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ID PMID Title PublicationDate abstract
16642388 Stimulation of osteoclast formation by inflammatory synovial fluid. 2006 Jul Peri-articular bone resorption is a feature of arthritis due to crystal deposition and rheumatoid disease. Under these conditions, the synovial fluid contains numerous inflammatory cells that produce cytokines and growth factors which promote osteoclast formation. The aim of this study was to determine whether inflammatory synovial fluid stimulates the formation of osteoclasts. Synovial fluid from rheumatoid arthritis (RA), pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients was added to cultures (n=8) of human peripheral blood mononuclear cells (PBMCs) in the presence and absence of macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-kappaB ligand (RANKL). Osteoclast formation was assessed by the formation of cells positive for tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR) and the extent of lacunar resorption. The addition of 10% OA, RA and PPA synovial fluid to PBMC cultures resulted in the formation of numerous multinucleated or mononuclear TRAP(+) and VNR(+) cells which were capable of lacunar resorption. In contrast to PBMC cultures incubated with OA synovial fluid, there was marked stimulation of osteoclast formation and resorption in cultures containing inflammatory RA and PPA synovial fluid which contained high levels of tumour necrosis factor alpha, a factor which is known to stimulate RANKL-induced osteoclast formation.
16605137 Mast cells in autoantibody responses and arthritis. 2005 A pathogenic role for autoantibodies, immune complexes and mast cells has long been hypothesized in rheumatoid arthritis (RA). Recent studies demonstrating novel RA-associated autoantibodies and the efficacy of B cell-directed therapy have led to a renewed interest in the role of humoral immunity in RA. Mouse models of arthritis have provided further support for a direct pathogenic role of autoantibodies in the development of synovial inflammation. Interestingly, in antibody-mediated K/BxN serum transfer arthritis, mast cells have now been identified as a critical cellular mediator of autoantibody-driven joint inflammation. Here, we focus on the role of autoantibodies and mast cells in murine and human inflammatory arthritis.
17127202 Infection and musculoskeletal conditions: Rheumatologic complications of HIV infection. 2006 Dec The pandemic caused by the human immunodeficiency virus (HIV) has entered its second quarter-century, with 40 million people now affected worldwide - particularly in Africa, where the impact has been most devastating. A complex array of rheumatic disease manifestations has been described, including diseases specific to HIV infection such as HIV-associated arthritis and the diffuse infiltrative lymphocytosis syndrome; other conditions which occur prominently in HIV-positive individuals include vasculitis, reactive and psoriatic arthritis and HIV-associated polymyositis, opportunistic musculoskeletal infections, and finally disorders that were originally ameliorated by HIV infection, such as rheumatoid arthritis and lupus. Effective antiretroviral treatment ameliorates many of these disorders; however, the introduction of highly active antiretroviral treatment (HAART) has introduced a new spectrum of disorders and new challenges confronting the clinician, including osteonecrosis, rhabdomyolysis, and, with immune reconstitution, the appearance de novo of a variety of autoimmune disorders and phenomena.
16329650 The role of TNFalpha and IL-17 in the development of excess IL-1 signaling-induced inflamm 2006 IL-1 receptor antagonist (IL-1Ra)-deficient mice spontaneously develop several inflammatory diseases, resembling rheumatoid arthritis, aortitis, and psoriasis in humans. As adoptive T cell transplantation could induce arthritis and aortitis in recipient mice, it was suggested that an autoimmune process is involved in the development of diseases. In contrast, as dermatitis developed in scid/scid-IL-IRa-deficient mice and could not be induced by T cell transfer, a T cell-independent mechanism was suggested. The expression of proinflammatory cytokines was augmented at the inflammatory sites. The development of arthritis and aortitis was significantly suppressed by the deficiency of TNFalpha or IL-17. The development of dermatitis was also inhibited by the deficiency of TNFalpha. These observations suggest that TNFalpha and IL-17 play a crucial role in the development of autoimmunity downstream of IL-1 signaling, and excess IL-1 signaling-induced TNFalpha also induces skin inflammation in a T cell-independent manner.
16255653 Treatment of psoriatic arthritis with etanercept, a tumour necrosis factor antagonist. 2005 Nov Psoriatic arthritis (PsA) is a chronic spondylarthritis that occurs in approximately 23% of plaque psoriasis sufferers. Traditional treatments for rheumatoid arthritis have been used as the first therapeutic approach to treat this inflammatory disease, which has both joint and skin manifestations. However, due to the inefficiency of current disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs in stopping the progression of the joint disease, biologics have emerged as a hopeful alternative to PsA therapy. Etanercept was the first approved tumour necrosis factor-alpha (TNF-alpha) inhibitor for reducing the signs and symptoms of PsA, as well as preventing the progression of the disease. Etanercept is a fully human, soluble, dimeric fusion protein that has the ability to bind to two molecules of TNF, thereby rendering them biologically inactive. Two clinical trials have demonstrated that etanercept is generally a safe, efficacious and well-tolerated biologic therapy for the treatment of PsA.
16870087 Ultrasound imaging for the rheumatologist III. Ultrasonography of the hip. 2006 May Ultrasonography (US) is a reliable and useful diagnostic tool for the assessment of hip pathology. It depicts changes within the coxo-femoral joint (synovitis, erosions, osteophytes) and in the adjacent peri-articular tissues (calcifications, tendonitis, enthesitis, bursitis) in many rheumatic diseases (rheumatoid arthritis, spondyloarthritis, osteoarthritis, polymyalgia rheumatica ) and in some orthopaedic disorders (septic arthritis, trauma, abscess, painful hip after arthroplasty). It is commonly used both in adults and in children. In the assessment of hip joint pathology, US exerts considerable diagnostic supremacy over physical examination. In fact, by virtue of its size and position, reliable physical examination of the hip is often difficult thus making US particularly useful as a bedside tool for the evaluation of a painful hip. Hip US has also proven to be of great practical benefit when performing aspiration and injection within the joint and in the periarticular soft tissues. The relatively limited acoustic windows available to the US beam is the principal limitation to hip US thereby making detailed examination of some important structures impossible together with the interpretation of power Doppler signal sometimes unreliable. In addition, the deep location of the hip can confer further problems to US scanning in obese or particularly muscular subjects.
16357756 Gastrointestinal symptoms and their association with health-related quality of life of chi 2005 Aug OBJECTIVES: The objectives of this study were to perform an initial validation of the Gastrointestinal Symptom Scale for Kids (GISSK) in children with juvenile rheumatoid arthritis (JRA); and too evaluate the relationship between gastrointestinal (GI) symptoms and health-related quality of life (HRQOL) in JRA. METHODS: A convenience sample of 77 children (median age, 10 years; range, 2-18 years) with JRA requiring second-line agents and one of their parents were interviewed. GI symptoms during the preceding 1 week were measured using the GISSK, which consists of 2 components, a visual analog scale of GI symptom severity (GISSK-VAS) and an 8-item questionnaire (GISSK-Q; score 0-8; 0= no GI symptoms). Information on medications, joint involvement with arthritis, and a physician rating of disease activity were obtained. Patient-centered outcomes included the Childhood Health Assessment Questionnaire (CHAQ) to assess disability and discomfort. HRQOL was measured by the Pediatric Quality of Life Generic Core Scale (PedsQL-GC) and the Rheumatology Module (PedsQL-RM), as well as a visual analog scale (VAS-health). To determine test-retest reliability, the GISSK was completed by 40 parents twice within a 1- to 2-week period. To determine the quality of parent proxy-reporting, parent ratings were compared with those of their children aged 8 years or older. RESULTS: GI symptoms were present in the majority of the patients with JRA (58%). Compared with other patients with JRA, those with a GISSK-Q score of > or =2 had significantly lower HRQOL (PedsQL-GC: P < 0.04; PedsQL-RM: P < 0.05; VAS-health: P < 0.02) and more disability (CHAQ: P < 0.002), despite similar disease activity and joint findings. Similar relationships were observed for the GISSK-VAS with traditional outcomes and HRQOL. The test-retest reliability of the GISSK was good (ICCGISSK-Q = 0.60; ICCGISSK-VAS = 0.67). The quality of parent proxy-reporting was fair to good (ICCGISSK-Q = 0.47; ICCGISSK-VAS = 0.66). CONCLUSION: GI symptoms are frequent among children with JRA requiring advanced therapies and, if moderate or severe, are associated with significantly lower HRQOL. The GISSK is a reliable and valid measure of GI symptoms and their severity in JRA. This self-administered measure can be used to screen for GI symptoms in clinical practice and may be useful to assess the effects of medication changes on the perceived GI side effects in children with JRA.
15827045 Outcome following onset of juvenile idiopathic inflammatory arthritis: I. frequency of dif 2005 Aug OBJECTIVE: To determine the outcome, following the onset of juvenile idiopathic inflammatory arthritis, in terms of remission of disease activity, loss of function and structural damage based on a review of the available published data. METHODS: Electronic databases were searched for major studies publishing outcome data in the past 10 yr in juvenile idiopathic arthritis, juvenile rheumatoid arthritis and juvenile chronic arthritis, and 21 studies were selected. The proportions of children in the different categories of the outcomes of interest are described. Data were stratified where possible by disease subtype. RESULTS: There were major differences between the studies reviewed in terms of study design, case selection and the results obtained. In general, children with systemic- or polyarticular-onset disease were much less likely to go into remission than those with oligoarticular onset, although the remission rates in the latter group ranged from 36 to 84%. Several different approaches were used to assess functional outcome but the pattern of results between the different subgroups was the same as with remission. Similarly, children with polyarticular disease in all the cohorts reviewed were substantially more likely to have erosive radiological damage on follow-up. The rates of individual outcomes, even within a subgroup, varied considerably between studies and this does not appear to be explained solely by differences in methodology. CONCLUSIONS: There remains a considerable lack of clarity in the prognosis following onset of juvenile idiopathic arthritis for the major outcomes considered, although those with oligoarthritis at presentation have the best outcome. The ability to offer accurate prognosis is particularly important to both reassure parents and guide treatment at disease onset. To achieve this, large definitive prospective studies will be required.
16956438 The diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies in children wit 2006 Jul BACKGROUND: Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA). OBJECTIVE: To assess the clinical significance of anti-CCP antibodies in a cohort of patients with juvenile idiopathic arthritis (JIA) and if they can be used to identify patients with an unfavourable course of disease. METHODS: 68 serum samples were investigated. 45 patients were diagnosed with JIA (15 male and 30 female) aged 1.9-17.3 years (median 12.9 mean 11,0). 5 patients had polyarticular (RF negative), 2 polyarticular (RF positive), 25 oligoarticular JIA, 6 enthesitis related arthritis, 2 psoriatric arthritis, 3 patients had systemic disease and 2 unclassified arthritis. 23 samples were taken from patients with non-inflammatory cardiac diseases undergoing interventional cardiac therapy. Enzyme-linked immunosorbent assay (ELISA; Euroimmun, Lübeck, Germany) was used for the detection and quantification of anti-CCP antibodies in patients with JIA. RESULTS: Overall, anti-CCP antibodies were found in 2.9% (2/68) of all samples and in 4.4 % (2/45) patients with JIA. CONCLUSION: Anti-CCP antibodies are associated with RF positive polyarticular course of JIA. Anti-CCP antibodies are not relevant for other subgroups of JIA. Therefore anti-CCP Abs in patients with JIA should not be investigated routinely.
15801037 Development of Crohn's disease in a patient taking etanercept. 2005 Apr In addition to its well known proinflammatory effects, tumor necrosis factor-alpha (TNF-a) has complex effects on the growth, differentiation, and death of immune cells. TNF antagonists have had dramatic effects on the suppression of rheumatoid arthritis and other rheumatic inflammatory diseases. However, TNF inhibition of RA has led to an increased incidence of drug induced anti-dsDNA production, with cases of systemic lupus erythematosus as well as exacerbations of multiple sclerosis. While etanercept does not generally alter the course of Crohn's disease we describe a rare instance where this agent may have contributed to the development of clinically significant inflammatory bowel disease.
16045865 An unusual adverse drug reaction? 2005 Jul INTRODUCTION: Adult Still Disease (ASD) is a rare (incidence 1-1,6/1,000,000 in Europe) seronegative polyarthropathy diagnosed with clinical criteria, excluding other etiologies. Minocycline, a semisynthetic derivative of tetracycline, has been associated with many adverse effects. We present the case of a 18-years-old man with a high suspicion of an adverse drug reaction (ADR), that was finally diagnosed of ASD. MATERIAL AND METHODS: In order to exclude other diseases, laboratory test, radiology and allergological studies were performed. The results of the allergological studies excluded the possibility of an ADR. The rest of the results determined the diagnosis of ASD. CONCLUSION: It's necessary to emphasize the importance of an accurate differential diagnosis in cases like this, because many diseases may mimic an ADR, and may be underdiagnosed (or misdiagnosed).
16283417 Successful treatment of a patient with primary Sjögren's syndrome with Rituximab. 2006 Nov We report the course of a 55-year-old woman, the first patient with primary Sjögren's syndrome and distal renal tubular acidosis but without lymphoma to be treated with B-cell depletion using Rituximab. Rapidly after B-cell depletion, remarkable improvement in xerostomia occurred, while serological findings and tubular acidosis have been unchanged. In labial salivary gland biopsy, lymphocyte infiltration and particularly CD20-positive cells decreased strikingly. Aquaporin 1 (AQP-1) expression in myoepithelial cells was very low before treatment and increased noticeably. Apical AQP-5 in acinus cells likewise increased following Rituximab. In contrast, basolateral NKCC1 was expressed at unchanged intensity before and following Rituximab. The improvement has been sustained and still is most gratifying 10 months after treatment. B-cell depletion may be effective treatment in Sjögren's syndrome. Likewise, it may now be possible to separate the immunologic phenomena in Sjögren's syndrome from the consequences of prolonged hyposalivation when studying the pathophysiology of xerostomia.
15900628 The role of plasma high molecular weight kininogen in experimental intestinal and systemic 2005 Jan Inflammation is accompanied by activation of the plasma kallikrein-kinin system (KKS). KKS activation has been demonstrated in a variety of inflammatory human diseases. To further explore the participation of KKS in arthritis and inflammatory bowel disease, we used two experimental animal models in arthritis and enterocolitis. We found that activation of KKS is associated with arthritis induced by intraperitoneal injection of peptidoglycan-polysaccharide polymers (PG-PS) as well as the enterocolitis and systemic inflammation induced also by PG-PS when injected into the intestinal wall of genetically susceptible Lewis rats. We postulated that KKS participates in the pathogenesis of inflammatory reactions involved in cellular injury, coagulation, fibrinolysis, kinin formation, complement activation, cytokine secretion, and release of proteases. We demonstrated that therapy with a specific plasma kallikrein inhibitor modulated the experimental enterocolitis, arthritis, and systemic inflammation. The fact that deficiency of plasma high molecular weight kininogen in the genetically susceptible Lewis rat results in decreased chronic enterocolitis and systemic inflammation also supports our hypothesis. We suggest that KKS plays a similar role in idiopathic human intestinal inflammatory disease and arthritis, making kallikrein-kinin system proteins appealing targets for drug therapy in chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease.
16207332 Chronic development of collagen-induced arthritis is associated with arthritogenic antibod 2005 Antibodies against type II collagen (CII) are important in the development of collagen-induced arthritis (CIA) and possibly also in rheumatoid arthritis. We have determined the fine specificity and arthritogenicity of the antibody response to CII in chronic relapsing variants of CIA. Immunization with rat CII in B10.Q or B10.Q(BALB/cxB10.Q)F2 mice induces a chronic relapsing CIA. The antibody response to CII was determined by using triple-helical peptides of the major B cell epitopes. Each individual mouse had a unique epitope-specific response and this epitope predominance shifted distinctly during the course of the disease. In the B10.Q mice the antibodies specific for C1 and U1, and in the B10.Q(BALB/cxB10.Q)F2 mice the antibodies specific for C1, U1 and J1, correlated with the development of chronic arthritis. Injection of monoclonal antibodies against these epitopes induced relapses in chronic arthritic mice. The development of chronic relapsing arthritis, initially induced by CII immunization, is associated with an arthritogenic antibody response to certain CII epitopes.
15869827 [Neurological manifestations in Sjögren syndrome]. 2005 Aug PURPOSE: To describe clinical and physiopathological aspects of neurological involvement in neurological Sjögren syndrome (SS) and to overview biological markers and therapeutical aspects. CURRENT KNOWLEDGE AND KEY POINTS: Neurological complications during SS may occur between 8.5 and 70%. Peripheral nervous system (PNS) involvement is well none but data concerning central nervous system (CNS) symptoms have been rarely described. In the present study we detail more precisely the heterogeneity of the neurological manifestation in SS. Recently new biological of SS such as alpha-fodrin antibodies have been described but there interest remain controversial. Furthermore, therapeutical data are scarce and there is to date no consensual guidelines for the therapeutical approach. PERSPECTIVE: Recent data concerning neurological involvement in SS confirm the heterogeneity of clinical presentations that may mimic stroke or multiple sclerosis. They underline the need for new biological markers. Furthermore, multicentric, randomized trials should be assessed in order to give us some therapeutical guidelines.
15928619 Histopathology of persistent papules and plaques in adult-onset Still's disease. 2005 Jun BACKGROUND: Persistent plaques and linear pigmentation have been reported as specific skin lesions in some patients with adult-onset Still's disease (AOSD). OBJECTIVE: We sought to characterize the histologic findings of AOSD-associated persistent rash in 11 cases and correlate the histologic findings with the clinical features. METHODS: From 1988 to 2004, 17 cases fulfilling Yamaguchi's criteria for AOSD in our hospital were reviewed and 11 (65%) manifested persistent papules and plaques. The pathology of 13 biopsy specimens of persistent eruption from 9 patients was reviewed. RESULTS: The 11 patients consisted of 3 men and 8 women with age of onset ranging from 19 to 67 years (average 34.7 years). Evanescent Still's rash was recorded in 9 patients. The persistent rash manifested as pruritic, red, violaceous, or brownish scaly or crusted lichenoid papules and plaques usually widely distributed over the trunk, neck, face, and extensor sides of the extremities. Lesions arranged in a bizarre linear pattern resulting from scratching were noted in some patients. Three patients died of severe disease, systemic complications, or both. The histology of persistent papules and plaques was characterized by: (1) multiple individual necrotic keratinocytes, singly or in aggregates, mainly located in the upper epidermis, including the normal or parakeratotic horny layer; and (2) infiltration of lymphocytes and neutrophils in the papillary and middermis. Other less common findings included basal vacuolar alteration, nuclear dust, and subcorneal or intracorneal pustules. CONCLUSIONS: A clinically and pathologically distinct form of persistent lichenoid eruption was commonly observed in our patients with AOSD. The combination of multiple individual necrotic keratinocytes in the upper epidermis and a dermal infiltrate of neutrophils allow for histologic differentiation of this persistent eruption from most other lichenoid and interface dermatitides and may facilitate an earlier diagnosis of AOSD.
16015657 Etiology of reactive arthritis in Pan paniscus, P. troglodytes troglodytes, and P. troglod 2005 Jul The character of arthritis has not received the same attention in Pan paniscus as it has in P. troglodytes. Reactive arthritis (a form of spondyloarthropathy) in the latter has been considered to be either a sexually transmitted or an infectious-agent diarrhea-related disorder. The unique sexual promiscuity of P. paniscus enables us to distinguish between those hypotheses. The macerated skeletons of 139 adult P. paniscus, P. troglodytes troglodytes, and P. troglodytes schweinfurthii were macroscopically analyzed for osseous and articular pathologies. The sex of the animal was recorded at the time of acquisition. Twenty-one percent of the P. paniscus, 28% of the P. t. troglodytes, and 27% of the P. t. schweinfurthii specimens had peripheral and central joint erosive disease characteristic of spondyloarthropathy. Subchondral pauciarticular distribution and reactive new bone clearly distinguish this disease from rheumatoid arthritis, osteoarthritis, and direct bone/joint infection. The fact that P. paniscus and P. t. troglodytes were similar in terms of disease frequency makes the notion of sexual transmission unlikely. While the frequencies of spondyloarthropathy were indistinguishable among all species/subspecies studied, the patterns of joint involvement were disparate. The Pan paniscus and P. t. troglodytes home ranges are geographically separate. We assessed possible habitat factors (e.g., exposure to specific infectious agents of diarrhea) by comparing P. paniscus and P. t. troglodytes with P. t. schweinfurthii. The latter shared similar patterns and habitats (separated by the Congo River) with P. paniscus. The explanation offered for habitat-specific patterns is differential bacterial exposure-most likely Shigella or Yersinia in P. paniscus and P. t. schweinfurthii.
17023811 Henoch-Schönlein purpura after etanercept therapy for psoriasis. 2006 Oct Etanercept is a recombinant dimeric fusion protein consisting of a tumor necrosis factor-alpha receptor ligand-binding region linked to the Fc portion of human IgG. It is approved for use in the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, and psoriatic arthritis. Since 1998, there have been reports of vasculitic adverse events, including necrotizing vasculitis and leukocytoclastic vasculitis. In addition, the adverse events reporting system of the U.S. Food and Drug Administration has recorded 35 cases of leukocytoclastic vasculitis, 20 after etanercept therapy and 15 after infliximab. Most cases of cutaneous vasculitis describe development of symptoms within 3 months of etanercept use. In only one case report was direct immunofluorescence performed on tissue and no specific immunoreactivity found. We describe the first case of Henoch-Schönlein purpura with acute renal failure associated with increase in etanercept dose after 11 months of use for treatment of psoriasis. Discontinuation of the drug and treatment with a course of systemic steroids led to the complete resolution of the vasculitis and improvement of renal function. Vasculitis occurring even during chronic use of antitumor necrosis factor agents must be considered as possibly related to the therapy.
16633923 Guidelines for the proper use of etanercept in Japan. 2006 Application of biological agents targeting inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) dramatically caused a paradigm shift in the treatment of rheumatoid arthritis (RA). Infliximab, a chimeric anti-TNF-alpha monoclonal antibody, has initially been introduced to Japan in 2003 and shown to be dramatically effective in alleviating arthritis refractory to conventional treatment. However, serious adverse events such as bacterial pneumonia, tuberculosis, and Pneumocystis jiroveci pneumonia were reported to be in relatively high incidence; i.e., 2%, 0.3%, and 0.4%, respectively, in a strict postmarketing surveillance of an initial 4000 cases in Japan. Etancercept, a recombinant chimeric protein consisting of p75 TNF-alpha receptor and human IgG, was subsequently introduced to Japan in March of 2005. We therefore drew up treatment guidelines for the use of etanercept to avoid potential serous adverse events, since only approximately 150 cases have been included in the clinical study of etanercept in Japan. The guidelines were initially designed by the principal investigators (N.M, T.T., K.E.) of rheumatoid arthritis study groups of the Ministry of Health, Labor and Welfare (MHLW), Japan, and finally approved by the board of directors of the Japan College of Rheumatology. The MHLW assigned a duty to the pharmaceutical companies to perform a complete postmarketing surveillance of an initial 3000 cases to explore any adverse events, and this was performed according to the treatment guidelines shown in this article.
16134723 Therapy of ankylosing spondylitis. Part II: biological therapies in the spondyloarthritide 2005 May Therapeutic options for patients with active and severe spondylarthritis (SpA) have been fairly limited in the past decades. There is now accumulating evidence that biological therapy with agents directed against tumour necrosis factor-alpha (TNF-alpha) is highly efficacious in the spondyloarthritides, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The TNF blocking agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis (RA) in Europe and the USA. In contrast to rheumatoid arthritis (RA) disease-modifying anti-rheumatic drugs (DMARDs) have limited efficacy in SpA. No DMARDs are available for AS patients with active spinal disease. Thus, for AS patients whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs (NSAIDs), therapy with TNF blockers may be considered as a first-line treatment. For infliximab, a dose of 3-5 mg/kg seems to be required, and intervals between 6 and 12 weeks are necessary to suppress disease activity continually. The standard dosage of etanercept is 2 x 25 mg subcutaneously (s.c.) per week. There are very few studies with adalimumab (standard dose in RA 20-40 mg s.c. every 1-2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. There is some evidence that both agents also work in other SpA, especially in PsA. Withdrawal of long-term therapy in AS patients led to relapses of disease after several months. Less radiographic progression after 2 years of continuous treatment with infliximab compared to conventional therapy has been suggested in a small study. Serious adverse events on anti-TNF therapy have remained rare. However, severe infections, including tuberculosis, have been reported. These can be largely prevented by appropriate screening. The benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.