100%) patch test also applied as control.
• Note: when comparing to sunscreen agents in Chapter 132, octyl = ethylhexyl.

Interpretation of Photopatch Tests

• UVA dose usually the lower of: 5 J/cm² or 50% of MED to UVA.
• Patterns: unirradiated vs UVA-irradiated reaction determines photoallergy, contact allergy + photoallergy, or contact allergy alone.

Pathology

• Phototoxicity: scattered necrotic keratinocytes ("sunburn cells") + superficial dermal infiltrate of primarily lymphocytes and neutrophils.
• Photoallergy: epidermal spongiosis + superficial dermal lymphohistiocytic infiltrate, indistinguishable from other spongiotic dermatitis causes.

Differential diagnosis

• Phototoxic reactions vs ordinary sunburn (requires more UVR exposure) and LE.
• Photoallergic reactions vs other dermatitis in sun-exposed areas, particularly airborne contact dermatitis and atopic dermatitis.
• Airborne contact dermatitis: all exposed sites involved (including upper eyelids, submental region, postauricular areas) — these are frequently spared in photoallergic contact dermatitis.

Treatment

• Identification and avoidance of offending agent of prime importance.
• If discontinuation not possible: strict photoprotection (UVB and UVA) required.
• Analgesia may help for both reaction types.
• Topical corticosteroids; short courses of systemic corticosteroids for severe flares of photoallergic dermatitis.
• Occasionally, evening dosing of phototoxic drug so peak systemic levels occur at night.

• Cutaneous porphyrias (Ch. 49): most obvious example of endogenous-agent photosensitivity.
• Mechanism of porphyrin-induced phototoxicity involves reactive oxygen species, complement system, mast cells, and neutrophils (Fig. 87.20 pathway: Sun + Porphyrin → excited state porphyrin → reactive oxygen species → inflammatory mediator cells → phototoxicity).
• Smith–Lemli–Opitz syndrome: AR disorder; early-onset photosensitivity to UVA in 55%–75% of patients.
• Frequency: 1 in 40,000 conceptions.
• Mutations in DHCR7 (encodes 7-dehydrocholesterol reductase) → accumulation of 7-dehydrocholesterol.
• Mechanism of photosensitivity unknown.
• Pellagra: due to niacin deficiency; associated with photosensitivity; pathogenesis unclear.

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Key features

• Primary underlying disease not caused, but exacerbated (sometimes severely) by sun exposure.
• Phototesting usually normal, with LE the exception.
• Therapy focuses on treatment of underlying disease.

Introduction and history

• Reasons for aggravation poorly studied, except for LE (Ch. 41).

Epidemiology

• Occur worldwide; prevalence in photodermatology referral centers as a group: 15%–25%.

Clinical features

• Primary dermatosis mildly or severely exacerbated by UVR, usually within minutes to hours, sometimes a day or more later.
• Exacerbated eruption usually limited to sites characteristically involved by underlying condition; less often involves all sun-exposed skin.

Pathology

• Histology is that of underlying dermatosis.

Differential diagnosis

• Recognized by features of underlying skin disease.
• Often includes PMLE in DDx — PMLE typically papular and mildly pruritic, negative lupus serology, can be induced by photoprovocation tests (~80% of patients) — but this requires repeated daily UVR exposures, not commonly done.
• PMLE may coexist with photoaggravated dermatoses, particularly LE.
• Photoaggravated atopic dermatitis: confirmed AD history + photosensitivity + positive phototest results.

Treatment

• Focus on underlying disorder and photoprotection.
• Topical corticosteroids and low-dose NB-UVB may help.
• Rarely, short courses of oral corticosteroids required.

• Acne vulgaris
• Atopic dermatitis
• Bullous pemphigoid
• Carcinoid syndrome
• Cutaneous T cell lymphoma (Sézary syndrome)
• Darier disease (keratosis follicularis)
• Dermatomyositis
• Disseminated superficial actinic porokeratosis
• Erythema multiforme
• Hailey–Hailey disease (familial benign chronic pemphigus)
• Hartnup syndrome
• Lichen planus and lichenoid drug eruptions
• Lupus erythematosus
• Pellagra
• Pemphigus, including pemphigus foliaceus (erythematosus)
• Pityriasis rubra pilaris
• Psoriasis (in some patients)
• Reticular erythematous mucinosis (REM)
• Rosacea
• Seborrheic dermatitis
• Grover disease (transient acantholytic dermatosis)
• Viral infections, including herpes simplex, exanthems

• Also known as transient (and later persistent) acantholytic dermatosis.
• Most common in White men over 40 with significant photodamage.
• Some patients flare in summer, others in winter.
• Pruritic, often crusted, skin-colored to pink papules and papulovesicles on trunk, primarily sun-exposed sites.
• Exacerbating factors: UV exposure, sweating, heat, occasionally friction and ionizing radiation.
• Lesions may resolve over weeks to months but commonly recur.
• Histology — 4 major patterns (sometimes combined):
• Darier disease-like (hypergranulosis, focal acantholytic dyskeratosis, overlying column of parakeratosis).
• Hailey–Hailey disease-like (obvious acantholysis, few dyskeratotic cells).
• Pemphigus vulgaris- or foliaceus-like (suprabasal split, acantholytic cells, foci of "tombstoning").
• Spongiosis with acantholysis (mononuclear cells in dermis/epidermis).
• Rarely, multinucleated acantholytic cells — termed pseudoherpetic pattern.
• Some cases resemble Dowling-Degos disease histopathologically.
• Differential diagnosis: folliculitis, miliaria rubra, arthropod bites, multiple lichenoid keratoses, early pemphigus foliaceus, and (when chronic) Darier disease.
• Except for the latter two, histologic exam allows distinction.
• Focal nature of histologic findings, negative immunofluorescence microscopy, lack of additional clinical features (e.g. palmar keratoses, longitudinal erythronychia with notching) → points to Grover disease.
• Treatment: topical agents (corticosteroids, pramoxine, calcineurin inhibitors, vitamin D analogues), oral antihistamines, avoidance of exacerbating factors.
• Oral retinoids, PUVA, UVA1 tried with some success; most recently, dupilumab.

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Key features

• Acute/subacute effects: acute inflammatory erythema (sunburn), pigment darkening, delayed pigmentation, epidermal hyperplasia, immunologic changes, vitamin D3 synthesis.
• Visible light: can induce pigmentation in darker skin phototypes and immediate erythema in fair-skinned individuals.
• Chronic effects: photoaging and photocarcinogenesis (keratinocyte carcinomas and melanoma).
• Underlying mechanisms reviewed in Chapter 86.

• Primarily result of UVR absorption by DNA/RNA and possible interaction of visible light with opsin-3 on melanocytes in darkly pigmented individuals.

Acute inflammatory erythema (sunburn)

• In terrestrial sunlight, wavelengths around 300 nm are the most erythemogenic.
• MED in skin phototype I: ~30 mJ/cm² (300 J/m²) for broadband UVB (280–320 nm); 30 J/cm² (300 kJ/m²) for broadband UVA (320–400 nm).
• UVB-induced sunburn pain thought to result from activation of epidermal TRPV4 ion channels.
• Brief immediate erythema within seconds in a few individuals, lasting minutes.
• Typical delayed bright red sunburn appearance: begins within 30 minutes to 8 hours, peaks at 12–24 hours, diminishes over hours to days (UVB).
• UVA-alone reaction: deeper red, usually more persistent.
• After excessive exposure: edema, blistering; if widespread → systemic symptoms (chills, malaise).
• Followed by pruritus and desquamation over days to weeks.
• Lighter skin phototypes: visible light can produce immediate erythema.
• Photoprotection is the best preventive measure.
• Treatment: fluid intake, emollients, topical corticosteroids, oral NSAIDs/steroidal anti-inflammatory agents.
• Placebo-controlled trial, 20 healthy adults: 200,000 IU vitamin D3 administered 1 hour after experimental sunburn → reduced proinflammatory mediators (e.g. TNF), reduced skin redness, increased anti-inflammatory mediator arginase-1 (in those with higher serum vitamin D3 levels).

Pigment darkening and delayed tanning

• Immediate, often grayish, darkening lasting 10–20 minutes, occurs within seconds of ~2–12 J/cm² UVA irradiation; response can last up to 3 months.
• Darkly pigmented individuals: blue spectrum of visible light induces similar changes, possibly via opsin-3 absorption.
• Immediate pigment darkening: transient changes from photo-oxidative darkening and cellular redistribution of melanin within melanocytes.
• Persistent pigment darkening: pigmentation persisting >2 hours post-irradiation; brownish, lasts up to 24 hours; also due to oxidation of pre-existing melanin.
• Blends with delayed pigmentation (tanning): develops in genetically competent individuals over hours to days, persists weeks to months.
• Follows ~40 mJ/cm² broadband UVB (slightly above MED, especially fair-skinned) and 15–20 J/cm² broadband UVA (slightly less than MED).
• Results in mild decrease in sunburning sensitivity (factor of 2 to 4).

Epidermal hyperplasia

• Lasts about a month; occurs over hours to days following UVB (generally not UVA) exposure.
• Due to markedly increased mitotic rate and DNA/RNA/protein synthesis, after several initial hours of inactivity.
• Hyperplasia of viable epidermis + thickening of stratum corneum → several-fold protection against later sunburning; adds to and may exceed delayed tanning protection (especially fair-skinned).
• Generally neither visible nor palpable.

Immunologic changes

• UVB and UVA alter epidermal Langerhans cell function, generate suppressor T lymphocytes, change cutaneous cytokine profile.
• Detailed in Chapter 86.

Vitamin D3 synthesis

• UVB (maximum: 300 ± 5 nm) quickly converts epidermal 7-dehydrocholesterol into previtamin D3.
• Isomerizes to vitamin D3 (cholecalciferol) → converted in liver to 25-hydroxyvitamin D → converted in kidneys to 1,25-dihydroxyvitamin D (active form).
• UVR-induced vitamin D3 synthesis maximal at suberythemogenic doses.
• Action spectrum for vitamin D synthesis similar to that for DNA damage.
• Ideally, vitamin D homeostasis achieved via incidental outdoor daylight exposure + dietary sources rather than intentional sun/tanning bed exposure.

Other changes

• Otherwise healthy, non-medicated individuals may develop photo-onycholysis and increased skin fragility with blistering (pseudoporphyria) after intense sun/tanning bed exposure.
• Mid-dermal elastolysis: patches of finely wrinkled skin, loss of elastic fibers in mid-reticular dermis (Ch. 99); onset frequently associated with intense UVR exposure.
• Brachioradial pruritus: primary pruritus of outer arm, associated with cervical radiculopathy; UVR may act as trigger in many patients (Ch. 6).

Photoaging in fair-skinned patients

• Solar (actinic) elastosis: thickened skin with yellow hue; most common on face, neck, extensor mid arms.
• More widespread in tropical climates, especially with minimal constitutive pigmentation.
• Histology: marked increase in abnormal, altered dermal elastic fibers.
• Cutis rhomboidalis nuchae: similar changes on posterior neck; deep furrowing with leathery texture.
• Solar lentigo: light brown to dark brown, even-colored or reticulated macule/patch in sun-exposed areas (usually multiple); dorsal hands, extensor forearms, upper trunk, face most affected (Ch. 109).
• Histology: elongation and hyperpigmentation of rete ridges + mild increase in melanocyte number.
• Ephelide (freckle): light red-brown to medium brown macule, usually <6 mm; sun-exposed, clustered, more apparent after sun exposure (Ch. 112).
• Histology: hyperpigmentation of basal layer WITHOUT elongation of rete ridges.
• Idiopathic guttate hypomelanosis: favors chronically sun-exposed extremities (forearms, shins), typically spares face; well-demarcated hypopigmented macules, 3–10 mm (Ch. 66).
• Poikiloderma of Civatte: reticulated red to red-brown patches of telangiectasias sparing perifollicular skin; most common on lateral neck in fair-skinned individuals with significant cumulative sun exposure.
• Characteristic sparing of central submental region.
• Mild atrophy and hyperpigmentation sometimes present.
• Histology: telangiectasias, mild epidermal atrophy, melanophages, dermal solar elastosis.
• Favre–Racouchot syndrome: multiple large open comedones on lateral/inferior periorbital area, with marked surrounding solar elastosis; cigarette smoking may be a cofactor in some patients.
• Histology: dilated pilosebaceous openings, cyst-like spaces filled with horny material, marked solar elastosis.
• Solar purpura: occurs in cumulatively photodamaged areas subject to trauma (dorsal hands, extensor forearms, shins); resolves over weeks, may leave brown hemosiderin discoloration; often accompanied by skin fragility.
• Adult colloid milium: translucent yellow papules, 1–3 mm; numerous, closely spaced, in chronically sun-exposed sites (neck, face, dorsal hands).
• Histology: homogeneous masses of PAS-positive, diastase-resistant colloid in papillary dermis; positive staining with thioflavin T and Congo red in some cases.
• Nature of colloid debated; may represent elastin degeneration in some forms.
• Erosive pustular dermatosis of the scalp: sterile pustules, keratotic crusts, erosions, mild inflammation in atrophic photodamaged bald scalp skin; similar findings can occur elsewhere with atrophic/fragile skin (e.g. lower extremities with venous hypertension, sites of neonatal injury; Ch. 25).
• Acquired elastotic hemangiomas: erythematous plaques within actinically damaged skin, usually neck or upper extremities.
• Histology: horizontal proliferation of capillaries in upper reticular dermis + prominent solar elastosis.
• Full list of cutaneous signs of significant photodamage:
• Common: solar elastosis, cutis rhomboidalis nuchae, wrinkling (coarse > fine), Favre–Racouchot syndrome, poikiloderma of Civatte ("red neck"), solar purpura and hemosiderin deposition, fragility and skin tears, pseudoscars, erosive pustular dermatosis, dyschromia (including idiopathic guttate hypomelanosis), solar lentigines, ephelides, weathering nodules.
• Uncommon: acquired elastotic hemangioma, adult colloid milium, elastoma of Dubreuilh, elastotic nodules of the ear, keratoelastoidosis marginalis, solar elastotic bands.
• Neoplasms: actinic keratoses, SCC, BCC, cutaneous melanoma (including lentigo maligna), Merkel cell carcinoma.
• Skin tear classification scheme:
• 1a: tear can be realigned to normal anatomic location, flap color not pale/dusky/darkened.
• 2a: tear cannot be realigned to normal anatomic location, flap color not pale/dusky/darkened.
• 1b: tear can be realigned, flap color pale/dusky/darkened.
• 2b: tear cannot be realigned, flap color pale/dusky/darkened.
• 3: skin flap absent.

Photoaging in patients with dark skin phototypes

• Photoaging much less pronounced and has delayed onset vs fair-skinned individuals.
• East Asians (Chinese, Japanese, Koreans, Filipinas): small seborrheic keratoses, melasma, mottled hyperpigmentation common; wrinkles fine, usually not before age 50.
• South Asians (Indians, Pakistanis, Sri Lankans, Bangladeshis): often darker than East Asians; dyspigmentation and fine wrinkles are primary signs.
• Lightly pigmented Latinos: changes similar to White individuals.
• Brown-skinned Latinos: photoage similar to South Asians.
• Black-skinned individuals (African-Americans, Afro-Caribbeans, Africans): wide range of skin phototypes (III–VI); dyspigmentation common, fine wrinkles appear late in life.

Photocarcinogenesis

• Chronic sun exposure associated with development of AKs, SCC, BCC, melanoma (particularly lentigo maligna).
• SCCs tend to develop within chronically sun-exposed areas in fair-skinned individuals; e.g. people migrating to Australia early in life have higher SCC risk than those arriving when older.
• BCC incidence higher in native-born Australians than immigrants; statistically significant association between intermittent sun exposure and BCC risk.
• Sunscreen use → decrease in development of AKs, SCC, melanoma, and to a lesser extent BCC.
• Tanning bed exposure associated with increased risk of cutaneous melanoma, SCC, and BCC.
• In populations with greater proportion of darkly pigmented individuals: higher melanoma incidence associated with increased UV index and lower latitude seen only in non-Latino White populations, NOT in Black or Latino populations.

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• Cutaneous erythema is a normal response to UVR exposure — termed photosensitivity.
• Abnormal photosensitivity: cutaneous responses to sunlight (UVR and/or visible radiation) falling outside healthy-population ranges — skin reddening at lower doses, and/or reactions of abnormal morphology (rash during/after sun exposure).
• Classification of cutaneous photosensitivity diseases:
• Idiopathic (immunological): polymorphic light eruption (PLE), juvenile spring eruption (JSE), actinic prurigo (AP), chronic actinic dermatitis (CAD), solar urticaria (SU), hydroa vacciniforme (HV).
• Genophotodermatoses (Chapter 76).
• Metabolic (Chapter 61).
• Drug- or chemical-induced photosensitivity: endogenous (porphyrias, Chapter 58); exogenous (systemic or topical drug/chemical photosensitivity).
• Photoaggravated skin diseases.
• Idiopathic (immunological) photodermatoses are commonest due to high PLE prevalence. Genophotodermatoses are rare. Photoaggravated diseases are relatively common and often hard to distinguish clinically from specific photodermatoses — emphasising the importance of phototesting.

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• Recurrent, delayed-onset, abnormal reaction to sunlight (or artificial UVR), resolving without scarring; several morphological variants hence "polymorphic."
• Synonyms: polymorphous light eruption (PMLE); juvenile springtime eruption (arguably a variant); spring and summer eruption of the elbows (probably a variant); benign summer light eruption (probably a variant); Taiwanese solar dermatitis (probably a variant).

• Common; severity varies widely, can markedly affect quality of life.
• Diagnosis usually straightforward, based on history; investigations to exclude alternatives not usually required.
• Management: photoprotection, natural hardening advice, prophylactic topical/systemic corticosteroid, sometimes prophylactic phototherapy; uncommonly other immunosuppression needed.
• Actinic prurigo was historically sometimes included within PLE but is now a distinct entity.

• Commonest cause of photosensitivity in many parts of the world. High point prevalence (10–20%) in selected northern European/North American populations. Lower prevalence in a Chinese population survey but still the most common photodermatosis diagnosed. Occurs more frequently further from the equator but reported near the equator too.
• Age: usually starts before 30 years; onset later in 25% of 545 Dundee patients.
• Sex: much commoner in females.
• Ethnicity: most frequently reported in Northern Europe/North America but also described among African, African American, Chinese, and Indian populations.

• LE (systemic, subacute cutaneous, discoid): questionnaire survey found 49% of LE respondents might also have PLE; another survey corroborated; however, prospective follow-up of 94 PLE patients found no increased LE risk — any increased risk is small.
• Actinic prurigo: PLE may be more common in AP patients — 35% of AP patients also reported PLE symptoms.
• Photosensitive psoriasis: no evidence PLE and psoriasis co-occur more than chance, but PLE is the most frequent trigger for photosensitive psoriasis.
• Other reported (probably coincidental) associations: hepatitis C (with apparent beneficial IFN-α2a effect on PLE in one report; another report describes an eruption at covered IFN-α2a injection sites sharing PLE histological features); solar urticaria; aquagenic urticaria; unusual PLE localisation at sites of vitiligo or naevoid telangiectasia; common variable hypogammaglobulinaemia (improved with IV immunoglobulin); autoimmune thyroid disease (unconfirmed genuine association, both conditions common).

• Believed to be a delayed-type hypersensitivity response to a UV-induced allergen (photoallergen).
• Supported by: nature of lymphocytic infiltrate (mainly T-helper cells early, predominantly T-suppressor cells at 72h); pattern of adhesion molecule expression resembling contact dermatitis.
• Cause unknown; multifactorial pathogenesis suspected — possibly autoimmune, with abnormal delayed hypersensitivity to an undetermined endogenous molecule.
• Impaired apoptotic cell clearance may facilitate photo-induced autoantigen development; impaired UV-induced immunosuppression may then enable lesion manifestation.
• Implicated: pro-inflammatory cytokines (IL-1 family, particularly IL-36α and γ, and IL-31), altered regulatory T cells and dermal dendritic cells, differential antimicrobial peptide expression, IL-15 expression — pathways need further clarification.
• Relative wavelength intensity at different latitudes may play a role, uncertain if causative or just unmasking.
• Impression that it begins after particularly intense UVR exposure (sunbathing, sunbeds) — possibly leading to autosensitisation.
• Evidence: less UVR suppression of the induction phase of delayed hypersensitivity responses in PLE patients than non-PLE — may predispose to autosensitisation; fits with PLE patients appearing less prone to skin cancer than expected from sun avoidance alone (perhaps easier antigen recognition after UVR = better immunological skin cancer protection but more prone to PLE).

• More frequent at higher latitudes. Impression (unconfirmed) that greater prior sunlight exposure followed by more intermittent, less intense exposure predisposes to PLE.

• Superficial and deep, predominantly perivascular, dermal inflammatory cell infiltrate — mainly T lymphocytes, CD4+ in early lesions, CD8+ later.
• Upper dermal oedema common.
• Absence of dermal acid mucopolysaccharide deposits suggested to help distinguish from LE, but not always useful in practice.
• Some basal liquefaction not uncommon but less marked than LE. Spongiosis may be found, especially in papulovesicular PLE.
• Direct immunofluorescence negative.

• Previous suggestion of Chlamydia triggering not substantiated.

• Positive family history in 12–46% of patients (expect ~10–20% background). 15% of monozygotic twin pairs vs 5% of dizygotic twin pairs had PLE — confirms inherited component. Genetic modelling in PLE/AP families further confirms significant inherited component.

• UVR and occasionally visible light exposure important. One China report suggests higher altitude association (may have included AP cases). Contraceptive pill once considered relevant, now not implicated. Disease may be less severe post-menopause (unproven causality; may reflect natural tendency to diminish over time).

• History: trigger time from as little as 10 min to several hours of exposure; then delay until intensely itchy eruption develops at photo-exposed sites.
• "Priming phenomenon": need for 2–3 days of initial exposure before PLE occurs (particularly those affected only on sunny holidays).
• Delay after exposure until onset usually ≥6 hours; often not noted until evening/night or the following day.
• Early-onset variant: onset as soon as 30 min after first exposure — may cause diagnostic confusion with solar urticaria.
• With sunlight avoidance, resolves within a few days to 2 weeks. Longer duration reasons: unclear history (postinflammatory change confusion), true persistence from inadequate avoidance, secondary "eczematisation" (particularly atopics; consider sunscreen contact/photocontact reactions).
• Unexplained, unusually prolonged rash raises suspicion of LE or AP.
• Presentation:
• Typically affects only sunlight-exposed sites (exceptions explained by UV transmission through clothing).
• Face sparing in 28% of 549 patients, and dorsal hands sparing common — presumed tolerance from repeated perennial exposure ("hardening"), also seen as PLE decline late in summer.
• Facial involvement more common in children.
• Localised forms reported (e.g. at sites of brachial neuropathy).
• Generally non-scarring unless secondary excoriation prominent.
• Exposure source: usually sunlight (direct, through window glass, or thin clothing); sunbeds also implicated (including a case only at a site exposed to pressure while irradiated); many patients use sunbeds hoping for prophylaxis, often report "worst ever" PLE from this. Occupational sources: arc welding, photocopying equipment.

• Most frequent: mixed papulovesicular; closely followed by plaque and papular/micropapular; vesiculobullous and erythema multiforme-like variants uncommon.
• Rarely reported: insect bite-like (strophula), "sine eruptione" (typical time course, no visible rash), purpuric/haemorrhagic subtypes.
• Some suggest papulovesicular or purpuric variants should be distinct entities — but as aetiology of subtypes unknown and treatment approach the same, best regarded as variants of one condition.
• PLE is "often monomorphic within individuals" but some have different morphologies at different sites (e.g. oedematous plaques on face, papulovesicular on forearms).
• PLESAPS (Polymorphic Light Eruption with Severe Abnormal Phototesting Sensitivity): severe photosensitivity within the PLE spectrum; may be referred for photodiagnostic investigation to exclude CAD — but time course and UVB desensitisation response more typical of PLE than CAD.

• Immediate-onset PLE: consider solar urticaria (idiopathic or secondary to drugs, lupus, porphyria).
• Cutaneous LE excluded if lesions last >3 weeks.
• Jessner lymphocytic infiltrate possible differential but usually clear distinction.
• AP distinguished by early age of onset and dorsal nose/lip/conjunctival involvement.
• CAD occasionally needs consideration (e.g. pre-existing atopic eczema — PLE-triggered photoaggravated eczema vs CAD).

• Key issue is quality-of-life impact (holiday-only vs recurrent spring/summer vs, uncommonly, sunny winter days). Various PLE severity scores developed for clinical trials.

• Sunscreen allergy/photoallergy can complicate PLE.
• Reassurance: PLE patients have lower skin cancer risk than non-PLE, even accounting for increased sun avoidance.

• 94 Finnish patients followed to mean 32 years: 24% resolution, 51% milder disease.
• Registry study: usually a long-term course but symptoms usually improve over time.
• One report: negative provocation tests → more likely remission than positive tests (not yet replicated across centres).
• Dundee: substantial proportion needing repeated yearly prophylactic phototherapy eventually resolved/markedly improved and stopped attending (unclear if spontaneous or treatment-related).

• Monochromator phototesting: most patients don't need it; reserved for more severe/atypical disease. Most have normal MEDs; moderately reduced UVA and/or UVB thresholds in ~one-third tested. Uncommon subset (PLESAPS) show severe abnormal photosensitivity — important to distinguish from CAD.
• Provocation testing: occasionally provoked by small monochromator fields or during MED/MPD determination (papular response at threshold erythema dose, sometimes lower). Usually requires larger fields (4–6 cm diameter square to whole body) and often iterative testing with repeated daily exposures — up to 4 successive daily doses needed for 90% positive provocation in one series. High UVA doses near erythema threshold may be necessary. Site choice matters — most centres use arms/legs (natural eruption sites), though non-usually-exposed sites may give better prognostic info (less useful for initial diagnosis). UVA induces PLE in more patients than UVB in most series, but UVB can also reproduce PLE (localised testing and whole-body UVB treatment experience).
• Photopatch testing: may reveal coexistent contact/photocontact allergy to sunscreens.
• Autoantibody screen (ANA, anti-Ro, anti-La): always done if phototherapy/PUVA considered, or atypical LE-suspicious features present. ANA screening not very specific but reasonably sensitive — negative is reassuring; low-titre positive (often seen in PLE) hard to interpret and can be disregarded if unaccompanied by anti-Ro/anti-La and no LE clinical pointers. High ANA titres (unless explained e.g. Sjögren) should usually mean phototherapy avoidance unless UVA1 available (also usable in LE).
• Porphyrin screen: consider PCT (vesiculobullous PLE differential) or EPP (early-onset PLE differential); plasma spectrofluorimetry quick, worth requesting even with low suspicion.
• HLA class II typing: useful if AP suspected — absence of HLA-DR4 helps rule out AP (supports PLE); presence of DRB1*0407 subtype helps confirm AP.
• Skin biopsy histopathology: usually unnecessary, can help in atypical cases.

• Depends on severity, patient wishes, risk-benefit.
• First line: sun avoidance and protective measures sufficient for most mild/moderate cases; sunlight avoidance important for all. Avoid unnecessary intense exposure (e.g. sunny holidays); total avoidance NOT recommended (low-level sub-triggering exposure helps natural hardening). UV-absorbing window film for severely affected. Avoid 11am–3pm sun; tightly woven clothing. Broad-spectrum high-SPF sunscreens applied correctly (thickly, evenly, frequently). Vitamin D intake/supplementation advice important given sun avoidance.
• Second line: prophylactic phototherapy/photochemotherapy — main second-line therapy.
• RCT evidence: narrow-band (TL-01) UVB as effective as PUVA; PUVA more effective than broad-band UVB. UVA1 therapy can be used, though has also been reported to trigger unusually prolonged PLE. UVA "rush hardening" beneficial in some cases but time-intensive, not generally required.
• Spring courses "harden" the skin (tanning, epidermal thickening, immune effects); no treatment allows unlimited exposure; prudent to limit prophylactic treatment, worth trialling without "desensitisation" in previous responders.
• Regimen factors: timing (too early → loss of effect before natural UVR top-up), whole body vs normally exposed sites only, managing PLE provoked during therapy, number of exposures, post-course advice.
• Typical regimen: narrowband UVB 3×/week for 5 weeks in springtime; optimal methodology not rigorously investigated. One retrospective study (15 patients, severe PLE): 88% sustained benefit from narrowband UVB twice weekly for a month — shorter courses may also work.
• PLE provoked during desensitisation phototherapy in the majority of patients (vs minority for other indications like psoriasis); lower dose increments and post-treatment topical corticosteroids usually enable course completion.
• Prednisolone at PLE onset (holiday-type exposure population) slightly but significantly shortened eruption duration.
• Potent-to-very-potent topical corticosteroid daily from day before to day 3 of a holiday can help prevent PLE (not fully evidence-supported).
• Experimental second line systemic therapies:
• β-Carotene: disappointing — RCT crossover: 15% "excellent" response vs 0% on placebo; lesser improvements similar regardless. Blinding challenging (colour change). Another study small beneficial effect; larger-dose replication failed.
• Antimalarials: minimal if any benefit in controlled trials.
• Omega-3 PUFA (fish oil): preliminary study showed statistically significant effect; unknown if clinically translatable.
• E. coli filtrate and nicotinamide: encouraging early studies not replicated, not used clinically.
• Polypodium leucotomos extract (antioxidant/anti-inflammatory): uncontrolled studies suggest value.
• Vitamin D analogue: RCT suggested prophylactic application beneficial.
• Third line: long-term immunosuppressives — azathioprine, ciclosporin — for refractory cases.

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• Recurrent blistering eruption affecting upper pinnae of boys/young men with intense spring sunlight exposure.
• Synonyms: benign springtime eruption, "lambing ears," dermatitis vernalis aurium, spring perniosis.

• Far more common than typically recognised; usually a nuisance not severe; sunlight relationship usually clear-cut, so medical advice often not sought.

• Common among boys/young men with intense sun exposure. Found in 12% of New Zealand schoolboys examined in springtime. Reported among schoolchildren, lambing-season farmers, military personnel.
• Sex: typically males — possibly hairstyle differences leaving upper pinnae more exposed.
• Ethnicity: mainly reported in those of European ancestry.
• Associated diseases: can occur with PLE; some categorise as a PLE variant.

• Not well defined; considered similar to PLE.
• Predisposing factors: more common in males with short hair and prominent ears.

• Dermal, perivascular, mononuclear cell infiltration on recent-onset biopsies; later, epidermal ulceration and acanthosis.

• Reported in outbreaks (e.g. military conscripts) — likely shared hairstyle/sun exposure rather than infectious. One case reported association with Parvo-B19, not replicated; no causative organism identified.

• No strong genetic component identified. Seems more common in countries with distinct seasons.

• History: blisters (sometimes coalescing, usually unilocular) on upper pinnae after a few days of sunlight exposure; pruritus and papules usually also present.
• Presentation: blisters and papules on upper pinnae.

• May be a PLE variant. Erythema multiforme can appear similar, as (rarely) can EPP, hydroa vacciniforme, bullous LE.

• No standard scheme; DLQI used for QoL.

• None described.

• No good-quality follow-up studies; may recur over a few years but appears to spontaneously resolve.

• Diagnosis based on history/examination. Rarely need to exclude porphyria or lupus in atypical presentations. Phototesting not usually undertaken; monochromator responses typically normal; iterative UVA provocation may be positive.

• Advice on benign nature/expected spontaneous resolution. Growing hair to cover upper pinnae (occupation permitting) usually all that's required.
• Treatment ladder:
• First line: sunlight avoidance (best via hair cover).
• Second line: topical broad-spectrum sunscreen; natural desensitisation via repeated low-level, less intense sun exposure.
• Third line: rarely, prophylactic (desensitisation) phototherapy (narrow-band UVB as for PLE) may be appropriate.

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• Distinct photodermatosis: perennial (worse in summer) itchy papules/vesicles during acute flares, persistent eroded nodules and/or dermatitic patches (sometimes covered sites), scarring, dorsal nose involvement, frequently cheilitis and conjunctivitis.
• Synonyms: hereditary polymorphous light eruption of American Indians, Hutchinson's summer prurigo, photodermatitis in North American Indians, hydroa aestivale (term also used for other photodermatoses).

• Rare in Europe, common in some populations in the Americas. Abnormal photosensitivity (UVA, UVB) often severe but generally gradually improves, especially with onset before age 10 (usual in Native American/European cases). Classic AP clinically distinct, some overlap with severe PLE. Managed similarly to PLE; thalidomide may be needed when severe.

• Prevalence: ~3 per 100,000 (Scotland) to ~10% among some isolated susceptible populations. Occurs in most parts of the world.
• Age: most commonly starts in childhood.
• Sex: commoner in females.
• Ethnicity: more common in those of Native American ancestry.
• Associated diseases: can be complicated by sunscreen allergy.

• UVR exposure important; action spectrum usually UVB and UVA (rarely UVA only).
• Possible shared pathomechanism with PLE — some consider AP essentially a persistent PLE form in genetically susceptible individuals.
• Considered immunological: delayed hypersensitivity reaction; chromophore(s)/photo-antigen(s) unknown.
• Lack of Langerhans cell migration after UV irradiation in AP patients with abnormal phototesting supports aberrant UV-induced immunosuppression hypothesis.

• Dermal, perivascular, mononuclear cell infiltration on recent-onset biopsies; later epidermal ulceration, acanthosis, fibrosis. Cheilitis histopathology said characteristic, with a predominant follicular pattern; changes elsewhere non-specific.

• Strong genetic component, familial inheritance. Majority of AP patients have HLA-DR4 (common in most populations); >two-thirds express DRB10407 subtype (usually rare). Other allele associations reported (e.g. HLA DRB1*03:01 in Singaporean Chinese AP patients).

• More frequent at high altitude, with exceptions (e.g. high prevalence among Chimila Native American people near sea level in Colombia).

• History: may begin at any age but most commonly childhood; late-onset variants reported (particularly Asia). First-decade symptom presentation typical, chronic and perennial disease, distinct UVR-related flares — common across ethnicities/geography. Very itchy: early pink papules or small nodules/plaques, sometimes vesicles, rapidly excoriated/crusted/scabbed, often with "eczematisation" and subsequent scarring. Ocular symptoms, lip soreness/inflammation also common.
• Presentation: face (including dorsal nose) and distal limbs most affected, lesser involvement of covered sites; buttocks in severe cases. Hypo-/hyperpigmented resolving lesions and scars. Cheilitis and conjunctivitis — more common/severe in Native American populations than western European/Asian ancestry.
• Clinical variants: Native American form considered by some as distinct — cheilitis/conjunctivitis frequency/severity greater in this population.

• Severe PLE (especially with atopic eczema), widespread florid insect bite reactions, photoaggravated atopic eczema, nodular prurigo, hydroa vacciniforme.

• No standard scheme; DLQI used.

• Secondary staphylococcal (sometimes streptococcal) infection; scarring with chronic disease.

• Typically spontaneously improves, may resolve by teenage years/early adulthood (proportion unknown); persistence into adulthood can occur — caution advised on early prognosis.

• Diagnosis based largely on history (age of onset, distribution, dorsal nose involvement helpful clue), supported by examination.
• Monochromator phototesting important: severe abnormal photosensitivity in most cases, sometimes as marked as CAD, far more prominent than most PLE. Iterative UVA provocation testing usually provokes abnormal papular response. Abnormal photosensitivity may also be seen on narrowband UVB MED testing and compact fluorescent lamp exposure.
• HLA typing not diagnostic but helpful in doubtful cases — absence of HLA-DR4 makes AP unlikely; presence of DRB1*0407 subtype supportive.
• Antinuclear/extractable nuclear antibodies and porphyria biochemical screening usually indicated (exclude mimics).
• Lesional histopathology can help.
• Photoaggravated atopic eczema/nodular prurigo distinguished clinically; insect bites by shorter time course/asymmetry; phototesting normal in these.
• Diagnosis may be uncertain early on, requiring evolution follow-up.

• Initial: sunlight avoidance advice (behavioural, clothing, hats, sunscreen, window film) and potent/very potent topical corticosteroids.
• Window film UV-absorbing properties may reduce via photodegradation — may need replacement every ~5 years.
• If insufficient: add springtime narrow-band UVB or PUVA — usually only photo-exposed sites treated. Potent topical steroid immediately after each exposure reduces flare risk. Vitamin D supplements commonly required.
• In Scotland, systemic treatment uncommonly needed; more often necessary where phototherapy availability is limited and in countries with intense year-round sun.
• Antimalarials and β-carotene sometimes tried, uncertain value.
• Thalidomide may be more useful but restricted by teratogenicity and irreversible peripheral neuropathy risk; low-dose thalidomide may be more safely used in children with AP than in adults with lupus — occasionally required in severe disease with appropriate monitoring.
• Pentoxifylline (anti-TNF-α effects) worth considering before thalidomide (more attractive safety profile).
• Ciclosporin or dupilumab efficacy reported in single case reports of children with AP.
• Treatment ladder:
• First line: sunlight avoidance; potent/very potent topical corticosteroids; narrow-band (TL-01) UVB phototherapy.
• Second line: PUVA; thalidomide (not of child-bearing potential).
• Third line: β-carotene; pentoxifylline; tetracycline and vitamin E; oral corticosteroids; azathioprine; chloroquine; topical ciclosporin; oral ciclosporin; dupilumab.

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• Chronic dermatitis mainly affecting photo-exposed sites, associated with abnormal photosensitivity; requires both clinical picture and phototesting abnormalities of dermatitis morphology.
• Synonyms: actinic reticuloid, photosensitive eczema, photosensitivity dermatitis/actinic reticuloid, persistent light reaction.

• Persistent/recurring dermatitis predominantly at photo-exposed sites with objective photosensitivity, usually to broad-band predominantly UVB wavelengths.
• CAD encompasses four previously separate diagnoses: (i) actinic reticuloid (pseudolymphomatous infiltrative changes with broad-band photosensitivity); (ii) photosensitive eczema (photo-exposed site dermatitis + UVB photosensitivity); (iii) photosensitivity dermatitis/actinic reticuloid (features of both, broad-band photosensitivity); (iv) persistent light reactors (photocontact allergy, positive photopatch tests usually to halogenated salicylanilides or musk ambrette, developed persistent photosensitivity without ongoing photoallergen exposure).
• Consensus view: all four are part of the same heterogeneous disease, CAD.

• Occurs worldwide, commoner in temperate climates. Second most commonly diagnosed idiopathic photodermatosis after PLE in photodiagnostic units (7–17% of investigated patients).
• Tayside, Scotland: 1 in 2000 of those aged ≥75 years. Estimated overall prevalence: 1–5 per 10,000.
• Age: typically elderly males; younger onset/females observed, usually with atopic eczema. Three studies (NY/Japan, Melbourne, Dundee): mean age at diagnosis 60–62.7 years.
• Sex: male:female ratio 2.6–7.1:1; in CAD arising in higher skin phototypes, female:male ratio 2:1.
• Ethnicity: occurs in any skin phototype; younger-onset CAD over-represents higher skin phototypes.
• Associated diseases: associated with contact/photocontact allergy in most patients; uncommon to develop CAD without pre-existing dermatitis. Lengthy prodrome of dermatitis before photosensitivity — one study of 34 patients: 23% had prior persistent dermatitis history >20 years. Increasingly recognised in young atopic eczema patients, particularly skin phototypes IV–VI. HIV association reported. CAD + solar urticaria concurrence seen in three patients (unlikely coincidental given rarity of both).

• Not fully understood; considered immunological basis — supported by contact/photocontact allergy associations, atopic eczema, immunosuppressive drug response, HIV association.
• Photoactive drug role considered but not substantiated.
• Prolonged prodrome (atopic/allergic eczema) before photosensitivity suggests persistent T-cell activation required to trigger photosensitivity, though doesn't explain de novo cases.
• Light exposure alone appears to suffice as trigger without identifiable photoallergen/allergen.
• Most plausible hypothesis: delayed cell-mediated hypersensitivity to unknown endogenous photo-induced antigen(s), similar to allergic contact dermatitis mechanisms.
• Early lesional skin studies: predominance of CD8 cytotoxic suppressor T cells (similar to established ACD), CD4 helper T cells increased in early stages.
• Mediator studies: upregulation of adhesion molecules (E-selectin, VCAM1, ICAM1) and IL-1, -6, -8 in both CAD and ACD.
• Antigen/photoantigen nature unknown; photochemical modification of an endogenous protein rendering it antigenic seems plausible. In vitro: photoallergen tetrachlorosalicylanilide photo-oxidised histidine and modified carrier protein albumin, rendering it weakly antigenic — relevance in vivo unclear since contact/photocontact allergy isn't a CAD prerequisite.
• Other unsubstantiated theories: retained photoallergen, altered kynurenic acid metabolism, abnormal oxidative stress handling; Langerhans cell role undefined. Photoreactivity of lactones to thymidine reported of interest but doesn't explain lactone-allergy-free CAD cases.
• Antibody-mediated immunity appears normal; serum total IgE can be raised in some cases but not a prerequisite, unclear pathophysiological role.

• Dermatitis of various types.

• Not specific. Acutely: epidermal spongiosis, acanthosis, upper dermal perivascular lymphohistiocytic infiltrate. Chronically: epidermal hyperplasia, deep dermal inflammatory infiltrate, increased perivascular histiocytes, granulomatous changes.
• Mast cells in early lesions; eosinophils, plasma cells, atypical large hyperchromatic convoluted nuclei, mitoses may be evident; Langerhans cells can be increased.
• Chronic phase: lichenification and pseudolymphomatous (actinic reticuloid) changes with epidermotropism and atypical lymphocytes — may be difficult to distinguish from mycosis fungoides. Atypical circulating cells can occur but distinguishable from Sézary syndrome by immunophenotyping and T-cell-receptor rearrangement studies.
• Occasional lymphoma reports in CAD patients, but longer-term follow-up study showed no increased lymphoreticular/other malignancy risk.
• Biopsy of abnormal eczematous phototest site shows acute spongiotic dermatitis.

• Sporadic disease, no genetic factors identified to date. Differential gene expression vs controls observed (inflammation/immunity genes) — clinical relevance unclear, may identify future therapeutic targets.

• More common with multiple contact allergies. Recent Korea association between increased CAD incidence and climate change (increased sun exposure hours, air humidity) — requires further study.

• History: pruritic, recurrent/persistent dermatitis predominantly at photo-exposed sites, worse in summer. Some patients unaware of sunlight association (pre-existing dermatitis pattern change, seasonal change, perennial broad-band photosensitivity symptoms with covered site involvement). Only 21% have no preceding dermatitis history. Most have atopic, contact allergic, seborrhoeic, or endogenous hand eczema history, often for many years — difficult to pinpoint photosensitivity onset.
• Presentation: diverse, can vary within the same patient. Persistent uninterrupted inflammation can develop pseudo-lymphomatous areas — only site of activity in winter, more extensive photo-exposed dermatitis in summer.
• Acute: redness, exudation, vesicular dermatitis at photo-exposed sites.
• Chronic: lichenification, pseudo-lymphomatous infiltrative plaques, alopecia, ectropion, hyper-/hypopigmentation (can appear vitiliginous).
• Higher skin phototypes (IV–VI): nodular prurigo-like morphology, lichenoid and pigmentary changes.
• Exam: removal of clothes/hats/watches/spectacles important — sharp cut-off at protection sites may be seen.
• 34-patient study: 44% covered-site involvement, 15% erythroderma. May have concurrent palmar/plantar dermatitis.
• Clinical variants: morphology ranges from atypical photosensitive presentation to more contact-allergic-dermatitis picture. Pseudo-lymphomatous (actinic reticuloid) and nodular prurigo-like changes; can present as unexplained erythroderma.

• No specific objective measure; DLQI useful. Wavelength dependence/degree of photosensitivity on monochromator phototesting and multiple allergens presence give some prognostic info.
• 51-patient study: association between total IgE level and chemokine CCR4 expression and disease severity; 72-patient study: association between total IgE, eosinophil count, and Th2 immunity shift and severity (clinical significance needs further investigation, as IgE isn't raised in all cases).

• Airborne contact dermatitis: typically involves upper eyelids/under nose and chin, spares back of neck.
• Photoaggravated atopic/seborrhoeic eczema may be clinically indistinguishable.
• Drug-induced photosensitivity and cutaneous T-cell lymphoma (especially with erythroderma) must be considered.
• CAD presenting as cutis verticis gyrata documented.

• Most have pre-existing/concurrent eczema (endogenous, atopic, seborrhoeic, contact allergic); sunscreen allergy/photoallergy may occur.

• Generally symptomatic improvement with light/allergen avoidance after diagnosis.
• Scotland retrospective study: abnormal photosensitivity resolved in 1 in 10 by 5-year follow-up, 1 in 5 at 10 years, 1 in 2 by 15 years. Severe UVB photosensitivity at diagnosis + ≥2 separate contact allergens → poorer resolution prognosis.
• Contact allergies usually (not always) persist. Unclear if prognosis differs for young-onset presentation.
• No erythroderma → normal life expectancy, no evidence of increased lymphoreticular/other malignancy risk.

• Phototesting: monochromator phototesting to UV and visible wavelengths across the solar spectrum is investigation of choice. Abnormal erythemal responses (MED at each waveband) most apparent 24h post-testing, becoming dermatitic.
• Most CAD patients have predominant UVB sensitivity; many also have UVA and visible wavelengths involved (100% UVB, 88% UVA, 59% at 400nm, 26% at 500nm in one series).
• Isolated UVA sensitivity reported but rare — if seen, suspect drug photosensitivity.
• Action spectrum for CAD dermatitis induction similar to normal erythemal "sunburn" but occurs at much lower doses.
• Requires sufficient clear back skin; if limited, solar simulator phototesting as initial screen. Broad-band UV provocation testing gives less wavelength-dependency info than monochromator.
• CAD may be unexpectedly picked up by MED testing prior to phototherapy (e.g. suspected photoaggravated atopic eczema) — highlights importance of routine MED/small area phototesting before phototherapy as a safety measure.
• Potent topical corticosteroids on the back in the preceding week may suppress responses — avoid. One study showed no erythemal response suppression from 30mg/day prednisolone in healthy volunteers, but as low as 10mg/day may suppress abnormal responses in CAD — consider this. Effect of other systemic immunosuppressants on abnormal phototesting unknown.
• Patch and photopatch testing: essential investigation. Photopatch testing helpful when practicable.
• 86-patient study: positive patch and/or photopatch tests in 74%, diverse common allergens. Young CAD patients also commonly positive.
• Allergens (often multiple): fragrances, rubber additives, nickel, colophony, medicaments, sunscreens.
• Plant contact allergy very common (Asteraceae/Compositae, lichens, oleoresins). One study: 36% positive patch test to sesquiterpene lactone; standard screen can miss significant plant allergy (daisy, dandelion, thistle — positive in up to 23% if tested specifically). Asteraceae are also phototoxic (not photoallergic) — need not be included in photopatch series.
• Sunscreen allergic/photoallergic reactions common given regular use; benzophenones, dibenzoylmethanes, octycrylene most likely culprits, but allergen profile changes over time.
• Photopatch testing is investigation of choice, though difficult/impossible in significant photosensitivity, relevance of positives sometimes unclear. Four separate CAD studies: positive reactions 12–33% — always consider if unexplained deterioration. Contact/photocontact allergy prodrome can last years before photosensitivity develops.
• Photoaggravated atopic/seborrhoeic eczema: phototesting normal. Airborne contact allergy or photocontact allergy: phototesting normal, patch/photopatch positive. Drug-induced photosensitivity: usually predominant UVA sensitivity in patient taking a photoactive drug, eruption usually not eczematous. Erythrodermic CAD: exclude Sézary/T-cell lymphoma (usually normal phototesting if feasible; T-cell receptor gene rearrangement studies confirm CAD's polyclonal nature if in doubt). Cutaneous lupus and porphyrias generally don't clinically confuse with CAD but should be excluded.

• Establish diagnosis, exclude drug photosensitivity, define action spectrum — all paramount. Consider day-to-day life impact.
• If taking a photoactive drug (e.g. thiazide, quinine): stop if feasible, repeat phototesting 3–6 months later.
• Management: prevent flares, suppress active disease. Careful UVR (and visible light if necessary) avoidance via behavioural modification, hats, clothing, education, high-factor broad-spectrum non-fragranced low-allergenic sunscreens.
• Visible light sensitivity: add a large-particle, pigmentary-grade, reflectant sunscreen (e.g. Dundee cream) to broad-spectrum product.
• UVA sensitivity: UV-absorbing window film helpful.
• TV/computers/artificial lighting usually not a problem, but compact fluorescent lamps (emit more UV) pose risk for severely photosensitive patients including CAD — consider risk of artificial light sources, particularly for visible light photosensitivity.
• Allergens/photoallergens identified and avoided indefinitely. Vitamin D intake/supplementation. Repeat phototesting/patch testing at intervals to check for changes and new allergens.
• First line: very potent/potent topical corticosteroids.
• Second line: in-patient nursing behind visible/UV-absorbing window film if feasible. Topical tacrolimus or pimecrolimus can be effective. Systemic glucocorticoids for acute flares if topical inadequate. PUVA may be effective if tolerated (may need systemic glucocorticoid cover). UVB phototherapy may be effective but often not feasible due to UVB photosensitivity degree, though possible in higher skin phototype CAD patients. UVA rush hardening may be considered. Phototherapy/PUVA often requires systemic glucocorticoid cover early to prevent flares.
• Third line: RCT showed clinical benefit (not phototesting-assessed) with azathioprine 150mg/day (steroid-sparing, following TPMT measurement pre-treatment). Also reported effective (case reports/small series): hydroxychloroquine, ciclosporin, mycophenolate mofetil, hydroxyurea, etretinate, danazol, thioguanine, topical nitrogen mustard, thalidomide, infliximab, apremilast, IFN-α, colostrum-macrophage-activating factor.
• Avoid combining photo(chemo)therapy with systemic immunosuppressants, particularly ciclosporin, due to photocarcinogenic risk.
• Emerging dupilumab data: good/partial clinical response in some, photosensitivity improvement less marked but can be significant — consider for CAD with concomitant atopic dermatitis.
• JAK inhibitors (e.g. tofacitinib) may be options but need further evaluation.

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• Can be primary (idiopathic) or secondary to drugs, chemicals, porphyria, or lupus.
• Idiopathic SU: immunological photodermatosis based on a type 1 immediate hypersensitivity reaction to poorly defined photo-induced antigen(s); characterised by immediate urticaria following UVA, visible, and (less commonly) UVB exposure.
• Synonym: solar angio-oedema.

• Uncommon immunological photodermatosis, usually idiopathic, urticaria on exposed sites within minutes of UVR/visible light exposure, resolving within about an hour.

• Uncommon: 2.2–17.8% of tertiary photodiagnostic centre diagnoses (lower figures with higher skin phototype IV–VI populations — possibly more commonly diagnosed in lighter-skinned populations). Worldwide reports.
• Scotland study: prevalence 3.1 per 100,000. Estimated overall prevalence 1–5 per 10,000. Trend to increasing prevalence suggested but not substantiated.
• Age: any age, peak incidence 3rd–5th decades; paediatric cases reported (onset 1 month–2 years), similar characteristics/treatment response to adults.
• Sex: more common in females.
• Ethnicity: occurs in all groups; one US study showed higher relative frequency in white vs black people.
• Associated diseases: may coexist with other urticaria types and other photodermatoses (PLE, CAD, AP). No increased atopy prevalence.

• May be an allergic type 1 hypersensitivity response, mediated at least partly by histamine and other agents.
• Proposed pathway: photochemical alteration of an endogenous chromophore by UVR/visible light → antigen → recognised by specific IgE on mast cells → degranulation, histamine/mediator release → increased vascular permeability, dermal oedema.
• Secondary SU: drug or porphyrin presumably acts as the chromophore.
• Some patients have a detectable circulating "photoallergen" factor; early studies demonstrated passive transfer to normal individuals (not done now for ethical reasons); behaves like a globulin, MW 25–1000 kDa.
• Provocation wavelengths vary between and within patients — suggests a range of photoallergens activated by UVR/visible light.
• Photoaugmentary and photoinhibitory wavelength mechanisms poorly understood; augmentation spectra investigations indicate induction of an urticaria-forming factor, with potential for severe SU or anaphylaxis provocation. Infrared radiation may also exacerbate SU responses.
• Heterogeneous therapeutic responses suggest multiple pathways.
• Histamine implicated (antihistamines at least partially effective in most cases); other mediators likely involved: leukotrienes, platelet-activating factor, substance P, serotonin, acetylcholine — non-histamine mediator role not fully defined.
• Tolerance induction mechanism (e.g. narrow-band UVB) unclear — probably immunomodulation, immunosuppression, stratum corneum thickening, pigmentation.

• Within minutes of irradiation: cutaneous perivascular infiltrate of neutrophils, eosinophils, mast cells; followed by dermal vessel endothelial cell swelling and dermal oedema. Occasional vasculitic features. Histology not significantly different from other urticaria causes; biopsy only if diagnostic doubt.

• Sporadic; no genetic factors identified yet (molecular genetic analysis planned).

• History: sudden, clearly recalled onset. Most (63%) have perennial symptoms (UVA/visible light photosensitivity). Itch, burning, redness, weals within seconds to minutes of exposure. Minority: pruritic skin reddening alone (urticarial weals elicited on phototesting).
• Any photo-exposed site affected; most (76%) also involved through lightly clothed sites (loose-weave fabric doesn't protect UVA/visible light). Sparing under layered clothes, watches, footwear.
• Most (83%) troubled by SU triggered through window glass.
• Hardening not typically reported, though some have lesser face/hand involvement; refractory period after acute episode (more resistant for a few hours).
• Most: urticarial lesions resolve within 2h; abnormal erythema at exposed sites may persist 24h.
• Sunbed exposure can trigger; large exposed areas → systemic symptoms: malaise, headache, photophobia, wheeze, nausea, dizziness, rarely hypotension and anaphylaxis. Exacerbation by internal lighting (particularly low-energy compact fluorescent sources), rarely infrared radiation.
• Presentation: acute episode shows skin reddening and urticaria at photo-exposed/lightly clothed sites; may show no abnormal signs if not seen acutely.
• Clinical variants: infrequent delayed-onset and more persistent SU reports (phototesting essential to distinguish from early-onset PLE). Occasional leucocytoclastic vasculitis changes. Rare reports of SU at fixed reproducible sites or bruising sites. Systemic symptoms and rarely anaphylaxis. Solar angio-oedema appears to be an SU variant.

• Exclude secondary causes: drugs (tetracyclines, fluoroquinolones, chlorpromazine, some NSAIDs notably benoxaprofen [no longer available], repirinast, topical tar/pitch, atorvastatin, some sunscreens e.g. benzophenones); progesterone association reported in one case (unsubstantiated). Porphyria (EPP, PCT, particularly with 430–460nm photosensitivity) and lupus must be excluded. Other urticaria causes considered, particularly heat-induced urticaria.

• No formal classification; DLQI for QoL impact.

• Anxiety and depression can occur. May have other urticarias (particularly physical). Reported with concomitant PLE, CAD, AP. Churg–Strauss syndrome association reported in one case (may be significant given rarity of both). Contact/photocontact sunscreen allergy may occur.

• Chronic disease in the majority. One report: 58% resolution chance by 5 years; second report (87 patients, 60 followed up): only 12% resolution by 5 years, 36% by 15 years. Large Spain review (224 patients): those with only visible or natural light sensitivity more likely to fully resolve.

• Consider secondary causes (drug history, porphyria, lupus).
• Monochromator phototesting is investigation of choice: skin reddening, oedema, weal, flare within minutes at phototest sites, resolving over an hour or so, often with delayed abnormal skin reddening at 24h. Determine immediate minimal urticarial dose (MUD) and 24h MED at each waveband. Most have fairly broad action spectrum, longer UVA and shorter visible wavelengths most commonly involved.
• If strongly suspected but not detected on monochromator testing: broader-spectrum sources (solar simulator, natural sunlight) advised — rarely SU only provoked by wavelength interaction.
• Augmentation and inhibition spectra useful for management and severe SU/anaphylaxis risk awareness. Action spectrum may change over time — follow-up phototesting needed.
• If severe/unresponsive: intradermal testing with irradiated autologous serum/plasma may indicate potential plasmapheresis benefit but only positive in a minority.

• Anxiety/depression common — psychological support may be needed. Photoprotection alone usually inadequate unless mild, but important. Behavioural sun avoidance, layered tightly woven dark clothing, broad-brimmed hats. Window film useful (blocks UVA but many patients also visible-light sensitive, so may not suffice). Vitamin D attention. Broad spectrum high-protection sunscreens with reflectant sunscreens (Dundee cream) for shorter visible spectrum protection.
• First line: one-third complete response, one-third partial response to non-sedating H1 antihistamines, remainder no response. Most effective at reducing/abolishing weal and flare, not immediate/delayed skin reddening. May need higher doses/combinations; synergistic benefit with sunscreens. Addition of H2 antagonist and/or leukotriene receptor antagonist may add benefit. Variation between patients — several agents/higher doses often needed.
• Second line: doxepin, ketotifen, chromoglycate, montelukast — may help individually (not thoroughly evaluated given rarity). Dihydroxyacetone "sunless tan" of limited use.
• Desensitisation using natural/artificial light possible, determined by wavelength dependency/severity. Natural tolerance via graded daylight exposure possible for some (many too sensitive).
• Phototherapy beneficial if tolerated. Maximal sensitivity often UVA1/visible spectrum — narrow-band UVB responses often normal and can be successfully used (baseline MED before phototherapy needed as 24h MED may be reduced).
• Effective desensitisation reported with narrow-band UVB, UVA, PUVA (benefit may be short-lived; home desensitisation may be considered). UVA rush hardening (frequent sub-urticaria-triggering broad-band UVA exposures, several times/day, before/with PUVA or alone) may be beneficial; rarely cautious UVA1 hardening successful.
• Phototesting for SU action spectrum, immediate MUD, delayed MED (or MPD for PUVA) essential before desensitisation. Combine with antihistamines throughout; usually administered to photo-exposed sites only; some natural daylight exposure needed post-course to prolong tolerance.
• Third line: severe recalcitrant disease, limited evidence base (mostly single cases/small series). Ciclosporin, systemic glucocorticoids, other immunosuppressants may be considered. β-Carotene and hydroxychloroquine unlikely effective. IV immunoglobulins effective in some, ineffective in others. Plasmapheresis for severely affected (especially with positive intradermal test) — sustained remission not guaranteed even in responders, specialist centres only, not without risks.
• Omalizumab (anti-IgE monoclonal antibody): increasingly reported efficacy, clinical/phototesting improvement or resolution, long-term efficacy feasible, though also reports of lack of effect. Response may be immediate and life-changing; higher doses/prolonged treatment sometimes needed.
• Oral Polypodium leukotomos and α-MSH analogues used experimentally in small numbers, need further study.
• Disease is heterogeneous — one treatment approach doesn't suit all.

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• Rare acquired photodermatosis, usually in children, characteristic photo-exposed site vesicles, crusts, and varioliform scars.
• Synonym: hydroa aestivale.

• Described by Bazin in 1862. Usually presents in the first decade, typified by vesicles, (often haemorrhagic) crusting, and subsequently varioliform scars at photo-exposed sites.

• Rare. Scottish review of 17 patients: prevalence estimated ≥0.34 per 100,000 (may be reducing over years). Estimated overall prevalence: 1–9 per 1,000,000.
• Age: typically children; bimodal onset (1–7 years or 12–16 years), mean 7.9 years (range 1–16, n=17). Exceptional infancy or later onset cases persisting into elderly age.
• Sex: initial reports suggested female predominance; more recent review indicates equal sex distribution, though may present earlier (mean 6.7 years) and shorter duration in females vs males (mean 8.7 years).
• Ethnicity: occurs in all ethnic groups.

• Aetiology unknown. UVA wavelengths implicated in lesion provocation (spring/summer sunlight or artificial UV). Chromophore(s) undefined.
• EBV infection role proposed: latent virus found in dermal inflammatory infiltrate of South-East Asian HV patients — may represent an HV-like EBV clinical presentation.
• HV-like presentation reported in an aggressive form of paediatric T-cell lymphoma, possibly EBV-driven, usually clinically distinct from classical HV.
• Increasing reports clarify chronic EBV role in HV-like T-/NK-cell lymphoproliferative disorder (HVLPD), particularly Latin America and Asia. HVLPD extremely rare in Europe/America. 16-patient HVLPD study (11 years): older age at presentation, non-white, markedly elevated EBV DNA levels → more likely systemic disease, poorer prognosis.
• HLA-DR4 tissue typing association suggested for familial cases, unconfirmed given rarity.
• Earlier reports of impaired DNA repair in vitro and pyridoxine photoproduct implication not confirmed.

• Positive UVA provocation site biopsy: non-specific acute histology — reticulate keratinocyte degeneration, spongiosis, perivascular infiltrate (lymphocytes, histiocytes, neutrophils). A few days later, usually diagnostic: ulceration, epidermal necrosis, papillary oedema, upper dermal necrosis, subsequent scarring. Direct immunofluorescence typically negative.

• Usually sporadic; familial cases reported, including identical twins.

• History: seasonal spring/summer symptoms. Following 15 min to a few hours of direct or window-glass-transmitted light, intensely pruritic crops of papules/vesicles (often on background of redness/oedema) occur at exposed sites within 12–24h. Burning sensation/pain possible; vesicle fluid often becomes haemorrhagic. Systemic malaise/fever during acute episodes possible.
• Presentation: commonest sites — cheeks, nose, ears, back of hands. As vesicles resolve → haemorrhagic crusting → detaching leaves varioliform scarring, can be severe. Subungual haemorrhage can occur. Rarely cartilage destruction (ears, nose) or digit contractures.
• Eyes may be affected: photophobia, conjunctivitis, keratitis, anterior uveitis, corneal clouding/neovascularisation, scarring, visual impairment. Oral mucosal involvement rare but possible.

• Important to exclude bullous LE, EPP, Hartnup disease. Also consider and rule out HVLPD (particularly non-white patients with systemic/ocular/oral involvement features). AP also in differential.

• No specific classification; DLQI may help.

• Significant scarring, ocular complications, rarely cartilage destruction.

• Classical HV usually improves and resolves in later teenage years, mean disease duration 9 years. Persistence into middle age can occur.

• FBC, ANAs, extractable nuclear antigens, porphyrin biochemistry undertaken.
• EBV DNA levels should be measured — markedly elevated levels associated with possible HVLPD progression, particularly in non-white patients and atypical disease.
• Urinary amino acids may be requested. Normal in classical HV.
• Monochromator phototesting may be normal or more typically shows predominantly UVA sensitivity. Repeated artificial UVA provocation usually induces lesions (papules, vesicles, sometimes purpura), indistinguishable from those from natural sunlight.
• Negative photoprovocation with artificial sources suggested as a good prognostic factor.

• Photoprotection (behavioural modification, clothing, hats, sunglasses, UV-absorbing window film, broad spectrum high SPF sunscreen) important. Vitamin D optimisation. Psychological support may be needed.
• First line: photoprotection and topical corticosteroid use in active disease.
• Second line: springtime desensitisation with narrow-band UVB phototherapy can be successful — 60% of patients found beneficial in one study. PUVA used less often (most patients children).
• Third line: given rarity, evidence base limited to case reports/series. Oral glucocorticoids, β-carotene, azathioprine, ciclosporin, antimalarials tried (unproven benefit). Dietary fish oil may help but generally poorly tolerated. Thalidomide appears ineffective. Weigh systemic toxicity risks against a disease that usually resolves with time despite significant morbidity.

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• Abnormal cutaneous reactions to UVR and visible radiation induced by photosensitising drugs/chemicals; subdivided by systemic vs topical administration.
• Synonyms/inclusions: phototoxicity, exaggerated sunburn, photoallergy, pseudoporphyria, skin fragility, photo-induced telangiectasia, topical photocontact allergy, drug-induced lupus.

• Diverse presentations; phototoxicity ("exaggerated sunburn") most common. Important not to miss — reversible if drug exposure stopped.

• Can theoretically occur in anyone on first exposure, but idiosyncratic/genetic factors mean not all exposed become photosensitive.
• Systemic drug-induced photosensitivity: 2–15% of tertiary photodiagnostic unit diagnoses.
• Cystic fibrosis/ciprofloxacin questionnaire study: 48.4% reported increased sun sensitivity vs ~2.4% controls.
• Topical drug/chemical photosensitivity more likely in regular sunscreen users or topical NSAID users (latter most used in continental Europe, particularly France, Portugal, Spain).
• Age: older patients (polypharmacy including photoactive drugs) more at risk.
• Sex: not a determinant.
• Ethnicity: all ethnicities/skin phototypes affected.

• Several mechanisms, most requiring oxygen, resulting in toxic photosensitiser and substrate species. Most systemic drug photosensitivity is phototoxic (non-immunological). Clinical manifestations depend on subcellular localisation of drug/photoactive metabolites; diverse. Topical drugs/chemicals may also cause phototoxicity.
• Selective list of exogenous photosensitisers:
• Systemic: diuretics (thiazides, furosemide, nalidixic acid); antibiotics (fluoroquinolones, tetracyclines*, sulphonamides); NSAIDs†; quinine; hydroxychloroquine; antipsychotics (phenothiazines/chlorpromazine†); cardiology drugs (amiodarone, calcium antagonists, ACE inhibitors, statins); sulphonylureas; retinoids; psoralens†; antifungals (voriconazole, itraconazole, ketoconazole); pirfenidone; proton pump inhibitors; antihepatitis C drugs; leflunomide; venlafaxine; escitalopram; celecoxib; exogenous porphyrins for PDT; azathioprine; fibrates; pyridoxine B6; targeted anticancer drugs (vemurafenib, dabrafenib, encorafenib, nivolumab, vandetanib, imatinib); biologics (anti-TNF, denosumab).
• *Doxycycline and demeclocycline are phototoxic; minocycline may cause drug-induced LE.
• †Can also cause photosensitivity via topical application.
• Topical: psoralens (phototoxic); polycyclic aromatic hydrocarbons (phototoxic); dyes (phototoxic); phenothiazines/chlorproethazine (phototoxic and photoallergic); halogenated salicylanilides (mainly photoallergic); fragrances (phototoxic and photoallergic); sunscreens (phototoxic and photoallergic); NSAIDs (phototoxic and photoallergic).
• Classical phototoxic drugs (thiazides, NSAIDs, quinine) remain most common culprits; vigilance needed for newer drug culprits.
• Mechanisms of photosensitivity: phototoxicity, pseudoporphyria, photoallergy, lichenoid, lupus, pellagra.
• Awareness needed of drugs causing photosensitivity via multiple mechanisms (e.g. thiazides and proton pump inhibitors — phototoxic OR drug-induced lupus).
• Photoallergy uncommon/poorly defined with systemic drugs; most frequent with topical sunscreens, NSAIDs, less commonly certain fragrances. Sunscreens are the commonest topical photoallergens.
• Topical phototoxicity: dyestuffs and psoralen-containing plants (phytophotodermatitis).

• Commonest picture: phototoxic reaction — epidermal necrosis, apoptotic keratinocytes, mild inflammation. Lesional histology may show interface lupus-like or lichenoid changes, erythema multiforme, or be indistinguishable from PCT in less frequent presentations. Spongiotic dermatitis occurs but not typical except in photoallergy (usually topical agents).

• Likely genetic predisposing factors to specific-agent drug photosensitisation, not defined.

• History: typically immediate burning sensation at sun-exposed sites, often with skin reddening, sometimes urticaria; commonly also delayed skin reddening, sometimes blistering. Time course drug-dependent — often peaks 24h (sunburn-like); psoralens produce delayed skin reddening peaking 72–120h after exposure.
• More common with new drug/dose increase, but can occur after prolonged use. Calcium antagonists particularly: photo-exposed-site telangiectasia may only develop after months to years. Other drugs also associated with photo-distributed telangiectasia — thorough drug history essential. Non-prescribed drugs/supplements should be probed.
• Presentation (patterns and culprit examples):
• Immediate burning, prickling, subsequent pigmentation: amiodarone, chlorpromazine, Photofrin, Foscan, topical tars/pitches.
• Exaggerated sunburn: thiazides, fluoroquinolones, quinine, tetracyclines, amiodarone, chlorpromazine.
• Delayed skin reddening and pigmentation: psoralens.
• Pseudoporphyria: NSAIDs (particularly naproxen, diclofenac, piroxicam), frusemide, nalidixic acid, tetracyclines, fluoroquinolones, retinoids.
• Photo-exposed site telangiectasia: calcium antagonists.
• Lupus (Chapter 117); Lichenoid (Chapter 117).
• Reddening, blistering, oedema, urticaria may be seen acutely. Uncommonly photo-distributed purpura (e.g. levofloxacin). Occasional extension/erythroderma. Lichenoid dermatitis (e.g. thiazides, NSAIDs). Pseudoporphyria: photo-exposed-site fragility, blistering, milia, scarring — indistinguishable from PCT/variegate porphyria but porphyrins normal, thought due to chronic drug-induced phototoxic damage at the DEJ; NSAIDs common culprits. Drug-induced lupus uncommon (thiazides, PPIs, others). Pellagra rare but triggerable by isoniazid, phenytoin, others. Drug-induced photo-distributed telangiectasia/angiomas reported with calcium antagonists and venlafaxine. Photo-onycholysis reported with doxycycline and psoralens.
• Topical: diverse — tars, pitches, plants, dyes, NSAIDs, fragrances, halogenated salicylanilides, phenothiazines, sunscreen chemicals. Skin contact with psoralen-containing sap (Umbelliferae, Rutaceae plant families, citrus fruits) + UVA → phototoxic reaction: linear/angular skin reddening apparent 48–72h later at contact sites, blistering, subsequent pigmentation (phytophotodermatitis) — may be confused with non-accidental injury. Specific clinical patterns: "strimmer's dermatitis," "Berloque dermatitis."
• Organic sunscreen chemicals, fragrances, NSAIDs can be both phototoxic and photoallergic — photoallergic requires prior sensitisation, so not on first exposure, may extend beyond exposed sites and become generalised dermatitis with continued exposure.
• "Persistent light reaction" reports mostly fall within the CAD spectrum; no convincing evidence for long-term continued photosensitivity after drug photosensitiser cessation.
• Prolonged pigmentation can occur after systemic/topical phototoxicity — e.g. linear hyperpigmentation streaks persisting months after phytophotodermatitis. Reticulate hyperpigmentation reported with diltiazem. Leucomelanoderma can occur from drug phototoxicity (particularly thiazides, quinine, also pirfenidone) — from melanocyte dysfunction. Chlorpromazine and amiodarone photosensitivity often complicated by prolonged pigmentation; acneiform eruption on photo-exposed sites with amiodarone.

• Depending on presentation: CAD, PCT, variegate porphyria, LE, idiopathic SU, cutaneous T-cell lymphoma (if erythrodermic).

• No formal classification.

• Role in photocarcinogenesis unclear, though recent evidence supports possible associations between photosensitising drug use and SCC, BCC, melanoma risk.
• Psoralens are definitely photomutagenic — repeated PUVA increases skin cancer risk.
• Role of other photoactive drugs unclear, but abnormal lentigines and increased skin cancers (SCC, melanoma) observed with voriconazole; skin tumours induced in mice exposed to fluoroquinolones + light.
• Azathioprine causes UVA photosensitivity and is photomutagenic.
• Photosensitivity reported with BRAF inhibitors for melanoma; these patients also markedly increased SCC risk.
• Potential acute/chronic ocular damage should be considered (most drug photosensitivity involves UVA/visible light). Photodegradation of the drug may also potentially reduce drug efficacy.
• Establish photoactive drug use before/during UV phototherapy courses — some drugs may increase skin reddening episode risk during treatment.

• Resolution time course off the drug depends on bioavailability and photoactive metabolite half-life.
• Psoralen photosensitivity clears within a few hours (strong saturable first-pass metabolism); fluoroquinolones and chlorpromazine within 48h.
• Other drugs take much longer: thiazide photosensitivity may last 3–6 months; systemic porphyrins for PDT detectable at 3 months (clinical photosensitivity may resolve within a few weeks); quinine photosensitivity may last several months; amiodarone effects may last a year or more after stopping. Hydroxychloroquine photosensitivity may also be of long duration after cessation. Skin fragility may persist for many months; pigmentation and telangiectasia can remain longer.

• Monochromator phototesting while on the drug, repeated after a period off the drug (interval depending on drug/metabolite kinetics).
• Most photoactive drugs have maximal UVA absorption — photosensitivity usually restricted to or disproportionately involves UVA. Some drugs (quinine, thiazides) extend into UVB. Others (fluoroquinolones, systemic PDT porphyrin drugs) cause visible light photosensitivity. Some drugs (NSAIDs, phenothiazines, calcium antagonists) may lower narrow-band UVB MED in phototherapy referrals.
• Screening for porphyria and lupus should always be undertaken. Histology may be informative.
• Photopatch testing: investigation of choice for suspected topical photocontact allergy; not reliable for systemic drug photosensitivity.
• In vitro, ex vivo, and controlled healthy volunteer drug phototoxicity studies increasingly important, requested by regulatory authorities (FDA, EU).

• Recognition and cessation of the suspected drug/chemical essential; vigilance about new culprits. Distinguishing drug photosensitivity from CAD can be challenging — disproportionate UVA sensitivity favours drug cause, disproportionate UVB sensitivity favours CAD. If in doubt, stop suspected drug and repeat phototesting off-drug.
• Non-phototoxic alternatives exist for most drugs. If drug can't be stopped, dosage reduction may help. Photoprotection (broad spectrum and reflectant sunscreens) important until resolution.
• First line: stop the drug, improve photoprotection, symptomatic treatment (emollients, topical corticosteroids).
• Second line: if drug can't be stopped (e.g. amiodarone), induction of tolerance using narrow-band UVB or PUVA may help.

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• Synonyms: light-exacerbated, photo-exacerbated dermatoses.
• A range of skin diseases can be aggravated/exacerbated by natural or artificial UV/visible radiation, though they also occur without sun exposure.
• Relatively common — may represent almost a third of patients diagnosed at tertiary photodiagnostic units.
• Heterogeneous group; generally only a proportion of patients experience photoaggravation and may/may not be aware of sunlight's triggering role.
• Photoaggravated skin diseases: psoriasis; eczema (atopic, seborrhoeic, allergic contact, pompholyx); acne vulgaris; actinic folliculitis; rosacea and facial telangiectasia; herpes simplex and other viral exanthems; erythema multiforme; lupus erythematosus (LE); Jessner lymphocytic infiltrate/LE tumidus; lymphocytoma cutis; lichen planus; bullous pemphigoid; pemphigus and Hailey–Hailey disease; linear IgA disease; dermatitis herpetiformis; dermatomyositis; Darier disease and transient acantholytic dermatosis; disseminated superficial actinic porokeratosis; pellagra; mycosis fungoides; melasma; vitiligo; pityriasis rubra pilaris; reticular erythematous mucinosis; urticaria; actinic granuloma; keratosis pilaris; Sweet syndrome.
• Photoprotection and treating the underlying disorder are the mainstay management approaches.
• Example: psoriasis and eczema generally IMPROVE with sun exposure, but in a minority (~10% or fewer) worsen — may manifest as a photo-exposed-site flare initially, then spreading to covered skin; may be attributable to sunlight heat or, often for psoriasis/eczema, a disease flare at sites where PLE (or other photosensitivity disease) has been induced.
• Some photoaggravated conditions generally phototherapy-responsive (psoriasis, eczema) may be successfully treated by cautious UVB phototherapy or PUVA use. This should usually be AVOIDED in other photoaggravated conditions such as bullous pemphigoid, dermatomyositis, or cutaneous lupus.

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• Detailed history essential. Relationship with sunlight is clear-cut for many (e.g. only spring/summer, sun-exposed sites, as in PLE), but may be unclear in perennial photosensitivity, covered site involvement, or erythroderma.
• Important information: age at disease onset and duration, sex, atopy presence, occupation/hobbies, family history, drug/chemical exposure (systemic and topical).
• Some conditions most likely present in childhood: XP, EPP, AP, HV; CAD more likely older males (though can occur young with coexistent atopic eczema). Positive family history likely in XP and EPP.
• Exposure details: perennial or seasonal? Type/duration (direct sunlight, window glass-transmitted, artificial internal lighting, sunbed, or combination)? Window-glass triggering indicates UVA/visible light role — seen in several photodermatoses (particularly drug photosensitivity, PLE, SU), not usual in XP or normal sunburn.
• Latent period (trigger to eruption) and time course (peak, resolution) important. Typical PLE: a few hours exposure → rash later that day → peaks next day → resolves 2–3 days. SU: a few minutes exposure → immediate urticaria → resolves within 1–2h.
• Hardening presence (less likely on habitually exposed face/hand-back sites, less easy to provoke later summer) — often seen in PLE.
• Symptoms: pruritus (many photodermatoses, e.g. PLE, CAD); pain/burning on exposure (raises EPP or drug photosensitivity possibility). Distribution: photo-exposed only, or covered sites too (common in AP, CAD)? Occurs through clothing (SU)? Morphology from history critical if presenting without active signs in winter — papulovesicular characteristic of PLE, urticated weals hallmark of SU, haemorrhagic vesicles/crusts in HV, scarring in HV/AP/EPP. Exaggerated "sunburn" reddening in drug photosensitivity and XP (delayed peak 2–3 days or later); note increased sunburning susceptibility doesn't always occur in XP — may present earlier with skin cancers. Systemic features relevant diagnostically (e.g. SLE, HV, SU). Consider concomitant contact/photocontact allergy (sunscreen adverse effects history) — patients may not be aware.

• Prominent photo-exposed sites to examine: bald scalp, forehead, malar surfaces, nose, chin, ear rims, mastoid and sternomastoid sites, anterior/sides/back of neck.
• Sparing may occur in shadows: sideburns, spectacles, hairline, deep forehead creases, under nose/chin/lower lip, behind ears (Wilkinson triangle), upper eyelids.
• Dorsa of hands (especially thenar) and feet, extensor limb surfaces may be involved — with sparing of web spaces, distal phalanges, under watch straps/rings/footwear.
• Covered site involvement usually to a lesser extent.
• Distribution/nature important: papulovesicular (PLE, JSE); eczematous (CAD); fragility (PCT, pseudoporphyria); associated features (cheilitis, conjunctivitis in AP).
• Look for scarring even in inactive disease (HV, EPP, PCT, AP); other relevant signs: lentigines and/or hypopigmented macules in earlier XP stages, with premalignant dysplastic changes/skin cancer as disease progresses; pigmentation in drug photosensitivity.
• Skin reddening may be less obvious in skin phototypes IV–VI; in phototypes V/VI, dermatitis may more commonly present with papular, lichenoid, or nodular prurigo-type morphology.

• Clinical assessment (history + examination) should give a good idea of diagnosis or narrow differential, but absolute confidence usually not possible clinically — refer for further investigation.

• Usually undertaken at specialist photodiagnostic centres (quality-controlled optical equipment, calibrated metering, spectroradiometry essential). Tailored to presentation/suspected diagnosis.
• Narrow-waveband phototesting: mainstay — monochromator phototesting using a filtered high-pressure xenon arc lamp to deliver relatively monochromatic UV/visible light across the solar spectrum at precise doses on back skin. Feasible in children with sufficient back space/stillness; even babies (limited testing).
• Immediate and delayed erythemal responses assessed via MEDs at each waveband, compared with normal population data relevant to local skin phototype distribution.
• Skin reddening may be less obvious in phototypes IV–VI — good lighting/angle critical; palpation essential (subtle oedema without obvious reddening may be the only indicator in higher phototypes).
• Enables abnormal photosensitivity diagnosis, wavelength dependency, degree of photosensitivity. 24h MEDs are the main assessment point generally; SU uses immediate MUDs. Morphology of responses important (e.g. eczematous in CAD) confirming diagnosis.
• Also used at follow-up to assess treatment response or spontaneous improvement.
• Iterative provocation testing: larger area, broad-band source (often UVA) at a natural rash site, particularly useful in PLE and AP. Solar simulator phototesting may have a role if limited back space; induces skin reddening mainly via UVB, so cruder screen with less wavelength detail. Emission characteristics (e.g. infrared presence) should be well characterised as it may influence provocation ease.
• Other phototesting methods: MED (or MPD for PUVA) for a phototherapy light source should always be determined to exclude abnormal photosensitivity before treatment. Compact fluorescent lamps (replacing tungsten filament) emit more UV, posing risk for severely light-sensitive patients — phototesting with these sources can define individual risk, not routinely used.
• Photopatch and patch testing: undertaken if photo-exposed site eczematous eruption and/or suspected contact allergic dermatitis; essential for CAD patients. Photopatch testing uses standardised European methodology for suspected photocontact allergy, which may mimic/complicate other photodermatoses. Commonest photoallergens: sunscreen chemicals, then topical NSAIDs, occasionally topical phenothiazines — confirmed across Europe, North/South America, New Zealand, Thailand reports (requires regular review).
• Consider based on presentation, particularly in photosensitive patients (e.g. CAD) who regularly use sunscreens and show unexplained deterioration.
• Method: duplicate photoallergen series applied; one set irradiated 24–48h later with suberythemal UVA dose, readings 48h post-irradiation. Additional delayed readings at 96h not fully investigated but may be relevant for some photoallergens. Ensures photocontact allergy (vs contact allergy) isn't missed (some sunscreen chemicals only allergenic when irradiated). May be difficult to perform/interpret if patient is severely photosensitive, but should be undertaken if possible.
• Other investigations: exclude lupus (ANA, extractable nuclear antigens — anti-SSA/Ro, anti-SSB/La). Exclude porphyria when indicated — plasma spectrofluorimetry usually suffices for low suspicion, more detailed quantitative blood (plasma/red cells)/urine/faeces analysis when indicated. HLA typing if AP suspected. Histology of existing/provoked rash may be informative (e.g. HV) but rarely diagnostic. Genophotodermatosis suspicion: skin and blood samples for DNA repair activity and genetic studies (Chapter 76). Rare metabolic/biochemical/nutritional disorders occasionally need ruling out (amino acidurias, Smith-Lemli-Opitz syndrome, pellagra). Vitamin D levels measured for strictly photoprotecting patients, replacement advised if deficient (≤25 nmol/L).
• Deep phenotyping through guided photodiagnostic investigations has facilitated identification of new diagnostic entities: actinic folliculitis, PLESAPS, broadspectrum abnormal localised photosensitivity syndrome (BALPS).

• Photoprotection: rests on correct diagnosis and knowledge of the action spectrum. General approaches: behavioural modification, seeking shade, avoiding direct sun 11am–3pm. Advise increased relative exposure from reflection (sand, water, snow, light pavements) and significant UVR exposure possible on cloudy days. Tightly woven, dark, layered clothing; wide-brimmed hats. Regular liberal broad spectrum high-factor sunscreens every 2–3h.
• In practice, sunscreens offer only 25–33% of the stated protection against normal sunburn — SPF30 effectively offers SPF10; patients must know sunscreen limitations.
• Tailor sunscreen advice to abnormal photosensitivity nature — visible light sensitivity (SU, CAD, cutaneous porphyria): add reflectant sunscreen (e.g. Dundee cream) for additional visible spectrum protection. UVA sensitivity: UV-blocking window film for car/home/work — loses protection after ~5 years from photodegradation, may need replacement.
• Natural hardening: complete sun avoidance generally not advisable (except XP) — major adverse health/well-being impact. In some photodermatoses (particularly PLE), threshold photosensitivity can improve via natural hardening (tolerance) from regular sub-triggering low-level sun exposure.
• Vitamin D: advice on optimising dietary intake and supplements where necessary.
• Quality of life: major adverse impact, particularly chronic/severe disease, should not be underestimated; psychological support may be required; recognition/management of anxiety and depression essential.
• Overall approach: subdivided into prevention and treatment, with prevention the main goal. Active disease treated conventionally, often topical glucocorticoids (e.g. PLE or CAD suppression).
• Light-based therapies: photo(chemo)therapy may induce tolerance when not achievable through natural exposure, most commonly used for idiopathic (immunological) photodermatoses (e.g. PLE), can be used in other disorders too. Knowledge of abnormal photosensitivity characteristics essential for selecting desensitisation regimen. Systemic therapies (immunosuppressants/immunomodulatory agents) may be required in severe disease.
• Specific therapeutic measures: disease-specific, discussed in relevant chapter sections.

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Polymorphic Light Eruption (PMLE)

• Prevalence: Most common idiopathic photodermatosis.
• Clinical: Pruritic erythematous papules, vesicles, or plaques appearing 1 to 47 hours after initial intense sun exposure in spring/early summer on sun-exposed sites (chest, arms); displays hardening effect (improves throughout summer).

Porphyria Cutanea Tarda (PCT)

• Enzyme Defect: Deficiency of Uroporphyrinogen Decarboxylase (UROD).
• Clinical: Cutaneous fragility, tense bullae, erosions, milia, hyperpigmentation, and facial temporal hypertrichosis on sun-exposed dorsal hands.
• Triggers: Alcohol, Estrogens, Iron overload, Hepatitis C Virus (HCV), Hemochromatosis (HFE C282Y mutation).
• Diagnostic Finding: Elevated Uroporphyrin I in urine (displays coral-pink / orange-pink fluorescence under Wood's lamp).
• Treatment: Therapeutic Phlebotomy (target ferritin <20 ng/mL), Low-Dose Hydroxychloroquine (100 mg twice weekly), direct-acting antivirals for HCV.

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Vitiligo

• Pathophysiology: Autoimmune destruction of epidermal melanocytes.
• Clinical: Well-demarcated, chalk-white, depigmented macules and patches. Wood\'s Lamp accentuates bright blue-white depigmentation.
• Autoimmune Associations: Autoimmune thyroid disease (Hashimoto's/Graves'), Alopecia Areata, Type 1 Diabetes, Addison's disease.
• Treatment: Topical Corticosteroids, Topical Tacrolimus/Pimecrolimus, Topical Ruxolitinib 1.5% Cream (Opzelura) (JAK inhibitor approved for non-segmental vitiligo), NB-UVB phototherapy, Excimer laser.

Melasma (Chloasma / "Mask of Pregnancy")

• Clinical: Acquired hyperpigmentation on sun-exposed facial areas (cheeks, forehead, upper lip, chin) in women.
• Etiology: Driven by Estrogen / Progesterone and exposure to UVA and Visible Light.
• Treatment: Broad-spectrum tinted sunscreens (containing Iron Oxide to block visible light), Triple Combination Cream (Fluocinolone 0.01% + Hydroquinone 4% + Tretinoin 0.05% [Tri-Luma]), oral Tranexamic Acid.

Oculocutaneous Albinism (OCA)

• Pathophysiology: Autosomal recessive deficiency of Tyrosinase (OCA1) or P protein (OCA2), causing complete absence or marked reduction of melanin synthesis in skin, hair, and eyes. High risk of cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma.

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