|DEFINITION AND CLASSIFICATION|
Drug-induced photosensitivity: cutaneous adverse events due to exposure to a drug and either ultraviolet (UV) or visible radiation. Reactions can be classified as either photoallergic or phototoxic drug eruptions, though distinguishing between the two reactions can be difficult and usually does not affect management.
The following criteria must be met to be considered as a photosensitive drug eruption:
• Occurs only in the context of radiation
• Drug or one of its metabolites must be present in the skin at the time of exposure to radiation
• Drug and/or its metabolites must be able to absorb either visible or UV radiation
|Photoallergic drug eruption||Phototoxic drug eruption|
|Description||Immune-mediated mechanism of action. Response is not dose-related. Occurs after repeated exposure to the drug||More frequent and result from direct cellular damage. May be dose-dependent. Reaction can be seen with initial exposure to the drug|
|Pathophysiology||Type IV hypersensitivity reaction||Direct tissue injury|
|Clinical appearance||Eczematous||Exaggerated sunburn reaction with erythema, itching, and burning|
|Localization||May spread outside exposed areas||Only exposed areas|
|Histology||Epidermal spongiosis, exocytosis of lymphocytes and a perivascular inflammatory infiltrate||Necrotic keratinocytes, predominantly lymphocytic and neutrophilic dermal infiltrate|
Most cases of drug-induced photosensitivity can be diagnosed based on physical examination, detailed clinical history, and knowledge of drug classes typically implicated in photosensitive reactions. Specialized testing is not necessary to make the diagnosis for most patients. However, in cases where there is no prior literature to support a photosensitive reaction to a given drug, or where the diagnosis itself is in question, implementing phototesting, photopatch testing, or rechallenge testing can be useful.
|Generic||Brand||Type of Reaction||Notes|
|ceftazidime||Fortaz, Tazicef||Increased susceptibility to sunburn|
|ciprofloxacin||Cipro||Mild phototoxic potential. Photo-induced purpura have been reported. Persistent sequalae from phototoxicity in lung-transplant recipient on long-term immunosuppressive therapy||Typically a return to baseline 1wk after drug discontinuation|
|levofloxacin||—||Mild phototoxic potential. Photo-induced purpura have been reported.|
|moxifloxacin||Avelox||More photostable and least phototoxic|
|ofloxacin||—||Moderate to severe sunburn reactions|
|doxycycline2||Doryx, Vibramycin||Mild sunburn-like reactions with erythema and burning in sun-exposed areas; photodermatitis; solar urticaria, actinic granuloma, lichenoid reactions, nail dystrophy with photo-induced onycholysis, dyschromia. Nail effects can be delayed in presentation up to 2wks following sun exposure||Severe doxycycline-induced photo-onycholysis can occur at doses as low as 20mg/day in children|
|minocycline||Minocin, Solodyn||Generally not considered to be significant cause|
|dapsone||—||Phototoxic and photoallergic drug eruptions|
|griseofulvin||—||Not a potent photosensitizer. UVA implicated in photosensitivity|
|itraconazole||Sporanox, Tolsura||Photosensitivity in predominantly phototoxic pattern. Erythema, edema, vesicles in sun-exposed areas||Side effects reported following 5-day course oral therapy for candidiasis|
|voriconazole2||Vfend||Classic phototoxicity patterns, cheilitis, pseudoporphyria, photo-onycholysis||Second most commonly reported culprit in phototoxicity reactions. More likely in patients receiving long-term prophylactic therapy. Photosensitive eruptions occur months after drug initiation. Acute photodermatitis usually resolves upon discontinuation, however, photoaging and development of melanoma and squamous cell carcinoma in previously affected areas have been reported (esp. in children).|
|atovaquone/ proguanil||Malarone||Blisters and skin sloughing on sun-exposed areas||Occurred within hours of exposure and resolved within days of discontinuation. Confirmed by photopatch testing.|
|chloroquine||—||Drug-induced photodermatoses||Also used for photoprotective effects in photosensitivity conditions (eg, polymorphous light eruption, SLE). Occur within days to weeks of starting drug and resolve after discontinuation.|
|quinine||Qualaquin||Photoallergic and phototoxic reactions. Photosensitive dermatosis (edematous, eczematous, lichenoid); photo-onycholysis||Routinely confirmed by photopatch testing|
|efavirenz||Sustiva||Photosensitive eruptions (eg, polymorphous light eruption, porphyria cutanea tarda, actinic prurigo, chronic actinic dermatitis, photosensitive granuloma annulare, lichenoid photoeruption)||Photosensitive eruptions can occur in HIV patients, independent of drug|
|isoniazid||—||Photosensitive dermatoses, lichenoid eruption||Confirmed by photopatch and re-challenge testing|
|pyrazinamide||—||Photosensitive dermatoses||Confirmed by re-challenge testing|
|Antihypertensives: ACE Inhibitors|
|Antihypertensives: Angiotensin Receptor Blockers|
|furosemide||Lasix||Bullous eruptions (mimicking Brunsting-Perry-type presentation of localized bullous pemphigoid)|
|hydrochlorothiazide2||—||Exaggerated sunburn reactions, eczematous lesions in photodistributed pattern, lichenoid eruptions, photoleukomelanoderma||Chronic eczematous photosensitivity reported lasting months to years after discontinuation|
|triamterene||Dyrenium||Photosensitivity||Confirmed by photopatch testing|
|Antihypertensives: Calcium Channel Blockers|
|amlodipine||Norvasc||Photodistributed facial telangiectasia||May cross react with nifedipine|
|diltiazem||Cardizem||Photodistributed hyperpigmentation, photosensitive dermatitis|
|nifedipine||Procardia||Photodistributed facial telangiectasia, photodermatitis||May cross react with amlodipine|
|amiodarone2||—||Burning/tingling sensation in sun-exposed skin followed by development of erythema and eczema, pseudoporphyria; blue-grey hyperpigmentation on sun-exposed areas||Hyperpigmentation seen in long-term, high-dose therapy. Resolves within months of discontinuation; pigmentation fades over 1-2yrs.|
|dronedarone||Multaq||Photosensitivity||Significantly less phototoxic than amiodarone|
|quinidine||—||Eczematous dermatitis, lichenoid eruption, livedoid purpuric eruption, photoallergic reaction|
|atorvastatin||Lipitor||Edematous erythema on sun-exposed areas|
|fenofibrate||Tricor||Eczematous photosensitivity, lichenoid photosensitivity|
|pravastatin||Pravachol||Photodistributed erythema multiforme|
|simvastatin||Zocor||Persistent photodistributed dermatitis, photodistributed erythema multiforme|
|bicalutamide||Casodex||Photosensitivity||Seen in patients with prostate cancer|
|capecitabine||Xeloda||Photodistributed lichenoid eruptions||Less photosensitizing than fluorouracil. Alternative treatment for those unable to tolerate fluorouracil|
|dacarbazine||—||Photosensitive eruptions||Can switch to temozolomide if unable to tolerate|
|fluorouracil||—||Photosensitive eruptions, enhanced sunburn reactions, photodistributed hyperpigmentation, polymorphous light eruption-like reactions|
|flutamide||—||Photosensitivity||Seen in patients with prostate cancer|
|hydroxyurea||Droxia, Hydrea||Photodistributed dermatitis, photodistributed granulomatous rash||Seen in patients with chronic myeloid leukemia|
|imatinib||Gleevec||Exaggerated sunburn reactions, photo-induced dermatitis, pseudoporphyria||Seen in patients treated for chronic myelogenous leukemia. Dermatitis may resolve upon drug withdrawal and recur upon rechallenge|
|paclitaxel||Abraxane||Photodistributed erythema multiforme, onycholysis||Photosensitive reactions also reported for nab-paclitaxel|
|vandetanib||Caprelsa||Photodistributed erythematous, vesiculobullous eruption, erythema multiforme-like lesions, pigmentation in photo-exposed areas||Seen in patients treated for thyroid, lung, and hepatocellular carcinoma|
|celecoxib||Celebrex||Photoallergic reactions and pseudoporphyria|
|indomethacin||Indocin||Pseudoporphyria, erythema multiforme, lichenoid eruptions|
|naproxen2||Aleve||Pseudoporphyria, erythema multiforme, lichenoid eruptions||Most photosensitizing potential|
|oxaprozin||Daypro||Pseudoporphyria, erythema multiforme, lichenoid eruptions|
|piroxicam2||Feldene||Vesiculobullous, eczematous, lichenoid reactions|
|sulindac||—||Pseudoporphyria, erythema multiforme, lichenoid eruptions|
|escitalopram||Lexapro||Erythroderma on sun-exposed areas|
|imipramine||Tofranil||Photodistributed erythema, blue-grey hyperpigmentation in photodistributed areas||Hyperpigmentation seen in long-term use|
|paroxetine||Paxil||Photosensitivity, photodistributed granuloma annulare|
|sertraline||Zoloft||Macular erythematous photoallergic reaction|
|venlafaxine||Effexor XR||Photodistributed telangiectasia|
|chlorpromazine2||—||Exaggerated sunburn reactions, lichenoid reactions, bullous eruptions; photodistributed slate-grey to violaceous hyperpigmentation||Hyperpigmentation seen in long-term, high-dose therapy. Routinely confirmed by photopatch testing.|
|clozapine||Clozaril||Photosensitivity, vasculitis, erythema multiforme, skin pigmentation|
|thioridazine2||—||Photodistributed slate-grey to violaceous hyperpigmentation||Seen in long-term, high-dose therapy|
|alprazolam||Xanax||Pruritic erythema in sun-exposed areas|
|chlordiazepoxide||—||Photo-induced eczematous eruption|
|carbamazepine||Tegretol||Photosensitive eczematous eruptions, lichenoid eruptions||Carbamazepine-induced facial burns occured in one patient due to prolonged use of a photocopier|
|clopidogrel||Plavix||Lichenoid photodistributed eruption|
|esomeprazole||Nexium||Photosensitive dermatitis||Resolved upon discontinuation|
|ethinyl estradiol||—||Photosensitive eruptions, erythematous vesicular eruptions|
|glyburide||Diabeta, Glynase||Eczematous photodermatitis|
|isotretinoin||Absorica, Amnesteem||No clinical or experimental evidence confirming isotretinoin-induced photosensitivity|
|metformin||Fortamet||Erythematous and eczematous photosensitivity eruptions|
|pirfenidone||Esbriet||Exfoliative erythema, photoleukomelanoderma|
|—||Papulosquamous eruption on sun-exposed skin||Normalization upon discontinuation. No recurrence upon re-initiation|
|sitagliptin||Januvia||Prolonged photosensitive eruption|
|PREVENTION AND MANAGEMENT|
• Caution patients of the potential reaction for drugs considered to be potent photosensitizers; monitor.
• Emphasize sun avoidance and sun protection upon treatment initiation.
• Discontinue offending drug once diagnosis of drug-induced photosensitivity is made. Implement secondary preventive measures (eg, sun avoidance esp. during peak daylight hours, use of sun protective clothing and sunscreens with both UVA and UVB protection) if drug discontinuation is not possible.
• Administer medication in the evening if appropriate.
• Use of topical or systemic corticosteroids may be helpful to treat drug-induced photosensitive eruptions in symptomatic patients.
Key: ACE = angiotensin-converting enzyme; SLE = systemic lupus erythematosus
1 Drugs that have been reported in medical literature to cause clinical photosensitivity are listed. Most of this literature consist of case reports and case series. Due to underreporting, it is difficult to ascertain the true incidence of photosensitivity reactions. Topically administered drugs that cause photosensitivity have been excluded, as well as drugs that cause photosensitivity as part of their desired mechanism of action.
2 Considered to be potent and common causes of photosensitivity.
Not an inclusive list of medications and/or official indications. Please see drug monograph at www.eMPR.com and/or contact company for full drug labeling.
|Adapted from Blakely KM, Drucker AM, Rosen CF. Drug-Induced Photosensitivity – An Update: Culprit Drugs, Prevention and Management. Drug Safety. 2019; 42:827-847. https://doi.org/10.1007/s40264-019-00806-5.
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