How to diagnose spondyloarthritis early? Accuracy of peripheral enthesitis detection by power Doppler ultrasonography.

OBJECTIVE: Early diagnosis of spondyloarthritis (SpA) is sometimes difficult owing to the lack of reliable diagnostic criteria. The objective of this study was to determine the diagnostic accuracy of detecting enthesitis by power Doppler ultrasonography (PDUS) in patients with suspected SpA. METHODS: A prospective single-centre cohort study was performed in patients with symptoms suggestive of SpA (inflammatory back pain, arthritis, enthesitis or dactylitis, HLAB27+ uveitis) who underwent clinical examination, pelvic x-ray, MRI of lumbar spine/sacroiliac joints, HLA-B typing and other tests judged useful for diagnosis. Blinded PDUS examination of seven sites of enthesitis was performed at baseline. The gold standard was the diagnosis made by the referring rheumatologist according to the development of symptoms and findings, blinded to PDUS results, during routine follow-up for up to 2 years. RESULTS: Between November 2002 and October 2004, 118 patients were included in the study. After 2 years a definite diagnosis was retained for 99 patients (51 SpA and 48 non-SpA). PDUS detection of at least one vascularised enthesis provided good predictive value for diagnosing SpA (sensitivity 76.5%; specificity 81.3%; positive likelihood ratio 4.1; OR 14.1; p<0.0001). Vascularised enthesitis detected by PDUS and Amor's criteria were the only independent contributors to a diagnosis of SpA in multivariate logistic regression (c-index=0.87). Alternatively, CART analysis resulted in a highly sensitive and specific diagnostic tree by combining PDUS with Amor's criteria. CONCLUSIONS: PDUS appears to be a valuable first-line diagnostic tool to confirm a diagnosis of SpA.

Eosinophilic fasciitis: a rare skin sclerosis.

Eosinophilic fasciitis (Schulman's syndrome) is a rare disease with specific clinical symptoms such as the groove sign which facilitate diagnosis. We report a typical case of eosinophilic fasciitis in an otherwise healthy 49-year-old man who presented with "prayer and groove signs". Histological analysis showed sclerosis and eosinophilic infiltration of the fascia. The patient was successfully treated with systemic corticotherapy and Cyclosporine. A short review of the clinicopathological features of the lesions is presented.

Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene.

Mutations identified in the fibrillin-1 (FBN1) gene have been associated with Marfan syndrome (MFS). Molecular analysis of the gene is classically performed in probands with MFS to offer diagnosis for at-risk relatives and in children highly suspected of MFS. However, FBN1 gene mutations are found in an ill-defined group of diseases termed 'type I fibrillinopathies', which are associated with an increased risk of aortic dilatation and dissection. Thus, there is growing awareness of the need to identify these non-MFS probands, for which FBN1 gene screening should be performed. To answer this need we compiled the molecular data obtained from the screening of the FBN1 gene in 586 probands, which had been addressed to our laboratory for molecular diagnosis. In this group, the efficacy of FBN1 gene screening was high in classical MFS probands (72.5%,), low (58%) in those referred for incomplete MFS and only slight (14.3%) for patients referred as possible MFS. Using recursive partitioning, we found that the best predictor of the identification of a mutation in the FBN1 gene was the presence of features in at least three organ systems, combining one major, and various minor criteria. We also show that our original recommendation of two systems involved with at least one with major criterion represents the minimal criteria because in probands not meeting these criteria, the yield of mutation identification drastically falls. This recommendation should help clinicians and biologists in identifying probands with a high probability of carrying a FBN1 gene mutation, and thus optimize biological resources.

How to evaluate and improve the reliability of power Doppler ultrasonography for assessing enthesitis in spondylarthritis.

OBJECTIVE: To evaluate and improve the reliability of power Doppler ultrasonography (PDUS) for detecting and scoring enthesitis in patients with spondylarthitis, using a 3-step procedure. METHODS: In the first step, we evaluated the reliability of 5 sonographers by bilaterally scanning 5 entheses twice in 5 patients. In the second step, starting from disagreements observed during the first step, we established consensus guidelines. The sonographers' implementation was further evaluated in 2 reliability exercises: one on 60 PDUS enthesitis images and the other by scanning 5 new patients. In the third step, we performed a final reliability evaluation of 5 additional patients after 1 year. Kappa coefficients (kappa) as well as variance component analysis (VCA) and generalizability theory (GT) were used to assess reliability. RESULTS: The initial intra- and interobserver reliability were poor, especially for detecting and scoring Doppler signal. VCA and GT showed that most variability was accounted for by interaction between sonographer and enthesis. Implementation of consensus guidelines was associated with a significant improvement in Doppler reliability between the first and second steps (mean interobserver kappa increased from 0.13 to 0.51 for binary Doppler scoring in patients; P < 0.005), which persisted in the third step (mean interobserver kappa = 0.57). The high GT coefficients reached in the last steps supported such improvement. CONCLUSION: The 3-step procedure used in this study to standardize PDUS technique was associated with a significant improvement in interobserver reliability for detecting enthesitis in spondylarthritis patients. Such an approach can be useful to standardize PDUS assessment of musculoskeletal disorders.

Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders.

TGFBR1 and TGFBR2 gene mutations have been associated with Marfan syndrome types 1 and 2, Loeys-Dietz syndrome and isolated familial thoracic aortic aneurysms or dissection. In order to investigate the molecular and clinical spectrum of TGFBR2 mutations we screened the gene in 457 probands suspected of being affected with Marfan syndrome or related disorders that had been referred to our laboratory for molecular diagnosis. We identified and report 23 mutations and 20 polymorphisms. Subsequently, we screened the TGFBR1 gene in the first 74 patients for whom no defect had been found, and identified 6 novel mutations and 12 polymorphisms. Mutation-carrying probands displayed at referral a large clinical spectrum ranging from the Loeys-Dietz syndrome and neonatal Marfan syndrome to isolated aortic aneurysm. Furthermore, a TGFBR1 gene mutation was found in a Shprintzen-Goldberg syndrome patient. Finally, we observed that the yield of mutation detection within the two genes was very low : 4.8% for classical MFS, 4.6% for incomplete MFS and 1% for TAAD in the TGFBR2 gene; 6.2%, 6.2% and 7% respectively in the TGFBR1 gene; in contrast to LDS, where the yield was exceptionally high (87.5%).

Prosthetic hip infection caused by Tropheryma whipplei.

We report a case of prosthetic hip infection due to Tropheryma whipplei in a 74-year-old man not previously known to have Whipple's disease. Diagnosis was based on systematic 16S rRNA gene amplification and sequencing of samples obtained during revision hip arthroplasty.

Perceptions in 7700 patients with rheumatoid arthritis compared to their families and physicians.

OBJECTIVE: To compare perceptions of patients with rheumatoid arthritis (RA) to those of their families and usual physicians regarding pain and subjective experience of the disease. METHODS: Questionnaires were mailed to patients listed in the files of a non-profit patient organization (Association Française des Polyarthritiques). Each patient, one family member (or close friend), and the usual physician were each asked to complete a questionnaire. Concordance among replies made by patients, family/friends, and physicians was evaluated using the kappa coefficient. RESULTS: Questionnaires were sent to 20,468 patients, among whom 7702 (38%) mailed back adequate data. The family member was usually the spouse (70%) and the usual physician a rheumatologist (68%). Joint pain was described by patients as variable (80%) and unpredictable (68%). Patients reported a need to push themselves (86%), frustration (86%), anxiety about possible disease progression (89%), and being prevented from making plans for the future (6%). A negative impact was reported on recreational activities (84%), work (56%), and family life and sexuality (51%). Concordance was excellent for pain severity (kappa>0.90) and good for the main joint-pain characteristics and experience of the disease (kappa>0.70), although family members tended to overestimate, and physicians to underestimate, the intensity of the pain. CONCLUSION: We found good overall agreement between perceptions of patients, their families, and their physicians, despite differences between these last two groups. Our qualitative analysis showed not only a major physical impact of the disease, but also marked negative psychosocial effects.

Bone mineral density in Marfan syndrome. A large case-control study.

OBJECTIVE: To measure bone mineral density (BMD) in a group of patients meeting Gand criteria for Marfan syndrome, comparatively with a group of healthy controls. METHODS: Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD at the hip and wrist in 130 patients seen at the Multidisciplinary Marfan Clinic, Paris, France. Results were compared to values in the database of the absorptiometry machine (Hologic QDR100) and to values in 72 healthy height-matched controls including 35 whose body mass index (BMI) values were similar to those in the patients. RESULTS: A history of fractures was noted in 32 (24.6%) patients. Z-score values were significantly decreased in the patients compared to the Hologic database values at the femoral neck (-1.190+/-0.098, P<0.0001) and wrist (-1.403+/-1.06; P < 0.001). Patients had significantly lower BMD values at the femoral neck compared to the height-matched controls (0.841+/-0.15 versus 1.010+/-0.017; P<0.0001). BMD values were also significantly lower in the patients compared to the controls of similar height and BMI. BMD values did not correlate with history of fractures or acetabular protrusion. In the patients, BMD values lower than -2.5 correlated with presence of dural ectasia. CONCLUSION: Men and women with Marfan syndrome have significant osteopenia independent from BMI.

Unusual evolution of Waldenström's macroglobulinemia into osteolytic myeloma.

We report the unusual transformation of a case of Waldenström's macroglobulinemia (WM) into IgM multiple myeloma (MM). The initial clinical and biological presentation of the disease was typical smouldering WM, with lymphocytic infiltration of the bone marrow. Five years later, signs of transformation appeared: the patient presented with diffuse osteolytic bone lesions without organomegaly, and the bone marrow was infiltrated with characteristic malignant plasma cells. Electron microscopy (EM) examination showed that the endoplasmic reticulum (ER) of the dysmorphic plasma cells contained monoclonal IgM. Immunolabeling for calreticulin, a resident protein of the ER, demonstrated unequivocally that the characteristic intranuclear inclusions were indeed part of ER. Flow cytometry revealed an MM profile for the cellular proliferation. Molecular biology performed on the final marrow could only retrieve a single cellular clone. In conclusion, this is the first documented description of the transformation of typical WM into an aggressive form of MM.

[Inflammatory arthritis of the elderly]. / Rhumatisme inflammatoire sujet âgé.

Inflammatory arthritis of the elderly have growned new interest because of their frequency and also because new syndromes or subsets of arthritis of the young adults have been recently described. The originality of seropositive rheumatoid arthritis beginning after 70 years old is that management and prognosis are not different from early onset a RA. Various subsets of mild seronegative arthritis of the elderly that pose diagnostic problems with polymyalgia rheumatism (PMR) are also described. New syndromes, at least partly, presents as an original expression of late onset arthritis. Theses syndromes are characterized by rapid onset of arthritis with pitting non inflammatory oedema (RS3PE, described by McCarthy). Same syndromes resistant to steroids will reveal hemopathy or metastastic carcinoma. Late onset of inflammatory spondylarthropathy presenting as undifferentiated arthritis, fever, loss of weight and large oedemia is probably the most original presentation of arthritis specific to old males.

Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients.

BACKGROUND: Methotrexate and nonsteroidal antiinflammatory drugs are frequently coadministered in the treatment of rheumatoid arthritis (RA). OBJECTIVE: To evaluate the effect of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, on methotrexate pharmacokinetics and short-term safety in patients with RA. METHODS: This multicenter, randomized, double-blind, placebo-controlled crossover study enrolled 18 patients (mean age 49.1 y) with stable RA. Patients were randomized to receive methotrexate 7.5-15 mg orally once weekly plus either lumiracoxib 400 mg/day or placebo for 7 days. Patients then received the other treatment combination for an additional 7 days. Serial blood and urine were collected for 24 hours after the methotrexate dose on day 1 (methotrexate alone) and days 8 and 15 (combination treatment). RESULTS: Plasma methotrexate pharmacokinetics (AUC(0-t), maximum concentration [C(max)], time to C(max)) and methotrexate protein binding were similar for methotrexate alone (108.0 ng.h/mL, 26.7 ng/mL, 1.5 h, and 57.1%, respectively), methotrexate/lumiracoxib (110.2 ng.h/mL, 27.5 ng/mL, 1.0 h, and 53.7%, respectively), and methotrexate/placebo (101.8 ng.h/mL, 22.6 ng/mL, 1.0 h, and 57.0%, respectively). Similarly, no clinically significant difference was found in the urinary excretion of methotrexate. Mean exposure to the 7-OH metabolite was lower when methotrexate was given with lumiracoxib compared with placebo, shown by a reduction in AUC and C(max), although similar amounts of the metabolite were recovered in urine following both lumiracoxib and placebo. Coadministration of methotrexate and lumiracoxib was well tolerated. CONCLUSIONS: Lumiracoxib had no significant effect on the pharmacokinetics, protein binding, or urinary excretion of coadministered methotrexate in patients with RA.