The study objective was to report treatment with an interleukin (IL)-1 receptor antagonist, anakinra, in patients with multiorgan Behcet's disease (BD). Comparison of clinical manifestations, previous treatments, markers of inflammation, concomitant medications, treatment regimen modifications, relapses, and adverse events before and during anakinra administration among patients with BD were evaluated. Nine BD patients (mean age 34.55 ± 16.30 years) refractory to tumor necrosis factor blockers and standardized therapies are reported in our survey. Their mean age at disease onset was 25 ± 13.88 years and their overall disease duration was 9.55 ± 5.33 years. All patients were positive for the HLA-B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out of nine patients promptly responded, and most of them were maintained on 100 mg of daily anakinra with low doses of prednisone. However, most patients experienced a relapse in one or more clinical manifestations over time (mean time to relapse 29 ± 21.65 weeks), and only one patient remained completely under control on anakinra monotherapy. Despite a relapse in one or more disease manifestations, treatment was continued in most patients for a mean period of 13.75 ± 6.49 months. No serious adverse events occurred. Eight out of nine refractory BD patients showed a prompt improvement after starting anakinra, supporting the concept that IL-1 plays a pathological role in this disease. Nevertheless, after several months, most patients experienced a relapse. It remains unclear whether increasing the dose of anakinra would have prevented the reoccurrence of disease activity.

US is potentially a useful tool for the diagnosis of CPPD but universally accepted definitions and further testing are necessary in order to assess the role of the technique in the diagnostic process.

The deposition of CPP crystals involves at least two sites with a mean of four sites involved in most patients affected by CPPD and is therefore an oligoarticular or polyarticular disease.

Background The diagnosis of calcium pyrophosphate crystal (CPP) deposition disease (CPPD) is mainly based on the synovial fluid analysis and Xrays. US has demonstrated high sensitivity and specificity values for diagnosing CPPD compared to synovial fluid analysis as the gold standard (1), but less is known about sensitivity and specificity of synovial fluid analysis itself. Objectives to compare ultrasonography and synovial fluid analysis performances in the diagnosis of CPPD using a real gold standard. Methods We enrolled in our study all patients waiting to undergo knee replacement surgery due to severe osteoarthritis. Each patient underwent US examination of the knee, focusing on the menisci and the hyaline cartilage, the day prior to surgery, scoring each site according to the presence/absence of CPP as defined previously (1). The day of the surgery, synovial fluid of the knee (if present) was aspirated by the surgeon. After surgery, the menisci, condyles and the synovial fluid were retrieved and examined microscopically. Synovial fluid analysis was performed on wet preparations. For the meniscus and cartilage microscopic analysis, six samples were collected, either from the surface and from the internal of the structure trying to cover a large part of it. All slides were observed under transmitted light microscopy and by compensated polarised microscopy. A dichotomous score was given for the presence/absence of CPP. US and microscopic analysis were performed by different operators, blind to each other's findings. Sensitivity and specificity of US and synovial fluid were calculated using microscopic findings of the menisci and cartilage as the gold standard. Results we enrolled in the study 32 patients (9 males), mean age of 74 years old (±7). Synovial fluid has been collected from 24 patients. If we consider all the structures examined with US (both menisci and cartilage of both condyles), were positive for CPP 22 patients while synovial fluid analysis was positive for 11 patients. At microscopic examination of the speciments, 21 patients were positive for CPP in at least one of the structures examined. US demonstrated a sensitivity of 95% (CI95: ±0.01) with PPV =0.91 and specificity of 81% (CI95: ±0.23) and a NPV =0.90 while respective values for synovial fluid microscopic analysis were 73% (CI95: ±0.22) with PPV of 1 and 100% (CI95: ±0) with NPV of 0.69. Conclusions US demonstrated higher sensitivity values for identifying CPP deposits in the knee joint than synovial fluid analysis. Specificity values on the other had were higher for the microscopic analysis as expected. Globally we believe that for its intrinsic characteristics, the non invasive nature, for the high values of both specificity and specificity, and last but not least, for the capability to address differential diagnosis US should be the first exam ti be performed when CPPD disease is suspected. As this study demonstrates, the presence of CPP crystals in the synovial fluid, definitely confirms the diagnosis but a negative microscopi...

SummaryClodronate is the father of bisphosphonates. For over three decades it has been subject of study in biological and clinical areas, proving to be an extremely interesting molecule from different points of view. It has been the first drug for osteoporosis that can be administered pulsatorily (once every 15 days or once a week). This, along with good tolerability, has been the first cause of its success, when there were no solid data in literature about its antifracture efficacy. There are three published studies that prove its antifracture effect: two by McCloskey published in 2004 and 2007 on BMR, and our study about fracture prevention in corticosteroids OP. In these studies a dose of 800 mg/day orally administered or 100 mg/week I.M. was used, and they are basically the same if you consider that clodronate absorption, orally administered, is on average 1.9%. However, a series of works where higher doses were used (1600 mg orally administered) with greater effectiveness on bone mass, especially in higher risk populations, lead us to consider the use of 200 mg i.m. formulation. First of all, we proved densitometric equivalence of 200 mg i.m./14 days and 100 mg i.m./week in a first study; then, in a second study, we proved a greater densitometric efficacy of 200 mg/week compared to 100 mg/week, clearer at femoral level, where the drug had not proven to prevent femoral fracture because of inadequate bone mass increase at that level. Moreover, as for ibandronate case, monthly dose was doubled compared to pivotal trial, in order to maximize the effects on femoral bone mass and therefore prevent femoral fractures. Consequently, on the basis of the risk envelope, whether it is identified according to BMD and the presence of one risk factor at least or more correctly identified through risk chart (FRAX or DeFRA), you can put forward a differential use of 100 mg i.m. and 200 mg i.m., weekly, "off-label" or every 14 days, adjusting doses in relation to fracture risk and painful symptoms gravity, as well as improving its ease of use and therefore assist compliance. Common experience and clinical and biological works have proved that clodronate has an analgesic effect that can be increased by doubling the doses. The analgesic effect is present not only with patients with fractures, but also with patients suffering from osteoarthritis or arthritis. Therefore, the drug would fit well in the therapeutic program of rheumatic patient, also because of its symptomatic effects. Clodronate at small doses (2 mg) could also have protective effects on cartilage (introduction of intra-articular formulation is expected) and at 10-100 fold higher doses it has certainly anti-inflammatory effects and more specifically antimacrophage and anticytokine effects (IL-1, IL-6, TNFalpha, PGE). These effects are amplified by putting clodronate in monolayer liposomes. This drug, therefore, has to be considered as adjuvant in arthritis therapy, whose origin can be linked to a strong osteoclastic activation caused by an increase of cytokines and...