Acquired Idiopathic Generalized Anhidrosis as a Late‐Onset Immune‐Related Adverse Event of Pembrolizumab in a Patient With Lung Adenocarcinoma: A Case Report and Review of the Literature

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.