A Systematic Review of Dermatologic Findings in Adults With Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition driven by aberrant cytotoxic immune overactivation that manifests with nonspecific findings, making the diagnosis challenging. The objective of this systematic review was to outline the diagnostic criteria for HLH and cutaneous findings of HLH in adults. A PubMed search of articles indexed for MEDLINE and subsequent reference searches yielded 60 articles that were included in the review. Cutaneous manifestations were categorized into 3 groups: direct manifestations of HLH (category I); secondary complications and dermatologic sequelae of HLH (category II); and manifestations of the underlying etiology of secondary HLH (category III). Limitations of this study included lack of clarity in diagnosis of HLH, inclusion of lower-quality evidence, and qualitative nature of review. Despite these limitations, awareness of which dermatologic conditions are associated with HLH may aid in diagnosis of this condition. The results of this study highlight the need for further understanding of the nonspecific eruptions attributed to HLH, the clinical and pathologic differentiation between drug rash with eosinophilia and systemic symptoms (DRESS) syndrome/drug-induced hypersensitivity syndrome (DIHS) and HLH, and the correlation between the severity of skin manifestations and disease severity in HLH.