Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A rare adverse reaction to azathioprine in Vogt-Koyanagi-Harada disease

A 44-year-old female with Vogt-Koyanagi-Harada disease was treated with three doses of pulse corticosteroids and was subsequently continued on oral steroids (60 mg/day) and oral azathioprine (50 mg three times a day). Forty-five days after starting treatment, she developed itching all over the body, including the scalp, accompanied by high-grade fever (103°F) with chills, mild joint pain, nausea, and vomiting. She also developed erythematous maculopapular rashes, initially appearing on all extremities and later involving the trunk. The rash was associated with scaling over the scalp and facial folds, along with ulceration and peeling of mucosal surfaces [Fig. 1]. Routine blood investigations revealed leucocytosis, raised C-reactive protein (198 mg/L), and erythrocyte sedimentation rate (48 mm/hr). Her absolute eosinophil count was 1,250/µL. She was started on antipyretics, broad-spectrum antibiotics, and antihistamines. Her serologies for dengue, malaria, and typhoid were negative, and her blood and urine cultures were normal. As her symptoms did not subside, she sought further treatment at a higher center for dermatology consultation, where she was diagnosed with Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), confirmed by a skin punch biopsy. Azathioprine was discontinued, and she was advised to stop all other medications except oral corticosteroids. Her symptoms improved, her fever subsided within two days of stopping azathioprine, and she recovered within two weeks, with complete resolution of the skin rash [Fig. 2].Figure 1: External photograph showing skin rashes in a 44-year-old female with Vogt-Koyanagi-Harada disease who developed drug reaction with eosinophilia and systemic symptoms (DRESS) following treatment with Azathioprine. Erythematous maculopapular rashes are seen in her hands. The rash was associated with scaling over facial folds, along with ulceration and peeling of mucosal surfacesFigure 2: (a and b) Resolution of skin rashes after discontinuation of azathioprineDiscussion DRESS is a severe, T cell-mediated drug reaction with combinations of cutaneous, hematologic, and internal organ involvement.[1] The most common DRESS-inducing agents are anticonvulsants, allopurinol, sulphonamides, and antibiotics. Rarely, azathioprine can also cause DRESS.[2] It is assumed that DRESS is the result of a complex interaction between drug exposure, genetic predisposition, and viral reactivation.[3] Symptoms start within 2–12 weeks of initiation of azathioprine and resolve within 15 days.[2] Diagnosis of DRESS is challenging due to the delayed onset of cutaneous manifestations, which might be confused with other severe cutaneous adverse drug reactions. Skin biopsy in DRESS may reveal features such as spongiosis, acanthosis, basal cell vacuolization, and a lymphocytic infiltrate predominantly in the papillary dermis and around blood vessels.[4] Eosinophils, atypical lymphocytes, and occasionally granulomas may also be variably present. The overall mortality in DRESS syndrome is about 10%.[1] Hence, timely recognition and early initiation of treatment with discontinuation of the offending agent are necessary. Informed consent Written informed consent was obtained from the patient for publication of images. Authors’ contributions Dr. RK prepared the draft, Dr. PDM was involved in patient management, provided additional inputs, and finalized the manuscript. Both authors reviewed the final manuscript. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given consent for images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.