Cutaneous Langerhans cell histiocytosis and other systemic inflammatory or autoimmune disease manifestations in the setting of clonal hematopoiesis

The clinical manifestations and pathophysiology of clonal hematopoiesis (CH)-associated immunological dysfunction are poorly understood. We describe an elderly woman with CH who developed various systemic inflammatory or autoimmune diseases (SIADs), including cutaneous Langerhans cell histiocytosis (LCH) and temporal arteritis. Sequencing of the LCH revealed somatic oncogenic mutations in MAP2K1, IDH2, and SRSF2, with enrichment of the latter two in her peripheral blood at high allele frequencies. These findings raise concern for the future development of a myeloid malignancy. Given the mounting evidence for adult-onset autoinflammatory conditions caused by somatic blood mutations, we suspect CH-mediated immune dysregulation is contributing to her multi-organ involvement by a combination of SIADs.