Coronary artery ectasia in Crohn’s disease

Abstract

Coronary artery ectasia (CAE) can be ascribed, in the majority of cases, to coronary atherosclerosis. Nevertheless, the presence of isolated ectatic lesions without obstructive coronary artery disease and the association of CAE with several autoimmune diseases characterised by systemic vascular involvement suggest that the pathogenesis of CAE may extend beyond coronary atherosclerosis. We herein report the case of a 56-year-old male patient with Crohn’s disease and isolated CAE, who has been found positive for IgM and IgA antiendothelial cell antibodies, and discuss a potential pathogenic mechanism.

Background

Coronary artery ectasia (CAE) may be encountered in 0.3%–4.9% of patients undergoing coronary angiography,¹ and it is usually ascribed to coronary atherosclerosis, as a result of the expansive arterial remodelling the coronary vasculature undergoes in the presence of an atherosclerotic lesion.² The pathogenesis of CAE is suggested to occur through more than one molecular mechanism.³ Nevertheless, the presence of isolated ectatic lesions without obstructive coronary artery disease and the association of CAE with several autoimmune diseases characterised by systemic vascular involvement suggest that the pathogenesis of CAE may extend beyond coronary atherosclerosis.⁴ Crohn’s disease is a chronic idiopathic disorder causing inflammation of the gastrointestinal tract with a prevalence of 0.3% in Europe.⁵ We report the case of a 56-year-old male patient with Crohn’s disease and isolated CAE and discuss a potential pathogenic mechanism.

Case presentation

The patient was admitted to our clinic 3 weeks after the onset of angina pectoris. He had a positive history of hypertension and smoking and had been diagnosed with histologically proven ileal Crohn’s disease 3 years before. At the time of his admission to our clinic the patient was in remission on mesalamine therapy. The physical examination was unremarkable.

Investigations

Complete blood count and erythrocyte sedimentation rate (ESR) were within normal limits, and no markers of myocardial necrosis were detected. Using single photon emission CT myocardial perfusion imaging, reversible perfusion defects in the mid and the apical inferior segments of the left ventricle were identified. On coronary angiography, there were no significant stenoses observed; however, slow coronary flow was evident in all three major epicardial arteries and especially the right coronary artery, with corrected thrombolysis in myocardial infarction frame counts of 36, 38 and 48 for the left anterior descending, the circumflex and the right coronary arteries, respectively (figure 1). Furthermore, diffuse ectatic involvement of the proximal, mid and distal right coronary artery was observed, with a maximal luminal diameter of the mid-segment of 5.75 mm, as estimated by quantitative coronary angiography analysis. Further serological testing using indirect immunofluorescence on HEp-2 cells and ethanol-fixed neutrophils detected no antinuclear or antineutrophil cytoplasmic antibodies. Using a previously described ELISA, we detected the presence of IgM and IgA antiendothelial cell antibodies (AECA), whereas IgG AECAs were not detected.⁶

Figure 1.

Coronary angiogram showing diffuse ectasia affecting the right coronary artery (A), compared with the left coronary artery (B).

Treatment

The patient was discharged on antiplatelet treatment.

Outcome and follow-up

The patient has had an uneventful 2-year clinical course.

Discussion

To the best of our knowledge this is only the second report of a patient with CAE and Crohn’s disease.⁷ CAE denotes an inappropriate dilatation of the coronary artery tree, and has been defined as the presence of a coronary segment exceeding in diameter the normal, adjacent, segments by 1.5 times.⁴ Using MRI, CAE has been reported to be a common, unrecognised characteristic of patients with systemic vasculitides.⁸ In this context, CAE is a probable finding in a patient with Crohn’s disease, since Crohn’s disease has been associated with vasculitis affecting large, medium or small-sized vessels.⁹ In large-sized vessels, the most common vasculitis reported in patients with Crohn’s disease is Takayasu’s arteritis (TA),⁹ which affects mainly the aorta and its main branches, including the coronary, carotid, pulmonary and renal arteries, leading to stenoses or dilatations of the affected vessels.¹⁰ Coronary involvement with aneurysm formation is less common in TA, however several cases have been reported to date.⁹ Our patient did not present with acute phase symptoms, or other features suggestive of TA, such as pulse deficits, arterial bruits or an elevated ESR. Of note, we have detected the presence of IgA and IgM AECA in our patient. We have previously provided evidence of an increased prevalence of IgA AECA in patients with CAE compared with controls.⁶ AECAs are often detectable in patients with systemic vasculitis or systemic autoimmune disease associated with secondary vascular injury.¹¹ There is evidence of a significant pathogenic role for AECA, since they may exert direct cytotoxic effects on endothelial cells (EC) and induce EC apoptosis.^{11 12} Furthermore, AECA may activate ECs and induce the expression of adhesion molecules, and the production of proinflammatory cytokines.^{13 14} The presence of AECA may also be mechanistically associated with the observation of diffuse slow coronary flow in our patient. In subjects with CAE, disease extent is related to the impairment of coronary circulation and to inflammatory activation.¹⁵ Slow coronary flow may be observed irrespective of CAE extent,¹⁶ which has been attributed to microvascular dysfunction.¹⁶ Slow coronary flow has been shown to correlate with markers of endothelial dysfunction such as plasma asymmetric dimethylarginine levels and flow-mediated dilatation.¹⁷ There is some evidence that the presence of AECA may be associated with endothelial dysfunction in patients with mixed connective tissue disease¹⁸ and in patients with arterial disease.¹⁹ The presence of circulating AECA in approximately 20% of patients with Crohn’s disease has been a consistent finding, however their clinical relevance has not been identified.²⁰ The association between AECA and vasculitis, or CAE in specific, in patients with Crohn’s disease should be further investigated.

Learning points.

• Coronary artery ectasia (CAE) is suggested to have more pathogenic mechanisms than coronary atherosclerosis.

• CAE could be a common feature of systemic vasculitides and therefore also a feature of Crohn’s disease.

• IgM and IgA antiendothelial cell antibodies, which are found to be present in patients with Crohn’s disease, are evidenced to induce inflammatory processes and apoptosis on endothelial cell, thereby being a possible causative agent of CAE.