Immunoglobulin G4 (IgG4)-Related Disease With a Biphasic Clinical Course of Spontaneous Remission and Relapse: A Case Report of Diagnostic Reasoning

Immunoglobulin G4-related disease (IgG4-RD) can affect multiple organs, but reports of a biphasic clinical course characterized by metachronous multiorgan involvement, where distinct organ lesions emerge sequentially separated by a prolonged latent period, are uncommon. We report the case of a 46-year-old Japanese man. On Day 1, he developed autoimmune pancreatitis (AIP), which achieved clinical and radiological spontaneous remission without any immunosuppressive treatment. After an asymptomatic latent period of approximately 2.5 years (Month 32), he developed a metachronous relapse presenting as IgG4-related sclerosing cholangitis (IgG4-SC). Initial blood tests at our department during the relapse revealed a distinct enzyme dissociation: a markedly elevated gamma-glutamyl transferase (GGT) level (1,569 U/L) juxtaposed with a disproportionately lower alkaline phosphatase elevation (261 U/L). Based on characteristic magnetic resonance cholangiopancreatography findings, markedly elevated serum total IgG (2,155 mg/dL) and IgG4 (573 mg/dL), and a documented history of AIP (where initial endoscopic ultrasound-guided fine-needle aspiration had excluded pancreatic malignancy), a clinical diagnosis of IgG4-SC was established. Treatment with oral prednisolone (PSL; 40 mg/day) was initiated, resulting in rapid biochemical, morphological, and clinical improvement. During the steroid tapering phase, the patient developed trimethoprim-sulfamethoxazole-induced liver injury. This was accurately differentiated from disease relapse and successfully managed by promptly discontinuing the offending drug. The patient is currently maintaining clinical remission on a maintenance dose of PSL (5 mg/day). This case highlights an uncommon biphasic and metachronous course of IgG4-RD. It underscores the importance of precise diagnostic reasoning by integrating the patient's previous clinical history, recognizing enzyme dissociation patterns, and astutely differentiating drug-induced liver injury to prevent unnecessary steroid escalation during long-term management.