Psoriatic arthritis screening by the dermatologist: development and first validation of the 'PURE-4 scale'.

BACKGROUND: Dermatologists are recommended to ask psoriasis patients about musculoskeletal complaints to allow early detection and treatment of psoriatic arthritis (PsA). Screening tools have been developed to help identify patients warranting further rheumatologic assessment, but evidence suggests room for improvement in their diagnostic value and ease of use for outpatient practice. OBJECTIVE: To develop and internally validate a brief tool for dermatologists to screen patients to refer to a rheumatologist for PsA diagnosis. METHODS: After the literature review, 23 items were selected, covering pain at various locations and inflammatory signs of PsA. The validation study was conducted in medically diagnosed psoriasis patients consecutively recruited between 2012 and 2014 (Saint Joseph Hospital, Paris, France). Patients were enrolled by a dermatologist who helped to complete the questionnaire. Diagnosis of PsA was established by a rheumatologist based on CASPAR criteria. Multivariate logistic regression models were performed to build the scale, assessing discrimination through sensitivity, specificity and area under the ROC curve (AUC). Final model was internally validated using bootstrapping techniques. RESULTS: One hundred and sixty-eight patients were recruited, of whom nine were excluded for known PsA and 21 did not attend the rheumatologist consultation. Of 137 included patients (median age 43 years, 59.6% men), 21 (15.3%) had a PsA diagnosis. Final regression model retained four independent items, including evocative signs of dactylitis, inflammatory heel pain, bilateral buttock pain and peripheral joint pain with swelling in patients aged <50. A total score (the PURE-4) was computed (0-4 points) that demonstrated excellent discriminative power (AUC = 87.6%; Sensitivity = 85.7% and Specificity = 83.6% at the threshold of ≥1/4 points), with no evidence for over-optimism in bootstrapped internal validation. CONCLUSION: These findings demonstrate the good diagnostic properties of a new screening scale using only four easy-to-collect items. If confirmed in other populations, it may prove useful in outpatient dermatology clinics for triage of psoriasis patients requiring further assessment by the rheumatologist.

Relationship between SNPs and expression level for candidate genes in rheumatoid arthritis.

OBJECTIVES: The study of polymorphisms of genes differentially expressed may lead to the identification of putative causal genetic variants in multifactorial diseases such as rheumatoid arthritis (RA). Based on preceding transcriptomic results, we genotyped 10 single nucleotide polymorphisms (SNPs) belonging to six genes (S100A8, RNASE2, PGLYRP1, RUNX3, IL2RB, and LY96) showing the highest fold change (> 1.9) when level of expression was compared between RA patients and controls. These SNPs were then analysed to evaluate their role in RA. METHOD: The relationship between gene expression and genotypes of SNPs was first investigated by Kruskal-Wallis and Mann-Whitney tests in RA patients and controls. The genetic association of these SNPs with RA were then analysed using family-based association tests in trio families. RESULTS: We found that RNASE2 gene expression was related to rs2013109 genotypes in 14 RA patients (p = 0.030). The association study in a discovery sample of 200 French trio families revealed a significant association with RA for one SNP, PGLYRP1-rs2041992 (p = 0.019); this association was stronger in trios where RA patients carried the HLA-DRB1 shared epitope (SE) (p = 0.003). However, this association was not found in a replication sample of 240 European trio families (p = 0.6). CONCLUSIONS: Family-based association tests did not reveal an association between RA and any SNP of the candidate genes tested. However, RNASE2 gene expression was differentially expressed in RA patients considering a sequence polymorphism. This result led us to highlight the potential disease-specific regulation for this candidate gene in RA.

Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects.

OBJECTIVES: The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young female subjects. DESIGN: Systematic case-control study of incident ADs associated with quadrivalent HPV vaccination in young women across France. PARTICIPANTS AND SETTING: A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14-26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain-Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice. ANALYSIS: Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs. RESULTS: Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 [95% confidence interval (CI) 0.5-1.5]. The individual ORs were 1.0 (95% CI 0.4-2.6) for ITP, 0.3 (95% CI 0.1-0.9) for MS, 0.8 (95% CI 0.3-2.4) for connective disorders and 1.2 (95% CI 0.4-3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain-Barré syndrome or thyroiditis. CONCLUSIONS: No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.

Primary osteoarthritis of hip, knee, and hand in relation to occupational exposure.

AIM: To identify occupations with excess prevalence of osteoarthritis of the knee, hip, and hand in a nationwide survey and to compare occupations with and without excess prevalence with regard to biomechanical stresses and severity of osteoarthritis. METHODS: Patients presenting with osteoarthritis of the knee, hip, or hand were recruited throughout France by their treating physician who collected information on history, including age at onset, occupation, and occupational stresses to joints. Severity was assessed using joint specific functional status questionnaires: Lequesne for the hip and knee and Dreiser for the hand. The distribution of osteoarthritis patients by occupation was compared with the distribution of occupations in all workers in France to obtain prevalence rate ratios. RESULTS: Occupations with the greatest prevalence rate ratio were female cleaners (6.2; 95% CI 4.6 to 8.0), women in the clothing industry (5.0; 95% CI 3.9 to 6.3), male masons and other construction workers (2.9; 95% CI 2.6 to 3.3), and agriculture male and female workers (2.8; 95% CI 2.5 to 3.2). A twofold greater prevalence rate was observed within certain occupations between self-employed and salaried workers. Early onset of osteoarthritis was seen in the more heavy labour jobs with almost 40% of patients reporting their first symptoms before the age of 50. CONCLUSION: The early onset and severity of osteoarthritis in certain occupations warrants an urgent need for occupation specific studies for the development and evaluation of preventive strategies in this leading cause of disability in Western countries.

Primary osteoarthritis and occupations: a national cross sectional survey of 10 412 symptomatic patients.

AIMS: To describe the age standardised prevalence of symptomatic osteoarthritis (OA) in a nationwide cross sectional survey of 10 412 patients in France, and their functional and work limitations. METHODS: Cases in the survey were compared with their expected counterpart by age, gender, and occupational groupings using data from the 1998 French National Survey on Health Impairment and Disability. RESULTS: Women represented 66.2% of the sample; mean age was 66.2 years. One third of patients had OA of the knee, 16% of the hip, and 12% of the hand; a third had multiple joint OA. Peak prevalence of symptomatic OA was in the 60-69 year category in women and in the 70-79 year category in men. Agricultural workers showed a significant excess prevalence of OA, with an observed to expected (O/E) ratio of 1.7 in women and 2.3 in men. Linear trends in prevalences between white collar, "mixed" collar, and blue collar workers were also significant, with odds ratios respectively of 1.0, 2.9, and 2.6 in women and 1.0, 1.2, and 1.7 in men. Specific excess prevalence was found in women among housekeepers (O/E 4.4), and in men among unskilled labour workers (O/E 10.3) and truck drivers (O/E 6.7). Total work disability was highest among blue collar workers and partial disability among agricultural workers. CONCLUSION: Results contribute to the mounting evidence that OA is potentially aetiologically linked to occupation in a sizeable segment of the population and that OA can no longer be considered an inevitable disease of ageing.

Cellular activation products in osteoarthritis synovial fluid.

In order to address the issue of the role of mast cells (MC) and nitric oxide (NO) in rheumatic synovial-fluid diseases, synovial fluid (SF) collected from the knee of patients with osteoarthritis (OA), articular chondrocalcinosis (ACC) or rheumatoid arthritis (RA) was examined for the levels of mast cells (MC), histamine, tryptase, phospholipase A2 and nitrite. MC counts were found to be elevated in the SF of OA patients as compared with RA patients. Histamine content in SF parallelled the number of MC. Tryptase levels were elevated in OA in comparison to RA and ACC, but the difference was not statistically significant. Identical PLA2 levels were recorded among the 3 groups. Nitrite concentrations were also higher in SF from OA patients as compared to RA patients. These results suggest that mast cells (MC), in association with various inflammatory cells, may contribute to inflammation and cartilage breakdown in osteoarthritis (OA).

[Inducible nitric oxide synthase expression and nitric oxide production by monocytes in systemic sclerosis]. / Expression de la NO synthase inductible et production du monoxyde d'azote par les cellules mononucléées sanguines dans la sclérodermie systémique.

We investigated nitric oxide (NO) production and inducible NO synthase (iNOS) expression by cultured peripheral blood mononuclear cells (PBMC) in systemic sclerosis (SSc). Eighteen patients with SSc were compared to two control groups: 16 rheumatoid arthritis patients (RA) and 23 mechanical sciatica patients. The sum of nitrites and nitrates was determined by fluorimetry in sera and spectrophotometry in supernatants. Inducible iNOS was detected in cultured PBMC by immunofluorescence, immunoblot and flow cytometry with or without IL-1 beta + TNF alpha, IL-4 or IFN gamma from day 1 to day 5. NO metabolite concentrations in the plasma were lower in SSc (34.3 mumol/l +/- 2.63 SEM) than in RA (48.3 mumol/l +/- 2.2; p < 0.02) and sciatica (43.3 mumol/l +/- 5.24; p < 0.03) patients. iNOS was detected in cultured monocytes in the 3 groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. The concentrations of NO metabolites are decreased in SSc patients and the induction of iNOS in PBMC is delayed. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may suggest therapeutic implications.

[Lung diseases and treatment with methotrexate in rheumatoid arthritis]. / Pneumopathies et traitement par le méthotrexate dans la polyarthrite rhumatoïde.

Methotrexate (MTX) is used as sequential treatment of rheumatoid arthritis in doses ranging from 5 to 20 mg per week, but its effectiveness is impaired by undesirable and sometimes severe side-effects, notably on the lungs. We report three cases of lung disease in patients with rheumatoid arthritis under MTX therapy. Two patients had a lung infection caused by Escherichia coli and Pneumocystis carinii respectively and the third patient was a case of fatal pneumonia imputed to MTX. The signs and symptoms of these acute infectious or iatrogenic lung diseases are not specific. Bronchial endoscopy with bronchoalveolar lavage usually leads to a diagnostic of opportunistic infection, but it may also show an isolated excess, in both number and percentage, of alveolar leucocytes, pointing to a drug-induced pneumopathy. Acute respiratory failure due to MTX-induced pneumonia is not uncommon. It rapidly regresses either spontaneously or under corticosteroid therapy, but a number of deaths, as in our last patient, have been reported. The occurrence of these lung diseases is unrelated to the total dose of MTX. Reintroducing MTX does not mean that the condition will necessarily recur, but this can only be done in the absence of any other possible treatment.

[Value of the self-evaluation of functional and painful disorders for the differentiation between fibromyalgia and inflammatory rheumatic diseases]. / Interet de l'auto-evaluation des troubles fonctionnels et douloureux pour la distinction entre fibromyalgie et rhumatisme inflammatoire.

The authors sought to determine whether the self-report questionnaire developed by L.F. Callahan and T. Pincus is of use for the diagnosis of fibromyalgia when severe and/or chronic pain raises doubts as to an inflammatory rheumatic disease. This questionnaire evaluates the ratio between pain severity assessed on a visual analog scale and impairment of activities of daily living. High values suggest fibromyalgia, whereas low values occur in rheumatoid arthritis patients. The French translation of the questionnaire was completed by 15 fibromyalgia patients and 22 patients with inflammatory arthritic syndrome of whom 15 had rheumatoid arthritis. Mean pain/impairment ratio was 5.85 +/- 0.68 (SEM) in the fibromyalgia group versus 3.01 +/- 0.38 in the inflammatory rheumatism group. This difference was highly significant (p = 0.001 by Student's t test). The rheumatoid arthritis subgroup was also significantly different from the fibromyalgia group (p = 0.003). These findings are very similar to those reported by Callahan and Pincus. Our data confirm the value of this simple self-evaluation tool. In practice, ratios greater than 5 suggest fibromyalgia whereas ratios under 3 support the diagnosis of rheumatoid arthritis.

[Paraparesis of lower limbs caused by apophyseal joint cyst]. / Paraparésie des membres inférieurs par kyste articulaire postérieur.

A case of paraparesis due to an apophyseal joint cyst is reported. Full recovery occurred following surgical removal of the cyst. A review of the literature found approximately 60 cases of nerve root pain due to a synovial apophyseal joint cyst. Only very few patients had neurological loss. Facet joint cysts must be differentiated from spinal tumors. Computed tomography and above all magnetic resonance imaging provide valuable diagnostic and therapeutic information.

[Treatment of refractory rheumatoid polyarthritis by extracorporeal photochemotherapy]. / Traitement de la polyarthrite rhumatoïde réfractaire par photochimiothérapie extra-corporelle.

Extracorporeal photochemotherapy (EPC) has been used to treat cutaneous T-cell lymphomas as well as a number of immune-mediated disorders. Seven patients above 50 years of age with refractory rheumatoid arthritis (RA) were treated by EPC. Mononuclear cells were harvested, exposed to ultraviolet A light in the presence of 8-methoxypsoralen, then reinfused into the patient. This procedure was repeated eight times over a three-week period. Improvements in clinical parameters were seen in every case as early as the second week and persisted throughout the duration of EPC. Improvements for more than three months were observed in two patients. C-reactive protein levels declined during the treatment period. No adverse reactions were recorded. The mechanism of action of EPC in RA requires elucidation and a controlled study is needed to confirm the efficacy of this technique.

[Paget disease, complicated by Ki-1 lymphoma with G-CSF growth factor secretion]. / Maladie de Paget compliquée d'un lymphome Ki-1 avec sécrétion de facteur de croissance G-CSF.

Development of lysis within an area of pagetic bone suggests a sarcoma. We report the case of a 61-year-old woman who had increasingly severe pain in her right hip and a decline in general health. The roentgenogram of the pelvis showed previously known pagetic lesions of the right half of the pelvis and osteolysis of the roof of the acetabulum. Additional imaging studies (ultrasonography, computed tomography, and magnetic resonance imaging) disclosed a pelvic tumor extending on either side of the right ilium. The peripheral white blood cell count was markedly elevated (93,000/mm3) as a result of inappropriate secretion of granulocyte-colony-stimulating factor. The tumor was an anaplastic large cell lymphoma of T-cell origin with CD30 positivity, i.e., a Ki-1 lymphoma. Most CD30-positive lymphomas are high-grade tumors. There has been only one previous report of Ki-1 lymphoma with production of granulocyte-colony-stimulating factor and hyperleukocytosis. It has been suggested that cytokines may influence tumor growth. Unusual features in our case include development of the Ki-1 lymphoma in an area of pagetic bone and presence of a leukemic syndrome due to increased production of a growth factor.

[Chemolysis of intravertebral disk hernia and spinal syndrome]. / Hernie intra-spongieuse, nucléolyse et syndrome rachidien.

The authors report a 31 year old patient who underwent L5-S1 chemonucleolysis. The prenucleolysis discogram disclosed intravertebral discal displacement. Severe spinal symptoms and development of geodes in the endplates adjacent to the treated disk occurred after the procedure. This case suggests that intraosseous discal displacement may be a risk factor for postchymopapain nucleolysis discitis and may contraindicate chemonucleolysis.

Biological markers in inflammatory rheumatic diseases.

Biological markers of inflammation are useful for the diagnosis and the monitoring of inflammatory rheumatisms and connective tissue diseases. These markers are not specific, and often poorly correlate with the long term evolution of the disease. C-reactive protein (CRP) is a sensitive marker, and is used to monitor inflammatory and infectious diseases. In rheumatoid arthritis (RA), CRP correlates with disease activity and response to therapy, and CRP levels are influenced by disease-modifying drugs and corticosteroids. Serum amyloid A (SAA) is another acute phase protein (APP) which appears in RA as a more sensitive marker than CRP. Several antinuclear antibodies serve as markers of systemic disorders; they are not implicated in the disease by themselves, but their production could be related to the genetic background underlying the pathogenesis of the disease. In systemic lupus erythematosus (SLE), the titer of anti-ds DNA antibodies often correlates with disease activity. DNA is poorly immunogenic and the production of anti-ds DNA antibodies could be linked to the association of DNA with more immunogenic protein antigens. Cellular DNA is associated with proteins in nucleosomes and it now appears more appropriate to consider the anti-DNA antibody production as a response to a DNA-protein complex. Antibodies can be directed to histones and DNA-protein complexes such as transcription or replication complexes. Antibodies to ribonuclear proteins are associated with different disease subsets and help to define the prognosis in SLE and connective tissue diseases. The identification of antibodies directed against proteins and RNA components is still a field of research.

[Lipids, lipoproteins, arterial accidents and oral contraceptives]. / Lipides, lipoproteines, accidents arteriels et contraceptifs oraux.

PIP: This work reviews lipoprotein metabolism and relationships to atherosclerosis, examines the nature of arterial accidents and lipid modifications that occur with oral contraceptive (OC) use, and assesses the practical consequences for OC prescription. Cholesterol, triglycerides, and phospholipids are not soluble in aqueous milieus, and their transport in plasma is provided by macromolecules comprising a protein part and a lipid part. 5 types of these lipoproteins are distinguished by their relative richness in lipids and protein and by the nature of their proteins. The chylomicrons carry exogenous triglycerides to the peripheral tissues and cholesterol of dietary origin to the liver. Very low density lipoprotein (VLDL) cholesterol is secreted by the liver and transports triglycerides and cholesterol of endogenous origin. Low denisty lipoprotein (LDL) cholesterol originates in the degradation of VLDL cholesterol and transports cholesterol to the cells. High density lipoprotein (HDL) cholesterol is secreted by the liver and intestines or formed in the course of degradation of chylomicrons and VLDL cholesterol. Its role is to carry excess cholesterol in the peripheral tissues to the liver for elimination in the bile. Cholesterol thus follows 2 different pathways in the body: a path from the liver to the peripheral cells, whose markers are LDL and VLDL cholesterol and the plasma apoprotein B, and a path of return of excess cholesterol from the tissues and especially the arteries to the liver, marked by HDL cholesterol and the plasma apoprotein A. Only a proper balance between the 2 flows can prevent an excess of cholesterol in the arteries and the consequent constitution of atherosclerotic lesions. LDL and to a lesser extent VLDL cholesterol are strongly and positively correlated to atherogenic risk, while HDL cholesterol is negatively correlated to risk, independently of other risk factors. Arterial accidents occurring with OC use do not seem to be atheromatous in nature. A study by the Lipid Research Clinics of 2000 OC users and nonusers found that users had higher levels of total cholesterol, of triglycerides, and of LDL and VLDL cholesterol, while the elevation of HDL cholesterol was minimal. The effects of combinations of hormones in OCs depend on their composition. OCs with high or medium doses of estrogen cause an elevation in total cholesterol, triglycerides, and LDL and VLDL cholesterol. HDL cholesterol rises slightly with 19 norsteroids and declines with norgestrel. The ratio of total to HDL cholesterol is on the whole increased. OCs with low estrogen doses induce a decline inHDL cholesterol while the levels of total cholesterol and triglycerides remain unchanged. High dose progestin-only pills induce increases in LDL and decreases in HDL cholestrol. Total cholesterol tends to increases with 19 norsteroids and decline with noregestrel while triglycerides vary slightly. With smaller doses of progestin, less intense effects may be seen. The theoretic atherogenic risk determined by the levels and ratio of total and HDL cholesterol is thus increased with some hormonal combinations. OCs can be prescribed for women with normal lipid balance after a pretreatment lipid profile determination. Lipid balance should be reassessed regularly. OCs are contraindicated in cases of moderate or severe hypercholesterolemia and primary hypo HDLemia. Combined OCs may be used in cases of mild hyperlipoproteinemia in which other contraceptive methods are not possible if regular monitoring is provided.^ieng

[Treatment of rheumatoid polyarthritis with methotrexate]. / Traitement de la polyarthrite rhumatoïde par le méthotrexate.

This retrospective study involved 60 patients (7 men, 53 women) with rheumatoid arthritis (RA) and given methotrexate between 1985 and 1990. The mean time that RA had been present was 12 years and more than half of the patients had received more than 3 types of general treatment in the past. The mean total duration of MTX was 17.3 months, with a total dose of 790 mg. The efficacy of MTX was confirmed by a significant improvement in clinical and laboratory parameters. Treatment was withdrawn permanently in 21 cases (35% of patients). Adverse reactions, responsible for two thirds of treatment withdrawals (14/21) occurred in most instances during the first year of treatment. Hepatic toxicity was commonest. Two cases of aplasia were reported as well as 3 cases of pneumonitis, one fatal. These involved two cases of secondary infection and one of pneumonitis directly imputable to MTX. Withdrawals for inefficacy were rare, occurring in less than 10 p. cent of patients. Treatment continuation rates were 77 p. cent at 1 year, 66 p. cent at 18 months, 55 p. cent at 2 years, 42 p. cent at 3 years and 32 p. cent at 4 years. MTX is effective treatment for RA but is not free of adverse reactions, sometimes potentially fatal. Prolonged monitoring is necessary because of the sometimes delayed onset of adverse reactions.