Immunoglobulin G4-related masses surrounding coronary arteries: a case report

Background Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with high serum IgG4 levels affecting various organs, such as the pancreas, lacrimal and salivary glands, thyroid, kidney, and lung. Typical cardiovascular manifestations of IgG4-RD include periaortitis, coronary arteritis, and pericarditis. However, reports of IgG4-RD associated with coronary arteritis are rare. Here, we report a case of IgG4-related masses surrounding the coronary arteries. Case summary A 59-year-old man was referred to our hospital because of mediastinal masses detected by computed tomography (CT). Coronary CT angiography revealed masses surrounding the right coronary artery and the left anterior descending coronary artery. An elevated serum level of IgG4 and histological findings led to the diagnosis of IgG4-related coronary arteritis with mass formation. Coronary angiography showed numerous feeding arteries to the masses, which were demonstrated as multiple microchannels in the intravascular ultrasound (IVUS) images. Discussion IgG4-RD involving the cardiovascular system has been reported. However, coronary artery disease associated with IgG4-RD is very rare, and the mechanism of mass formation in IgG4-related coronary arteritis is unclear. In our case, within the cardiovascular system, IgG4-RD was limited to the coronary arteries, suggesting that the affected coronary arteries may provide the necessary blood supply to the mass, thus, aiding its growth. These findings were supported by the images from coronary angiography and IVUS.

Early anti IL-1 treatment replaces steroids in refractory Kawasaki disease: clinical experience from two case reports

Refractory Kawasaki disease (KD) is related to a major risk of coronary arteries abnormalities and its treatment is not standardized. In this regard, anakinra (ANA), an interleukin (IL)-1 receptor antagonist, represents an emerging therapeutic option. We report two cases of children, diagnosed with KD, nonresponsive to two doses of intravenous immunoglobulins, successfully treated with ANA, without a prior use of steroids. Patient 2 developed a coronary dilatation, that improved significantly after ANA therapy. Our experience highlights IL-1 blockade effectiveness in reducing KD inflammation and suggests ANA adoption as second-line therapy, with a timesaving and steroid-sparing strategy. Our results, combined with the evidence of the IL-1 key role in KD and coronary arteritis pathogenesis and to the recent clinical evidence reported by the KAWAKINRA trial, encourage an earlier recourse to ANA in patients with refractory KD, in order to fight inflammation, and to treat and prevent the development of coronary artery aneurysms. Further studies are needed to better define the place of IL-1 blockade in KD step-up treatment.

Abstract 13069: NLRP3 Inflammasome Promotes Vasculitis of Kawasaki Disease

Introduction: Kawasaki disease (KD) is a systemic febrile syndrome which causes coronary arteritis. Candida albicans water-soluble fraction (CAWS) is a mannoprotein-β-glucan complex obtained from the culture supernatant of Candida albicans , and frequently used as a murine KD model, because administration ofCAWS induces coronary arteritis. NLRP3 inflammasome is a large multiprotein complex (NLRP3, ASC and caspase-1), and regulates the release of the potent inflammatory cytokine IL-1β. We hypothesized that NLRP3 inflammasome-mediated IL-1β had a pivotal role in the pathogenesis of CAWS-induced vasculitis. Methods and Results: In vivo : The protein level of IL-1β in the hearts was increased by CAWS administration. Activation of caspase-1 was detected around the coronary arteries by FLICA assay. Histological study showed that incidence and severity of CAWS-induced vasculitis, macrophage infiltration, and fibrosis were suppressed in NLRP3-, ASC- and IL-1β-deficient mice (Fig. A). In vitro : Bone marrow-derived dendritic cells (BMDCs) produced IL-1β by CAWS stimulation, which was suppressed by the anti-Dectin-2 antibody or caspase-1 inhibitor. The CAWS-induced IL-1β production was also suppressed in NLRP3-, ASC-, and caspase-1-deficient BMDCs (Fig. B). CAWS induced mitochondrial reactive oxygen species (mtROS) production, and Mito-TEMPO, a mtROS inhibitor, suppressed CAWS-induced caspase-1 activation (Fig. C) and IL-β production. In addition, CAWS-induced mtROS production was suppressed by Syk or JNK inhibitor. Furthermore, Syk or JNK inhibitor suppressed CAWS-induced NF-κB activation and subsequent IL-1β production. Conclusion: These findings demonstrated that NLRP3 inflammasome activation through Dectin-2/Syk/JNK-mediated mtROS plays a pivotal role in CAWS-induced vasculitis. CAWS also induced priming signal through Dectin-2/Syk/JNK/NF-κB pathway. Our finding indicates NLRP3 inflammasome as a new therapeutic target of KD.

Abstract 13574: A Rare Case of Giant Cell Arteritis With Coronary Artery Involvement

Introduction: Coronary artery involvement in patients with systemic vasculitis is relatively rare, but can be life threatening. There is a well-known occurrence of coronary artery vasculitis in Kawasaki disease and Takayasu arteritis, however, coronary arteritis caused by giant cell arteritis (GCA) has been documented in only a handful of reports. Case report: A 65-year-old woman with a history of GCA complicated by cerebrovascular stenosis s/p bypass and coronary artery disease (CAD) s/p DES to mid-left anterior descending (LAD) 3 years prior, without cardiac risk factors, who presented with shortness of breath and 2-3 hours of progressive non-radiating pressure like midsternal chest pain. Vital signs were stable with an unremarkable physical exam. EKG showed new T-wave inversions in V4-V6, I, II, aVL. Labs were significant for Trop T 0.17 and CRP 2.02. Echocardiogram showed EF 30% with wall motion abnormalities (ECHO 9 months prior showed EF 69% with no wall motion abnormalities). Coronary angiography revealed 99% in-stent-restenosis (ISR) of mid-LAD, 50% tubular OM1 stenosis, and 100% RCA occlusion with right-to-right collateral (figure 2). The patient underwent CABG with a left internal mammary artery graft to LAD and saphenous vein graft to RCA. Post-operative EF was 50%, and she was discharged on post-operative day 5. Discussion: In patients with systemic vasculitis and no identifiable CAD risk factors presenting with acute coronary syndrome, there has to be a high suspicion for coronary arteritis. Our case strongly suggests that GCA can involve the coronary arteries given the rapid progression of ISR with triple vessel disease in the absence of cardiac risk factors. Although advancements in imaging techniques have led to improvements in the diagnosis of systemic vasculitis, standardized imaging for evaluating coronary vasculature is lacking. Larger retrospective case studies are needed in order to clearly delineate the association between GCA and CAD.