Photosensitivity

Photosensitivity is an abnormal cutaneous response to ultraviolet or visible light that is out of proportion to the exposure.

Radiation. Ultraviolet B (290 to 320 nm) causes sunburn and does not pass window glass. Ultraviolet A (320 to 400 nm) penetrates window glass and deeper skin layers. Visible light (400 to 700 nm) causes reactions in erythropoietic protoporphyria, solar urticaria and porphyria.

Classification

• Idiopathic photodermatoses: polymorphic light eruption, chronic actinic dermatitis, solar urticaria, actinic prurigo and hydroa vacciniforme.
• Drug or chemical induced: phototoxic (dose dependent, occurs in anyone given enough drug and light) and photoallergic (delayed type IV reaction in a sensitised person).
• Photoaggravated dermatoses: lupus, dermatomyositis, atopic dermatitis, rosacea, psoriasis, pemphigus, Darier disease and herpes simplex.
• Metabolic: porphyrias and pellagra.
• Genetic DNA repair disorders: xeroderma pigmentosum, Cockayne syndrome, trichothiodystrophy and Bloom syndrome.

Timing. Phototoxic reactions appear within minutes to 24 hours and look like severe sunburn. Photoallergic reactions appear 24 to 72 hours after exposure with eczema that can spread beyond exposed skin. Polymorphic light eruption starts hours to 2 days after the first sun of the season and settles in 7 to 10 days without scarring. Solar urticaria appears within minutes. Pain or burning within minutes without a visible rash, starting in childhood, is typical of erythropoietic protoporphyria.

Distribution. Exposed sites (face, V of the neck, dorsal hands and forearms) are affected, with sparing of the upper eyelids, retroauricular area, submental skin and skin folds. Involvement through window glass indicates ultraviolet A or visible light.

Mechanisms. Phototoxicity produces direct cell damage from drug or porphyrin excited by light. Photoallergy depends on a photoproduct acting as a hapten. Polymorphic light eruption is a delayed immune reaction to ultraviolet induced antigens. Xeroderma pigmentosum results from failure to repair ultraviolet DNA damage.

Key distinctions. Blisters, skin fragility, milia, and facial hypertrichosis on the dorsal hands suggest porphyria cutanea tarda. Severe burning in childhood with little skin change suggests erythropoietic protoporphyria. Marked sunburn after minimal exposure with freckling in a child suggests xeroderma pigmentosum.

History

• Time from exposure to onset, duration, season, indoor lighting, reactions through window glass, age at first onset, family history and previous episodes.
• Symptoms: burning, pain, itch, wheals, blisters, scarring and swelling.
• Drugs and chemicals in the preceding days to weeks: thiazides, furosemide, doxycycline and other tetracyclines, fluoroquinolones, naproxen and other NSAIDs (including topical ketoprofen), amiodarone, chlorpromazine, voriconazole, hydroxychloroquine, quinine, carbamazepine, sulphonamides, retinoids, griseofulvin, calcium channel blockers, St John's wort, vemurafenib and 5-fluorouracil.
• Plants and topicals: limes, figs, celery, parsley, bergamot perfumes, coal tar, psoralens, sunscreen filters (benzophenones), fragrances and antiseptics.
• Systemic features: joint pain, mouth ulcers, fever, hair loss, proximal weakness, dysphagia, diarrhoea, dementia or confusion (pellagra), abdominal pain, constipation, neuropsychiatric symptoms and dark or red urine (porphyria).
• Alcohol, hepatitis C, HIV, iron overload, malnutrition, maize dependent diet, and use of oestrogens.
• Eye symptoms, recurrent sunburn, early skin cancers, and developmental or neurological concerns in children.

Examination

• Exact distribution with sparing pattern, and morphology: erythema, papules, plaques or vesicles (polymorphic light eruption), wheals, eczema, lichenification (chronic actinic dermatitis), blisters, scars, milia and hypertrichosis (porphyria), waxy thickening and scarring (erythropoietic protoporphyria), and freckling with poikiloderma (xeroderma pigmentosum).
• Casal necklace (dermatitis at the neck base) in pellagra, photo-onycholysis, lips and eyes.
• Malar rash, scarring plaques and scalp changes (lupus), heliotrope rash, Gottron papules and proximal weakness (dermatomyositis).
• Liver size and stigmata of chronic liver disease, joints, lymph nodes, neurological signs and skin cancers.
• Skin type (Fitzpatrick) and signs of malnutrition.

Red flags

• Severe abdominal pain, vomiting, constipation, tachycardia, hypertension, confusion, seizures, hyponatraemia or dark urine (acute porphyria).
• Extreme sunburn from minimal exposure in an infant or child, with freckling, ocular surface disease or neurological regression (xeroderma pigmentosum, Cockayne syndrome).
• Photosensitive rash with haematuria, proteinuria, cytopenias, serositis or neurological signs (lupus).
• Proximal weakness, dysphagia or dyspnoea (dermatomyositis).
• Diarrhoea, dementia and dermatitis (pellagra).
• Jaundice or abdominal pain in erythropoietic protoporphyria (cholestatic liver disease).
• Mucosal erosions and blistering after a drug (Stevens-Johnson syndrome).
• Erythroderma.
• Facial swelling, fever and necrotic papules in a child (hydroa vacciniforme like lymphoproliferative disorder).
• Suspected skin cancer.

Special groups

• Children: polymorphic light eruption, solar urticaria, erythropoietic protoporphyria, xeroderma pigmentosum and actinic prurigo. Avoid tetracyclines and fluoroquinolones.
• Pregnancy: polymorphic light eruption can flare. Avoid psoralens. Use mineral sunscreens and mild topical corticosteroid.
• Older adults: drug induced reactions, chronic actinic dermatitis, lupus and skin cancer.
• Skin of colour: erythema is less visible, so ask about burning and look for pigment change. Sunscreen use and strict avoidance can cause vitamin D deficiency.
• Region specific: pellagra with maize dependent diets or malnutrition, HIV associated photosensitivity, plant sap reactions, and traditional remedies.

Idiopathic photodermatoses

• Polymorphic light eruption.
• Chronic actinic dermatitis.
• Solar urticaria.
• Actinic prurigo.
• Hydroa vacciniforme.
• Hydroa vacciniforme like lymphoproliferative disorder.
• Juvenile spring eruption.

Drug and chemical induced

• Phototoxic drug reaction (tetracyclines, fluoroquinolones, amiodarone, thiazides, voriconazole, NSAIDs, phenothiazines, vemurafenib).
• Photoallergic drug reaction (NSAIDs, sunscreen filters, fragrances, antiseptics).
• Phytophotodermatitis.
• Pseudoporphyria.
• Photo-onycholysis.

Photoaggravated and autoimmune

• Systemic lupus erythematosus.
• Subacute cutaneous lupus.
• Discoid lupus erythematosus.
• Dermatomyositis.
• Atopic dermatitis.
• Rosacea.
• Psoriasis.
• Pemphigus foliaceus.
• Darier disease.
• Recurrent herpes simplex.

Metabolic

• Porphyria cutanea tarda.
• Erythropoietic protoporphyria.
• Variegate porphyria.
• Hereditary coproporphyria.
• Congenital erythropoietic porphyria.
• Pellagra and Hartnup disease.
• Carcinoid syndrome with pellagra.

Genetic

• Xeroderma pigmentosum.
• Cockayne syndrome.
• Trichothiodystrophy.
• Bloom syndrome.
• Rothmund-Thomson syndrome.
• Oculocutaneous albinism.

Mimics

• Sunburn from normal exposure.
• Airborne allergic contact dermatitis.
• Seborrhoeic dermatitis.
• Mycosis fungoides and Sezary syndrome.
• Erythema multiforme.
• Pellagra like dermatitis from isoniazid.

Step 1. Pattern and timing. Decide between idiopathic, drug related, systemic and genetic causes using onset, distribution, season and wavelength clues.

Step 2. Drug and chemical review. List every systemic and topical exposure in the 2 weeks before onset and withdraw suspected agents.

Step 3. First line tests

• Full blood count, ESR, CRP, urea, creatinine, urinalysis, liver tests, glucose, and ferritin.
• ANA, anti Ro (SSA), anti La, anti dsDNA and complement when lupus is possible. Anti Ro positivity is typical of subacute cutaneous lupus.
• Creatine kinase and myositis antibodies when proximal weakness exists.
• Hepatitis C and HIV tests, and pregnancy test in women of reproductive age.

Step 4. Porphyria screen for blistering, scarring, dark urine, painful immediate reactions, unexplained cholestasis or abdominal pain.

• Plasma porphyrins by fluorescence emission scanning (peak near 620 nm in porphyria cutanea tarda, 626 to 628 nm in variegate porphyria, 634 nm in erythropoietic protoporphyria), with urine and faecal porphyrins to separate subtypes.
• Total erythrocyte protoporphyrin when erythropoietic protoporphyria is possible, with fractionation (free protoporphyrin markedly raised).
• Spot urine porphobilinogen during an acute attack. Protect samples from light and treat on clinical grounds without waiting for confirmation.
• In porphyria cutanea tarda check ferritin, transferrin saturation, HFE genotype, hepatitis C, HIV, glucose and liver tests.
• Genetic testing (FECH, UROD, HMBS, PPOX, CPOX, and DNA repair genes) in specialist centres.

Step 5. Photobiology testing

• Monochromator or broadband phototesting to measure the minimal erythema dose and thresholds for ultraviolet B, ultraviolet A and visible light.
• Photoprovocation testing for polymorphic light eruption on 3 consecutive days.
• Photopatch testing with duplicate allergen series (one set irradiated with ultraviolet A) for photoallergy. Routine patch testing for chronic actinic dermatitis (often positive to fragrances and sesquiterpene lactones).
• Perform testing while off topical and systemic immunosuppression where possible.

Step 6. Skin biopsy (4 mm punch). Polymorphic light eruption shows a perivascular lymphocytic infiltrate with papillary dermal oedema. Lupus shows interface dermatitis with dermal mucin, and direct immunofluorescence adds specificity. Porphyria cutanea tarda shows a subepidermal blister with festooning and thickened vessel walls, and pseudoporphyria looks identical, so porphyrin results distinguish them.

Step 7. Other. Niacin status and diet review for pellagra (diagnosis is clinical and confirmed by response to nicotinamide). Liver tests and ultrasound in erythropoietic protoporphyria. 25 hydroxyvitamin D in patients practising strict sun avoidance. Ophthalmology and neurological assessment in suspected xeroderma pigmentosum.

Limits. Phototesting is available only at specialist centres. Plasma and urine porphyrin tests must be protected from light. Porphobilinogen may be normal between attacks in variegate porphyria and hereditary coproporphyria, so use faecal porphyrins. Photopatch tests are often negative in photoallergy to systemic drugs.

Immediate

• Acute porphyria attack: admit. Give haem arginate 3 mg/kg intravenously once daily for 4 days (infused over 30 minutes through a large vein), or, when unavailable, carbohydrate loading of at least 300 g glucose daily (for example 10% dextrose) with sodium monitoring because of hyponatraemia. Stop precipitating drugs (barbiturates, sulphonamides, rifampicin, griseofulvin, oestrogens, many anticonvulsants), treat pain with opioids and nausea with ondansetron, and give a beta blocker for tachycardia. Seizures: benzodiazepines or levetiracetam, avoiding phenytoin, carbamazepine and valproate.
• Anaphylaxis from solar urticaria: adrenaline 0.5 mg intramuscularly, repeated every 5 minutes if no response.
• Extensive blistering sunburn or phototoxic burn: cool compresses, analgesia, fluids and burn wound care. Admit for over 15% body surface area, systemic features or children.
• Severe cutaneous drug reaction: admission and drug withdrawal.

Sunburn care. Cool compresses, paracetamol 1 g orally every 6 hours (maximum 4 g daily; 3 g daily in hepatic impairment, chronic alcohol use or weight under 50 kg), and mometasone furoate 0.1% once daily for 3 to 5 days. Avoid topical anaesthetics and benzocaine.

Photoprotection (all patients)

• Broad spectrum sunscreen SPF 50 or more with high ultraviolet A protection, applied at about 2 mg/cm2 (about 35 mL for an adult whole body), 20 minutes before exposure and every 2 hours. Tinted sunscreens with iron oxide protect against visible light.
• Physical filters (zinc oxide, titanium dioxide) for sensitive and photoallergic skin.
• Ultraviolet protective clothing, wide brimmed hat, sunglasses, and avoidance of midday sun (10:00 to 16:00).
• Window film or laminated glass for ultraviolet A transmitted through car and office windows.
• Vitamin D: check 25 hydroxyvitamin D and give cholecalciferol 800 to 2,000 IU orally once daily when sun avoidance is strict.

Cause directed

• Phototoxic and photoallergic drug reactions: stop the drug and switch to a nonphotosensitising alternative where possible. Topical mometasone furoate 0.1% once daily for 5 to 7 days. Photoallergy can persist for months. Amiodarone: reduce the dose to the lowest effective level.
• Polymorphic light eruption: mometasone furoate 0.1% once daily for 3 to 5 days, or prednisolone 20 to 30 mg orally daily for 3 to 5 days in severe flares. Prevention: gradual sun exposure, and narrowband ultraviolet B or psoralen with ultraviolet A phototherapy 2 to 3 times each week for 4 to 6 weeks before the sunny season. Hydroxychloroquine 200 mg orally twice daily (maximum 5 mg/kg of actual body weight daily) before sun exposure has limited evidence.
• Solar urticaria: second generation antihistamine up to 4 times the licensed dose (for example cetirizine 10 mg up to four times daily, maximum 40 mg daily), omalizumab 150 to 300 mg subcutaneously every 4 weeks (specialist), and phototherapy hardening.
• Chronic actinic dermatitis: strict photoprotection and allergen avoidance, clobetasol propionate 0.05% once daily for up to 2 weeks (maximum 50 g in any week, not on the face), tacrolimus 0.1% ointment twice daily on the face, and short courses of prednisolone 20 to 40 mg orally daily. Azathioprine 1 to 2.5 mg/kg daily (after TPMT or NUDT15 testing), ciclosporin 3 to 5 mg/kg orally daily in 2 divided doses, or mycophenolate mofetil 1 g orally twice daily for refractory disease (specialist).
• Actinic prurigo: sunscreens, topical corticosteroids and, in specialist care, thalidomide 50 to 100 mg orally at night (teratogenic with pregnancy prevention required, neuropathy and thrombosis risk).
• Lupus: photoprotection, hydroxychloroquine 200 to 400 mg orally daily (maximum 5 mg/kg of actual body weight daily) with baseline and annual retinal screening after 5 years, topical corticosteroid or tacrolimus, and rheumatology review.
• Dermatomyositis: prednisolone 0.5 to 1 mg/kg orally daily (maximum 80 mg daily) with a steroid sparing agent, strict photoprotection and malignancy screening.
• Porphyria cutanea tarda: stop alcohol, oestrogens and iron, treat hepatitis C and HIV, and give venesection of 450 mL every 2 weeks until ferritin reaches about 20 micrograms/L (defer when haemoglobin is under 11 g/dL), or hydroxychloroquine 100 mg orally twice weekly (monitor liver tests; avoid usual dosing, which can cause acute hepatic injury in this condition).
• Erythropoietic protoporphyria: strict photoprotection, afamelanotide 16 mg subcutaneous implant every 60 days (up to 4 implants each year; specialist), and liver tests with erythrocyte protoporphyrin every 6 to 12 months. Beta carotene 60 to 180 mg orally daily has limited evidence. Report jaundice or abdominal pain urgently.
• Pellagra: nicotinamide 300 mg orally daily in divided doses for 3 to 4 weeks, with a balanced diet, treatment of alcohol dependence, and pyridoxine with isoniazid.
• Xeroderma pigmentosum: lifelong strict ultraviolet protection, skin and eye examination every 3 to 6 months, early excision of lesions, genetic counselling, and specialist chemoprevention (acitretin or isotretinoin).
• Phytophotodermatitis: wash the skin, avoid the plant sap, and apply mometasone furoate 0.1% once daily for 5 to 7 days. Pigment fades over weeks to months.

Monitoring. Review at 2 to 4 weeks, then every 3 months. Photograph lesions. Annual skin cancer examination in xeroderma pigmentosum, lupus and chronic actinic dermatitis. Check liver tests and vitamin D at each review.

Referral and escalation. Same day review for acute porphyria. Dermatology and photobiology for suspected polymorphic light eruption not controlled with simple measures, photoallergy, chronic actinic dermatitis and actinic prurigo. Rheumatology for lupus and dermatomyositis. Hepatology and haematology for porphyria. Paediatric genetics and ophthalmology for suspected xeroderma pigmentosum and Cockayne syndrome.

Admission criteria. Acute porphyria attack, extensive blistering burns, severe cutaneous drug reaction, anaphylaxis, dermatomyositis with dysphagia, and lupus with organ involvement.

Disposition. Most patients are managed in primary care. Safety net advice: return for abdominal pain with dark urine, blistering, fever, muscle weakness, mouth or eye sores, jaundice, a changing mole, or a nonhealing sore.