Eosinophilic granulomatosis with polyangiitis: case report and literature review

Vardah Alam; Alexandra M. Nanzer

doi:10.1183/20734735.0170-2022

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FIGURE 1
Three clinical phases of eosinophilic granulomatosis with polyangiitis.
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FIGURE 2
a) Eosinophilic tissue infiltration. b) Vasculitic rash in a patient with eosinophilic granulomatosis with polyangiitis (EGPA). c) Cardiac magnetic resonance imaging (MRI), T2W MRI showing an area of high signal in an acutely injured, inflamed inferior wall in a patient with EGPA (image courtesy of Tevfik Ismail, Consultant Cardiologist, Guy's and St Thomas' NHS Trust). d, e) Computed tomography (CT) of the chest showing peribronchovascular and patchy ground-glass opacification in a 45-year-old male patient (d) and 48-year-old female (e) patient with EGPA. Images in panels a, b, d and e are the authors’ own, all images are published with patient consent.

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TABLE 1

Clinical and genetic subset of eosinophilic granulomatosis with polyangiitis and anti-neutrophil cytoplasmic antibody (ANCA) status

	ANCA positive	ANCA negative
Genetic association	HLA DQA1 and HLA DRB1	GPA33 and IL-5/IRF1
Pathogenesis	Vasculitis Similar to other ANCA-associated vasculitis syndromes	Eosinophilic infiltration Similar to asthma
Organ involvement	Glomerulonephritis Alveolar haemorrhage Peripheral neuropathy	Pulmonary infiltrates Cardiomyopathy Purpura

TABLE 2

The 2022 American College of Rheumatology/European Alliance of Associations eosinophilic granulomatosis with polyangiitis classification criteria

Clinical criteria	Obstructive airway disease	+3
	Nasal polyps	+3
	Mononeuritis multiplex	+1
Laboratory criteria	Blood eosinophil count ≥1×10⁹ cells per L	+5
	Biopsy evidence of extravascular eosinophilic inflammation	+2
	Positive test for cytoplasmic antineutrophilic cytoplasmic antibodies (cANCA) or anti-proteinase 3 (PR3) antibodies	−3
	Haematuria	−1

Reproduced from [41] with permission.

TABLE 3

The European Respiratory Society eosinophilic granulomatosis with polyangiitis diagnostic criteria

Asthma

Blood eosinophil count ≥1×10⁹ cells per L

And at least two of the following:

ANCA positivity (myeloperoxidase or proteinase 3)

Palpable purpura

Alveolar haemorrhage

Glomerulonephritis

Cardiomyopathy

Histopathological evidence of eosinophilic vasculitis

Sino-nasal disease

Non-fixed pulmonary infiltrates

Mono or polyneuropathy

Information from [13].

TABLE 4

Summary of trials investigating the use of anti-IgE and anti-IL-5/5R monoclonal antibodies in EGPA

Name of biologic and target	First author [ref.], year	Study type	Number of patients, other immunosuppresants	Remission or response definition and end-points	Results
Rituximab, anti-CD20	Teixeira [66], 2019	Retrospective cohort study	69 patients; other immunosuppressants allowed but not specified	Vasculitic end-point: BVAS of 0 with <5 mg·day⁻¹ of oral glucocorticoid	58% of patients achieved remission with 7% being in remission with no corticosteroid need. 54% of patients relapsed by 24 months. ANCA-positive patients had a significantly longer relapse-free survival time than ANCA-negative. The median prednisolone dose reduced at 6, 12 and 24 months from 12.5 to 7, 7.5 and 5 mg·day⁻¹.
	Thiel [64], 2017	Retrospective cohort study	14 patients; methotrexate, azathioprine, MMF	Vasculitic end-point: BVAS of 0 and ≤7.5 mg·day⁻¹ of prednisolone	28 patients with severe organ threatening EGPA previously refractory to other immunosuppressive treatment regimens were treated with rituximab (n=14) or cyclophosphamide (n=14). 36% on rituximab and 29% on cyclophosphamide achieved complete remission at 48 months. Both groups had a significant decrease in median prednisolone dose.
	Mohammad [63], 2016	Retrospective cohort study	41 patients; MMF, azathioprine, cyclophosphamide, methotrexate, i.v. immunoglobulin	Vasculitic end-point: BVAS of 0 with <7.5 mg·day⁻¹ of oral glucocorticoid	49% of patients achieved remission with 5% not requiring glucocorticoids at 12 months. 10% of patients relapsed after achieving remission. The average oral glucocorticoid requirement decreased. ANCA-positive patients had a higher remission rate at 12 months.
Omalizumab, anti-IgE	Celebi Sozener[67], 2018	Retrospective cohort study	18 patients; other immunosuppressants allowed but not specified	Eosinophilic end-point: Absence of asthma and/or ENT exacerbations with a prednisolone dosage of ≤7.5 mg day⁻¹	Full response in 55.6% of patients, no response in 38.9%. Daily OCS dose and asthma exacerbations reduced over 52 weeks.
Omalizumab, anti-IgE	Jachiet [68], 2016	Retrospective cohort study	17 patients; MMF, azathioprine, methotrexate	Eosinophilic and vasculitic end-points: Response: absence of asthma and/or sino-nasal exacerbations with prednisolone dose <7.5 mg·day⁻¹ BVAS and CRP levels	Full response in 35%, partial response in 30% of patients on ≥7.5 mg·day⁻¹ of prednisolone. Reducing OCS was potentially associated with severe EGPA flares.
Reslizumab, anti-IL-5	Manka [69], 2021	Open-label pilot study	10 patients; MMF, azathioprine, methotrexate	Eosinophilic and vasculitic end-points: Worsening symptoms needing increased mOCS, physiological and blood markers	Reduction in OCS dose. At the end of the trial, 75% of patients were receiving OCS ≤5 mg and 37.5% of patients received 0 mg. 67.25% of patients were able to taper their OCS dose without having an exacerbation of their symptoms. Improvement of BVAS.
Reslizumab, anti-IL-5	Kent [70], 2020	Prospective cohort study	9 patients; continuation of other immunosuppressants not mentioned	Eosinophilic and vasculitic end-points: ACQ-7 score, mini-AQLQ, FEV₁, BVAS, peripheral eosinophil count	Significant reduction in OCS dose from 23.4 mg·day⁻¹ to 5.9 mg·day⁻¹ at 48 months. All patients had a ≥50% reduction of median OCS dose. Significant improvement in mini-AQLQ score but not in ACQ-7 score, BVAS and spirometry.
Mepolizumab, anti-IL-5	Bettiol [15], 2022	Retrospective cohort study	191 patients; MMF, azathioprine, methotrexate, cyclosporine, rituximab, i.v. immunoglobulin	Vasculitic and eosinophilic end-point: Response: No disease activity (BVAS=0) and prednisolone or prednisone dose (or equivalent) of ≤4 mg·day⁻¹ Relapse includes worsening asthma symptoms	30.4% and 35.7% of patients achieved complete response at 12 and 24 months. 31% of patients relapsed after remission for a median of 6 months.
	Steinfeld [71], 2019	Randomised, placebo-controlled double-blind parallel-group trial	68 patients; other immunosuppressants allowed but not specified	Vasculitic and eosinophilic end-points: Remission: No disease activity (BVAS=0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg·day⁻¹ Relapse: BVAS >0 or worsening ACQ-6	53% of patients achieved remission in the mepolizumab group versus 19% in the placebo group. 57% of patients in the mepolizumab group were able to reduce their OCS dose by ≥50% compared with 21% in the placebo group. 18% of patients were relapse-free in the placebo group compared with 44% in the mepolizumab group.
	Wechsler [13], 2017	Double-blind, parallel-group phase 3 trial	68 patients; other immunosuppressants allowed but not specified	Vasculitic and eosinophilic end-points: Remission: No disease activity (BVAS=0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg·day⁻¹ Relapse includes worsening asthma symptoms	28% of patients receiving mepolizumab and 3% of placebo patients experienced ≥24 weeks of accrued remission. 32% of patients in the mepolizumab group versus 3% in the placebo group achieved remission at both 36 weeks and 48 weeks. Remission didn't occur in 47% of patients in the mepolizumab and 81% of patients in the placebo group. The relapse rate was 1.14 in the mepolizumab group and 2.27 in the placebo group.
Benralizumab, anti-IL-5R	Guntur [46], 2021	Prospective open-label pilot study	10 patients; MMF, azathioprine, methotrexate	Eosinophilic and vasculitic end-points: Worsening symptoms needing increase in mOCS, ACQ, AQLQ, BVAS, physiological and blood markers	Mean OCS dose reduced at the end of the trial period from 15 mg·day⁻¹ to 2 mg·day⁻¹. Mean annualised exacerbation rate was lowest during treatment period compared with the pre- and post-treatment period. No difference in BVAS was noted at the beginning and end of the study.
Benralizumab, anti-IL-5R	Nanzer [14], 2020	Retrospective study	11 patients; continuation of other immunosuppressants not mentioned	Eosinophilic and vasculitic end-points: ACQ-7 score, mini-AQLQ, FEV₁, BVAS, peripheral eosinophil count	At 24 weeks, the median reduction in OCS dose was 50%. 73% of patients reduced their dose by over 50%. At 48 weeks, the median reduction in OCS dose was 65%. 89% of patients were able to reduce their dose by over 50%. A significant improvement was noted in BVAS at 24 and 48 weeks.

IL: interleukin; EGPA: eosinophilic granulomatosis with polyangiitis; BVAS: Birmingham Vasculitis Activity Score; ANCA: anti-neutrophil cytoplasmic antibody; MMF: mycophenolate mofetil; ENT: ear, nose and throat; OCS: oral corticosteroid; CRP: C-reactive protein; mOCS: maintenance OCS; ACQ: Asthma Control Questionnaire; AQLQ: Asthma Quality of Life Questionnaire; FEV₁: forced expiratory volume in 1 s.