A panel of oxidative stress assays does not provide supplementary diagnostic information in Behcet's disease patients

Published onlineJournal ArticleBACKGROUND: Recent findings suggest a role of oxidative stress in the pathogenesis of Behcet's disease (BD), but the utility of oxidative stress-associated assays in offering diagnostic information or in the monitoring of disease activity is largely unassessed. OBJECTIVE AND METHODS: We aimed to measure oxidative and inflammatory markers, along with the markers of reactive nitrogen species, S-nitrosothiols and 3-nitrotyrosine, in BD patients (n = 100) and healthy volunteers (n = 50). These markers were evaluated in regard to their role in the pathogenesis of BD as well as their relation to clinical presentation, disease activity and duration. RESULTS: Median values for erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, and IL-18 levels, as well as myeloperoxidase (MPO) activity, were statistically higher in the patient group compared to controls. Some inflammation markers (ESR, neutrophil and leukocyte counts) were statistically higher (p 0.05 in all statistical comparisons), nor was there any difference in median levels of these oxidative stress markers in active disease versus disease remission. S-nitrosothiols and 3-nitrotyrosine were undetectable in BD plasma. CONCLUSIONS: The application of oxidative stress-associated measures to BD blood samples offered no supplemental diagnostic or disease activity information to that provided by standard laboratory measures of inflammation. S-nitrosothiols and 3-nitrotyrosine appeared not to be markers for active BD; thus the search for biochemical markers that will indicate the active period should be continued with larger studies

Interstitial cystitis: a rare manifestation of primary Sjögren’s syndrome, successfully treated with low dose cyclosporine

Chronic interstitial cystitis (IC), mostly affecting middle-aged women, is a very rare manifestation of primary Sjögren’s syndrome (pSS). Hereby, we report a 42-year-old woman with pSS, presenting with dysuria, urinary frequency, and suprapubic pain. She was diagnosed to have chronic IC, based upon the cystoscopic biopsy finding of chronic inflammation in the bladder wall. Systemic corticosteroid and azathioprine treatments together with local intravesical therapies were not effective. Therefore, cyclosporine (CSA) therapy was initiated. Initial low dose of CSA (1.5 mg/kg/d) improved the symptoms of the patient, with no requirement for dose increment. After 4 months of therapy, control cystoscopic biopsy showed that bladder inflammation regressed and IC improved. This case suggests that even low doses of CSA may be beneficial for treating chronic IC associated with pSS syndrome

Genetic Association of a Gain-of-Function IFNGR1 Polymorphism and the Intergenic Region LNCAROD/DKK1 With Behcet's Disease

Objective. Behçet’s disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behçet’s disease in a diverse multiethnic population.Methods. A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray- 24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed.Results. We identified 2 novel genetic susceptibility loci for Behçet’s disease, including a risk locus in IFNGR1(rs4896243) (odds ratio [OR] 1.25; P = 2.42 × 10−9) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 × 10−8). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide- stimulated monocytes. In addition, our results replicated the association (P 30 genetic susceptibility loci with a suggestive level of association (P < 5 × 10−5), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet’s disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated.Conclusion. We performed the largest genetic association study in Behçet’s disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Diagnosis and differential diagnosis of large-vessel vasculitides

WOS: 000457425100001PubMed ID: 30221327There are no universally accepted diagnostic criteria for large-vessel vasculitides (LVV), including giant cell arteritis (GCA) and Takayasu arteritis (TAK). Currently, available classification criteria cannot be used for the diagnosis of GCA and TAK. Early diagnosis of these two diseases is quite challenging in clinical practice and may be accomplished only by combining the patient symptoms, physical examination findings, blood test results, imaging findings, and biopsy results, if available. Awareness of red flags which lead the clinician to investigate TAK in a young patient with persistent systemic inflammation is helpful for the early diagnosis. It should be noted that clinical presentation may be highly variable in a subgroup of GCA patients with predominant large-vessel involvement (LVI) and without prominent cranial symptoms. Imaging modalities are especially helpful for the diagnosis of this subgroup. Differential diagnosis between older patients with TAK and this subgroup of GCA patients presenting with LVI may be difficult. Various pathologies may mimic LVV either by causing systemic inflammation and constitutional symptoms, or by causing lumen narrowing with or without aneurysm formation in the aorta and its branches. Differential diagnosis of aortitis is crucial. Infectious aortitis including mycotic aneurysms due to septicemia or endocarditis, as well as causes such as syphilis and mycobacterial infections should always be excluded. On the other hand, the presence of non-infectious aortitis is not unique for TAK and GCA. It should be noted that aortitis, other large-vessel involvement or both, may occasionally be seen in various other autoimmune pathologies including ANCA-positive vasculitides, Behcet's disease, ankylosing spondylitis, sarcoidosis, and Sjogren's syndrome. Besides, aortitis may be idiopathic and isolated. Atherosclerosis should always be considered in the differential diagnosis of LVV. Other pathologies which may mimic LVV include, but not limited to, congenital causes of aortic coarctation and middle aortic syndrome, immunoglobulin G4-related disease, and hereditary disorders of connective tissue such as Marfan syndrome and Ehler-Danlos syndrome

Coexistence of vasculitides with Familial Mediterranean Fever

WOS: 000295141300002PubMed ID: 21547384Familial Mediterranean fever (FMF) is the most common autoinflammatory disease characterized by recurrent self-limited attacks of fever accompanied with peritonitis, pleuritis, or arthritis. FMF may coexist with various systemic inflammatory diseases including vasculitides, spondyloarthritis, multiple sclerosis, and inflammatory bowel disease. Among these coexistences, this review concentrates on vasculitic disorders, with the aim of increasing the awareness of FMF-vasculitis association. This association does not merely show a coincidentally increased frequency of vasculitic disorders in FMF; rather, it seems that FMF patients might be at increased risk of developing vasculitis. Indeed, as also suggested by some authors, vasculitis might be an essential feature of FMF. Among the vasculitic disorders reported to be associated with FMF, Henoch-Schonlein purpura, and classical polyarteritis nodosa come the first, possibly followed up by protracted febrile myalgia. There is also an ongoing debate whether Beh double dagger et's disease (BD) more frequently seen in FMF than expected by chance alone. In this review, the associations of various vasculitic disorders with FMF and the possible pathogenic mechanisms underlying these associations, as well as the frequencies and clinical significances of FMF-related MEFV mutations in various vasculitides including BD, are discussed in the context of the available data

What is new in management of Takayasu arteritis?

WOS: 000410653700008PubMed ID: 28774475Management of Takayasu arteritis (TAK) is challenging mostly due to difficulties in assessing actual disease activity. The rational of medical treatment is to suppress both vascular and systemic inflammation with appropriate systemic immunosuppression, including corticosteroids and conventional immunosuppressive (IS) agents. In case of refractory disease activity, biologic agents such as TNF inhibitors and tocilizumab may be tried. In selected cases, endovascular interventions and surgical procedures may be indicated and should be performed during inactive disease. Among conventional IS agents, new data is available for leflunomide. On the other hand, most of the new information in the management of TAK arises from the growing experience with biologic agents used in resistant cases. Besides, there are potential new therapeutic targets which may be promising in the future for medical treatment of TAK. Finally, new trends in endovascular interventions for management of TAK deserve attention

Takayasu arteritis: an update

WOS: 000441766000001PubMed ID: 30114347Takayasu arteritis (TAK) is a challenging chronic, granulomatous, large-vessel systemic vasculitis, mostly due to difficulties in early diagnosis and assessing actual disease activity. Since there are no specific diagnostic laboratory tests, biomarkers, or autoantibodies, many patients experience considerable delay in diagnosis. Remembering the possibility of TAK together with the use of acute phase responses and appropriate imaging studies may be helpful for early diagnosis. Since there may be discrepancies between systemic and vascular wall inflammation, using only acute phase responses is not reliable in assessing current disease activity. Therefore, physical examination and new imaging findings should also be used to assess current disease activity. Despite its limitations, the Indian Takayasu Clinical Activity Score (ITAS2010) may also be helpful for this purpose. The rationale of medical treatment is to suppress both vascular and systemic inflammation with appropriate systemic immunosuppression, including corticosteroids and conventional immunosuppressive agents. In cases of refractory disease activity, leflunomide and biologic agents such as TNF inhibitors and tocilizumab may be tried. In selected cases with persistent lesions that cannot be reversed with medical treatment, endovascular interventions including balloon angioplasty, stent and stent graft replacement, or surgery may be tried. However, such procedures should be performed after suppression of inflammation, i.e. during inactive disease. Prognosis of TAK is probably getting better with lower mortality rates reported in recent years, probably due to the use of more effective medical treatments as well as the use of endovascular interventions when necessary and available

Management of Takayasu arteritis: a systematic review

WOS: 000335006500005PubMed ID: 24097290Assessment of the pattern and extent of arterial involvement and measurement of current disease activity are essential for the management of Takayasu arteritis (TA). Since there is no completed, placebo-controlled, randomized clinical trial, the level of evidence for management of TA is low, generally reflecting the results of open studies, case series and expert opinion. The most commonly used agents include corticosteroids and conventional immunosuppressive agents such as MTX, AZA, MMF and LEF. In patients who remain resistant and/or intolerant to these agents, biologic drugs including TNF inhibitors, rituximab and tocilizumab seem to be promising. Antiplatelet treatment may also lower the frequency of ischaemic events in TA. In the presence of short-segment, critical arterial stenosis, balloon angioplasty or stent graft replacement may be useful. On the other hand, long-segment stenosis with extensive periarterial fibrosis or occlusion requires surgical bypass of the affected segment, which is clearly associated with superior results compared with endovascular intervention. As a general rule, both endovascular intervention and surgical procedures should be avoided during the active phase of the disease. Earlier diagnosis, better assessment of disease activity and future clinical trials will obviously improve the management of TA