Introduction: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rapidly developing mucocutaneous reactions, existing as a spectrum based on skin involvement, generally triggered by medications. SJS/TEN-like systemic lupus erythematosus (SLE) is described in several case reports, although it remains uncommon. It presents as a diagnostic conundrum given that this bullous rash is not typically seen with lupus. Here, we describe a case of SLE masquerading as SJS.

Case Presentation: A 25-year-old male with mixed connective tissue disease (MCTD) and attention-deficit/hyperactivity disorder presented with a diffuse rash and oral mucosal involvement after a sore throat and fever. He had recently started Modafinil. Upon examination, he appeared ill, with a generalized maculopapular rash. Lab-work revealed thrombocytopenia, normocytic anemia, acute kidney injury (AKI), and transaminitis. Rheumatology was consulted, and initially recommended monitoring off Modafinil, with further work-up, including a skin biopsy (as rash appeared atypical for that seen in MCTD or lupus). Other consultants were also involved, including Dermatology, Nephrology, and Hematology-Oncology. Patient underwent a kidney biopsy and was started on IV Methylprednisolone 150 mg for three days, followed by Prednisone. Interestingly, skin biopsy findings indicated features of SJS (separation of the necrotic epidermis from the dermis, perivascular lymphocytic infiltrate); however, there were also atypical features (mixed-cell infiltrate with neutrophils). The sample was then sent out for a second opinion. The patient developed respiratory failure and pulmonary edema, necessitating intubation and transfer to the Intensive Care Unit for pressor support due to cardiogenic shock echocardiogram showed an ejection fraction of less than 30%. Given clinical deterioration with worsening cytopenias, transaminitis, AKI, hypocomplementemia, positive antinuclear-antibody, and double-stranded DNA (dsDNA), he was switched to IV Methylprednisolone 1 gram for three days, followed by a steroid taper. Elevated triglycerides (765 mg/dl) and ferritin (15,084 ng/ml) raised concerns for HLH, leading to the initiation of Rituximab (literature has shown use off-label for SLE, and benefit in certain viral-induced HLH). Kidney biopsy revealed acute tubular necrosis and Class 1 lupus nephritis. Ultimately, direct immunofluorescence of skin biopsy showed granular deposition of immunoglobulins and complement consistent with SLE.

The patient was also started on continuous renal replacement therapy. After receiving intravenous immunoglobulin (IVIG) for four days and Cefepime for Escherichia coli and Klebsiella bacteremia, he was weaned off pressors. Improvements were seen in complements, dsDNA, C-reactive protein, ferritin, and cytopenias. By discharge, dialysis was no longer needed, and he was started on Hydroxychloroquine, Prednisone taper, Atovaquone, and Spironolactone.

Discussion: This case highlights the diagnostic and therapeutic challenges of managing lupus-associated SJS/TEN. Initial biopsy findings were consistent with SJS, but atypical cells and subsequent immunofluorescence confirmed SLE. Key clinical indicators—hypocomplementemia, elevated dsDNA, and steroid-responsive cytopenias—pointed to an SJS/TEN-like lupus. Management was further complicated by conflicting reports on the use of steroids in SJS/TEN and the development of HLH, requiring an aggressive treatment approach. Differentiating SJS/TEN-like SLE from drug-induced SJS/TEN is crucial for appropriate management and prognosis.