Sudden cardiac death revealing extensive cardiovascular IgG4-related disease: a forensic autopsy case report

Cardiovascular IgG4-related disease (IgG4-RD) is a rare and potentially lethal condition that may remain entirely clinically silent until sudden death occurs. We report a forensic autopsy case of extensive cardiovascular IgG4-RD involving the ascending aorta, pericardium, coronary arteries and the intrinsic cardiac nerve plexuses a finding, that, to the best of our knowledge, has not been previously reported in cardiovascular IgG4-RD. A complete forensic autopsy was performed, including comprehensive gross examination of the heart and great vessels. Histopathological evaluation and immunohistochemical staining (IgG4 and IgG) were undertaken. The diagnosis was established according to the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria. The autopsy demonstrated diffuse fibroinflammatory involvement of multiple cardiovascular structures, including the ascending aorta, the pericardium, coronary arteries, myocardium, and intrinsic cardiac nerve plexuses. Histological examination revealed dense lymphoplasmacytic infiltrates with storiform fibrosis and abundant IgG4-positive plasma cells at all affected sites, with a maximum count of 32 IgG4- positive cells plasma cells per high power field (HPF) and an IgG4/IgG ratio exceeding 40%. The cumulative ACR/EULAR score reached 31 points, confirming IgG4-RD. The coexistence of extensive myocardial fibrosis and inflammatory infiltration surrounding the intrinsic cardiac autonomic nerve plexuses raises the possibility of a previously unrecognized arrhythmogenic mechanism that may have contributed to the fatal event. This case expands the clinicopathological spectrum of cardiovascular IgG4-RD by documenting previously unreported involvement of the intrinsic cardiac nerve plexus. It underscores that IgG4-RD remains clinically silent despite extensive cardiovascular damage and may present solely as sudden cardiac death. A meticulous forensic autopsy, complemented by targeted histopathological and immunohistochemical investigations, is essential for establishing the diagnosis.