Search

The immune response against posttranslationally modified (PTM) antigens, in particular the generation of anti-citrullinated protein antibodies (ACPA), is a very specific hallmark of rheumatoid arthritis. The factors that initiate this immune response and the triggers that stimulate the transition from asymptomatic autoimmunity to autoimmune disease are so far unknown. Genetic risk factors and the maturation of the ACPA response prior to the onset of arthritis indicate an important role for helper T cells in this process. Antigens that trigger this process, however, remain to be defined. Notably, recent data demonstrate that ACPA do not only recognize citrullinated protein antigens. Other posttranslational protein modifications such as homocitrulline and acetyllysine are also recognized. This cross-reactivity towards different PTM antigens was found for various monoclonal ACPA and broadens the spectrum of antigens that can stimulate and activate ACPA-expressing B cells. Also, it suggests that such B cells could receive help from autoreactive but also from non-autoreactive T cells. This review summarizes these recent findings and provides insight into their potential relevance for the disease rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic and progressive systemic disease of the connective tissue, which is particularly manifested with destructive alterations to the joints. Inflammatory reactions in the synovium lead to the influx of peripheral inflammatory cells as well as the activation of local cells. Released growth factors, chemokines and especially cytokines play a key role in chronic inflammatory responses. In addition to the central lymphocytes, the T and B cells and their subpopulations, locally resident cells, such as neutrophils, macrophages and fibroblasts as well as cells of bone metabolism are activated by the inflammatory milieu and contribute to and drive inflammation and tissue damage. The destruction of cartilage and bone substance by local tissue cells, synovial fibroblasts and osteoclasts is characteristic for this disease. Untreated, the local inflammatory and destructive processes as well as systemic inflammatory factors lead to progressive and irreversible joint destruction. Cellular and immunological processes in RA are closely interwoven; therefore, besides the general inhibition of immunological processes, specific inhibition of central key molecules can reduce or completely stop the inflammatory destructive processes; however, a high heterogeneity can be observed among RA patients and disease progression. Therefore, an expansion of the therapeutic options is desirable as not all patients are able to equally benefit from the therapeutic treatment. It is important to characterize new molecular mechanisms, which could lead to the development of new therapeutic options. Some of the more recent insights are summarized in this overview.

Nontuberculous mycobacterial (NTM) are found ubiquitously in the environment and are usually of low pathogenicity. Infection occurs via inhalation of aerosols, and some species may cause severe infections. The incidence of NTM infections is rising worldwide. The risk of developing NTM disease depends on the susceptibility of the host as well as the frequency and duration of exposure. In addition to congenital immune deficiencies and immunosuppressive therapy, structural lung and systemic diseases, including rheumatoid arthritis (RA), are associated with an increased risk for NTM infections. The immune response to NTM is complex and relies on the interplay between professional phagocytes and lymphoid cells. This interplay is concerted by three key cytokines: interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Targeted immunotherapies, e. g., treatment with TNF inhibitors, interfere with these essential pathways and increase the risk of NTM infection significantly. This review focuses on the relationship between the immune response to NTM and intrinsic and iatrogenic dispositions for NTM infection, with an emphasis on RA.

Introduction: To investigate the additive systemic inflammatory process of rheumatoid arthritis (RA) in arterial hypertension patients, structural and morphological changes of the retina and optic nerve head were assessed by modern topographic technologies. Similarities of underlying vascular mechanisms between RA and arterial hypertension are interesting and have not been researched in depth. The aim of this study is to evaluate changes of RA and arterial hypertension with the optic coherence topography (OCT) and Heidelberg retina tomography (HRT III), to validate RA changes in comparison to arterial hypertension only patients and, finally, if these methods are useful to detect the chronic inflammatory influence of the RA on the eye., Methods: In this prospective study design, data of 18 patients with RA and arterial hypertension (55.3 ± 4.31 years old), positive for antibodies against cyclic citrullinated peptides, 21 patients with arterial hypertension (54.2 ± 4.18 years old) and 19 healthy subjects (53.1 ± 3.25 years old) were included. Intensive ophthalmologic and internistic screening tests were carried out in all subjects. All participants were investigated for the retinal nerve fiber layer (RNFL) and macula thickness with the OCT (Carl Zeiss AG Germany) and for stereometric parameters of the optic nerve head with the Heidelberg Retina Tomograph III (Heidelberg Engineering Germany). The pachymetry was conducted by the Orbscan II system (Bausch & Lomb). Statistical data were assessed by SPSS, v20.0., Results: No significant differences were found in visual function, diastolic and systolic blood pressure. RNFL, and macular thickness (Stratus-OCT) were almost consistent between the groups and even the main stereometric parameters measured with HRT III showed no significant differences., Conclusion: Contrary to our study hypothesis no structural and morphological changes could be detected in patients with arterial hypertension without RA compared to healthy subjects. Furthermore, no RA-specific effects could be shown in comparison with the hypertension group. Thus, the used examination techniques are not suitable to prove the systemic inflammatory influence of RA on the eye.

The T and B lymphocytes in secondary lymphoid organs, such as the spleen and lymph nodes, normally reliably protect our body from infectious diseases; however, in rheumatoid arthritis they infiltrate tissues and substantially contribute to tissue destruction in rheumatic joints by production of inflammatory chemokines and autoreactive antibodies. It was previously unclear whether these lymphocytes infiltrate tissues as fully differentiated effector cells from neighboring lymph nodes or whether they are locally generated. A recent study has now shown that T and B cells actively cooperate together even outside lymphoid tissue. A follicular T‑helper cell-like population promotes the local generation of germinal center-like B cells and high-affinity plasma cells.

Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis and according to the ACR-EULAR 2010 guidelines represent an important serological marker for the diagnosis of the disease. Patients with rheumatoid arthritis who are positive for ACPA display more severe bone erosion and have an overall poorer prognosis in progression of the disease compared to ACPA negative patients. For a long time it was unknown how ACPA exactly affect bone homeostasis. In this article, recent findings about the mechanisms by which ACPA contribute to bone loss are discussed.

Impairments of the immune system play an important role in all immun-mediated rheumatic diseases. Recently, the following news were reported: · Early aging of the immune system with thymus insufficiency has now been reported for both patients with rheumatoid arthritis and axial spondyloarthritis, without prethymic lack of progenitors at least in rheumatoid arthritis.. · For giant cell arteritis, the most frequent vasculitis in the elderly, an increased expression of IL-17A in temporal artery biopsies coincides with good prognosis and reponse to glucocorticoids.. · Concerning immunosenescence in systemic lupus erythematosus, BAFF appears to have an important role for relapses after B-cell depletion.. For the future it can be anticipated that the use of unified classification criteria for rheumatic diseases (as with the new 2012 EULAR / ACR classification criteria for polymyalgia rheumatica) will ensure better comparability of immunological studies also in the elderly., (© Georg Thieme Verlag KG Stuttgart · New York.)

Immunodiagnostics play an important role in the differential diagnostics of arthritis but the test results must be interpreted with respect to the clinical context. The detection of antibodies against citrullinated proteins has significantly improved the immunodiagnostics of arthritis, whereas the importance of testing for rheumatoid factor has decreased due to the low specificity. Antibodies against carbamylated or oxidized proteins will expand the immunodiagnostics of arthritis (especially rheumatoid arthritis) in the future. In contrast, the determination of cytokine concentrations in plasma or synovial fluid plays a subordinate role in the differential diagnostics of arthritis. Indirect immunofluorescence continues to be the gold standard in the detection of antinuclear antibodies (ANA) and in the case of positive results further testing for antigen specificity should be carried out. The presence of ANA is not necessarily associated with autoimmune diseases. An example of a non-pathogenic ANA is anti-DFS70 antibodies.

The increased incidence of certain tumor entities in chronic inflammation and infections as well as the increased tumor risk under immunosuppression, illustrate the multiple and complex influences of the immune system on tumor pathogenesis. It is therefore conceivable that immunomodulatory therapy for rheumatoid arthritis (RA) could also influence the risk of malignancies, apart from treating the underlying disease. Basic scientific research studies have identified various signal transduction pathways that are relevant for tumorigenesis and tumor defense mechanisms. This review presents the current knowledge on the effects of the immune system on the occurrence of cancer and tries, where possible, to relate it to specific treatment options.

Background: B cells play a key role in the pathogenesis of various rheumatic autoimmune diseases and have therefore become an important therapeutic target. Rituximab is a chimeric monoclonal anti-CD20 antibody that induces a nearly complete, transient depletion of peripheral CD20-positive B cells. In 2006 rituximab received approval for use in patients with rheumatoid arthritis (RA) and in 2013 for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)., Objectives: In this review various clinically relevant aspects of B cell therapy in RA patients are discussed, including its role in the therapeutic algorithm as well as data on long-term efficacy and safety.

Plasma cells are specialized terminally differentiated B cells that synthesize and secrete antibodies to maintain humoral immunity. By the production of pathogenic antibodies, plasma cells contribute to the development of many conditions, such as autoimmune disorders, transplant rejection and allergies. Two different plasma cell compartments can independently generate different types of pathogenic antibodies: (1) short-lived plasmablasts (proliferating precursors of mature plasma cells) and plasma cells, which live only as long as B cells are activated. Consequently, these cells cause disease flares that respond to immunosuppressive drugs and B cell targeting therapies. (2) Long-lived non-proliferating memory plasma cells, which survive in niches in bone marrow and inflamed tissues for months, years or a lifetime independent of B or T cell help or antigen contact. Because they do not respond to immunosuppressants or treatment targeting B cells, they are responsible for refractory chronic conditions. Therefore, long-lived memory plasma cells in particular have emerged as important therapeutic targets and strategies to target these cells are discussed in this article. So far long-lived plasma cells can only be depleted by immunoablative therapy with antithymocyte globulin in the setting of stem cell transplantation or by treatment with proteasome inhibitors approved for multiple myeloma. These strategies provide options for treating refractory autoantibody-mediated diseases. One interesting approach aims at an antigen-specific elimination of target plasma cells without depleting the protective plasma cells responsible for maintaining humoral immunity.

Background: Although the present understanding of the immunopathogenesis of rheumatoid inflammation is still incomplete, there is substantial evidence that effector CD4+ T helper (Th) cells play a central role., Results: In recent years, in addition to the established Th cell subsets Th1 and Th2 cells, other subsets, such as Th9, Th17, Th22 and T follicular helper (Tfh) cells have been described. Defining the contribution of T cells in the initiation and maintenance of inflammation has been augmented by the identification of functionally distinct subsets of effector Th cells that can be classified based on their cytokine and transcription factor profiles., Conclusion: Increasing knowledge of the role of these various T cell populations in chronic inflammation provides a better understanding and insights into the pathogenic mechanisms and chronification of rheumatic diseases.

In the 1970s and 1980s the course of rheumatoid arthritis (RA) could be defined as fateful despite the introduction of methotrexate as well as other immunosuppressive treatments. In most patients at this time RA was combined with an early disability due a progressive destruction of joints. In addition, comorbidity was known to be one of the major causes for a decreased life expectancy. These less than optimal options for treating RA patients led to intensive research in the pathogenesis with the aim to develop new treatment principles. Based on the increasing knowledge of pathogenically important mechanisms, so-called biologicals were developed targeting T and B cells and proinflammatory cytokines, such as tumor necrosis factor alpha. Over the past 10 years the repertoire of biologicals for treating RA has steadily and significantly increased, which was necessary especially for those patients classified as non-responders to available biological compounds. In the present overview cellular structures, T and B cells as well as cells of the monocyte/macrophage system are discussed as targets for immune interventions.

Biologicals revolutionized the therapy of chronic inflammatory diseases in gastroenterology, rheumatology and dermatology in the last decade. The first generation biologicals mainly targeted against the pro-inflammatory cytokine TNF-α. The evolution of these therapies in the last years led to the development of new antibodies and to the admission of first generation "generic" biologics - the biosimilars. Biosimilars are not a fundamental new pharmacological development for existing substances, however they have the potential to lead to enormous cost savings in healthcare without reducing the level of care for patients. Biosimilars are not identical with the originator, but in an extensive biosimilarity exercise including analytical, preclinical and comparative clinical studies it was shown that the biosimilars could demonstrate comparability in all relevant aspects with the originator.In September 2013, the Infliximab biosimilars (Inflectra(®), Remsina(®)) were the first biosimilars for monoclonal antibodies to be authorized by the EMA for use in the European Union. By demonstrating the therapeutic similarity only in one indication (rheumatoid arthritis) the EMA agreed with an extrapolation also to all approved indications of the originator. This could be a relevant problem in clinical practice. Therefore, comparative studies with the originator are required in all approved indications.After expiration of the national patent protection in beginning of 2015, the infliximab biosimilars will be launched on the market in Germany and will be part of the therapeutic arsenal in gastroenterology, rheumatology and dermatology. Interchangeability (Switching) of biosimilars with the originator will be subject of an important discussion with the health care providers. Regardless of the biosimilars EMA-approval, several potential problems (efficacy, extrapolation, switching, long-term safety) should be the topic of intensive long-term registries in the future., (© Georg Thieme Verlag KG Stuttgart · New York.)

The increasing gain of knowledge regarding the mechanistic details of the pathogenesis of chronic inflammatory diseases e. g. of rheumatic origin, chronic viral infections and atherosclerosis have revealed in conjunction with detailed insights in acute inflammation interesting similarities and differences. Cytokines such as IL-1 and tumour necrosis factor-α are proximal components of inflammatory cascades of systemic mediators activating the endothelium which leads to an endothelial dysfunction and moreover alter the balance within lymphocytic subpopulations containing distinct arsenals of secretory mediators such as interferons, interleukins and chemokines. Proinflammatory lymphocyte subtypes are TH1 und TH17 cells whereas Treg and TH2 cells are anti-inflammatory opponents. Since several years, interleukin-1- and TNF-antagonists have expanded the spectrum of drugs against rheumatic diseases and are currently studied in the setting of cardiovascular prevention with positive results on surrogate parameters. On the other hand efforts are undertaken to test the hypothesis if the pleiotropic effects of statins may have a positive influence on rheumatoid arthritis., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The prognosis of rheumatoid arthritis has been substantially improved by the treatment with biologics; however, it is still unclear which combination of biological and conventional disease-modifying antirheumatic drugs (DMARDs) is optimal to achieve remission as in clinical trials biologics were mainly studied in combination with methotrexate or as monotherapy. There are, however data that the efficacy of tumor necrosis factor (TNF) inhibitors is better in combination with methotrexate, whereas the efficacy of tocilizumab is optimal even as a monotherapy. In this article the differing dependence of TNF inhibitors and of tocilizumab on the combination with methotrexate is explained from the viewpoint of an immunologist., Methods: A selective search and evaluation of the literature were carried out in relation to the mechanism of action of TNF inhibitors, tocilizumab and methotrexate in rheumatoid arthritis., Results and Conclusions: Methotrexate mainly targets the activation of T and B lymphocytes and TNF inhibitors suppress monocytes and myeloid dendritic cells. Tocilizumab corrects the errant activation and differentiation of T and B lymphocytes and in addition inhibits monocytes, dendritic cells and neutrophils. Therefore, TNF inhibitors and methotrexate act optimally only in combination to exert an effect on all components of the cellular immune system in rheumatoid arthritis. In contrast, tocilizumab has a broad mode of action even in monotherapy.

Autoimmune diseases are a clinically heterogeneous group of disorders that represent a challenge for the general practitioner in daily routine. Except for rheumatoid arthritis, which is one of the most frequent autoimmune diseases with a prevalence of approximately 1 % of the population, systemic autoimmune disorders are rare. Thus outside specialized wards it might be a challenge to diagnose the underlying autoimmune disease considering the often kaleidoscopic clinical manifestations. Together with careful anamnesis and suspicious clinical symptoms determination of specific autoantibodies can support the suspected diagnosis. The Austrian group of the European autoimmune standardization initiative (EASI) firstly published this guide 2009 with the aim to provide a map through the jungle of the biomarkers for autoimmune diseases for the general practitioner.

The Fc fragments of pathogenic IgG autoantibodies in patients with rheumatoid arthritis are low-galactosylated and low-sialylated. In contrast, high-galactosylated and high-sialylated antigen-specific IgG antibodies are sufficient to inhibit a pro-inflammatory immune response in an antigen-specific manner and might be a promising therapeutic tool to re-establish tolerance against defined self-antigens in autoimmune patients.

The special program "Osteoimmunology" under the leadership of the Universities of Erlangen, Jena, Gießen and Münster, is investigating in 27 projects clarification approaches on the causes of inflammatory rheumatic diseases, such as rheumatoid arthritis and ankylosing spondylitis with the aim of developing new forms of treatment. The molecular mechanisms involved in bone damage and the interaction between the immune system and bone and cartilage are topics of research.

Twelve years ago the tumour necrosis factor (TNF) inhibitors revolutionised the therapy of rheumatoid arthritis and other inflammatory rheumatic diseases. Today, in addition to anti-cytokine strategies, immunosuppressive biologicals have been developed that delete B-lymphocytes or inhibit the activation of T-lymphocytes. The spectrum of indications for these protein drugs will broaden substantially in the near future and will likely include also diseases with orphan status (incidence below 1:10'000). Used in the right indication and with knowledge of molecular effects as well as clinical adverse effects these new drugs do not appear to be more dangerous than conventional disease modifying agents (DMARDs).

MicroRNAs are small non-coding RNAs which are crucial for the fine regulation of gene expression. Recent results suggest that these molecules display multifaceted functions in B-cells and T-cells in rheumatic inflammatory diseases.

Rheumatoid arthritis (RA) is still associated with an increased mortality mainly due to an increase in cardiovascular risk. This increase is not solely explained by traditional cardiovascular risk factors but also by disease characteristics, e.g. inflammation, positive rheumatoid factor and anti-citrullinated peptide antibodies (ACPA). Control of disease activity with disease-modifying drugs (DMARDs) was shown to reduce cardiovascular risk in RA patients. Use of non-steroidal antirheumatic drugs (NSAIDs) and glucocorticoids might be associated with an increased risk. The EULAR recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis have been established. These recommendations are based on national guidelines regarding control of traditional cardiovascular risk factors.

Degenerative ageing processes are to a great extent responsible for organ-specific morbidity and mortality among our population. The incidence of many autoimmune diseases also increases significantly with age, as is evident with rheumatoid arthritis (RA) for example. From an immunological and pathogenetic perspective, that the changes in the immune system of RA patients is comparable to the physiological ageing process seen in healthy individuals approximately 20 years later is of great interest. Despite the manifold functional changes seen in the immune system of older people, the incidence of infection in very elderly patients with RA is only marginally increased, such that immune suppression in older RA patients should be carried out just as consequently as in younger patients. Age-related changes and diseases in other organ systems should receive particular attention, since such complications can have a negative effect on the course of the autoimmune disease as well as the rate of side effects.

Epigenetic modifications are heritable changes in genome function that occur without a change in DNA sequence. They turn genes on or off by small chemical modifications. Thereby, they change the structure of the DNA making them accessible or not for transcription factors or other DNA binding molecules. MicroRNAs are a new class of regulatory non-coding RNAs that modulate gene expression and influences epigenetic mechanisms. miRNAs offer novel mechanisms of therapeutic strategies for cancer and autoimmune diseases. Here, we summarize which miRNAs play a role in rheumatic diseases and their biological function.

Viruses are common etiologic agents of acute polyarthritis worldwide. Rheumatic symptoms are often accompanied by other viral symptoms such as fever, rash, myalgia or nausea, but isolated arthritis may occur resembling or imitating early rheumatoid arthritis. In Europe and North America, the most common arthritogenic viruses include parvovirus B19, rubella, hepatitis B and C, whereas mosquito-borne alpha-viruses are endemic in Africa, Australia, the western Pacific and South America. The latter have attracted the interest of European rheumatologists due to the increasing number of tourists travelling to these regions. Viruses may cause arthritis via various mechanisms, including direct synovial infection leading to cell lysis, immune complex formation or pro-inflammatory cytokine induction. Indirect viral pathogenic effects may induce autoimmune reactions via bystander activation or epitope spreading.

The introduction of biological disease-modifying drugs (DMARDs) has substantially improved the treatment options for patients with rheumatoid arthritis. However, infectious complications represent the most common side effects of these drugs, including severe infections as well as rare opportunistic infections. Treating patients on biological DMARDs is therefore one of the biggest challenges in rheumatology care. The present review describes the current state of knowledge regarding frequency and type of infectious complications associated with biological DMARDs. The article focuses mainly on risk management, in particular on diagnosis and recurrence prevention of tuberculosis and reactivation of hepatitis B virus infection. Furthermore, we discuss the importance of vaccinations in primary disease prevention in patients with rheumatoid arthritis.

Activated CD4+ T-cells are found in joints of patients with rheumatoid arthritis and are involved in the joint destroying autoimmune response. Besides proinflammatory cytokine production T-cells are indispensable for the activation of B-cells, the so-called T-cell help for B-cells. However, the recognition of autoantigens by T-cells seems of utmost importance for the pathogenesis of rheumatoid arthritis. Selective inhibition of this process is therefore one of the most interesting therapeutic targets for the future.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased mortality, largely as a consequence of cardiovascular (CV) disease. Studies found relative risk ratios of 2 for myocardial infarction in RA and up to 7 for myocardial infarction in SLE patients.Beyond the traditional CV risk factors, chronic systemic inflammation has been shown to be a crucial factor in atherosclerosis development and progression from endothelial dysfunction to plaque rupture and thrombosis. Numerous studies have shown that atherosclerosis is not a passive process characterized by accumulation of lipids in the vessel walls, but rather represents active inflammation of the vasculature. Inflammatory cells such as macrophages, monocytes and T cells play an important role in the development of both RA and atherosclerosis.According to the recently published EULAR recommendations for CV risk screening and management in patients with inflammatory arthritis, annual CV risk assessment is recommended for all patients with RA. Any CV risk factors identified should be optimally managed. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower CV risk.

Rheumatoid arthritis (RA) is a chronic rheumatic disease of unknown aetiology and variable severity. It is now well known that several risk factors are involved in its pathogenesis, including genetic factors and sex hormones as well as environmental factors, i.e. infections and stress. In particular stress is now recognised as an important risk factor for the onset and even more for the modulation of disease activity in RA. Many studies have clearly shown that chronic mild stress (family or professional stress) may lead to proinflammatory effects, increasing disease activity. Furthermore, a positive correlation between the stress level at the onset of RA and radiological progression could be demonstrated. The onset of RA was associated with moderate stress at work, underlining the possible interactions between the various stress systems and the immune system. In this respect it could be demonstrated that coping strategies reduce stress episodes and change stress management with a positive impact on disease activity in RA. However, more studies are warranted to further explore the pathophysiological implications of stress on onset and activity of chronic autoimmune diseases.

Autoimmune hemolysis is a rare complication of systemic rheumatic diseases. We report on a 68-year-old female patient with established, long-standing rheumatoid arthritis, who complained of progressive weakness and worsening of her arthralgia under therapy with leflunomide. Physical and laboratory examination revealed autoimmune hemolysis due to cold agglutinin disease. As hemolysis and arthritis were refractory to steroid treatment, B-cell depletion with rituximab was performed leading to a marked reduction of hemolytic parameters as well as remission of her rheumatoid arthritis.

Background: A high incidence of infections has been reported in rheumatoid arthritis (RA) patients, either due to intrinsic factors or as a side effect of immunosuppressive agents used for treatment. The present article provides an overview of incidence and distribution patterns of septic complications in RA., Materials and Methods: We prospectively assessed all data from RA patients who underwent in-patient treatment for septic complications in the 3-year period from 01.01.2006 to 31.12.2009. All disease- and infection-specific data were gathered and analysed., Results: Of the 36 cases in total, infection was localized in the rheumatoid foot in 23 patients (64%) and at the lower extremities in 32 (89%). The bacterial spectrum was heterogenous, with Staphylococcus aureus representing the most frequent causative agent. In total, 34 of 36 cases were cured., Conclusions: Since approximately 2/3 of all infections occur in the rheumatoid foot, regular foot examinations to identify predisposing deformities and/or ensure early diagnosis of existing infections are recommended.

Ocular findings can be very typical for general disorders associated with rheumatological diseases. Of these ocular diseases, scleritis and uveitis are of particular significance. The present article discusses and attempts to solve the problems which can be seen when ocular inflammation is associated with rheumatological disorders. The identification of "uveitis" should not be sufficient to initiate diagnosis and therapy, but rather its localisation and, where possible, also its etiology should be known. These can usually be found with good clinical investigation and careful patient history. Only rarely are ocular and rheumatological inflammation active at the same time, as will be discussed later using HLA-B27-associated uveitis and juvenile idiopathic arthritis-associated uveitis as examples. It is important in the case of ocular inflammation that the indication for treatment be made by an ophthalmologist. Finally, the role of the rheumatologist in the treatment of this patient group will be described in detail.

Eye involvement is a frequent finding in patients with rheumatoid arthritis and may represent the leading clinical manifestation of disease. In this context, all components of the visual organ might be affected. The main spectrum of eye involvement comprises keratoconjunctivitis sicca, episcleritis and scleritis as well as ulcerative keratitis. As with the underlying disease, autoimmune reactions based on a patient's genetic predisposition are assumed to be of significance in disease pathogenesis. Emerging evidence also points to additional morphological and physiological ocular characteristics in the pathogenesis of the various ocular pathologies. This article gives an overview of clinical aspects, pathogenetic background as well as therapeutic options for ocular involvement in rheumatoid arthritis.