S5562 Inflammatory Polyarthritis as the Initial Presentation of Hereditary Hemochromatosis With Compound Heterozygosity C282Y/H63D

Introduction: Hereditary hemochromatosis (HH) is an iron overload disorder caused by hemostatic iron regulator (HFE) gene mutations. In White European populations, over 90% of cases involve C282Y homozygosity, while 2-7% involve C282Y/H63D compound heterozygosity. We report a case of HH with compound heterozygosity presenting as inflammatory polyarthritis. Case Description/Methods: A 47-year-old White man with history of hypertension presented with 2 weeks of progressive inflammatory polyarthritis involving his left ankle, left wrist, left elbow, and bilateral knees, leading to immobility. He also had a history of recurrent bilateral knee pain requiring steroid injections. Joint x-rays showed diffuse chondrocalcinosis. Labs revealed liver injury (aspartate aminotransferase [AST] 69, alanine aminotransferase 156, total bilirubin 2.0, alkaline phosphatase 210, and international normalized ratio 1.4) without alcohol use. He underwent serologic work-up, arthrocentesis, imaging, and biopsy to evaluate the etiology. Serologic work-up revealed leukocytosis (14.4), elevated ESR (>130 mm/hr), CRP (30.71 mg/dL), and ferritin of 2561 with normal transferrin saturation (32%). Rheumatoid factor (13) and IgA (582) were mildly elevated; other infectious and autoimmune tests were negative. Arthrocentesis attempts yielded minimal fluid without bacteria or crystals. Medical records revealed elevated ferritin (745) and AST (43) 9 years prior. HFE mutation analysis at that time identified the patient as a compound heterozygote for C282Y and H63D mutations. Repeat mutation analysis confirmed prior results. Liver biopsy during admission showed diffuse 1+ to 2+ hepatocyte iron deposition concerning for HH. Calcium pyrophosphate deposition disease (CPPD) was concluded to be the cause of his inflammatory polyarthritis given presence of chondrocalcinosis on x-rays. Despite treatment with prednisone, colchicine, and anakinra, symptoms persisted until high-dose intravenous methylprednisone was added. His very resistant CPPD arthritis suggested an underlying precipitating factor, in this case HH. He was discharged on a prednisone taper and colchicine and initiated on phlebotomy treatments to lower ferritin below 100. Discussion: C282Y/H63D compound heterozygosity in HH has low penetrance with only 0.5-2% of patients exhibiting iron overload-related disease. We report a case where this genotype presented as severe, treatment-resistant CPPD. In patients with severe inflammatory polyarthritis and transaminitis, HH precipitating CPPD should be considered as early management can help prevent organ damage.