Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low back pain is a frequent symptom to consult the general practioner or the osteo-articular specialist. It is important to identify patients with inflammatory back pain (5 to 10 %) because the management and the treatment are different. Spondylarthropathies, especially ankylosing spondylitis (AS) are the most frequently encountered. The inflammatory characteristics of pain give clues for the diagnosis and allow to make appropriate management. Biological tests and imaging from X rays to MRI are used. As therapy is primarily based on NSAID use, in case of unsatifactory response in peripheral arthritis, disease modyfing drugs such as salazopyrine and methotexate (MTX) are used. Anti TNF are used in AS patients unresponsive to previous therapy (infliximab, etanercept, adalimumab) with a response in 50% of the patients. Etanercept is however not indicated in patients with uveitis.
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PMID:[Inflammatory low back pain]. 1795 23

The therapeutic use of tumor necrosis factor a (TNFa) antagonists has added a highly effective treatment in the field of inflammatory musculoskeletal, skin, and bowel diseases. Most of the side effects of these very potential agents, like infections or skin reactions, were predictable; the development of psoriatic lesions was not, as they are very successfully used to treat psoriasis and psoriatic arthritis, too. There is a number of cases of anti-TNFa-induced psoriatic lesions in the literature, some of them developing with the use of two agents in the same patient, clearly suggesting a class effect. We report an additional series of 12 cases from a total of 300 patients (>800 patient years) and hypothesize on several mechanisms for the explanation of this paradoxical phenomenon namely, local action of TNF, dysregulation of regulatory T cells, or, finally, imbalance between TNF and interferon-a locally. Further studies are needed to elucidate the exact pathogenesis of these manifestations, so that the use of these agents will not only have changed the course of diseases like rheumatoid arthritis or ankylosing spondylitis but may also aid our in depth understanding of the underlying process of disease.
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PMID:Tumor necrosis factor-a antagonist-induced psoriasis: yet another paradox in medicine. 1799 92

TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response. This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease. TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways. These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration. Vascular endothelial cells respond to TNF by undergoing a number of pro-inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis. The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis. The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases.
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PMID:TNF-mediated inflammatory disease. 1816 52

Infliximab is a monoclonal antibody directed against TNF-alpha. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role.
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PMID:Manifestation of palmoplantar pustulosis during or after infliximab therapy for plaque-type psoriasis: report on five cases. 1823 25

The aim of the study was to evaluate factors that influence health status and work disability in patients with ankylosing spondylitis (AS) in the Czech Republic. Data were collected in a retrospective fashion directly from patients with AS using mailed questionnaires containing questions regarding sociodemographic characteristics of patients, the course of their disease, therapy, rehabilitation, quality of life, and ability to work. HAQ-DI (Health Assessment Questionnaire-Disability Index) and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) were also included in the questionnaires; 1,008 questionnaires were suitable for further statistical analysis. The average age +/- SD of patients was 50.2 +/- 10.7 years, the average symptom duration was 23.0 +/- 11.6 years. Mean time from first symptoms to diagnosis was 9.1 years. Full disability had been awarded to 303 patients (30%) at some point of their disease. Twenty seven percent of patients reported receiving full disability pension for 10 or more years. Four hundred fifty six subjects (45%) were currently or had been previously receiving partial disability pension. Receiving disability pension was more frequent among men (64%) compared to women (56%) (P = 0.012), despite the fact that women had higher BASDAI (P < 0.001) and HAQ-DI (P = 0.004) scores. Patients with a family history of AS had higher BASDAI and HAQ-DI scores (P = 0.001 and P = 0.008, respectively) compared to patients without a family history of AS. BASDAI and HAQ-DI scores correlated with age and duration of illness, younger patients and those with shorter disease duration had lower values. Fifty eight percent of patients reported a BASDAI score > or =4 (current cutoff value for initiation of biological therapy), but only 1% of patients were treated by anti TNF alpha agents within the last year. Seven hundred ninety one patients underwent spa treatment in the previous year; 96% of them experienced improvement of their health condition.
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PMID:Factors influencing health status and disability of patients with ankylosing spondylitis in the Czech Republic. 1824 79

It is recommended to evaluate the presence of latent tuberculosis infection (LTBI) before initiating antitumor necrosis factor alpha (anti-TNF) therapy for rheumatologic diseases. We aimed to present the follow-up results of 192 patients with rheumatologic diseases before anti-TNF therapy for LTBI. We enrolled 192 patients who were given anti-TNF therapy for their rheumatologic diseases between April 2005 and January 2008. The demographic characteristics of the patients were recorded. Chest X-ray was obtained and tuberculin skin test (TST) was performed in all patients before anti-TNF therapy. LTBI was assessed by detailed history of close contact with infectious cases within the last year, abnormal chest radiography, and positive TST (> or =5 mm) before initiating anti-TNF therapy. Patients with anti-TNF therapy were followed with 2-month intervals for active tuberculosis by pulmonary and extrapulmonary symptoms, physical examination, and chest X-ray. Of 192 patients, 104 (54.2%) patients were women, age (mean +/- SD) 43.1 +/- 12.7 years and 88 (45.8%) patients were men, age (mean +/- SD) 39.3 +/- 11.2 years. Ninety-one (47.4%) of them had rheumatoid arthritis (RA); 92 (47.9%) had ankylosing spondylitis (AS), and nine (4.7%) had psoriatic arthritis. Isoniazid treatment was started in 129 (67.2%) patients in whom LTBI was detected. No significant difference was observed for TST positivity (TST > or = 5 mm) between the patients with RA and AS (p = 0.101). Similarly, no significant difference was also observed for TST positivity between the patients who received immunosuppressive therapy and those who did not (p = 0.154). Only three (1.6%) patients developed active tuberculosis at the study period. We suggested that in despite of the presence of rheumatologic disease and/or immunosuppressive therapy, TST is an acceptable and available diagnostic test for detecting LTBI before anti-TNF therapy.
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PMID:The evaluation of latent tuberculosis in rheumatologic diseases for anti-TNF therapy: experience with 192 patients. 1832 Jan 37

Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible loss of function. The reported incidence varies from 2-5 cases per 100.000 individuals per year in the general populations to 70 cases per 100.000 individuals annually among patients with rheumatoid arthritis (RA). Predisposing factors are immunosuppressive and corticosteroids therapy and RA "itself". The expected decrease in incidence of SA was not seen over the last 20 years period but we can, on the contrary, expect an increase in the frequency of its appearance because of the population ageing, the increasingly prosthetic joint replacement, the ability of the bacteria to evade clearance by the host immune response and the rapidly growing number of patients with RA, ankylosing spondylitis and psoriatic arthritis treated with tumour necrosis factor alpha (TNF alpha) antagonists. Up to now there have been conflicting reports regarding joint infections in patients under anti-TNF therapy but according to data from Deutsch as well as the British register there might be an increase in the incidence of joint infections in anti-TNF treated patients. Microscopic analysis and culture of synovial fluid are fundamental diagnostic tools in the evaluation of possible joint sepsis. Sonographic guidance of arthrocentesis led to successful aspiration of difficult-to-access joints as shoulder and hip. There is controversy over which mode of drainage of septic synovial fluid should be employed but needle aspiration appear to be preferable to surgical treatment as an initial mode of treatment of SA. Rheumatologists should have a central role in the diagnosis and management of SA.
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PMID:[Septic arthritis: what is the role for the rheumatologist?]. 1843 19

All of the three well-known TNF alpha inhibitors (infliximab, adalimumab and etanercept) have a rapidly occurring and long-lasting effect in ankylosing spondylitis (AS). The IL-1 antagonist, anakinra, has been investigated in two open label studies with partially conflicting results. Apart from infusion reactions and local reactions which rarely are of clinical importance, infections appear significantly more often in the TNF alpha inhibitor groups compared to placebo groups. Most of the infections observed have been minor, but serious infections, including tuberculosis, have been described.
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PMID:[Biological treatment of ankylosing spondylitis]. 1856 98

IL-23 is the main inductor in Th17 polarization of naive T cells, inducing IL-17 production. IL-17 has been demonstrated to be elevated in ankylosing spondylitis (AS). The p40 subunit is common to IL-12 and IL-23. We assessed serum and synovial levels of p40 IL12/23 in spondyloarthropathy (SpA) patients and the evolution under anti-TNF. SpA patients fulfilling ESSG criteria were included. Healthy volunteers served as controls. P40 IL12/23 was assessed using Human Quantikine ELISA (R&D Systems), and at the same time, BASDAI, ESR, CRP, IL-17, MMP-3. Patients treated with anti-TNF were evaluated again after 10 weeks of treatment. Statistical analysis used Mann Whitney and correlation tests. Twenty-seven SpA outpatients (20 men), mean age 40.3 years, mean disease duration 10.5 years, HLA B27 positive n = 21, peripheral arthritis n = 8, mean BASDAI 45.7, mean CRP 30.7 mg/l, and 24 controls (12 men), mean age 50.4 years, were included. There is no statistical difference in serum levels of p40IL12/23 between patients (mean 77.8 pg/ml) and controls (103 pg/ml) and between patients with axial and peripheral involvement. Levels were higher in HLA B-27 negative patients (p = 0.02). No statistical correlation was found between p40 IL12/40 serum levels and each of BASDAI, ESR, CRP, serum levels of IL 17, MMP 3. Fourteen AS patients were treated with TNF blockers. Whereas significant reduction in BASDAI, ESR, and CRP were obvious after treatment, there was no significant change in serum level of p40 IL12/23. Mean levels of synovial p40 IL12/23 were higher in SpA patients (n = 6; mean 536 pg/ml) compared to osteoarthritis patients (n = 3; 133 pg/ml) and compared with paired serum SpA levels. These results suggest that serum levels of p40 IL-12/23 may not be considered as a biologic tool of disease activity assessment in SpA patients.
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PMID:Serum and synovial fluid levels of p40 IL12/23 in spondyloarthropathy patients. 1882 61

There has been a burgeoning interest in the spondyloarthritides (SpAs) due to a confluence of elements. Basic science research has provided new insight into the unique pathophysiology of synovium, enthesium, and bone, highlighting the important differences from rheumatoid arthritis (RA). Through collaborative research of international working groups, classification criteria for psoriatic arthritis (PsA) and ankylosing spondylitis (AS) have been developed or are being refined to aid characterization and diagnosis of SpAs and aid in research. These same working groups, under the umbrella of Outcome Measures in Rheumatology Clinical Trials (OMERACT), have developed domain core sets to be measured in clinical trials and registries, and which allow validation of reliable outcome measures. Both through clinical trials and observational data from national clinical registries, the relative effectiveness and safety of old and new therapies are being demonstrated. This has been particularly shown with long-term data on anti-TNF therapy. Newer anti-TNF therapies are being developed, as are treatments with different mechanisms of action in order to treat patients who do not have long-term effectiveness or develop side effects to older disease modifying therapy and anti-TNFs. International treatment recommendations have been or are being developed based on the evidence base from clinical trials.
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PMID:Spondyloarthritis update: new insights regarding classifcation, pathophysiology, and management. 1893 33


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