Ehlers–Danlos syndrome type IV as the etiology of spontaneous coronary artery rupture

As you know, the Journal of Cardiology Cases is one of the formal journals of the Japanese College of Cardiology, and has been published as an online E-journal specializing in case reports since January 2010. Every issue has contained clinically interesting and valuable case reports, and the significance of this journal is increasing. As a new initiative, we will now begin carrying Editorial Comments for particularly interesting reports. The case reported by Ohyama et al. [1] was honored with a Case Report Award in 2011. It is therefore with great pleasure that I write the first of these editorial comments on that case report, and I thank the Editor-in-Chief for giving me this opportunity.

Ehlers–Danlos syndrome type IV (EDS type IV) is characterized by thin and translucent skin, easy bruising, a characteristic facial appearance (i.e. thin lips and philtrum, small chin, thin nose, large eyes), and arterial, intestinal and/or uterine fragility [2]. In childhood, inguinal hernia, pneumothorax, and recurrent joint subluxation or dislocation can occur. Vascular dissection or rupture, gastrointestinal perforation, and organ rupture are the presenting signs in the majority of adults identified with EDS type IV. Arterial rupture may be preceded by aneurysm, arteriovenous fistulae or aortic dissection, but may also occur spontaneously. Such complications are dramatic and often unexpected, presenting as sudden death, stroke and its neurologic sequelae, acute abdomen, retroperitoneal bleeding, uterine rupture at delivery, and/or shock. Because families with EDS type IV are often identified only after a severe complication or death, it is likely that individuals/families with COL3A1 mutations having a mild phenotype do not seek medical attention and, therefore, go undetected. In addition, because of the rarity of this disorder, it is not usually considered and nonvascular complications rarely raise diagnostic suspicion of EDS type IV.

EDS type IV is very rare; its incidence is estimated to be around 1:50,000 [2]. In this very unusual case, the authors began to suspect EDS type IV from the history of bilateral carotid-cavernous fistula (CCF) and the characteristic physical findings, including thin and translucent skin, atrophic scars on both knees, and hypermobility of the joints of the toes. It surprises us very much that the authors suspected EDS Type IV from the presence of cardiac tamponade caused by spontaneous coronary artery rupture (SCAR) with myocardial infarction stemming from multiple coronary spasms, and that they were able to make a correct diagnosis before a search of the genes. Indeed, this may be the first reported case of multiple SCAR with EDS Type IV.

In 2009, Shrestha et al. reported a case of SCAR in a 43-year-old male who presented with sudden onset chest pain and hemodynamic collapse, but no significant abnormal electrocardiogram changes and no elevation of serum troponin [3]. Moreover, the SCAR was an isolated perforation of the posterior descending artery with spurting of fresh arterial blood from the surface of the heart. It was not multiple SCAR. Although the authors introduced this case as the first report of primary SCAR in a young and healthy male without a previous history of atherosclerotic disease, as revealed by multidetector dual-source 64-slice computed tomography coronary angiography, it seems highly plausible that EDS was the underlying disease. Unfortunately, the authors did not mention this possibility.

In most of the reported cases of SCAR, the patient presented with clinical symptoms suggestive of acute coronary syndrome or acute aortic dissection. Shrestha et al. suggest that it is difficult to establish any etiological pattern or underlying disease for the occurrence of SCAR [3]. They also point out that the possible etiologies for the occurrence of SCAR include external rupture of a localized atheromatous plaque ulcer, which could also be a nidus for SCAD, as well as other localized coronary pathologies, such as aneurysm, inflammatory processes, and localized trauma. However, it is now clear that while the potential etiologies of SCAR suggested by Shrestha et al. are reasonable, their list is not complete. From the case reported by Ohyama et al., we can see that EDS Type IV is a possible etiogenic disease underlying SCAR that should be taken into consideration when we make a differential diagnosis.

Another important point raised by this case is that multiple coronary spasms may be induced by cardiac tamponade caused by SCAR, which may lead to acute myocardial infarction. Unfortunately, it must be difficult and may be contraindicated to confirm the relationship between coronary spasm and myocardial infarction caused by possible underlying EDS Type IV, which would make it reasonable and proper to question the author's interpretation. Nishiyama et al. reported on a 43-year-old male patient with EDS type IV and acute myocardial infarction without organic coronary stenosis, but complicated by pneumothorax, subcutaneous and mediastinal emphysema, and splenic artery rupture [4]. They suggested that there is a close linkage between the detected point mutation in the COL3A1 gene and the phenotype of familial myocardial infarction. If so, the case presented by Ohyama et al. may prompt one to reconsider the relationship between the point mutation specified in COL3A1 and vasospasm. If for no other reason, this case is valuable because it makes that important point.

So what is it that is most important to take away with us from this case? It is a core tenet that we clinicians can reach agreement on individual cases, a core tenet that we can analyze each case, in part by comparing it with past experience, and a core tenet that we seek to know a patient's true clinical condition. In that context, it can be said that Ohyama et al. conducted themselves in a manner that we clinicians most value.

As a measure taken against disease and death, medical care has been with humans since their origin. When medical care was very primitive, everything was learned from experience. Through time and with wisdom, “medical care” was transformed to “medicine,” a system of study, like mathematics, physics, and chemistry, but we continue to empirically learn medical care. During the 20th century, in particular, which can be said without exaggeration to be the century of the life sciences, doctors renowned primarily for their experience disappeared. The emphasis shifted to scientific analysis and away from experience as the use of medicine (i.e. performance of medical care using scientific techniques) to make diagnoses became nearly universal. Nonetheless, it remains true that careful repeated analysis of individual cases enables one to obtain experience that continues to be a driving force for medical development. The number of cases one personally experiences during a career is limited, and may be much affected by one's specialty. It is therefore highly important we all gain common experience through the reporting of valuable cases such as this one in JC Case.