特発性後天性全身性無汗症

Acquired Idiopathic Generalized Anhidrosis (AIGA) is a rare but potentially debilitating condition characterized by sudden loss of sweating without an identifiable neurologic or structural cause. A previously healthy 31‑year‑old active duty male presented with an acute onset generalized anhidrosis that rapidly progressed to near complete body involvement, severely limiting his ability to perform in a heat‑intensive operational environment. Punch biopsies from the left arm and lower back demonstrated superficial and deep periadnexal lymphocytic infiltrates. Immunostaining with Tryptase, CD117, and CD3 highlighted periadnexal mast cells and lymphocytes, supporting the diagnosis of AIGA. Given the broad differential for anhidrosis-including sympathetic pathway dysfunction at multiple levels-skin biopsy can be an important diagnostic tool. AIGA predominantly affects young, active males and significantly impairs heat tolerance, posing particular risk to athletes and military personnel who rely on intact thermoregulation. Prior reports describe favorable responses to systemic corticosteroids, especially when initiated early. Our patient was treated with systemic steroids and experienced rapid restoration of sweating and full return to duty within weeks. This case underscores the importance of recognizing AIGA as a rare yet highly treatable condition and highlights the value of timely clinicopathologic correlation to restore function in operationally essential personnel.

BACKGROUND: Acquired 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. METHODS: Fourteen 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. RESULTS: Inflammatory 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. Double immunostaining identified CD68+ macrophages as the main source of CCL22 in periductal regions. Serum Macrophage migration inhibitory factor (MIF) levels were significantly higher in steroid-resistant cases, whereas MIF expression within sweat ducts was markedly reduced, suggesting disruption of local immune privilege. CONCLUSIONS: These findings suggest that AIGA involves a macrophage-CCL22-Th1-IFN-γ inflammatory axis associated with collapse of sweat duct immune privilege. Serum MIF may serve as a potential biomarker for predicting steroid responsiveness.

Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder of sweating that can be life-threatening owing to the risk of heat stroke. AIGA as an immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs) has been reported in only three cases. We report a 69-year-old man with unresectable lung adenocarcinoma (cT1N2M1b, Stage 4A) with hepatic metastasis who developed generalized anhidrosis after approximately 2 years (30 cycles) of pembrolizumab monotherapy. EGFR, ALK, and ROS1 were negative, and programmed death-ligand 1 (PD-L1) tumor proportion score (TPS; 22C3 antibody) was 90%-100%. Sweat testing revealed anhidrosis exceeding 75% of the body surface. Acetylcholine injection testing indicated idiopathic pure sudomotor failure (IPSF)-type dysfunction. Skin biopsy revealed site-dependent findings: peri-eccrine lymphocytic infiltration involving the sweat glands and ducts in the sweating area (axilla) and prominent peri-eccrine fibrosis in the anhidrotic area (left forearm). Serum carcinoembryonic antigen (CEA) was elevated to 16.7 ng/mL without tumor progression, prompting diagnostic workup including colonoscopy, which revealed no abnormalities. The patient was treated with three courses of methylprednisolone pulse therapy (1000 mg/day × 3 days) over 7 months and fexofenadine, resulting in partial sweating recovery and CEA decline to 3.0 ng/mL. Pembrolizumab was continued throughout without interruption, and the patient maintained durable stable disease (SD) over approximately 45 months (alive at last follow-up). This case demonstrates the histopathological spectrum of ICI-induced AIGA from inflammation to fibrosis within a single patient, and highlights CEA elevation as both a diagnostic clue and a potential pitfall in oncological practice.

Patients with acquired idiopathic generalized anhidrosis (AIGA) present with reduced sweating and impaired thermoregulation, which causes body temperature to increase quickly during exercise or in a hot environment. A 14-year-old girl was admitted with a variety of symptoms and prolonged fever of unknown origin. AIGA was diagnosed because of a discrepancy between deep body temperature (tympanic membrane) and body surface temperature (axillary), and she was treated. Careful history taking and physical examination are essential for patients with fever of unknown origin.

Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder characterized by systemic anhidrosis or hypohidrosis of unknown etiology. Although autoimmune responses targeting eccrine glands and/or ducts have been proposed as a potential mechanism, the pathophysiology remains largely unclear. Corticosteroid pulse therapy is widely used for treatment, yet its mechanism of action is not fully understood. To elucidate the underlying mechanisms, we analyzed skin lesions from patients with AIGA before and after corticosteroid pulse therapy through histological and single-cell RNA-sequencing analyses. AIGA cases were histologically classified into pauci-inflammatory, mild inflammatory, and severe inflammatory types on the basis of lymphocytic infiltration around the eccrine unit. Corticosteroid pulse therapy improved sweating function across all groups, including pauci-inflammatory cases with little immune infiltration. Single-cell RNA sequencing of pauci-inflammatory AIGA skin revealed significant upregulation of eccrine marker genes such as MUCL1 and DCD alongside downregulation of cellular stress response pathways associated with unfolded protein responses after therapy. Immunohistochemistry confirmed increased expression of eccrine markers and reduced cellular stress markers, including advanced glycation end products and 4-hydroxynonenal, in eccrine glands after treatment. These findings suggest that unfolded protein response-associated cellular stress-mediated eccrine dysfunction contributes to AIGA pathogenesis, providing a basis for exploring cellular stress modulation as a potential therapeutic approach.