Clinical impact of ceruloplasmin levels at ANCA-associated vasculitis diagnosis.

OBJECTIVES: Ceruloplasmin is an inhibitor of myeloperoxidase (MPO) activity that plays an important role in the pathophysiology of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study aimed to evaluate the prognostic impact of serum level of ceruloplasmin at diagnosis in patients with anti-MPO antibody-positive AAV. METHODS: This retrospective monocentric study in Caen University Hospital involved all consecutive adult anti-MPO antibody-positive patients with microscopic polyangiitis or granulomatosis with polyangiitis, diagnosed between January 2010 and January 2022 with available serum sample at inclusion. Patients outcomes were analyzed from two subgroups constituted according to the median serum level of ceruloplasmin. The same analyses were then performed in anti-proteinase 3 (PR3) antibody-positive patients. RESULTS: Within the 92 patients analyzed, 50 patients had anti-MPO antibodies with a median ceruloplasmin level of 0.44 [quartiles 1-3, 0.40-0.49] g/L and a median Birmingham Vasculitis Activity Score of 19 [14-22]. After a median follow-up period of 40 [22-86] months, 13 (26%) patients had died: 10 (40%) in the low ceruloplasmin group and 3 (12%) in the high ceruloplasmin group (p = 0.03), with a significantly worse survival rate in the low ceruloplasmin group (p = 0.021). No significant differences in relapse rate or renal failure was observed between the two groups. The same analyses performed in the group of AAV patients with anti-PR3 antibody did not show any differences. CONCLUSION: In anti-MPO AAV patients, serum level of ceruloplasmin at diagnosis seems to be associated with a significant impact on survival.

Biologics in Hypereosinophilic Syndrome and Eosinophilic Granulomatosis with Polyangiitis.

Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are complex disorders defined by blood and tissue eosinophilia and heterogeneous clinical manifestations. Historically, the mainstay of therapy for both conditions has been systemic glucocorticoids. However, recent availability of biologics that directly or indirectly target eosinophils has provided new avenues to pursue improved outcomes with decreased toxicity. In this article, we summarize the evidence supporting the use of specific biologics in HES and/or EGPA and provide a framework for their clinical use in patients.

ANCA-negative granulomatosis polyangiitis: an airway emergency.

Granulomatosis polyangiitis (GPA) is an autoimmune condition causing inflammation of small blood vessels. It is a rare disorder that may affect various parts of the body. The diagnosis is often based on clinical examination, laboratory investigations and tissue biopsy. In about 10-20% of patients, the anti-neutrophilic cytoplasmic antibody (ANCA) can be negative, and histology maybe inconclusive, which can lead to diagnostic uncertainty. Failure to treat vasculitis can lead to morbidity and even mortality. We present a case report of a gentleman who was presented with an airway emergency with inflammation of the nasal cavity and subglottic involvement amounting to airway stenosis. His ANCA was negative and tissue biopsy from the subglottis was inconclusive. He underwent urgent dilatation of his airway, local therapies to the nose and was commenced on 10 cycles of cyclophosphamide. A follow-up of over 4 years has not shown any relapse of his disease clinically or biochemically. We discuss the clinical findings, diagnostic dilemma and multidisciplinary management of this life-threatening condition.

Granulomatosis with Polyangiitis Discovered Because of Repeated Upper Eyelid Swelling.

Background and objectives: The initial symptom that triggers granulomatosis with polyangiitis (GPA) diagnosis is rarely ocular. We describe a case with a single ocular lesion identified as probable GPA due to proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positivity according to the diagnostic criteria of the Ministry of Health in Japan; the lesion repeatedly worsened. Materials and methods: A 25-year-old female visited the Department of Ophthalmology, Asahi General Hospital, with upper eyelid swelling and conjunctival and episcleral hyperemia of the left eye. Both hordeolum and eyelid cellulitis were suspected, as the condition was resistant to treatment with antibiotic eye drops. Episcleritis was suspected due to localized hyperemia in the upper part of the eye. Upon treatment with antibacterial agents and steroid eye drops, the swelling and the hyperemia repeatedly worsened every week. Results: Blood samples were positive for PR3-ANCA, and GPA with an isolated ocular lesion was considered. After oral steroid treatment, the patient had no recurrence for 4 years. There was no systemic involvement in the upper respiratory tract, lungs, or kidneys. Conclusions: Diagnosing GPA with ocular symptoms as initial manifestations is challenging. GPA should be considered in treatment-resistant eyelid, orbital, and episcleral lesions, even at a young age.

Mesenchymal stem cell therapy in eosinophilic granulomatosis with polyangiitis-related lower limb gangrene: a case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), a rare but life-threatening systemic vasculitis, is distinguished by marked eosinophilia and presents with diverse symptoms, including asthma, cutaneous purpura, ecchymosis, skin necrosis, cardiac lesions, peripheral neuropathy, and necrotizing vasculitis. The etiology of EGPA involves a complex interaction among humoral, adaptive, innate, and allergic immune responses. Standard treatment employs prolonged high-dose glucocorticoid therapy, which is critical for survival; however, some patients' symptoms cannot be relieved. CASE REPORT: This case report details the medical management of an 11-year-old patient with EGPA, who was at risk of bilateral lower limb amputation due to differential arterial occlusion and severe, necrotizing vasculitis-induced gangrene in both feet. Treatment modalities administered included systemic infusion of Umbilical Cord Mesenchymal Stem Cells (UC-MSCs), targeted gastrocnemius muscle injections, and application of a Placenta-Derived Mesenchymal Stem Cells (PD-MSCs) hydrogel. RESULTS: After receiving a four-month regimen of allogeneic mesenchymal stem cell therapy via intravenous and local administration, the patient showed normalized eosinophil counts, reestablished blood flow in the dorsal arteries, and marked improvement in foot ulcerations. CONCLUSION: Mesenchymal stem cell therapy is a promising option for severe EGPA cases refractory to glucocorticoids.

COVID-19-induced granulomatosis with polyangiitis: A case report of a 16-year-old East Asian and literature review.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is divided into granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. It is one of the most severe and potentially fatal autoimmune inflammatory conditions. The etiology and pathology of AAV are complex and poorly understood. Since the onset of the Coronavirus Disease 2019 (COVID-19) pandemic, numerous reports have documented GPA cases following COVID-19, suggesting a potential link between COVID-19 and the development of GPA. This case report discusses a 16-year-old East Asian boy who developed GPA with diffuse alveolar hemorrhage after contracting COVID-19. Additionally, a literature review was conducted to gain a deeper understanding of this disorder. METHODS: The study involved a retrospective analysis of the data of a case of GPA post-COVID-19 infection, aiming to summarize the clinical characteristics of GPA post-COVID-19 infection through a search of databases (PubMed, Wanfang Data, and CNKI), supplemented by standard searches in Google Scholar, Cochrane, Scopus, and LitCovid, and to conduct a comprehensive analysis of the literature. RESULTS: A total of 12 cases were identified and, when combined with the present case, yielded 13 cases of GPA post-COVID-19 infection, comprising 5 males and 8 females with an average age of (40.6 ± 19.5) years. The interval between COVID-19 infection and the diagnosis of GPA varied from 1 day to 3 months across all cases. Mortality was reported at 7.7% (1/13). The most common clinical manifestations included cough (69.2%) and dyspnea (46.1%). Computed tomography scans revealed ground-glass opacities and multifocal pulmonary nodules. In all cases, positive findings for c-ANCA and protease 3-antibody were observed. Renal involvement was observed in more than half of the patients.

[BRONCHOPULMONARY ASPERGILLOSIS WITH COMORBID GRANULOMATOUS POLYANGIITIS IN A PATIENT WHO PRESENTED WITH EXOPHTHALMOS: A CASE REPORT].

There have been no reports of the coexistence of allergic bronchopulmonary aspergillosis (ABPA) and granulomatosis with polyangiitis (GPA). The first case of ABPA with comorbid GPA that developed exophthalmos is reported. A 69-year-old man was referred to our hospital for exophthalmos, fever, anorexia and weight loss. The patient had been diagnosed with ABPA six years earlier, which had been repeatedly treated but recurred with oral corticosteroids with or without antifungal therapy. The laboratory data on referral showed elevations of the white blood cell count, C-reactive protein and specific immunoglobulin E against Aspergillus fumigatus, but antineutrophil cytoplasmic antibody was not positive. Urinalysis showed proteinuria. Paranasal sinus and chest computed tomography showed sinusitis with osteochondral destruction, bronchiectasis, mucus plugging, and a pulmonary nodule. Orbital magnetic resonance imaging showed swelling of the medial rectus muscle and peripheral mass. The intraorbital tissue biopsy showed a necrotic granuloma and necrotizing vasculitis. The patient was diagnosed with GPA, on the basis of the Ministry of Health, Labour and Welfare's criteria of Japan. The patient was treated with induction therapy consisting of glucocorticoids and rituximab, and his symptoms improved. Though the pathogenesis common to ABPA and GPA remains unknown, neutrophilic inflammation induced by airway Aspergillus persistent infection might be involved. Study of further cases is needed.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis.

This case report describes a 40-year-old male patient with severe cardiac failure due to eosinophilic granulomatosis with polyangiitis (EGPA) and myocarditis. The fast diagnostic approach with cardiac MRI (CMR) and immunosuppressive treatment with glucocorticoid and cyclophosphamide near-normalized the patient's cardiac function. Myocarditis due to EGPA is rare, however life-threatening, so a systematic approach and early CMR should be considered in patients with known asthma presenting with eosinophilia and cardiac involvement.

Coexistence of Pulmonary Thromboembolism, Pulmonary Tuberculosis and Granulomatosis with Polyangiitis: A flimsy triple dribble.

Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease with multi-system involvement. It involves the upper respiratory tract, lungs and kidneys. A 36-year-old female patient presented to a tertiary care referral hospital in Central India in 2023 with complaints of low-grade fever, dry cough and loss of appetite initially followed by dyspnoea, purpuric skin lesions, right lower limb swelling with pain and redness. Her chest radiograph revealed right upper lobe cavitary lesion with consolidation in the right lower lobe. Mycobacterium tuberculosis was detected in sputum and broncho alveolar lavage via cartridge based nucleic acid amplification assay. Later, computed tomography pulmonary angiography revealed bilateral pulmonary artery thromboembolism. Furthermore, her cytoplasmic-antineutrophil cytoplasmic antibody test was positive, serum creatinine was rising, urine microscopy had red cell casts and lower limb venous doppler revealed deep venous thrombosis. Histopathological examination of the skin lesion revealed vasculitis. Based on these findings, the patient was diagnosed with GPA. The patient improved with pulse steroids, cyclophosphamide, anticoagulants and anti-tuberculous therapy.

A discussion on a suspected case with EGPA after maintenance hemodialysis for 5 years and related literature analysis: A case report.

RATIONALE: Pathological featuring by necrotizing granulomatous inflammation of peripheral blood and tissues with increased eosinophils infiltrating small and medium vessels, eosinophilic granulomatosis with polyangiitis (EGPA), a family of rare antineutrophil cytoplasmic antibody (ANCA) associated with systemic vasculitis. With low morbidity, diverse clinical manifestations, and difficult early diagnosis, the majority of patients are confirmed after multiple organ damages, thus missing the best treatment time and having a poor prognosis. About 25% to 30% of EGPA cases have been reported to suffer from the renal disease, and there are few studies on EGPA complicated with kidney damage, most of them on ANCA-positive patients. Generally, the initial diagnosis of EGPA on maintenance hemodialysis is even rare. We report a case of a patient with maintenance hemodialysis for 5 years and then was diagnosed with EGPA. PATIENT CONCERNS: The female patient, 54-year-old, having maintenance hemodialysis for 5 years consecutively, was hospitalized for the recurring rash in the past 3 years and then exacerbation in the last 2 months. With the previous history of bronchial asthma having attacked frequently recently, it could be observed from peripheral blood that the eosinophils increased, from the cardiac color ultrasound that it was prone to eosinophilic endocarditis, from 5 tests for vasculitis that P-ANCA and MPO-AB were positive. DIAGNOSES: The patient's onset is renal dysfunction, with maintenance hemodialysis for 5 years, recurrent lung infections, combined with eye lesions, scattered skin rashes, P-ANCA positive, MPO-AB positive, asthma present, eosinophil absolute value 1.60 × 109/L, total score >6 points, diagnosis considering EGPA. INTERVENTIONS: Due to multiple organ damage, the patient received treatment with a combination of steroids and cyclophosphamide. OUTCOMES: After 2 days, the patient's rash significantly darkened compared to before, wheezing improved, and eosinophils returned to normal levels. LESSONS: The ANCA test shall be put on the high agenda for patients presenting with kidney failure at first. Meanwhile, the neglected immune monitoring for patients with dialysis tells us that it is of great significance for this kind of patient to have immune monitoring in the early diagnosis of EGPA.

Facial Paralysis in Otitis Media Due to Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA), formerly Wegener's granulomatosis, commonly presents primarily with otitis media and hearing loss, as well as upper and lower respiratory symptoms. However, facial nerve paralysis is a rare manifestation of this uncommon necrotizing vasculitis. We report a patient with facial paralysis accompanied by otitis media. In further studies, our patient was diagnosed with GPA, which was neglected before. In such a presentation, acute suppurative otitis media is the most likely cause of the facial paralysis, but GPA must also be considered, especially in cases with new-onset, painful serous otitis, acute otitis media, or pale granulation tissue in the middle ear, in adults with no previous history of Eustachian tube dysfunction.

A case of eosinophilic granulomatosis with polyangiitis combined with pulmonary tuberculosis: A case report.

RATIONALE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare autoimmune disease that can affect multiple organ systems. The standard treatment mainly relies on glucocorticoids and immunosuppressive agents. In our study, we present an EGPA patient who had pulmonary tuberculous mycobacteria infection, such cases are rarely reported. PATIENT CONCERNS: A 71-year-old male patient was diagnosed with EGPA (systemic type) and pulmonary tuberculosis simultaneously. DIAGNOSES: The Five-Factor score indicated that the patient required glucocorticoids combined with immunosuppressive agents for induction therapy, however, the use of immunosuppressive agents would significantly inhibit antituberculosis treatment. Nowadays, treating active autoimmune disease in patients with infections remains a clinical challenge. INTERVENTIONS: Considering the patient did not show life-threatening or severe organ involvement and reduced the effect of antituberculosis immunity, we used glucocorticoids alone. OUTCOMES: Finally, the patient had no adverse events, the eosinophil counts were markedly decreased and symptoms of EGPA were relieved. LESSONS: The patient of EGPA combined with pulmonary tuberculosis successfully treated with glucocorticoids alone may provide significant support in selecting the appropriate treatments for similar cases in the future.

The utility of orbital imaging in the evaluation of orbital disease.

PURPOSE: This study investigates the accuracy of either computerized tomography (CT) or magnetic resonance imaging (MRI) for the evaluation of various orbital diseases. METHODS: We collected 126 CT scans and 65 MRI scans from 144 subjects and asked two radiologists to interpret the images without clinical information. Images included 14 with a clinical diagnosis of orbital infection, 144 with orbital inflammation, and 33 with orbital neoplasm. The inflammatory diseases included thyroid eye disease (TED, n = 69), non-specific orbital inflammation (NSOI, n = 44), IgG4-related disease (IgG4-RD, n = 15), sarcoidosis (Sarcoid, n = 9), granulomatosis with polyangiitis (GPA, n = 5), and Erdheim-Chester disease (ECD, n = 2). RESULTS: The balanced accuracy (BA) for the two radiologists ranged from 0.87 to 0.90 for cellulitis, 0.81 to 0.86 for inflammation, and 0.82 to 0.85 for neoplasm. Radiologists were excellent at recognizing GPA (BA = 0.98 to 0.99) and very good for TED (BA = 0.80 to 0.86). They also did well identifying IgG4-RD (BA = 0.75 to 0.77), but slightly less well for NSOI (BA = 0.69 to 0.75) and poorly for Sarcoid (BA = 0.48 to 0.50). CONCLUSIONS: CT or MRI scanning contributes to the evaluation of patients with orbital disease, but accuracy does varies based depending on the diagnosis. We could not evaluate issues such as determination of disease activity, variability based on the unit used for imaging or the skills beyond those of our two specialized neuroradiologists. Future studies should directly compare the two imaging modalities and assess the utility of imaging to determine disease activity.

Distinct pulmonary patterns in ANCA-associated vasculitides: insights from a retrospective single center cohort study.

ANCA-associated vasculitides (AAV) comprise granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis. All forms may involve different organ systems, yet kidney and lung involvement are common and fatal in many cases. Here, we aimed to determine the predictive value of pulmonary disease manifestation and individual CT findings in AAV patients. Available CT scans and clinical information on mortality, renal outcomes, occurrence of relapses and damage scores were analysed retrospectively from a tertiary rheumatology center in Germany. We included a total of 94 AAV patients (49 with GPA, 41 with MPA). Forty-four patients had lung involvement with available CT scans, 70.5% of which with GPA and 72.7% with renal involvement. Nodule formation and cavities were more frequent among GPA patients, whereas ground-glass opacities (GGO), ILD and pleural effusion were observed predominantly in MPA patients. Over a median follow-up of 37 months, GPA patients had a slightly higher overall mortality, whereas end-stage kidney failure rates were significantly increased in MPA patients. Relapse frequencies were comparable between both entities. The presence of GGO and pleural effusion were associated with higher relapse rates, whereas nodules were negatively correlated with relapses. Notably, RTX-treated patients had less infections as compared to individuals under different therapies. Our data demonstrate the outstanding importance of characteristic CT patterns in AAV diagnosis assessment. Especially certain CT patterns including GGO and pleura effusion may help to identify patients who are at higher risk for relapsing disease.

Literature review and case study of recurrent EPGA with elevated IgG4 and positive HBsAg successfully treated with rituximab.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of autoimmune vasculitis. The involvement of IgG4 and HBsAg in EGPA is less common but can occur and may present unique challenges in management. CASE PRESENTATION: We present a case study of a 70-year-old female diagnosed with EGPA confirmed via renal biopsy. She initially presented with recurrent purpura, diarrhea and progressive numbness in the hands and feet, accompanied by general weakness. Complete remission was achieved with a one-year course of prednisone acetate and cyclophosphamide treatment. However, upon discontinuation of self-medication, the disease relapsed, manifesting as a generalized rash and weakness in the extremities.Skin biopsy revealed eosinophil infiltration, with inflammatory cells predominantly surrounding blood vessels. Notably, during treatment, the patient's hepatitis B markers transitioned from negative to positive for HBsAg. Subsequent administration of entecavir, along with monitoring for a decrease in HBV DNA levels, preceded the initiation of steroids and rituximab to attain remission once more. Among the remaining 15 patients analyzed, all exhibited elevated serum IgG4 levels, with none testing positive for hepatitis B. Notably, only one patient was diagnosed with immunoglobulin G4-related disease (IgG4-RD), suggesting that elevated IgG4 levels alone may not necessarily indicate IgG4-RD. CONCLUSIONS: Our case report highlights the first instance of recurrent EGPA accompanied by elevated IgG4 and positivity for hepatitis B, which was successfully treated with rituximab. In cases of concurrent hepatitis B, rituximab treatment may be considered once viral replication is under control. However, emphasis on maintenance therapy is crucial following the induction of disease remission.