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

A 64-Year-Old Woman with Chest Pain, Limb Weakness, and Endometrial Cancer

Necrotizing autoimmune myopathy (NAM) is a rare subgroup of idiopathic inflammatory myopathies (IIM). This pathology usually affects proximal limb muscles and in some cases the myocardium. Patients usually display proximal limb weakness. Muscular biopsy is required to confirm the diagnosis. We report the case of a 64-year-old woman with an atypical first presentation of NAM, manifested by chest pain in the context of metastatic endometrial cancer. The diagnosis of NAM was however made when she returned a second time with proximal limb weakness. A treatment with prednisone was then initiated, to which rituximab was rapidly associated, beside a specific chemotherapy

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

Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

Background. Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design. A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion. This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration. Netherlands Trial Register (NTR1636)

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products

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.


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