A Diagnostic Dilemma: IgG4-Related Kidney Disease in a Patient with Ulcerative Colitis

Introduction: IgG4-related disease is a rare systemic disorder characterized by the formation of fibro-inflammatory, tumor-like masses in almost any organ. Plasma cell rich tubulointerstitial nephritis is the most common renal manifestation. Ulcerative colitis is generally considered an exclusion criteria in the diagnosis of IgG4-RD. Case Description: A 63-year-old male with ulcerative colitis on vedolizumab was referred by his PCP for further evaluation of AKI (Cr of 1.8 mg/dL from 1.1 mg/dL at baseline), bilateral lower extremity edema, and newly elevated SBP to 160s. One year prior, he developed non-granulomatous dacryoadenitis with focal fibrosis (treated with methotrexate) and a pre-sacral mass of unclear etiology, both of which raised suspicion for IgG4-related disease but biopsy findings were inconclusive. Initial evaluation of kidney involvement revealed UACR 2517mg/g, low serum C3 (5 mg/dL), low serum C4 (6 mg/dL), elevated IgG4 (184 mg/dL), with negative ANA, anti-ds DNA, anti-PLA2R and cryoglobulins. Renal biopsy showed marked endocapillary hypercellularity characterized by mesangial and subendothelial deposits (C3 and IgG on immunofluorescence) with scattered subepithelial deposits. There was also an acute tubulointerstitial nephritis with a lymphoplasmacytic infiltrate, mild fibrosis, and prominent tubular basement membrane deposits (IgG and C1q). IgG4 preparations showed scattered single cells and clusters with a cell count of 17/hpf. He subsequently received 2 doses of rituximab with a concurrent steroid taper. His kidney function has since improved, with UACR 35 mg/g and Cr 1.5 mg/dL. Discussion: The confluence of findings in this case do not provide a clear diagnosis given prior inconclusive biopsies, but IgG4-related disease is the most compelling synthesis of lymphoplasmacytic tubulointerstitial nephritis with fibrosis and increased IgG4+ plasma cells alongside glomerular involvement and two separate extra-renal mass lesions (pre-sacral and dacryoadenitis). Although ulcerative colitis is associated with elevated IgG4 levels and is considered an exclusion criteria for the diagnosis of IgG4-RD, both diseases can co-exist and no other diagnosis fully explains the clinical picture.