Ten-year follow-up of a case of eosinophilic granulomatous with polyangiitis

Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg–Strauss syndrome, is an antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis, characterized by systemic necrotizing vasculitis with extravascular granulomas and eosinophilia.¹ The global pooled prevalence of EGPA was 1.7 per million persons.² The clinical features of EGPA typically manifest in several sequential phases: the prodromal phase, the eosinophilic phase and the vasculitic phase, which are not always clearly distinguishable.³ Given its systemic nature, diagnosing EGPA can be challenging.

We present the case of a 68-year-old Chinese male, with a height of 168 cm and weight of 80 kg, who underwent nearly a decade of follow-up since the onset of his illness in 2014.

The patient was admitted to our hospital in September 2014 due to a significant exacerbation of chest tightness and asthma, mild oedema in both lower limbs and pleomorphic rash on both thighs, calves and dorsum of feet (Figure 1A,B). Subsequently, the patient gradually developed a low fever, soreness in the lower back and shoulders and a tingling sensation in the skin on the soles of the feet. His past medical history revealed a diagnosis of bronchial asthma 9 years ago (with regular inhalation of salmeterol/fluticasone), and there were no traditional risk factors for cardiovascular disease.

Upon presentation, he was classified as New York Heart Association (NYHA) II–III. Vital signs included a body temperature of 37.9°C, heart rate of 110 beats/min, blood pressure of 133/87 mmHg and peripheral blood oxygen saturation of 96%. Clinical examination revealed no jugular vein distention. Heart sounds were audible with no murmurs or additional sounds. Lung auscultation demonstrated thick breathing sounds in both lungs, with a large amount of fine and moist rales heard in both lower lungs, and occasional wheezing sounds during exhalation. No abnormalities were noted in the abdomen, while moderate concave oedema was observed in both lower limbs. Polymorphic rashes were visible on both thighs, calves and dorsum of feet, partially fused into patches, protruding above the skin surface without fading, itching, blisters or ulcers. The nervous system examination revealed no obvious abnormalities.

Laboratory examination revealed the following results: WBC of 13.14 × 10⁹/L, with eosinophils elevated to 42.5%, blood IgE level of 707 IU/mL (reference value <100), myocardial enzymes including CK at 97 u/L (reference value 55–170), CK-MB at 5 u/L (reference value <16), LDH at 767 u/L (elevated), TNI at 2.06 ng/ml (elevated, reference value <0.12) and BNP at 10000 pg/mL (elevated, reference value <450). Echocardiography revealed left atrioventricular enlargement, with a substantial mass measuring about 30 × 27 mm found in the left ventricular apical cavity, exhibiting uneven internal echo and partial liquefaction foci. The mass was closely connected with the apical myocardium, and although the systolic activity of the apical myocardium was weakened, the mass moved synchronously with the contraction of the heart. Pulmonary artery systolic pressure was measured at 30 mmHg, with an EF value of 49%. The left ventricular apical mass was also identified on Cardiac magnetic resonance imaging (CMR) (Figure 2A–F). Lung CT demonstrated interstitial changes in both lungs, pneumonia in both lungs and aneurysmal dilation of the main pulmonary artery.

Upon admission, the patient received nasal catheter oxygen inhalation, methylprednisolone injection at 80 mg QD, milrinone injection at 10 mg QD, lidocaine, propafenone for antiarrhythmic therapy, furosemide, spironolactone for diuretic therapy and low molecular weight heparin calcium for anticoagulation. Following these treatments, the rash rapidly subsided, and dyspnoea significantly improved. Three days later, intravenous methylprednisolone was discontinued, and prednisone tablets were initiated at 40 mg Po QD. On 29 October 2014, the patient was discharged from the hospital in improved condition. Discharge medical advice included prednisone tablets at 25 mg Po QD, Seretide 500 μg inhaled bid and warfarin tablets at 1.25 tablets Po QD.

After discharge, the patient's condition remained stable, and prednisone was gradually tapered. On 18 November 2014, the patient visited a specialized cardiac hospital. Echocardiography revealed a 39 × 21 mm medium-sized echogenic mass attached to the apical part of the left ventricle, nearly filling the apical part of the heart, suspected to be cardiac thrombus or tumour. The physician recommended conservative management with ongoing observation. By the end of November 2014, he independently discontinued the use of prednisone tablets. He was then prescribed 320 μg bid of budesonide/formoterol, 10 mg QD of Singulair and two tablets tid of Asmeton.

On 28 April 2015, the patient presented with fever, cough and pain in the plantar skin and calf muscles, accompanied by a small rash on the lower limbs. He also experienced chest tightness and breathlessness after activity, with wet rales heard in his lungs. Upon hospitalization, a significant increase in eosinophil count was noted, with negative specific IgE, rheumatoid antibody, ANCA and parasitic antibody. CT of the paranasal sinuses revealed mucosal thickening of the maxillary sinus and sphenoid sinus. Pulmonary function tests demonstrated mild mixed ventilation dysfunction, normal diffusion function, negative diastolic test and normal FeNO. Following 3 days of glucocorticoid treatment, the eosinophil count returned to normal, leading to a diagnosis of EGPA. Long-term treatment with methylprednisolone tablets markedly alleviated cough, dyspnoea and heart failure, with normalization of eosinophil count and IgE levels. Subsequent to discharge, the glucocorticoid dose was gradually tapered. Echocardiography indicated a gradual reduction in the size of the mass within the left ventricle (32 × 17 mm).

By August 2015, the methylprednisolone tablet dose was reduced to 4 mg/day for long-term maintenance therapy, with no recurrence of asthma symptoms or rash attacks (Figure 3).

On 31 May 2016, warfarin and boligao were introduced as part of the treatment regimen. As a result, the apical space-occupying lesion began to decrease gradually. By 25 June 2023, cardiac ultrasound revealed a high echo mass measuring approximately 7 × 14 mm in the apical part of the left ventricle, with unclear boundaries with the muscle layer (Figure 2G). It was determined to be a myocardial eosinophilic granuloma resulting from EGPA.

The patient received follow-up care from a multidisciplinary team. In 2023, he experienced two episodes of ventricular tachycardia and underwent ICD implantation. Presently, the patient's condition is stable.

Although EGPA belongs to the spectrum of ANCA-associated vasculitis, more than 50% of patients with EGPA are ANCA negative.³ Over 90% of EGPA patients had a history of bronchial asthma.⁴ As a rare multi-system disease, it may affect the skin, eyes, ears, nose, throat, kidneys, intestine, lungs, nerves and the heart.⁵ Cardiac involvement occurred in up to 62% of EGPA cases and was more common in ANCA-negative patients with higher blood eosinophil counts,⁶ being the main cause of morbidity and mortality and an important sign of poor prognosis.⁷

Being a rare disease, EGPA often goes unrecognized, and EGPA manifestations may mimic other diseases and may vary in severity at presentation. When the patient first visited the hospital in 2014, he received symptomatic treatment and was discharged with improvement, but the patient's disease could not be identified. At the patient's second onset, ANCA was negative, and combined with the patient's previous history and the involvement of the cutaneous and cardiac systems, EGPA was finally diagnosed. The patient's symptoms were similar to those of a 48-year-old woman reported in 2021 with acute heart failure and cutaneous lesions.⁸

The patient developed heart failure during the course of the disease. Echocardiography revealed a mass at the apex of the left ventricle, cardiac tumours or cardiac thrombosis was highly suspected, but the nature of the mass could not be determined due to the lack of a pathological biopsy. Given the diagnostic benefits of CMR for soft tissues, we performed CMR on the patient. The CMR findings suggested a low likelihood of a tumour. Considering the patient's condition, we opted against surgical intervention and instead opted for ongoing surveillance, aligning with the recommendations from the specialized cardiology hospital. It was identified as a thrombus in 2016, and anti-immune and antithrombotic treatment was adopted. After nearly 10 years of follow-up with EGPA treatment, it was observed that the mass gradually shrank (from 39 × 21 mm in 2014 to 7 × 14 mm in 2023), indicating a myocardial eosinophilic granuloma.

Several cases of ventricular intracardiac masses have been reported in the literature.^9-12 Regarding whether it is thrombosis or eosinophilic granuloma and how to treat it, there is still some debate, but a mass formed due to cardiac involvement in EGPA responds well to immunosuppressive and antithrombotic treatment.¹³

A case of a 44-year-old woman diagnosed with EGPA has been presented, reporting the regression of a mass of the left ventricle involving the mitral valve after therapy to avoid surgery,⁹ highlighting the importance of a comprehensive, multidisciplinary approach to patients with EGPA with cardiac involvement.

There are differing opinions when faced with an intracardiac mass in systemic autoimmunity. Consider management with immunosuppression rather than anticoagulation, as the mass could resolve rapidly. The left ventricular outflow mass of a 35-year-old Black Saudi man resolved shortly after pulse steroids, indicating an inflammatory mass.¹⁰ In the EGPA case of a 53-year-old man, multiple mobile structures originating from the left ventricular septum disappeared completely after 10 days of steroid therapy.¹¹

However, in the CSS case of a 47-year-old woman, there was almost complete resolution of the gigantic thrombus attached to the left ventricular walls in 7 days, resulting from the low molecular weight heparin regimen.¹² The response to immunosuppressive therapy later, according to the recommendation from a rheumatologist, was satisfactory. Medical management with specific aetiology (anticoagulation or immunosuppression) and heart failure treatment resulted in clinical improvement, but the cause and treatment of heart masses in EGPA cases remain to be further explored.

In 2014, there were few case reports about EGPA, and doctors faced challenges in diagnosing and treating patients with this condition. Once the patient's condition stabilized, a long-term maintenance dose of methylprednisolone was administered, effectively controlling respiratory symptoms. Blood routine results indicated eosinophil levels remained within the normal range. Despite several attempts to discontinue steroid use, each resulted in symptom rebound (Figure 1C). Long-term use of methylprednisolone tablets at 5 mg/day for maintenance therapy is crucial. During episodes of upper respiratory tract infections or pneumonia, exacerbation of breathing difficulties and lower limb oedema may occur, necessitating temporary treatment with methylprednisolone at 40 mg/day for 3–5 days. For EGPA patients, immunotherapy should be continued long term even after eosinophil stabilization, with dosage gradually tapered to maintenance levels.

In conclusion, diagnosing EGPA remains challenging, and the development of predictive biomarkers would significantly enhance the ability to determine its clinical course. As emphasized by the recommendations of the European Society of Cardiology Heart Failure Guidelines,¹⁴ investigating specific causes of heart failure is crucial, as aetiological treatment of the underlying disease is paramount, along with guideline-directed medical therapy to manage patients' clinical condition and prognosis. The 10-year follow-up of the patient demonstrated that long-term use of low-dose glucocorticoid maintenance therapy effectively controlled the condition, offering insights for developing subsequent treatment strategies for EGPA.

None declared.

This study was supported by the Specialized Department of Shanghai Chinese Traditional Medicine Project (No. ZYTSZK1-05).