Beyond Sweet Syndrome: Untangling the Threads of Histiocytoid Sweet Syndrome and Cutaneous Myeloid Neoplasia

Histiocytoid Sweet syndrome (H-SS) is a variant of Sweet syndrome characterized by an infiltrate of immature, "histiocytoid," myeloid cells. Myelodysplastic syndrome involving the skin (MDS cutis) and Vacuoles, E1-enzyme, X chromosome, Autoinflammation, Somatic (VEXAS) syndrome may clinically and histopathologically resemble H-SS. However, there are important differences between these entities. Using next generation sequencing, genetic relationships between skin infiltrates resembling H-SS and bone marrow infiltrates of MDS have been established in MDS cutis. In addition, MDS cutis demonstrates myelodysplasia. A subset of cases previously included with H-SS represent VEXAS syndrome, a severe and often fatal autoinflammatory disorder. Distinguishing these entities from H-SS has important treatment and prognostic implications.