Neutrophil Cytoplasmic Antibodies Research Articles

Peripheral Ischemia and Necrosis Revealing Buerger's Disease in an Internal Medicine Department

Buerger's disease is a systemic vasculitis strongly correlated with tobacco use. It entails a heavy socio-occupational impact. We report the case of a 26-year-old patient with ischemia of the lower limbs revealing Buerger’s disease. He is known smoker with passive exposure to Indian hemp. He was seen for ischemic foot pain that had been progressing for a year. Involvement began in the left big toe. Subsequently, hyperalgesic necrotic lesions were observed on the 3rd, 4th and 5th toes of the foot. Biological investigations revealed an inflammatory syndrome with normocytic anemia and increased C-reactive protein. Retroviral, syphilitic, Hepatitis B and C viruses and SARS-CoV-2 serologies were negative. Antinuclear antibodies were initially borderline at 100 IU with speckled fluorescence, then negative on control. Neutrophil cytoplasmic antibodies and antiphospholipid antibodies were negative. Investigation of thrombophilia was non-contributory, notably factor V mutation testing, antithrombin III assay, proteins C and S and fibrinogen. An arterial ultrasound revealed extensive arterial thrombosis with thickening of the femoral arterial vessel walls. Thromboangiitis obliterans was confirmed and the patient was put on corticosteroids and adjuvant therapy. Surgical treatment was performed 4 months later. Buerger's disease is a serious vascular disorder which must be diagnosed very early in order to prevent complications. Early smoking cessation leads to remission in the early phase.

Atypical Anti-GBM with ANCA Vasculitis- A Rarest of the Rare Entity: Index Case from Eastern India

Anti-glomerular basement membrane (GBM) antibody glomerulonephritis is an extremely rare glomerular disease. Around 90% of the patients are positive for serum anti-GBM antibodies while up to 10% can be negative. In such patients, only a kidney biopsy can reveal the anti-GBM disease it is then labeled as an atypical anti-GBM disease. Though anti-GBM disease can be associated with Anti Neutrophil Cytoplasmic Antibodies (ANCA) positivity, it is extremely rare to find atypical anti-GBM with ANCA positivity so much so that till now there are very few such cases reported from across the world. The case presented here is one such case where the patient presented with adult-onset nephrotic syndrome features with active urinary sediments and mildly deranged renal function. Myeloperoxidase (MPO) ANCA was positive and it was considered ANCA-associated crescentic glomerulonephritis (GN) but after the renal biopsy the picture was of anti-GBM disease. She was treated with pulse methylprednisolone but her creatinine increased in the meantime and considering anti-GBM she was put on Plasma Exchange (PLEX). She received 5 sessions of PLEX after which her renal function improved. She was also planned for Rituximab which could not be given due to local infection. As there are no protocols for treating such cases because of the extremely rare nature of the presentation, this case will increase the understanding of such presentations for the clinicians. This will help to plan for building the approach for such cases.

Systemic vasculitis associated with anti neutrophil cytoplasmic antibodies in Bulgaria – epidemiological, health-demographic and clinical-pharmacological real-world data

Systemic vasculitis associated with anti neutrophil cytoplasmic antibodies in Bulgaria – epidemiological, health-demographic and clinical-pharmacological real-world data

Digital Ulceration in a Patient with Interstitial Lung Disease: An Unusual Case of Microscopic Polyangiitis

OBJECTIVES Microscopic polyangiitis (MPA) is part of the associated vasculitis family of the neutrophil cytoplasmic antibody (ANCA). MPA can be distinguished by its positivity for antibodies against myeloperoxidase (MPO-ANCA). The condition can involve any organ of the body, particularly the lungs, kidneys, and skin. This case highlights an atypical case of MPA in which a patient had interstitial lung disease (ILD) and later developed a vasculitic skin lesion without renal involvement. A 65-year-old female already diagnosed with ILD was evaluated for digital ulcers associated with bilateral pins and needle sensation in both upper and lower limbs. Examination revealed lesions on the index and middle finger of the left hand. The MPO-ANCA antibody test was positive, and a diagnosis of MPA was made based on a skin lesion biopsy. There was subsequent initiation of combination therapy consisting of azathioprine, hydroxychloroquine, prednisolone, and nifedipine. The patient was instructed for close follow-up. This case report highlights the importance of considering an underlying vasculitis in patients with ILD and emphasizes the significance of a thorough diagnostic evaluation and multidisciplinary management. This case also highlights that patients with interstitial lung diseases should be evaluated for secondary causes, and early treatment of the exact causes can prevent the late sequelae of the disease, such as skin manifestations in this patient.

The development of anticyclic citrullinated peptide (anti-CCP) antibody following severe COVID-19.

The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID-19). This study was conducted to clarify the occurrence of autoantibodies (AABs) associated with systemic autoimmune rheumatic diseases (SARDs) in hospitalized patients with a moderate, severe, and critical form of COVID-19. The serum samples obtained from 176 hospitalized COVID-19 patients were investigated in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID-19. Also, the serum samples collected from healthy subjects before the COVID-19 pandemic were used as controls (N = 176). The antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), cytoplasmic-anti neutrophil cytoplasmic antibody (c-ANCA), perinuclear ANCA (p-ANCA), antiphospholipid antibodies (aPLs), and anticyclic citrullinated peptide (anti-CCP) occurrence was evaluated using a solid-phase enzyme-linked immunosorbent assay (ELISA). The results showed that the occurrence of ANAs, anti-dsDNA, anti-CCP, c-ANCA, and p-ANCA was significantly higher in the COVID-19 patients compared to serum obtained from healthy subjects (p < .0001, p < .0001, p < .0001, p < .05, and p < .001, respectively). The positive number of anti-CCP tests increased significantly in severe COVID-19 compared to the moderate group (p < .01). Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases. To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti-CCP in a severe form of COVID-19.

#6722 A RARE CASE OF ACUTE KIDNEY INJURY IN A PATIENT GRANULOMATOSIS WITH POLYANGIITIS, MONOCLONAL GAMMOPATHY WITH RENAL SIGNIFICANCE AND AMYLOIDOSIS

Abstract Introduction Anti - neutrophil cytoplasmic antibody /ANCA/- associated vasculitis is a small vessel vasculitis. It is a rare, autoimmune, inflammatory disease, with undetermined etiology, including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis. It could lead to pauci - immune necrotizing and crescentic glomerulonephritis and rapidly progressive glomerulonephritis. Monoclonal gammopathy of renal significance /MGRS/ is a plasma cell or B-cell disorder that could lead to renal impairment due to production of monoclonal protein, which do not meet the criteria for myeloma multiplex. There is a significant higher risk in progression to end stage renal disease/ESRD/ in groups with renal vasculitis and concomitant disease due to nonrenal factors. Clinical case We present a rare clinical case of a patient with combination of ANCA -vasculitis, MGRS and amyloidosis. A 60 year-old male patient with deteriorated renal function was presented to the clinic. Chronic congestive heart failure, arterial hypertension, situs inversus, anemic syndrome, hepatosplenomegaly were reported as concomitant diseases. Due to progressive worsening of renal function emergency hemodialysis treatment was initiated through temporary vascular access. Against the background of several chronic diseases, which could lead to chronic kidney failure, the echographic image of the kidneys stands out. Both kidneys are enlarged, with increased echogenicity of the parenchyma as in a diffuse renal process. The performed immunological tests confirm the diagnosis of granulomatosis with polyangiitis /formerly called Wegener's/, PR3-105,7. The results for the screened viral infections was negative. An episode of severe pulmonary edema was registered in the context of obstruction of the hemodialysis catheter due to coagulation disorders. The renal biopsy supports the diagnosis of vasculitis, crescentic glomerulonephritis - in advanced stage of development, probably a morphological manifestation of secondary nephropathy. An interesting finding is the presence of amyloidosis /AL/. The immunofixation blood test identify monoclonal IgG kappa type component. A sternal puncture, SPECT/CT was performed and diagnosis of multiple myeloma was excluded. Pathogenic treatment with corticosteroids and cyclophosphamide was initiated. In addition a short-term change in vision is observed in the context of the underlying disease. A consultation with ophthalmologist and neurologist was held, confirming cerebral arteritis. At this stage the recovery of renal function is incomplete. High flux membrane were used during dialysis treatment to reduce large and middle sized molecules. In addition, for the treatment of light chain amyloidisis, bortezomib was considered. Conclusion This clinical case emphasizes on the need to precisely clarify the cause that led to acute kidney injury. A thorough search for the underlying disease causing the deterioration of kidney function is critical for the renal outcome. The reasons for incomplete recovery of renal function during active treatment of vasculitis should be sought in underlying diseases-arterial hypertension, chronic heart failure, amyloidosis. Discussion Younger patients with lower eGFR at the onset of ANCA-associated vasculitis and no concomitant disease show significant improvement in renal function by the end of the first year regardless the need of dialysis treatment. Patients with severe accompanying disease have slow and insufficient improvement in renal function due to the prevalence of higher percentage of globally sclerotic glomeruli. Considering the severe prognosis of ANCA-associated vasculitis it is crucial to start early treatment. The state of the renal function at the first year of pathogenic treatment along with the pathological findings of the renal biopsy could be a predictors for the renal function course.

Role of Complement in Kidney Diseases - New Aspects

Complement is a central part of the immune system. In the human body, complement is responsible for recognition of infectious microbes, for coordinating the adaptive immune response, controlling homeotic reactions and for the non-inflammatory removal of modified self-cells and infectious microbes. Complement is also closely linked to another proteolytic cascade, the coagulation system. Defective activation and altered complement regulation drives pathology of several severe human kidney diseases.This manuscript summarizes the latest developments on the role of complement in kidney diseases, on new complement inhibitors and on recent complement targeting therapies. In particular focusing on diseases (1) atypical Hemolytic Uremic Syndrome, (2) C3 Glomerulopathy, (3) Anti Neutrophil Cytoplasmic Antibody Mediated Vasculitis, (4) IgA Nephropathy, (5) Membranous Glomerulopathy, (6) Systemic Lupus Erythematosus, (7) Transplant rejection and (8) COVID 19 Infection-Triggered Kidney Diseases. More excitement is generated in this field, as more and more complement mediated diseases can be treated. Several complement targeting compounds are approved by the EMA and FDA and an increasing number of new candidates are in late phase clinical trials. In addition, clinical guidelines are developed for Diagnosis and Therapy of complement mediated diseases, new biomarkers are evaluated in clinical studies, and diagnostic guidelines are in development. The recent Covid infections showed a clear link of complement in thrombo inflammation, which ultimately results in kidney damage. These aspects have increased further the focus of complement inhibitors in COVID infections.

Clinical and Prognostic Significance of p-ANCA Positivity in Idiopathic Pulmonary Fibrosis: A Retrospective Observational Study.

Perinuclear Anti Neutrophil Cytoplasmic Antibody (p-ANCA) is a serological marker of Microscopic Polyangiitis (MPA), a vasculitis associated with lung involvement potentially mimicking Idiopathic Pulmonary Fibrosis (IPF). In this study, we evaluated the role of p-ANCA in predicting clinical evolution and prognosis in a cohort of IPF patients. In this observational, retrospective, case-control study, we compared 18 patients with an IPF diagnosis and p-ANCA positivity with 36 patients with seronegative IPF, matched for age and sex. IPF patients with and without p-ANCA showed similar lung function decline during the follow-up, but IPF p-ANCA+ showed better survival. Half of IPF p-ANCA+ patients were classified as MPA for the development of renal involvement (55%) or skin signs (45%). The progression towards MPA was associated with high levels of Rheumatoid Factor (RF) at baseline. In conclusion, p-ANCA, mainly when associated with RF, could predict the evolution of Usual Interstitial Pneumonia (UIP) towards a definite vasculitis in patients, with a better prognosis compared with IPF. In this view, ANCA testing should be included in the diagnostic workup of UIP patients.

血胸を伴う出血性ショックを来した左胃動脈瘤破裂の1例(A ruptured aneurysm of left gastric artery that progressed to right hemothorax: a case report)

症例は50歳代女性，心窩部痛と呼吸苦で発症し，近医にて胸水を指摘されて前医を受診した。前医では，単純CT検査で血性胸腹水，食道壁肥厚，膵周囲の脂肪織濃度の上昇を認め，2日間加療したが改善を認めないため精査目的に当院へ紹介された。来院時，四肢末梢に湿潤を認め，脈拍110/分，血圧80/50mmHg（ドパミン9μg/kg/min）であった。造影CT検査で右血性胸水と食道裂孔ヘルニア，胸部中部以下の食道から胃噴門部小弯側にかけての血腫を認めたが，食道や肺野など胸部には出血源を認めなかった。腹腔内には血性腹水とともに，胸部中部食道周囲から胃小彎側に連続する血腫を認め，内部に直径1.5cmの左胃動脈瘤を認めた。左胃動脈瘤破裂による出血が，食道裂孔を介して縦隔へ進展し，胸腔内に穿破して血胸に至ったものと推測した。血胸に対して単回の胸腔穿刺，左胃動脈瘤破裂に対して血管造影による塞栓術を施行した。翌日から経口摂取を開始し，血胸が再燃することもなく経過は良好で，第22病日に自宅退院した。腹部内臓動脈瘤破裂による出血が食道裂孔を介して胸腔内に穿破し，血胸を契機に診断された稀な症例を経験したので報告する。 A 59–year–old woman visited her local hospital with dyspnea and epigastric pain. A chest X–ray showed a right pleural effusion. The patient consulted a second hospital where she was treated for two days, but due to her unstable vital signs, she was transferred to our hospital. A contrast–enhanced CT scan revealed a right hemothorax and esophageal hiatal hernia. While there was no source of bleeding in the thoracic cavity, there was an intra–abdominal hemorrhage from a ruptured aneurysm of the left gastric artery. The suspected cause of the hemothorax was bleeding from a ruptured aneurysm that entered the thoracic cavity through the esophageal hiatus. We performed a transcatheter arterial embolization for the ruptured aneurysm. After treatment, the patient recovered without significant incidents and was discharged on the 22nd day of hospitalization. We speculated that the hemorrhage from the rupture of the gastric aneurysm extended through the esophageal hiatus into the mediastinum and perforated into the thoracic cavity, resulting in a hemothorax. Since such conditions are rare, we will report this case with a review of the literature. 腹部内臓動脈瘤は破裂すれば出血性ショックにより致死的状況に至ることもある重篤な疾患である。本邦の腹部内臓動脈瘤破裂として報告されている症例の多くは腹腔内出血による出血性ショックを呈している 1, 2。しかし，今回我々は左胃動脈瘤破裂による出血が食道裂孔ヘルニアを介して縦隔，胸腔内へ進展し，出血性ショックを来した症例を経験したので，文献的考察を加えて報告する。 本論文は，個人情報保護法に基づいて匿名化がなされており，本人から論文報告に関する同意を得ている。また，本論文は倫理委員会の承諾を要する事項として該当しない。 症 例：50歳代の女性 主 訴：心窩部痛 現病歴：搬送6日前に突然の心窩部痛，呼吸困難感が出現し，食事摂取ができなくなった。搬送2日前に近医を受診したところ，胸水を指摘され前医を紹介された。前医受診時より血圧が低下しており，単純CT検査で血性胸腹水，食道壁肥厚，膵周囲の脂肪織濃度の上昇を認め急性膵炎などが疑われた。2日間の入院加療後も改善に乏しく，循環動態の維持にカテコラミン投与を要する状態となったため，当院救命救急センターへ搬送された。 既往歴：特記事項なし 生活歴：ビール１本/日，喫煙なし 来院時現症：意識清明。軽度の呼吸困難感の訴えを認めるが呼吸促拍はなく，呼吸数22/分，酸素飽和度97%（3L/min），顔面蒼白，四肢末梢に冷感湿潤を認め，脈拍110/分，血圧80/50mmHg（ドパミン 9µg/kg/min）。左背部痛の訴えがあるものの圧痛は認めなかった。 血液検査：RBC 213×104 /μL，Hb 6.7g/dL（前医受診時 Hb 9.8g/dL）と著明な貧血を認めた。血小板数や凝固検査には異常を認めなかった。 画像検査：胸腹部造影CT検査；胸部CTでは右血胸，滑脱型食道裂孔ヘルニアを認め，周囲に縦隔血腫，左少量胸水を認めた。腹部CTでは直径1.5cmの左胃動脈瘤を認め（Fig. 1a），周囲の血腫は胸部中部食道周囲から胃小弯側へ連続していた（Fig. 1b）。左肝動脈は左胃動脈から分岐しており，肝左葉外側区に微小動脈瘤を認めた。食道や肺野には出血源を認めなかった。 An enhanced CT scan of the abdomen revealed a pseudoaneurysm of the left gastric artery. Computed tomography (CT) of the chest showed a right massive hemothorax，a slipped esophageal hiatal hernia, and a mediastinal fluid collection (black arrow). 搬入後経過：乳酸リンゲル液の急速輸液を行うとともに輸血を開始した。搬入後より呼吸困難感が増悪し，仰臥位の維持が困難となったため，右血胸に対し慎重に胸腔穿刺を施行したところ，約830mLの血性排液を認めた。穿刺後，呼吸困難感の改善を認め，輸血投与後よりバイタルサインの安定を得た。左胃動脈瘤からの出血が食道裂孔ヘルニアを介して血胸に進展したものと推測し，動脈瘤に対して緊急interventional radiology（IVR）による止血術を行う方針とした。 腹部血管造影：腹腔動脈からの造影では，直径1.5cmの左胃動脈瘤を認め（Fig. 2a），瘤よりも近位より分岐する左胃動脈分枝，瘤末梢から分岐する左肝動脈を金属コイルでisolationし，瘤内をNBCA（n–butyl–2–cyanoacrylate）により塞栓した（Fig. 2b）。 Celiac artery angiography showed a pseudoaneurysm of the left gastric artery and left hepatic artery. Transcatheter arterial embolization (TAE) was done successfully. Arterial flow for the aneurysm was shut out. 入院後経過：後日判明したmyeloperoxidase–anti–neutrophil cytoplasmic antibodies（MPO–ANCA）や，proteinase–3–anti–neutrophil cytoplasmic antibodies （PR3–ANCA）などの血管炎マーカーはいずれも陰性であり，微小動脈瘤形成の所見から，臨床的に節性動脈中膜壊死（segmental arterial mediolysis: SAM）と診断した。濃厚赤血球4単位の輸血投与と緊急IVR後は循環動態の安定が得られた。呼吸器症状も改善し第2病日から経口摂取を開始した。胸水の再貯留は認めず，その後も血胸が再燃することはなかった。IVR後大きな合併症なく経過は良好で，第22病日に独歩で退院した。その後発症から1年までの時点では，新たな動脈瘤の形成もなく経過している。 腹部内臓動脈瘤は比較的稀な疾患であり，その発生頻度は0.01～2%とされている。Stanleyらの腹部内臓動脈瘤1,118例の集計によると，脾動脈が最も多く656例（58.7%），次いで肝動脈が227例（20.2%），上腸間膜動脈瘤89例（7.9%）と続くのに対し，胃動脈瘤は53例（4.7%）であると報告されている 3。 腹部内臓動脈瘤の成因としては，動脈硬化，神経線維種症I型やEhlers–Danlos症候群などの先天性疾患，腹部外傷，ベーチェット病や高安病，多発血管炎などの膠原病，正中弓状靭帯圧迫症候群，慢性膵炎などの炎症性疾患などがあるが，近年画像診断の進歩に伴って，SAMが注目されている 4。SAMは1976年にSlavinらにより提唱された疾患概念 5で，腹部内臓動脈の中膜が分節性に融解し動脈瘤を呈する病態である。稲田らの報告によると，SAMと診断された患者の35.7%に多発動脈瘤を認めており，一般的には異所性，異時性に動脈瘤を形成することが多いとされている 6。 SAMの確定診断は切除標本からの病理学的診断によってなされていたが，近年，画像診断の進歩や開腹手術と比較して低侵襲であるIVRが動脈瘤治療の第一選択となってきており，病理学的確診が得られる機会が少なくなってきた。内山ら 7は腹部内臓動脈瘤の中で，①中高年の患者，②炎症性変化や動脈硬化性病変などの基礎疾患がない患者，③突然の腹腔内出血で発症，④血管造影で血管の数珠状の不正な拡張と狭小化を認める，の4項目をSAMの特徴とし，これに合致するものをSAMと診断する臨床的診断基準を提唱している。本症例においては，中年女性であること，非動脈硬化性，非炎症性であること，血管造影検査で左胃動脈だけでなく左肝動脈外側区領域にも動脈瘤を形成し，特徴的な数珠状変化も認めていたことから臨床的にSAMと診断した。 また，胃動脈瘤の中では左胃動脈瘤破裂が最も多く報告されている。医学中央雑誌による検索では，左胃動脈瘤破裂の本邦報告例は25例であり，いずれも腹腔内出血あるいは消化管出血によるショック症状で搬送されていた。海外においては，腹部内臓動脈瘤破裂に伴い胸水貯留を呈した症例についての報告 8, 9, 10が散見される。一般に，腹部内臓動脈瘤破裂は血性腹水の貯留を認めるが，本症例の場合は血胸を呈していた。横隔膜を隔てた液体成分の移動に関して，腹腔内圧の上昇に伴い，横隔膜小孔を通じて胸腔内へ液体成分が漏出した症例報告がみられる。本症例では，滑脱型食道裂孔ヘルニアが存在し，腹腔内における血腫が食道裂孔を介して腹腔から縦隔へ連続していた。食道裂孔は伸縮性を持つ約3cmの筋性管で，左右の横隔膜脚内側縁により境界される。食道裂孔を形成する筋束は右脚の内側部から送られ，これが食道を包むようにめぐっており，下部食道～胃噴門部は横隔食道膜という靭帯に固定されている。食道裂孔ヘルニアとは，加齢によりこの横隔食道膜が弛緩することにより胃の一部が胸腔側に逸脱した状態である。食道は漿膜を持たず，周囲は疎な結合組織と脂肪組織に覆われているため，食道胃接合部手術における剥離は容易である。また，右胸腔とは薄い食道臓器鞘で接していることから，剥離操作時には右胸腔開放に注意を要する。腹部内臓動脈瘤破裂症例で，合併する食道裂孔ヘルニアを通じて胸腔穿破，胸水貯留を来した報告は少数にみられ 11, 12，食道裂孔ヘルニア内の胃穿孔から縦隔気腫や膿瘍を形成した報告例 13もある。また，慢性膵炎における仮性膵嚢胞で，嚢胞が後腹膜を頭側へ進展することで食道裂孔を貫き，胸腔へ穿破，内瘻を形成したことで膵性胸水貯留を来した症例も報告されている 14。食道裂孔部が弛緩した状態では，食道周囲の結合組織が疎であることによる血腫の下縦隔への進展，そこに接する胸膜穿破が起こりうると考える。本症例は，画像診断では血胸の原因となる病変を肺，胸膜，食道に認めず，単回の胸腔穿刺ドレナージとIVRによる止血術で血胸の再燃を認めなかった。左胃動脈瘤破裂による出血が，腹腔内の圧が上昇したことで，最も抵抗の少ない食道裂孔ヘルニア部から疎な結合組織を通じて縦隔へ進展し，壁側胸膜を穿破して血胸に至ったものと推測した。 右血胸を伴い出血性ショックを呈した左胃動脈瘤破裂の症例を経験した。腹腔内を出血源とする血液が，食道裂孔ヘルニアを介して主に胸腔内へと進展した可能性が考えられた。 共著者全員が利益相反はない。

317 Case of Goodpasture syndrome With Double-Positive Anti-Glomerular Basement Membrane (GBM) and Myeloperoxidase-Anti Neutrophil Cytoplasmic Antibodies (MPO-ANCA)

317 Case of Goodpasture syndrome With Double-Positive Anti-Glomerular Basement Membrane (GBM) and Myeloperoxidase-Anti Neutrophil Cytoplasmic Antibodies (MPO-ANCA)

Meloxicam-associated immune thrombocytopenia

A 71 year old man presented with a 24 hour history of a pruritic rash on his bilateral lower extremities, petechiae and purpura. 3 days prior he saw an Ophthalmologist for eye dryness and pain. He was prescribed eye drops and Meloxicam. After taking Meloxicam, he developed petechiae and purpura in both lower extremities (Figure 1) prompting him to seek medical care. Admission complete blood count revealed a platelet count of 3,000 (reference range, 142,000-424,000 per microliter). He was started on empiric intravenous immunoglobulin (IVIG) therapy and methylprednisolone for suspected immune thrombocytopenic purpura (ITP). Evaluation for hidden secondary causes of ITP was unremarkable: comprehensive metabolic panel, antinuclear antibody, cytoplasmic antineutrophil cytoplasmic antibodies, perinuclear anti neutrophil cytoplasmic antibodies, Hepatitis panel, HIV 1 &amp; 2, Helicobacter pylori, urinary toxicology test, Vitamin B12 level, rheumatoid factor, double stranded DNA, Epstein Barr virus (EBV) PCR, Varicella Zoster virus (VZV) PCR, Cytomegalovirus PCR, CD5, CD19, CD20, CD23 and antiphospholipid antibodies. Computed tomography with contrast of the abdomen/pelvis, chest and brain were all unremarkable. Hematology consultant recommended a five day course of IVIG 400 mg/kg and methylprednisolone 125 mg IV before discharge. Upon discharge, the platelet count had risen to 15,000. He was prescribed prednisone and instructed to follow-up with hematology.

Atypical presentation of multiple sclerosis – A few points to ponder

The article by Dr. Aishwarya Angadi has brilliantly highlighted how multiple sclerosis can present as unilateral internuclear ophthalmoplegia. The author has meticulously examined the patient and presented it along with the detailed neurological findings. Early detection of multiple sclerosis can go a long way in reducing the morbidity of the disease through timely treatment and intervention. From an academic point of view, there are a few points that I would like to contribute. Since the patient complained of visual blurring, subclinical optic neuritis should have been ruled out with a visually evoked potential test.[1] In the cerebrospinal fluid study, the number of oligoclonal bands is significant for the prognosis of multiple sclerosis.[2] In a case of multiple sclerosis, NeuroMyelitis Optica Immunoglobulin G (NMOIgG) and anti-Myelin Oligodendrocyte Glycoprotein (anti-MOG) antibody should be tested.[345] Lesions on Magnetic Resonance Imaging (MRI) should fulfil McDonald's criteria to qualify as those of multiple sclerosis. MRI orbit is relevant in this case. Also, MRI brainstem should show lesions in the medial longitudinal fasciculus to explain the internuclear ophthalmoplegia. As this patient was positive for Anti Neutrophil Cytoplasmic Antibodies (ANCA), autoimmune vasculitis should also be ruled out. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

De novo and relapsing necrotizing vasculitis after COVID-19 vaccination.

ABSTRACTWe describe five cases of severe necrotizing vasculitis following the RNA-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including four relapsing anti neutrophil cytoplasmic antibodies (ANCA) vasculitis, 27 days (1–60) after vaccination and one patient with quiescent chronic hepatitis B and de novo polyarteritis nodosa (PAN) 21 days after vaccination. Ten other cases were reported to the French national pharmacovigilance database: six patients with ANCA-associated vasculitis and four patients with PAN (first symptoms 19 days on average after vaccination). Five of these 10 patients developed kidney dysfunction. In conclusion, coronavirus disease 2019 (COVID-19) vaccines can be associated with de novo or recurrent ANCA vasculitis or PAN. Attention should be paid to patients with known ANCA vasculitis or patients with a history of hepatitis B infection.

POS-160 CLINICAL AND HISTOMORPHOLOGICAL SPECTRUM OF CRESCENTIC GLOMERULONEPHRITIS FROM SOUTHERN INDIA-A SINGLE CENTER EXPERIENCE

Proliferative extracapillary (crescentic) glomerulonephritis on histology portends a poor clinical prognosis and is commonly associated with etiologies such as anti glomerular basement membrane disease (anti-GBM), anti neutrophil cytoplasmic antibody (ANCA) vasculitis, Infection related glomerulonephritis (IRGN).There is a heterogeneity in etiologies reported from SouthAsia. This study evaluates clinical and histological spectrum of crescentic glomerulonephritis (CrGN) presented to our institute.

POS-156 MANAGEMENT AND OUTCOMES OF ANCA ASSOCIATED VASCULITIS AT A TERTIARY HEALTHCARE FACILITY

Anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare disorder with annual incidence estimated to be around 1.3 per 100,000 population. Renal involvement is one of the main predictors of mortality and morbidity, with approximately 30% of patients with renal involvement progressing to ESRD after 5 years. Renal biopsy can provide a definite diagnosis, and may predict the renal prognosis in AAV. Limited data is available on its management and outcomes, thus we aim to assess this at our tertiary care renal facility. This was a retrospective cohort study. We included patients with a documented diagnosis of ANCA positive vasculitis between 1st of January 2012 to the 31st December 2017, with a follow up period until 31st December 2019. Using a standardized data collection form we recorded the number of patients who had a renal biopsy, the induction and maintenance therapies used, along with relapse induction and maintenance therapies. At the end of the follow-up period outcomes were divided into progression to end-stage renal disease (ESRD), death, established chronic kidney disease (CKD), and preservation of renal function. Data of thirty-six patients were included in the final study. The patient baseline characteristics are listed in Table 1. Thirty-two patients (94.1%) had a documented renal biopsy. The majority of patients (66.7%) had cyclophosphamide for induction, followed by rituximab (19.4%). Seven patients (19.4%) had a documented relapse during the study period, 4 MPO+ and 3 PR3+. Six patients (85.7%) had rituximab as an induction therapy for relapse. The majority of patients were on azathioprine (61.1%) as maintenance therapy after induction. This was similar to the maintenance therapy used after relapse (57.1%). Progression to ESRD occurred in 11 (30.6%), death in 4 (11.1%), established CKD in 15 (41.7%), and preservation of renal function in 6 (16.7%) patients by the end of the follow up period. While cyclophosphamide remains the choice of induction immunosuppresion therapy, we favour rituximab as an induction agent in relapse of AAV. However despite aggressive immunosuppresion therapy the incidence of ESRD and death remains high in these patients. The current management and outcomes are comparable to present international guidelines and cohorts. We look forward to new updates and therapies to improve outcomes in AAV.

A 38 Years Old Man with ANCA Negative Wegener’s Granulomatosis Vasculitis with Type 2 Diabetes Mellitus and Electrolyte Imbalance: A Case Report

A B S T R A C TBackground: Wegener's granulomatosis is a very rare long-term systemicdisorder, in which granuloma formation occurs and inflammation of bloodvessels (vasculitis). The cause of disorder is not yet known, but geneticfactors are thought to play an important role. Clinical symptoms are oftensimilar to other disorders, making diagnosis difficult. However, earlydiagnosis is very important in order to provide effective management.Objective: Diagnosis and management in a rare case of Wegener’sgranulomatosis vasculitis, especially it was found with other comorbidities.Methods: This case report showed a-38-years-old-man that came to theemergency room of Dr Moewardi Hospital with complaints of swellingaccompanied by redness and stiff on the face, hands and feet that worseningsince 7 days ago. He also complained of fever fluctuating, nasal congestionaccompanied by clear discharge and sometimes hearing loss in the rightear. Since the last 3 months, he was often experience similar complaints.History of diabetes was recognized by the patient for 5 years, but he did notregularly take medication. Results: In this case, examination of vital signswithin normal limits. Physical examination revealed a saddle nose with cleardischarge, swelling and redness around the face, hands and feet. Laboratorytests showed hemoglobin 12.9 g/dl, HbA1c 8.4%, sodium level 128 mmol/L,potassium level 3.1 mmol/L, calcium level 1.12 mmol/L. The Anti -Neutrophil Cytoplasmic Antibodies (ANCAs) and Anti Nuclear Antibody(ANA) Indirect Immunofluorescence (IF) method were negative.Electrocardiogram and chest x-ray examination within normal limits.Histopathological examination revealed epidermal atrophy and multiplegranulomas of the dermis. The patient underwent treatment for 10 dayswith tappering-off dose steroid, immunosuppressants, insulin, calcium,and potassium preparations therapy. Conclusions: Wegener’sgranulomatosis vasculitis is a rare case. Prompt and accurate diagnosis andmanagement will prevent poor progression of them, especially it was foundwith other comorbidities.

Necrotising Cutaneous Lesions in Anti Neutrophil Cytoplasmic Antibodies- Associated Vasculitis Mimicking Necrotising Fasciitis

Necrotising vasculitis is a very rare occurrence and commonly caused by an underlying autoimmune pathology. Anti Neutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis is an established cause for cutaneous manifestations of necrotising vasculitis, and is associated with multisystemic involvement, in which presentations of one system may feature predominantly and lead to misdiagnosis. A 33-year-old male presented with acute history of shortness of breath and necrotising blisters over both his ankles and arms. He was initially provisionally diagnosed with necrotising fasciitis, which was eventually ruled out as the serological biomarkers (including low level of C3 and presence of cytoplasmic type of ANCA on indirect immunofluorescence) drew suspicion of an autoimmune pathology. A multidisciplinary approach led to the commencement of steroid, which improved the patient’s condition rapidly. The histological examination of sample from the skin biopsy later confirmed the diagnosis of ANCA-Associated Vasculitis (AAV). The patient eventually recovered with excellent outcomes. Despite its rarity, any abnormal skin lesion may be a subtle presentation of necrotising cutaneous vasculitis. A high index of suspicion through a multidisciplinary approach, coupled with meticulous investigative process including serological biomarkers and skin biopsy, helps to avoid misdiagnosis which may be detrimental to the patient.

Supervised Machine Learning for Semi-Quantification of Extracellular DNA in Glomerulonephritis.

Glomerular cell death is a pathological feature of myeloperoxidase anti neutrophil cytoplasmic antibody associated vasculitis (MPO-AAV). Extracellular deoxyribonucleic acid (ecDNA) is released during different forms of cell death including apoptosis, necrosis, necroptosis, neutrophil extracellular traps (NETs) and pyroptosis. Measurement of this cell death is time consuming with several different biomarkers required to identify the different biochemical forms of cell death. Measurement of ecDNA is generally conducted in serum and urine as a surrogate for renal damage, not in the actual target organ where the pathological injury occurs. The current difficulty in investigating ecDNA in the kidney is the lack of methods for formalin fixed paraffin embedded tissue (FFPE) both experimentally and in archived human kidney biopsies. This protocol provides a summary of the steps required to stain for ecDNA in FFPE tissue (both human and murine), quench autofluorescence and measure the ecDNA in the resulting images using a machine learning tool from the publicly available open source ImageJ plugin trainable Weka segmentation. Trainable Weka segmentation is applied to ecDNA within the glomeruli where the program learns to classify ecDNA. This classifier is applied to subsequent acquired kidney images, reducing the need for manual annotations of each individual image. The adaptability of the trainable Weka segmentation is demonstrated further in kidney tissue from experimental murine anti-MPO glomerulonephritis (GN), to identify NETs and ecMPO, common pathological contributors to anti-MPO GN. This method provides objective analysis of ecDNA in kidney tissue that demonstrates clearly the efficacy in which the trainable Weka segmentation program can distinguish ecDNA between healthy normal kidney tissue and diseased kidney tissue. This protocol can easily be adapted to identify ecDNA, NETs and ecMPO in other organs.

Granulomatosis with polyangiitis(wegener’s granulomatosis); an important rare differential diagnosis for generalized hyperplastic gingivitis.

Granulomatosis with polyangiitis (GPA) formerly known as Wegener’s granulomatosis is a rare lifethreatening disease which can affect multiple organs of the body including oral cavity. The oral manifestation of GPA has been named as strawberry gingivitis due to its characteristic features. We report a case of GPA in a 68-year-old lady who presented with Strawberry gingivitis as the initial symptom and successfully managed with prednisone and cyclophosphamide. This case demonstrates an orofacial manifestation of a systemic disease which emphasises the importance of awareness of this kind of manifestations among dental professionals in order to facilitate early diagnosis. Key words: Anti neutrophil cytoplasmic antibody, Granulomatosis with polyangiitis, Strawberry gingivitis.

39. Atypical presentation of giant cell arteritis confirmed on brain biopsy

39. Atypical presentation of giant cell arteritis confirmed on brain biopsy