Pseudoxanthoma elasticum resulting in acute coronary syndrome

Abstract

Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder that causes elastic tissue degeneration in the skin, eyes, and cardiovascular system. Gastrointestinal bleeding and fundus hemorrhage are serious complications associated with PXE prognosis as well as cardiovascular involvement. This is a rare case of acute coronary syndrome in a PXE patient with high bleeding risk.

Learning objective

Pseudoxanthoma elasticum (PXE) resulting in acute coronary syndrome (ACS) is rare. Given PXE patients are generally at very high bleeding risk, antithrombotic therapy as secondary prevention after ACS onset should be taken into full consideration.

Introduction

Pseudoxanthoma elasticum (PXE) is a rare, late-onset, hereditary disorder characterized by calcification and fragmentation of elastic fibers [1]. Clinical manifestations of PXE are mainly seen in the skin, eyes, and cardiovascular system. Although peripheral artery calcification is the most common cardiovascular manifestation, coronary artery disease is one of the serious complications which should be considered [1], [2]. However, development of acute coronary syndrome (ACS) in PXE patients is rarely reported [3]. Moreover, it is known that gastrointestinal bleeding and fundus hemorrhage are serious complications associated with PXE prognosis [1]. Therefore, antithrombotic therapy after ACS onset can be a serious concern. This case illustrates ACS occurring in a patient with PXE who was at very high risk for bleeding.

Case report

A 72-year-old woman visited our emergency department complaining of chest pain. The patient was diagnosed as having PXE. She had yellowish papules in her axilla (Fig. 1A) and angioid streaks in her bilateral eyes (Fig. 1B), both of which are typical PXE features. Furthermore, contrast-enhanced computed tomography revealed peripheral vascular calcifications (Fig. 1C). Histopathological examinations of her skin lesion revealed fragmentation and calcification of mid-dermal elastic fibers, confirming PXE diagnosis three months before the onset of the event (Fig. 1D).

Fig. 1.

(A) Skin lesion including yellowish papules in the axilla. (B) Fundus photograph showing angioid streaks. (C) Contrast-enhanced computed tomography showing diffuse peripheral vascular calcifications. (D) Histopathological examinations showing fragmentation (Elastica van Gieson staining) and calcification of mid-dermal elastic fibers (Von Kossa staining). (E) Coronary angiography showing occluded left circumflex artery (LCX) with multiple-vessel disease. (F) Optical coherence tomography showing diffuse atherosclerotic lesions with thrombus. (G) Fundus photograph showing hemorrhage.

Although her 12-lead electrocardiogram showed no significant ST-segment elevation, persistent chest pain with elevated high-sensitivity cardiac troponin I (49 pg/ml; normal range, 0.0–26.1 pg/ml) was observed. Therefore, non-ST elevation ACS was suspected. The patient was in the high-risk group for ACS for the following reasons: persistent chest pain, elevated cardiac troponin, and high GRACE risk score >140 (Her GRACE risk score was 150). These met a class IA recommendation for early invasive treatment strategy in the JCS guidelines. Therefore, we decided to perform emergent coronary angiography (CAG) for percutaneous coronary intervention (PCI). Emergent CAG showed an occluded left circumflex artery (LCX) with multiple-vessel disease (Fig. 1E). Thrombolysis in myocardial infarction (TIMI) 2 flow was achieved by pre-dilatation using 2.0-mm sized balloon and thrombus aspiration. Optical coherence tomography (OCT) showed diffuse atherosclerotic lesions with thrombus (Fig. 1F). Moreover, the OCT showed presence of thrombus overlying an intact fibrous cap. Plaque rupture or calcified nodules were not detected. Based on these OCT findings, the ACS etiology in the present case was thought to be plaque erosion. The patient had a history of gastric bleeding and choroidal neovascularization-related subretinal hemorrhage (Fig. 1G). Considering the very high bleeding risk associated with PXE, we selected the stentless strategy with a drug-coated balloon. After adjunctive lesion preparation using a cutting balloon (2.0/10 mm), ballooning with a 2.0/15 mm sized drug-coated balloon (SeQuent Please, B Braun, Melsungen, Germany) was performed. After the procedure, TIMI 3 flow was successfully acquired without complications. Fig. 2 shows the PCI procedure in the present case. We initiated dual antiplatelet therapy with aspirin and low-dose prasugrel (2.5 mg) and switched to single antiplatelet therapy with low-dose prasugrel alone a week after PCI. During the six-month follow-up, we observed no bleeding complications and cardiovascular events.

Fig. 2.

(A) Preprocedural coronary angiography (CAG) showing totally occluded left circumflex artery (LCX). (B) CAG showing thrombolysis in myocardial infarction (TIMI) 2 flow after pre-dilatation and thrombus aspiration. (C) CAG showing ballooning using drug-coated balloon (DCB). (D) Final CAG showing TIMI 3 flow.

PCI, percutaneous coronary intervention.

Discussion

Regarding PXE patients, there are two important clinical points which we should note. First, PXE is rare as a disease associated with the occurrence of ACS. Second, PXE patients are at very high bleeding risk.

PXE, a rare disease involved in the occurrence of ACS

PXE is a rare disease, but cardiovascular complications due to narrowing of small and medium-sized arteries commonly result in peripheral artery disease, coronary artery disease, and renovascular hypertension [1]. These cardiovascular manifestations of PXE progress regardless of known cardiovascular risk factors such as smoking, diabetes mellitus, dyslipidemia, and hypertension. To date, there is no therapeutic approach for the cardiovascular complications. However, general coronary risk factor control is mandatory to minimize the progression of cardiovascular complications [1], [3]. This case had a controlled hypertension and received aggressive lipid-lowering therapy targeting below 70 mg/dl before the onset of ACS.

PXE patients with a very high bleeding risk

Given PXE patients have very high bleeding risk, secondary prevention of cardiovascular events such as ACS by antithrombotic therapy requires full consideration [3]. General bleeding and thrombotic risk scores are shown in Online Fig. 1. In addition of these risk scores, in the Japanese high bleeding risk criteria, 4 major and 3 minor criteria was met in the patient, indicating high bleeding risk [4]. Therefore, the present case is generally considered to be at high risk for both bleeding and thrombosis excluding the fact that she has PXE. In addition, the present case had a vision loss due to repeated subretinal hemorrhages associated with PXE. Several studies suggested that the safety and efficacy of drug-coated balloon-only strategy with 1-month dual antiplatelet therapy (DAPT) in patients at high bleeding risk [5], [6]. However, we thought even 1-month DAPT was risky for the patient because there is a serious concern about blindness by recurrent subretinal hemorrhages. Considering the very high bleeding risk, our cardiovascular team decided 1-week DAPT following drug-coated balloon-only strategy as a tailor-made medicine after consultation with the patient. Although it might be possible to further shorten the DAPT duration or single-antiplatelet therapy for drug-coated balloon-only strategy in patients at high bleeding risk, further investigations are needed to clarify the issue [6]. Moreover, a low-maintenance dose of prasugrel 2.5 mg is commercially available in low-body weight (≤50 kg) ACS patients considering high bleeding risk in Japan [7], [8]. The patient weighed <50 kg and was given a maintenance dose of prasugrel 2.5 mg. Low-dose prasugrel following stentless PCI for ACS might be considered in PXE patients with very high bleeding risk.

The following is the supplementary data related to this article.

Declaration of competing interest

The authors declare that there is no conflict of interest.