Adult-onset Still's disease with hemophagocytic lymphohistiocytosis and minimal change disease.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by diverse etiologies and a high risk of misdiagnosis. Autoinflammatory disorders, such as adult-onset Still's disease (AOSD), are often underrecognized as contributing factors. Minimal change disease (MCD) represents an exceedingly rare renal complication in the context of HLH. This report describes the case of an adult female diagnosed with Epstein-Barr virus (EBV)-associated HLH. Initial therapy with etoposide and dexamethasone yielded a partial response; however, disease relapse occurred, accompanied by the development of significant proteinuria. Renal biopsy confirmed a diagnosis of MCD. Administration of rituximab led to complete remission of the nephrotic syndrome, although HLH activity persisted. A subsequent skin biopsy revealed perivascular infiltration composed predominantly of lymphocytes and neutrophils. In combination with clinical features such as high-grade fever and rash, these findings supported a diagnosis of AOSD. Adjustment of the treatment regimen to include corticosteroids and methotrexate resulted in complete remission of HLH. This case underscores the importance of re-evaluating the underlying cause in patients with HLH who demonstrate an inadequate therapeutic response. MCD may represent a renal manifestation of immune dysregulation associated with HLH. A multidisciplinary approach is essential for improving diagnostic precision and optimizing treatment in complex presentations of HLH.