Case Presentation: 41-year-old Hispanic man presented for reevaluation of the swellings on his forearms newly associated with Raynaud’s phenomenon on his fingers. He initially presented 5 years prior with swellings on his forearms and groin, red eyes, dry eyes and dry mouth all worsening over a 6-month period. On initial physical exam, he was found to have conjunctival hyperemia, xerophthalmia, bilateral pterygium, xerostomia, parotid enlargement, multiple 1-2cm nodular swellings on his forearms and inguinal lymphadenopathy. Suspected of having an autoimmune condition, he underwent extensive rheumatologic workup including total IgG with subclasses which were unremarkable. CT abdomen and pelvis revealed a large inguinal lymph node. Core biopsy was suspicious for lymphoma though inconclusive, but excisional biopsy was diagnostic of IgG4-RD. Treatment included prednisone 60mg oral daily with tapering over several months down to the current maintenance dose of 5mg. He had significant relief over time but with the current dose of prednisone, his symptoms now included Raynaud’s phenomenon. On reevaluation, physical exam revealed improvement in the previously seen abnormal ocular, oral, parotid, forearms and inguinal lymph node findings. To rule out retroperitoneal and aortic disease as sometimes seen in IgG4-RD, he underwent surveillance MRI-PET of the chest, abdomen and pelvis with unremarkable findings. Given initial appropriate response to steroid therapy, he was maintained on a higher dose prednisone taper with consideration for rituximab if adequate control not achieved later.

Discussion: IgG4-related disease (IgG4-RD) is a condition that consists of related disorders that share particular clinical, pathologic, and serologic features. These clinical histopathologic features include tumor-like growths in organs, lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells in tissues, variable degrees of fibrosis with characteristic “storiform” pattern, obliterative phlebitis and tissue eosinophilia. Serum IgG4 levels are elevated in 60-70% of affected patients and normal in the remaining 30-40% despite the presence of typical histopathological changes in tissues. Here we present a case of IgG4-RD in a patient with normal circulating IgG4 levels in the serum but high concentrations in the lymph node with elusive clinical significance.

Conclusions: The pathogenesis of IgG4-RD is poorly understood and elevations in the serum and tissue IgG4 concentrations are nonspecific and must be approached in the right clinical context. This case highlights the importance of excisional biopsy for a more definitive diagnosis in patients suspected of having IgG4-RD in whom core biopsy is undiagnostic or inconclusive. In cases of confirmed disease, it has been suggested that elevations in the serum IgG4 concentration appear to identify a subset of patients with a severe disease phenotype. In patients with the disease who have normal serum IgG4 levels as in the case presented here, the underlying determinants of this paradoxical discordance and their full spectrum of clinical implications are unclear and remain to be elucidated.