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A growing number of health insurance data analyses show an increase in the prevalence of rheumatoid arthritis (RA) in Germany. The studies refer to the claims diagnosis of RA, which is more frequent in recent years compared to earlier periods. Depending on the case definition, the numbers vary between 0.6% and 1.4% of the adult population. In this paper, the different studies are reviewed with regard to their data sources, the case definitions of RA and the frequency of the diagnosis. Due to the lack of clinical validation, the prevalence cannot be precisely determined from claims data., (© 2022. The Author(s).)

Introduction: Peripheral arthritis is the most common presenting complaint in clinical rheumatology. Unequivocal identification of the underlying entity can be difficult, particularly at an early stage. Such cases are commonly referred to as undifferentiated peripheral inflammatory arthritis (UPIA). Since evidence-based recommendations for the clinical management of UPIA are lacking, this international 3e initiative convened 697 rheumatologists from 17 countries to develop appropriate recommendations., Methods: Based on a systematic literature research in Medline, EMBASE, Cochrane Library, and the ACR/EULAR abstracts of 2007/2008, 10 multinational recommendations were developed by 3 rounds of a Delphi process. In Germany, a national group of experts worked on 3 additional recommendations using the same method. The recommendations were discussed among the members of the 3e initiative and the degree of consensus was analyzed as well as the potential impact of the recommendations on clinical practice., Results: A total of 39,756 references were identified, of which 250 were systematically reviewed for the development of 10 multinational recommendations concerning differential diagnosis, diagnostic and prognostic value of clinical assessments, laboratory tests and imaging techniques, and monitoring of UPIA. In addition, 3 national recommendations on the diagnostic and prognostic value of a response to anti-inflammatory therapy on the analysis of synovial fluid and on enthesitis were developed by the German experts based on 35 out of 5542 references., Conclusions: The article translates the 2011 published original paper of the international 3e initiative (Machado et al., Ann Rheum Dis 70:15-24, 2011) and reports the methods and results of the national vote and the additional 3 national recommendations.

One of the areas of research in the Rheumatology Competence Network deals with health services research. It evaluates the structures and outcomes of rheumatological care. The paper presents selected results from the projects in the field of health services research. Data for rheumatoid arthritis are presented according to the criteria for the inclusion of diseases in new health care programs ("Disease Management"). The national database of the German Collaborative Arthritis Centers and cohort studies show the high individual and economic burden of disease in rheumatoid arthritis. Treatment by rheumatologists and non-rheumatologists differs greatly and leads to different outcomes. There is great potential for improvement. Data on practice variation within the rheumatologic subspecialty are used for quality management. The involvement of rheumatology into new concepts of care offers the chance to show the effectiveness of rheumatologic care and to enhance existing forms of cooperation.

Clinical quality management in rheumatoid arthritis (RA) aims at reducing inflammatory activity and pain in the short term and damage and disability in the long term. In the "Swiss Clinical Quality Management in rheumatoid arthritis" (SCQM) project, which started in 1997, a measurement-improvement system with feedback reports allows the rheumatologists to follow their RA patients with the aim of improving the quality of outcome. Inflammatory activity is measured with the Disease Activity Score (DAS28) and the Rheumatoid Arthritis Disease Activity Index questionnaire (RADAI), damage with an X-ray score and disability with the Stanford Health Assessment Questionnaire (HAQ). The feedback is used by the individual rheumatologist to optimize the therapy of his/her RA patients. Beside the aim of improving the quality of treatment, the SCQM projects wants to build a Swiss cohort of RA patients, to improve the collaboration of rheumatologists in the clinic and in practice and to establish standards of treatment in RA. In this paper we describe the SCQM project in detail, we show two cases illustrating the usefulness of the SCQM in the management of individual RA patients, and we present the cross sectional analysis of the first 1223 RA patients included in the project.

Autoreactivity plays a major role in the pathogenesis of RA. The rheumatoid factor has been and still is for now more than 50 years the only autoreactivity that is clinically applied in the diagnosis of RA. This well reflects the current way of thinking that a single antigen or a single cause drives an individual into disease. Although by now many other autoantigens and autoreactivities have been described, their discovery was always on the search for the one and only autoreactivity that causes RA. This includes also immune reactivities directed against xenogenic antigens. But, none of the known RA-associated autoreactivities is present in all RA patients and none of them occurs exclusively in RA. Thus, the observed sensitivities and specificities are well below 100%. Therefore, RA has often been postulated to consist of various immunological subentities with similar clinical symptoms. Nevertheless, none of the autoreactivities correlates with a distinct clinical feature or course of disease. It is about time to say good-bye to the idea that a single antigen or immunoreactvity causes and maintains rheumatoid arthritis. In this paper we present RA as the clinical outcome of an immune system that has shifted from a healthy to an autoimmune steady state. This is accomplished by many different reactivities and autoreactivities that occur either in parallel or one after the other. The entirety of the known RA-associated reactivities and (auto)antigens is presented in detail. The major RA-relevant autoantigens comprise BiP, citrulline, the Sa-antigen, hnRNP A2, p205, IgG, calpastatin, calreticulin, collagen and the shared HLA-DR epitope. The accumulation of factor--involving autoreactivities, cytokines, environmental and genetic factors--that challenge the normal regulatory mechanisms of the immune system lead to a regulatory catastrophe. In individuals developing the clinical features of RA the immune system has been regulated to a new--autoimmune--steady state. This attractor "rheumatoid arthritis" has many features of what has originally been described by Irun Cohen as the immunological homunculus: The healthy immune system is configured such as to direct its attention to major self-antigens. Thus it creates an autoreactivity to many autoantigens as a prerequisite for regulatory mechanisms that are sufficient to control them. The shift from the normal to rheumatoid attractor involves the inflammatory cytokines TNF-alpha, IL-1 and IL-6, autoreactive T- and B cells directed at a variety of synovial and systemic antigens, activated dendritic cells and macrophages, tissue destruction and genetic factors such as the association with shared epitope. Environmental factors involved may also, but do not necessarily, include infection. With the appearance of clinical features of RA, naive, potentially autoreactive T cells infiltrate the synovial compartment and become activated by dendritic cells and other APCs. The autoantigenic peptides that are presented to these T cells are derived from inflammatory cell and tissue destruction as well as from tissue repair and remodeling processes. These T cells proliferate and either provide help to B cells with the specificity to the same antigens or cause direct cytopathic tissue damage. Thereby, more and novel antigens are generated, released and presented again to naive or primed autoreactive T cells. These processes involving cytokines, tissue destruction and autoreactive T cells are sufficient to maintain RA even without the permanent presence of a triggering agent. The recursive autoimmune processes are well consistent with the finding of the many different autoreactivities in RA and their respective sensitivities and specificities. The massive influx of T cells into the arthritic joint is accompanied by the anergization of over 90% of T cells in this compartment--which further substantiates the concept of the RA attractor within the self-regulating immune system. Thereby, the RA-attracted immune system is not able to completely downregulate the inflammation and the local tissue damage/repair. Thus, the immune system is permanently stimulated and suddenly by chance shifts to a stable state different from the healthy system--reaching the wide fields of rheumatoid arthritis which in itself is self-sustaining as the healthy state before disease onset.

Patients with rheumatic diseases are commonly treated as an outpatient in their local environment or are referred to specialized centers. Two recently founded day-patient clinics in Berlin and Frankfurt/Rhein-Main (Germany) for patients suffering from rheumatic diseases will be evaluated for their medical outcome and cost-effectiveness of comprehensive treatment of RA patients in stages of high inflammatory activity and progressive disability. The study design will be prospective, controlled, and randomized to compare outpatient and day-patient treatment. The case-control study design with matched pairs within the network of collaborative arthritis centers will be used to compare day-patient and inpatient treatment. The paper contains a review of studies published in English or German language dealing with day-patient treatment of RA patients.

Over the past years, antioxidants, and particularly vitamin E, have received considerable attention in the treatment of human diseases. In rheumatology, interest has been given to the treatment and prevention of rheumatoid arthritis and osteoarthritis. However, the concept of using antioxidant nutrients as potential remedies is not new. As early as the sixties, first case reports have described beneficial effects of vitamin E in the therapy of osteoarthritis. Nonetheless, most of the following studies were not conducted properly, thus, not allowing valid inferences about the efficacy of vitamin E. Newer studies with sound methodology have shown a beneficial effect in rheumatic diseases, mainly in the reduction of pain. This paper reviews current and past studies about vitamin E in the treatment of rheumatic diseases.

Therapy of rheumatoid arthritis with a combination of several disease-modifying drugs aims to better control of the disease than achievable by monotherapy. Subsequent to a paper written two years ago, this publication reviews studies dealing with combination therapy issued mainly in 1995 and 1996. Most studies deal with MTX as one of the partners. Beneficial results were reported for the combination of methotrexate with antimalarials, cyclosporine or sulfasalazine. The triple combination of methotrexate with hydroxychloroquine and azathioprine is especially promising although the studies presented up to now are still insufficient for its final assessment, due to methodologic problems. Similarly, the value of the combination of sulfasalazine with injectable gold, of sulfasalazine with methotrexate and hydroxychloroquine, or of methotrexate with injectable gold is still uncertain.

Using "paper patients" we compared the therapeutic approaches of general practitioners and rheumatologists to rheumatoid arthritis and to osteoarthritis of the knee. The mailed survey contained a mild, a moderate and a severe case of rheumatoid arthritis (RA) and a case of osteoarthritis (OA) of the knee. 111 out of 252 general practitioners and 78 out of 132 rheumatologists selected at random participated in the study. We found that rheumatologists would choose more non-steroidal anti-inflammatory drugs (NSAID), disease modifying antirheumatic drugs (DMARD), steroids and physical therapy. In case 4 (OA of the knee) rheumatologists would more frequently recommend analgesics, local steroids, occupational therapy, surgery and ortheses. Primary care physicians on the other hand prescribed more chondroprotective agents. Patients with RA and OA of the knee would be treated differently by primary care physicians and rheumatologists. In order to develop a more uniform therapeutical concept and therefore to reach a better management of the rheumatic patient, a close co-operation of the two physician groups is needed.

The retardation of radiological progression is one of the most important characteristics of a disease-modifying effect of an antirheumatic drug. For the following overview 10 trials were identified dealing with x-ray progression under treatment with parenteral gold. Nine of these trials were randomised parallel studies, one was a retrospective long-term observational study, all had a control group, in five this control group was treated with placebo, in two trials parenteral gold was compared with another DMARD (auranofin and methotrexate, respectively), in two trials different doses of gold were compared and in two trials the radiological progression during the first 6 months was compared with the following treatment period (in one of these trials gold was compared with methotrexate as well). The duration of treatment and follow-up was up to 1 year in two trials, up to 2 years in six, and over 2 years in only two studies. There is a great number of limitations in these studies: for instance, there was a large number of withdrawals who were not followed, x-rays were available for evaluation only in a relatively small proportion of treated patients in five studies, in six studies the disease duration was over 2 years at baseline, which limits the evaluability of x-ray progression for technical reasons. In one study juxta articular osteoporosis and joint swelling were evaluated; but these parameters are very difficult to evaluate in a multicenter study because of the different quality of the films. In spite of all limitations and reservations with the studies reviewed the published results indicate a reduction of radiological progression with parenteral gold treatment of rheumatoid arthritis patients: in the placebo-controlled studies outcome in the gold group was significantly better than in the placebo group. The study of the Empire Rheumatism Council failed to show a significant difference compared to the control group after 30 months, but the patients had been treated sufficiently only for 5 months. The study of Cats indicated a better outcome in the group of patients with a high gold dose, which is confirmed by the retrospective analysis of Luukkainen. In a comparison between 113 patients treated with parenteral gold and 119 patients treated with auranofin for 1 year Larsen found a significantly smaller progression in the patients treated with parenteral gold. In a patient population of 73 and 53 the difference between methotrexate and parenteral gold was too small to be detectable, but the progression curve was significantly flattened after the first 6 months, indicating a treatment effect. In a macroradiographic study the erosion surface area increased during the first 6 months of gold treatment, it did not change during the second 6 months, and decreased during the third 6 months together with healing of erosions. In conclusion, the studies reviewed in this paper indicate a disease-modifying potency of parenteral gold treatment, especially when the treatment is started early and sufficiently dosed.

Rheumatoid arthritis is a chronic inflammatory disease mainly affecting the joints. The etiology is still unknown, but it shows several clinical and laboratory features of an autoimmune process. The conventional medical therapy consisting of a combination of analgetic and antiphlogistic agents with so called slow acting drugs is often not satisfactory and fails to persistently suppress disease activity. Therefore, therapeutic alternatives are necessary which are provided by a new generation of immunosuppressing agents including monoclonal antibodies. The paper will summarize some therapeutic approaches using monoclonal antibodies towards cell surface antigens or soluble mediators of inflammation for therapy of rheumatoid arthritis.

Although the etiology of rheumatoid arthritis is still unknown, our knowledge of pathophysiologic mechanisms in this disease has markedly increased. Especially the immunological characterization of cells involved in the inflammatory process and their secretory products (cytokines) allowed new experimental therapeutic approaches. Apparently, the cytokines TNF alpha, IL-1, and IL-6, predominantly produced by accessory cells, play an important role in the actual articular and extraarticular inflammation. Therefore, several pilot studies employed various methods to inhibit the effects of these proinflammatory cytokines. This paper provides an overview about initial results of these studies and an outlook with regard to future developments.

This paper tries to associate psychosomatic manifestations of the locomotion-system to one of the following four diagnosis: 1) conversion disorder, 2) anxiety disorder, 3) depressive mood disorder, 4) somatization disorder. For each of these diagnosis definition, clinical manifestation, diagnostic and differential-diagnostic criteria are mentioned. The diagnostic criteria can easily be associated to the new ICD-10 (V)F diagnosis.

The sonographic examination of the shoulder has established itself in the diagnostic spectrum of the imaging methods. Especially the results of the rotator cuff have contributed to the fact, that arthrosonography is now indisputable for the shoulder examination. In this paper another scan--the examination through the fossa axillaris--is added to the standard ones, to find the early changes of the shoulder capsule in order to receive efficient results in discovering the omarthritis.

Important physiological parameters such as blood pressure, ECG and others are measured today on a continuous basis or at fixed intervals and are documented together with the date and the time. Individual results and subjective data are ascertained through questioning the patient, observation or patient's self-assessment and are documented with paper and pencil, without having any certainty of the exact time of ascertainment or that such is comprehensible. Battery-operated microcomputers have been developed in the form of electronic diaries (E.D.) for patients. Upon emitting an auditory signal, the questions appear in the computer display, and the questions are then correspondingly answered by the patient. These answers are fed to the permanent data store and are transferred on-line and processed at a later time in a PC. The time and data of the entries are simultaneously registered and are included in the complete document when it is later printed out. A capacity of 64 kbytes suffices to accommodate the data collected; likewise, the battery is sufficient for constant use. The entries are made as categorical data or numerically. Free-style entries are not possible. With the aid of a specially-developed program, the courses of a chronic pain syndrome in patients with degenerative joint diseases were studied. The percentage change in the pain course, benefit risk considerations, prognoses with the aid of sequential analyses and plausibility criteria can be calculated from the data. The advantages of this new instrument are its simple handling and reliable functioning. Its disadvantage is that it lacks the possibility to allow free-style entries.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper describes an experimental method for the assessment of analgesic effects of NSAIDs in healthy human volunteers. Pain was induced by repeated controlled pinching of interdigital webs. The painfulness of the stimulus was assessed by the subjects at regular intervals on an electronically controlled visual analog scale. Furthermore, computer supported infrared thermography, laser Doppler flowmetry and photoplethysmography were used to measure the cutaneous vascular reactions. The results of two double-blind cross-over studies are described in which analgesic effects of acetylsalecylic acid, ibuprofen, and dipyrone were significantly demonstrated. In one of the studies it was also shown that ibuprofen reduced the local stimulus-induced vasodilatation. In summary, this algesimetric model seems to be suited to demonstrate the analgesic and perhaps also the antiinflammatory effects of NSAIDs in healthy subjects.

The present paper reviews the different therapeutic uses of D-penicillamine and outlines the dosage regimen of D-penicillamine for treatment of rheumatoid arthritis. While many open clinical trials are published, only a few controlled, double-blind studies investigate the "optimal" dosing of D-penicillamine. From these findings, a uniform regimen cannot be named but the heterogenous appearance of chronic polyarthritis requires an individual therapy. In order to minimize the risk of side effects, however, it is necessary to follow the guideline "go low--go slow" as postulated by Jaffe.

The recent demonstration of ultramicroscopic "virus-like" cell inclusions in various organs in patients with collagen and autoimmune diseases suggest that viruses may play an aetiological role in these diseases. This paper reports briefly on some of the evidence for such "virus-like" structures in different cells of the synovial membrane from two patients with rheumatoid arthritis. The inclusions were localised in the vaculoes of the endoplasmatic reticulum of endothelial cells, lymphocytes, macrophages, fibroblasts and perithelial cells. They appear as tubular bodies of approximately 250 A. diameter. The tubules join together so that they form a 3-dimensional network. The possible viral or non-viral nature of these inclusions is discussed. A ultramicroscopical resemblance to the RNA-containing paramyxo-viruses suggests their virus nature. However, the negative results in testing with serum antibodies and immunofluorescence techniques argue against this. The authors suggest that the demonstration of these inclusions in other than collagen diseases points more in the direction of the correlation of these inclusions with immune globulin synthesis rather than the presence of a virus.

This paper is the result of a symposium that addressed the problem of disablement and social pension for patients with psychosomatic-rheumatological complaints. This especially concerns patients suffering from psychosomatic manifestation at the locomotor apparatus, who are increasingly disabled and necessitating a pension, without actual somatic findings justifying a vocational disablement. Primarily it is a clinical picture of a generalized tendomyopathy, often underestimated in its importance. Definitions, causes, and clinical pictures are presented. A critical phase decisive for the disablement, the personality of the would-be pensioner, considerations for the physician regarding diagnostic and therapeutic efforts, elements of time and environment, and conditions at the work-place are discussed. In some cases a pension will be unavoidable and justifiable, even if the somatic findings seem not to be sufficient. The psychogenic picture must be carefully determined differentiated from simulation; determining the cause of aggravation is essential.

In arthritis surgery "urgent" indications are a relatively subjective definition--apart from few exceptions. The aim of this paper is to give a substantiated classification--under practical aspects--for frequently occurring rheumatoid lesions in all parts of the locomotor system requiring surgical treatment.

Rheumatoid arthritis is a chronic lifelong disease, facts which must be considered when concepts of therapy are developed. This paper reports retrospectively analyzed results of long-term therapy using D-penicillamine. One-hundred-sixteen patients were selected for critical analysis from among 257 treated patients. Judgment was made according to the parameters: inflammation activity, radiological progression, remission rate, clinical outcome-measurement. The results show that the clinical course of the disease is influenced by the treatment and they confirm the need for long-term therapy with an emphasis on immunomodulation.

Interactions between C1q and collagen are thought to be due to the similarity in the structure of collagen and part of C1q. In the present paper immunological and biochemical aspects of this similarity were explored. It was found that one of nine rabbit anticollagen sera studied showed a clearcut reactivity with C1q, while anticollagenantibody-positive sera and synovial fluids of patients with rheumatoid arthritis did not display any cross-reactivity with C1q. Eleven of twenty collagen-immunized guinea pigs, however, demonstrated cellular cross-reactivity with CLF, the collagen-like fragment of C1q. Gel filtration studies indicated the formation of complexes between CLF and collagen, simulating immunological inhibition of anti-C1q-antibody by collagen. Human RA synovial collagenase was found capable of splitting C1q at a position within its collagen-like fragment. The importance of the interactions between collagen and C1q for the pathological events characterizing RA is discussed.

Previous reports describe the presence of immunoglobulins and complement components within rheumatoid articular cartilage, thereby suggesting an effect of immune complexes on the formation of pannus. This hypothesis is reinvestigated in this paper. As confirmed in our work, the superficial layer of rheumatoid hyaline cartilage may fulfill the immunohistological criteria for the presence of immune complexes. In osteoarthritis, however, a noninflammatory disease not mediated by immunologic mechanisms, similar results can be obtained. The presence of immune-proteins within hyaline cartilage therefore requires a cautious interpretation. Hyaline cartilage in rheumatoid arthritis is replaced by granulation tissue growing not only at its surface (pannus), but also in subchondral bone. We therefore also thoroughly investigated deep layers of hyaline cartilage in the vicinity of such subchondral tissue, but could not obtain any evidence for the presence of immune complexes therein. The growth of subchondral granulation tissue and the accumulation of PMN in the region of its junction with hyaline cartilage therefore appear to be independent of immune complexes within rheumatoid hyaline cartilage. It is suggested on the basis of these data that immune complexes possibly present in hyaline cartilage do not play an essential role in the formation of granulation tissue replacing cartilage in rheumatoid arthritis. It is, however, not entirely excluded that during advanced stages of rheumatic cartilage degradation immune complexes are formed within the matrix or carried into it from the extra-cartilaginous environment, and that they may then contribute to further cartilage destruction by enzyme release during phagocytic processes.

The paper takes a retrospective view back to the historical beginning of roentgenology. The development of radiology of bone and joints is high-lighted with special respect of rheumatology. Completeness was not intended regarding the size of this paper. It is shown, especially to our younger colleagues, how hard it was in the past 90 years to achieve our today-knowledge in x-ray-diagnostic. Three factors determined Roentgenology to become an indispensable method. The continuing development and improving of efficient x-ray-machines. The development and improving of investigation methods. The scientific workup of radiological signs leading to radiomorphologic features. Some milestones of technical development of conventional radiology are listed up. Also, innovations in microelectronics. Computed tomography and Magnetic Resonance are listed up. Remarks are made about costs of "big machines" and about declining knowledge in conventional radiology in young american radiologists. Recommendations are made for efficient collaboration of rheumatologists and radiologists.