BackgroundRituximab (Rtx), a novel biological, having B cell depletion mechanism is an anti- CD 20 antibody and is found to be useful in patients of ANCA associated vasculitis. In AAV the disease activity correlates with increased circulating B cells. Rituximab has been found to be useful in depleting these B cells. According to the RAVE study, Rituximab was shown to be non-inferior to Cyclophosphamide in inducing remission. It also showed that the regimen (Rtx) may be superior to the standard regimen of Cyclophosphamide and glucocorticoids for remission induction in severe relapsing ANCA-associated vasculitis.In our study, B cell therapy was given in those patients only who had persistent disease activity or relapse.ObjectivesTo assess response of Rtx in relapsed /refractory cases of AAV and show that it is a good therapeutic stratergy in such cases.MethodsIn our cohort there were 49 patients of ANCA associated vasculitis, diagnosed by clinical and serological criteria, (by both ELISA and IFA) classified according to ACR criteria and supported, wherever possible, by biopsy. In this prospective study, patients were seen during January 2012 to January 2017. A total of 15 patients received Rituximab for various reasons. Rituximab (Rtx) was given as 1 gram infusion on day 1 and day 15 as induction therapy and subsequently 6 monthly maintenance doses of 500 mg were administered. No other immunosuppression other than steroids were given.ResultsMedian follow up was 22 months. All patients had recieved Cyclophosphamide (median dose 6 grams) and 1mg/kg glucorticoids at onset. Among the patients who received Rituximab, all had anti PR3 antibody positive & all were GPA clinically. 14 patients (93.33%) had lung involvement, renal involvement was seen in 7 (46.6%) patients, 13 (86.6%) patients had upper respiratory tract involvement, 6 (40%) had ophthalmic involvement. Nervous system involvement was seen in 5 (33.3%) and myocarditis was seen in 3 (20%) each. 3 (20%) patients had gangrene.Indications for receiving Rtx were heterogenous. It was given for involvement of lung, renal, ophthalmic, upper respiratory and nervous system in 6 (40%), 3 (20%), 3 (20%), 1 (6.66%) and 1 (6.66%) respectively. Whereas 1 (6.66%) patient received Rtx for persistent disease activity.12 out of 15 patients (80%) achieved remission at mean follow up of 3 months while one achieved at 6 months follow up & all maintained continued remission. 1 patient was due for 3-month follow up. 1 patient died due to lung infection during the course. 4 patients had permanent morbidities/organ damage which they already had before starting Rtx. Only one patient had infusion reaction at the end of 1st induction however she remained in remission after the first dose itself.Conclusions86.6% patients achieved remission after Rtx and remained in continous remission at median follow up of 22 months. Rtx is a very good therapeutic strategy for refractory/relapsed especially PR3+ AAV also it can be used as a maintenance regimen for long term.References Stone JH, Merkel PA, ...

BackgroundIt is often difficult to classify small vessel vasculitis, especially AAV, as Granulomatosis polyangitis [GPA], Microscopic polyangitis [MPA], Eosinophilic granulomatosis polyangitis [EGPA] & Idiopathic cresentic glomerulonephritis. But with the discovery of ANCA, rheumatologists divide this as ANCA positive or negative vasculitis.ObjectivesTo classify AAV as anti-proteinase 3 (PR3) antibody+ or anti-myeloperoxidase (MPO) antibody + & compare their clinical presentation & outcome.Methods49 patients were included in our study from August 2011 till January 2017. Patients were classified according to PR3 and MPO serology [based on ELISA].ResultsMedian follow up was 18 months. PR3 + were 38 and 11 patients were MPO+. GPA was significantly higher in PR3 Group vs MPO group [36 (94.7%) vs 1 (9.1%) p<0.0001*] while MPA was significantly lower in PR3 group as compared to MPO (2 [5.3%] vs 5 [45.45%] p=0.001*). All EGPAs were MP0+ (4 [36.35%]). 48 fulfilled ACR clinical criteria for GPA/MPA or EGPA. 1 patient with arteritic anterior ischemic optic neuropathy without any other major organ involvement had significantly higher titres of MPO antibodies & was sorted as unclassified AAV. None were idiopathic crescentic glomerulonephritis in our cohort. 18 were biopsy proven [15 PR3+vs 3 MPO+]. Lung involvement was significantly higher in PR3 group than MPO group (32 [84.2%] vs 6 [54.5%] p=0.037*).Kidney involvement was also more in PR3 group but was not statistically significant (20 [52.6%] vs 4 [36.4%] p=0.341). Upper respiratory involvement was significantly higher in PR3 group (26 [68.4%] vs 3 [27.3%] p=0.014*).Comparision between manifestations of ophthalmic, cardiac, peripheral vascular system & nervous systems of PR3+ & MPO+ groups was not statistically significant.Complete remission without permanent organ damage was seen in 16 (42%) vs 6 (54.5%) in PR3 and MPO groups respectively (p=0.465). Frequency of relapse/refractory disease, though higher in PR3 group, was not statistically significant (PR3 vs MPO, 10 [26.3%] vs 1 [9.1%] p=0.228). Rates of morbidity & mortality were not significant statistically between PR3 & MPO groups (11 [28.9%] vs 2 [18.2%] p=0.476 & 3 [7.9%] vs 1 [9.1%] p=0.899 respectively). Similar comparisons were made between those who were classified clinically as GPA, MPA & EGPA with respect to remission, relapse, morbidity and mortality. All EGPAs achieved remission. Comparison between groups when divided as GPA & PR3 and MPA & MPO did not show statistical significance. 15 patients (all clinically GPA & PR3+) of the cohort [39.5%] received rituximab for relapse/refractory disease during/after initial induction therapy with cyclophosphamide & steroids.ConclusionsIn this study, we did not find any advantage of clinical classification over serological. Wrongly diagnosing patients when disease is still evolving & inter-clinician bias are eliminated when classifying patients according to serology. Classification as PR3 & MPO is simpler and universal.References Hunder, G. G. et al. The American Colleg...

BackgroundDiffuse alveolar haemorrhage (DAH) is a feature of several immune and nonimmune disorders. Failure to diagnose and treat DAH syndromes in their early stages may lead to acute respiratory failure, CKD and death. Prognosis is poor with in-hospital mortality ranging from 20% to 100%. Immune related DAH is monophasic and if treated early and achieved remission, long term outcome is good.ObjectivesTo evaluate the therapeutic response and long term outcome in patients with Immune related (AAV & SLE) DAH.MethodsA retrospective review of medical records of patients admitted under Rheumatology and Clinical immunology department with Immune related DAH was made with regards to their presentation, treatment & response, mortality, morbidity and long term outcome. Study was performed after approval and ethical clearence from IRB.ResultsFrom June 2012 to Augst 2016, 18 patients (15 were AAV related & 3 as SLE related) were admitted. Amongst AAV patients, PR3 positive were 11 & MPO positive were 4. Fourteen patients were females and 4 males, age ranged from 14 – 68 yrs (median=54.5 yrs). Mean duration of disease before onset of DAH was 3 months. Nine (50%) patients had associated kidney and musculoskeletal involvement. Eleven (61.11%) patients were admitted under ICU care requiring artificial ventilation. Pulse methylprednisolone injections were given in 15 (83.33%), Cyclophosphamide in 13 (72.22%), IVIg in 2 (11.11%), plasmapheresis in 7 (38.88%) patients. Time from first consultation to pulse methylprednisolone was in range from 1 to 5 days. Out of 18, 11 patients achieved remission. In hospital mortality was seen in 5 (27.77%) patients, all were AAV (MPO+=3, PR3+=2), all were complicated with sepsis with MODS before death. Out of 7 who received plasmapheresis, 2 patients (28.4%) died, 2 patients developed CKD (dialysis independent). Duration of ICU& hospital stay in days ranged from 3 to 28 days & 2 to 40 days respectively. Mean follow up was 16 months (range 11–42 months) on OPD visits. Two had relapse on follow up (1 nephritis, 1 persistant cavities with episcleritis) who were given Rituximab. Total 5 (38.46%) received Rituximab out of which 2 were refractory to Cyclophosphamide, 2 had relapse & 1 concomitantly. Eight patients (44.44%) developed morbidity in the form of dialysis independent-CKD in 4 (PR3+ in 2, MPO+ in 1 and Lupus nephritis in 1) with concomitant cataract in 1, ILD in 2, hearing loss in 1 and finger amputation in 1). All 13 patients who survived are in remission. Ongoing maintenance treatment is Azatjioprine in 5, Mycophenolate mofetil in 3 and Rituximab in 3 patients.ConclusionsHigh index of suspicion with early diagnosis and treatment results in low mortality and better long term outcome. All mortality was because of delay in diagnosis. Rituximab is effective in achieving remission in refractory as well as relapsed casesReferences Yi Lin, MD, et al. J Clin Rheumatol. 2009 Oct;15(7):341–4.Diffuse alveolar hemorrhage in systemic lupus erythematosus: risk factors and clinical outcome: results from ...

BackgroundSLE is characterised by excessive production of various autoantibodies and correlation of these antibodies with organ involvement may help to evaluate disease severity and long term prognosis. NBTE is a rare cardiac manifestation of SLE with prevalence rate varying from 6%–11%. Many, but no all, studies have shown association of NBTE with anti phospholipid antibodies, but, except this association, data regarding clinical, laboratory and serological characteristics of NBTE is sketchy. We designed this study to evauate profile of patients having NBTE in SLE.Objectives1. To study the prevalenence of NBTE in SLE patients.2. To study association of NBTE with clinical and laboratory characteristics and serological profile.MethodsAll consecutive SLE inpatients and outpatients attending the department of Rheumatology from September 2015 to December 2017 were enrolled. Patients subjected to 2D Echo were included and their demographic, clinical, laboratory and serological profile were recorded. Serological profile was studied with Blue diver kit which is an immunodot blot assay measuring autoantibodies against 25 ENA. Anti cardiolipin and anti beta 2 glycoprotein antibody were tested by ELISA. Study was approved by an independent ethics committee [ECR/282].ResultsTotal number of patients enrolled in study were 355 out of which 213 had undergone 2DEcho. NBTE was found in 33 (15.49%) patients. Among all autoantibodies studied, we found that the presence of anti-Nucleosome antibody, LAC, ACL and B2GP1 were significantly associated with NBTE (p<0.05). Myocarditis, valvular lesions and Pulmonary Hypertension were more common in NBTE group (p value: 0.012,<0.0001 and 0.013 respectively).We also noticed that there is a statistically significant association between presence of NBTE with APLA syndrome and Thrombotic events (p value<0.0001 and 0.005 respectively).Tab.1 Significant Serological association of SLE patients with NBTE.AntibodiesSLE With NBTE-33 (15.49%)SLE without NBTE-180P value Anti-nucleosome27 (81.8)32 (17.7)<0.0001LAC16/30 (53.3)31/149 (20.8)0.0002ACL (Ig M and IgG)9/303013/128 (10.1)0.004B2GP-1(Ig M and IgG)6/22209/103 (8.73)0.033APLA profile was available in 30 patients of NBTE and 147 patients not having NBTE. Out of this, positivity for APLA antibodies were seen in 17 (56.6%) and 36 (24.4%) patients respectively [p:0.005]. 82.3% patients with Anti phospholipid antibodies had APLA syndrome in NBTE group while in NBTE group 48.5% patients having Anti phospholipid antibodies had APLA syndrome. Thus, presence of NBTE increased the possibility of developing APLA syndrome in patients having positive serology for anti phospholipid antibodiesTab.2 Significant Clinical and laboratory characteristic of SLE patients with NBTE.Organ involvementSLE with NBTE-33SLE without NBTE-180p- value Myocarditis11270.012Valvulopathy104<0.0001PAH9210.013Thrombotic events8160.005APLA syndrome1417<0.0001ConclusionsPresence of Anti nucleosome antibody, LAC, Anti cardiolipin and anti beta 2 glycoprotein antibodies may predict presen...

BackgroundStudies in Autoimmune Inflammatory Myositis (AIM) have shown that certain antibodies have a role in the diagnosis and prognosis of patients with myositis. This ongoing study presents the preliminary data of 48 patients of Indian AIM.ObjectivesTo study the prevalence of Myositis specific and Myositis Associated antibodies (MSA and MAA respectively) in Indian patients with AIM and to correlate these antibodies with clinical features.MethodsAll consecutive patients with Inflammatory myositis (satisfying the Bohan and Peter criteria, 1975 attending the Rheumatology and Clinical Immunology department of Medanta hospital from November 2016 to October 2017 were included prospectively and divided into groups as Dermatomyositis (DM), Polymyositis (PM), CTD associated myositis (CTD-M), Cancer associated myositis (CAM) and Juvenile Myositis (JM). Their clinical data and sera were collected after obtaining informed consent. Sera was analysed for IgG antibodies against Jo-1, PL-7, PL-12, EJ, SRP, Mi-2, MDA-5, TIF1γ, SAE1, SAE2, NXP2 and SSA/R052kD using the microELISA technique (BlueDriver Dot Myositis12 SAE IgG kit). Their ENA was also recorded (Blue DriverQuantrix-ANA25 Screen IgG kit d-tek). Results were read by the BlueScan scanner and value ≥10 were considered positive. The study was approved by the Ethics committee of Medanta hospital.ResultsThere were 48 patients in the cohort (M:F=12:36) with the mean age of 41.3 years and a median disease duration of 30 months. Nineteen of them were DM, 19 were PM, 5 were CTD-M, 2 were CAM and 3 were JM. 58.3% were ANA positive and MSA were positive in 37.5% of the cohort, MSA being mutually exclusive. Antibodies against Mi-2 were present in 6 patients (12.5%), Jo-1 antibodies in 5 (10.4%), 2 (4.1%) patients each had PL-7 and SRP antibodies. One patient (2%) each had MDA-5, NXP2 and TIf1γ antibodies. MAAs were seen in 39.5% of the cohort with antibodies against Ro, RNP and PM- Scl seen in 16 (33.3%), 2 (4.1%) and 1 (2%) respectively. Mi-2 antibodies were seen only in DM and JM group. The lone patient who had MDA-5 antibody had amyopathic DM. Malignancy screening was negative in NXP2 and TIF1γ antibody positive patients.ConclusionsMSA were present in almost 40% of the cohort. Mi-2 antibodies were associated with rash and none had ILD whereas Jo-1 antibodies were associated with mechanic hands, arthritis and ILD. With further recruitment of patients in this ongoing study, we hope to get more robust data in future.Disclosure of InterestNone declaredAbstract SAT0504 – Table 1Myositis Antibody distribution according to clinical features.Proximal muscle weakness (%) (n=46)Pharyngeal muscle weakness (%) (n=17)Rash (%) (n=28)Mechanic hands (%) (n=5)Raynaud’s (%) (n=11)Digital Ulcer (%) (n=2)Arthritis (%) (n=13)ILD (%) (n=11)Total (n=48) Myositis Specific AntibodiesMI-26 (13)2 (11.7)6 (21.4)01 (9)01 (7.6)06 (12.5)JO-14 (8.6)1 (5.8)3 (10.7)3 (60)2 (18.1)03 (23)4 (36.3)5 (10.4)NON JO-I ARS (PL-7)1 (2.1)02 (7.1)02 (18.1)001 (9)2 (4.1)SRP2 (4.3)0000001 (9)2 (4.1)MDA-5001 (3.5)1 (20)1 (9)...