Coronary Vasospasm in Eosinophilic Granulomatosis With Polyangiitis Presenting as Acute Coronary Syndrome Treated With Anti-IL-5

Abstract

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis that may involve the coronary arteries, even in ANCA-negative cases.

Case Summary

A 58-year-old woman with a history of asthma, eosinophilia, and prior percutaneous coronary interventions presented with exertional dyspnea and chest tingling. Electrocardiogram showed transient anterior ST-segment elevations. Coronary angiography revealed multivessel coronary vasospasm with 100% occlusion of the mid left anterior descending artery, reversible with intracoronary nitroglycerin. Laboratory work-up confirmed ANCA-negative EGPA. The patient was initially treated with steroids and vasodilators, then transitioned to benralizumab owing to disease recurrence and steroid dependence. Her symptoms resolved, and eosinophil counts remained suppressed.

Discussion

Cardiac involvement in EGPA is uncommon but potentially fatal. This case highlights the importance of considering EGPA in recurrent acute coronary syndrome with eosinophilia and demonstrates the successful use of IL-5–targeted biologic therapy.

Take-Home Messages

EGPA should be considered in recurrent acute coronary syndrome with eosinophilia. Benralizumab offers a steroid-sparing strategy in cardiac EGPA.

Visual Summary

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis that primarily affects small- to medium-sized vessels¹ and is characterized by asthma, eosinophilia, and necrotizing vasculitis. Cardiac involvement is a significant concern in EGPA and is associated with high morbidity and mortality.²

Take-Home Messages

• •Consider EGPA in patients with recurrent ACS and peripheral eosinophilia, as eosinophil-driven coronary vasospasm can mimic true myocardial infarction.
• •IL-5–targeted biologics represent a promising, steroid-sparing approach for managing EGPA with cardiac involvement.

Coronary vasculitis in the context of EGPA is a rare cardiac manifestation of the disease that can lead to complications such as coronary vasospasm, acute coronary syndrome (ACS), and spontaneous coronary artery dissection (SCAD).² The pathophysiology involves eosinophilic infiltration and inflammation of the coronary vessels, which can result in vasospasm and structural damage to the coronary arteries.³ We report a patient with antineutrophil cytoplasmic antibody (ANCA)–negative EGPA with extensive coronary involvement, presenting with ACS attributed to coronary vasospasms.

History of Presentation

A 58-year-old woman presented with progressive exertional dyspnea and recurrent chest tingling, though she denied overt chest pain or tightness. She reported poorly controlled asthma and noted that she had recently been trialing alternative inhaled corticosteroid regimens to minimize interactions with her coronary vasospasm medications. In the days prior to presentation, she developed worsening shortness of breath, cough, and anxiety, accompanied by episodes of chest tingling suggestive of an exacerbation.

On arrival to the emergency department, the patient was hemodynamically stable. Cardiopulmonary examination was notable for bilateral wheezing, without murmurs, rubs, or gallops. No peripheral edema or rash was present. The initial electrocardiogram (ECG) demonstrated normal sinus rhythm with diffuse hyperacute T waves. A repeat ECG revealed transient anterior ST-segment elevations, prompting activation of a code STEMI (ST-segment elevation myocardial infarction).

Past Medical History

The patient's medical history included coronary artery disease with prior percutaneous coronary interventions to the right coronary artery and left circumflex artery (LCx), vasospastic (Prinzmetal) angina, chronic eosinophilia, nasal polyps, and uncontrolled asthma. She was a kidney donor in March 2022. In May 2023, she was diagnosed with ANCA-negative EGPA after presenting with STEMI.

Differential Diagnosis

Differential diagnoses included ACS concerning for STEMI, EGPA-related coronary vasospasm, SCAD, eosinophilic myocarditis, and pulmonary embolism.

Investigations

The patient's initial ECG demonstrated diffuse hyperacute T waves, and a repeat tracing revealed transient anterior ST-segment elevations (Figure 1A). Cardiac biomarkers were notable for a high-sensitivity troponin I level of 0.116 ng/mL, consistent with myocardial injury. Coronary angiography showed complete occlusion of the mid left anterior descending artery (LAD) with TIMI flow grade 0, along with diffuse spasm involving the LAD, first diagonal branch, and LCx. The first and second obtuse marginal branches demonstrated 70% to 99% stenosis, while the right coronary artery contained a patent stent with minor stenosis and evidence suggestive of prior SCAD (Figure 2A, Table 1). During the catheterization, significant clot burden was observed in the LAD, LCx, and large diagonal branch, prompting a comprehensive hypercoagulable work-up. Testing revealed normal beta-2 glycoprotein and anticardiolipin antibodies, normal Factor II and Factor V Leiden assays, and negative results for lupus anticoagulant, protein C, protein S, antithrombin III, and prothrombin gene mutations.

Figure 1.

12-Lead ECGs on Admission and at Follow-Up

(A) ECG on admission shows sinus tachycardia with ST-segment elevation in leads V₃ to V₆, I, and aVL, with reciprocal ST-segment depression in leads II, III, and aVF, consistent with an anterolateral ischemic pattern. (B) Follow-up ECG demonstrating resolution of ST-segment elevation with deep, symmetric T-wave inversions in the anterior precordial leads (V₂-V₄), consistent with reperfusion changes after anterior wall ischemia. ECG = electrocardiogram.

Figure 2.

Prereperfusion and Postreperfusion Coronary Angiography

(A) Enhanced coronary angiography image showing diffuse spasm in the LAD and first diagonal branch territory before revascularization, consistent with EGPA-related vasospasm. (B) Post–nitroglycerin administration showing improved luminal caliber in affected coronary segments. Panels (A) and (B) shows a comparison of diffuse vasospasm in the LAD between prereperfusion and postreperfusion with partial resolution, demonstrating EGPA vasoreactivity. EGPA = eosinophilic granulomatosis with polyangiitis; LAD = left anterior descending artery; LAO = left anterior oblique; RAO = right anterior oblique.

Table 1.

Diagnostic Work-Up and Laboratory Test Findings in EGPA-Related Coronary Vasospasm

Category	Test/Value	Result	Reference	Interpretation
Hematologic	Absolute eosinophil count WBC count	>1.5 × 103/μL 15.10 × 103/μL	1.0-0.70 × 103/μL 4.80-10.80 × 103/μL	Consistent with eosinophilia
Rheumatologic panel	ANCA	Negative	—	ANCA-negative EGPA
Inflammatory markers	ESR CRP	25 mm/h <2.9 mg/L	0-30 mm/h 0.0-3.0 mg/L	Less systemic inflammation
Cardiac markers	Troponin I/T	0.116 ng/mL	≤0.059 ng/mL	Myocardial injury from vasospasm
Genetic/other	BCR-ABL1 FISH	Negative	—	Rule out clonal eosinophilia

The table summarizes the diagnostic work-up and shows EGPA's unique profile.

ANCA = antineutrophil cytoplasmic antibody; CRP = C-reactive protein; EGPA = eosinophilic granulomatosis with polyangiitis; ESR = erythrocyte sedimentation rate; FISH = fluorescence in situ hybridization; WBC = white blood cell.

Laboratory studies confirmed an elevated absolute eosinophil count (>1.5 × 10³/μL) in the setting of chronic mild leukocytosis. Given these findings, further hematologic evaluation was pursued. Flow cytometry and BCR-ABL1 FISH (fluorescence in situ hybridization) testing were negative. Bone marrow biopsy demonstrated normocellular marrow for age (50%-55%), with approximately 25% eosinophilia. Maturing trilineage hematopoiesis was preserved, with an adequate number of morphologically normal megakaryocytes. No evidence of acute leukemia, increased blasts, myelodysplasia, lymphocytosis, granulomas, or metastatic infiltration was observed. Additional rheumatologic work-ups, including ANA (antinuclear antibody), anti-dsDNA (anti-double-stranded DNA), ANCA, and rheumatoid factor—were negative, and inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) were normal (Table 2).

Table 2.

Angiographic Features in EGPA-Related Coronary Vasospasm

Vessel	Finding	Interpretation
LM	Grossly patent	No significant stenosis
LAD	Mid-LAD 100% occluded, TIMI flow grade 0	Active vasospasm with ischemia
D1	Severe spasm, 9% diffuse stenosis	Dynamic vasoreactivity
LCx	Diffuse spasm, OM1/OM2 70%-99% stenosis	Multivessel involvement, reversible
RCA	Patent stent, minor stenosis	Possible SCAD seen previously

The table integrates angiographic data into a quick-reference clinical table.

D1 = first diagonal branch; EGPA = eosinophilic granulomatosis with polyangiitis; LAD = left anterior descending artery; LCx = left circumflex artery; LM = left main artery; OM1 = first obtuse marginal branch; OM2 = second obtuse marginal branch; RCA = right coronary artery; SCAD = spontaneous coronary artery dissection.

Management

In the catheterization laboratory, intracoronary and systemic nitroglycerin administration resulted in prompt resolution of the coronary vasospasm and improvement in symptoms (Figure 2B). The patient did have a dissection of the right coronary artery, which was likely related to spontaneous coronary artery dissection She was initiated on dual antiplatelet therapy and calcium-channel blockers. Prednisone 40 mg daily was started and was gradually tapered. For long-term disease control, she was transitioned to benralizumab, metoprolol XL 12.5 mg, isosorbide, and ranolazine, which led to stabilization of symptoms and sustained suppression of eosinophil counts.

Outcome and Follow-Up

The patient experienced clinical stabilization, with no further admissions for acute coronary events after initiation of benralizumab. Her asthma and systemic EGPA symptoms improved, and her eosinophil counts remained suppressed. Continued follow-up showed no recurrence of chest symptoms or ECG changes (Figure 1B).

Discussion

Our patient's presentation with worsening dyspnea, chest tingling, diffuse hyperacute T waves, and transient ST-segment elevations, followed by angiographic confirmation of severe, diffuse coronary vasospasm responsive to intracoronary nitroglycerin, is characteristic of ACS precipitated by EGPA-related endothelial dysfunction and vasoreactivity. This patient had 3 admissions for acute STEMI in 1 year. The mechanism of action of coronary vasospasm in EGPA is primarily mediated by eosinophil-driven vascular injury and inflammation.^4,5 In EGPA, marked eosinophilia leads to infiltration of eosinophils into vascular tissues, including the coronary arteries. Activated eosinophils release cytotoxic granule proteins (such as major basic protein, eosinophil cationic protein, and eosinophil peroxidase), reactive oxygen species, and proinflammatory cytokines, which cause direct endothelial injury, promote smooth muscle hyper-reactivity, and induce local vasoconstriction.^6,7

This eosinophil-mediated endothelial dysfunction increases vascular tone and predisposes to coronary vasospasm. Additionally, the inflammatory milieu in EGPA, characterized by Th2 cytokines (notably IL-5), further sustains eosinophil activation and survival, amplifying vascular injury and spasms. Case reports and clinical observations have documented that coronary vasospasm in EGPA can be refractory to standard vasodilators⁸ and is often responsive to corticosteroids or anti-IL-5 therapy, underscoring the central role of eosinophilic inflammation rather than classic atherosclerotic or ANCA-mediated vasculitis.^6,7,9 Current management strategies for ACS in the setting of EGPA are not standardized, relying instead on principles extrapolated from general ACS management, vasospastic angina treatment, and systemic vasculitis therapy, largely informed by case reports and case series. Acutely, relief of ischemia via vasodilators (intracoronary/systemic nitroglycerin, calcium-channel blockers) is critical, as demonstrated by our patient's response during cardiac catheterization.

However, long-term therapy is still aimed at controlling the underlying EGPA. Initial treatment often involves high-dose glucocorticoids, followed by maintenance immunosuppression. Our patient's transition from prednisone to benralizumab, an anti-IL-5 biologic, was aimed at controlling eosinophilic inflammation driving both the systemic disease and potentially the coronary manifestations and reflects treatment approach from recent literature.^6,7 Benralizumab is an anti-IL-5Rα monoclonal antibody that rapidly and nearly completely depletes eosinophils in blood and tissue, directly targeting the eosinophil-driven vascular inflammation central to EGPA pathogenesis and coronary vasospasm (Figure 3). The recommended dose for EGPA is 30 mg subcutaneously every 4 weeks. Although direct evidence for benralizumab specifically in coronary vasospasm is limited, its mechanism of depleting eosinophils supports its use in EGPA patients with cardiac manifestations; however, further studies are needed to clarify its impact on coronary vasospasm outcomes (Figure 4).6, 7, 8, 9, 10 Although rare, SCAD has been reported in association with EGPA, suggesting that eosinophilic inflammation may contribute to vascular fragility and dissection.¹⁰

Figure 3.

Mechanism of Action of Benralizumab

Benralizumab binds to the IL-5 receptor alpha chain (IL-5Rα) on eosinophils and basophils and induces antibody-dependent cell-mediated cytotoxicity (ADCC) via natural killer (NK) cells, leading to apoptosis and depletion of eosinophils. Source: Reproduced from Pelaia et al.¹¹

Figure 4.

Comparative Mechanisms of IL-5 Targeted Biologics

Comparative mechanisms of IL-5 targeted biologics. Unlike mepolizumab and reslizumab, benralizumab directly targets IL-5Rα and engages NK cells via its afucosylated Fc domain, leading to enhanced ADCC. Source: Reproduced from Menzella et al.¹²

Limitations

This report describes a single case and therefore cannot establish causality or determine the efficacy of benralizumab in the management of coronary vasospasm associated with EGPA. Future studies, including multicenter registries and prospective case series, are warranted to further define therapeutic outcomes, identify predictors of response, and refine treatment strategies in this rare but clinically significant presentation.

Conclusions

This case highlights the rare but significant cardiac manifestations of EGPA, specifically recurrent STEMI secondary to severe, diffuse coronary vasospasm. Our patient's clinical course—marked by recurrent ACS events, angiographic findings of reversible spasm, and responsiveness to intracoronary nitroglycerin and no further admissions for ACS after initiation of benralizumab—demonstrates the role of eosinophil-mediated endothelial dysfunction and vasoreactivity as key pathogenic mechanisms in EGPA-related coronary involvement. Traditional vasodilator therapy remains essential in the acute setting; however, long-term management requires targeting the underlying eosinophilic inflammation.

The patient's transition to benralizumab, an anti-IL-5 receptor monoclonal antibody, reflects a growing body of evidence supporting biologic therapy in EGPA to suppress eosinophil-driven vascular inflammation. Although the efficacy of benralizumab in coronary vasospasm is not yet well established, its mechanism of near-complete eosinophil depletion makes it a promising therapeutic option for EGPA patients with cardiac involvement. This case emphasizes the importance of recognizing EGPA as a cause of recurrent ACS and the need for further research to establish standardized treatment protocols for vasospasm in this context.

Visual Summary.

Timeline of the Case

Time	Events
Initial presentation	Middle-aged woman with history of kidney donation, CAD, and asthma presented with progressive dyspnea and chest tingling. ECG showed diffuse hyperacute T waves and transient ST-segment elevations.
Day 1	Emergent coronary angiography revealed 100% occlusion in the mid-LAD and multivessel coronary vasospasm. Vasospasm resolved with intracoronary nitroglycerin.
Day 1	Initiated dual antiplatelet therapy and calcium-channel blockers. Eosinophilia noted; work-up confirmed ANCA-negative EGPA.
Day 3	Started on oral prednisone 40 mg daily.
Day 60	Subsequent outpatient evaluation led to transition to benralizumab for eosinophil-targeted therapy after a slow steroid taper over 2 months.
Day 120	No recurrent ACS symptoms after biologic initiation. Asthma and systemic symptoms improved. Patient remained stable with suppressed eosinophil count on follow-up.

ACS = acute coronary syndrome; ANCA = antineutrophil cytoplasmic antibody; CAD = coronary artery disease; ECG = electrocardiogram; EGPA = eosinophilic granulomatosis with polyangiitis; LAD = left anterior descending artery.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.