Toxic epidermal necrolysis as a result of chlorthalidone and cyclophosphamide combination

ABSTRACT

Case report Introduction: Toxic epidermal necrolysis (TEN), is an immune-mediated disease characterized by severe mucocutaneous symptoms and is the result of an inflammatory response that leads to keratinocyte necrosis and perivascular lymphocyte infiltration, mostly drug-related. Case report A 35-year- old male, with a history of recently diagnosed systemic lupus under treatment with prednisone, hydroxychloroquine, mycophenolate and cotrimoxazole forte evolves with persistent proteinuria, it is decided to add losartan, chlorthalidone and atorvastatin. Nevertheless despite immunosuppression, proteinuria and skin involvement persisted, so mycophenolate was suspended and a bolus of cyclophosphamide 1 g was administered. Eight weeks after adjusting treatment, the patient went to the emergency department due to a confluent, pruritic, maculopapular rash with blistering lesions on the trunk, upper limbs, face, and oral mucosa, associated with fever over 38degreeC, that evolved during one week. On admission, the following was confirmed confluent erythematous macular exanthem associated with multiple flaccid blisters on the chest, upper limbs and neck, Nikolsky's sign (+), keratoconjunctivitis and dryness on the lips. Admission tests included complete blood count with no leukocytosis or eosinophilia, ESR 29 mm/hr, C-RP 19.8 mg/L, no liver profile abnormalities, creatinine 0.8 mg/dl, and urine test with proteinuria 300 mg/dl. Negative infectious study for mycoplasma, herpes 6 virus, cytomegalovirus, Epstein barr virus, hepatitis A, B, C, E and SARS-COV2 virus. Due to severe mucosal skin involvement, TEN/SJS was suspected v/s (TEN)-like Lupus presentation, drugs used prior to admission (chlorthalidone, losartan, atorvastatin) were discontinued, and treatment was started with Hydrocortisone 100 mg every 8 hours IV, Immunoglobulin 2 g/kg daily IV for 4 days, plus skin and mucous membrane care. Patient had a favorable evolution, with resolution of skin and mucosal lesions and no signs of infection. Skin biopsy showed necrotic epidermis, necrotic basal keratinocytes, and sparse lymphocytic inflammatory infiltrate in the papillary dermis, consistent with erythema multiforme/toxic epidermal necrolysis. Conclusion(s) Extensive mucosal involvement is one of the cardinal signs of the presentation of SJS/ETN and given its severity, a high index of suspicion is important with the consequent suspension of suspected drugs and support management for a favorable evolution. In this case the suspected culprit drug was the combination of cyclophosphamide and chlorthalidone, due to reports of increased toxicity of cyclophosphamide in combination with diuretic drugs.