IgG4 related disease: a novel association with hypertrophic osteoarthropathy

Abstract

IgG4 related disease (IgG4-RD) is a recently recognized disease that has several associated clinical phenotypes including autoimmune pancreatitis, sclerosing cholangitis, major salivary gland enlargement (Mikulicz disease), orbital pseudotumor, retroperitoneal fibrosis, and inflammatory vascular disease manifesting as aortitis or coronary artery calcification. Histopathology of affected organs shows lymphoplasmacytic infiltrations with a predominance of IgG4-positive plasma cells in the affected tissue and an increased number of eosinophils. Serum IgG4 levels are elevated in two-thirds of patients, and IgE is also often elevated. We report here the first known associated case of presumed IgG4-RD with hypertrophic osteoarthropathy. Hypertrophic osteoarthropathy (HOA) is frequently a paraneoplastic disease of bone, but HOA can be associated with chronic infection, chronic pulmonary disease, cardiac shunts, and cirrhosis. HOA is a clinical diagnosis consisting of arthralgia, digital clubbing, and periostosis of tubular bones seen on imaging with or without synovial effusion. Our 35 yo male LatinX patient presented with typical clinical symptoms of HOA that were confirmed on imaging. During the negative work up for malignancy, disproportionate-for-age coronary artery calcification was identified, which prompted an evaluation for IgG4-RD. The patient also had lung disease (peribronchial thickening), atopic dermatitis, subtle clubbing, elevated IgE, elevated IgG4 (9× normal), and eosinophilia. The patient's symptoms and inflammatory markers improved on prednisone and methotrexate, but a decision to treat with rituximab was made after having to discontinue methotrexate for transaminitis. Rituximab has been used in patients with IgG4-RD with some success, and our patient continues to improve in his skin, respiratory, and bone symptoms with reduction in IgG4, inflammatory markers, and bone turnover markers (alkaline phosphatase).