P0373MEPOLIZUMAB THERAPY FOR EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA) - ONE YEAR FOLLOW-UP STUDY USING ANTI-IL5 AS A STEROID SPARING THERAPEUTIC APPROACH

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Allyson Egan ◽  
Pasupathy Sivasothy ◽  
Robin Gore ◽  
Marcos MartinezDel-Pero ◽  
Lisa Willcocks ◽  
...  

Abstract Background and Aims EGPA is a small vessel vasculitis characterised by the presence of tissue eosinophilia, necrotising vasculitis and granulomatous inflammation1. Typically, a prodromal asthmatic phase, leads to an eosinophilic stage, which can evolve to include the presence of vasculitis with renal manifestations. In the recent randomised, placebo-controlled MIRRA trial for relapsing and refractory EGPA, adjuvant therapy with anti-IL5 mAB Mepolizumab [MEPO] at 300mg s/c monthly, accrued longer times in remission, reduced steroid exposure and reduced relapse rates2. The aim of our study was to analyse the response and outcome for EGPA patients who received 100mg s/c of MEPO monthly for a minimum of 52 weeks, with particular focus on the steroid minimisation benefits. Method This retrospective, descriptive study analysed 13 patients with EGPA, who received 100mg s/m monthly MEPO therapy under the eosinophilic asthma care-pathway. Time points of assessment included MEPO commencement [M0] and 12 [M12] months. Results One patient had MEPO switched to Rituximab to treat both EGPA and new onset rheumatoid arthritis Conclusion The relapsing nature of EGPA places a potential dependency of therapy on steroids for asthmatic and vasculitic flares. This underscores the importance of targeted pathway specific biologic therapy to minimise steroid exposure, prevent tissue damage and ensure early response to therapy. This study demonstrates that anti-IL5 serves as a favourable model with steroid minimisation, improvement in asthma control questionnaire, reduction in BVAS and eosinophil counts at the 100mg s/c dosage. ANCA positive serology normalised in all four patients, independent of subtype. Well tolerated, it demonstrated considerable clinical benefit, with 12 patients [92.3%] continuing anti-IL5 therapy beyond 12 months. Adjuvant therapy with conventional immunosuppressants was well tolerated and renal function was preserved. ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. J.C.Jenette, et al Revised International Chapel Hil Consensus Conference Nomenclature of Vasculitides. 65, 1–11 (2013). 2. Wechsler, M. E. et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N. Engl. J. Med. 376, 1921–1932 (2017).

Chest Imaging ◽  
2019 ◽  
pp. 355-359
Author(s):  
Felipe Martínez

Vasculitis refers to inflammation of blood vessel walls that results in vascular wall destruction and ischemic injury to affected organs. Common vasculitides discussed herein include Takayasu arteritis (TAK), giant cell arteritis (GCA), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides such as granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA), and anti-glomerular basement membrane (anti-GBM) disease or Goodpasture syndrome. Vasculitides are further subcategorized depending of the size of the predominantly affected vessels: large, medium and small vessel vasculitis. The affected vessel size strongly influences the clinical and imaging manifestations of the disease. Intrathoracic involvement is more common in small and large vessel vasculitides. Diffuse alveolar hemorrhage (DAH), a common manifestation of vasculitis, is considered a syndrome rather than a specific entity and will be discussed in this chapter. However, it should be noted that DAH may also result from non-vasculitic etiologies. The work up and diagnosis of patients with primary vasculitides is challenging and requires close collaboration between the clinician, the radiologist and the pathologist. Radiographic abnormalities are non specific or may be absent. CT and MRI are the imaging modalities of choice for the evaluation and follow up of these patients, and should be considered despite normal radiographics.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_3) ◽  
pp. iii84-iii94 ◽  
Author(s):  
Giorgio Trivioli ◽  
Benjamin Terrier ◽  
Augusto Vaglio

Abstract Eosinophilic granulomatosis with polyangiitis is characterized by asthma, blood and tissue eosinophilia and small-vessel vasculitis. The clinical presentation is variable, but two main clinic-pathologic subsets can be distinguished: one hallmarked by positive ANCA and predominant ‘vasculitic’ manifestations (e.g. glomerulonephritis, purpura and mononeuritis multiplex) and the other by negative ANCA and prominent ‘eosinophilic’ manifestations (e.g. lung infiltrates and cardiomyopathy). The pathogenesis is not fully understood but probably results from the interplay between T and B cells and eosinophils. Eosinophilic granulomatosis with polyangiitis must be differentiated from several conditions, including hypereosinophilic syndromes and other small-vessel vasculitides. The overall survival is good; however, patients frequently relapse and have persistent symptoms. The recently developed monoclonal antibodies targeting B cells and eosinophilopoietic cytokines such as IL-5 are emerging as valid alternatives to conventional immunosuppressive therapies. In this review, we discuss the essential features of eosinophilic granulomatosis with polyangiitis, with particular respect to the most relevant issues concerning clinical presentation and management.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Carlos Martínez-Rivera ◽  
Ignasi Garcia-Olivé ◽  
Blanca Urrutia-Royo ◽  
Maria Basagaña-Torrento ◽  
Antoni Rosell ◽  
...  

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease that is associated with severe uncontrolled eosinophilic asthma. Eosinophils play an important pathogenic role in the development of both diseases. Benralizumab is an antieosinophilic monoclonal antibody that binds to the α subunit of the human interleukin 5 receptor that is expressed on the surface of the eosinophil and basophil. We present the first case of rapid improvement in symptoms and lung function during admission for exacerbation of a severe eosinophilic asthma associated with EGPA. Case presentation A 57-year-old man diagnosed with severe eosinophilic asthma associated to EGPA was admitted to the Pulmonology Department due to severe bronchospasm. At admission he presented 2300 eosinophils/µl. Despite intensive bronchodilator treatment, intravenous methylprednisolone at a dose of 80 mg/d, oxygen therapy, and budesonide nebulization, the patient continued to present daily episodes of bronchospasm. Ten days after admission, with blood eosinophil levels of 1700 cells/µl, benralizumab 30 mg sc was administered. That day, the Forced Expiratory Volume in the first second (FEV1) was 28% of the theoretical value (1150 ml). AT three days, FEV1 increased to 110 ml (31%). On the 9th day FEV1 was 51% (2100 ml). The blood eosinophil level on the 9th day was 0 cells/µl. Conclusions The rapid improvement of FEV1 is in line with studies based on clinical trials that found improvement after two days in peak flow and one phase II study that showed rapid response in exacerbation of asthma in the emergency room. The antieosinophilic effect at 24 h and the effect in different tissues determine the rapid improvement and the potential advantage of benralizumab in the treatment of EGPA. This case suggests the usefulness of benralizumab in patients with EGPA and eosinophilic severe asthma who show bronchospasm refractory to conventional treatment during a hospitalization due to asthma exacerbation.


2021 ◽  
Vol 14 (9) ◽  
pp. e243395
Author(s):  
Wataru Shiraishi ◽  
Yoshitaka Tsujimoto ◽  
Tomoko Shiraishi

The most common neurological manifestation of eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is mononeuritis multiplex caused by small-vessel vasculitis. In contrast, central nervous system involvement is rare. Among EGPA-associated central nervous system disorders, there are only a few reported cases of hypertrophic pachymeningitis (HP). Here, we report a patient with EGPA with headache and ophthalmoplegia who presented with HP and had a dural biopsy. The biopsy specimen showed lymphocytic inflammatory cell infiltration without EGPA-specific findings, that is, eosinophilic infiltration, granuloma or angiitis. To the best of our knowledge, there are no previous reports of EGPA-associated HP pathology. Here, we report the first case presentation of a patient with EGPA-associated HP with pathological findings.


2015 ◽  
Vol 2015 ◽  
pp. 1-3
Author(s):  
Carlos R. Camara-Lemarroy ◽  
Adrian Infante-Valenzuela ◽  
Hector J. Villareal-Montemayor ◽  
Carlos A. Soto-Rincon ◽  
Javier A. Davila-Olalde ◽  
...  

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs) which commonly affects the peripheral nervous system. A 38-year-old female with a history of asthma presented with a 2-week history of bilateral lower extremity paresthesias that progressed to symmetric ascending paralysis. Nerve conduction studies could not rule out Guillain-Barre syndrome (GBS) and plasmapheresis was considered. Her blood work revealed marked eosinophilia (>50%), she had purpuric lesions in her legs, and a head magnetic resonance image showed evidence of pansinusitis. Coupled with a history of asthma we suspected EGPA-associated neuropathy and started steroid treatment. The patient showed rapid and significant improvement. ANCAs were later reported positive. ANCA-associated vasculitides present most often as mononeuritis multiplex, but they can mimic GBS and should always be considered in the differential diagnosis, since the treatment strategies for these conditions are radically different.


2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
D. D. K. Abeyaratne ◽  
C. Liyanapathirana ◽  
C. L. Fonseka ◽  
P. W. M. C. S. B. Wijekoon

Background. Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody- (ANCA-) associated small vessel vasculitis with multisystem involvement. It is characterized with asthma, eosinophilia, and renal and peripheral nervous system involvement. However, EGPA presenting with bullous skin eruption is an uncommon dermatological manifestation. We report a rare case of EGPA overlapped with mixed essential cryoglobulinemia presenting with a bullous skin eruption. Case Presentation. A 49-year-old female presented with bilateral lower limb erythematous bullous rash with bilateral lower limb numbness. She had bilateral ankle edema with frothyuria and a recent onset wheeze. Blood investigations revealed a marked peripheral eosinophilia with positive P-ANCA. Skin biopsy was suggestive of leukocytoclastic vasculitis. She also had positive cryoglobulins with a high rheumatoid factor titre. The patient was diagnosed of having EGPA with overlapping mixed essential cryoglobulinemia. Her skin eruptions and systemic manifestations improved with prednisolone and cyclophosphamide therapy. Conclusion. EGPA can rarely present with a bullous skin eruption and may rarely associate with secondary cryoglobulinemia. Early recognition of these rare manifestations and prompt treatment would prevent further complications and death.


Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 359-365 ◽  
Author(s):  
Cécile-Audrey Durel ◽  
Renato A Sinico ◽  
Vitor Teixeira ◽  
David Jayne ◽  
Xavier Belenfant ◽  
...  

Abstract Objective Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort. Methods We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy. Results Sixty-three patients [27 women, median age 60 years (18–83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1–296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation. Conclusion Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases.


Author(s):  
Lota Ozola ◽  
Elīna Aleksejeva ◽  
Diāna Stoldere ◽  
Ineta Grantiņa ◽  
Zane Dāvidsone ◽  
...  

Eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis. It is a multisystem disorder and can affect every organ system. EGPA is a rare disease, with an estimated prevalence of 1/70,000–100,000 in Europe. As its onset usually occurs in adulthood, data from paediatric patients are limited. We present here a very rare practical EGPA clinical case involving a paediatric patient. Presently, data on mepolizumab usage in paediatric patients are limited, with only a few case reports published.


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