Fluconazole-induced drug rash with eosinophilia and systemic symptoms syndrome: a case report.

Abstract

Background: Drug rash with eosinophilia and systemic symptoms syndrome is a severe T-cell-mediated adverse drug reaction characterized by a skin rash, fever, hematologic abnormalities, and internal organ involvement following prolonged exposure to a causative medication. Drugs associated with drug rash with eosinophilia and systemic symptoms syndrome include anticonvulsants, allopurinol, antibiotics, and nonsteroidal anti-inflammatory drugs. Fluconazole is an exceedingly rare cause of drug rash with eosinophilia and systemic symptoms syndrome, with only one previously reported case in abstract form. We present a case of a woman with pulmonary coccidioidomycosis who developed fluconazole-induced drug rash with eosinophilia and systemic symptoms syndrome, presenting with an unusual clinical feature.

Case presentation: A 19-year-old Hispanic woman was taking fluconazole for pulmonary coccidioidomycosis. A total of 30 days after starting fluconazole, she developed a generalized skin rash. Despite this, she continued taking the medication. Then 1 week later, she experienced facial swelling and a sensation of "throat closing." She also developed fever, axillary lymphadenopathy, eosinophilia, atypical lymphocytes, and hepatitis. Fluconazole was discontinued, and she was treated with intravenous methylprednisolone, which led to an overall improvement in her condition. During hospitalization, her antifungal therapy was switched to posaconazole. However, within 24 hours, she again experienced the "throat closing" sensation, which was relieved with an epinephrine injection. The patient was discharged on Day 6 with oral methylprednisolone. Again, 9 days after discharge, her symptoms recurred, including facial swelling and new skin rashes. She was readmitted and treated with famotidine, corticosteroids, and diphenhydramine. Her general condition and skin rashes gradually improved, with complete resolution of the rash 3 months after the initial eruption.

Conclusion: We present a case of a woman with pulmonary coccidioidomycosis who developed drug rash with eosinophilia and systemic symptoms syndrome induced by fluconazole. Our case meets Bocquet's diagnostic criteria and is categorized as "definite" drug rash with eosinophilia and systemic symptoms by the Registry of Severe Cutaneous Adverse Reactions. Drug rash with eosinophilia and systemic symptoms syndrome is a T-cell-mediated type IV hypersensitivity reaction; however, our patient also exhibited a unique symptom-a sensation of "throat closing"-suggestive of angioedema and a Type I hypersensitivity component. This symptom appeared while she continued fluconazole after the onset of drug rash with eosinophilia and systemic symptoms syndrome and recurred upon the initiation of posaconazole. Although both fluconazole and posaconazole belong to the triazole antifungal class, true allergic cross-reactivity medicated by IgE is rare probably due to their structural differences. This suggests cross-reactivity may occur even with structurally unrelated drugs in drug rash with eosinophilia and systemic symptoms syndrome. Clinicians managing suspected cases of drug rash with eosinophilia and systemic symptoms syndrome should promptly discontinue the offending drug and exercise caution when prescribing alternative medications to minimize the risk of further hypersensitivity reactions.