Drug-Induced Photosensitivity
DRUG-INDUCED PHOTOSENSITIVITY
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
Incidence Low High
Pathophysiology Type IV hypersensitivity reaction Direct tissue injury
Onset >24hrs <24hrs
Clinical appearance Eczematous Exaggerated sunburn reaction with erythema, itching, and burning
Localization May spread outside exposed areas Only exposed areas
Pigmentary changes Unusual Frequent
Histology Epidermal spongiosis, exocytosis of lymphocytes and a perivascular inflammatory infiltrate Necrotic keratinocytes, predominantly lymphocytic and neutrophilic dermal infiltrate
DIAGNOSIS

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.

PHOTOSENSITIZING DRUGS1
Generic Brand Type of Reaction Notes
ANTIMICROBIALS
Antibiotics: Beta-Lactams
cefotaxime Photodistributed telangiectasia  
ceftazidime Fortaz, Tazicef Increased susceptibility to sunburn
Antibiotics: Fluoroquinolones
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 Levaquin Mild phototoxic potential. Photo-induced purpura have been reported.
moxifloxacin Avelox More photostable and least phototoxic
ofloxacin Moderate to severe sunburn reactions
Antibiotics: Tetracyclines
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
tetracycline2
Antibiotics: Others
dapsone Phototoxic and photoallergic drug eruptions
trimethoprim Photosensitivity
Antifungals
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
ketoconazole Photodermatitis
terbinafine Solar urticaria
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).
Antimalarials
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.
hydroxychloroquine Plaquenil
quinine Qualaquin Photoallergic and phototoxic reactions. Photosensitive dermatosis (edematous, eczematous, lichenoid); photo-onycholysis Routinely confirmed by photopatch testing
Antiretrovirals
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
tenofovir Vemlidy, Viread
Antituberculosis
isoniazid Photosensitive dermatoses, lichenoid eruption Confirmed by photopatch and re-challenge testing
pyrazinamide Photosensitive dermatoses Confirmed by re-challenge testing
CARDIOVASCULAR AGENTS
Antihypertensives: ACE Inhibitors
enalapril Vasotec Photosensitivity
quinapril Accupril
ramipril Altace
Antihypertensives: Angiotensin Receptor Blockers
candesartan Atacand Photosensitivity
irbesartan Avapro
losartan Cozaar
olmesartan Benicar
telmisartan Micardis
valsartan Diovan
Antihypertensives: Diuretics
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
indapamide Photo-onycholysis
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
Antihypertensives: Others
methyldopa Photosensitivity
Antiarrhythmics
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.
Nexterone
dronedarone Multaq Photosensitivity Significantly less phototoxic than amiodarone
quinidine Eczematous dermatitis, lichenoid eruption, livedoid purpuric eruption, photoallergic reaction
Cholesterol-Lowering Agents
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
CHEMOTHERAPY
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
crizotinib Xalkori Phototoxicity
dacarbazine Photosensitive eruptions Can switch to temozolomide if unable to tolerate
doxorubicin Doxil Photosensitivity
epirubicin Ellence Bullous eruption
erlotinib Tarceva Photosensitivity
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
vemurafenib2 Zelboraf Phototoxicity Common culprit
vinblastine Photosensitivity
NSAIDS
celecoxib Celebrex Photoallergic reactions and pseudoporphyria
diclofenac Arthrotec Photo-onycholysis
indomethacin Indocin Pseudoporphyria, erythema multiforme, lichenoid eruptions
meclofenamate
nabumetone
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
PSYCHOTROPIC AGENTS
Antidepressants
citalopram Celexa Photodistributed hyperpigmentation
clomipramine Anafranil Photoallergy
escitalopram Lexapro Erythroderma on sun-exposed areas
fluoxetine Prozac Erythema, blisters
fluvoxamine Photosensitivity
imipramine Tofranil Photodistributed erythema, blue-grey hyperpigmentation in photodistributed areas Hyperpigmentation seen in long-term use
paroxetine Paxil Photosensitivity, photodistributed granuloma annulare
phenelzine Nardil Clinical photosensitivity
sertraline Zoloft Macular erythematous photoallergic reaction
venlafaxine Effexor XR Photodistributed telangiectasia
Antipsychotics
aripiprazole Abilify Photo-onycholysis
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
haloperidol Haldol Photosensitive dermatitis
olanzapine Zyprexa Photo-onycholysis
risperidone Risperdal Photosensitivity
thioridazine2 Photodistributed slate-grey to violaceous hyperpigmentation Seen in long-term, high-dose therapy
Anxiolytics
alprazolam Xanax Pruritic erythema in sun-exposed areas
chlordiazepoxide Photo-induced eczematous eruption
OTHERS
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
diphenhydramine Benadryl Photosensitivity
eculizumab Soliris
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
leflunomide Arava Photosensitivity
mesalamine Lialda, Pentasa
mesna Mesnex
metformin Fortamet Erythematous and eczematous photosensitivity eruptions
pantoprazole Protonix Photosensitivity
pirfenidone Esbriet Exfoliative erythema, photoleukomelanoderma
ranitidine

Zantac Papulosquamous eruption on sun-exposed skin Normalization upon discontinuation. No recurrence upon re-initiation
sitagliptin Januvia Prolonged photosensitive eruption
tocilizumab Actemra Photosensitivity
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.

NOTES

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.

REFERENCES
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.

Created 2/2020

This article originally appeared on MPR