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.

[Peripheral Neuropathy in Eosinophilic Granulomatosis with Polyangiitis].

Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic autoantibody-associated vasculitis secondary to inflammation of the small vessels. EGPA-induced neuropathy develops in approximately 90% of patients with peripheral blood eosinophilia and may lead to serious complications of the peripheral nervous system, necessitating emergency therapeutic intervention.

A case of eosinophilic granulomatosis with polyangiitis associated with diffuse alveolar haemorrhage: A case report and case-based review.

A 76-year-old man with bronchial asthma was admitted for respiratory failure and bloody sputum. A significant drop in haemoglobin and multiple consolidations supported clinical diagnosis of diffuse alveolar haemorrhage (AH). Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was positive and urinalysis suggested glomerulonephritis. Based on eosinophilia, sinusitis, peripheral nerve involvement, and leukocytoclastic vasculitis, he was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) associated with AH. Our case-based review suggested that male predominance (65%), high positivity for ANCA (88%), and a high frequency of renal involvement (45%) may be characteristic of AH in EGPA. Although AH is rare in EGPA, we should be aware of this life-threatening complication.

[Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy].

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

[Bronchial asthma and allergic rhinitis-The skin sample reveals a severe systemic disease]. / Asthma bronchiale und allergische Rhinitis ­ die Hautprobe offenbart eine schwerwiegende Systemerkrankung.

This article reports the case of a 30-year-old female patient who suffered for many years from initially unspecific symptoms, such as recurrent, nonallergic and noninfectious sinusitis, late-onset bronchial asthma and pronounced lymphadenopathy; however, the correct diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) could only be made by histological investigations after the appearance of skin symptoms. The EGPA is a severe systemic disease which, if left untreated, can cause multiple organ damage and even be fatal. With adequate treatment the disease is mild in more than 90% of cases and patients can even completely recover. By making the correct diagnosis, the patient could be successfully treated and the risk of late manifestations and subsequent damage with a potentially fatal outcome was reduced.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 2: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (eGPA) are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of GPA and eGPA were collected and reported in this review. RESULTS: 467 references were discovered during literature review process. In total, 42 references for GPA and 35 references for eGPA were included in this review. CONCLUSION: GPA and eGPA are vasculitis syndromes which commonly present in the context of multisystem disease. For GPA, pulmonary and renal disease are common; for eGPA a history of asthma is nearly ubiquitous. Sinonasal disease is a very common feature for both disease processes and may precede the development of systemic symptoms in many patients. Clinical work up and diagnosis is complex and generally requires multidisciplinary care. Treatment primarily consists of immunosuppressive agents, and a number of steroids, steroid sparing agents, and biologics have been shown to be effective. The role of sinus surgery includes tissue biopsy for diagnosis, functional surgery for symptom management in select cases, and reconstruction of cosmetic and functional defects.

Evaluation of Ministry of Health, Labour and Welfare diagnostic criteria for antineutrophil cytoplasmic antibody-associated vasculitis compared to ACR/EULAR 2022 classification criteria.

OBJECTIVE: This study aimed to evaluate the Ministry of Health, Labour and Welfare (MHLW) diagnostic criteria for antineutrophil cytoplasmic antibody-associated vasculitis compared to the new American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria. METHODS: Two nationwide cohort studies were used, and participants were categorised as having eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 and MHLW criteria. RESULTS: Of the entire patient population, only 10 (2.1%) were unclassifiable according to the MHLW probable criteria, while a significant number of patients (71.3%) met at least two criteria. The MHLW probable criteria for MPA had some challenges in differentiating between MPA and eosinophilic granulomatosis with polyangiitis, and the same was true for MHLW probable criteria for GPA in differentiating MPA from GPA. Nevertheless, improved classification results were obtained when the MHLW probable criteria were applied in the order of eosinophilic granulomatosis with polyangiitis, MPA, and GPA. CONCLUSIONS: The application of MHLW criteria could categorise a substantial number of patients with antineutrophil cytoplasmic antibody-associated vasculitis into one of the three antineutrophil cytoplasmic antibody-associated vasculitis diseases. The classification was in accordance with the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria when considering the order of application.

A case of subarachnoid haemorrhage associated with MPO-ANCA-positive eosinophilic granulomatosis with polyangiitis, successfully treated with glucocorticoid, cyclophosphamide, and mepolizumab.

Subarachnoid haemorrhage (SAH) is a quite rare but serious central nervous system complication of eosinophilic granulomatosis with polyangiitis (EGPA). We report a case of myeloperoxidase antineutrophil cytoplasmic antibody-positive EGPA in which SAH developed during glucocorticoid induction pulse therapy for skin purpura, peripheral neuropathy, and rapidly progressive glomerulonephritis. In addition to high-dose glucocorticoid and intravenous cyclophosphamide, we administered mepolizumab, a humanised anti-interleukin-5 monoclonal antibody, and this resulted in remission of the SAH. Although the pathogenesis of SAH in EGPA is not fully understood, both necrotising vasculitis and eosinophilic inflammation are thought to be involved. In addition to prompt intensive immunosuppressive therapy, mepolizumab should be considered for SAH associated with EGPA.

[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.

Acute paraplegia in a patient with eosinophilic granulomatosis and polyangiitis with 20 years of evolution: case report.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare and necrotizing vasculitis of small and medium vessels with a heterogeneous presentation, multiorgan involvement, characterized by the presence of chronic rhinosinusitis, asthma, and peripheral eosinophilia. Nervous system involvement is frequent, especially in the peripheral nervous system (PNS), in the form of mononeuritis multiplex. However, subarachnoid and cerebral hemorrhage, cerebral infarction, cranial nerve palsies, and cortical blindness have also been reported in the literature. Initial therapy involves systemic GC, which are not free of complications. We present the case of a patient with EGPA of more than 20 years duration who suddenly developed bilateral paresthesia of the lower limbs and urinary retention. The neurological exam revealed paraplegia with a sensorial level in D4; the MRI showed spinal cord compression in the D2-D7 level, and the patient was emergently submitted to surgical decompression. The histopathology of the surgical specimen demonstrated the presence of epidural adipose tissue with multiple vasculitic lesions. The effects of systemic corticosteroid therapy may contribute to abnormal fat deposition in various body segments, including the neuroaxis, leading to the development of epidural lipomatosis. However, the intra-lesional vasculitic character is a unique manifestation of myelopathy that has shown us to have a more aggressive attitude.

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.

[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.

Diagnostic challenge of Creutzfeldt-Jakob disease in a patient with multimorbidity: a case-report.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its subtype, and may include dementia, visual hallucinations, myoclonus, ataxia, (extra)pyramidal signs and akinetic mutism. In the early course of disease however, several clinical symptoms of CJD may mimic those of co-existing morbidities. CASE PRESENTATION: We report a male in his 60s with a history of situs inversus totalis and Churg Strauss syndrome, who presented with speech fluency disturbances, neuropsychiatric symptoms and allodynia, a few months after becoming a widower. Initially presumed a bereavement disorder along with a flare-up of Churg Strauss, his symptoms gradually worsened with apraxia, myoclonic jerks and eventually, akinetic mutism. MRI revealed hyperintensities at the caudate nucleus and thalami, while the cerebrospinal fluid was positive for the 14-3-3 protein and the real-time quick test, making the diagnosis of CJD highly probable. This case illustrates the complexities that may arise in diagnosing CJD when pre-existing multimorbidity may cloud the clinical presentation. We also discuss the potential mechanisms underlying the co-occurrence of three rare conditions (situs inversus totalis, Churg Strauss syndrome, CJD) in one patient, taking into consideration the possibility of coincidence as well as common underlying factors. CONCLUSIONS: The diagnosis of CJD may be easily missed when its clinical symptoms are obscured by those of pre-existing (rare) multimorbidity. This case highlights that when the multimorbidity has neurological manifestations, an extensive evaluation remains crucial to establish the diagnosis, minimize the risk of prion-transmission and provide appropriate guidance to patients and their caregivers.