Dronedarone-induced phototoxic dermatitis.

Drug-induced photosensitivity (DIP) occurs when a medication causes an unexpected eruption on sun-exposed skin.1-3 We present a case of a patient with severe dronedarone-induced phototoxicity. An 85-year-old woman, with a past medical history of atrial fibrillation, chronic kidney disease, hypertension, and hyperlipidemia, was admitted with a 3-day onset of severe painful and itchy rash that developed after she had spent time swimming outdoors. One month prior, she was prescribed dronedarone for rate control of her atrial fibrillation. On examination, she had crusted erosions, patches, plaques, and tense bullae on an erythematous base on her face, upper trunk, and bilateral extremities (Figure 1). A shave biopsy from the right lower extremity revealed sloughed epidermis with spongiosis, subepidermal vesiculation, scattered necrotic keratinocytes, and small foci of full-thickness epidermal necrosis with overlying parakeratosis and no significant inflammatory cell infiltrate (Figure 2). Direct immunofluorescence was negative. Given recent dronedarone initiation, the findings were most consistent with DIP. Dronedarone was discontinued, and the patient was rate controlled with diltiazem. She was treated with prednisone 40 mg for 5 days and triamcinolone 0.1% cream. The eruption had significantly improved, and she was discharged home 3 days later. Photosensitivity represents 8% of adverse cutaneous medication effects. Most DIP reactions are classified as phototoxic or photoallergic. There is often an overlap between the two patterns.1, 3 Phototoxicity is mediated by direct tissue and oxygen-mediated cell damage caused by a photoproduct. It is dose-dependent and manifests as a severe sunburn with erythema, edema, vesicles, and bullae, followed by hyperpigmentation. Phototoxicity is limited to sun-exposed areas and develops within minutes to hours of sun exposure, without delayed reactions. In contrast, photoallergy requires prior sensitization; it is caused by a photoproduct leading to a type IV hypersensitivity reaction and occurs at least 24 hours following sun exposure.3, 4 Photoallergy symptoms are similar to acute allergic contact dermatitis with vesicles and scaling that may develop on unexposed skin with no chronic phase.1, 3 Histologically, acute phototoxic dermatitis results in apoptotic keratinocytes with dermal edema and secondary infiltrate of neutrophils and lymphocytes, while photoallergic drug reactions are characterized by spongiosis, vesiculation, exocytosis of lymphocytes into the epidermis, and perivascular inflammation with or without eosinophils.2 Medications that can cause DIP include antibiotics, diuretics, antiarrhythmics, and NSAIDs, among others.1-3 Within antiarrhythmics, amiodarone is known to cause photosensitivity. Dronedarone is a newer version of amiodarone with improved safety profile.2, 3 However, dronedarone has been recently reported to cause DIP as well.1 The diagnosis of DIP is made based on the patient's clinical presentation, histology, and photopatch testing. Differential diagnosis of DIP includes phytophotodermatitis, pseudoporphyria, cutaneous lupus erythematosus, and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).2, 3 SJS/TEN is a rare but important differential diagnosis that also has an acute presentation preceding prodromal symptoms and mucosal involvement. Treatment of DIP includes discontinuation of the offending agent if possible and proper sun protection. In case of photoallergy, a permanent discontinuation of the offending agent is required. However, it is not required in case of phototoxicity if there is no alternative medication available and the patient uses proper sun protection. In addition, topical or systemic corticosteroids can be used.3, 4 In our case, the patient had improvement before the photopatch testing could be performed. Although photoxicity is the most likely diagnosis in our case, dronedarone can cause both types of reaction. Photopatch could be a valuable adjunctive testing for the differential diagnosis.5 In conclusion, DIP is a rare and serious dronedarone-related adverse reaction. Patients taking dronedarone should be advised to wear proper sun protection.