Patterns of clinical presentation in Takayasu's arteritis.

OBJECTIVE: Takayasu's arteritis (TAK) is a clinically heterogenous disease. Patterns of clinical presentation in TAK at diagnosis have not been well described, and a "triphasic pattern" of constitutional symptoms evolving into vascular inflammation and fibrosis has been reported but never systematically evaluated. METHODS: Patients with TAK were prospectively recruited from the National Institutes of Health (NIH) and the Vasculitis Clinical Research Consortium (VCRC). Based on clinical presentation at diagnosis, patients were divided into five categories: (1) constitutional symptoms alone, (2) carotidynia, (3) other vascular-associated symptoms, (4) major ischemic event, or (5) asymptomatic. Associated clinical characteristics were evaluated in each category. Preceding symptoms were also assessed to determine the presence of a triphasic disease pattern. RESULTS: A total of 275 patients with TAK were included (VCRC=208; NIH=67). Similar heterogeneity of clinical presentation was identified in each cohort: constitutional symptoms (8%), carotidynia (13-15%), other vascular symptoms (43-47%), major ischemic event (28-30%), and asymptomatic (2-6%). An increased relative proportion of males was seen in patients who presented with constitutional symptoms or were asymptomatic at diagnosis (p<0.01). Patients who presented with constitutional symptoms and major ischemic events were youngest at diagnosis. Patients in the asymptomatic group were oldest at diagnosis and often were not treated (p<0.01). Relapse was most frequent in patients who presented with carotidynia (p<0.01). A minority of patients (19%) who presented with a major ischemic event reported a triphasic pattern of disease. CONCLUSION: There are diverse clinical presentations at diagnosis in TAK. Patients do not necessarily progress sequentially through phases of disease.

Assessment of damage in Takayasu's arteritis.

OBJECTIVE: To assess the progression and the factors associated with damage in Takayasu's arteritis (TAK) patients during routine follow-up. METHODS: Patients diagnosed with TAK and had >6 months follow-up were enrolled in this study retrospectively. Takayasu's arteritis damage score (TADS) and vasculitis damage index (VDI) were determined at diagnosis and at the end of the follow-up and variables associated with damage scores were assessed. RESULTS: One-hundred fourteen patients (F/M: 101/13) were included in the study. The mean age at diagnosis, median symptom duration at baseline visit and mean follow-up duration were 35.3±13.3 years, 12 (0-360) months and 76.9±51.4 months, respectively. Median VDI score was 4.0 (1-8) and median TADS score was 7.0 (1-15) at baseline assessment. At the end of the follow-up, median VDI score increased to 5.0 (1-17) and TADS score to 8.0 (1-19). The median number of disease-related items were higher in TADS (8 items vs 4 items). At least one new corticosteroid (CS)-related damage item occurred in 35 patients (31%). Age at symptom-onset and cumulative CS doses were predictor factors for higher VDI score (≥5), whereas age at symptom-onset and disease duration were associated with increase in TADS (≥8). Gender and number of relapses were not associated with damage scores. CONCLUSION: Damage assessment with VDI seems to capture treatment-related damage better, whereas TADS provides some additional information on disease-related damage in Takayasu's arteritis. Older age at symptom onset, disease duration and cumulative CS dose were associated with higher damage scores. The relapse frequency did not influence the damage level in our routine-follow-up of TAK patients.

Poor obstetric outcomes in Indian women with Takayasu arteritis.

INTRODUCTION: Takayasu's arteritis (TA) affects young women in the childbearing age group. We studied obstetric outcomes in these patients before and after disease onset. METHODS: Women aged more than 18 years with Takayasu's arteritis (ACR 1990 criteria) were included. Demographic data, clinical features, disease activity using Indian Takayasu Arteritis clinical score (ITAS), Disease Extent Index for TA (DEI.TaK) and damage assessment using TA Damage score (TA), history of conception and maternal and fetal outcomes were recorded from hospital records and telephonic interview. Results are in median and IQR. RESULTS: Of the 64 women interviewed, aged 29 (24-38) years and disease duration 5 (4-10) years, 74 and 38 pregnancies had occurred before and after disease diagnosis in 29 and 20 women respectively. In eight, the diagnosis was made during pregnancy. Age at disease onset was 22 (18-30) years. Type 5 disease was the most common (n = 32, 59.3%), and an equal number of patients had Ishikawa's class I and II disease (n = 26, 40.6%). Median ITAS (n = 44) was 13 (7-16), DEI.Tak 12.5 (9-16.75) and TADS 8 (6.5-10). Twenty-five patients wanted to get pregnant, of which 8 (32%) did not do so because of their disease. Fifteen were unmarried of whom 6 did not marry due to disease. Obstetric outcomes were poorer in pregnancies that occurred after the onset of disease as compared with those before it (RR = 1.5, p = 0.01). Pregnancies after the onset of TA carried a very high risk of maternal [RR3.9 (1.8-8.5), P < 0.001] as well as fetal complications [RR = 2.0 (1.2-3.4), p = 0.001]. Hypertension was the most common maternal complication and occurred most often in the last trimester. The baby weight at birth was lower in pregnancies after disease (2.3 vs. 3.0, p = 0.01). Wong's score greater than or equal to 4 predicted lower birth weight (p = 0.04). ITAS, ITAS-A, DEI. Tak and TADS could not predict obstetric outcomes, and ITAS score exhibited moderate correlation with DEI. Tak (r = 0.78) and TADS (r = 0.58). CONCLUSION: Women with TA suffer from extremely high risk of poor maternal and foetal outcomes. Wong's scoring can be useful to predict birth weight.

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.

A Rare Case of Takayasu's Arteritis with Aortic Arch Branching Pattern Variation in a Young Female.

Takayasu's arteritis, formerly known as "pulseless disease", is a chronic inflammatory disease which affects the aorta and its main branches. The prevalence of this disease is higher in Asian countries and among young women. Depending on the progress of the disease, the symptoms and prognosis of the disease is different. Herein, we report the case of a 31-year-old woman with Takayasu's arteritis in the Iranian population. In this case, the size of the aorta and the main branches increased and the large artery walls were thickened. Narrowing of the right and left subclavian artery, carotid artery and left vertebral artery were obvious in these patients. In addition, an anatomic variation was observed in the aortic arch branches. In this patient, the left vertebral artery was branched directly from the aortic arch instead of the left subclavian artery. Hepatomegaly and splenomegaly, indicating a chronic inflammatory disease, were also observed in this case.

Novel Biomarkers for the Precisive Diagnosis and Activity Classification of Takayasu Arteritis.

BACKGROUND: Establishing the diagnosis and determining disease activity of Takayasu arteritis (TA) remains challenging. Novel biomarkers might help to solve this problem. METHODS: In the screening phase, by using large-scale protein arrays detecting samples from 90 subjects (TA active, 29; TA inactive 31; and controls, 30). In the validation phase, by using enzyme-linked immunosorbent assay (ELISA), potential biomarkers for TA diagnosis, and activity classification were measured in independent cohorts, respectively. RESULTS: In the screening phase, 18 cytokines significantly differentially enriched between TA patients and controls and another 15 cytokines significantly differentially enriched between TA patient in active and inactive status were identified (adjusted P<0.05). In the validation phase, TIMP (tissue inhibitor of metalloproteinases)-1 was identified as a specific biomarker for TA diagnosis that a cutoff value of 221.86 µg/L could provide a specificity of 89.58% and a positive predictive value of 0.92. Meanwhile, we found it unreliable to use a single biomarker for TA activity classification. Considering this, we further built a logistic regression model based on multiple cytokines, including CA (cancer antigen) 125, FLRG (follistatin-related protein), IGFBP (insulin-like growth factor-binding protein)-2, CA15-3, GROa (growth-regulated alpha protein), LYVE (lymphatic vessel endothelial hyaluronic acid receptor)-1, ULBP (UL16-binding protein)-2, and CD (cluster of differentiation) 99, with an area under the curve reaching 0.909 for discriminating TA activity status. CONCLUSIONS: This study suggested TIMP-1 as a specific biomarker for TA diagnosis with a cutoff value of 221.86 µg/L. Furthermore, we provided a logistic regression model based on 8 biomarkers for the precisive activity classification of TA with an area under the curve of 0.909.

Takayasu arteritis: A distinct syndrome of large vessel vasculitis: A view point by late Professor Paul Bacon.

Takayasu arteritis (TA), despite being classified as a large vessel vasculitis, has distinct genetic, pathological and clinical features as compared to giant cell arteritis. It is a rare disease seen more commonly in Asian countries. The challenge lies in assessing the degree of inflammation in a narrowed vessel and immunosuppressive therapy improves inflammatory features but is unable to open up an occluded vessel. It may have a positive effect on retarding further occlusion. Like antineutrophil cytoplasmic antibody-associated vasculitis, TA needs a collaborative effort to do randomized controlled therapy to provide benefit to patients.

Classification of large vessel vasculitis: Can we separate giant cell arteritis from Takayasu arteritis?

The two main variants of large vessel vasculitis include Takayasu arteritis and giant cell arteritis. While these two conditions have historically been considered different conditions, recent evidence questions whether they are a spectrum of the same disease. Classification criteria are limited in distinguishing between cases with phenotypic overlap. The limitations of the current criteria and directions of future research are reviewed.

Are the 1990 American College of Rheumatology vasculitis classification criteria still valid?

Objectives: Advances in diagnostic techniques have led to better distinction between types of vasculitis, potentially affecting the utility of the 1990 ACR classification criteria for vasculitis. This study tested the performance of these criteria in a contemporary vasculitis cohort. Methods: The Diagnosis and Classification in Vasculitis Study provided detailed clinical, serological, pathological and radiological data from patients with primary systemic vasculitis and clinical context-specific comparator conditions. Fulfilment of six ACR criteria sets and their diagnostic performance was evaluated in patients with a given type of vasculitis and its comparator conditions. Results: Data from 1095 patients with primary systemic vasculitis and 415 with comparator conditions were available. For classification, sensitivities and specificities for ACR classification criteria were, respectively, 81.1% and 94.9% for GCA; 73.6% and 98.3% for Takayasu's arteritis; 65.6% and 88.7% for granulomatosis with polyangiitis; 57.0% and 99.8% for eosinophilic granulomatosis with polyangiitis; 40.6% and 87.8% for polyarteritis nodosa; 28.9% and 88.5% for microscopic polyangiitis; and 72.7% and 96.3% for IgA-vasculitis. Overall sensitivity was 67.1%. Of cases identified by their respective criteria, 16.9% also met criteria for other vasculitides. Diagnostic specificity ranged from 64.2 to 98.9%; overall, 113/415 comparators (27.2%) fulfilled at least one of the ACR classification criteria sets. Conclusion: Since publication of the ACR criteria for vasculitis, the sensitivity for each type of vasculitis, except GCA, has diminished, although the specificities have remained high, highlighting the need for updated classification criteria.

Clinical analysis: 13 cases of pregnancy complicated with Takayasu arteritis.

OBJECTIVES: To investigate the clinical features, disposition, and effect of pregnancy complicated with Takayasu arteritis (P-TA) on maternal and fetal outcomes. MATERIAL AND METHODS: The clinical data (diagnosis and treatment, peri-pregnancy monitoring, and pregnancy outcomes) of patients with P-TA treated in our hospital between September 2007 and April 2016 were analyzed retrospectively. RESULTS: Among the 13 P-TA cases, seven were diagnosed before pregnancy, and six were diagnosed during pregnancy; six cases were diagnosed as the generalized type, and seven cases were diagnosed as the cephalic-brachial type; six cases were in the stable stage, and seven cases were in the active stage. All the cases in the active stage underwent glucocorticoid therapy. Four cases developed complications, including cardiac dysfunction combined with preeclampsia in two cases, preeclampsia in one case, and stroke in one case. Eleven patients successfully delivered (nine cases of full-term delivery and two cases of premature delivery); one patient had late miscarriage; one patient had missed abortion. All the parturients survived and delivered 11 neonates (nine full-term neonates and two premature neonates) and one low-birth-weight neonate; no neonatal asphyxia or death occurred. CONCLUSIONS: Patients with P-TA can have better maternal and child outcomes through timely diagnosis and treatment, dynamic monitoring, or timely pregnancy termination.

Inflammatory disease of the aorta: patterns and classification of giant cell aortitis, Takayasu arteritis, and nonsyndromic aortitis.

OBJECTIVE: Inflammatory diseases of the aorta, other than those of known infective etiology, are poorly understood. We analyzed a large series of affected patients who had histologic diagnoses with a view to improving the classification of the extent of aortitis to enable a more targeted approach of treatment. METHODS: Between 1996 and 2012, we operated on 7551 patients with ascending or aortic arch disease, of whom 279 had clinically diagnosed inflammatory disease. Of these, 156 (2%) were found to have aortitis on histologic examination. RESULTS: Patients were divided into 4 histologically based groups: giant cell aortitis, 31% (49/156); Takayasu arteritis, 5.1% (8/156); isolated aortitis, 59% (92/156); and other, 4.5% (7/156). Patterns of anatomic extent were also analyzed, and in particular it was noted that giant cell aortitis and isolated aortitis had more extensive disease. In addition, specimen analysis suggested early indications of unrecognized preexistent infections. Death after surgery occurred in 3.2% (5/156), and stroke in 1.9% (3/156). Kaplan-Meier survival at 8 years was 55%. We present a classification for disease extent and management. CONCLUSIONS: Aortitis continues to be a conundrum; however, good results are achievable with surgery. Intervention should be based on a clearer understanding of the histologic pattern and extent of disease, which helps in subsequent targeted disease management.

Diagnostic and classification criteria of Takayasu arteritis.

Takayasu arteritis (TA) is a chronic large vessel vasculitis that affects aorta, its main branches and pulmonary arteries. The inflammatory process results in stenosis, occlusion, dilation or aneurysm formation in the arterial wall. TA has been described in different parts of the world and affects predominantly young individuals (<50 years of age). Patients with TA may present constitutional symptoms, vascular pain (e.g. carotidynia) and typical features such as limb claudication, decreased or absent peripheral pulses, vascular bruits, hypertension, and reduction or discrepancies in blood pressure between arms. A proper diagnosis of TA is an important issue since delays may result in significant morbidity. The definition of TA was included in the 1994 and 2012 Chapel Hill Consensus Conference and TA was categorized as a large vessel vasculitis. The first diagnostic criteria for TA were developed by Ishikawa in 1988 and modified by Sharma et al., in 1995. Two sets of classification criteria were developed for TA to include patients in epidemiologic studies and clinical trials: the 1990 ACR Classification Criteria for TA and the Classification Criteria for childhood TA proposed by the European League Against Rheumatism (EULAR), the Pediatric Rheumatology European Society (PRES) and by the Pediatric Rheumatology International Trials Organization (PRINTO) to be used for patients younger than 18 years. The Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) is an international effort that is under way to develop a single classification system and a validated set of diagnostic criteria for systemic vasculitides using data-driven methods.

[Takayasu's arteritis in Tunisia: a monocentric study of 11 patients]. / La maladie de Takayasu en Tunisie: etude mono-centrique de 11 cas.

BACKGROUND: Takayasu's disease is a chronic inflammatory arteritis involving large vessels in young women. AIM: To assess the clinical, laboratory, and radiological features and course of Takayasu arteritis in Tunisia. METHODS: This retrospective study analyzed 11 patients with Takayasu arteritis between 1999 and 2010 who met the criteria for inclusion proposed by the American College of Rheumatology (ACR). RESULTS: The file review identified 11 women, with a mean age at diagnosis of 29.1 years (range: 17-50 years). Our series included involvement of the aortic arch and its branches in 8 cases, while only 3 cases of the abdominal aorta. Arterial hypertension due to stenosis of the renal arteries was noted in 4 cases. Aortic insufficiency and pulmonary hypertension were noted in one case. In all, 3 patients had type I disease, 3 type V and one type IV. In all, 4 patients had glucocorticoid treatment, and one needed immunosuppressive therapy. Three patients required surgical intervention. Our patients were followed for a mean period of 67.5 months. Disease remained stable in all patients. CONCLUSION: Despite the small number of our patients, the clinical manifestations, angiographic data and course in our study were similar to those in other reported series.

[Systemic vasculitides classification]. / Classification des vascularites systémiques.

Systemic vasculitides are inflammatory diseases of blood vessels of various sizes, which mechanisms are different according to diseases. Classification can be made according to vessel size, histology and pathogenesis. Giant cell arteritis comprises Horton's disease and Takayasu's arteritis. Different mechanisms have been individualized in the group of necrotizing vasculitides: some are associated with ANCA and other to immune complexes. Other mechanisms have not been yet identified. One of the major purposes of classification is to describe adequately diseases and their outcome, then to treat them appropriately.

EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria.

OBJECTIVES: To validate the previously proposed classification criteria for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). METHODS: Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis