BackgroundThe role of Th17 cells in the pathogenesis of human autoimmune diseases is elusive.To gain insights into the role of Th17 cells in human autoimmune diseases, the authors analysed Th17 cells in patients with prototypic autoimmune diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA).Methods and Results Th17 cells were analysed in well-defi ned homogeneous cohorts of patients: treatment-naive patients with active early RA (n=6; disease duration 2.8 months; disease activity score 28 (DAS28) 5.0) and PsA (n=9; disease duration 2.3 months), and patients with established RA responding or not responding to therapy with methotrexate/adalimumab (n=1; mean disease duration 68 months).Healthy individuals and patients with osteoarthritis were used as control cohorts.Th17 cell frequencies and IL17 production strongly correlated with systemic disease activity at both the onset and the progression of the diseases.They were reduced to control levels in response to clinically effective treatment.Th17 cells were enriched in the joints, and increased frequencies of synovial Th17 cells expressed CCR4 and CCR6, indicative of selective migration of Th17 cells to the joints.The intrinsically elevated expression of the master transcription factor for Th17 cells, RORC, accompanied by biased Th17 cell development and a resistance of Th17 cells from the patients to natural on July 29, 2023 by guest.
To study the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).IL-22 serum levels were measured in patients with early, treatment-naive RA (n=49) and in 45 age- and sex-matched healthy individuals as controls. Patients were assessed clinically and radiographically at baseline and followed up for 2 years. Correlations of IL-22 serum levels were sought with parameters of disease activity, serological markers, demographic factors and the incidence of erosions. IL-22 production by peripheral blood T cells was investigated by intracellular flow cytometry.24 of 49 patients with RA demonstrated elevated IL-22 levels compared with the range of healthy controls. At baseline, a high percentage of these patients (8/24, 33%) demonstrated bone erosions, whereas only one patient (4%) from the group with normal IL-22 had erosions. During the 2 years of follow-up, six additional patients with increased IL-22 at baseline developed erosions. In contrast, none of the patients in whom IL-22 levels were normal developed erosions despite similar treatment regimens. Multivariate regression analysis accounting for other parameters predictive for erosions, such as the presence of rheumatoid factor or anti-cyclic citrullinated peptide antibodies and disease activity, showed that elevated IL-22 baseline levels were independently and significantly associated with erosive RA. Cellular analysis demonstrated enhanced expression of IL-22 from CD4 T cells in RA.IL-22 is elevated in the serum of half of the patients with RA. Elevated serum IL-22 allows discrimination between patients with different radiographic progression and indicates a possible involvement of IL-22 in the pathophysiology of RA.
Introduction. At first sight, chronic recurrent multifocal osteomyelitis (CRMO) and Schnitzler's disease are diagnoses of exclusion and can be similar in their manifestation. Methods. In this paper we present the reevaluation of the 13-year-old diagnosis of chronic recurrent osteomyelitis of a 58-year-old man with chronic ostealgia, night sweat, and pruritic urticarial lesions on the extremities and trunk. For further examination, we performed blood analysis, bone and skin biopsies, CT scans, and magnetic resonance imaging. Results. Laboratory findings showed increased inflammation parameters. Magnetic resonance imaging (MRI) revealed a diffuse bone marrow infiltration. A bone and skin biopsy showed a sclerotic bone marrow involvement and a superficial dermal and perivascular infiltrate of neutrophils. Based on these findings, the diagnosis of Schnitzler's disease was made. Conclusion. Here, we want to present Schnitzler's disease as an important differential diagnosis to CRMO in adults presenting with signs suggestive of CRMO.
The impact of physical exercise on joints and tendons is still a matter of debate. The aim of this study was to investigate with ultrasound the acute effects of extreme physical exercise on knee and ankle joints and their surrounding structures in trained athletes. Participants of the Munich marathon were examined by arthrosonography before and after long distance running. Ultrasound assessment included grey scale and power Doppler examination of the knee and talocrural joints with surrounding tendons. Findings consistent with joint effusion, tendon and/or entheseal pathologies were documented. In addition to the ultrasound evaluation, information on training habits and past or present arthralgia or joint swelling was gathered. One Hundred Five runners completed both the pre- and post-excercise ultrasound assessments (baseline and follow-up), resulting in the sonographic evaluation of 420 knee and talocrural joints. At baseline, 105 knee (50) and 38 talocrural joints (18.1) showed effusions, compared to 100 knee (47.6) and 33 talocrural joints (15.7 %) at follow-up. The differences were not significant (p > 0.05 each). Effusion size did not correlate with the timepoint of ultrasound assessment and was independent of covariates such as gender, age or running distance. Hypervascularity of the patellar tendon was detected in 21 cases (10.0 %) at follow-up in contrast to one at baseline (p < 0.001). This observation was more frequent in male than in female participants (p < 0.05). Acute physical stress is significantly associated with hypervascularity of the patellar tendon. No significant changes of synovial effusion were detected in knee and talocrural joints.
The effect of extreme physical exercise on joint effusions is unclear. Previous data are controversial concerning the impact of physical exercise on joint structures.
Objectives
An ultrasound (US) evaluation was performed to investigate if long distance running causes effusion of knees and ankles and enthesitis or tendovaginitis of the patellar tendon or of the tendons around the ankles.
Methods
119 participants of the Munich Marathon, performing a full distance or half distance marathon in October 2012 were included in the study. Ultrasound examination of both knees and ankles was performed with a gray scale grading from 0-3 between 48 and 16 h before the event (baseline (BL)). In addition, the medial and lateral tendons of the ankles were examined for tendovaginitis and both patellar tendons were examined for enthesitis with power-doppler. The participants were asked to fill out a questionnaire about age, bodyweight, workout and arthralgia or joint swelling. Immediately after the longdistance run a second ultrasound examination of the same structures was performed (follow-up (FU)) and the participants were asked to fill out a second questionnaire about their complaints during the run.
Results
105 runners completed both ultrasound examinations and questionnaires (61 marathon and 44 half marathon runners). 210 knees were examined, 98 joints (47%) showed an effusion at BL. At follow-up 98 joint effusions were found (p > 0.05). No changes were seen in 135 knees (64%) between BL and FU. In 75 knees (36%), an alteration was detected at FU with 39 knees showed a new or progressive (3 knees) joint effusion, and 36 knees with effusion at BL showed regressive (2 knees) or no effusion any more. Enthesitis of the patellar tendon was detected by power-doppler in one knee at BL and persisted at FU, while new enthesitides at this location were found in 20 examinations (p < 0.001). Of 210 examined ankles, 38 showed an effusion at BL. At FU, 32 ankles with effusion were counted (p > 0.05). 173 (82%) ankles showed a stable finding at BL and FU, while in 37 an alteration was detected. 15 joints showed a new or progressive (1 ankle) effusion, 22 ankles with effusion at BL showed regressive (3 ankles) or dissolved effusion at FU. Only one medial tendovaginitis was detected at FU.
Conclusions
Long distance running does not cause joint effusion in knees or ankles or tendovaginitis of the ankles´ tendons, but a significant increase of enthesitides of the patellar tendons.
Abstract Objective To delineate the role of Th17 cells in the pathogenesis of autoimmune arthritides. Methods Th17 cells were analyzed in well‐defined homogeneous cohorts of patients with the prototypical autoimmune arthritides rheumatoid arthritis (RA) and psoriatic arthritis (PsA), grouped according to patients who had very early active RA (n = 36; mean disease duration 2.8 months, Disease Activity Score in 28 joints 5.0) and those who had very early active PsA (n = 20; mean disease duration 2.3 months), none of whom had received treatment with glucocorticoids or disease‐modifying antirheumatic drugs, as well as patients with established RA (n = 21; mean disease duration 68 months) who were considered either responders or nonresponders to therapy. Groups of healthy individuals and patients with osteoarthritis (a noninflammatory arthritis) were used as control cohorts. Expression of T lineage–specific transcription factors (RORC, T‐bet, GATA‐3, and FoxP3) and the response of CD4 T cells to Th17 cell–inducing conditions were analyzed in vitro. Results The frequencies of Th17 cells and levels of interleukin‐17 strongly correlated with systemic disease activity at both the onset and the progression of RA or PsA. The values were reduced to control levels in patients with treatment‐controlled disease activity. Th17 cells were enriched in the joints, and increased frequencies of synovial Th17 cells expressed CCR4 and CCR6, indicative of selective migration of Th17 cells to the joints. The intrinsically elevated expression of RORC, accompanied by biased Th17 cell development, and the resistance of Th17 cells to a natural cytokine antagonist in patients with RA and patients with PsA were suggestive of the underlying molecular mechanisms of uncontrolled Th17 activity in these patients. Conclusion Th17 cells play an important role in inflammation in human autoimmune arthritides, both at the onset and in established disease.
Ultrasound (US) assessment of MCP and PIP joints in RA can be performed using a palmar and/or a dorsal approach. At the moment, there is no clear preference for either method and well-validated US scores such as the US-7 score include both approaches for a comprehensive evaluation. However, the frequency of synovitic findings seems to differ considerably depending on the approach used.
Objectives
To clarify the role of palmar versus dorsal US assessment in patients with RA.
Methods
Patients with newly diagnosed and therapy-naive RA were included in the study. Ultrasound was performed with grey scale (GSUS) and power Doppler (PDUS) of the MCP and PIP joints, using the dorsal and palmar approach. Synovitic findings in GSUS and PDUS were graded semiquantitatively as specified before. After the initial assessment, patients were treated according to national guidelines and were seen on a regular outpatient basis. Clinical and sonographic reevaluation was performed at month 6. Concordances of palmar and dorsal GSUS and PDUS at baseline and at month 6 were calculated as the sum of all double positive joints and double negative joints divided by all joints. Double positive joints were defined as joints with GSUS and PDUS findings, single positive joints were defined as joints with either GSUS or PDUS findings, double negative joints were defined as joints without GSUS and PDUS findings.
Results
Data of 50 RA patients was available for analysis. At baseline, palmar GSUS identified synovitic findings in 27.2% of MCP and PIP joints, while dorsal GSUS was positive in 28.8% (palmar versus dorsal not significant). Palmar PDUS was positive in 4.0% of MCP and PIP joints, compared to 18.3% of positive findings with dorsal PDUS (palmar versus dorsal p < 0.05). At month 6, palmar GSUS identified synovitic findings in 31.9% of MCP and PIP joints, while synovitic findings identified with dorsal GSUS decreased to 13.9% (palmar versus dorsal p < 0.05). Palmar PDUS was positive in 3.7% of MCP and PIP joints at month 6, while dorsal PDUS was positive in 6.6% (palmar versus dorsal p < 0.05 for MCP joints). Concordances of palmar GSUS and PDUS was 0.77 at baseline, compared to 0.89 of dorsal GSUS and PDUS (palmar versus dorsal < 0.05). At month 6, concordances of palmar GSUS and PDUS was 0.70, while concordances of dorsal GSUS and PDUS was 0.93 (palmar versus dorsal < 0.05).
Conclusions
We observed significant discrepancies of the performances of GSUS and PDUS depending on whether the palmar or dorsal approach was used. These discrepancies were found at two time points with different disease activities. Palmar and dorsal GSUS performed similar at baseline, but the sensitivity to change was significantly better on the dorsal side. PDUS detected significantly more signals from the dorsal side at both time points. Of note, we found that the dorsal approach yields significantly better concordances of GSUS and PDUS than the palmar approach. Assuming that "double positive" joints, i.e. joints with GSUS and PDUS findings, more specifically represent true synovitic joints than only single positive joints, the dorsal approach performs better than the palmar approach. Further analysis is needed to clarify the specific advantages and limitations of both approaches.
Objective To investigate the clinical relevance of grade 1 findings on gray‐scale ultrasound (GSUS) of the joints in patients with rheumatoid arthritis (RA). Methods We examined the wrists and small joints of 100 patients with early or established RA and 30 healthy controls, using GSUS and power Doppler ultrasound (PDUS). Independent clinical assessment of all joints for tenderness and swelling according to the European League Against Rheumatism examination technique was performed. Joints with grade 1 findings on GSUS were identified, and associations with swelling, pain, and findings on PDUS were assessed. Grade 1 findings on GSUS in patients with early RA were reassessed after 6 months of antirheumatic treatment. Results Grade 1 results represented the majority of all GSUS findings in patients with RA and were also frequently recorded in healthy controls. Grade 1 GSUS findings were not associated with tenderness, swelling, or positive results on PDUS. In comparison to joints with grade 2 and grade 3 findings on GSUS, joints with grade 1 findings were less likely to respond to treatment. Conclusion The present results indicate that grade 1 findings on GSUS have limited clinical relevance.
