Preliminary classification criteria for the cryoglobulinaemic vasculitis.

BACKGROUND: To develop preliminary classification criteria for the cryoglobulinaemic syndrome or cryoglobulinaemic vasculitis (CV). METHODS: Study part I developed a questionnaire for CV to be included in the formal, second part (study part II). Positivity of serum cryoglobulins was defined by experts as an essential condition for CV classification. In study part II, a core set of classification items (questionnaire, clinical and laboratory items, as agreed) was tested in three groups of patients and controls-that is, group A (new patients with the CV), group B (controls with serum cryoglobulins but lacking CV) and group C (controls without serum cryoglobulins but with features which can be observed in CV). RESULTS: In study part I (188 cases, 284 controls), a positive response to at least two of three selected questions showed a sensitivity of 81.9% and a specificity of 83.5% for CV. This questionnaire was employed and validated in study part II, which included 272 patients in group A and 228 controls in group B. The final classification criteria for CV, by pooling data from group A and group B, required the positivity of questionnaire plus clinical, questionnaire plus laboratory, or clinical plus laboratory items, or all the three, providing a sensitivity of 88.5% and a specificity of 93.6% for CV. By comparing data in group A versus group C (425 controls), the same classification criteria showed a sensitivity 88.5% and a specificity 97.0% for CV. CONCLUSION: Classification criteria for CV were developed, and now need validation.

Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis associated with rheumatoid arthritis.

OBJECTIVE: To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV). METHODS: 1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids. RESULTS: We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other. CONCLUSIONS: This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients.

Usefulness of mouse models to study the pathogenesis of Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disorder characterized by ocular and oral dryness as well as systemic manifestations. The immunopathogenesis of SS is complex with different intricate factors. Because of the delay in the appearance of symptoms and due to ethical issues it is very difficult to study the wide array of factors intervening in the pathogenesis of SS in human patients. To circumvent this problem, different animal models have been elaborated for studying the different subsets of the aspects of the physiopathology of this disease. In this review, we focus on the mouse models that have been established to deepen our insight into the immunopathogenesis of SS.

[Anti-CCP antibody test: diagnostic and pronostic values in rheumatoid arthritis]. / Les anticorps anti-peptides cycliques citrullinés (anti-CCP): intérêt diagnostique et pronostique dans la polyarthrite rhumatoïde.

Rheumatoid arthritis is an auto-immune disorder which diagnosis is based on clinical, radiological and biological criteria. Disease progression is characterized by appearance of bone erosions and progressive articular deformations which attenuate functional mobility. Only rheumatoid factor is actually considered as biological factor among recognized diagnostical criteria despite its weak sensibility and specificity rates. Anti-cyclic citrullinated peptides antibodies are directed toward citrullinated isoforms of some filaggrin's epitopes. Their sensitivity and specificity reach respectively 80 and 99%. Their presence is correlated to disease activity and to bone erosions development. They allow early identification and treatment of rheumatoid arthritis affected patients which is actually considered as a priority.

Primary Sjögren's syndrome associated with pneumatosis cystoides coli.

We report the case of a 43-year-old woman with primary Sjögren's syndrome, according to Americano-European criteria. Eighteen months after the diagnosis, the patient presented pneumatosis cystoides coli (PCC), which resolved with medical treatment consisting of diet and cisapride. Four years after this episode, the patient has not developed clinical features of another systemic inflammatory rheumatic disease and PCC has not relapsed. To the best of our knowledge, the association between primary Sjögren' syndrome and PCC has never been reported. Physiopathology and treatment of PCC are discussed.

A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus ciclosporin in patients with active psoriatic arthritis.

OBJECTIVES: To evaluate the safety and efficacy of adding ciclosporin A (CSA) to the treatment of patients with psoriatic arthritis (PsA) demonstrating an incomplete response to methotrexate (MTX) monotherapy. METHODS: In a 12 month, randomised, double blind, placebo controlled trial at five centres in three countries, 72 patients with active PsA with an incomplete response to MTX were randomised to receive either CSA (n = 38) or placebo (n = 34). Patients underwent full clinical and radiological assessment and, in addition, high resolution ultrasound (HRUS) was performed at one centre. An intention to treat (last observation carried forward) analysis was employed. RESULTS: Some significant improvements were noted at 12 months in both groups. However, in the active but not the placebo arm there were significant improvements in swollen joint count, mean (SD), from 11.7 (9.7) to 6.7 (6.5) (p<0.001) and C reactive protein, from 17.4 (14.5) to 12.7 (14.3) mg/l (p<0.05) as compared with baseline. The Psoriasis Area and Severity Index (PASI) score improved in the active group (2 (2.3) to 0.8 (1.3)) as compared with placebo (2.2 (2.7) to 1.9 (2.8)), p<0.001, and synovitis detected by HRUS (33 patients, 285 joints) was reduced by 33% in the active group compared with 6% in the placebo group (p<0.05). No improvement in Health Assessment Questionnaire or pain scores was detected. CONCLUSIONS: Synovitis detected by HRUS was significantly reduced. Combining CSA and MTX treatment in patients with active PsA, and a partial response to MTX, significantly improves the signs of inflammation but not pain or quality of life.

Results from a patient survey to assess gastrointestinal burden of non-steroidal anti-inflammatory drug therapy contrasted with a review of data from EVA to determine satisfaction with rofecoxib.

Non-steroidal anti-inflammatory drugs (NSAIDs) have frequently been linked with unpleasant gastrointestinal (GI) side-effects such as dyspepsia and ulcers. The present study investigated the burden of NSAID therapy from a patient perspective and also reviewed previously published data on satisfaction with a less gastrotoxic anti-inflammatory drug, rofecoxib. A questionnaire was sent to > 6000 members of the Norwegian Rheumatism Association requesting information on use and toxicity of NSAID therapy and requirements for supplementary gastroprotective and analgesic medication. The questionnaire confirmed a high incidence of NSAID use. About two-thirds of users changed brands of NSAIDs at least once, usually because of adverse effects and poor efficacy. Supplementary over-the-counter (OTC) and prescription analgesics were required by 72 and 59% of patients, respectively, while OTC and prescription gastroprotective agents to treat NSAID toxicity were required by 35 and 30%. This new patient-focused survey showed that treatment with conventional NSAIDs was unsatisfactory in terms of GI toxicity and sub-optimal pain relief. Reviewing EVA (Experience with VIOXX in Arthritis) data showed that there was a high level of approval for rofecoxib, with > 80% of 74,192 osteoarthritis (OA) patients expressing a preference for continuing such therapy. Preference for rofecoxib was significantly higher among patients with prior experience of conventional NSAIDs or other OA-specific medication. In EVA, the reduced GI toxicity of rofecoxib previously reported in other studies appeared to translate into a strong preference to continue this therapy in a large sample of patients. This is not surprising, given the poor satisfaction with NSAIDs highlighted by the Norwegian survey.

[The rheumatology and physical medicine department]. / Le Service de Rhumatologie et de Médecine Physique.

Actually, 18 rheumatologists and specialists in physical therapy are collaborating in the Department, allowing to develop possibilities for the diagnosis and therapeutic challenge of patients suffering from disorders of the locomotor system. Accordingly, the knowledge, the know-how, the experience plus the willingness to make a good job are used for helping the patient, for contributing to medical progress and also for the education of future medical doctors. Our department has significantly contributed to a better understanding and therapeutic approach of rheumatoid arthritis, Sjogren's syndrome, aseptic necrosis, osteoporosis, osteoarthritis, and inflammation; it has been among the first in the world to offer new therapeutic modalities, otherwise not accessible and, to help a series of hopeless patients. In addition, a new sector for a performing rehabilitation has been recently developed. Accordingly, during these mast twenty years, a performing department with a motivated team has been developed offering a maximum of medical services for the community and ready for the challenges of tomorrow.

Infliximab in patients with primary Sjögren's syndrome: a pilot study.

OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine involved in the pathogenesis of Sjögren's syndrome (SS), and blockade of TNFalpha may reduce the activity of the disease. The purpose of this study was to evaluate the safety and potential efficacy of infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody, in patients with active primary SS. METHODS: This was a single-center, open-label pilot study. Sixteen patients with active primary SS received 3 infusions of infliximab (3 mg/kg) at 0, 2, and 6 weeks. Standard clinical assessment, complete ophthalmologic testing, and functional evaluation of salivary flow were performed at baseline and at weeks 2, 6, 10, and 14. RESULTS: All patients completed the study. There was statistically significant improvement in all clinical and functional parameters, including global assessments (patient's global assessment, patient's assessment of pain and fatigue, physician's global assessment), erythrocyte sedimentation rate, salivary flow rate, the Schirmer I test, tender joint count, fatigue score, and dry eyes and dry mouth. This clinical benefit was observed at week 2 and was maintained throughout the study and the 2-month followup period. The treatment was well tolerated in all patients, and no significant adverse events were seen. No lupus-like syndrome was observed, and no anti-double-stranded DNA antibodies were observed that were attributable to infliximab therapy. CONCLUSION: In patients with active primary SS, a loading-dose regimen of 3 infusions of infliximab provided a fast and significant clinical benefit without major adverse reactions. It was possible to maintain statistically significant improvement for up to 8 weeks after the third infusion.

Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjögren's syndrome patients.

Patients with Sjögren's syndrome (SS) suffer from deficient secretion of saliva due to an autoimmune destruction of salivary glands, however, glandular dysfunction also occurs without destruction. Based upon its abnormal distribution in SS salivary glands, a potential role for the water channel protein aquaporin-5 (AQP5) is proposed in the pathogenesis of SS. The immunohistochemical distribution of AQP5 was compared in minor salivary gland biopsies obtained from women after informed consent: primary SS (53.2 +/- 14 years old, n = 10), healthy volunteers (46.2 +/- 17 years old, n = 10), patients with sarcoidosis (37 and 48 years old), and patients with non-specific sialoadenitis (54 and 61 years old). Biopsies from normal subjects revealed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, biopsies from SS patients revealed AQP5 primarily at the basal membranes of the acinus. The AQP5 distribution in biopsies from patients with other dry mouth disorders, such as non-specific sialoadenitis or sarcoidosis, was similar to biopsies from control subjects. Computer-assisted microscopy was performed to quantitatively evaluate AQP5 distribution in the immunoreactive acini of both SS and control subjects. Biopsies from SS patients had higher labeling indices (percentage of acinus area immunoreactive for AQP5) at the basal membrane when compared with biopsies from control subjects. In contrast, biopsies of SS patients exhibited lower labeling indices at the apical membrane when compared with biopsies from control subjects. To verify the specificity of the AQP5 antibody, Western blot analysis was performed on membranes from Xenopus oocytes injected with AQP5 cRNA or on membranes from minor salivary glands of control subjects and SS patients. In each case, the immunoblots had a 27 kd band, corresponding to the expected molecular weight of AQP5. Abnormal distribution of AQP5 in salivary gland acini is likely to contribute to the deficiency of fluid secretion, which is a defining feature of Sjögren's syndrome.

Patient and physician satisfaction with rofecoxib in osteoarthritis: results of the EVA (experience with VIOXX in arthritis) survey.

A nationwide survey was undertaken among 74,192 patients with osteoarthritis (OA) and 5986 physicians (including 5265 general practitioners [GPs]) in Belgium to evaluate satisfaction with the selective cyclo-oxygenase-2 inhibitor rofecoxib (12.5 or 25 mg, given once a day for an average of 30 days). Rofecoxib was considered by patients to be a very effective treatment for OA, with satisfaction scores of good or very good in the domains of pain, mobility and general satisfaction. More than 80% of GP-treated patients expressed a wish to continue rofecoxib therapy. Preference for rofecoxib was especially strong in patients (n = 45,453) who had previously been treated with conventional non-steroldal anti-inflammatory drugs (NSAIDs), notably patients who had used diclofenac, ibuprofen and nimesulide. Physicians also expressed high satisfaction with rofecoxib, with more than 80% of surveyed physicians indicating a wish to continue prescribing the drug. The results of this large survey demonstrate a clear preference for rofecoxib over conventional NSAIDs in a substantial majority of OA patients. The satisfactory pain relief and excellent gastrointestinal safety profile of rofecoxib demonstrated in earlier controlled trials are likely to have been factors in patients' preferences for rofecoxib over NSAIDs.

Improving care practices for patients with multidrug-resistant organisms: one facility's evolution.

The care of patients with multidrug-resistant organisms (MDROs) varies in rehabilitation settings. Implementation of strict contact isolation in some facilities may limit patients from reaching their rehabilitation goals. This article describes our rehabilitation and long-term acute care facility's efforts to develop a policy that would enable patients with MDROs to meet their rehabilitation goals within a safe environment. A multidisciplinary team developed a two-track care process allowing staff to quickly identify appropriate activities for these patients. The team also developed educational materials for staff and families, addressed cleaning practices, and standardized the criteria for follow-up cultures and discontinuation of isolation. The MDRO policy was instituted throughout the hospital in August 1999. The incidence of nosocomially acquired MDROs has decreased slightly from the baseline rate of .076 per 100 patient days to .039 per 100 patient days during the 4-month period following the implementation of the policy.

Prolactin up-regulates cathepsin B and D expression in minor salivary glands of patients with Sjögren's syndrome.

Various proteases are expressed in the minor salivary glands (MSG) of patients with Sjögren's syndrome (SS), and as we have already shown, prolactin is neosynthesized in the acinar cells of patients with SS. The present study aims to characterize the influence of PRL on the expression of cathepsin B and D in the MSG of patients with SS. Cathepsin B and D expression was investigated immunohistochemically in MSG of 30 patients with SS and 15 healthy volunteers. The presence of cathepsin B and D mRNAs was checked in three SS patients and three control subjects by means of reverse transcription-polymerase chain reaction (RT-PCR). The specificity of the anti-cathepsin B and D antibodies used for the immunohistochemistry was checked by means of western blotting analysis. The influence of prolactin on the immunohistochemical expression of cathepsin B and D was quantitatively assayed by computer-assisted microscopy at three different doses (5, 50, and 500 ng/ml) on eight MSGs (four control subjects and four patients with SS) maintained ex vivo under organotypic cultures. This influence was also investigated at the mRNA level. Whereas cathepsin B immunopositivity was absent from glandular epithelial cells of healthy subjects and only slightly present in SS patients, cathepsin D immunoreactivity was considerably greater (p < 0.0001) in both the acini and the ducts of patients with SS as compared with control subjects. Cathepsin B, but not D, was also expressed in about 20% of infiltrating mononuclear cells of SS patients. Treatment of both healthy and SS minor salivary glands with PRL significantly (p < 0.05 top < 0.0001) enhanced cathepsin B and D expression in acinar and ductal cells at both protein and mRNA levels. PRL produced locally in MSGs of SS patients, but not those of healthy subjects, could play a role in the pathogenesis of Sjogren's syndrome, if only through the activation of proteolytic activity on the part of cathepsins B and D.

Labeled neoglycoproteins and human lectins as diagnostic and potential functional markers in salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: The profile of glycans and their recognition by endogenous receptors (lectins) are increasingly attributed to disease process. Monitoring this can provide information on the pathogenesis of Sjögren's syndrome (SS). Commonly, plant lectins are employed for phenomenological glycan mapping. To go beyond this approach restricted to binding of exogenous probes, new markers measure ligand properties of glycans to human (not plant) lectins and the presence of sugar receptors completing a protein-carbohydrate recognition system. Carrier-immobilized sugar epitopes (neoglycoproteins) and purified human lectins establish this innovative panel. METHODS: The host defence molecules mannan binding lectin, serum amyloid P component, and the macrophage migration inhibitory factor-binding sarcolectin, selected for their involvement in cell destructive mechanisms, were purified and labeled. The plant lectins SNA and MAA were employed to monitor regulation of potential ligand sites for I-type lectins and galectins. Asialofetuin was tested as a "pan-galectin selective" probe. The specific binding characteristics were determined by quantitative morphometry and statistical analysis. RESULTS: Diagnostic information emerged from this analysis. The percentage of stained tissue area was significantly different between SS and control specimens after processing with GlcNAc and Man-bearing neoglycoproteins and the 2 tested serum lectins. For separation of cases of primary and secondary SS, the staining intensity with the asialoglycoprotein, sarcolectin, and the exogenous alpha2,6-sialylated glycan-binding lectin SNA was statistically significant. CONCLUSION: Saccharide-presenting probes to measure the cellular capacity to bind glycan epitopes and human lectins as sensors for endogenous binding sites have proven to be useful as diagnostic tools. We suggest the differences we observed reflect aberrations from the normal cellular homeostasis with relevance for the pathogenesis of SS and its manifestation as a primary or secondary syndrome.

Big prolactin 60 kDa is overexpressed in salivary glandular epithelial cells from patients with Sjögren's syndrome.

Characterization of endogenous synthesis of prolactin (PRL) proteins and their cellular localization in labial salivary glands of patients with Sjogren's syndrome (SS) were achieved. PRL, PRL-receptors (PRL-R), and S100A6 protein were detected by immunohistochemistry. In situ prolactin synthesis was investigated in controls and SS patients by ex vivo incubation of minor salivary glands biopsies and immunoprecipitation assay. Increased PRL-immunoreactivity was found in cytoplasmic acinar epithelial cells in SS patients compared with normal subjects. PRL-R was distributed only in ductal epithelial cells in which S100A6 protein (a PRL-R-associated protein) was also present. PRL, PRL-R, or S100A6-immunoreactivity was not detected in infiltrating mononuclear cells. Immunoprecipitation demonstrated that PRL synthesis occurred in minor salivary glands with increased synthesis of two distinct PRL-like proteins (one major band at 60 kDa and a minor at 16 kDa) in SS glands compared with normal glands. Expression of PRL gene was demonstrated in SS salivary glands using RT-PCR. A positive correlation was found between the presence of PRL-like proteins in acinar epithelial cells of SS patients and clinical extraglandular manifestations. The presence of anti-Ro and anti-La antibodies also positively correlated with a higher percentage of PRL in acinar epithelial cells. In conclusion, PRL-like proteins are synthetized and overexpressed in glandular epithelial cells of labial salivary glands from SS patients and correlate with the aggressiveness of the disease.

Sialic acid residues in the labial salivary glands from Sjögren's syndrome patients.

OBJECTIVE: To investigate the composition and expression of sialic acid in the labial salivary glands (LSG) in Sjögren's syndrome (SS). METHODS: LSG of 19 patients with primary SS (n = 11) or secondary SS (n = 8) were studied. Specimens from 7 healthy women served as controls. Computer-assisted microscopy was employed to quantitatively determine the percentage of positive structures, the staining intensity and the heterogeneity for the 4 biotinylated plant lectins Tritricum vulgaris L. (WGA), Maackia amurensis (MAA), Sambucus nigra (SNA) and Canavalia ensiformis L. (Con A). RESULTS: In the acini there was a significant decrease in the staining heterogeneity of WGA in SS compared to controls; the same was observed with respect to MAA staining in the connective tissue and extralobular ducts. In the intralobular ducts, primary SS differed from normal and secondary SS mainly in terms of a decrease in the percentage of positively labeled MAA tissue. In addition, Con A stained acinar cells were significantly more numerous in secondary SS compared with primary SS. CONCLUSION: Differences in the degree of glycoconjugate sialylation were found in SS labial salivary glands, and may play a role in the disease process.

Zidovudine in primary Sjögren's syndrome.

OBJECTIVE: To evaluate the efficacy of the administration of zidovudine (AZT), an antiretroviral drug, in patients with primary Sjögren's syndrome (SS). METHODS: Seven female patients (age 57 +/- 8.6 yr) with primary SS were enrolled in an open, uncontrolled trial of AZT (250 mg b.i.d.) for the treatment of primary SS. The efficacy variables were oral and ocular dryness symptoms, fatigue, tender points, physician's and patient's global assessments (GA), ocular function tests (fluorescein tear break-up time, Schirmer's test, Rose Bengal staining) and laboratory parameters [erythrocyte sedimentation rate (ESR), serum IgG, IgA and IgM]. RESULTS: A significant improvement was observed in all subjective manifestations, as well as the objective parameters of ocular dryness. The treatment was well tolerated, except for mild and transitory gastrointestinal disturbances in 6/7 patients. Laboratory parameters did not change significantly. The clinical benefit persisted in 5/7 patients 1 month after the end of therapy. CONCLUSION: AZT seems to be effective and well tolerated in patients with primary SS.