Clinical course of 602 patients with Takayasu's arteritis: comparison between Childhood-onset versus adult onset disease.

OBJECTIVES: To describe the clinical profile of Asian Indian patients with Takayasu's arteritis (TAK) and to compare clinical features and outcome of childhood-onset Takayasu's arteritis (cTAK) with adult-onset TAK (aTAK). METHODS: Data related to clinical features and response to treatment of patients with cTAK (age of onset <16 years) and aTAK from a large observational cohort in our tertiary care teaching hospital were noted and compared. RESULTS: Altogether, 602 patients (cTAK = 119; aTAK = 483) were studied. Patients with cTAK had a blunted female: male ratio; but fever, elevated acute phase reactants, involvement of abdominal aorta or its branches, hypertension, abdominal pain, elevated serum creatinine and cardiomyopathy were more common in cTAK as compared with aTAK. Patients with aTAK were more likely to have aortic-arch disease and claudication than cTAK. During follow-up, complete remission was more common in cTAK (87% vs 66%; P < 0.01), but subsequent relapses were equally common (30% vs 27%; P = 0.63). Independent associations of disease duration at presentation with disease extent [Disease Extent Index in TAK (DEI.Tak)] and damage [TAK Damage Score (TADS)] were observed (P ≤ 0.01). Moreover, 54% of patients with symptom duration of >5 years at presentation still continued to have elevated CRP suggesting continued and active inflammation warranting escalation or inititation of immunosuppression. CONCLUSION: Patients with cTAK are more likely to have arterial disease below the diaphragm, systemic inflammation and achieve remission. Disease of the aortic arch is more common in patients with aTAK. Longer duration of symptoms prior to initiation of immunosuppression, thereby leading to extensive disease and damage, reflects ongoing disease activity as the rule rather than exception in untreated TAK.

Derivation of an angiographically based classification system in Takayasu's arteritis: an observational study from India and North America.

OBJECTIVES: To develop and replicate, using data-driven methods, a novel classification system in Takayasu's arteritis based on distribution of arterial lesions. METHODS: Patients were included from four international cohorts at major academic centres: India (Christian Medical College Vellore); North America (National Institutes of Health, Vasculitis Clinical Research Consortium and Cleveland Clinic Foundation). All patients underwent whole-body angiography of the aorta and branch vessels, with categorization of arterial damage (stenosis, occlusion or aneurysm) in 13 territories. K-means cluster analysis was performed to identify subgroups of patients based on pattern of angiographic involvement. Cluster groups were identified in the Indian cohort and independently replicated in the North American cohorts. RESULTS: A total of 806 patients with Takayasu's arteritis from India (n = 581) and North America (n = 225) were included. Three distinct clusters defined by arterial damage were identified in the Indian cohort and replicated in each of the North American cohorts. Patients in cluster one had significantly more disease in the abdominal aorta, renal and mesenteric arteries (P < 0.01). Patients in cluster two had significantly more bilateral disease in the carotid and subclavian arteries (P < 0.01). Compared with clusters one and two, patients in cluster three had asymmetric disease with fewer involved territories (P < 0.01). Demographics, clinical symptoms and clinical outcomes differed by cluster. CONCLUSION: This large study in Takayasu's arteritis identified and replicated three novel subsets of patients based on patterns of arterial damage. Angiographic-based disease classification requires validation by demonstrating potential aetiological or prognostic implications.

Long-term outcome of 251 patients with Takayasu arteritis on combination immunosuppressant therapy: Single centre experience from a large tertiary care teaching hospital in Southern India.

INTRODUCTION: Long-term outcome studies in Takayasu arteritis (TA) are few and limited by small sample size. In this study, we analysed the outcome of treatment in a large series of TA patients with a minimum follow-up period of ≥12 months by objective instruments. MATERIALS AND METHODS: Patients with TA satisfying the 1990 ACR, Ishikawa's, Sharma's or EULAR/PRESS criteria were recruited from our clinics between 1998 and 2016. Only patients with a minimum follow up of 12 months were studied. Data related to clinical presentation, disease extent (DEI.Tak score), activity [Indian Takayasu arteritis clinical activity score, that is, ITAS-A (CRP)] and damage score [Takayasu arteritis damage score (TADS)], angiography and treatment were collected for all patients. Response to treatment was categorised as complete response (CR), partial response (PR) or refractory disease. Patients with sustained CR on prednisolone dose of ≤5mg/day were classified as having sustained inactive disease. Appropriate statistical tests were used for parametric and non-parametric data. Relapse free survival was projected by Kaplan-Meir curve. Cox proportional hazards regression plot was used to compare the efficacy of medications. Predictors of sustained response were identified by logistic regression and a prediction model was constructed. RESULTS: Among 503 TA patients examined during study period, 251 had follow-up of ≥12 months and were included in this study. Median follow-up duration was 42 months (IQR: 24-81, maximum 240 months). Patients (81.7% females, mean age of 29.2 ± 11.8 years, symptom duration of 24 [6-70] months) were treated by a uniform protocol that included high dose steroids (n = 239) plus concurrent steroid-sparing immunosuppressant (n = 235) with mycophenolate in majority. Biological agents (n = 44 patients) and revascularisation procedures were used in symptomatic patients after control of disease activity. At 1st follow-up, CR (ITAS2010 = 0, CRP < 6mg/L and non-progressive disease on angiography) was observed in 173 (68.9%), partial response (PR) in 42 (16.7%) and no response was seen in only 36 (14%) patients. CR was sustained till the last follow up in 116 (65.9%) of 173 patients with initial CR, while 87 (49.4%) of them achieved sustained inactive disease. Disease activity relapsed at a median duration of 37 (29.9-44.1) months in 56 patients. Cumulative relapse free survival was 93%, 73%, 66% and 52% at 1, 3, 5 and 10 years, respectively. Baseline CRP < 6.2, DEI.Tak < 9 and angiographic type 4 disease predicted sustained inactive disease and a model comprising these parameters showed sensitivity and specificity of 70% and 61.1%. Two fatalities were observed. New vascular lesions during follow up were observed in 50 (19.9%) patients. Overall, 92.8% had at least one period of CR or PR while 7.2% were refractory to treatment till the last follow up. Damage progression (∆TADS > 1) was arrested in 68% of patients and was lower in patients with sustained inactive disease [0 (0-1)] as compared to the rest [1 (0-2.75)], p = 0.000. Both early response as well as cumulative hazard for relapse were similar between patients initiated on 0.5 and 1mg/kg/day steroids. CONCLUSIONS: Our strategy of upfront combination immunosuppressant therapy stabilised disease activity in 92.8% of patients, while 7.2% had true refractory disease. Relapse free survival was 66% at 5 years and 52% at 10 years. Damage progression was arrested in 68% and only 2 fatalities were observed. Initial steroid dose of 0.5mg/kg/day had similar efficacy as 1mg/kg/day dose.

Clinical utility of anti-C1q antibody in primary and secondary vasculitic conditions.

OBJECTIVE: Anti-C1q antibodies (Anti-C1q Ab) are seen in hypocomplementemic urticarial vasculitis syndrome (HUVS), infection-associated vasculitis such as hepatitis C virus-related vasculitis and in autoimmune diseases such as rheumatoid vasculitis, polyarteritis nodosa, giant cell arteritis, vascular Behcet's disease, and cryoglobulin associated vasculitis. Aim of this study is to evaluate the presence of Anti-C1q Ab in vasculitis and to determine if any difference exists between primary and secondary vasculitis in relation to this antibody. PATIENTS AND METHODS: Consecutive patients with diagnosis of either a primary or secondary vasculitis were recruited. Primary vasculitis were diagnosed by the American College of Rheumatology 1990 criteria. Clinical features and serological markers were noted. Anti-C1q Ab was assayed by commercially available ELISA kit (Demeditec Diagnostics GmbH, Germany). RESULTS: Sixty-four patients were recruited for the study comprising of 41 primary vasculitis and 23 secondary vasculitis cases. No difference in Anti-C1q Ab levels between primary and secondary vasculitis was noted. Four patients were positive for Anti-C1q Ab out of the 64 patients. Of the four, one patient was diagnosed as HUVS, 2 patients as systemic lupus erythermatosus with vasculitis (16.7%) and another patient was diagnosed as rheumatoid arthritis with vasculitis (14.28%). Anti-C1q Ab negatively correlated with age and C3, but it correlated positively with erythrocyte sedimentation rate (ESR) in vascultic patients. CONCLUSION: Presence of anti-C1q Ab did not differ between the patients with primary and secondary vasculitis. Anti-C1q Ab titers correlated with younger age, high ESR, and low C3 in patients with vasculitis in our study.