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1.
J Eur Acad Dermatol Venereol ; 32(11): 1950-1953, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29430720

ABSTRACT

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.


Subject(s)
Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/epidemiology , Dermatologists , Early Diagnosis , Mass Screening/organization & administration , Adult , Age Distribution , Area Under Curve , Cohort Studies , Female , France/epidemiology , Humans , Incidence , Logistic Models , Male , Middle Aged , Predictive Value of Tests , Program Evaluation , Psoriasis/diagnosis , Psoriasis/epidemiology , ROC Curve , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Distribution
2.
Ann Rheum Dis ; 76(1): 29-42, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27457514

ABSTRACT

BACKGROUND: New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. METHODS: The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach. RESULTS: Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended. CONCLUSIONS: These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.


Subject(s)
Gout Suppressants/therapeutic use , Gout/drug therapy , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Delphi Technique , Directive Counseling , Evidence-Based Medicine , Gout/blood , Gout/therapy , Humans , Interleukin-1/antagonists & inhibitors , Life Style , Patient Education as Topic , Symptom Flare Up , Uric Acid/blood
3.
Lupus ; 25(7): 735-40, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26876692

ABSTRACT

OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.


Subject(s)
Antirheumatic Agents/blood , Hydroxychloroquine/blood , Lupus Erythematosus, Systemic/blood , Quality of Life , Adult , Double-Blind Method , Female , France , Humans , Linear Models , Male , Middle Aged
4.
Ann Rheum Dis ; 74(9): 1684-90, 2015 Sep.
Article in English | MEDLINE | ID: mdl-24796335

ABSTRACT

OBJECTIVES: In France, the prevalence of gout is currently unknown. We aimed to design a questionnaire to detect gout that would be suitable for use in a telephone survey by non-physicians and assessed its performance. METHODS: We designed a 62-item questionnaire covering comorbidities, clinical features and treatment of gout. In a case-control study, we enrolled patients with a history of arthritis who had undergone arthrocentesis for synovial fluid analysis and crystal detection. Cases were patients with crystal-proven gout and controls were patients who had arthritis and effusion with no monosodium urate crystals in synovial fluid. The questionnaire was administered by phone to cases and controls by non-physicians who were unaware of the patient diagnosis. Logistic regression analysis and classification and regression trees were used to select items discriminating cases and controls. RESULTS: We interviewed 246 patients (102 cases and 142 controls). Two logistic regression models (sensitivity 88.0% and 87.5%; specificity 93.0% and 89.8%, respectively) and one classification and regression tree model (sensitivity 81.4%, specificity 93.7%) revealed 11 informative items that allowed for classifying 90.0%, 88.8% and 88.5% of patients, respectively. CONCLUSIONS: We developed a questionnaire to detect gout containing 11 items that is fast and suitable for use in a telephone survey by non-physicians. The questionnaire demonstrated good properties for discriminating patients with and without gout. It will be administered in a large sample of the general population to estimate the prevalence of gout in France.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Gout/diagnosis , Osteoarthritis/diagnosis , Spondylarthropathies/diagnosis , Adult , Aged , Arthritis/diagnosis , Arthritis/epidemiology , Arthritis, Rheumatoid/epidemiology , Case-Control Studies , Epidemiologic Studies , France/epidemiology , Gout/epidemiology , Humans , Logistic Models , Middle Aged , Osteoarthritis/epidemiology , Sensitivity and Specificity , Spondylarthropathies/epidemiology , Surveys and Questionnaires , Telephone
5.
Osteoporos Int ; 25(11): 2573-80, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25027110

ABSTRACT

UNLABELLED: Wilson's disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures. INTRODUCTION: Wilson's disease (WD) is characterized by copper deposition, especially in the liver and central nervous system. Two studies showed a high prevalence of osteoporosis in WD patients. We wanted to assess the prevalent fractures and bone mineral density (BMD) and to identify risk factors for bone loss and fractures in a large group of WD patients. METHODS: In this prospective cross-sectional survey at National center of reference for WD, we included 85 patients, 47 women, and 38 men, with a mean age of 35 ± 10 years, and mean time from diagnosis to study of 21 ± 9 years; 57 (67%) patients had neurological signs. Peripheral fractures, prevalent radiological vertebral fractures (VFx), and dual-energy X-ray absorptiometry BMD measurements at the femoral neck (FN) and lumbar spine (LS) were studied. RESULTS: Mean LS and FN Z-score was normal (-0.37 ± 1.20 at LS and -0.06 ± 1.20 at FN). BMI <19 kg/m(2) and amenorrhea were associated with low BMD. Prevalent peripheral fractures were noted in 43 (51%) and VF in 7 (8%) patients. Severity of neurological involvement and male sex was associated with peripheral fractures, whereas older age, severe neurological involvement, and low BMD and Z-score values were associated with VF. CONCLUSION: Our data showing normal BMD overall do not support routine bone status evaluation in adults with WD. However, patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk factors for fractures and may require specific monitoring.


Subject(s)
Hepatolenticular Degeneration/complications , Osteoporotic Fractures/etiology , Absorptiometry, Photon/methods , Adult , Aged , Biomarkers/blood , Bone Density/physiology , Cross-Sectional Studies , Female , Femur Neck/physiopathology , Hepatolenticular Degeneration/physiopathology , Humans , Lumbar Vertebrae/physiopathology , Male , Middle Aged , Osteoporotic Fractures/physiopathology , Spinal Fractures/etiology , Spinal Fractures/physiopathology , Young Adult
6.
Br J Dermatol ; 171(3): 646-9, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24684162

ABSTRACT

BACKGROUND: Palmoplantar pustular psoriasis is a clinical psoriasis variant characterised by a high impact on quality of life and poor response to biologics approved for plaque type psoriasis.The recombinant interleukin-1 (IL-1) receptor antagonist anakinra has been recently used for the treatment of isolated refractory cases of generalised pustular psoriasis with contrasted results. OBJECTIVES: To report the clinical response in two patients treated with anakinra as salvage therapy in two patients with severe palmoplantar pustular psoriasis refractory to currently available antipsoriatic systemic therapies. METHODS: Anakinra was given subcutaneously at the daily dose of 100 mg, and clinical response was evaluated using the palmoplantar psoriasis area and severity index (PPPASI). RESULTS: Only partial and transient responses were observed in both patients, who had to stop anakinra due to lack of efficacy and to side effects. CONCLUSION: Anakinra appears to provide only partial clinical improvement in refractory palmoplantar pustular psoriasis. Prospective clinical studies on larger populations are warranted to investigate more accurately both efficacy and safety of IL-1-inhibiting strategies in pustular psoriasis.


Subject(s)
Dermatologic Agents/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Psoriasis/drug therapy , Aged , Humans , Male , Middle Aged , Treatment Outcome
7.
Osteoarthritis Cartilage ; 20(11): 1399-408, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22885567

ABSTRACT

OBJECTIVE: Basic calcium phosphate (BCP) crystals, including octacalcium phosphate (OCP), carbonated-apatite (CA) and hydroxyapatite (HA) crystals are associated with destructive forms of osteoarthritis. Mechanisms of BCP-induced cartilage breakdown remain incompletely understood. We assessed the ability of BCP to induce changes in intracellular calcium (iCa(2+)) content and oscillations and the role of iCa(2+) in BCP-induced cartilage degradation. METHODS: Bovine articular chondrocytes (BACs) and bovine cartilage explants (BCEs) were stimulated with BCP or monosodium urate (MSU) crystals. iCa(2+) levels were determined by spectrofluorimetry and oscillations by confocal microscopy. mRNA expression of matrix metalloproteinase 3 (MMP-3), a disintegrin and metalloprotease with thrombospondin-like motifs 4 (ADAMTS-4) and ADAMTS-5 was assessed by quantitative real-time PCR. Glycosaminoglycan (GAG) release was measured in the supernatants of BCE cultures. RESULTS: All three BCP crystals significantly increased iCa(2+) content. OCP also induced iCa(2+) oscillations. Rate of BACs displaying iCa(2+) oscillations increased over time, with a peak after 20 min of stimulation. OCP-induced iCa(2+) oscillations involved both extracellular Ca(2+) (eCa(2+)) influx and iCa(2+) stores. Indeed, OCP-induced iCa(2+) oscillations decreased rapidly in Ca(2+)-free medium. Both voltage- and non-voltage-dependent Ca(2+) channels were involved in eCa(2+) influx. BCP crystal-induced variation in iCa(2+) content was associated with BCP crystal-induced cartilage matrix degradation. However, iCa²(+) was not associated with OCP crystal-induced mRNA expression of MMP-3, ADAMTS-4 or ADAMTS-5. CONCLUSION: BCP crystals can induce variation in iCa(2+) content and oscillations in articular chondrocytes. Furthermore, BCP crystal-induced changes in iCa(2+) content play a pivotal role in BCP catabolic effects on articular cartilage.


Subject(s)
Calcium Phosphates/pharmacology , Calcium Signaling/drug effects , Cartilage, Articular/pathology , Chondrocytes/pathology , Animals , Calcium Channel Blockers/pharmacology , Calcium Phosphates/metabolism , Calcium Signaling/physiology , Cartilage, Articular/drug effects , Cartilage, Articular/metabolism , Cattle , Cells, Cultured , Chondrocytes/drug effects , Chondrocytes/metabolism , Crystallization , Drug Antagonism , Female , Proteoglycans/metabolism
8.
Reumatismo ; 63(4): 276-83, 2012 Jan 19.
Article in English | MEDLINE | ID: mdl-22303534

ABSTRACT

Gout is a very common joint disease which is due to chronic hyperuricemia and its related articular involvements. Yet it can be cured when appropriately managed. Comprehensive management of gout involves correct identification and addressing all causes of hyperuricemia, treating and preventing attacks of gouty inflammation (using colchicine NSAIDs, and/or steroids), and lowering serum urate (SUA) to an appropriate target level indefinitely. The ideal SUA target is, at a minimum, less than 6 mg/dL (60 mg/L or 360 µmol/L), or even less than 5 mg/dL in patients with tophi. The SUA target should remain at less than 6 mg/dL for long in all gout patients, especially until tophi have resolved. Patient education and adherence to therapy are key point to the optimal management of gout, aspects which are often neglected. Adherence can be monitored in part by continuing, regular assessment of the SUA level. More difficult cases of gout often need a combination of urate lowering therapy (ULT) for both refractory hyperuricemia and chronic tophaceous arthritis. Chronic tophaceous gouty arthropathy which do not respond adequately to optimized oral ULT might benefit from the use of pegloticase, when this is available in, for example, Italy and other European countries. By contrast, in calcium pyrophosphate (CPP) crystal deposition disease (CPPD), as evidenced by pseudo gout attacks or chronic polyarthritis, similar anti-inflammatory strategies have been recommended, but there have as yet been no controlled trials. Of note, there is no treatment for the underlying metabolic disorders able to control the CPPD. Management of crystal-induced arthropathies (CIA) depends not only on clinical expression, namely acute attacks or chronic arthropathy, but also on the underlying metabolic disorder. We will mainly focus on gout as an archetype of CIA.


Subject(s)
Chondrocalcinosis/therapy , Gout Suppressants/therapeutic use , Gout/therapy , Hyperuricemia/therapy , Arthritis, Gouty/therapy , Humans , Life Style , Medication Adherence , Patient Education as Topic , Practice Guidelines as Topic , Treatment Outcome
9.
Eur Respir J ; 35(3): 681-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19608586

ABSTRACT

The anti-CD20 antibody rituximab has been reported to induce a heterogeneous spectrum of lung disorders. The aim of the present study was to critically review data on the clinical presentations, causality assessments and management strategies of lung diseases possibly related to rituximab. A systematic literature review was performed on English-language reports in PubMed until September 2008. Cases of lung diseases ascribed to rituximab (n = 45) were identified, with three time-to-onset patterns. The most common presentation was acute/subacute hypoxaemic organising pneumonia (n = 37), starting 2 weeks after the last infusion (often around the fourth cycle) and resolving, in most cases, provided glucocorticoid therapy was given early. Acute respiratory distress syndrome occurred in five patients, within a few hours and usually after the first infusion. In the remaining three patients, macronodular organising pneumonia developed insidiously long after rituximab therapy and responded to steroids. Eight patients died. Based on time to onset, symptoms, and responses to discontinuation and rechallenge with rituximab and other drugs, 13 cases were highly compatible and 32 compatible with rituximab-induced lung disease. Knowledge of these presentations of rituximab-induced lung disease should prove helpful for diagnosis and causality assessment purposes. Time-to-onset data, suggesting different pathogenic mechanisms, support closer clinical and perhaps radiological monitoring between infusions, particularly in patients with a history of reversible respiratory symptoms.


Subject(s)
Antibodies, Monoclonal/adverse effects , Biological Factors/adverse effects , Lung Diseases, Interstitial/chemically induced , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived , Drug Hypersensitivity/physiopathology , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/chemically induced , Rituximab
10.
Scand J Rheumatol ; 39(1): 93-6, 2010.
Article in English | MEDLINE | ID: mdl-20132078

ABSTRACT

OBJECTIVE: Fractures occurring at the site of a tophus have rarely been described in gout. In this paper we review the occurrence, clinical features, and outcome of fractures in tophaceous gout. METHOD: A PubMed search was conducted to identify the relevant literature, following our experience with two patients who developed tophaceous fractures after minor or no trauma. RESULTS: A total of 13 patients were analysed. Eleven cases of tophaceous fracture have been reported since 1950. Common features are: known and long-standing gout with tophi; minor or absence of trauma; specific locations include seven patients with patella bone fractures. Other sites include the cervical spine in two patients, the first and fifth metatarsal, and a phalanx in one patient each, the ilium and pubic bones in one, the medial malleola, and the femoral neck in the latter case. CONCLUSIONS: Monosodium urate (MSU) crystals can contribute to bone lesions by reducing osteoblastic activity and are associated with enhanced osteoclast activity in the vicinity of tophi. Mild trauma triggers MSU crystal release from tophi, resulting in cell activation and production of cytokines and proteases. This could enhance bone erosion leading ultimately to bone fragility and fracture. Our cases exemplify a rare cause of spontaneous fracture. Gouty tophus should be considered when facing a lytic lesion with fracture.


Subject(s)
Ankle Injuries/etiology , Arthritis, Gouty/complications , Fractures, Spontaneous/etiology , Toes/injuries , Aged , Ankle Injuries/diagnostic imaging , Ankle Injuries/rehabilitation , Arthritis, Gouty/diagnostic imaging , Follow-Up Studies , Fractures, Spontaneous/diagnostic imaging , Fractures, Spontaneous/rehabilitation , Gout/complications , Gout/diagnosis , Humans , Immobilization/methods , Male , Radiography , Severity of Illness Index , Splints , Toes/diagnostic imaging , Treatment Outcome
11.
Ann Rheum Dis ; 67(11): 1617-25, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18218665

ABSTRACT

OBJECTIVES: Basic calcium phosphate (BCP) crystals (octacalcium phosphate (OCP), carbapatite (CA) and hydroxyapatite (HA)) are associated with severe forms of osteoarthritis. In advanced osteoarthritis, cartilage shows chondrocyte apoptosis, overexpression of annexin 5 (A5) and BCP crystal deposition within matrix vesicles. We assessed in vitro whether BCP crystals and overexpression of A5 increased chondrocyte apoptosis. METHODS: Apoptosis was induced by BCP crystals, tumour necrosis factor (TNF)-alpha (20 ng/ml) and Fas ligand (20 ng/ml) in normal articular chondrocytes (control) and in A5 overexpressed chondrocytes, performed by adenovirus infection. Apoptosis was assessed by caspase 3 (Cas3) activity, and DNA fragmentation. RESULTS: All BCP crystals, TNF-alpha and Fas ligand induced chondrocyte apoptosis as demonstrated by decreased cell viability and increased Cas3 activity and DNA fragmentation. TUNEL (terminal deoxyribonucleotide transferase-mediated dUTP nick end-labelling)-positive staining chondrocytes were increased by OCP (12.4 (5.2)%), CA (9.6 (2.6)%) and HA (9.2 (3.0)%) crystals and TNF-alpha (9.6 (2.4)%) stimulation compared with control (3.1 (1.9)%). BCP crystals increased Cas3 activity in a dose-dependent fashion. BCP-crystal-induced chondrocyte apoptosis was independent from TNF-alpha and interleukin-1beta pathways but required cell-crystal contact and intralysosomal crystal dissolution. Indeed, preincubation with ammonium chloride, a lysosomal inhibitor of BCP crystal dissolution, significantly decreased BCP-crystal-induced Cas3 activity. Finally, overexpression of A5 enhanced BCP crystal- and TNF-alpha-induced chondrocyte apoptosis. CONCLUSIONS: Overexpression of A5 and the presence of BCP crystals observed in advanced osteoarthritis contributed to chondrocyte apoptosis. Our results suggest a new pathophysiological mechanism for calcium-containing crystal arthropathies.


Subject(s)
Annexin A5/physiology , Apoptosis/drug effects , Calcium Phosphates/pharmacology , Cartilage, Articular/drug effects , Chondrocytes/drug effects , Animals , Annexin A5/metabolism , Apoptosis/physiology , Calcium Phosphates/metabolism , Cartilage, Articular/cytology , Cartilage, Articular/metabolism , Caspase 3/metabolism , Cattle , Cells, Cultured , Chondrocytes/metabolism , Crystallization , DNA Fragmentation , Tumor Necrosis Factor-alpha/physiology , Uric Acid/metabolism
12.
Clin Exp Rheumatol ; 26(6): 1083-6, 2008.
Article in English | MEDLINE | ID: mdl-19210874

ABSTRACT

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by hyperplasia of fibro-blast-like synoviocytes (FLSs), in part due to apoptosis resistance. Adrenomedullin, an anti-apoptotic peptide, is secreted more by RA than osteoarthritis FLSs. Adrenomedullin binds to a heterodimeric functional receptor, of calcitonin receptor-like receptor (CRLR) coupled with a receptor activity-modifying protein-2 (RAMP-2), which is also overexpressed by rheumatoid synoviocytes. Since adrenomedullin decreases RA FLS apoptosis, possibly contributing to the development of pannus, study of adrenomedullin and its receptor genes might reveal a linkage and association in French Caucasian RA trio families. METHODS: Within each of 100 families, one RA-affected patient and both parents underwent genotyping for polymorphisms of adrenomedullin, CRLR and RAMP-2, by PCR-restricted fragment-length polymorphism (RFLP) or Taqman 5' allelic discrimination assay. Statistical analysis relied on the transmission disequilibrium test, the affected family-based controls and the genotype relative risk. Haplotypes of CRLR were inferred, and linkage and association studies were performed. RESULTS: No significant transmission disequilibrium or association between the three genes and RA was observed. CRLR haplotypes revealed two major haplotypes, but no significant linkage with RA. CONCLUSION: Our findings provided no significant linkage or association of adrenomedullin and CRLR-RAMP-2 genes with RA in the studied trio families. The two CRLR polymorphisms rs3771076 and rs3771084 should be investigated in larger samples.


Subject(s)
Adrenomedullin/genetics , Arthritis, Rheumatoid/ethnology , Arthritis, Rheumatoid/genetics , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Receptors, Calcitonin/genetics , Adult , Calcitonin Receptor-Like Protein , Family Health , Female , France/epidemiology , Genetic Predisposition to Disease/ethnology , Haplotypes , Humans , Linkage Disequilibrium , Male , Polymorphism, Restriction Fragment Length , Receptor Activity-Modifying Proteins , Risk Factors , White People/statistics & numerical data , Young Adult
13.
Clin Rheumatol ; 35(4): 857-61, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26801332

ABSTRACT

Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor α (anti-TNFα) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 ≥ 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0-28.8) kg/m(2). The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1-29.9] vs 24.9 [22.0-27.1], P = 0.38), EULAR good response (25.9 [22.8-30.0] vs 25.4 [22.0-28.4], P = 0.61), and remission (25.1 [22.5-28.6] vs 25.4 [22.0-28.9], P = 0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Rheumatoid/drug therapy , Body Mass Index , Adult , Antirheumatic Agents/therapeutic use , Blood Sedimentation , Body Weight , C-Reactive Protein/metabolism , Female , Humans , Male , Middle Aged , Overweight , Remission Induction , Retrospective Studies , Tumor Necrosis Factor-alpha/metabolism
14.
Clin Exp Rheumatol ; 23(3): 303-10, 2005.
Article in English | MEDLINE | ID: mdl-15971417

ABSTRACT

OBJECTIVE: To determine the diagnostic value of serum and synovial procalcitonin (PCT) for bacterial arthritis and to determine the cellular origin of synovial PCT. METHODS: A prospective study enrolled 42 patients with acute arthritis including 11 bacterial arthritis, 18 rheumatoid arthritis and 13 crystal induced arthritis. Diagnostic values of serum and synovial PCT levels were determined by a immunoluminometric assay (Lumitest PCT) and compared to those of classical inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, synovial fluid cellularity and both serum and synovial IL-6 and TNF alpha). Using fibroblast-like synoviocyte (FLS) cultures derived from rheumatoid arthritis (n = 4) and osteo-arthritis (n = 3) synovium, with or without stimulation by lipopolysaccharid or recombinant streptococcal protein 1/II, we attempted to determine whether synovial cells could be a source of PCT. RESULTS: Serum PCT was the best parameter to distinguish patients with acute bacterial arthritis from patients with crystal induced arthritis or rheumatoid arthritis. In setting of an acute arthritis serum PCT (> 0.5 ng/mL) achieved 55% sensitivity and 94% specificity for the diagnosis of bacterial arthritis, while CRP (> 50 mg/L) had 100% sensitivity but poor specificity (40%). Serum PCT appeared to be higher in patients with septic arthritis resulting from "systemic infection" than in cases resulting from direct inoculation. Synovial PCT was not useful to discriminate between infectious and non infectious arthritis in clinical practice. PCT could not be detected at significant levels in the conditioned medium from fibroblast-like synoviocyte cultures. CONCLUSION: Serum PCT is a poorly sensitive but specific marker of bacterial arthritis. Use of serum PCT in association with CRP could nevertheless be useful in an emergency situation for the diagnosis of bacterial arthritis.


Subject(s)
Arthritis/diagnosis , Calcitonin/blood , Chemistry, Clinical/methods , Protein Precursors/blood , Rheumatology/methods , Synovial Membrane/metabolism , Acute Disease , Aged , Arthritis/blood , Calcitonin Gene-Related Peptide , Cells, Cultured , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Lipopolysaccharides/pharmacology , Male , Middle Aged , Prospective Studies , ROC Curve , Synovial Membrane/pathology
15.
Arthritis Rheumatol ; 67(8): 2176-84, 2015 May.
Article in English | MEDLINE | ID: mdl-25989906

ABSTRACT

OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Antirheumatic Agents/pharmacokinetics , Hydroxychloroquine/pharmacokinetics , Lupus Erythematosus, Systemic/drug therapy , Adult , Antirheumatic Agents/blood , Antirheumatic Agents/therapeutic use , Body Mass Index , Creatinine/blood , Female , Humans , Hydroxychloroquine/blood , Hydroxychloroquine/therapeutic use , Leukocyte Count , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/complications , Male , Middle Aged , Multivariate Analysis , Neutrophils/cytology , Obesity/complications , Renal Insufficiency, Chronic/complications , Retrospective Studies , Thrombocytopenia , Time Factors , Young Adult
16.
Clin Pharmacol Ther ; 44(4): 442-52, 1988 Oct.
Article in English | MEDLINE | ID: mdl-2901930

ABSTRACT

The reciprocal effects on pharmacokinetic parameters after a single oral dose of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and sulindac and repeated oral doses of the H2-receptor antagonists cimetidine and ranitidine were determined in two groups of nine healthy subjects each (indomethacin and sulindac groups). Administration of NSAIDs increased the AUC and decreased the oral clearance and apparent volume of distribution of the H2-receptor antagonists without modifying their t1/2. Urinary data and observed modifications in ranitidine and cimetidine metabolites seem to justify a greater increase of H2-receptor antagonist bioavailability with indomethacin (p less than 0.05) than with sulindac (NS). The administration of ranitidine significantly reduced the sulindac volume of distribution without modifying its clearance, which caused an increase in the maximum concentration and a decrease in the t1/2 (p less than 0.05). The effects of cimetidine on the two NSAIDs were more intense than the effect of ranitidine: the decrease in sulindac volume of distribution (p less than 0.02) was accompanied by a significant reduction in sulindac clearance (p less than 0.05). AUC and urinary amounts of sulindac's sulfone metabolite were decreased. These results show that NSAIDs increased the bioavailability of H2-receptor antagonists, and that the latter drugs decrease the volume of distribution of NSAIDs. Furthermore, cimetidine modifies the oxidation metabolism of sulindac.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Histamine H2 Antagonists/pharmacokinetics , Adult , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Biological Availability , Cimetidine/pharmacokinetics , Drug Interactions , Humans , Indomethacin/pharmacology , Male , Ranitidine/pharmacokinetics , Sulindac/pharmacology
17.
Medicine (Baltimore) ; 78(5): 309-20, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10499072

ABSTRACT

Spinal tuberculosis (TB) accounts for about 2% of all cases of TB. New methods of diagnosis such as magnetic resonance imaging (MRI) or percutaneous needle biopsy have emerged. Two distinct patterns of spinal TB can be identified, the classic form, called spondylodiscitis (SPD) in this article, and an increasingly common atypical form characterized by spondylitis without disk involvement (SPwD). We conducted a retrospective study of patients with spinal TB managed in the area of Paris, France, between 1980 and 1994 with the goal of defining the characteristics of spinal TB and comparing SPD to SPwD. The 103 consecutive patients included in our study had TB confirmed by bacteriologic and/or histologic studies of specimens from spinal or paraspinal lesions (93 patients) or from extraspinal skeletal lesions (10 patients). Sixty-eight percent of patients were foreign-born subjects from developing countries. None of our patients was HIV-positive. SPD accounted for 48% of cases and SPwD for 52%. Patients with SPwD were younger and more likely to be foreign-born and to have multiple skeletal TB lesions. Neurologic manifestations were observed in 50% of patients, with no differences between the SPD and SPwD groups. Of the 44 patients investigated by MRI, 6 had normal plain radiographs; MRI was consistently positive and demonstrated epidural involvement in 77% of cases. Bacteriologic and histologic yields were similar for surgical biopsy (n = 16) and for percutaneous needle aspiration and/or biopsy (n = 77). Cultures for Mycobacterium tuberculosis were positive in 83% of patients, and no strains were resistant to rifampin. Median duration of antituberculous chemotherapy was 14 months. Surgical treatment was performed in 24% of patients. There were 2 TB-related deaths. Our data suggest that SPwD may now be the most common pattern of spinal TB in foreign-born subjects in industrialized countries. The reasons for this remain to be elucidated.


Subject(s)
Tuberculosis, Spinal/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antibiotics, Antitubercular/therapeutic use , Biopsy, Needle , Cause of Death , Developed Countries/statistics & numerical data , Developing Countries/statistics & numerical data , Discitis/epidemiology , Discitis/microbiology , Emigration and Immigration/statistics & numerical data , Female , France/epidemiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Paris/epidemiology , Retrospective Studies , Rifampin/therapeutic use , Spondylitis/epidemiology , Spondylitis/microbiology , Tuberculosis, Osteoarticular/epidemiology , Tuberculosis, Spinal/drug therapy , Tuberculosis, Spinal/surgery
18.
Am J Med ; 90(1): 111-7, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1986577

ABSTRACT

A 61-year-old man presented with ascites in the course of agnogenic myeloid metaplasia (AMM). Ascitic fluid was exudative and contained mature and immature leukocytes, erythroid cells, and megakaryocytes as observed on a bone marrow smear. Peritoneal biopsy showed myeloid metaplasia, and liver biopsy revealed intrasinusoidal myeloid metaplasia and peliosis. Ascites cleared after abdominal radiotherapy but treatment resulted in transient aplasia. Subsequently, portal hypertension was demonstrated by hepatic transjugular catheterization. Complications of splenomegaly led to splenectomy and splenorenal shunt followed by fatal acute hepatitis and septic shock. A review of the literature and an analysis of mechanisms of ascites occurring in AMM, especially peritoneal implants of myeloid tissue and occurrence of peliosis in myeloproliferative disorders, are presented.


Subject(s)
Ascites/etiology , Hematopoiesis, Extramedullary , Peliosis Hepatis/complications , Primary Myelofibrosis/complications , Adult , Humans , Liver/physiopathology , Male , Middle Aged , Peritoneum/physiopathology , Primary Myelofibrosis/physiopathology
19.
Semin Arthritis Rheum ; 29(6): 360-7, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10924021

ABSTRACT

OBJECTIVE: Malignancies are among the well-established causes of vasculitis. We studied the association between adult Henoch-Schonlein purpura (HSP) and malignant neoplasms. METHODS: We retrospectively reviewed 14 cases of adult HSP diagnosed during a 6-year period and found a malignant neoplasm in four. Fifteen reports of adult HSP with malignant disease were identified in the literature. These 19 cases were compared with 158 adults who had HSP but no malignancy and who where reported in the literature. RESULTS: Most (63%) of the malignant neoplasms associated with adult HSP were solid tumors: lung, n = 6; prostate, n = 2; breast, n = 1; renal, n = 1; stomach, n = 1; and small bowel, n = 1. Hematologic malignancies (37%) included non-Hodgkin lymphoma, n = 2; Hodgkin disease, n = 2; IgA multiple myeloma, n = 1; myeloproliferative disease, n = 1; and myelodysplastic syndrome, n = 1. Patients with malignancy were older (median age, 59 years), were more likely to be male (M/F = 8.5), had joint involvement more frequently (95%), and had a lower frequency of prior acute infection than those without malignancy. A typical paraneoplastic course was documented in only two cases. CONCLUSIONS: Epidemiological studies are needed to determine the association between adult HSP and malignancy. In practice, it may be wise to suspect a malignancy in men older than 40 years of age who develop HSP in the absence of a precipitating factor. Pathogenic hypotheses involve tumor antigens or abnormal IgA production leading to immune complex formation.


Subject(s)
IgA Vasculitis/complications , Neoplasms/complications , Adult , Aged , Female , Humans , Male , Middle Aged , Paraneoplastic Syndromes/complications , Retrospective Studies
20.
Chest ; 97(2): 495-8, 1990 Feb.
Article in English | MEDLINE | ID: mdl-2298082

ABSTRACT

A 79-year-old man was given a cumulative dose of 16.5 g of nilutamide for treatment of prostate cancer. He then presented with a respiratory illness having clinical, radiologic and functional characteristics of interstitial pneumonitis. No other cause of pneumonitis was found. Bronchoalveolar lavage showed a lymphocytic alveolitis with an inverted lymphocyte subset ratio. After an 11-week period of drug withdrawal, clinical, radiologic and functional improvement was observed along with a normal alveolar lymphocytosis. Nilutamide therapy was then resumed for five weeks and induced the recurrence of clinical, functional and alveolar abnormalities. Nilutamide treatment was finally stopped and two months later, clinical and functional abnormalities resolved. This observation seems to exemplify the possible diagnostic value of coupling provocation test with BAL cell data in hypersensitivity pneumonitis induced by drugs. In addition, these data support the role of a cell-mediated immunologic mechanism in the pathogenesis of nilutamide-induced pneumonitis.


Subject(s)
Alveolitis, Extrinsic Allergic/chemically induced , Antineoplastic Agents/adverse effects , Imidazoles/adverse effects , Imidazolidines , Aged , Alveolitis, Extrinsic Allergic/diagnosis , Antineoplastic Agents/therapeutic use , Bronchoalveolar Lavage Fluid/cytology , Humans , Imidazoles/therapeutic use , Male , Prostatic Neoplasms/drug therapy
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