ImportanceTrimethoprim-sulfamethoxazole (TMP-SMX) hypersensitivity reaction, ranging from circulatory shock to aseptic meningitis and respiratory failure, is a potentially life-threatening condition with dermatologic relevance.ObjectiveTo describe the mucocutaneous findings and clinical features of TMP-SMX hypersensitivity reaction.Design, Setting, and ParticipantsThis was a retrospective case series study of 7 patients who developed a characteristic rash, hemodynamic changes, and end-organ dysfunction after treatment with TMP-SMX at a large university hospital system during January 2013 to March 2022.ExposuresTreatment with TMP-SMX within 2 weeks of the reaction.Main Outcome and MeasuresDescriptions of the condition, including the demographic information of the affected population, the reaction timeline, and mucocutaneous and clinical features.ResultsThe cohort comprised 7 patients (median [range] age, 20 [15-66] years; 4 female and 3 male). The most common mucocutaneous findings were generalized sunburn-like erythema without scale, conjunctivitis, and mild facial and acral edema. Three patients had previous exposure to TMP-SMX and developed symptoms in 1 day or less, while those without prior exposure presented from 4 to 11 days after drug initiation. Among the 7 patients, 6 had fever, 7 had hypotension, and 7 had tachycardia. All patients had lymphopenia and evidence of end-organ dysfunction with either kidney or liver involvement. Median (range) time to resolution was 72 (48-96) hours.Conclusions and RelevanceThis retrospective case series indicates that SCoRCH (sudden conjunctivitis, lymphopenia, and rash combined with hemodynamic changes) should be considered in the differential diagnosis of patients presenting with acute generalized sunburn-like erythema, conjunctivitis, systemic symptoms, and hemodynamic changes in the setting of recent TMP-SMX use.