Concurrent IgG4-Related Disease and Giant Cell Arteritis: A Rare Case Study Katrina R. Gener, DO, Ekaterina Simakova, MD Wellington Regional Medical Center, Wellington, FL; Family Arthritis Center, Jupiter, FL

Summary: Background: IgG4 related disease is a rare systemic, immune-mediated disorder that can affect many organ systems including pancreas, kidneys, lungs, and vasculature. Although rare, it can present alongside various vasculitides and giant cell arteritis, as seen in this particular case. Case: A 65-year-old male presents with recurrent episodes of visual impairment including instances of loss of vision. 13 years prior, he presented with symptoms concerning for giant cell arteritis (GCA) and an erythrocyte sedimentation rate (ESR) elevation up to 130 mm/hour. He underwent bilateral temporal artery biopsy which showed superficial and focal mild temporal arteritis. Patient developed retinal hemorrhage of the right eye and central retinal artery occlusion of the left eye. He was treated with intravenous corticosteroids and transitioned to oral prednisone with plans to establish care with a rheumatologist. Later on, he developed chronic dyspnea and pleural effusions were seen on chest radiography. Thoracentesis with fluid analysis was consistent with inflammatory changes. Contrast-enhanced CT imaging of the chest revealed multifocal mildly enlarged lymph nodes of indeterminate etiology. A biopsy of an enlarged lymph node demonstrated reactive fibrosis, chronic inflammation with a central residual reactive lymph node, and positive IgG4 testing. Furthermore, pathology indicated focal fibrosis within the salivary gland and reactive lymphoid hyperplasia nodes characterized by CD138 positive and IgG4 positive plasma cells. CT imaging of the abdomen demonstrated an infiltrative and inflammatory process involving stranding throughout the retroperitoneum, ascending colon and duodenum. CT biopsy retroperitoneum showed chronically inflamed fibrous connective tissue with rare small non-caseating granulomas and significant background staining for IgG. Laboratory evaluation revealed elevated levels of IgG, with a result of 145 mg/dL (normal: 25-113 mg/dL). Patient was diagnosed with IgG4 related disease and giant cell arteritis. His renal function deteriorated, seen by a rise in creatinine levels ranging between 1.5-1.8 and an estimated glomerular filtration rate (eGFR) of 38. Microhematuria was noted on urinalysis, and a renal needle core biopsy showed acute interstitial nephritis with exceedingly rare IgG4+ plasma cells. Patient was initiated on rituximab therapy and tapered steroid regimens. Although his IgG4 related disease was effectively managed, recurrent episodes of giant cell arteritis persisted. The patient was transitioned to tocilizumab because of recurring GCA flares, but developed worsening symptoms including a rash on his lower extremities resembling a leukocytoclastic vasculitis, and was restarted on rituximab. Biopsy reported perivascular lymphocytic infiltration with hemosiderin deposition. Today, his rash has resolved, he continues on rituximab therapy and 5 mg of prednisone daily with normalization of his inflammatory markers and minimal symptomatology. Discussion: This is a unique presentation of the rare manifestations of IgG4 disease alongside giant cell arteritis. Due to proven giant cells and IgG4 positive plasma cells seen on the pathology from the temporal artery and kidney biopsy, eliminating other forms of vasculitis. Additionally, negative ANCA levels were confirmed. Given the patient's history of recurrent giant cell arteritis and worsening vision loss, treatment with high-dose steroids was crucial. Despite the efficacy of tocilizumab in preventing GCA flare-ups, the emergence of a vasculitic rash prompted a therapeutic switch to rituximab. Conclusion: While infrequent, it is important to acknowledge that IgG4 related disease can have many diverse manifestations. Furthermore, the concurrent occurrence of vasculitides alongside IgG4-related diseases is exceptionally rare. Medications that have been shown to be efficacious in IgG4 related disease and vasculitis include steroids and rituximab. Surgical interventions may be used to remove any obstructions caused by manifestations of the disease.