Eosinophilic granulomatous polyangiitis with central nervous system involvement in children: a case report and literature review.

Objective: To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA). Methods: A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition. Results: A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils. Conclusion: The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.

The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 266 AAV patients.

OBJECTIVES: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry. METHODS: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019. RESULTS: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%). CONCLUSIONS: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.

Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Benralizumab, a monoclonal antibody against the interleukin-5α receptor expressed on eosinophils, may be an option for treating EGPA. METHODS: We conducted a multicenter, double-blind, phase 3, randomized, active-controlled noninferiority trial to evaluate the efficacy and safety of benralizumab as compared with mepolizumab. Adults with relapsing or refractory EGPA who were receiving standard care were randomly assigned in a 1:1 ratio to receive benralizumab (30 mg) or mepolizumab (300 mg) subcutaneously every 4 weeks for 52 weeks. The primary end point was remission at weeks 36 and 48 (prespecified noninferiority margin, -25 percentage points). Secondary end points included the accrued duration of remission, time to first relapse, oral glucocorticoid use, eosinophil count, and safety. RESULTS: A total of 140 patients underwent randomization (70 assigned to each group). The adjusted percentage of patients with remission at weeks 36 and 48 was 59% in the benralizumab group and 56% in the mepolizumab group (difference, 3 percentage points; 95% confidence interval [CI], -13 to 18; P = 0.73 for superiority), showing noninferiority but not superiority of benralizumab to mepolizumab. The accrued duration of remission and the time to first relapse were similar in the two groups. Complete withdrawal of oral glucocorticoids during weeks 48 through 52 was achieved in 41% of the patients who received benralizumab and 26% of those who received mepolizumab. The mean (±SD) blood eosinophil count at baseline was 306.0±225.0 per microliter in the benralizumab group and 384.9±563.6 per microliter in the mepolizumab group, decreasing to 32.4±40.8 and 71.8±54.4 per microliter, respectively, at week 52. Adverse events were reported in 90% of the patients in the benralizumab group and 96% of those in the mepolizumab group; serious adverse events were reported in 6% and 13%, respectively. CONCLUSIONS: Benralizumab was noninferior to mepolizumab for the induction of remission in patients with relapsing or refractory EGPA. (Funded by AstraZeneca; MANDARA ClinicalTrials.gov number, NCT04157348.).

Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. OBJECTIVE: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. METHODS: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. RESULTS: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. CONCLUSIONS: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.

Safety of dupilumab in T2 airways conditions: focus on eosinophilia across trials and real-life evidence.

INTRODUCTION: Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, effectively blocks both IL-4 and IL-13 mediated pathways. Its introduction has represented a significant advancement in the treatment of severe asthma and other Type 2 (T2) conditions, including nasal polyps, atopic dermatitis, and eosinophilic esophagitis. To date, Dupilumab has demonstrated optimal efficacy and safety profile. AREAS COVERED: The safety profile of dupilumab has been extensively studied, especially for its effects on blood eosinophil count. Transient eosinophil increase during treatment is typically insignificant from a clinical point of view and related to its mechanism of action. Rare cases of hyper-eosinophilia associated with clinical conditions like eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) have been reported. Those cases are often related to the drug's steroid-sparing effect or the natural trajectory of the underlying disease rather than a direct cause-effect relationship with dupilumab. EXPERT OPINION: The management of hyper-eosinophilia during dupilumab treatment requires comprehensive diagnostic work-up and strict follow-up monitoring for early detection of systemic disease progression in order to avoid unnecessary discontinuation of an effective treatment. This approach highlights the importance of a personalized treatment.

Azathioprine vs methotrexate in eosinophilic granulomatosis with polyangiitis: a monocentric retrospective study.

OBJECTIVES: To analyse the effectiveness, safety and steroid-sparing effect of AZA and MTX as induction of remission and maintenance treatment in eosinophilic granulomatosis with polyangiitis. METHODS: We retrospectively collected data from 57 patients divided into four groups according to treatment: MTX/AZA as first-line agents (MTX1/AZA1) in non-severe disease or as second-line maintenance therapy (MTX2/AZA2) in severe disease previously treated with CYC/rituximab. During the first 5 years of treatment with AZA/MTX we compared the groups according to: remission rate [defined as R1: BVAS = 0; R2: BVAS = 0 with prednisone ≤5 mg/day; R3 (MIRRA definition): BVAS = 0 with prednisone ≤3.75 mg/day], persistence on therapy, cumulative glucocorticoid (GC) dose, relapse and adverse events (AEs). RESULTS: There were no significant differences in remission rates (R1) in each group (63% in MTX1 vs 75% in AZA1, P = 0.53; 91% in MTX2 vs 71% in AZA2, P = 0.23). MTX1 allowed R2 more frequently in the first 6 months compared with AZA1 (54% vs 12%, P = 0.04); no patients receiving AZA1 achieved R3 up to the first 18 months (vs 35% in MTX1, P = 0.07). The cumulative GC dose was lower for MTX2 vs AZA2 (6 g vs 10.7 g at 5 years, P = 0.03). MTX caused more AEs compared with AZA (66% vs 30%, P = 0.004), without affecting the suspension rate. No differences emerged in time-to-first relapse, although fewer patients treated with AZA2 had asthma/ENT relapses (23% vs 64%, P = 0.04). CONCLUSION: A significant proportion of patients achieved remission with both MTX and AZA. MTX1 had an earlier remission on a lower GC dose but MTX2 had a better steroid-sparing effect.

Pregnancies in women with antineutrophil cytoplasmatic antibody associated vasculitis.

PURPOSE OF REVIEW: Antineutrophil cytoplasmatic antibody associated vasculitis (AAV) usually manifests after age fifty, thus making it very rare during reproductive age. Although rare, AAV, particularly eosinophilic granulomatosis with polyangiitis, can manifest at a younger age. AAV can also appear for the first time during pregnancy. RECENT FINDINGS: Data from pregnant patients with AAV mostly derive from case reports or retrospective studies, with an absolute number of <100 published cases. Therefore, numbers of results of pregnancy outcome vary widely. SUMMARY: As with other chronic autoimmune diseases, patients and infants seem to be at a higher risk for preterm delivery, intrauterine growth retardation and preeclampsia. Possible treatment for AAV in pregnancy depends upon gestational age and include glucocorticosteroids, azathioprine, intravenous immunoglobulins, and in severe cases rituximab and even cyclophosphamide. Plasma exchange might be an option in selected patients. Aside from cyclophosphamide these medications can also be used during breastfeeding. Acetylsalicylic-acid 100-150 mg/day reduces the risk of preeclampsia, also in this population. Patients should be counseled prior to conception and medication that is suitable for pregnancy should be established early on. During pregnancy, we recommend close monitoring of disease activity, blood pressure and ideally to co-consult with a gynecologist in an interdisciplinary approach.

[Eosinophilic small vessel vasculites (EGPA) a hidden severe asthma comorbitity].

A 72-year-old woman presented to the emergency department due to worsening dyspnea. She had been diagnosed with asthma a year earlier. At arrival, her oxygen saturation was only 84%. During lung auscultation, wheezing was noted over all lung fields. A blood test showed a significant increase in eosinophils in peripheral blood, highest value of 1.4 x 10E9/L. Further investigations in the respiratory ward showed a positive MPO-ANCA, which, together with clinical features of asthma, chronic rhinosinusitis with polyps, mononeuritis multiplex and eosinophilia, led to the diagnosis of eosinophilic granulomatosis with polyangiitis, or what used to be called Churg-Strauss syndrome. Corticosteroid treatment was initiated and subsequently tapered down when treatment with mepolizumab was started, which is an IL-5 inhibitor. Her symptoms quickly became much better. Frequent exacerbations and pulmonary symptoms became things of the past.

Eosinophilic Granulomatosis With Polyangiitis Following COVID-19 Vaccination: A Case Report.

The current emergence of the coronavirus disease 2019 (COVID-19) pandemic and the possible side effects of COVID-19 mRNA vaccination remain worrisome. Few cases of vaccination-related side effects, such as vasculitis, have been reported. Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a type of vasculitis characterized by the histological richness of eosinophils, asthma, polyneuropathy, sinusitis, and skin or lung involvement. Here, we report the first case of new onset EGPA following COVID-19 vaccination in Korea. A 71-year old woman developed a skin rash and presented with progressive weakness of the upper and lower extremities after the BNT162b2 vaccination (Pfizer-BioNTech). She was diagnosed with EGPA and her symptoms improved after systemic steroid and immunosuppressant therapy. Although it is very rare, clinicians should be aware that EGPA may occur after COVID-19 vaccination.

ANCA-negative ANCA-associated vasculitis: pitfalls of the 'vasculitis screen'.

Despite its recognition as an 'ANCA-associated vasculitis' (AAV), eosinophilic granulomatosis with polyangiitis (EGPA) is ANCA negative in up to 60% of cases. Herein, we report the case of a young man with a clinical syndrome highly suggestive of EGPA but with repeated negative ANCA serology, ultimately presenting with cardiac arrest before recognition of the primary systemic vasculitis, whereupon he received successful induction therapy with high dose glucocorticoids and cyclophosphamide. The case illustrates the importance of awareness of ANCA negative AAV among general physicians in order to minimise morbidity and mortality.

Dupilumab suppresses relapsing chronic eosinophilic pneumonia with severe asthma.

Dupilumab-induced hypereosinophilia is mediated by blockade of the IL-4/IL-13 pathway, which reduces eosinophil migration from peripheral blood. The increase in peripheral blood eosinophils may lead to chronic eosinophilic pneumonia (CEP) and/or eosinophilic granulomatosis with polyangiitis, but a direct causal connection between dupilumab and eosinophilic lung diseases has not been established. A 33-year-old Japanese woman with bronchial asthma since age three was treated with fluticasone propionate plus salmeterol twice daily after several asthma exacerbations at age 17. Her course was complicated by CEP at age 33 which resolved without the need for systemic steroids. However, in the four months following resolution of her CEP, the patient had three asthma exacerbations, and a recurrence of CEP, with blood leukocytes of 8500/µL, of which 25.0% were eosinophils. She was treated with prednisolone 50 mg/day, but she could not continue this dose due to the onset of myalgia. Then she had relapsing CEP twice within three months. She was treated with prednisolone 15 mg/day for CEP, but she had persistent asthma for more than one month; dupilumab was added at 600 mg, followed by 300 mg every two weeks. In the first month of treatment with dupilumab, the patient's asthma symptoms resolved completely, and she had only one relapse of CEP. In 12 months of follow-up, she had neither an asthma exacerbation nor another relapse of CEP. Dupilumab may be a promising treatment for patients with refractory asthma complicated by recurring CEP and undesirable steroid side effects.

Eosinophilic granulomatosis with polyangiitis: sequential use of mepolizumab following rituximab for inadequate asthma control despite vasculitis remission.

We report the case of a 54-year-old woman with antineutrophilic cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis presenting with mononeuritis multiplex, intestinal hemorrhage, cardiomyopathy, fever, and worsening asthma symptoms. She was initially treated with steroids and cyclophosphamide but eventually required rituximab to control a vasculitis flare. However, her asthmatic symptoms did not improve, despite attaining vasculitis remission. Symptoms abated only after the treatment transition to mepolizumab. After a 1-year interval, there were no further episodes of asthma exacerbation and no requirement for systemic steroid therapy. This report reinforces the use of rituximab for induction and maintenance of remission in patients with eosinophilic granulomatosis with polyangiitis and predominant vasculitic manifestations, whereas mepolizumab demonstrated better control of the persistent eosinophilic manifestations, ensuing sustained remission and improved quality of life.

[Anti-IL-5 in severe asthma associated with eosinophilic granulomatosis with polyangiitis. Real-life study]. / Anti-IL-5 dans l'asthme sévère associé à une granulomatose éosinophilique avec polyangéite. Étude en vie réelle.

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of necrotizing vasculitis affecting small vessels and typically characterized by severe glucocorticoid (GC)-dependent eosinophilic asthma. While mepolizumab, which is indicated at a dose of 100mg/4weeks in severe eosinophilic asthma, has been shown to be an effective treatment for EGPA-related asthma at a dose of 300mg/4weeks, it was only recently approved at this dose. METHODS: This retrospective, single-center, observational study was conducted to investigate over a 5-year period (2014-2019) the effect of mepolizumab 100mg/4weeks at 12months in patients with EGPA and glucocorticoid-dependant severe asthma. Response to treatment was defined as reduction in daily dose of oral corticosteroids to at most 5mg/day or reduction in annual exacerbation by at least 50%. RESULTS: Thirty patients were included, of whom twenty-three were treated (two were not fully evaluable). Among the 21 evaluable treated patients, 13 (62%) had responded at 12months. At baseline, non-responders had lower FEV1 levels and lower blood eosinophil levels than responders. CONCLUSIONS: Mepolizumab at a "severe asthma" dose (100mg/4weeks) is effective in treatment of GC-dependent severe asthma in most patients with EGPA.

Characteristics and Disease Burden of Patients With Eosinophilic Granulomatosis With Polyangiitis Initiating Mepolizumab in the United States.

BACKGROUND/OBJECTIVE: Although the high disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA) has been established, the disease burden in patients initiating mepolizumab in real-world practice is poorly understood. This study aimed to assess characteristics and burden of real-world patients with EGPA initiating mepolizumab. METHODS: This was a database study (GSK study ID: 214156) of US patients (≥12 years old) with EGPA and ≥1 mepolizumab claim (index date) identified from the Merative MarketScan Commercial and Medicare Supplemental Databases (November 1, 2015, to March 31, 2020). Outcomes assessed in the 12-month baseline period before index (inclusive) included patient characteristics, treatment use, EGPA relapses, asthma exacerbations, health care resource utilization, and costs. RESULTS: In the 103 patients included (mean age, 51.1 years; 63.1% female), the most common manifestations were asthma (89.3%), chronic sinusitis (57.3%), and allergic rhinitis (43.7%). In total, 91.3% of patients had ≥1 oral corticosteroid (OCS) claim (median dose, 7.4 mg/d prednisone-equivalent), 45.6% were chronic OCS users (≥10 mg/d during the 90 days preindex), 99.0% had ≥1 EGPA-related relapse, and 62.1% ≥1 asthma exacerbation. During the baseline period, 26.2% and 97.1% of patients had EGPA-related inpatient admissions and office visits, respectively. Median all-cause total health care costs per patient were $33,298, with total outpatient costs ($16,452) representing the largest driver. CONCLUSIONS: Before initiating mepolizumab, a substantial real-world EGPA disease burden is evident for patients, with resulting impact on health care systems, and indicative of unmet medical needs. Mepolizumab treatment, with a demonstrated positive clinical benefit-risk profile may represent a useful treatment option for reducing EGPA disease burden.

Eosinophilic granulomatosis polyangiitis (EGPA) complicated with periaortitis, precipitating role of dupilumab? A case report a review of the literature.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an ANCA-associated vasculitis that affects small size vessels. Only four cases of periaortitis associated with EGPA have been reported in the literature. We report the case of a 67-year-old woman with EGPA who developed periaortitis 11 months after the initiation of dupilumab for uncontrolled asthma with hypereosinophilia. Complete remission of the periaortitis, and of EGPA, was obtained after switching from dupilumab to mepolizumab combined with oral prednisone therapy. Dupilumab has been associated with hypereosinophilia, that is usually asymptomatic and transitory, but symptomatic cases including EGPA were exceptionally reported. Although causality has not yet been established, caution is advisable when prescribing dupilumab for uncontrolled asthma with features that might suggest EGPA.