Triple immune impairment in an elderly patient with IgG4-AIP and MGUS complicated by dual severe infections over 3 years: A case report

RATIONALE: Reports of IgG4-related autoimmune pancreatitis (IgG4-AIP) combined with monoclonal gammopathy of undetermined significance (MGUS) are mostly limited to short-term follow-up and single infectious complications. To date, no published literature has described octogenarian patients with this overlap complicated by 2 severe concurrent opportunistic infections together with 3-year serial immune-biomarker monitoring. Long-term follow-up data regarding multiple opportunistic infections under continuous immunosuppressive therapy remain scarce for this rare clinical entity. PATIENT CONCERNS: An 82-year-old male patient was diagnosed with IgG4-AIP superimposed by IgGλ-type MGUS. Markedly elevated serum IgG4 (3278.00 μg/mL) and a monoclonal paraprotein level of 2.34 g/L were noted at baseline. Initial combined glucocorticoid-based immunosuppressive therapy partially improved pancreatic lesions. Subsequently, he developed concurrent Staphylococcus hominis bacteremia and active pulmonary tuberculosis. DIAGNOSES: Three-tier superimposed immune impairment, consisting of chronic IgG4-related inflammation, MGUS-associated clonal plasma-cell dysregulation, and drug-induced lymphopenia, was considered the key driver for the dual life-threatening opportunistic infections. INTERVENTIONS: Standardized antibacterial and antituberculosis therapeutic regimens were administered to treat the dual infections. Immunosuppressive strategies were adjusted for this high-risk geriatric patient. OUTCOMES: Complete resolution of infectious lesions was achieved. Over the 36-month longitudinal surveillance period, serum paraprotein remained stable without progression to multiple myeloma, while serum IgG4 concentrations fluctuated independently of MGUS activity. Serial immune profiling confirmed persistent cellular immunodeficiency in this elderly MGUS carrier. This constitutes the first reported octogenarian patient with overlapping IgG4‑AIP and IgGλ‑MGUS suffering from dual severe opportunistic infections following immunosuppressive therapy. LESSONS: Persistent cellular immunodeficiency substantially elevates the risk of life-threatening opportunistic infections in elderly patients with concomitant IgG4-AIP and MGUS. Cyclophosphamide should be used with extreme caution in this vulnerable geriatric subgroup. Pathogenetic mechanisms, infectious risk factors, and preventive considerations for this rare overlapping immune disorder deserve clinical attention.