[Further development of regional early care-Many roads lead to Rome : Developmental stages of four established rheumatological early care concepts in different regions of Germany]. / Regionale Frühversorgung weiterentwickeln ­ Viele Wege führen nach Rom : Entwicklungsetappen von 4 etablierten rheumatologischen Frühversorgungskonzepten in verschiedenen Regionen Deutschlands.

In order to shorten the prognostically relevant waiting time until diagnosis and initiation of appropriate treatment in inflammatory rheumatic diseases, rheumatological centers in many regions across Germany have established and continuously developed specific early care concepts. Evaluated models from Altötting·Burghausen, Berlin Buch, Düsseldorf and Heidelberg and their developmental stages as a response to internal and external challenges are presented in this overview. The transparent publication of the developmental steps and the exchange of experiences aim at promoting new early care concepts in other regions and continuing the joint dialogue for improvement of the early detection and quality of care of inflammatory rheumatic diseases in Germany.

[Improved early diagnostics of rheumatic diseases : Monocentric experiences with an open rheumatological specialist consultation]. / Verbesserte Frühdiagnostik rheumatischer Erkrankungen : Monozentrische Erfahrungen mit einer offenen fachärztlich rheumatologischen Sprechstunde.

AIM OF THE PROJECT: To establish an open rheumatological outpatient consultation service for early diagnosis of inflammatory rheumatic diseases and initiation of further diagnostics and treatment. METHODS: In 2015 an open consultation service was initiated for patients with signs of an early rheumatic disease after referral by primary care physicians. Patients could attend once a week without the need for a prior appointment if they fulfilled at least one of the following criteria: positive rheumatoid factor, increased CRP, anti-CCP antibody or antinuclear antibody, joint pain or back pain for over 3 months, swollen joints, fever of unknown origin or acute muscle pain with or without headache of unknown origin. This article presents the results of the retrospective descriptive data analysis of the first 2 years of this project. RESULTS: A total of 1262 patients were treated with an average of approximately 20 patients per consultation. In nearly half of the patients an inflammatory rheumatological disease could be diagnosed and immediate diagnostic and treatment measures could be initiated. The diagnostic delay for patients with rheumatoid arthritis was 12 weeks, for patients with polymyalgia rheumatica 11 weeks and for patients with psoriatic arthritis or axial spondylarthritis 18 and 44 weeks, respectively. The time expenditure was a total of 4-5 h per week for an experienced rheumatologist and a specialized rheumatology nurse. CONCLUSION: Through this open rheumatological outpatient consultation a low threshold opportunity for the early diagnosis of rheumatologic diseases could be established. The diagnostic delay for many rheumatological diseases could be considerably shortened. Cooperation with rheumatologists in private practice guaranteed the subsequent specialized rheumatological care of the identified patients in the early stages of their illness.

Diagnosis of early Takayasu arteritis with sonography.

OBJECTIVE: Takayasu arteritis is a large-vessel vasculitis that occurs predominantly in young females. The diagnosis is not usually established before arterial stenoses or occlusions are present. The aim of the study was to find out if sonography can aid in the diagnosis of the disease in earlier stages. METHODS: We describe three patients with early disease who had no haemodynamically relevant stenoses. They are compared with nine patients who were diagnosed in the stenotic/occlusive stage of the disease. All patients were German Caucasian females. Colour Doppler sonography and angiography were performed in all cases. RESULTS: Patients with early disease had general symptoms of fatigue and arthralgia and laboratory signs of inflammation, but neither bruits nor decrease of pulse rate. Sonography of the carotid and subclavian arteries demonstrated a characteristic, homogeneous, midechoic, circumferential thickening of the wall. At this stage of the disease it was difficult to get unequivocal results with angiography. In all nine remaining patients, sonography also demonstrated inflammation of the subclavian or carotid arteries, as did angiography in eight of these patients. CONCLUSION: Sonography of the carotid and subclavian arteries aids in the detection of early Takayasu arteritis. In young females with unclear symptoms and laboratory findings of generalized inflammation, the primary extracranial branches of the aortic arch should be investigated by sonography to detect early Takayasu arteritis.

Vasculitis of the internal carotid artery in Wegener's granulomatosis: comparison of ultrasonography, angiography, and MRI.

A 37-year old male with newly diagnosed, untreated Wegener's granulomatosis including glomerulonephritis, sinusitis, conjunctivitis, arthralgias, and positive cANCA, developed a pulsating tumor in the left submandibular region and a reversible ischemic neurologic deficit. Ultrasonography revealed both a hyperechoic wall thickening of the left proximal internal carotid artery as is known in Takayasu's arteritis and a surrounding hypoechoic region typical for perivasculitis. The wall thickening and the perivascular infiltrate could be less clearly seen by MRI. Ultrasonography, angiography, and MRI demonstrated a 3 cm long, 30%, stenosis. Angiography and MRI additionally found a more distally located kinking of the internal carotid artery that was missed by ultrasonography. Carotid artery vasculitis is a rare complication of Wegener's granulomatosis. In this case ultrasonography was superior to angiography and MRI to visualize the artery wall and the surrounding tissue, but it failed to evaluate the whole distance of the vessel.

Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis.

OBJECTIVE: To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: Computed tomography-assisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization. RESULTS: Dense cellular infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+ cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/- 16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique. CONCLUSION: The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI joints of 5 patients with active AS. The finding of abundant TNF alpha message in these joints could have implications regarding potential immunotherapeutic approaches to this disease. TGF beta might be involved in new bone formation in AS.

Divergent T-cell cytokine patterns in inflammatory arthritis.

A major immunoregulatory mechanism in inflammatory infections and allergic diseases is the control of the balance of cytokines secreted by Th1/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseases; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune disease. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Th1-like pattern whereas in reactive arthritis interferon gamma expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confirmed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic disease by means of inhibitory cytokines.

Analysis of cytokine profiles in synovial T cell clones from chlamydial reactive arthritis patients: predominance of the Th1 subset.

Subpopulations of human T cells (Th0, Th1 and Th2) can be distinguished by their cytokine-secretion pattern. Evidence is increasing from other studies that the outcome of a human disease may depend on the subpopulation of T cells that predominates at the site of inflammation. Reactive arthritis serves as a useful model of chronic inflammatory diseases, because the triggering antigen can be identified. Using this triggering antigen we raised 33 T cell clones reactive with Chlamydia trachomatis and 25 T cell clones that were not reactive, all from the synovial fluid of two patients suffering from Chlamydia-induced arthritis. Their cytokine secretion patterns for interferon-gamma (IFN-gamma), IL-2 and IL-4 were analysed, as also were mRNAs for IFN-gamma and IL-10 by in situ hybridization. Out of the 33 antigen-reactive clones 23 showed a Th1 pattern with IFN-gamma but not IL-4 secretion, while the remaining 10 exhibited a Th0 pattern. The clones that did not react with Chlamydia expressed all patterns of cytokine secretion, including a Th2 pattern, thus providing a control population that excludes bias in the sampling procedure. CD4 and CD8 clones displayed a similar cytokine-secretion pattern. In addition this study demonstrates for the first time the expression of IL-10 mRNA in T cell clones derived from synovial fluid, and this was not confined to the Th2 subset. The Th1 response that Chlamydia provoke can be regarded as appropriate for such an obligate intracellular pathogen.