Diagnose und Therapie der Kalziumpyrophosphatkristall-induzierten Arthropathie

Zusammenfassung: Die Bezeichnung Kalziumpyrophosphatdihydrat-Kristallarthropathie (CPPD-KA) beschreibt eine Gruppe von häufigen und potenziell schweren metabolischen Arthropathien. Dabei bilden sich CPPD-Kristalle, die sich in einer Knorpelmatrix ablagern (Chondrokalzinose) und entzündliche und/oder destruktive Mechanismen auslösen. Die meisten Fälle sind idiopathisch, aber auch Hyperparathyreoidismus, Hämochromatose, Hypomagnesämie und Hypophosphatasämie können eine Chondrokalzinose fördern oder auslösen. Bei einem frühen Krankheitsbeginn (≤60Jahre) muss daher auf eine dieser Stoffwechselstörungen, insbesondere Hämochromatose, hin untersucht werden. Die Prävalenz von CPPD-KA in der Allgemeinbevölkerung liegt bei 10-15% bei 65- bis 75-Jährigen und bei >40% bei über 80-Jährigen. Die Erkrankung verläuft zwar oft asymptomatisch, kann aber auch zu schweren akuten Anfällen von entzündlicher Arthritis (Pseudogicht) sowie verschiedenen chronischen Arthropathien, z.B. pseudorheumatoider Arthritis, Pseudoosteoarthritis und pseudoneuropathischer Gelenkerkrankung führen. CPPD-Kristalle können sich auch in den Schleimbeuteln, Bändern und Sehnen ablagern und eine Entzündung und/oder Rupturen verursachen. Die Diagnose beruht auf der Analyse der Synovialflüssigkeit (positiv doppelbrechende CPPD-Kristalle sichtbar durch kompensierte polarisierte Lichtmikroskopie) und der Röntgenuntersuchung (punktförmige und linear röntgendichte Bereiche in Faserknorpel und hyalinem Knorpel). Behandelt wird im Wesentlichen symptomatisch, da kein Medikament bekannt ist, das das Fortschreiten der Gelenkzerstörung aufhalten kann. Nichtsteroidale Antirheumatika (NSAR) und intraartikuläre oder systemische Glukokortikoide (bei längerem Einsatz nur geringe Mengen!) sind am besten zur Therapie geeignet. Bei wiederkehrender Pseudogicht kann Colchicin helfen, zur Prävention eignet sich Magnesium. In einer kleinen, nichtkontrollierten Patientenserie zeigte Methotrexat eine interessante Wirksamkeit. Es kann eingesetzt werden, wenn andere Mittel erfolglos bleibe

Augmentation of osteochondral repair with hyperbaric oxygenation: a rabbit study

<p>Abstract</p> <p>Background</p> <p>Current treatments for osteochondral injuries often result in suboptimal healing. We hypothesized that the combination of hyperbaric oxygen (HBO) and fibrin would be superior to either method alone in treating full-thickness osteochondral defects.</p> <p>Methods</p> <p>Osteochondral repair was evaluated in 4 treatment groups (control, fibrin, HBO, and HBO+fibrin groups) at 2-12 weeks after surgical injury. Forty adult male New Zealand white rabbits underwent arthrotomy and osteochondral surgery on both knees. Two osteochondral defects were created in each femoral condyle, one in a weight-bearing area and the other in a non-weight-bearing area. An exogenous fibrin clot was placed in each defect in the right knee. Left knee defects were left empty. Half of the rabbits then underwent hyperbaric oxygen therapy. The defects in the 4 treatment groups were then examined histologically at 2, 4, 6, 8, and 12 weeks after surgery.</p> <p>Results</p> <p>The HBO+fibrin group showed more rapid and more uniform repair than the control and fibrin only groups, but was not significantly different from the group receiving HBO alone. In the 2 HBO groups, organized repair and good integration with adjacent cartilage were seen at 8 weeks; complete regeneration was observed at 12 weeks.</p> <p>Conclusions</p> <p>HBO significantly accelerated the repair of osteochondral defects in this rabbit model; however, the addition of fibrin produced no further improvement.</p

Effect of dynamic compressive loading and its combination with a growth factor on the chondrocytic phenotype of 3-dimensional scaffold-embedded chondrocytes

Background and purpose Three-dimensionally (3D-) embedded chondrocytes have been suggested to maintain the chondrocytic phenotype. Furthermore, mechanical stress and growth factors have been found to be capable of enhancing cell proliferation and ECM synthesis. We investigated the effect of mechanical loading and growth factors on reactivation of the 3D-embedded chondrocytes

Intravenous gammaglobulins in refractory polymyositis: lower dose for maintenance treatment is effective

OBJECTIVES—To test lower dose immunoglobulins as a maintenance treatment in a patient with refractory polymyositis.
METHODS—In a patient with longstanding refractory polymyositis, intravenous (IV) immunoglobulin treatment was introduced at a standard dose (2 g/kg monthly). After a few treatment courses, doses were reduced to 0.8 g/kg monthly, allowing perfusion over one single day.
RESULTS—Although response to the standard dose was only partial, reduction of subsequent doses did not alter the evolution. On the contrary, the evolution was marked by further improvement, which has been sustained over the following year.
CONCLUSION—Lower dose IV immunoglobulins as a maintenance treatment were used with excellent results in a case of refractory polymyositis allowing considerable reduction in treatment costs. Further trials should be undertaken to evaluate this interesting alternative.


Benefits of a programme taking advantage of patient‐instructors to teach and assess musculoskeletal skills in medical students

AIM: To evaluate a rheumatoid arthritis patient‐instructor‐based formation–assessment programme for its ability to improve and assess musculoskeletal knowledge and skills in third‐year medical students. METHODS: (1) The quality of our musculoskeletal teaching was assessed before patient‐instructor intervention through an open‐questions test (pre‐test) and performance record forms (PRFs) filled in by the patient‐instructors. (2) The improvement afforded by patient‐instructors was evaluated through a second (identical) open‐questions test (post‐test). (3) The resulting skills in the students were further assessed by an individual patient‐instructors physical status record form (PSRF), filled in by the students. RESULTS: Pre‐tests and post‐tests showed an improvement in correct answers from a mean score of 39% to 47%. The history‐taking questions that obtained <50% scores in the pre‐test mostly dealt with the consequences of a chronic illness. Intervention of patient‐instructors especially improved knowledge of the psychosocial aspects and side effects of drugs. With regard to physical examination, patient‐instructors makedly improved the identification of assessment of signs of active and chronic inflammation. PRF analysis showed that 10 of 28 questions answered by <50% of the students were related to disease characteristics of rheumatoid arthritis, extra‐articular signs, side effects of drugs and psychosocial aspects. Analysis of the PSRF indicated that the weakness of our students' physical examination abilities in particular is related to recognising the types of swelling and differentiating tenderness from pain on motion. CONCLUSION: This study proves the considerable benefits of the involvement of patient‐instructors in the teaching and assessment of clinical skills in students

Association of rheumatoid factors and anti‐filaggrin antibodies with severity of erosions in rheumatoid arthritis

Objectives. To evaluate and to compare the association of two types of autoantibodies—rheumatoid factors (RF) and anti‐filaggrin antibodies (AFA)—with clinical severity and joint damage progression in rheumatoid arthritis (RA) patients. Methods. In a cross‐sectional study, we determined RF and AFA titres in 199 RA patients and 65 controls. Erosions apparent on X‐rays were quantified using the Larsen score in 143 patients, and the distribution of these scores was studied according to disease duration in patients who were positive and negative for RF and AFA. Results. RF were detected in 72% and AFA in 47% of RA patients. AFA were highly specific for RA (100%). RF positivity was correlated with the presence of subcutaneous nodules, sicca syndrome and the severity of erosions for a given disease duration. AFA positivity was correlated only with the presence of the HLA‐DRB1 shared epitope. Conclusions. Since no significant correlation was observed between joint damage progression and AFA positivity, the determination of AFA does not appear to be useful in assessing the prognosis of RA. However, AFA, which appear early in RA, could be helpful for the diagnosis of RA in patients who do not fulfil four American College of Rheumatology criteri

Evidence for differential acquired drug resistance to anti‐tumour necrosis factor agents in rheumatoid arthritis

BACKGROUND: Acquired drug resistance or gradual drug failure has been described with most disease modifying antirheumatic drugs (DMARDs) and is also starting to be recognised with anti‐tumour necrosis factor (anti‐TNF) agents. OBJECTIVE: To study acquired drug resistance to anti‐TNF agents in rheumatoid arthritis (RA). METHODS: Swiss health authorities requested continuous monitoring of patients receiving biological agents. Intensification of co‐therapy with traditional DMARDs, gradual dose escalation, and drug discontinuation rates in all patients receiving infliximab, etanercept, or adalimumab, adjusting for potential confounders, were analysed. Intensification of DMARD co‐therapy and time to discontinuation of the three anti‐TNF agents were analysed using a proportional hazards models. Dose escalation and evolution of RA disease activity (DAS28) were analysed using a longitudinal regression model. RESULTS: 1198 patients contributing 1450 patient‐years of anti‐TNF treatment met the inclusion criteria. The rate of intensification of traditional DMARD co‐therapy over time was significantly higher with infliximab (hazards ratio = 1.73 (99% confidence interval (CI) 1.19 to 2.51)) than with the two other agents. Infliximab also showed significant dose escalation over time, with an average dose increase of +12% (99% CI 8% to 16%) after 1 year, and +18% (99% CI 11% to 25%) after 2 years. No significant differences in discontinuation rates were seen between the three anti‐TNF agents (ANOVA, p = 0.67). Evolution of disease activity over time indicated a lower therapeutic response to infliximab (DAS28, p<0.001) compared with etanercept, after 6 months' treatment. CONCLUSIONS: In this population, infliximab was associated with a higher risk of requiring intensification of DMARD co‐therapy than the other anti‐TNF agents and a significant dose escalation over time. Analysis of RA disease activity indicated a reduced therapeutic response to infliximab after the first 6 months of treatment, suggestive of acquired drug resistance

Epaule douloureuse atraumatique: diagnostic radiologique

Shoulder pain is a common cause of consultation in primary care medicine. A detailed history and a carefully carried out physical exam allow to orientate the diagnosis towards an intrinsic or extrinsic cause and to the differential diagnosis. Rotator cuff injury is the most frequent affection. Plain radiography will often be done in first intention since it identifies direct or indirect signs associated with certain pathologies. Ultrasonography is an excellent way of evaluating soft tissue injury and allows a diagnosis in most cases (rotator cuff injury, tendinopathy of the long head of the biceps, bursitis, effusion, calcifications). Other imaging studies may be carried out depending on the pathology suspected

Methotrexate as an alternative therapy for chronic calcium pyrophosphate deposition disease: an exploratory analysis

OBJECTIVE: To evaluate the effectiveness of methotrexate (MTX), which works not only as an immunosuppressant, but also as a potent antiinflammatory agent, as an alternative therapeutic option for patients with severe calcium pyrophosphate deposition disease (CPDD) who fail to respond to standard therapy with nonsteroidal antiinflammatory drugs and/or glucocorticoids. METHODS: We analyzed, in 2 university hospitals in Switzerland, consecutive patients with CPDD that was resistant to classic treatment and were subsequently treated with MTX. Before and after initiation of MTX therapy, we quantified the frequency of pseudogout attacks, pain intensity, the number of swollen and tender joints, and inflammatory biomarkers. Clinical and biologic side effects of MTX and patients satisfaction with MTX treatment were also evaluated. RESULTS: The study included 5 patients treated with low dosages of MTX (5-20 mg/week). The mean followup time with MTX was 50.4 months (range 6-81 months). All patients reported an excellent clinical response, with marked improvement within a mean period of 7.4 weeks. A significant decrease in pain intensity (P &lt; 0.0001), swollen and tender joint counts (P &lt; 0.0001), and frequency of attacks was observed. The biomarkers of inflammation decreased markedly when systematically analyzed (3 patients). No significant side effects were reported. CONCLUSION: This study suggests that MTX could be a valuable therapeutic option for severe CPDD that is refractory to conventional therapy