Case Presentation: An 81-year-old man with neurocognitive disorder, diabetes, hypertension, autoimmune sclerosing pancreatitis, and treated pulmonary tuberculosis presented with acute, painful right-sided neck swelling. On admission, he was afebrile and normotensive. Exam was notable for large, tender cervical mass without buccal lesions, and auscultation demonstrated decreased breath sounds over the right lung field. Labs revealed Hgb 10.9 g/dL, K 6 mmol/L (3.5- 5.2 mmol/L), Cr 2.35 mg/dL (0.7-1.3 mg/dL), CRP 44.5 mg/L (< 1 mg/L). Imaging revealed generalized adenopathy, soft-tissue infiltration in the neck, bilateral lung consolidation, right-sided nodularity, and a right pleural effusion. Pleural fluid analysis showed lymphocytes 56%, pleural protein 8.3 g/dL, LDH 185 U/L, and glucose 66 mg/dL. Blood and pleural fluid cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). A pleural catheter was placed on the right side, and a total of 2700 ml of bloody exudative fluid was drained. The patient was treated with antibiotics. Tuberculosis testing was negative, serum protein electrophoresis demonstrated polyclonal gammopathy, and serum IgG4 was elevated to 1029.1mg/dL (10-123 mg/dL). Fine-needle aspiration and bone marrow biopsy results were negative for malignant and infectious processes. Lymph node biopsy showed plasma cell infiltrates (CD138-positive), storiform fibrosis, with an IgG4/IgG ratio of approximately 0.6, confirming IgG4 related disease (IgG4-RD). The patient was started on high-dose prednisone and had improvement in neck swelling and lymphadenopathy. He was discharged on prednisone taper with outpatient follow-up.
Discussion: Acute generalized adenopathy in adults requires a comprehensive diagnostic approach, as infections, malignant, granulomatous disease-mediated, and immune-mediated conditions often overlap clinically and radiographically. This case presents the challenge of evaluating adenopathy in a patient with a severe bacterial infection and an underlying immune disorder. The patient had definitive evidence of disseminated MSSA infection, including bacteremia, lymphadenitis, and infected hemorrhagic pleural effusion, which could independently account for his cervical swelling and systemic inflammation. However, persistent adenopathy despite appropriate antibiotics, along with a history of autoimmune pancreatitis, polyclonal gammopathy, and elevated serum IgG4 levels, raised suspicion of concomitant IgG4-RD, an immune mediated fibroinflammtory condition which can affect multiple organs. Tissue sampling was required to confirm the diagnosis, with core biopsy demonstrating characteristic IgG4-rich plasma cell infiltrates and storiform fibrosis. The patient’s clinical improvement with prednisone further supported IgG4-RD as a contributor to his presentation.
Conclusions: This case highlights the diagnostic uncertainty arising from overlapping infectious and autoimmune phenomena, emphasizing the importance of reassessing the underlying etiology when lymphadenopathy fails to resolve with antimicrobial therapy. Prompt recognition of dual pathology is essential to avoid premature patient discharge, incomplete diagnostic work-up, and delay in immunomodulatory treatment. Clinicians should consider the possibility of coexisting etiologies, particularly when therapeutic responses diverge from anticipated response to clinical therapy.