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 ...

BackgroundStudies have shown a correlation between Tuberculosis (TB) and Takayasu arteritis (TA). Some even postulate that infection with TB is required for the initiation of aortoarteritis. Hence, this project was undertaken to find an association of TB and TA by studying the prevalence of Latent Tuberculosis Infection (LTBI) in Indian TA patients.ObjectivesTo study the prevalence of LTBI in Indian TA patients and see whether LTBI is more in these patients as compared to the historical cohort (40% in Indian population).MethodsThis was a cross sectional observational study. All consecutive patients with TA (satisfying the ACR 1990 criteria) were included prospectively from a period of May 2016 to December 2017. Their clinical, laboratory and radiological data were collected after obtaining informed consent. Patients were divided into groups based on the angiographic classification. LTBI was assessed by the Mantoux test and Quantiferon TB Gold test. Mantoux test (MT) was done with 5TU and results were read after 48–72 hours. An induration more than 10 mm was considered positive. Quantiferon TB Gold assay (QTB) was done by ELISA technique and (patient minus control) value >0.35 IU/ml was considered positive. A positive result of MT and /or QTB was considered positive for LTBI. Chest X-ray was included to access evidence of past or active TB lesions. Active infection was defined as clinical and microbiological and /or radiological evidence of TB. The study was approved by the Ethics committee of Medanta hospital.ResultsOut of 66 consecutive TA patients, 46 patients had tests available for LTBI and these were included in the analysis. The mean age of the cohort was 34.9 years with a median disease duration of 24 months. Males consisted of 11 patients whereas females formed the majority i.e. 35 patients (M: F= 1: 3.1). Angiographic Type V (54.3%) was the commonest in the cohort followed by Type IIB (17.3%), Type IV, I, IIA and III (15.2%, 8.6%, 2.1% and 2.1% respectively). LTBI positivity was present in 32.6% of the cohort; with 5 patients (10.8%) having both tests positive. 6 patients were MT positive without being QTB positive and 4 patients were only QTB positive. Eight patients had history of Tuberculosis out of which 1 was diagnosed with TB and TA simultaneously. Four patients were diagnosed as TA during the course of Anti tubercular treatment (ATT) between 4 to 6 months, whereas the rest were diagnosed after ATT completion. The mean duration of Anti tubercular treatment was 8 months. Koch’s contact was seen in 7 patients.Abstract FRI0507 – Table 1Patient characteristics and LTBICharacteristicValuePercentage (%) n=46MT positive only613QTB positive only48.6Both MT and QTB positive510.8LTBI positive1532.6n=8H/O TB8/4617.3TB LN450Pulmonary TB (progression)112.5Intestinal TB225TBM112.5Empirical ATT for PUO112.5MT225QTB00Both112.5n=7TB contact7/4615.2MT114.2QTB00Both00ConclusionsThe prevalence of LTBI in Indian Takayasu patients was 32.6%, which was not higher than the population prevalence (40% in the historical cohor...

BackgroundThe ANCA-associated vasculitides (AAV) are systemic autoimmune diseases affecting small and medium-sized blood vessels. Upper airways, lungs, and kidneys are variably involved in the different types of AAV, and the consequences of a missed or delayed diagnosis of renal vasculitis are potentially life-threatening. AAV may be classified into clinical syndromes or based on their serology (Anti-PR3 or Anti-MPO). Patient survival and the risk of end-stage renal disease are closely associated with renal functional status.ObjectivesThis study was undertaken to study the disease characteristics and outcomes in patients of AAV based on the presence or absence of renal involvement.MethodsThis was a longitudinal, observational study conducted at a tertiary care hospital in Northern India. Between February 2020 and December 2021, all consecutive adult patients diagnosed with AAV based on their autoantibody profiles (using indirect immunofluorescence and Line ImmunoAssay) and clinical features were included in this study after taking their informed consent. Demographic details, clinical features, laboratory parameters, disease activity, and mortality or morbidity outcomes of patients were analysed prospectively. All outcomes were compared between patients with and without renal involvement.ResultsA total of 112 patients were included in our study, with a median age of 51.5 years. 74 (66%) patients had renal involvement either in the form of Nephritic syndrome, Nephrotic syndrome, RPRF (Rapidly progressive renal failure), Nephritic nephrotic syndrome, or Asymptomatic Urinary Sediments. c-ANCA and PR3 positivity were seen in more than two-thirds of our population, without any significant correlation with organ involvement. Patients with renal disease had a significantly higher proportion with diffuse alveolar haemorrhage (32.4% vs 10.5%, p=0.05) and palpable purpura (19.6% vs 7.9%, p-0.025), but significantly lower occurrences of nasal pathology (14% vs 42%, p=0.001) and subglottic stenosis (1.4% vs 18.4%, p=0.001). Mean BVAS at enrolment was significantly higher in the renal group (20.9 vs 12.89). Remission was achieved in 50% and 47.4% of the patients with and without renal involvement respectively. Rates of relapse (19/74 vs 14/38), refractory disease, and mortality were not significantly different among the two subgroups. The commonest organ involvement in disease flare was pulmonary involvement. 21.6% of the patients developed CKD over a median follow-up period of 18 months.ConclusionKidney involvement is one of the commonest manifestations of AAV. Patients with renal involvement may have higher mean BVAS scores and an increased risk of developing alveolar haemorrhage and purpuric skin rash; while nasal pathology and subglottic stenosis occurred more frequently in patients without renal disease. Rates of remission, refractory disease, and mortality were almost similar, regardless of renal involvement, while relapses were numerically more in the non-renal AAV patients.References[1]Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St. Clair EW, Turkiewicz A, Tchao NK, Webber L. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. New England Journal of Medicine. 2010 Jul 15;363(3):221-32.[2]Córdova-Sánchez BM, Mejía-Vilet JM, Morales-Buenrostro LE, Loyola-Rodríguez G, Uribe-Uribe NO, Correa-Rotter R. Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement. Clinical rheumatology. 2016 Jul;35(7):1805-16.[3]Kronbichler A, Shin JI, Lee KH, Nakagomi D, Quintana LF, Busch M, Craven A, Luqmani RA, Merkel PA, Mayer G, Jayne DR. Clinical associations of renal involvement in ANCA-associated vasculitis. Autoimmunity Reviews. 2020 Apr 1;19(4):102495.Acknowledgements:NIL.Disclosure of InterestsNone Declared.