P57 IGG4-related disease causing sudden cardiac death

Abstract

Background: IgG4-related disease (IgG4-RD) is a chronic systemic inflammatory disorder presenting with mass lesions in various organs and showing plasma cell infiltration, storiform fibrosis and obliterative phlebitis on histology. IgG4-RD has previously been identified as a rare cause of sudden cardiac death (SCD) in case reports, but in settings where pathology has been unexpectedly found on post-mortem examination. To our knowledge, there are no published case reports of SCD in patients during treatment for IgG4-RD. Methods: A 43-year old chef with a 15 pack-year smoking history presented with portal vein thrombosis, widespread lymphadenopathy, proptosis and inflammatory lung changes. He was found to have IgG4- RD on submandibular lymph node biopsy with storiform fibrosis and abundance of IgG4-positive plasma cells. Test showed a high IgG and low complement levels and a persistent eosinophilia. He was anticoagulated with warfarin for the HPV thrombosis. Treatment with steroids (initially prednisolone 40mg/day) was initially successful and he continued at work and kept fit in the gym. There was also a good biochemical and radiological response to steroids, with normalisation of eosinophil count, IgG level, complements and CRP along with regression of imaging changes. After a period of 12 months steroid weaning (prednisolone 5mg) and having been well at OPD review, he was unexpectedly found dead at home. Post-mortem examination identified IgG4-RD coronary pan-arteritis as the cause of death. The finding of this unanticipated severe complication raises new questions about surveillance and prevention. Results: Coronary involvement in IgG4-RD is thought to be rare but may reflect difficulty obtaining coronary artery tissue and clinically silent disease remaining undiagnosed. A systematic review of IgG4-RD outcomes (7 studies comprising 294 patients, follow-up mean of 29 months) identified 26 deaths (8.8%). One was from an aneurysm and four from other cardiovascular disease, while most deaths were from disease progression or cancer. Case reports describe IgG4-RD coronary artery disease pathologies, including inflammatory pseudotumour, periarterial thickening, coronary artery aneurysm and coronary artery stenosis. Conclusion: This case raises important questions about identifying and monitoring for asymptomatic cardiovascular involvement in IgG4- RD. Steroid treatment may be less effective for coronary involvement, and in theory, could precipitate rupture or dilatation of the arteries. Recent IgG4-RD management guidelines have not addressed surveillance for cardiovascular disease. ECG and echocardiography are reasonable initial surveillance options, but we suggest clinicians have a low threshold for CT coronary angiography and/or cardiac MR. Invasive coronary angiography and CT-PET can then be used to provide additional information if required. We noted a normal CRP despite active coronary inflammation in our patient and therefore look forward to improved biomarkers for disease activity in IgG4-RD.