Eosinophilic granulomatosis with polyangiitis is an antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis with cardiac involvement in more than 60% of cases. Authors describe the case of a 48-year-old woman who presented with progressively worsening asthenia, dyspnoea and macular, non-painful, non-itchy cutaneous lesions. She had signs of congestion on clinical examination and a history of asthma and nasal polyps. Blood tests showed eosinophilia (11.2%), positive troponin I (9698 μg/L), elevated B-type natriuretic peptide (2047 pg/mL) and positive C reactive protein (6.68 mg/dL). Echocardiogram displayed moderate left ventricular enlargement, left ventricular ejection fraction of 28% and mild pericardial effusion. Levosimendan relieved the congestion. Additional testing confirmed positive antinuclear antibodies with ANCA-negative autoimmune pattern. Cardiac magnetic resonance showed severely depressed systolic function due to diffuse hypokinesia. Cardiac biopsy had intercellular oedema and eosinophilic infiltrate. Treatment with prednisolone and cyclophosphamide was started. This is a case of a rare disease presenting with life-threatening cardiac involvement.
- biological agents
- heart failure
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Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is an antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis, characterised by systemic necrotising vasculitis with extravascular granulomas and eosinophilia. It is a rare disease and has cardiac involvement in more than 60% of cases, being the main cause of morbidity and mortality and an important sign of poor prognosis.1 Life-threatening cardiac involvement is even more atypical and, as proved by this case, requires early diagnosis and proper treatment in order to achieve good outcomes.
A 48-year-old woman presented to the emergency department with asthenia and dyspnoea on exertion (New York Heart Association class III) that have been progressively worsening over 1 month. She denied fever, coughing, nasal discharge, palpitations and chest pain. When asked for skin involvement, she made reference to occasional macular, non-painful, non-itchy, self-limiting cutaneous lesions over her extremities, which had been on and off for the last 2 years. No other symptoms were found on the revision of organs and systems. The first clinical examination was notable for signs of severe congestion, with diminished bilateral breath sounds, jugular vein distension and peripheral oedema.
She had a previous medical history of asthma, allergic rhinitis and nasal polyps, with no recent acute exacerbations and regular appointments in otorhinolaryngology (ENT) and pneumology clinics. Her condition was managed with bronchodilators and inhaled corticosteroids, with apparent good control. She denied smoking and drinking habits. She lived in an urban area and worked as a pharmacist. She had no recent travel history.
Blood tests showed peripheral eosinophilia (0.7×109/L) with positive C reactive protein, positive troponin I and elevated B-type natriuretic peptide (table 1).
The ECG showed inverted T waves in lateral leads (aVL, V5-6), the chest X-ray proved bilateral pleural effusion and the abdominal ultrasound was notable for hepatomegaly and dilated suprahepatic veins. An urgent echocardiogram was performed and showed a dilated left ventricular with a severely depressed left ventricular ejection fraction (LVEF) and a mild pericardial effusion with normal valvular function (figure 1).
An additional laboratory workup revealed ANA-positive (1:320, with dense fine granular pattern) but ANCA-negative autoimmune pattern with negative anti-double-stranded DNA and normal concentration of serum complement proteins, C3 and C4.
All other requested serologies were negative (table 2).
A gadolinium-enhanced cardiac MRI confirmed a non-hypertrophied enlarged left ventricle (end-diastolic volume 168 mL) with severe reduction in systolic function due to diffuse hypokinesia and delayed subendocardial enhancement with a multisegment distribution (figure 2).
Finally, an endomyocardial biopsy revealed that myocytes maintained their usual morphology, with slight intercellular oedema and eosinophilic infiltrate (figure 3).
The patient was admitted to the cardiac care unit for stabilisation. She was treated with a levosimendan infusion, with good haemodynamic response. An EGPA with eosinophilic myocarditis was assumed and the patient was started on prednisolone (first in high dose: 500 mg for 3 days; and then 1 mg/kg/day) and cyclophosphamide (15 mg/kg/every 2 weeks for the first three cycles). A 10-cycle regimen of cyclophosphamide was planned, with a pulse every 3 weeks while reducing prednisolone after each pulse.
Outcome and follow-up
One month after discharge, she was observed at the outpatient heart failure clinic and showed significant improvement under spironolactone 25 mg/day, carvedilol 6.25 mg two times per day, sacubitril/valsartan 24/26 mg half+half/day, furosemide 40 mg two times per day, prednisolone 45 mg/day and calcium and vitamin D supplementation. The follow-up echocardiogram showed significant left ventricular remodelling, with normal end-diastolic indexed volume (56 mL/m2), maintaining a severely depressed systolic function (LVEF 34%); pericardial effusion was absent.
EGPA is a rare disease, with a prevalence ranging from 10.7 to 13 cases/million inhabitants and an incidence of 0.5–6.8 new cases/million inhabitants/year.1 Although its incidence is higher in asthmatic patients, EGPA remains poorly understood and often goes unrecognised, leading to poor clinical outcomes. Since 1951, when EGPA was first reported by Churg and Strauss, there have been several definitions and classification criteria, but remains the need for further consensus in order to establish optimal guidelines for its diagnosis and management.1 2
The clinical features of EGPA typically develop in several sequential phases, although these phases are not always clearly distinguishable: (1) the prodromal phase occurs among individuals in the second and third decades of life and is characterised by atopic disease, allergic rhinitis and asthma, (2) the eosinophilic phase includes peripheral blood eosinophilia and eosinophilic infiltration of multiple organs and (3) the vasculitic phase is characterised by a life-threatening systemic vasculitis of the medium and small vessels that is often associated with vascular and extravascular granulomatosis.3
Respiratory tract involvement is the most common form of presentation. Although EGPA belongs to the spectrum of ANCA-associated vasculitis, less than 50% of patients with EGPA are ANCA positive. Cardiac involvement is the major cause of early death and poor prognosis. Eosinophilic myocarditis is one of the morbidity and mortality causing factors and may result from various conditions that cause eosinophilia. Drug hypersensitivity has been described as one of the most common causes and must be taken into consideration. Second, eosinophilic myocarditis could be triggered by infections or may also be part of an idiopathic hypereosinophilic syndrome marked by eosinophilia and multiorgan involvement. When met the classification criteria, eosinophilic myocarditis can be associated with systemic eosinophilia such as in EGPA. In fact, cardiac involvement may be present in 62% of all EGPA cases, although it is symptomatic only in 26% and it is caused by activated eosinophils as well as vasculitis lesions in the myocardium and coronary arteries.4 Myocarditis may lead to postinflammatory fibrosis and restrictive cardiomyopathy, followed by congestive cardiac failure. The spectrum of clinical manifestations varies from coronary artery disease, primary arrhythmias, cardiomyopathy, acute constrictive pericarditis and myocarditis and eosinophilic pericardial effusion. The use of echocardiography and cardiac MRI has helped in detecting cardiac abnormalities even beyond the acute active phase of the disease like fibrosis or cardiomyopathy.4
Our patient was diagnosed after a life-threatening acute heart failure episode. Due to the severely depressed cardiac function, the administration of cyclophosphamide was performed during hospital admission. Within 6 weeks after starting remission-induction regimen with prednisolone and cyclophosphamide, the patient showed significant clinical improvement and subtle signs of reverse left ventricular remodelling. Maintenance therapy (with azathioprine or methotrexate) is recommended for patients with life-threatening and/or organ-threatening disease manifestations.1 Therefore, our patient will switch to azathioprine 2 mg/kg/day after the remission-induction regimen is completed. Additional biological treatment with mepolizumab, for example, may be needed in case of relapse or further cardiac involvement.5 Reducing glucocorticoid exposure and preventing treatment-related adverse events are major challenges and, among others, cardiovascular risk factors and osteoporosis should be screened and adequately managed.5
Patients with EGPA, mostly the ones with life-threatening and/or organ-threatening disease manifestations, should be monitored closely because new symptoms may be early signs of a vasculitis flare.1
Eosinophilic granulomatosis with polyangiitis’ (EGPA) prevalence is lower than that of other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. With fewer conducted trials, EGPA diagnosis can be challenging.
Being a rare disease, EGPA often goes unrecognised. Particularly in ANCA-negative patients, EGPA manifestations may mimic other diseases and may have a variable range of severity at presentation.
An accurate clinical history and differential diagnosis are fundamental; if the authors had not had an early and high level of suspicion and consequently requested the correct complementary exams, the window for proper treatment could have been missed leading to a poor outcome.
Contributors All the authors have contributed to the clinical approach and to the planning, conducting and reporting of the described clinical case. AF made the first diagnostic approach in the emergency room department, identified the acute heart failure and presented the first possible differential diagnosis. Then, together with JA and SC followed the patient during all the hospital admission time, discussing all the details in order to achieve the correct diagnose and start the adequate treatment. RB followed the patient after discharge to access the outcome and the long-term evolution. Regarding the case report, JA and AF collected the data and then, together with SC and RB, made the analysis and interpretation of all the available results and details of the clinical case. JA was responsible for the conception and design of the paper with the valuable collaboration of all the coauthors.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.