What are the features and management of coronary vasculitis?

Coronary Vasculitis: Features and Management

Clinical Features

Coronary vasculitis presents as a life-threatening inflammatory disease of coronary arteries that predominantly affects younger patients with more rapid disease progression than atherosclerotic disease, manifesting as pericarditis, myocarditis, coronary stenosis, aneurysms, spontaneous dissection, or vascular thrombosis. 1

Disease Entities Associated with Coronary Involvement

• Kawasaki disease is the most common medium-vessel vasculitis affecting coronary arteries, with coronary aneurysms developing in 15-20% of untreated patients 2
• Peak mortality occurs 15-45 days after fever onset when established coronary vasculitis coincides with marked platelet elevation and hypercoagulable state 2
• Takayasu arteritis commonly involves coronary arteries and can result in aortic incompetence, myocarditis, or coronary heart disease 3
• ANCA-associated vasculitis (particularly eosinophilic granulomatosis with polyangiitis) most commonly involves the heart among AAV subtypes, though coronary involvement remains rare 4, 3
• Polyarteritis nodosa affects medium-sized arteries including coronary vessels 2
• Giant cell arteritis can involve coronary arteries as part of large-vessel disease 2

Pathological Characteristics

• Endothelial cell activation with CD68 monocyte/macrophages, CD8 cytotoxic lymphocytes, and oligoclonal IgA plasma cells characterize the inflammatory infiltrate 2
• Early stages (7-9 days) show neutrophil influx transitioning to mononuclear cells with lymphocytes and IgA plasma cells 2
• Destruction of internal elastic lamina occurs with eventual fibroblastic proliferation and matrix metalloproteinase activity 2
• Isolated coronary arteritis predominantly affects the ostium and proximal coronary segments, causing stenotic lesions with rapid restenosis if untreated 5

Diagnostic Features

• Intravascular ultrasound demonstrates superiority in differentiating coronary vasculitis from atherosclerosis 5
• C-reactive protein and erythrocyte sedimentation rate may be grossly normal in isolated coronary arteritis, significantly lower than in systemic vasculitis 5
• Coronary angiography may show normal arteries or minimal stenosis despite clinical presentation, as provocative testing with intracoronary ergonovine can demonstrate coronary vasospasm 4
• Elevated cardiac troponins indicate myocardial injury, though sensitivity varies (troponin I elevated in only 34% of acute myocarditis cases) 2
• ECG findings include ST-segment changes, conduction abnormalities (first- to third-degree AV block, bundle branch block), arrhythmias, or low voltage 2

Management Algorithm

Severity Stratification

Disease severity must be categorized to guide treatment intensity, with organ-threatening or life-threatening manifestations requiring immediate aggressive immunosuppression. 2

• Severe/organ-threatening disease: Coronary stenosis, aneurysms, acute coronary syndrome, myocardial infarction, or heart failure
• Non-severe disease: Isolated pericarditis or mild myocarditis without hemodynamic compromise

Treatment for Severe Coronary Vasculitis

For organ-threatening or life-threatening coronary vasculitis, immediate treatment with high-dose glucocorticoids (prednisone 1 mg/kg/day, maximum 60 mg/day) combined with either cyclophosphamide OR rituximab is recommended. 2, 6

Remission Induction

• Cyclophosphamide: Oral 2 mg/kg/day (maximum 200 mg/day) or intravenous pulse therapy combined with glucocorticoids 2
• Pulsed cyclophosphamide achieves higher remission rates with lower toxicity than continuous oral therapy, though relapse risk may be higher 2
• Rituximab: 375 mg/m² weekly for 4 weeks achieves 91% remission rate in refractory ANCA-associated vasculitis 6
• Maintain high-dose glucocorticoids for minimum 1 month before gradual taper 6

Mandatory Prophylaxis

• Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole (800/160 mg alternate days or 400/80 mg daily) is required for all patients receiving cyclophosphamide 2, 6
• Mesna (2-mercaptoethanesulfonate sodium) should be given with pulse cyclophosphamide to bind toxic acrolein metabolites 2
• Bone protection with calcium, vitamin D, and bisphosphonates for all patients on glucocorticoids 6

Maintenance Therapy

After achieving remission, maintenance therapy with azathioprine (1-2 mg/kg/day), methotrexate, or rituximab should continue for at least 18 months. 2, 6

• Azathioprine 1-2 mg/kg/day is standard maintenance therapy 6
• Methotrexate or rituximab are alternatives for maintenance 2
• Structured clinical assessment rather than ANCA or B-cell testing alone should guide treatment decisions 2

Kawasaki Disease-Specific Management

Intravenous immunoglobulin (IVIG) 2 g/kg as single infusion within 10 days of fever onset combined with aspirin is the standard treatment for Kawasaki disease to prevent coronary aneurysms. 2

• Diagnosis requires fever ≥5 days plus 4 of 5 principal clinical criteria, or coronary artery disease detected by echocardiography with fever and ≥4 criteria 2
• Serial echocardiography is mandatory to detect coronary artery abnormalities 2

Refractory Disease Options

• Intravenous immunoglobulin 2 g/kg over 5 days for persistent low activity 6
• Mycophenolate mofetil 2 g/day for refractory cases 6
• Rituximab for cyclophosphamide-refractory disease 2, 6
• Plasma exchange should be considered for rapidly progressive disease 2

Monitoring Requirements

• Periodic urinalysis for all patients treated with cyclophosphamide to detect bladder cancer risk 2
• Serum immunoglobulin concentrations before each rituximab course to detect secondary immunodeficiency 2
• Blood glucose monitoring during glucocorticoid therapy 2
• Complete blood count monitoring for leucopenia requiring dose adjustment 2
• Cardiovascular risk factor screening and management given threefold increased cardiovascular event risk 3

Critical Management Principles

All patients with coronary vasculitis should be managed at or in close collaboration with centers of expertise, as these are rare, heterogeneous, and potentially life-threatening diseases requiring multidisciplinary care. 2

• Biopsy confirmation is strongly supportive when feasible, though invasive coronary biopsy carries bleeding risk 2
• Restenosis occurs rapidly in isolated coronary arteritis if not treated promptly with systemic glucocorticoids combined with immunosuppressive agents, especially cyclophosphamide 5
• Long-term follow-up with rapid access to specialist services is necessary as relapse may occur years after remission 2