Occupational Silica Exposure as a Potential Risk for Microscopic Polyangiitis.

Microscopic polyangiitis is an important and common component of cytoplasmic antibody-associated vasculitides that can lead to serious morbidity and even death. A clear causative etiology has not been identified. Although silica is well known to produce lung damage, the negative renal effects of silica exposure should not be overlooked. We present a case of renal dysfunction associated with silica exposure, its diagnosis by renal biopsy, and the treatment method used. Environmental or occupational silica exposure can cause microscopic polyangiitis. Working in occupations with increased risk of silica exposure may result in serious medical problems.

Microscopic Polyangiitis Following mRNA COVID-19 Vaccination: A Case Report.

Coronavirus disease 2019 (COVID-19) is one of the most widespread viral infections in human history. As a breakthrough against infection, vaccines have been developed to achieve herd immunity. Here, we report the first case of microscopic polyangiitis (MPA) following BNT162b2 vaccination in Korea. A 42-year-old man presented to the emergency room with general weakness, dyspnea, and edema after the second BNT162b2 vaccination. He had no medical history other than being treated for tuberculosis last year. Although his renal function was normal at last year, acute kidney injury was confirmed at the time of admission to the emergency room. His serum creatinine was 3.05 mg/dL. Routine urinalysis revealed proteinuria (3+) and hematuria. When additional tests were performed for suspected glomerulonephritis, the elevation of myeloperoxidase (MPO) antibody (38.6 IU/mL) was confirmed. Renal biopsy confirmed pauci-immune anti-neutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and MPA was diagnosed finally. As an induction therapy, a combination of glucocorticoid and rituximab was administered, and plasmapheresis was performed twice. He was discharged after the induction therapy and admitted to the outpatient clinic 34 days after induction therapy. During outpatient examination, his renal function had improved with serum creatinine 1.51 mg/dL. We suggest that MPA needs to be considered if patients have acute kidney injury, proteinuria, and hematuria after vaccination.

Complement profile in microscopic polyangiitis and granulomatosis with polyangiitis: analysis using sera from a nationwide prospective cohort study.

OBJECTIVE: The complement cascade, especially the alternative pathway of complement, has been shown in basic research to be associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). We aimed to elucidate relationships between serum complement components and clinical characteristics in AAV. METHOD: In a nationwide prospective cohort study (RemIT-JAV-RPGN), we measured the serum levels of C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, factor B, factor D, factor H, factor I, mannose-binding lectin, and properdin in 52 patients with microscopic polyangiitis (MPA) and 39 patients with granulomatosis with polyangiitis (GPA). RESULTS: The properdin level of MPA and GPA was significantly lower than that of healthy donors. The properdin level was negatively correlated with the Birmingham Vasculitis Activity Score (BVAS) (ρ = -0.2148, p = 0.0409). The factor D level at 6 months was significantly positively correlated with the Vasculitis Damage Index (VDI) at 6, 12, and 24 months (ρ = 0.4207, 0.4132, and 0.3115, respectively). Patients with a higher ratio of C5a to C5 had higher neutrophil percentage and serum immunoglobulin G levels, and significantly lower creatinine levels. Cluster analysis divided the MPA and GPA patients into three subgroups. A principal component (PC) analysis aggregated 15 types of complements into alternative pathway-related PC 1 and complement classical pathway and common pathway-related PC 2. CONCLUSIONS: The serum levels of properdin and factor D were correlated with the BVAS and the VDI in MPA and GPA, respectively. Our analyses suggested the pathological heterogeneity of MPA and GPA from the aspect of complement components.

Microscopic polyangiitis in a case of silica exposure: a rare presentation.

A 28-year-old male was admitted for breathlessness, haemoptysis, fever and fatigue. The patient had occupational exposure to silica dust. Arterial blood gas test ABG revealed hypoxemic respiratory failure. Chest CT demonstrated ground glass opacities with interlobular septal thickening and small centrilobular nodules with patchy areas of consolidation in bilateral lungs. He was mechanically ventilated for refractory hypoxemia. The treatment with cyclophosphamide and methylprednisolone lead to recovery and extubation. The final diagnosis was diffuse alveolar haemorrhage due to perinuclear antineutrophil cytoplasmic antibody (ANCA)-associated microscopic polyangiitis (p-ANCA-associated MPA). In a tuberculosis endemic country, for patients presenting with diffuse alveolar haemorrhage (DAH), with history of silica exposure, differential diagnosis of ANCA associated vasculitis must be considered.

The color of skin: purple diseases of the skin, nails, and mucosa.

The color purple can be seen in several types of eruptions including inflammatory dermatoses like lichen planus, infectious dermatoses like ecthyma gangrenosum, neoplasms like Kaposi sarcoma, and vasculitis and vasculopathy. The current review focuses on the clinical appearance, pathophysiology, and treatment of several vasculitides and vasculopathies including capillaritis, cutaneous small-vessel vasculitis, immunoglobulin A (IgA) vasculitis, cryoglobulinemia, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosum, warfarin-induced skin necrosis, heparin-induced thrombocytopenia, purpura fulminans, antiphospholipid antibody syndrome, calciphylaxis, levamisole-induced vasculopathy, and thrombotic thrombocytopenic purpura. Dermatologists play a central role in treating patients with cutaneous vasculitis and vasculopathy and may have the opportunity to facilitate identification of systemic disease by diagnosing cutaneous vasculitis and vasculopathy.

The effect and possible clinical efficacy of in vivo inhibition of neutrophil extracellular traps by blockade of PI3K-gamma on the pathogenesis of microscopic polyangiitis.

OBJECTIVE: Neutrophil extracellular traps (NETs) are peculiar structures composed of the externalized chromatin with intracellular proteins and formed by activated neutrophils in a reactive oxygen species (ROS)-dependent manner. Aberrant NETs are considered to be autoantigens for anti-neutrophil cytoplasmic antibodies (ANCAs) underling the development of microscopic polyangiitis (MPA). However, little is known regarding the therapeutic efficacy of in vivo inhibition of NET formation (NETosis) on MPA pathogenesis. This study determines whether reducing NETosis prevents ANCA production and improves characteristic involvement. METHODS: A mouse model of MPA induced by administering a novel extract from Candida albicans was devised. By applying this method to mice lacking phosphoinositide 3-kinase gamma (PI3K-gamma), which is indispensable for ROS production in neutrophils, we investigated the levels of in vivo NETs, ANCA titers and histological damage. RESULTS: Our model exhibited accumulation of NETs in vivo, elevation of ANCA titers and characteristic pathologies mimicking human MPA, including small-vessel vasculitis and crescentic glomerulonephritis. Strikingly, these abnormalities were reduced by genetically and/or pharmacologically blocking PI3K-gamma. Moreover, a pharmacological PI3K-gamma blockade decreased the levels of human NETs. CONCLUSION: Our results suggest that in vivo inhibition of NETosis by blocking PI3K-gamma could be a promising therapeutic strategy for the pathogenesis of MPA.

Antineutrophil cytoplasmic antibody-associated vasculitis in Taiwan: A hospital-based study with reference to the population-based National Health Insurance database.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), comprises a group of diseases with significant morbidity and mortality. The incidence and relative frequency of GPA/MPA/CSS are different all over the world. The epidemiology of AAV in Taiwan is still not clear. METHODS: The current study aimed to provide a population-based estimate of the annual incidence of GPA using the Taiwan National Health Insurance (NHI) research database and a single hospital-based estimate of the relative frequency of AAV in Taiwan. RESULTS: The annual incidence of GPA in Taiwan was 0.37 per million patient-years (95% Poisson rate confidence interval: 0.30-0.45) from 1997 to 2008, according to the NHI database. In our hospital, 24 patients were newly diagnosed with AAV between 2003 and 2011, including eight patients with GPA, 14 with MPA, and two with CSS. The ratio of the number of patients with GPA to that of MPA was 0.57. CONCLUSION: The current results provide an estimate of the annual incidence of GPA and the relative frequency of AAV in the Chinese Han community in Taiwan. Such geoepidemiology information may help illuminate the interaction between ethnic background and environment in these autoimmune diseases.

Pneumomediastinum in a patient with microscopic polyangiitis preceded by interstitial pneumonia.

A 73-year-old woman was diagnosed with interstitial pneumonia in 2006; however, the disease was not progressive. Four years later, purpura, peripheral neuropathy, and increased levels of myeloperoxidase anti-neutrophil cytoplasmic antibodies (583 EU/mL) and C-reactive protein (2.27 mg/dL) were observed, and a diagnosis of microscopic polyangiitis was made. Treatment with prednisolone and azathioprine was initiated. However, on the 35th hospital day, chest computed tomography showed pneumomediastinum and subcutaneous emphysema without aggravation of the interstitial pneumonia. To our knowledge, this is the first report of pneumomediastinum as a complication of microscopic polyangiitis associated with interstitial pneumonia.

[Vasculitis. New nomenclature of the Chapel Hill consensus conference 2012]. / Vaskulitis. Neue Nomenklatur der Chapel-Hill-Konsensuskonferenz 2012.

In recent years, many advances have been made in our understanding of vasculitis etiopathology as well as of different disease courses. The revised Chapel Hill Consensus Conference (CHCC) 2012 nomenclature reflects current knowledge about etiopathology, in addition to the descriptive principles of vessel size and type of inflammation. Anti-neutrophil cyptoplasmic antibody (ANCA)-associated vasculitides have been classified as a separate group, as opposed to immune complex small vessel vasculitis. In cases where consensus was achieved, eponyms have been replaced by systematic names, such as granulomatosis with polyangiitis (Wegener's) or eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Moreover, clinically important but less well-known types of vasculitis have now been included in the CHCC nomenclature. This article presents the changes, focussing on those types that are relevant to the histopathologist, and summarizes the results of important new articles on morphology and clinical picture of vasculitis.

Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis is a manifestation of microscopic polyangitis (MPA), and often precedes the detection of MPA. The prevalence and sequence of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and MPA in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) have not been precisely elucidated. METHODS: We enrolled 61 consecutive patients with IPF and measured the MPO-ANCA titers at initial presentation and during the follow-up period. Clinical, radiologic and histologic features of MPO-ANCA-positive cases were examined. RESULTS: Of 61 patients, 3 (4.9%) had positive MPO-ANCA titers at the initial presentation of IPF. During the disease course, MPO-ANCA-positive conversion occurred in 6 patients and the prevalence of ANCA increased to 14.8%. Among the nine patients positive for MPO-ANCA, two patients developed MPA during follow-up. Histologic features of MPO-ANCA-positive pulmonary fibrosis were compatible with the usual interstitial pneumonia pattern in which alveolar hemorrhage and capillaritis were not observed. The patients with MPO-ANCA-positive conversion showed increased percentages of bronchoalveolar lavage eosinophils and more frequent complication of pulmonary emphysema compared to those with MPO-ANCA-negative IPF. CONCLUSIONS: The findings of the present study demonstrated that patients with an initial diagnosis of IPF occasionally acquire MPO-ANCA, which develops to MPA during the disease course of IPF. The presence of pulmonary eosinophilia and low attenuation areas on computed tomography scans might be predictive of MPO-ANCA positive conversion.

Vasculitides associated with haematological malignancies: a case-based review.

Autoimmune phenomena including vasculitis are known to be associated with malignancy, especially those that are haematological in origin. Vasculitis syndromes associated with malignant disease include cutaneous leucocytoclastic vasculitis, polyarteritis nodosa, Churg-Strauss syndrome, microscopic polyangiitis, Wegener's granulomatosis and Henoch-Schönlein purpura. We describe a patient whose initial presentation with vasculitis led to the diagnosis of hairy cell leukaemia.

An aetiological & clinicopathological study on cutaneous vasculitis.

BACKGROUND & OBJECTIVES: Cutaneous vasculitis has protean clinical manifestations. It may be idiopathic or associated with a spectrum of conditions such as infections, drugs, etc. Skin is involved in both small vessel vasculitis (SVV) and medium vessel vasculitis (MVV). Overlapping features are seen between SVV and MVV. The histopathological features may not always relate with the clinical lesions. The aim of the present study was to evaluate the aetiological factors and clinicopathological association in patients with cutaneous vasculitis. METHODS: In this cross-sectional study, detailed history and clinical examination were done on patients with biopsy proven cutaneous vasculitis. Two skin biopsies were taken from each patient for routine histopathology and direct immunofluorescence. RESULTS: Of the 61 patients studied, hypersensitivity vasculitis (HSV) [23 (37.7%)] and Henoch Schonlein purpura (HSP) [16 (26.2%)] were the two most common forms. Systemic involvement was seen in 32 (52.45%) patients. Drugs were implicated in 12 (19.7%) cases, infections in 7 (11.4%) and connective tissue disorders in 4 (6.5%) cases. Histologically SVV was the most common pattern, seen in all the clinically diagnosed patients with SVV (47), and in 12 of the 14 clinically diagnosed patients with MVV. Direct immunofluorescence showed positivity for at least one immunoreactant in 62 per cent of the patients and the most common deposit was C3 followed by IgG, IgA and IgM. INTERPRETATION & CONCLUSIONS: Majority of our patients with cutaneous vasculitis were idiopathic. Histologically, SVV was seen in most of our patients. No association was seen between history of drug intake and tissue eosinophilia and also between histologically severe vasculitis and clinical severity. The presence of immunoreactant IgA was not specific for HSP.

[A case of microscopic polyangiitis with silicosis].

A 76-year-old man was admitted to our hospital because of increasing size of lung nodules, while he was under observation for silicosis at another hospital. As the result of bronchoscopic biopsy, it was confirmed that they were silicotic nodules. However, he was hospitalized again about one month later due to left spontaneous pneumothorax. The pneumothorax improved immediately by persistent drainage of the thoracic cavity, but he developed a fever on day 9, and ground-glass opacities in both lungs also became exacerbated in spite of our administration of antibiotics. In addition, the level of MPO-ANCA increased markedly and multiple 3-10mm sized purpurae was seen on the right thigh on day 29. Skin biopsy specimens revealed infiltration of histiocytes and lymphocytes around medium-sized vessels in lower dermis. We diagnosed microscopic polyangiitis, then treated with steroid and immunosuppressive therapy. Fever and radiological findings improved significantly from the day after initiation of steroid administration. The patient was discharged on day 92 because of the improvement of his respiratory condition. We report a case of microscopic polyangiitis with silicosis, which markedly improved by steroid and immunosuppressive therapy.

[Case of microscopic polyangiitis and giant cell arteritis after influenza vaccination].

We report a case of microscopic polyangiitis (mPA) and giant cell arteritis (GCA) (polyangiitis overlap syndrome) after influenza vaccination. A 67-year-old female with chronic kidney disease, who had been observed by a physician, presented fever and headache after immunization of influenza vaccine. She was diagnosed as having with mPA and GCA based on symptoms, worsening of renal function, biopsy of temporal artery (giant cell arteritis) and skin (microscopic polyangiitis), pulmonary involvement and the presence of myeloperoxidase-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA). She was treated with prednisolone (PSL) and the symptoms were improved. However, two months later she was presented with general physical weariness. She was diagnosed as having with pneumocystis pneumonia, cytomegalovirus infection and cryptococcosis. Despite intensive treatment, she was died and autopsy was performed. The present case suggests that the influenza vaccination may cause different types of vasculitis, mPA and GCA, through the common mechanism in pathophysiology. This patient is also the first case of mPA and GCA proven by histological examination.

Pathogenesis of lung vasculitis.

Vasculitides that affect the lung represent a diverse group of diseases with various systemic clinical manifestations, and include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis), Churg-Strauss syndrome (CSS), and anti-glomerular basement membrane (anti-GBM) disease (Goodpasture syndrome). The etiologies of these diseases remain largely unknown. Although the pathogenic mechanisms of each differ, these diseases overlap by the presence of anti-neutrophil cytoplasmic autoantibodies in the vast majority of patients with MPA and GPA, and a substantial minority of patients with CSS and anti-GBM disease. This article reviews the current understanding of the pathogenesis of these four disease entities.