Hypertrophic Pachymeningitis, Associated with Eosinophilic Granulomatosis with Polyangiitis, and ANCA-Negative Serology.

Background: Hypertrophic pachymeningitis (HP) is a disease with diverse aetiologies, including the autoimmune one, either associated with antineutrophil cytoplasmic antibodies or immunoglobulin G4. Case description: A 65-year-old woman with a history of systemic arterial hypertension, presented with intense progressive headaches. HP and hemispheric vasogenic oedema were observed by nuclear magnetic resonance (NMR) study. During the six months before the headache, she had developed progressive hearing loss which she attributed to age. A biopsy of dura mater showed necrotising vasculitis with peripheral inflammatory infiltrate, made up of accumulations of epithelioid cells and multinucleated giant cells, and abundant eosinophils. A final diagnosis of HP with eosinophilic granulomatosis with polyangiitis (EGPA) was made. Discussion: The patient had eosinophilic granulomatosis with polyangiitis (EGPA) histology, ANCA-negative serology and HP. This case is important because it shows that EGPA seems to have a spectrum of clinical diseases, including HP with negative serology, and bilateral sensorineural hearing loss. Conclusion: We are facing a wide spectrum of EGPA, breaking the paradigm of only systemic involvement. LEARNING POINTS: Hypertrophic pachymeningitis (HP) has several aetiologies; if the systemic investigation is not contributory to a diagnosis, a meningeal biopsy is necessary.This is the first case report of HP, associated with eosinophilic granulomatosis with polyangiitis (EGPA), and ANCA-negative serology.EGPA is probably a spectrum of diseases with predominant systemic involvement, but there may be cases where there is histological evidence, without the systemic context or positive serology.

A Contemporaneous Onset of Eosinophilic Granulomatosis with Polyangiitis and Myasthenia Gravis: A Case Report.

Autoimmune neuromuscular disorders in patients with eosinophilic granulomatosis with polyangiitis (EGPA) are relatively uncommon. Although two cases of myasthenia gravis (MG) comorbid with EGPA have been reported, both patients developed EGPA several years after starting immunosuppressive treatment for MG. We herein report a 75-year-old man with a rare co-occurrence of EGPA and MG that developed simultaneously and was successfully treated with immunosuppressive therapy. Distinguishing the neurological symptoms of EGPA from complications of other neurological autoimmune diseases, such as MG, is crucial, especially in patients with eosinophilia.

Tezepelumab for refractory eosinophilic granulomatosis with polyangiitis-related asthma.

Conventional immunosuppressants are ineffective for the management of EGPA-related asthma. Tezepelumab is a human monoclonal antibody that inhibits thymic stromal lymphopoietin (TLSP) that has proven efficacy in several phase 3 studies for the treatment of asthma. We treated with off-label tezepelumab the first two patients with severe refractory EPGA-related asthma. These preliminary findings suggest that targeting upstream signaling of the T2 inflammatory pathway can improve symptoms, reduce BVAS and increase Asthma Control Test scores, even in patients with refractory asthma who have failed several previous lines of treatment. Nevertheless, by analogy with dupilumab-induced IL-4/13 blockade, the persistence of sputum eosinophilia (reported in both patients) raises questions as to whether TSLP inhibition could lead to a rebound of eosinophilia and potentially to eosinophil-related symptoms in patients with EGPA.

Granulomatosis With Polyangiitis as an Etiology of Silent Sinus Syndrome: A Case Report.

Silent sinus syndrome (SSS) is a rare condition characterized by the collapse of the maxillary sinus and the sinking of the eye socket (enophthalmos). Only around 100 cases of SSS have been reported so far. The underlying cause of this condition is the chronic obstruction of the osteomeatal complex, which leads to sinus contraction. In this case, we present a novel finding linking SSS with granulomatosis with polyangiitis (GPA). The patient described is a 39-year-old male who was diagnosed with SSS after a prolonged period of sinus pressure, headaches, epistaxis, and generalized congestion. Additionally, the patient reported a significant autoimmune history, including a previous occurrence of ANCA-mediated glomerulonephritis. Surgical intervention revealed the presence of significant granulation tissue, while histopathological examination identified areas of necrosis, vasculitis, and multinucleated giant cells consistent with GPA. This finding was further supported by the detection of positive blood c-ANCA. This case is particularly noteworthy as it is the first reported instance of GPA causing SSS. It serves as an excellent example to illustrate the underlying pathophysiology of SSS.

Granulomatosis With Polyangiitis: Cardiac, Renal, and Respiratory Involvement.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is an anti-neutrophilic cytoplasmic autoantibody (ANCA)-associated small-vessel vasculitis. Typically, it causes upper and lower respiratory tract necrotizing granulomatous inflammation and necrotizing glomerulonephritis. The diagnosis is made through clinical symptoms, positive antibody testing, imaging, and kidney biopsy. We describe the case of a man in his 60s who presented with multiple complications of GPA including rapidly progressive renal failure requiring dialysis, diffuse alveolar hemorrhage, acute respiratory distress syndrome (ARDS), circulatory shock, submassive pulmonary embolism, and biventricular and dilated cardiomyopathy.

Granulomatosis With Polyangiitis and Concomitant Superinfection: A Defying Diagnosis and Management Approach.

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis mainly involving the ear, nose, and upper and lower airways. Diagnosis is based on clinical manifestations, positive antineutrophil cytoplasmic antibodies (ANCA) serology, and histopathological findings. We report a case of inflammatory polyarthralgia with a high titer of rheumatoid factor (RF), which was revealed to be GPA after extensive diagnosis workup. However, the disease was complicated by superinfections, which delayed and limited immunosuppressive treatment. Methotrexate was at last initiated with antibiotic prophylaxis, and there was significant clinical improvement. This case underlines the importance of an adequate diagnosis workup and the difficulties that often arise when other entities are present.

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis: A case report.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA. CASE SUMMARY: The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence. CONCLUSION: For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

Application of biological agents in the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been traditionally treated using glucocorticoids and immunosuppressants. However, these treatment modes are associated with high recurrence AAV rates and adverse reactions. Therefore, treatment strategies for AAV need to be urgently optimized. The efficacy and safety of biological agents in the treatment of vasculitis have been clinically validated. This review comprehensively summarizes the evidence-based support for the clinical use of existing biological agents in AAV. The findings reveal that multiple biological agents not only effectively reduce the adverse reactions associated with glucocorticoids and immunosuppressants but also demonstrate significant therapeutic efficacy. Notably, rituximab, an anti-CD20 antibody, has emerged as a first-line treatment option for AAV. Mepolizumab has shown promising results in relapsed and refractory eosinophilic granulomatosis with polyangiitis. Other biological agents targeting cytokines, complement, and other pathways have also demonstrated clinical benefits in recent studies. The widespread application of biological agents provides new insights into the treatment of AAV and is expected to drive further clinical research. These advancements not only improve patient outcomes but also offer more possibilities and hope in the field of AAV treatment.

A Case of Overlapping Autoimmune Syndrome.

Overlapping autoimmune disorders are used to describe the coexistence of more than one autoimmune disease in the same patient. Mixed connective tissue disease (MCTD) and anti-synthetase syndrome (ASS) are autoimmune diseases that manifest with pulmonary involvement, presenting as persistent dyspnea. The coexistence of both conditions in the same patient is extremely rare. We herein report a case of a 44-year-old female who was diagnosed with MCTD with features of ASS (anti-Jo-1 antibody) in the setting of rheumatoid arthritis (anti-cyclic citrullinated peptide (anti-CCP) antibody), which shows temporary breathing improvement following treatment with corticosteroid and mycophenolate mofetil. However, after the completion of mycophenolate mofetil, she was found to be anti-Jo-1 antibody negative and anti-CCP antibody positive. Our case emphasizes the need to recognize overlapping autoimmune conditions in patients with complex clinical features and presentations with the immediate application of a comprehensive diagnostic approach and tailored treatment strategies. Early diagnosis and aggressive treatment are crucial for achieving remission and preventing organ damage.

Red flags for clinical suspicion of eosinophilic granulomatosis with polyangiitis (EGPA).

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), is a rare ANCA-associated systemic vasculitis. Its overlapping features with other vasculitic or eosinophilic diseases, and the wide and heterogeneous range of clinical manifestations, often result in a delay to diagnosis. OBJECTIVE: To identify red flags that raise a suspicion of EGPA to prompt diagnostic testing and to present an evidence-based clinical checklist tool for use in routine clinical practice. METHODS: Systematic literature review and expert consensus to identify a list of red flags based on clinical judgement. GRADE applied to generate a strength of recommendation for each red flag and to develop a checklist tool. RESULTS: 86 studies were included. 40 red flags were identified as relevant to raise a suspicion of EGPA and assessed by the experts as being clinically significant. Experts agreed that a diagnosis of EGPA should be considered in a patient aged ≥6 years with a blood eosinophil level >1000 cells/µL if untreated and >500 cells/µL if previously treated with any medication likely to have altered the blood eosinophil count. The presence of asthma and/or nasal polyposis should reinforce a suspicion of EGPA. Red flags of asthma, lung infiltrates, pericarditis, cardiomyopathy, polyneuropathy, biopsy with inflammatory eosinophilic infiltrates, palpable purpura, digital ischaemia and ANCA positivity, usually anti-myeloperoxidase, among others, were identified. CONCLUSION: The identification of a comprehensive set of red flags could be used to raise a suspicion of EGPA in patients with eosinophilia, providing clinicians with an evidence-based checklist tool that can be integrated into their practice.

Performance of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for antineutrophil cytoplasmic antibody-associated vasculitis in previously diagnosed adult patients from Türkiye.

Objectives: This study aimed to evaluate the applicability of the new 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria in Turkish adult patients previously diagnosed with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Patients and methods: One hundred sixty-four patients (96 males, 68 females; mean age: 49.6±14.4 years; range, 18 to 87 years) diagnosed with AAV by experienced rheumatologists between July 2016 and May 2022 were included in this retrospective cross-sectional study and reclassified based on the 1990 ACR criteria, the European Medicines Agency (EMEA) algorithm, and the 2022 ACR/EULAR criteria. For external validation, 83 patients (48 males, 35 females; mean age: 47.3±17.5 years; range, 19 to 81 years) diagnosed with immunoglobulin (Ig)A vasculitis were included. Results: One hundred twenty-six (76.8%) patients had granulomatosis with polyangiitis (GPA), 13 (7.9%) patients had eosinophilic granulomatosis with polyangiitis (EGPA), and 25 (15.2%) patients had microscopic polyangiitis (MPA). According to the criteria, the number of unclassified patients was nine (5.5%) for both the 2022 ACR/EULAR AAV classification criteria and the EMEA algorithm. The new criteria had an almost perfect agreement with the clinician's diagnosis (Cohen's kappa coefficient [κ]=0.858 for GPA, κ=0.820 for EGPA, and κ=0.847 for MPA). The kappa statistics for agreement of 2022 ACR/EULAR classification criteria with the EMEA algorithm were found 0.794 for GPA, 0.820 for EGPA, and 0.700 for MPA. None of the 83 patients diagnosed with IgA vasculitis could be classified as GPA, EGPA, or MPA using the new ACR/EULAR AAV classification criteria. Conclusion: The 2022 ACR/EULAR classification criteria for AAV showed substantial or perfect agreement with the clinical diagnosis and the EMEA algorithm.

The Evaluation of Changing the Eponym Churg-Strauss Syndrome Due to the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

Background: Eponyms do not describe any pathogenesis of a disease. So, there is no other way than to memorize the disease or anatomical area. Over the years, new nomenclatures have been suggested for some diseases due to a better understanding of the pathogenesis. In this article, the changes in the use of Churg-Strauss syndrome were investigated. Methods: In the study, a computerized search was performed using the PubMed database. Books and documents, clinical trials, editorials, meta-analyses, reviews, and case reports were included in the study. Data were obtained from the title of the database, and the variations or distribution by year for the nomenclature of the most related studies were evaluated. Results: Overall, 68.3% of the articles included CSS, 25.7% included eosinophilic granulomatous polyangiitis (EGPA), and 6.0% included both nomenclatures. When evaluated in terms of the distribution according to years, it was determined that there was a statistically significant increase in use in terms of EGPA. When evaluated among specific section journals, the highest rate was in Rheumatology (29.4%). The highest rate of using CSS was in the Rheumatology (25.1%) journals, followed by Pulmonary/Respiratory (17%), Cardiovascular (12%), and Allergy/Immunology/Biology (9.8%). The use of EGPA combined with CSS decreased in all the specific journals from 2012 to the present. Conclusions: The findings of the study revealed that the number of articles with the eponym of EGPA showed an increased frequency in contrast to a decreasing frequency for those with CSS during recent years. Today, with the elaboration of the disease pathogenesis and the increase in knowledge, the trend has shifted in this direction.

Classification Criteria for ANCA Associated Vasculitis - Ready for Prime Time?

PURPOSE OF REVIEW: This review aims to summarize the evolution and recent developments in the classification of ANCA associated vasculitis (AAV) and to summarize evaluations of the 2022 ACR/EULAR classification criteria of AAV in several cohorts. RECENT FINDINGS: The classification of AAV has been a field of controversy for some time. The parallel existence of classification criteria and disease definitions produced some overlap in classification, leading to challenges when comparing different cohorts. The 2022 ACR/EULAR classification criteria derived from the largest study ever conducted in vasculitis account for significant changes in vasculitis classification with the integration of ANCA and modern imaging. These criteria show good performance compared to previous ones but also raise questions as ANCA serotypes have substantial impact on classification. In addition, there are some discrepancies with earlier agreed histopathological features of AAV disease phenotypes. During the last 35 years, several sets of classification criteria have evolved to facilitate epidemiologic studies and clinical trials in AAV. While some of these criteria have been in use for many years, they were criticized due to either not using ANCA or not integrating surrogate markers for vasculitis but also due to overlapping when used in parallel. The long-awaited new ACR/EULAR criteria for AAV were published in 2022 and are the result of a large international study, introducing for the first time ANCA and modern imaging in the classification of AAV. Though the criteria show good performance, they bring several other challenges with practical application.

Subarachnoid Hemorrhaging with Multiple Cerebral Artery Stenoses after Initiating Remission Induction Therapy for Eosinophilic Granulomatosis with Polyangiitis: a Case Report.

We encountered a 64-year-old Japanese woman who developed subarachnoid hemorrhaging (SAH) with multiple cerebral artery stenoses during remission induction therapy for eosinophilic granulomatosis and polyangiitis (EGPA). The treatment involved intensified steroid pulse therapy and continued intravenous cyclophosphamide pulse therapy, which led to beneficial effects. Given the rarity of multiple EGPA-associated cerebral artery stenoses and SAH, it is crucial to differentiate them from other diseases. The mortality rate of EGPA complicated by intracranial hemorrhagic lesions, including SAH, is high. When headache is present at the onset of EGPA, the possibility of SAH must be considered.

Factors associated with drug retention of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: A multicentre REVEAL cohort study.

OBJECTIVES: To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort). METHODS: Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test. RESULTS: The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027). CONCLUSIONS: MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.

Combination Biologic Therapy with Mepolizumab and Dupilumab for Severe Eosinophilic Granulomatosis with Polyangiitis and Chronic Rhinosinusitis with Nasal Polyp.

We report the case of a 55-year-old female with eosinophilic granulomatosis with polyangiitis and chronic rhinosinusitis with nasal polyp. Rhinosinusitis recurred 6 months after full-house endoscopic sinus surgery. Although conventional treatment with azathioprine and mepolizumab with steroids was given, it was difficult to simultaneously control both rhinosinusitis and eosinophilic granulomatosis with polyangiitis. Clinical examinations showed polyps in the olfactory cleft, and the patient's anosmia gradually became persistent. Even after administering mepolizumab for a certain period of time, symptoms did not improve, but when the biologic agent was switched to dupilumab, an improvement in recalcitrant chronic rhinosinusitis with nasal polyp was observed. While dupilumab was administered intermittently for refractory chronic rhinosinusitis with nasal polyp, the rhinosinusitis improved and symptoms such as worsening of eosinophilic granulomatosis with polyangiitis paresthesia were observed. Both symptoms gradually subsided 19 months after starting intermittent administration, leading to the discontinuation of dupilumab administration. Rhinosinusitis in the setting of eosinophilic granulomatosis with polyangiitis may be refractory in some cases, and this case provides findings demonstrating the strong effect of dupilumab on eosinophilic inflammation.

Eosinophilic granulomatosis with polyangiitis and its association with montelukast: a case-based review.

The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.