CCL22-producing macrophages are associated with Th1-related sweat duct inflammation in acquired idiopathic generalized anhidrosis

BackgroundAcquired idiopathic generalized anhidrosis (AIGA) is a rare disorder characterized by generalized loss of sweating without identifiable causes. Because few biomarkers reflect its underlying mechanisms, diagnosis at the initial visit is often difficult.

Although steroid pulse therapy is widely used, approximately half of patients respond insufficiently. We therefore aimed to elucidate the immune mechanisms underlying AIGA and identify potential biomarkers for diagnosis and treatment response.MethodsFourteen patients with AIGA affecting more than 25% of body surface area were enrolled after exclusion of secondary causes of anhidrosis.

Serum levels of 40 cytokines and chemokines were quantified using a multiplex assay and correlated with clinical parameters. Skin biopsy specimens were analyzed by histology and immunohistochemistry to characterize inflammatory cell infiltration and identify cellular sources of selected mediators.ResultsInflammatory cell infiltration was consistently observed around sweat ducts, predominantly composed of CD4+ T cells.

Serum profiling revealed significant elevations of CCL22 and IFN-γ in AIGA compared with healthy controls, with a strong positive correlation between them. Consistently, the downstream chemokine CXCL10 was also increased.