Granulomatous Polyangiitis Research Articles

Eosinophilic granulomatosis with polyangitis: A new target for biologicals.

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic necrotizing granulomatous vasculitis in the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Nevertheless, EGPA has specific clinical, biological and histological properties different from other AAVs [microscopic polyangiitis (MPA) and granulomatous polyangiitis (GPA)]. Recently, thanks to the studies conducted to understand the pathophysiology of EGPA, unlike neutrophils in other AAVs, the main cells involved in EGPA have been observed to be eosinophils. The key role of eosinophils in EGPA and recent development of targeted agents to treat other eosinophil-related diseases have created new therapeutic opportunities for EGPA. Conventional treatment of EGPA relies mainly on agents that decrease inflammation. Cornerstone therapy is systemic glucocorticoids, used as monotherapy or in combination with immunosuppressive agents. However, new therapeutic approaches are needed especially for persistent asthma symptoms, refractory disease, relapses and problems associated with corticosteroid dependence. Recently, the first large-scale randomized controlled clinical trial on polyangiitis and eosinophilic granulomatosis has demonstrated the efficacy of eosinophil-targeted biotherapy anti-interleukin-5 (IL-5) mepolizumab, and is approved for the management of EGPA. This finding opens a new era for EGPA management. This review provides an overview of eosinophilic granulomatosis with polyangiitis in the light of new targeted biological therapies.

Relationship Between Familial Mediterranean Fever and Other Rheumatic Diseases: Coincidence or Coexistence?

Background: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease affecting mainly the ethnic groups of the Mediterranean basin. It has been reported that it can coexist with various systemic inflammatory diseases. This study aimed to obtain information on rheumatic diseases that accompany FMF and evaluate the relation between FMF and such diseases.
 Methods: Eighty-four patients diagnosed with FMF and have rheumatic disease comorbidity in the rheumatology clinic between January 2018 - March 2020 were included in this study. 
 Results: The most common accompanying rheumatic disease was spondyloarthritis with 36 patients. Vasculitides was the second common disease accompanying FMF with 22, followed by connective tissue disease in 13, rheumatoid arthritis in 5, juvenile idiopathic arthritis in 4, gout in 3, and hidradenitis suppurativa in 1 patients. The most common MEFV mutation observed was M694V. There was no significant difference in demographic characteristics and clinical manifestations between M694V mutation types. 
 Conclusions: In this study, the relation between FMF and various rheumatic diseases was determined. Two new conditions, eosinophilic granulomatous polyangiitis, and scleroderma were detected. The associations may be just coincidental or an extension of the common underlying pathology. To be aware of this association is important to early diagnosis and appropriate treatment.

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores. Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively. Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r = - 0.675) and ITAS scores (r = - 0.385), as well as with CRP and CRI. Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.

IgG4-related ophthalmopathy

IgG4-related disease is a chronic inflammatory fibrosing disease of unknown etiology, characterized by the presence of volumetric lesions that can clinically simulate malignant tumors, a pronounced IgG4-positive lymphoplasmacytic infiltrate, and an increase in the level of IgG4 in the blood serum. A special form of the disease is IgG4-related ophthalmopathy, which requires differential diagnosis with inflammatory pseudotumor, lymphoma and granulomatous polyangiitis. 7 clinical cases of IgG4-related ophthalmopathy are presented. It has been shown that follicle-like structures with the structure of a lymph node are formed in the tissues of the orbit. Along with a large number of cells in the inflammatory infiltrate expressing CD138, IgG and IgG4, there are CD8+ and CD68+ cells. IgG4-related ophthalmopathy is a rare manifestation of IgG4-related disease. Its morphogenesis involves not only IgG, IgG4 and CD138 positive plasma cells, which are diagnostic. CD8 and CD68- positive cells are involved too. They persisted in large quantity in the lymphohistiocytic infiltrate. The study of the lymphocyte population can help in revealing the pathogenesis and morphogenesis of this rare disease.

Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis.

Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation (P=0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3.

Clinical case of eosinophilic granulomatous polyangiitis debuted by myocardial infarction

The article presents clinical observations demonstrating the difficulties of diagnostic search in establishing the diagnosis of systemic vasculitis associated with antineutrophil cytoplasmic antibodies, which include a rare disease eosinophilic granulomatosis with polyangiitis (ChurgStrauss syndrome). Carefully collected anamnesis, participation of specialists of different profiles, retrospective analysis of laboratory and instrumental data allowed to verify the diagnosis, to prescribe adequate therapy. The aim of the publication is to discuss the need for early diagnosis of eosinophilic granulomatosis with polyangiitis, which can improve the effectiveness of therapy and improve the overall prognosis for this disease, taking into account modern approaches based on the main provisions of international recommendations that were prepared in 2015 with the participation of leading experts from Europe, USA and Canada and were called to become the basis for choosing a personalized patient therapy strategy. In some cases, the diagnosis of eosinophilic granulomatous polyangiitis is complicated by the diversity of the clinical picture, the non-simultaneous appearance of the main symptoms and the violation of the stages of the process. In the differential diagnosis of systemic vasculitis, assessment of initial clinical manifestations, testing for the presence of antibodies to the cytoplasm of neutrophils, multispiral computed tomography of the chest organs and diagnostic biopsy of the affected tissues are crucial. In the histological conclusion, a picture of focal ulcerative-necrotic lesions of the nasal mucosa with signs of vasculitis and a pronounced eosinophilic cell component of inflammation was noted. The distinctive features of this case include the onset of the disease with the development of myocardial infarction and early damage to the hearing organ in the form of cochlear neuritis, complicated by sensorineural hypoacusis. The combination of high doses of glucocorticosteroids and cyclophosphamide is still the gold standard for the treatment of severe cases, but the use of biological agents such as rituximab or mepolizumab seems to be a promising therapeutic alternative (4 figs, bibliography: 3 refs).

POS1217 THE PATTERN OF COVID 19 PANDEMIC AMONG PATIENTS WITH AUTOIMMUNE INFLAMMATORY RHEUMATIC DISEASES (AIIRD)

Background:The epidemiology of COVID19 among patients with AIIRD may be influenced by a dysregulated immune system, immunosuppressive therapies and behavioral patterns. Data regarding the epidemiology of COVID19 among patients with AIIRD is scarce.Objectives:To assess the pattern of COVID19 pandemic among patients with AIIRD compared to the general population in IsraelMethods:At the beginning of the COVID-19 pandemic, we established a national registry of patients with AIIRD, diagnosed with COVID-19, based on voluntary reporting by the treating rheumatologist. All the members of the Israeli Society of Rheumatology were encouraged to participate and repeatedly reminded to report any new cases. Rheumatology centers from 11 hospitals from the Northern and Central part of Israel participated in this study. The registry included demographic data, AIIRD diagnosis and duration, systemic organ involvement, co-morbidities, treatment (conventional synthetic disease modifying drugs (csDMARDs), biologic/targeted (b/ts) DMARDs, corticosteroids use, dose and treatment duration, date of COVID19 diagnosis, severity of the viral disease and complications, duration of hospitalization, if required, treatment for COVID 19, laboratory results and outcome. The diagnosis of COVID 19 was made by a positive SARS CoV2 PCR. The indications for SARS CoV2 PCR testing in Israel comprise clinical symptoms or exposure to a confirmed close contact. Severe illness was defined by SpO2 <94% in room air, respiratory rate of >30 breaths/min, PaO2/FiO2 <300 mm Hg, or lung infiltrates >50% on chest imaging.The epidemiological data regarding the number of COVID19 confirmed patients, the number of severe cases and the rate of mortality among the general population per day and per week, were extracted from the data dashboard of the Israeli Ministry of Health. We analyzed data from 02.2020 to 15.01.2021.Results:During the study period we experienced 3 waves of COVID 19 pandemic. The governmental management of COVID19 spread, at the beginning of the pandemic, included inforcement of severe travel restrictions and social distancing, followed eventually by a preventive lockdown, in spite of the relatively low number of cases. Easing of the restrictions, lifting the travel ban, opening of the commerce and schools led to 2 much more severe waves, which triggered 2 new lockdowns. Up to January 2021, 549763 Israelis had confirmed COVID19, 30% of whom had severe disease, 0.84% died (30% of the patients with severe disease).We identified 190 AIIRD patients (mean(SD) age 52(18), 30% males) who had confirmed COVID19. The weekly incidence curve of patients with rheumatic diseases correlated with the curve of the general population (Figure 1).Sixty-one % of the patients with AIIRD received csDMARDs, 41% were on b/tsDMARDs, 39% on chronic corticosteroids, 12% on ≥10mg prednisone. Forty-seven% of patients required hospitalization, 20% had severe COVID19. Sixteen patients (42% of patients with severe COVID19) (mean(SD), median age 64.7(15.4),67)) died (systemic sclerosis-4 patients, rheumatoid arthritis – 6, systemic lupus erythematosus – 2, antiphospholipid syndrome-2, granulomatous polyangiitis -1, polymyalgia rheumatica-1). The AIIRD was active in 56% of them, 50% received csDMARDs, none of them were on b/tsDMARDs, 31% received chronic prednisone>10 mg. All patients who died had at least 2 comorbidities.Conclusion:The pattern of spread of COVID19 in AIIRD patients is similar to the general population despite repeated mass media alerts for enhanced social distancing for elderly and immune suppressed patients. The disease tends to be more severe with enhanced mortality, especially in those with active AIIRD disease and organ involvement (lungs, heart, renal), older age and co-morbidities. A reporting bias cannot be excluded.Figure 1.Acknowledgements:Both first authors contributed equally to the manuscript.Disclosure of Interests:None declared.

POS-154 ASSOCIATION OF ANCA VASCULITIS AND CARDIOVASCULAR EVENTS: A POPULATION-BASED COHORT STUDY

ANCA associated vasculitis (AAV) increases the risk for cardiovascular (CV) disease; whether the elevated risk applies to all types of CV diseases or specific types is unclear. The objective of this study was to examine the association of AAV and adverse CV outcomes compared to the non-AAV population. We conducted a population-based, retrospective cohort study of adults (mean age 61 years, 51% female) with a new diagnosis of AAV in Ontario, Canada from 2007 to 2017. AAV was defined as receiving during a hospital encounter an ICD10 code for AAV (M313 granulomatous polyangiitis, M3131 granulomatous polynagiitis with renal involvement, M317 microscopic polyangiitis, or M301 allergic granulomatous angiitis). The main outcomes were major adverse CV events (MACE defined as myocardial infarction (MI), stroke or CV death), its individual components, atrial fibrillation (AF), and congestive heart failure (CHF), and were ascertained through hospital encounter ICD10 codes. Overlap propensity score weighting along with Cox proportional hazards models accounting for the competing risk of death were used to examine the association of AAV (n=1,520) and CV events in a matched (1:4) control cohort (n=5,834). Study participants were followed until first event of study outcome, death or end of the study period (31st March 2019). Over a mean follow-up of 3.8 years, individuals with AAV had a high cumulative incidence of MACE (15.4%), MI (6.6%), stroke (7.0%), AF (16.4%) and CHF (20.8%). AAV (compared to non-AAV) was not associated with a higher risk of MACE (sub-distribution hazard ratio [sHR] 1.05 95%CI 0.89-1.23), MI (sHR 1.15 95%CI 0.90 -1.47) or CV death (sHR 0.66 95%CI 0.49-0.89) but a higher risk of stroke (sHR 2.92 95%CI 1.76-4.85), AF (sHR 1.51 95%CI 1.30 to 1.75) and CHF (sHR 1.41 95%CI 1.22 to 1.63). The risks for all CV events (except CV death) were significantly elevated in the early period (90 days and 1 year) after AAV diagnosis compared to the non-AAV controls. Table. Cumulative incidences and risks for cardiovascular outcomes Tabled 1Follow-upGroupEvents (%)Cumulative incidence (%)sHR (95% CI)MACEFull studyControl642 (11.0)15.1AAV192 (12.6)15.41.05 (0.89 to 1.23)365-dayControl326 (5.6)5.6AAV126 (8.3)8.31.31 (1.07 to 1.62)90-dayControl162 (2.8)2.8AAV89 (5.9)5.91.87 (1.42 to 2.46)MIFull studyControl234 (4.0)5.8AAV77 (5.1)6.61.15 (0.90 to 1.47)365-dayControl115 (2.0)2.0AAV54 (3.6)3.61.52 (1.10 to 2.10)90-dayControl53 (0.9)0.9AAV42 (2.8)2.82.52 (1.63 to 3.88)Stroke/TIAFull studyControl205 (3.5)5.2AAV85 (5.6)7.01.49 (1.10 to 2.02)365-dayControl85 (1.5)1.5AAV47 (3.1)3.11.87 (1.25 to 2.80)90-dayControl37 (0.6)0.6AAV37 (2.4)2.42.92 (1.76 to 4.85)CV deathFull studyControl285 (4.9)6.2AAV54 (3.6)4.10.66 (0.49 to 0.89)365-dayControl158 (2.7)2.7AAV34 (2.2)2.20.81 (0.55 to 1.20)90-dayControl85 (1.5)1.5AAV17 (1.1)1.10.85 (0.46 to 1.56)AFFull studyControl460 (7.9)11.5AAV205 (13.5)16.41.51 (1.30 to 1.75)365-dayControl236 (4.1)4.1AAV148 (9.7)9.82.06 (1.71 to 2.48)90-dayControl131 (2.3)2.2AAV124 (8.2)8.23.33 (2.66 to 4.18)CHFFull studyControl598 (10.3)13.3AAV240 (15.8)20.81.41 (1.22 to 1.63)365-dayControl350 (6.0)6.0AAV177 (11.6)11.71.75 (1.48 to 2.07)90-dayControl170 (2.9)2.9AAV143 (9.4)9.42.65 (2.15 to 3.26) Open table in a new tab ANCA vasculitis is associated with a high risk of certain types of cardiovascular events, particularly in the early period following diagnosis.

Glomerulonephritis in AKI: From Pathogenesis to Therapeutic Intervention.

Acute kidney injury (AKI) is increasingly emerging as a global emergency. Sepsis, major surgery, and nephrotoxic drugs are the main causes of AKI in hospitalized patients. However, glomerulonephritis accounts for about 10% of AKI episodes in adults, mainly related to rapidly progressive glomerulonephritis resulting from granulomatous polyangiitis (GPA, Wegener granulomatosis), microscopic polyangiitis (MPA), and anti-glomerular basement membrane (GBM) disease. Also, diffuse proliferative lupus nephritis, immunoglobulin A nephropathy, post-streptococcal glomerulonephritis, mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, membranous nephropathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and scleroderma can induce acute renal failure. Early diagnosis of AKI due to glomerulonephritis is crucial for prompt, effective management to improve short- and long-term outcomes. Kidney biopsy is the gold standard for the diagnosis of glomerular disease, but it is not frequently performed in critically ill patients because of their clinical conditions. In this setting, a growing number of diagnostic assays can support the working hypothesis, including antineutrophil cytoplasmic antibodies (ANCAs), anti-double-stranded DNA antibodies, anti-GBM antibodies, antistreptolysin O and anti-DNase B antibodies, cryoglobulins, antiphospholipid antibodies, and complement levels. Therapeutic strategies in AKI patients with glomerulonephritis include high-dose corticosteroids, cyclophosphamide, and plasma exchange. This article reviews the wide spectrum of glomerulopathies associated with AKI, describing the immunological mechanisms underlying glomerular diseases and presenting an overview of the therapeutic options.

Efficacy of Rituximab Therapy for Oculomotor Nerve Palsy and Vision Loss Due to Granulomatous Polyangiitis

Efficacy of Rituximab Therapy for Oculomotor Nerve Palsy and Vision Loss Due to Granulomatous Polyangiitis

Ophthalmic Presentation of Undiagnosed Sinonasal Masses.

To evaluate clinical features of patients who first present with orbital symptoms and signs due to undiagnosed sinonasal pathology. Retrospective chart review for patients seen at Moorfields Eye Hospital between 1969 and 2020. Patient demographics and clinical features were reviewed. Four hundred and forty-eight patients (250 males; 56%) presented to ophthalmologists with undiagnosed sinonasal pathologies, the patients attending at an average age of 47 years and having first symptoms at an average age of 46 years. The commonest presenting symptoms were proptosis (153 patients; 34%), orbital ache or pain (133; 31%), periorbital swelling (130; 29%), and diplopia (98; 22%). Eighty-seven patients (20%) had a corrected acuity of 6/18 or worse, and 66 (16%) had an ipsilateral relative afferent pupillary defect. There was 2.3 mm relative exophthalmos (median 2 mm; range 0-17 mm) in patients with unilateral disease, an orbital mass was palpable in 218 patients (49%), ocular movements were reduced in 252/448 (56%), and nonaxial displacement of the globe was recorded in 296/424 (74%). The commonest pathologies were sinus mucoceles (38%), sinus carcinoma (11%), and granulomatous polyangiitis (10%). Multivariate regression analysis of mass lesions identified periorbital pain (odds ratio, 6.0; 95% confidence interval, 1.7-21.5; P = 0.005) and reduced motility (odds ratio, 3.2; 95% confidence interval, 1.1-9.0; P = 0.03) as features most predictive for undiagnosed sinonasal malignancy. This study describes a large group of patients in whom unknown midfacial masses presented initially to the ophthalmologist: Mucoceles and sinonasal malignancy were the commonest lesions, and nonaxial globe displacement-particularly inferolateral, lateral, or upward-is commonly associated with sinonasal pathology. Pain and reduced ocular movements significantly favor a malignant, rather than benign, tumor.

Marked neurological and immunological improvement in refractory eosinophilic granulomatous polyangiitis after treatment with mepolizumab, an anti‐interleukin‐5 antibody: A case report

AbstractBackgroundMepolizumab is an option for add‐on therapy in cases of refractory or relapsing eosinophilic granulomatous polyangiitis (EGPA). However, it has not been fully investigated if add‐on mepolizumab is effective for active refractory or active relapsing EGPA patients with life‐ and/or organ‐threatening manifestations, especially with severe neuropathy.Case presentationWe herein report on a 63‐year‐old man with severe progressive neuropathy secondary to active relapsing EGPA. In this case, the optimal dose of glucocorticoids and cyclophosphamide could not be used because of glaucoma and signet ring cell carcinoma. Add‐on therapy of mepolizumab showed prompt immunological remission and marked improvement in neurological manifestations.ConclusionsMepolizumab can be considered as an important induction therapy option for active relapsing or refractory EGPA. It has the potential to effectively improve neurological disturbances associated with severe neuropathy in EGPA.

Nasal and Lacrimal Sac Histopathology in Patients With Granulomatous Polyangiitis Undergoing Lacrimal Drainage Surgery.

To examine histological changes within nasal and lacrimal sac mucosa harvested from patients with granulomatous polyangiitis (GPA) who required lacrimal drainage surgery. As these patients were considered quiescent on clinical and serological grounds, particular attention was paid to the presence of active vasculitis. Retrospective noncomparative case series. Patients with GPA who had open lacrimal drainage surgery under the care of a single surgeon between 1991 and 2017. All patients had paired biopsies of both nasal and ipsilateral lacrimal sac mucosa. Biopsies of the nasal and lacrimal sac mucosa, taken from the operative site during either primary or revisional open dacryocystorhinostomy, were reported by experienced ophthalmic histopathologists. Outcome measures were the surgical appearance of the tissues and the proportion of each tissue showing histological evidence of active vasculitis, chronic inflammation with or without fibrosis, marked fibrosis without inflammation, or acute-on-chronic inflammatory changes. Paired tissues were available from 47 patients (25 females; 53%) who had undergone 64 procedures (57 primary, 7 revisional). All patients had systemic disease, this being known prior to surgery in 43 patients (with 41/43 on long-established systemic immunosuppression) and suspected clinically after the initial lacrimal examination in 4/47. Most lacrimal sacs and nasal spaces showed a variety of abnormalities, this commonly being extensive scarring. Despite most patients being considered to have inactive systemic GPA, active vasculitis was evident in 23/64 (36%) lacrimal sac biopsies and 32/64 (50%) nasal mucosal biopsies-suggesting that serological markers may not be reliable guide to disease activity where disease is of limited volume (as, for example, with limited sino-nasal disease). Chronic lymphocytic inflammation was present in a further 35/64 (55%) sacs-associated with marked fibrosis in 5-and a further 25/64 (41%) nasal biopsies (with fibrosis in 2). The lacrimal sac and nasal space are highly abnormal in most patients with GPA undergoing lacrimal drainage surgery. Despite having clinically and serologically inactive disease on established systemic immunotherapy, histological examination often shows unrecognized active vasculitis, which might indicate inadequate systemic immunosuppression for the underlying condition.Lacrimal sac and nasal mucosa from patients with granulomatous polyangiitis undergoing dacryocystorhinostomy usually show chronic lymphocytic inflammation with marked fibrosis, but up to half reveal active vasculitis despite long-established systemic immunosuppression and apparently "quiescent" disease.

Granulomatous interstitial nephritis in granulomatosis with polyangiitis mimicking leprosy: A case report

Granulomatous polyangiitis (GPA) is a small vessel vasculitis commonly affecting the upper and lower respiratory tracts and kidneys. About 90% of the cases are associated with ANCA, namely, PR3-ANCA and MPO-ANCA. Herein, we describe a patient of GPA who presented with anasarca, sensory neuropathy, recurrent upper airway congestion, epistaxis, and rapidly progressive glomerulonephritis. Granulomatous interstitial nephritis and necrotizing granulomatous inflammation of the nasal septum were found on biopsy of the kidney and nasal septum, respectively both of which are rare findings. PR3-ANCA and MPO–ANCA were negative. Fulfilling the ACR criteria, this case of GPA proves that biopsy is still the gold standard of diagnosis.

CHARACTERISTICS OF AUTOIMMUNE INFLAMMATION IN THE PATIENTS WITH LUNG TUBERCULOSIS

Tuberculosis is a granulomatous disease caused by Mycobacterium tuberculosis, being characterized by the development of caseous granulomas in various organs, mainly in lungs. M. tuberculosis is known to be a trigger for autoimmune inflammation, due to the possible mimicry of bacterial proteins as autoantigens. Recently, a significance of mesenchymal vimentin as an autoantigen in mycobacterial infections has been actively discussed. The aim of the present study was to determine autoantibodies for various vimentin modifications in the patients with tuberculosis.The study was performed in 2014-2017 and included 28 patients with pulmonary tuberculosis (group I), 30 patients with nonspecific lung diseases (group II): 15 with granulomatous polyangiitis, and 15 with different alveolites. Control group consisted of healthy subjects (n = 40). Concentration of antibodies to mutated citrullinated vimentin (anti-MCV) was measured using ELISA (ORGENTEC, Germany). The patients with elevated anti-MCV levels were tested for antibodies to cyclic citrullinated peptide (anti-CCP) using ELISA technique (EUROIMMUN, Germany). Statistical analysis was carried out using GraphPad Prism 6 (GraphPad Software, USA), Statistica 10 (Statsoft, USA) using nonparametric analysis of samples with Mann-Whitney and Chi-square criteria, and Spearman method for correlation analysis. The differences were considered statistically significant at p < 0.05.The anti-MCV concentrations were significantly higher in patients with tuberculosis (group I, 60.7% of cases, 17/28) than in group II, and control group (23.6 and 25.0% of cases, respectively). No statistically significant differences were revealed between the results of anti-MVC and anti-CCP levels in comparison group with the control group (p = 0.18).High levels of anti-MCV antibodies in the patients with pulmonary tuberculosis reflect an opportunity of developing autoimmune process in the disease pathogenesis. Measurement of plasma anti-MCV antibody concentrations may be important for correction of the therapy, especially upon administration of immunosuppressive and hormonal corticosteroid drugs. It has been shown that anti-CCP are not characteristic to the lung diseases.

Eosinophilic Myo-Pericarditis Presenting as Cardiac Tamponade

Eosinophilic myocarditis is a rare and acute life threatening condition often associated with drug reactions, eosinophilic granulomatous polyangiitis (formerly Churg-Strauss syndrome), Loeffler endomyocardial disease, parasite infections, and idiopathic hypereosinophilic syndrome. We describe a case of eosinophilic granulomatous polyangiitis presenting as progressive pericardial effusion and cardiac tamponade.

External dacryocystorhinostomy in patients with granulomatous polyangiitis.

To review the outcome for primary or revisional external dacryocystorhinostomy in patients with granulomatous polyangiitis. Retrospective case-note review to include age at presentation, duration of prior GPA, immunosuppression at time of surgery, nature of first lacrimal surgery, and symptomatic control. Forty-eight patients (25 female; 52%) presented at an average age of 50.5 years and 7 (15%) had prior lacrimal surgery on one (5/7; 71%) or both sides. The duration of systemic GPA varied, with 40% having disease for up to 3 years prior to lacrimal referral, and 41/48 (85%) being on systemic immunosuppression. Forty-eight patients had 71 affected drainage pathways-having symptoms for an average of 22 months (range <1 month to 7 years). Surgery was undertaken on 70/71 systems-62/70 primary DCRs (20 unilateral; 8 simultaneous bilateral; 13 sequential bilateral). Of nine systems with persistent symptoms after prior surgery, eight underwent revisional surgery (six unilateral; one sequential bilateral). With a follow-up of 2.5 years (range 3 months to 14 years), volume symptoms were cured in all 70 cases. Flow symptoms were controlled in 58/62 (94%) systems after primary DCR, and all eight after revisional surgery. Of four sides with persistent epiphora, one was cured with revisional DCR and three with placement of Jones' canalicular bypass tubes. Mucoid discharge, dacryocystitis and recurrent conjunctivitis were cured in all patients with GPA after either primary and revisional surgery. Continued epiphora was controlled in most patients with additional closed procedures.

Relationship Between Immunosuppressive Therapy and the Development of Infectious Complications Among Patients with Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis: A Single-center, Retrospective Observational Study.

IntroductionInfectious complications are the leading cause of death in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). However, the relationship between initial immunosuppressive therapy and the development of infectious complications and the details of infectious complications among patients with AAV are uncertain. We thus aimed to determine the association between initial immunosuppressive therapy and infectious complications.Material and methodsForty-seven patients with newly diagnosed AAV were enrolled in this retrospective observational study (patients with eosinophilic granulomatous polyangiitis were excluded). We statistically determined the association between types of initial immunosuppressive therapy (methylprednisolone pulse and/or cyclophosphamide therapy) and the development of infectious complications. In addition, we investigated the causes and timing of the onset of infectious complications.ResultsTwenty-one (21; 44.7%) patients required antibiotic, antimycotic, or antiviral therapy because of the development of infectious complications. Multiple logistic regression analyses adjusted for age and sex revealed that methylprednisolone pulse and cyclophosphamide therapy were significantly associated with the development of infectious complications (odds ratio (OR) 4.85, 95% confidence interval (CI) 1.09-21.5, p = 0.038; OR 5.32, 95% CI 1.28-22.2, p = 0.022, respectively). Bacterial pneumonia and sepsis occurred in 10 (47.6%) and 6 (28.6%) patients, respectively. Almost half of these infectious complications, including fungal infection, developed within six months from the start of initial treatment.ConclusionAmong patients with AAV, methylprednisolone pulse and cyclophosphamide therapy may increase the risk of developing infectious complications, such as pneumonia and sepsis, including fungal infection, particularly within six months from the initiation of treatment.

Hepatitis B Virus-associated Vasculitis: Multiple Cavitary Masses in the Lung Mimicking Granulomatous Polyangiitis

Hepatitis B virus (HBV) is one of the main causes of polyarteritis nodosa (PAN). We herein report a rare case of HBV-associated vasculitis presenting with multiple pulmonary nodules, mimicking granulomatous polyangiitis (GPA), with no abnormalities of the ear, nose, or kidney. A surgical lung biopsy revealed geographic necrosis surrounded by palisading granuloma and capillaritis. Because the HBV surface antigen was positive with a serum HBV-DNA level of 2.9 log10 copies/mL, we first treated the patient with entecavir and 2 weeks of prednisone 50 mg/day. The pulmonary nodules resolved, and seroconversion was observed after one month.

EOSINOPHILIC MYO-PERICARDITIS PRESENTING AS CARDIAC TEMPONADE

Eosinophilic myocarditis is a rare and acute life threatening condition often associated with drug reactions, eosinophilic granulomatous polyangiitis (formerly Churg-Strauss syndrome), Loeffler endomyocardial disease, parasite infections, and idiopathic hypereosinophilic syndrome. We describe a case