Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory conditions with heterogeneous triggers and overlapping clinical phenotypes. Diagnostic uncertainty is particularly challenging in resource-limited settings, where advanced molecular and immunophenotypic investigations are not readily available. A 31-year-old woman presented with recurrent febrile episodes, trilineage cytopenias, hyperferritinemia (peak 16,970 ng/mL [reference: 99% probability of HLH/MAS). A striking feature was the persistent dissociation between markedly elevated ferritin and low C-reactive protein (CRP) values (ratio < 0.002), consistent with a non-IL-6-dominant, interferon-γ-driven hyperinflammatory state. Based on this phenotype, a sequential treatment strategy combining therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and cyclosporine A (CyA) was implemented without cytotoxic chemotherapy. The patient demonstrated significant clinical and biochemical improvement, with resolution of cytopenias and progressive decline in ferritin. This case highlights the diagnostic overlap between autoimmune panniculitis, SPTCL, and HLH/MAS, and underscores the importance of phenotype-guided management in complex hyperinflammatory syndromes. It further illustrates that effective treatment can be achieved without cytotoxic therapy in selected patients, even in the absence of definitive molecular diagnosis.
Taha et al. (Wed,) studied this question.