Josiane Bourré-Tessier

Methotrexate Drug Interactions in the Treatment of Rheumatoid Arthritis: A Systematic Review

Objective. Patients with rheumatoid arthritis (RA) often have comorbidities that require multiple medications. Several of these medications may alter the efficacy or increase the toxicity of methotrexate (MTX). The purpose of our study was to determine which drugs used in combination with MTX (excluding disease modifying antirheumatic drugs, folic and folinic acid, corticosteroids, and biologic agents) enhance side effects or toxicity of MTX or lower its efficacy. Methods. A systematic literature search was performed with Medline, Embase, Cochrane Register and Database, and abstracts from the 2006/2007 annual congresses of the American College of Rheumatology and the European League Against Rheumatism. A manual search of the citation lists of retrieved publications was performed. Results. Of the 1172 articles identified, 67 were included: 21 pharmacokinetics studies, 5 observational studies, and 78 case reports. Most medications do not significantly affect the pharmacokinetics profile of MTX. Among the clinical studies, cytopenia and elevation of liver enzymes were the main reported toxicities. The use of trimethoprim-sulfamethoxazole (TMP-SMX) was mentioned as a risk factor for developing cytopenia in one observational study and in 17 case reports. Thirty case reports of cytopenia were attributed to the use of concomitant nonsteroidal antiinflammatory drugs, including acetylsalicylic acid. Two studies described mild abnormalities of liver enzymes with the use of isoniazid, and one study with the use of high-dose ASA. Conclusion. Based on the published literature, MTX has limited drug interactions, with the exception of TMP-SMX and high-dose ASA, which can exacerbate toxicity of MTX. The clinical significance of these interactions has not been substantiated by extensive clinical observations.

Association of Smoking With Cutaneous Manifestations in Systemic Lupus Erythematosus

To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE).

Prolonged corrected QT interval in anti-Ro/SSA–positive adults with systemic lupus erythematosus

To examine whether anti‐Ro/SSA antibodies are associated with an increased risk of corrected QT (QTc) prolongation, and to study the stability of this relationship over time.

Redefining Dermatomyositis: A Description of New Diagnostic Criteria That Differentiate Pure Dermatomyositis From Overlap Myositis With Dermatomyositis Features

AbstractDermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM.Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival.Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%).In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%).Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM.In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM.

Canadian Recommendations for Use of Methotrexate in Patients with Rheumatoid Arthritis

Objective. To develop recommendations for the use of methotrexate (MTX) in patients with rheumatoid arthritis. Methods. Canadian rheumatologists who participated in the international 3e Initiative in Rheumatology (evidence, expertise, exchange) in 2007–2008 formulated 5 unique Canadian questions. A bibliographic team systematically reviewed the relevant literature on these 5 topics. An expert committee consisting of 26 rheumatologists from across Canada was convened, and a set of recommendations was proposed based on the results of systematic reviews combined with expert opinions using a nominal group consensus process. Results. The 5 questions addressed drug interactions, predictors of response, strategies to reduce non-serious side effects, variables to assess clinical response, and incorporating patient preference into decision-making. The systematic review retrieved 93 pertinent articles; this evidence was presented to the expert committee during the interactive workshop. After extensive discussion and voting, a total of 9 recommendations were formulated: 2 on drug interactions, 1 on predictors of response, 2 on strategies to reduce non-serious side effects, 3 on variables to assess clinical response, and 1 on incorporating patient preferences into decision-making. The level of evidence and the strength of recommendations are reported. Agreement among panelists ranged from 85% to 100%. Conclusion. Nine recommendations pertaining to the use of MTX in daily practice were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement.

Features associated with cardiac abnormalities in systemic lupus erythematosus

Objectives. To determine the prevalence of echocardiographic abnormalities and identify associated clinical and laboratory features in a large systemic lupus erythematosus (SLE) cohort. Methods. Patients fulfilling ACR criteria for SLE underwent a transthoracic echocardiogram (TTE) between January 2005 and June 2006. Variables used as potential correlates included age, sex, ethnicity, lupus duration, lupus disease activity (SLEDAI), cumulative damage (SLICC/ACR damage index (DI)), arterial hypertension, diabetes, current smoking, medication use and laboratory data. Multivariate logistic regression was used to examine the association between TTE abnormalities and potential determinants. Results. For the 217 subjects with a TTE performed during the study, the main abnormalities were of the mitral valve (37.3%) and included thickening (25.4%) and insufficiency (25.8%). Other findings included pulmonary artery pressure (PAP) ≥ 30 mm Hg (10.1%), pericardial effusion (4.6%), hypokinesis (2.8%), and aortic insufficiency (3.7%). In multivariate analysis, mitral insufficiency was associated with the use of corticosteroids (OR 2.90; 95%CI 1.42–5.94) and hypokinesis with angiotensin-converting enzyme inhibitors (12.89; 1.06–157.18). Elevated PAP was associated with age (1.04; 1.01–1.07) and with DI (1.20; 1.01–1.42). Conclusion. Valvular abnormalities are frequent in patients with SLE, with mitral valve lesions occurring in over one third. TTE screening may be indicated in patients with SLE, especially for those with identified risk factors such as corticosteroid use.

Electrocardiographic Findings in Systemic Lupus Erythematosus: Data From an International Inception Cohort

To estimate the early prevalence of various electrocardiographic (EKG) abnormalities in patients with systemic lupus erythematosus (SLE) and to evaluate possible associations between repolarization changes (increased corrected QT [QTc] and QT dispersion [QTd]) and clinical and laboratory variables, including the anti‐Ro/SSA level and specificity (52 or 60 kd).

Cross-cultural Validation of a Disease-specific Patient-reported Outcome Measure for Systemic Lupus Erythematosus in Canada

Objective. The LupusPRO, a disease-targeted patient-reported outcome measure, was developed and validated in US patients with systemic lupus erythematosus (SLE). We report the results of the cross-cultural validation study of the English version of the LupusPRO among patients in Canada with SLE. Method. The LupusPRO was administered to English-speaking Canadian patients with SLE. Demographic, clinical, and serological characteristics were obtained, and the Medical Outcomes Study Short Form-36 (SF-36) and LupusPRO were administered. Disease activity was ascertained using the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the Lupus Foundation of America definition of flare (Yes/No). Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Physician disease activity and damage assessments were also ascertained using visual analog scales. A mail-back LupusPRO form was completed within 2–3 days of the index visit. Items tested were internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity or health status), and known-groups validity. Results. Participants were 123 Canadian patients with SLE (94% women); mean age was 47.7 (SD 14.8) years. The median (interquartile range) SELENA-SLEDAI and SDI were 4 (6) and 1 (3), respectively. The ICR of the LupusPRO domains ranged from 0.60 to 0.93, while the TRT range was 0.62–0.95. Measures observed were convergent and discriminant validity with corresponding domains of SF-36, criterion validity, and known-groups validity against disease activity, damage, and health status. Confirmatory factor analysis showed a good fit. Conclusion. The LupusPRO has fair psychometric properties among Canadian patients with SLE, and prospective studies to establish minimally important difference are continuing.

The French-Canadian validation of a disease-specific, patient-reported outcome measure for lupus.

Objectives The objective of this paper is to perform the cross-cultural validation of the French version of the LupusPRO, a disease-targeted patient-reported outcome measure, among systemic lupus erythematosus (SLE) patients in Canada. Methods The French version of the LupusPRO and the MOS SF-36 were administered; demographic, clinical and serological characteristics were obtained. Disease activity (SELENA-SLEDAI and the Lupus Foundation of America definition of flare) and damage (SLICC/ACR SDI) were assessed. Physician disease activity and damage assessments were ascertained using visual analog scales. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity, damage or health status) and known group validity were tested. Results A total of 99 French-Canadian SLE patients participated (97% women, mean (SD) age 45.2 (14.5) years). The median (IQR) SELENA-SLEDAI and SDI were 3.5 (6.0) and 1.0 (2.0), respectively. The ICR of the LupusPRO domains ranged from 0.81 to 0.93 (except for lupus symptoms, procreation and coping), while TRT ranged from 0.72 to 0.95. Convergent and discriminant validity, criterion validity and known group validity against disease activity, damage and health status measures were observed. Confirmatory factor analysis showed a good fit. Conclusion The LupusPRO has fair psychometric properties among French-Canadian patients with SLE.

Indigenous Lyme disease in Quebec.

To the Editor: Lyme disease is caused by the bacterium Borrelia burgdorferi , which is transmitted by ticks feeding on infected animals, mainly rodents and birds. Ixodes scapularis , also known as the blacklegged tick, is the most common vector in eastern North America1. Humans can acquire the pathogen when an infected tick feeds on them. Lyme disease was first recognized in the late 1970s in Connecticut, USA, where an epidemic of oligoarthritis occurred2. In the following years, expanding populations of I. scapularis were identified in northeastern and midwestern American states3. In the early 1990s, only one population of I. scapularis was documented in Canada, located in Ontario1. Since then, 13 established populations of I. scapularis have been progressively identified in Canada3. Recent evidence suggests that the risk of exposure to Lyme disease is increasing in the province of Quebec1,3,4. Studies indicate that I. scapularis is establishing itself in southern regions, near … Address correspondence to Dr. J. Bourre-Tessier, Division of Rheumatology, McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4. E-mail: josiane.bourre.tessier{at}umontreal.ca