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Within the variable course of ankylosing spondylitis (AS), peripheral arthritis, enthesitis, and involvement of other organs can add to the burden of the disease. The primary complaints of patients with spondyloarthritis (SpA) are pain, stiffness, fatigue, and limitation in activities and social participation. Instruments currently available for the assessment of patients with SpA focus predominantly on specific aspects of health such as pain, disease activity, and physical function and measure specific concepts like physical function and health-related quality of life (HR-QoL). However, the overall picture of impairments, limitations and restrictions in activities or social participation of patients with AS is not adequately assessed in SpA-specific questionnaires. Most of the existing questionnaires are not conceptualised with regard to their underlying construct. The International classification of functioning, disability and health (ICF) Core Set for AS may serve as an appropriate model and underlying construct to develop a health index, since the whole range of functioning and disability of patients with AS is captured. Based on these assumptions, ASAS developed for patients with SpA an instrument assessing health as operationalised by the ICF. The questionnaire was developed by preparing an item pool, linkage of the items to the comprehensive ICF core set for AS and test of the item pool in two cross-sectional studies. The analysis of the questionnaire and the response scale were done with Rasch analysis. Emphasis was on optimal targeting, the capacity of items to differentiate between different levels of health, and optimal coverage of items to the spectrum of ICF categories, so that the final questionnaire could represent as much of the entire range of difficulty levels as possible. The ASAS HI is a linear composite measure and includes 17 items which cover most of the ICF core set. Preliminary validity has been confirmed in a field test in 4 English-speaking countries. The ASAS HI should soon be used in clinical trials and in clinical practice to test its real life performance and to confirm that this new composite index captures relevant information on functioning and health of patients with AS.

The spondyloarthritides (SpA) are currently differentiated into axial and peripheral SpA. Patients with axial SpA (axSpA) may be further classified into the classical form ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). The SpA are genetically linked, and the subtypes including psoriatic arthritis (PsA) share characteristic clinical symptoms such as inflammatory back pain (IBP) and enthesitis. IMP can be due to sacroiliitis and spondylitis, enthesitis may occur with or without arthritis, and anterior uveitis, as well as other extraarticular manifestations such as psoriasis and chronic inflammatory bowel disease (IBD). In addition to clinical findings, imaging, mainly conventional radiography and magnetic resonance imaging (MRI), and laboratory results such as HLA B27 and CRP are important tools for classification and diagnosis of SpA. The Assessment of SpondyloArthritis international Society (ASAS), an international group of experts in the field of SpA since 1995, has published on assessments and outcome parameters in SpA. The publication of classification criteria for axSpA has now largely replaced the 1984 criteria for AS. However, the established cut-off between AS and nr-axSpA, 'definite' structural changes in the sacroiliac joints, has been recently debated because of limited reliability. Since imaging plays an important role in all criteria sets, the ASAS group has recently published definitions for inflammatory changes in the SIJ and the spine. The most important domains in AS are disease activity, function, spinal mobility, structural damage, and quality of life, some of which are discussed in this manuscript. For axSpA there are two major tools to assess disease activity, the BASDAI and the ASDAS, one for function, the BASFI, and several mobility measures including the BASMI. The AS Health Index (AS-HI) is introduced elsewhere in this supplement.

Methotrexate (MTX) is the anchor drug in the treatment of patients with rheumatoid arthritis (RA). MTX shows effects on disease activity and mortality. However, it is unclear whether the effect of MTX on mortality depends on its effect on disease activity.In a post-hoc analysis we analysed the data of our cohort established in Ratingen, Germany, and included all patients starting treatment with MTX (n=271) between 1980 and 1987. One year after baseline (BL), response to MTX treatment was assessed using a modified ACR 20 response. Follow-up data of 250 patients were available after 10 and 18 years.After 1 year, there were 66% responders and 20% non-responders; only 14% had discontinued MTX treatment due to side effects or lack of efficacy. Most patients continued MTX treatment irrespective of efficacy. Ten years after BL, 61% of the patients were still treated with MTX. After 18 years, the responder-group showed a standardised mortality ratio of 1.6 compared to 3.2 for the group of non-responders. However, when adjusting for age, gender, response to MTX treatment one year after BL, number of swollen joints and comorbidities after 10 years an independent association of continued MTX treatment with lower mortality was found for the period 10 to 18 years after BL (hazard ratio (HR): 0.63, 95% confidence interval: 0.43-0.92, p=0.015).In this cohort, the mortality lowering effect of continued MTX use was partly independent of its effect on disease activity. This finding may affect treatment decisions concerning RA patients with insufficient response to MTX.

Spondyloarthritides (SpA) are chronic inflammatory rheumatic diseases that usually affect the axial skeleton and may involve entheses and peripheral joints. The main subtypes are ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Other subtypes are reactive arthritis, arthritis associated with chronic inflammatory bowel diseases and undifferentiated axial and peripheral spondyloarthritis. Although SpA were regarded as variants of rheumatoid arthritis (RA) until the 1970s, it is now well established that the pathogenesis of SpA is quite different from that of RA. There is a lack of good clinical studies on glucocorticoid therapy in the SpA. While there is no reasonable doubt that intraarticular local therapies in SpA are as effective as in RA and other forms of arthritis, the evidence for a systemic use is at best marginal. While very high doses may be effective in some patients with AS, the possible value of low-dose corticosteroid therapy in patients with PsA has never been well addressed, with respect to either clinical efficacy or inhibition of radiographic progression. Future studies are needed to clarify this important issue for usual patient care.

Glucocorticoids (GCs) have been an invaluable tool in the treatment of patients with rheumatoid arthritis (RA) for decades, with a focus mainly on symptom management. In addition, several studies in the last 15 years have shown that GCs are also disease-modifying in patients with RA - which implies that they inhibit radiographic progression. These effects seem to be especially important in the early course of disease. Nonetheless, there is still a lack of knowledge concerning optimal therapeutic strategies with GCs, particularly regarding patient selection and optimal dosage schedules.

To study the long-term efficacy and safety of treatment with infliximab in patients with ankylosing spondylitis (AS) in a real life setting.AS patients from 6 European countries who had finished the 2-year trial ASSERT were invited to participate in the open- label investigator-driven study EASIC. At baseline, 2 groups were formed: patients of group 1 had not been treated with infliximab after ASSERT, while those of group 2 had continuously received it. Patients of group 1 were further subdivided in group 1a: patients with a relapse and 1b: in remission. All patients of group 1a and 2 continuously received infliximab for 96 weeks, mean dose 5 mg/kg, intervals 6-8 weeks. Patients of group 1b were also treated in case of relapse.A total of 103/149 patients (69%) were included in EASIC, 1.3 ± 0.9 years after the end of ASSERT: 9 in group 1a, 5 in group 1b and 89 in group 2. Most patients were male (83%), mean age 44 years. Most patients of group 2 completed the trial (86%) vs. only 5 of group 1 (33%) - mostly due to allergic reactions after readministration of infliximab. In total, there were 22 drop-outs due to 6 adverse events, 4 lack of efficacy, 3 planned pregnancy. All standard assessments indicated beneficial values over time, at week 96 significantly better than at baseline of ASSERT.The majority of patients were continuously and successfully treated with infliximab for 5 years, whereas discontinuation and reintroduction of therapy was less satisfactory due to the frequent occurrence of hypersensitivity reactions. Anti-TNF therapy with infliximab proved to be effective and safe on a long-term basis.

The inflammatory myopathies are a heterogeneous group of diseases including dermatomyositis, polymyositis, and inclusion body myositis. Few clinical trials have been reported in myositis, it is difficult to make definitive recommendations for the treatment of these potentially life threatening diseases. In addition to treatment with corticosteroids, immunosuppressive agents and immunomodulatory therapy are used to improve disease control and reduce the long-term side effects of corticosteroids. While these treatments are commonly used in routine clinical practice, the optimal therapeutic regimen remains unclear. However, most patients with dermatomyositis or polymyositis are treated with oral high-dose prednisone combined with azathioprine or methotrexate to facilitate tapering of prednisone.

Methotrexate (MTX) has been used for the treatment of rheumatic diseases, especially rheumatoid arthritis (RA), for some decades now. Although it had been known from pharmacokinetic studies for quite some time already that the bioavailability of MTX is superior when administered parenterally rather than orally, this had never been formally proven to be clinically relevant. In a recent randomised clinical trial, the two ways of administration have been directly compared. The fact that the patient group that received MTX s.c. had better clinical outcome than the oral group can be considered as proof that this hypothesis has now been confirmed. Although this result does not mean that every patient will be in need of parenteral administration of MTX, it suggests that very active patients and those with a worse prognosis may have more benefit from this strategy.

Sarcoidosis may present with symptoms related to involvement of joints, skin and lungs, as well as other organs. Corticosteroids are the basis of treatment of symptomatic sarcoidosis. Additional or alternative drugs may be required in chronic cases and when systemic corticosteroids are contraindicated. Cytotoxic agents seem to be of value in selected patients, but no controlled studies are available, and the published literature consists of small case series. Therefore, no international agreement exists regarding when these drugs should be used in patients with sarcoidosis. Methotrexate is generally the preferred agent for treatment of chronic sarcoidosis when corticosteroids have inadequate efficacy and/or severe adverse effects. In this review we discuss the available literature concerning the treatment of sarcoidosis with methotrexate.

Methotrexate (MTX) is the disease modifying antirheumatic 'anchor' drug for the treatment of patients with rheumatoid arthritis (RA). Despite its widespread use and the frequent need of elective orthopaedic and other types of surgical procedures in patients with RA, some confusion exists concerning the use of MTX in the perioperative period. Currently available data do not suggest a need to discontinue MTX because of surgery. There is some evidence that treatment with MTX is safe prior to and after elective surgical procedures. Importantly, disease activity is better controlled when MTX is not interrupted from weekly administration.

The history of classification and diagnostic criteria for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) is similar and different. Important criteria sets have been published for both disease in the mid eighties, for AS in 1984 and for RA in 1987. The leading clinical symptoms, inflammatory back pain (IBP) in AS and the predominant polyarticular symmetric involvement of the hands in RA were, of course, central, and so was morning stiffness as a major clinical sign of an inflammatory disease state. In RA, there was more focus on laboratory parameters (rheumatoid factor), while this could have been the case also in AS (HLA B27) but this was not recognized at this point in time. In contrast, imaging has played a more important role in AS - especially because the sacroiliac joints are involved in the vast majority of AS patients, while in RA radiographic changes of the joints of hands and feet may contribute to the diagnosis. However, in both diseases, early structural changes visualized by conventional radiography rather have prognostic impact since these patients are much more likely to progress in comparison to others who do not have cartilage and joint damage early in the course of the disease. Further developments of criteria for AS have broadened the spectrum of AS to spondyloarthritis (SpA) and axial SpA which covers most early forms. The leading clinical symptom is chronic back pain in young adults and IBP. New criteria for RA which include more patients with early disease and anti-CCP antibodies as new markers are being developed. This is important since early treatment strategies are increasingly and successfully used to treat inflammatory diseases more efficiently.

There are clear differences in the clinical picture and in the pathogenesis between rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Biologic agents targeting TNF-alpha are efficacious in both diseases, with some tendency to work even better in spondyloarthritides (SpA) on a clinical basis. However, anti-TNF therapy was shown to inhibit radiographic progression in RA but not in AS. This is probably due to the outstanding difference in pathogenesis: while in RA osteodestructive lesions such as erosions predominate, AS patients will rather develop osteoproliferative changes such as syndesmophytes. There is some evidence that anti-TNF agents may show longterm efficacy and acceptable safety profiles over 5-10 years. There are some differences between the agents.Whether the recent developments of targeted therapies in RA with agents such as rituximab, abatacept and tocilizumab will also work for AS is unknown at present.

Whether the differences in the clinical picture and in the pathogenesis between rheumatoid arthritis (RA) and ankylosing spondylitis (AS) will lead to different therapeutic approaches is unclear at present. Since anti-TNF-alpha agents and other biologics are not efficacious in all patients new developments are clearly needed.

The treatment of the two most frequent inflammatory rheumatic diseases rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has some similarities but in total more differences. Thus, therapy with non-steroidal anti-inflammatory agents (NSAIDs), conventional disease modifying anti-rheumatic drugs (DMARDs) and biologic agents has a different role in the management and different efficacy in AS and RA. This implies signs and symptoms, function, and structural damage. This is in part due to the different pathogenesis: (i) while the synovium is an important target in RA it is rather the bone in AS and (ii) while the pathology in RA is rather osteodestructive to cartilage and bone presenting with erosions, it is predominantly osteoproliferative in AS as indicated by syndesmophytes and ankylosis. Biologic agents targeting tumor necrosis factor (TNF-alpha) work clinically well in both diseases but, while they clearly inhibit structural damage in RA, they do not seem to have much influence on new bone formation in AS. DMARDs are efficacious in RA but less so in AS. NSAIDs are efficacious in both RA and AS, but they are considered first line of therapy in AS while they are rather adjunctive agents in RA. In AS, NSAIDs, potentially especially coxibs, may even prevent new bone formation due to their inhibitory effect on cyclooxygenase-2.

Except for morning stiffness, the clinical symptoms and the history of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) usually differ: the location in RA is mostly the hands and feet, and in AS rather the back. Patients with RA tend to be older (50 years) and female, while in AS there are somewhat more often male and younger (30 years) at onset of inflammatory back pain, the leading clinical symptom. The clinical examination of patients in the early phase of the disease is usually easier in RA, although arthralgia and arthritis may be difficult to differentiate. Joint counts are useful in states of high disease activity with polyarticular flares and more established disease. In comparison, in AS, young patients with back pain frequently show normal physical examens, a reduction of lateral spinal flexion and chest expansion are often the earliest signs which are also sensitive to change on therapy with biologics. The cervical spine may be affected in RA and AS - more frequently in advanced disease stages but rather early cases have been reported.

The rheumatic diseases not only bring pain, disability and poorer quality of life, but also a premature mortality which is often overlooked. Alongside mortality due to the direct complications of disease comes an increase in deaths related to specific therapies and indirect causes such as cancer and cardiovascular mortality. By comparing mortality and its causes in two of the most common inflammatory arthritides, rheumatoid arthritis and ankylosing spondylitis, common threads emerge which give us insight into the impact of chronic inflammatory disease and new directions for patient management.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease which causes pain along with loss of physical function and quality of life over many years. It has also been shown to increase mortality compared to the general population, independent of treatment modalities. Cardiovascular deaths are increased, and recent studies suggest both an abnormality of lipid regulation and microvascular changes. Increased rates of suicide, accidental death, and alcohol-related deaths have also been reported. This review examines rates and causes of increased mortality in AS and highlights a need to focus on cardiovascular risk factors and psychological health in addition to physical disability in patients with AS.

Schnitzler's syndrome is a rather rare disease which may appear in a rheumatologist's office because patients often report rheumatic symptoms with joint, bone and muscle pain. However, it is characterized by chronic urticaria, recurrent fever, liver and spleen enlargement, osteosclerosis, and lymphadenopathy, in conjunction with a serum IgM M component. A patient who had been treated with relatively high doses of corticosteroids for 10 years with insufficient response was treated with the IL-1 receptor antagonist anakinra, this led to a complete resolution of symptoms.

The challenge of managing knowledge is a difficult one, and it is no longer enough simply to conduct clinical trials. Quality of care requires the incorporation of research knowledge into clinical practice. As our knowledge of the chronic inflammatory rheumatic disease ankylosing spondylitis (AS) has grown, evidence-based recommendations for the early diagnosis and management of AS and scientifically-derived outcome measures have been developed to aid the clinician at the point of care. Some of these, including the ASAS/EULAR recommendations for the management of AS, are now being validated in national and international studies. This article discusses existing recommendations and the need for specific quality indicators in the field of AS.

The association between musculoskeletal features and lymphoproliferative disorders as well as the association of rheumatic diseases with an increased risk of malignancies is well-known.This paper describes three patients with inflammatory joint diseases treated with disease modifying antirheumatic drugs who developed lymphoproliferative disorders either of an abnormal type or with unusual clinical features.The difficulty in differentiating the musculoskeletal symptoms of an underlying lymphoproliferative disease from the features of the rheumatic disease itself with special regard to treatment with disease-modifying antirheumatic drugs including biologics is emphasised on the example of patient 1. Patient 2 presented with a rare type of lymphoma and had been mistakenly diagnosed as having seronegative RA. The last patient with oligoarthritis represents an example of the sarcoidosis-lymphoma syndrome.This article addresses several of the problems rheumatologists may experience with the various rheumatologic manifestations of lymphoproliferative disorders. Until more definitive data are available, patients who develop unexpected arthritis should be considered for histologic biopsy to rule out coexistent neoplasia.

Remission is a major goal of medical therapy in chronic disease. Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that affects the axial skeleton and other body structures, causing pain, stiffness, functional loss, and disability. Until recently only symptomatic therapies were available, and control was poor in patients with severe disease. However, the TNF antagonists have now changed this substantially. The concept of disease remission in AS has not received much attention in the current literature. There exists one set of partial remission criteria formally developed by the ASsessments in Ankylosing Spondylitis (ASAS) working group on the basis of clinical trials with nonsteroidal anti-inflammatory drugs for use in clinical trials. Furthermore, a state of low disease activity has been defined empirically in studies of anti-tumour necrosis factor (anti-TNF) therapy to describe clinically relevant treatment efficacy. As more effective therapies become available for AS, disease remission is increasingly regarded as an appropriate therapeutic goal that may then be translated into modification of progressive structural damage. There is a need to further define and evaluate current proposals concerning remission in AS.

AS and other spondyloarthritides (SpA) are mostly chronic inflammatory rheumatic diseases characterised by a strong association with HLA B27. Recent data from our group have suggested that AS patients have a diminished secretion capacity of inflammatory cytokines, possibly associated with HLA B27. The aim of this study was to identify CD4+ and CD8+ T cell subsets responsible for the observed lower cytokine secretion capacity in HLA B27-positives.Highly purified (98%) CD4+ and CD8+ T cells of HLA B27-positive AS patients (n = 13), healthy HLA B27-positive (n = 7) and -negative controls (n = 9) were stimulated for 6h with PMA/ Ionomycin and, after fixation, stained for surface markers CD45RA and CD27 and cytokines TNFalpha, IFNgamma, IL-4 and IL-10.CD27+ CD45RA- memory CD8+ T cells of HLA B27-positive subjects showed a significantly lower percentage of TNFalpha (median 71.4%) and IFNgamma production (median 69.7%) than HLA B27-negative controls (TNFalpha 85.1%; por = 0.027; IFNgamma 82.7%, por = 0.026). A similar result was also detected in CD27- CD45RA+ effector CD8+ T cells of which 43.2% produced TNFalpha and 66.3% IFNgamma in HLA B27-positive subjects, respectively, compared to 75.6% TNFalpha and 84.4% IFNgamma producing T cells in HLA B27-negatives (por = 0.045 and por = 0.062, respectively). For all CD4+ T cell subsets no significant differences between HLA B27-positive and HLA B27-negative donors were observed, regarding neither the frequency of IFNgamma, TNFalpha, IL-4 or IL-10 producers nor the coexpression of IFNgamma and IL-4 in memory subsets.HLA B27-positive subjects are characterized by a low proinflammatory cytokine production in CD8+ effector and memory T cell subsets. This suggests an influence of HLA B27 on cytokine production in antigen-experienced CD8+ T cells.

Outcome measures for the assessment of patients with ankylosing spondylitis (AS) have been the subject of considerable research in the last decade, largely through the contributions of the ASessments in Ankylosing Spondylitis (ASAS) International Working Group. This review focuses on the measurement of disease activity, physical function and structural damage in AS, both in daily patient care and to measure treatment response in clinical trials. The ASAS Core Sets for assessment in AS are an important tool to guide disease monitoring, and the domains they contain are discussed, along with other possible concepts important to patient care, including imaging and health-related quality of life. In clinical trials, the assessment of disease response to therapy using the ASAS Response Criteria is a valuable means of determining treatment efficacy and allows comparison of response across trials and interventions.

TNFalpha is expressed in high amounts at the site of inflammation in ankylosing spondylitis, which provided the basis to initiate treatment studies with TNF-blocking agents. We could show that the immunological effects of infliximab and etanercept differ in patients with AS, although the clinical effect was similarly good. While infliximab induced a downregulation of the production of the T-helper 1-cytokines IFNgamma and TNFalpha, etanercept treatment triggered rather an upregulation of these cytokines secreted by T cells after in vitro stimulation.

For treatment of the spondylarthropathies (SpA), of which ankylosing spondylitis (AS) is the prototype, there is no effective disease modifying treatment available. In contrast to rheumatoid arthritis (RA), few studies have been performed on the treatment of patients with AS with disease modifying antirheumatic drugs, none of which have proved clearly effective in axial disease. Many patients with AS carry a heavy burden of disease and AS itself is responsible for direct and indirect socioeconomic costs. To find an effective treatment for severe ankylosing spondylitis is therefore thought to be an unmet medical need. In the last four years several pilot studies and recently a few randomised controlled trials have raised good evidence that TNFalpha blockade is very effective in AS and other SpA. Disease activity, function and quality of life improved upon treatment with TNFalpha blockers. Thus, biologicals seem to represent a major breakthrough in the treatment of AS and other SpA. Side effects similar to those observed in RA treatment occur. But there is furthermore a need for safety data for long-term treatment with biologicals over several years. In the light of the high costs and the unknown long-term side effects, a definition for patients who might be candidates for such a treatment is needed. This article gives detailed information about current experience with the new treatment options in active and severe AS with anti-TNFalpha therapy.

Ankylosing spondylitis (AS), the prototype of the spondyloarthritides (SpA), is a disease subset but also a possible outcome of the SpA. Early diagnosis of sacroiliitis, the most frequent clinical symptom often accompanied by inflammatory back pain, and other inflammatory lesions of the spine such as spondylitis and spondylodiscitis, can be visualized early by magnetic resonance imaging (MRI). Chronic changes such as syndesmophytes are well detected by conventional x-rays of the spine, mostly lateral, in the lumbar spine also a.p. Active spinal inflammation can be demonstrated by MRI by using either the fat saturating STIR technique or by application of the contrast agent gadolinium-DTPA. This is especially useful in early and active disease, in young women and in children, and for the differential diagnosis of septic sacroilitis. Because of the efficacy of the novel biologic agents directed against TNFalpha such as infliximab and etanercept in SpA there is a need for spinal imaging techniques that are more sensitive than conventional x-rays. The available scoring tools are limited in their sensitivity to change. Novel approaches using MRI have been recently proposed.

There is a definite association of heart disease with ankylosing spondylitis (AS). The magnitude of this relationship is less clear. Three types of inflammatory affections can be differentiated: 1. aortitis and aortic insufficiency with the possible necessity of cardiac surgery, 2. conduction disturbances of the atrioventricular node with a probable subsequent indication for a pacemaker and 3. myocardial involvement with a possible compromise of left ventricular function. There seems to be an HLA B27-associated cardiac syndrome consisting of aortic root disease and conduction abnormalities. Patients can be recognized at pre-clinical stages. Prospective studies have not been performed. HLA B27-related heart disease does not seem to be associated with increased mortality.

Inflammation of spinal structures is a characteristic feature of the spondyloarthritides (SpA). The term SpA covers patients with inflammatory back pain and/or peripheral arthritis who can be further categorized. Ankylosing spondylitis (AS), the prototype of the SpA, the most frequent inflammatory spinal disease in adults, usually starts in the sacroiliac joints. Pathologic spinal changes occurring in AS are spondylitis, spondylodiscitis and inflammation and ankylosis also at other sites in the axial skeleton. In the later stages of AS such changes can be well recognized by spinal x-rays. In the early disease stages it has been more difficult to analyze the exact anatomic localization of spinal inflammation to date, because conventional imaging systems have only a limited capacity to demonstrate such changes early. There is some evidence that magnetic resonance imaging (MRI) with fat saturation and contrast enhanced MRI are useful to visualize early and late inflammatory changes in the sacroiliac joints. In this paper we report that MRI is also useful to localize the site of inflammation to distinct regions of the spine in AS and other SpA.

The development of the anti-TNF therapies is a milestone in the therapy of rheumatic diseases. As in all new treatment opportunities it is of concern whether all potential undesired side effects have been evaluated within the clinical trials which have lead to approval of the drugs. Postmarketing experience and pharmacovigilance programs are necessary to determine the overall safety profile of the new agents. From the clinical trials and the practical experience of the first years we know that side effects have occurred in patients treated with anti-TNF agents. Sufficient knowledge about these partly specific side effects is critical for rheumatologists who treat their patients with these very effective biologic drugs.

Spondylarthropathies (SpA) and connective tissue diseases (CTD) are clinically distinct entities which, at first glance, seem to have little in common. However, a link between SpA and CTD has recently been suggested by a study in which a higher prevalence of Sjögren's syndrome (SS) and sicca symptoms was reported in patients with ankylosing spondylitis (AS) and undifferentiated SpA (1). Another link between SpA and CTD is a possible side effect of a DMARD widely used to treat SpA: sulfasalazine (SAS). SAS was reported to induce antinuclear antibodies (ANA) and systemic lupus erythematosus (SLE)-like syndromes such as drug-induced lupus. This report describes a 54-year-old white male, HLA B27-positive AS patient with some syndesmophytes who, after 15 years of disease, developed SS with salivary gland involvement, Raynaud's syndrome and anti-Ro antibodies. Then, 20 years after the onset of AS, he became acutely ill, suffering severe myositis and myocarditis along with swollen hands and highly elevated autoantibody titers recognizing UIRNP; his condition was interpreted as mixed connective tissue disease (MCTD). The patient had been treated with SAS and azathioprine (AZA) alone several times during the last years because he had not tolerated other DMARDs. A combination of both drugs had been prescribed 3 weeks before a severe flair because of progredient high disease activity with painful peripheral arthritis of the MCP and PIP joints which, however, had not shown radiographic erosions. We describe the rare development of MCTD in an AS patient and report, for the first time, the onset of MCTD potentially triggered by sulfasalazine.

Acute neutrophilic dermatosis, also referred to as Sweet's syndrome according to the first description in 1964, occurs not only as an isolated phenomenon but also in the context of neoplastic and inflammatory diseases, occasionally including arthritides. Recently Sweet's syndrome has been reported in a small number of patients with chronic inflammatory bowel disease, mostly in advanced stages of the disease. Here, we describe the sudden outbreak of acute neutrophilic dermatosis in coincidence with the onset of severe Crohn's disease (CD) in a patient with long-standing ankylosing spondylitis (AS). This condition has not been described before and therefore Sweet's syndrome should be added to the spectrum of skin manifestations the rheumatologist has to think about in the context of the spondylarthropathies (SpA). Furthermore, this case report is of interest because the skin lesions of Sweet's syndrome are somewhat similar to psoriasis, which is a rather frequent feature of the spondylarthropathies. This article intends to clarify the clinical and histological differentiation between Sweet's syndrome, psoriatic skin lesions and erythema nodosum for the rheumatologist and stresses that these conditions must each be treated in a completely different manner.

Reactive arthritis (ReA) and rheumatoid arthritis (RA) are inflammatory joint diseases which differ in several clinical and immunological aspects. In both diseases locally activated T cells are considered important for pathogenesis. Subsets of T cells are demonstrated by staining with monoclonal antibodies recognizing isotypes of the common leukocyte antigen: CD45RA, which is considered to be a marker of native T cells, and CD45RO a marker of primed T cells; a third subset was also identified according to the staining intensity of CD45RB: CD45RBbright and CD45RBdim. The expression of these and the surface markers CD3, CD4, CD8, CD14 and CD56 was studied in synovial fluid (SF) and peripheral blood (PB) of patients with ReA (n = 11), RA (n = 10) and normal controls (n = 10) by three-colour immunocytometry. Significantly more CD45RBbright were found in the PB of patients with ReA (64.1%) and RA (63.5%) than in the SF of ReA (36.8%) and RA (40.6%) patients. However, when analyzed in relation to CD45RO, the CD45RO/CD45RBbright population was not significantly different between the SF and PB of patients with ReA (32.2% vs. 26.8%) and RA (30.6% vs. 28.1%), respectively. Among the three cellular subtypes of CD4+ lymphocytes demonstrated in this study (CD45RA/RBbright, CD45RO/CD45RBbright and CD45RO/CD45RBdim) none, in contrast to previous results of other groups, showed marked differences between ReA and RA in either of the compartments examined.