Coronary vasospasm in eosinophilic granulomatosis with polyangiitis

Rheumatology key message

• Eosinophilic granulomatosis with polyangiitis should be considered with recurrent vasospastic angina.

DEAR EDITOR, Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare small and medium vessel vasculitis with an incidence of around 0.9 per million population (95% CI: 0.2, 1.7) [1]. Many physicians may never see a new case of EGPA. Presenting features are variable and can occur in distinct episodes over many months or years. Diagnosis is therefore difficult, and EGPA may not always be considered.

We present the case of a 60-year-old man who attended our tertiary care centre on multiple occasions with chest pain. The initial 12-lead electrocardiogram demonstrated subtle anterior ST-segment elevation and high-sensitivity cardiac troponin I concentration was elevated at 120 ng/l. He underwent invasive coronary angiography and implantation of a drug eluting stent to a focal stenosis in the proximal left anterior descending artery. During the procedure he developed increasing chest pain and inferior ST-segment elevation associated with focal vasospasm in the right coronary artery. Intra-coronary nitro-glycerine was administered and a diagnosis of Prinzmetal’s angina was made. He was treated with dual anti-platelet therapy, oral nitrates and a calcium-channel blocker.

Symptoms recurred two weeks later, and he was diagnosed with a non-ST-segment elevation myocardial infarction. Repeat coronary angiography demonstrated a patent stent and a focal lesion in the posterior left ventricular branch of the right coronary artery. Intravascular optical frequency domain imaging demonstrated circumferential intimal thickening with focal coronary spasm, but no evidence of plaque rupture or dissection. Again, intra-coronary nitro-glycerine relieved his symptoms. Oral nicorandil was added to regular medical therapy; however, he continued to have daily nocturnal angina at rest. He developed postural dizziness and syncope due to maximal vasodilator therapy.

Four months later he represented with an inferior ST-segment elevation myocardial infarction complicated by transient complete heart block. Imaging demonstrated diffuse coronary vasospasm throughout the length of the right coronary artery involving both the posterior left ventricular branch and the posterior descending artery (Fig. 1A and B, Supplementary video S1, available at Rheumatology online). These angiographic appearances, along with symptoms and ST-segment elevation were relieved by intra-coronary nitro-glycerine (Fig. 1C, Supplementary video S2, available at Rheumatology online). Cardiac magnetic resonance imaging confirmed an inferior subendocardial myocardial infarction (Fig. 1D).

Fig. 1.

Patient imaging and histology

(A) Intravascular optical frequency domain imaging of the right coronary artery demonstrating circumferential thickening of the intimal layer and spasm. (B) Diffuse multi-focal coronary vasospasm (arrows). (C) Resolution of vasospasm following intra-coronary nitro-glycerine. (D) Cardiac magnetic resonance imaging demonstrating inferior subendocardial myocardial infarction (arrow). (E) Histology of nasal polyp excised showing eosinophilic infiltrates (arrow).

Over these same few months, he developed paraesthesia and clumsiness of both hands extending to the elbows in a glove distribution. A macular rash had developed over his shins, diagnosed as eczema. It was noted that for the preceding three years he had a persistent mild eosinophilia (10–20% total leucocytes) and had been diagnosed with adult-onset asthma four years earlier. He was troubled with recurrent sinusitis/rhinitis and had been seen several times by the otolaryngology department. An excised nasal polyp demonstrated widespread eosinophilic infiltrates (Fig. 1E).

At this point, a diagnosis of EGPA was considered. Investigations revealed eosinophilia (1.45 × 10⁹/l), normal renal and liver function, normal inflammatory markers (CRP <1mg/dl, ESR 13 mm/h), negative ANCA and normal serum angiotensin converting enzyme (ACE) level. A high-resolution CT chest and CT coronary angiogram identified hilar lymphadenopathy and small mediastinal nodes. An area of infiltration was seen in the left-lower lobe, thought to be secondary to infection or capillaritis and haemorrhage. The right coronary artery appeared normal with a coronary calcium score of 11Ag.

A diagnosis of EGPA was made based on the ACR criteria with the presence of asthma, eosinophilia >10% total leucocytes, polyneuropathy and paranasal sinusitis [2]. A trial of immunosuppression with prednisolone resulted in immediate resolution of angina and eosinophilia. His previously daily nocturnal anginal symptoms have not recurred 5 years later on mycophenolate mofetil as a steroid-sparing agent.

When considering a diagnosis of EGPA, ANCA is positive in only around 40% of cases [3]. The phenotype of EGPA is recognized to vary depending on ANCA status: ANCA-negative patients are more likely to have cardiac and lung involvement due to eosinophilia; ANCA-positive patients are more likely to have typical features of small vessel vasculitis (glomerulonephritis, purpura, mononeuritis) [4]. Cardiac features of disease include myopericarditis, coronary angiitis and congestive cardiac failure. Overall, cardiac involvement in EGPA is a poor prognostic feature. Vasospastic angina is rarely reported, with only a few cases in the literature [5–8]. Vasospastic angina results in myocardial ischaemia through sudden, often unprovoked, occlusive vasospasm of the coronary vessels. This can be life-threatening, with previous reports of ventricular fibrillation-induced cardiac arrest and cardiogenic shock requiring an intra-aortic balloon pump [6, 7]. Vessel wall inflammation and endothelial dysfunction is thought to be implicated. Coronary angiitis may result from eosinophil-stimulated release of local vasoactive substances including histamine, prostaglandin D2 and leukotrienes C4 and D4 [5].

This case highlights that this unusual diagnosis should be considered in patients with vasospastic angina, particularly if persistent, and confirms that anti-inflammatory treatment, rather than coronary stenting or vasodilators, can resolve symptoms.