An Overlap of Two Pathologies: Anti-Synthetase and IgG4-Related Disease

Abstract

Introduction. Anti-Synthetase Syndromes and IgG4-related diseases have rarely been seen together. We present a 38-year-old female with connective tissue disease-associated interstitial lung disease from Anti-Synthetase syndrome who eventually develops autoimmune pancreatitis from IgG4-related disease. Case Presentation. A 38-year-old African American female with facial rash, joint swelling, and morning stiffness was seen to have pulmonary fibrosis on CXR and CT chest. Subsequent bronchoscopy was inconclusive. She was treated for presumed mixed Connected Tissue Disease (CTD) and associated pulmonary fibrosis with Mycophenolate, Hydroxychloroquine, and Prednisone. Several months later, she had shortness of breath and was diagnosed with COVID-19. Her mycophenolate was held while she recovered with supplemental oxygen, but has required 2 to 3 liters of supplemental oxygen chronically since her COVID diagnosis. A repeat bronchoscopy with transbronchial and cryobiopsies was suggestive of Cryptogenic Organizing Pneumonia (COP) and negative for malignancy. At that time, blood work revealed positive melanoma differentiation-associated (MDA) protein 5 antibodies, high antinuclear antibodies (ANA) titers, positive anti-Sjögren's-syndrome antigen A (SSA) autoantibodies, weakly positive PL-12, and negative Jo-1. Additionally, the patient had elevated concentrations of IgG4. A repeat CT revealed fatty infiltration of the pancreas. Her MDA positivity qualified the patient to begin Rituximab infusions weekly for four weeks. Her shortness of breath continued to improve on her previously stated treatments. However, she presented to a local emergency department for acute abdominal pain. She was diagnosed with acute pancreatitis and improved after receiving intravenous fluids. Discussion. This patient has connective tissue disease associated with interstitial lung disease from Anti-Synthetase syndrome. She has positive anti-MDA-5 antibodies and cryobiopsy diagnosed COP, a known finding in Anti-Synthetase syndrome. It is also possible that this patient has overlapping IgG4-related disease, correlated by elevated concentrations of IgG4 and autoimmune pancreatitis. This overlap is not well studied, considering that the pathophysiology of Anti-Synthetase syndrome involves autoimmunity towards aminoacyl-tRNA synthetase while IgG4-related disease pathophysiology is not well known and could involve abnormal activation of CD4-positive T cells. Interestingly, this patient had fatty infiltration of her pancreas found on imaging before she was symptomatic for autoimmune pancreatitis. It is possible that both disease processes were not only active simultaneously but also complicated the progression of one another. Clinicians should consider IgG4-related diseases in patients with Anti-Synthetase Syndrome as it might explain a patient's clinical picture and even change management.