Myositis-Specific Antibodies and Myositis-Associated Antibodies in Patients With Idiopathic Inflammatory Myopathies From the PANLAR Myositis Study Group.

BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) are forms of idiopathic inflammatory myopathies (IIMs), which are associated with the production of autoantibodies that are useful in the diagnosis and prognosis of the disease. OBJECTIVE: The aim of this study was to determine the frequency of antinuclear autoantibodies (ANAs), myositis-specific autoantibodies (MSAs), and myositis-associated autoantibodies (MAAs) in 6 Latin American countries. METHODS: Two hundred ten patients with IIM were included in this cross-sectional study from 2014 to 2017: 112 from Mexico, 46 from Colombia, 20 from Peru, 16 from the Dominican Republic, 10 from Argentina, and 6 from Guatemala. Antinuclear autoantibodies were detected by indirect immunofluorescence on HEp-2 cells. MSAs and MAAs were tested by a line immunoassay method. Mann-Whitney U and χ2 tests were used for statistical analysis. RESULTS: Of the 210 IIM patients, 139 (66.2%) had DM, 59 (28%) PM, and 12 (5.7%) juvenile DM. The mean age was 43.5 (6-79 years); 158 (75.2%) were female, and 52 (24.8%) were male. The overall frequency of ANA was 60%. The most frequent patterns were fine speckled (AC-4) (78.3%) and cytoplasmic (AC-19) (6.45%). The most frequent MSA were anti-Mi-2 (38.5%) and anti-Jo-1 (11.9%). Anti-Mi-2 was more frequent in patients from Colombia (40.1%). The MAA more frequent were anti-Ro-52/TRIM21 (17.6%) and anti-PM-Scl75 (7.5%). CONCLUSIONS: This is the first study of ANA, MSA, and MAA in patients from 6 countries from the Panamerican League against Rheumatism myositis study group. We observed a general prevalence of 60% of ANA. In relation to MSA and MAA, anti-Mi-2 was the more frequent (38.5%).

Autoantibodies to Mi-2 alpha and Mi-2 beta in patients with idiopathic inflammatory myopathy.

OBJECTIVES: The objective of this study was to compare the results obtained from different assays for the detection of anti-Mi-2 antibodies, which are important markers in the diagnosis of DM. METHODS: The study included 82 patients (68 females/14 males), most of whom had DM (n = 57), followed by PM (n = 16) and juvenile DM (n = 9). All samples were tested using a novel particle-based multi-analyte technology (PMAT) (Inova Diagnostics, research use only) in parallel with a line immunoassay (LIA: Euroimmun). To assess clinical specificity for the PMAT assay, a total of 775 disease and healthy controls were tested. RESULTS: 29 samples were positive by at least one test for anti-Mi-2 antibodies. Of those, 24 were Mi-2ß LIA+, five were Mi-2α LIA+ and 23 Mi-2 PMAT+. The comparison shows varying agreement between the different methods (kappa 0.27-0.77). When LIA results were used as reference for receiver operating characteristics analysis, high area under the curve values were found for both PMAT vs LIA Mi-2α and LIA Mi-2ß. When analysing the results in the context of the myositis phenotype, PMAT associated closest with the DM phenotype. In the control group, 3/775 controls (all low levels) were anti-Mi-2+ resulting in a sensitivity and specificity of 28.1% and 99.6%, respectively. CONCLUSION: Overall, good agreement was found between LIA and PMAT for anti-Mi-2 antibodies, which is important for the standardization of autoantibodies. Anti-Mi-2ß antibodies measured by PMAT tend be more highly associated with the clinical phenotype of DM.

The economic burden of systemic lupus erythematosus in Mexico.

AIMS: Our cost of illness study aimed to provide an estimate of the burden related to systemic lupus erythematosus (SLE) in the Mexican context. METHODS: Our model was used to simulate the resource utilization and economic consequences over a period of 5 years for patients with SLE in Mexico. The model simulated four health states-three phenotypes of SLE, including mild, moderate, and severe states, and death. Clinical parameters were retrieved from the literature. Resource utilization in our model represents the most common practice in the Mexican healthcare system. These include disease management, transient events (e.g. infections, flares, and complications due to SLE-related organ damage), and indirect costs. Direct non-medical costs were not considered. One-way sensitivity analysis was performed. RESULTS: The number of targeted Mexican SLE patients was 57,754. The numbers of SLE patients diagnosed with mild, moderate, and severe phenotypes were 8,230, 44,291, and 5,233, respectively. Disease management costs, including the treatment of each phenotype and disease follow-up, were MXN 4 billion ($ 415 million); the costs of transient events (infections, flares, and consequences of SLE-related organ damage) were MXN 5 billion ($ 478 million). Productivity loss costs among adult employed Mexican patients with SLE were estimated at MXN 17 billion ($ 1.6 billion). The total SLE cost in Mexico over 5 years from the payer and societal perspectives is estimated at MXN 9 billion ($ 893 million) and 26 billion ($ 2.5 billion), respectively. Over 5 years, the costs per patient per year from the payer and societal perspectives were MXN 32,131($ 3,095) and MXN 91,661($ 8,830), respectively. CONCLUSION: The findings pointed out the substantial economic burden associated with SLE, including the costs of disease progression and SLE transient events, such as flare-ups, infections, and organ damage, in addition to productivity loss due to work capacity impairment.

Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

Geographical Latitude Remains as an Important Factor for the Prevalence of Some Myositis Autoantibodies: A Systematic Review.

The idiopathic inflammatory myopathies (IIM) are characterized by muscular weakness, cutaneous manifestations, muscle damage revealed by increase of muscular enzymes, muscle biopsy, electromyography and changes on magnetic resonance imaging. However, the hallmark of these IIM, is the development of myositis specific antibodies (MSA) or myositis associated antibodies (MAA). The theories about their presence in the serum of IIM is not known. Some studies have suggested that some of these MSA, such as anti-Mi-2 increases according to the intensity of UV radiation. There is scarce information about the environmental factors that might contribute in order to be considered as triggering factors as UV radiation might be. In this review, we analyzed the reported prevalence of MSAs and MAAs regarding to their geographical location and the possible relation with UV radiation. We collected the prevalence data of fifteen MSA and thirteen MAA from 22 countries around the world and we were able to observe a difference in prevalence between countries and continents. We found differences in anti-PL7, anti-Ro52, anti-La and anti-Ku prevalence according to UV radiation level. Otherwise, we observed that anti-Mi-2 prevalence increases near to the Equator meanwhile anti-MJ/NXP2 and anti-ARS prevalence had an opposite behavior increasing their prevalence in the geographical locations farther to the Equator. Our results highlighted the importance to include the UV radiation and other environmental factors in IIM studies, in order to clarify its association with MSA and MAA prevalence as well as its possible role in the immunopathogenesis of these diseases.

Clinical practice guidelines for the treatment of systemic lupus erythematosus by the Mexican College of Rheumatology. / Guía de práctica clínica para el manejo del lupus eritematoso sistémico propuesta por el Colegio Mexicano de Reumatología.

There are national and international clinical practice guidelines for systemic lupus erythematosus treatment. Nonetheless, most of them are not designed for the Mexican population or are devoted only to the treatment of certain disease manifestations, like lupus nephritis, or are designed for some physiological state like pregnancy. The Mexican College of Rheumatology aimed to create clinical practice guidelines that included the majority of the manifestations of systemic lupus erythematosus, and also incorporated guidelines in controversial situations like vaccination and the perioperative period. The present document introduces the «Clinical Practice Guidelines for the Treatment of Systemic Lupus Erythematosus¼ proposed by the Mexican College of Rheumatology, which could be useful mostly for non-rheumatologist physicians who need to treat patients with systemic lupus erythematosus without having the appropriate training in the field of rheumatology. In these guidelines, the reader will find recommendations on the management of general, articular, kidney, cardiovascular, pulmonary, neurological, hematologic and gastrointestinal manifestations, and recommendations on vaccination and treatment management during the perioperative period.

Correction to: Clinical predictors of remission and low disease activity in Latin American early rheumatoid arthritis: data from the GLADAR cohort.

The original version of this article, unfortunately, contained an error. The first and family name of Loreto Massardo was interchanged and is now presented correctly in this article.

Clinical predictors of remission and low disease activity in Latin American early rheumatoid arthritis: data from the GLADAR cohort.

OBJECTIVES: To identify baseline predictors of remission and low disease activity (LDA) in early rheumatoid arthritis (RA) from the GLADAR (Grupo Latino Americano De estudio de la Artritis Reumatoide) cohort. METHODS: Patients with 1- and 2-year follow-up visits were included. Remission and LDA were defined by DAS28-ESR (< 2.6 and ≤ 3.2, respectively). Baseline predictors examined were gender, ethnicity, age at diagnosis, socioeconomic status, symptoms' duration, DMARDs, RF, thrombocytosis, anemia, morning stiffness, DAS28-ESR (and its components), HAQ-DI, DMARDs and corticosteroid use, and Sharp-VDH score. Multivariable binary logistic regression models (excluding DAS28-ESR components to avoid over adjustment) were derived using a backward selection method (α-level set at 0.05). RESULTS: Four hundred ninety-eight patients were included. Remission and LDA/remission were met by 19.3% and 32.5% at the 1-year visit, respectively. For the 280 patients followed for 2 years, these outcomes were met by 24.3% and 38.9%, respectively. Predictors of remission at 1 year were a lower DAS28-ESR (OR 1.17; CI 1.07-1.27; p = 0.001) and HAQ-DI (OR 1.48; CI 1.04-2.10; p = 0.028). At 2 years, only DAS28-ESR (OR 1.40; CI 1.17-1.6; p < 0.001) was a predictor. Predictors of LDA/remission at 1 year were DAS28-ESR (OR 1.42; CI 1.26-1.61; p < 0.001), non-use of corticosteroid (OR 1.74; CI 1.11-2.44; p = 0.008), and male gender (OR 1.77; CI 1.2-2.63; p = 0.036). A lower baseline DAS28-ESR (OR 1.45; CI 1.23-1.70; p < 0.001) was the only predictor of LDA/remission at 2 years. CONCLUSIONS: A lower disease activity consistently predicted remission and LDA/remission at 1 and 2 years of follow-up in early RA patients from the GLADAR cohort. Key Points • In patients with early RA, a lower disease activity at first visit is a strong clinical predictor of achieving remission and LDA subsequently. • Other clinical predictors of remission and LDA to keep in mind in these patients are male gender, non-use of corticosteroids and low disability at baseline. • Not using corticosteroids at first visit is associated with a lower disease activity and predicts LDA/remission at 1 year in these patients.

Detection of autoantibodies to DSF70/LEDGFp75 in Mexican Hispanics using multiple complementary assay platforms.

PURPOSE: Antinuclear autoantibodies (ANA) targeting the dense fine speckled antigen DFS70, also known as lens epithelium-derived growth factor p75 (LEDGF/p75), are attracting attention due to their low frequency in systemic rheumatic diseases but increased frequency in clinical laboratory referrals and healthy individuals (HI). These ANA specifically recognize the stress protein DFS70/LEDGFp75, implicated in cancer, HIV-AIDS, and inflammation. While their frequency has been investigated in various ethnic populations, there is little information on their frequency among Hispanics/Latinos. In this study, we determined the frequency of anti-DFS70/LEDGFp75 autoantibodies in Mexican Hispanics using multiple detection platforms. METHODS: The frequency of anti-DFS70/LEDGFp75 antibodies was determined in 171 individuals, including 71 dermatomyositis (DM) patients, 47 rheumatoid arthritis (RA) patients, 30 obesity (OB) patients, and 23 HI. Antibody detection was achieved using four complementary assay platforms: indirect immunofluorescence, Western blotting, ELISA, and chemiluminescent immunoassay. RESULTS: We detected relatively low frequencies of anti-DFS70/LEDGFp75 antibodies in patients with DM (1.4%), RA (4.3%), and OB (6.6%), and elevated frequency (17.4%) in HI. A strong concordance between the different antibody detection platforms was observed. CONCLUSIONS: The low frequency of anti-DFS70/LEDGFp75 antibodies in Mexican patients with rheumatic diseases, but relatively higher frequency in HI, is consistent with previous observations with non-Hispanic populations, suggesting that geographic differences or ethnicity do not influence the frequency of these autoantibodies. Our results also highlight the importance of confirmatory assays for the accurate detection of these autoantibodies. Future studies with larger cohorts of healthy Hispanics/Latinos are needed to confirm if their anti-DFS70/LEDGFp75 antibody frequencies are significantly higher than in non-Hispanics.

Performance of an objective structured clinical examination in a national certification process of trainees in rheumatology.

OBJECTIVE: To assess reliability and validity of the objectively-structured clinical examination (OSCE) applied in postgraduate certification processes by the Mexican Board of Rheumatology. METHOD: Thirty-two (2013) and 38 (2014) Rheumatology trainees (RTs) underwent an OSCE consisting of 12 and 15 stations respectively, scored according to a validated check-list, as well as 300-multiple-choice 300 question examination (MCQ). Previously, 3 certified rheumatologists underwent a pilot-OSCE. A composite OSCE score was obtained for each participant and its performance examined. RESULTS: In 2013, OSCE mean score was 7.1±0.6 with none RT receiving a failing score while the MCQ score was 6.5±0.6 and 7 (21.9%) RTs receiving a failing (< 6) score. In 2014, the OSCE score was 6.7±0.6, with 3 (7.9%) RTs receiving a failing score (2 of them also failed MCQ) while the MCQ score was 6.4±0.5 and 7 (18.5%) RTs were disqualified (2 of them also failed OSCE). A significant correlation between the MCQ and the OSCE scores was observed in the 2013 (r=0.44; P=0.006). Certified rheumatologists performed better than RTs at both OSCE. Overall, 86% of RTs obtaining an OSCE passing score also obtained a MCQ passing score, while this was only 67% (P=.02) among those who obtained an OSCE failing score. Nine stations were applied at both consecutive years. Their performance was similar in both certification processes, with correlation coefficients ranging from 0.81 to 0.95 (P≤0.01). CONCLUSION: The OSCE is a valid and reliable tool to assess the Rheumatology clinical skills in RTs.

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part I.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphospholipid antibody syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and grading of recommendations, internal validation by peers, and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The various panels answered the 37 questions related to maternal and fetal care in SLE, RA, and APS, as well as to the use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. We present the recommendations for pregnant women with SLE in this first part. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with SLE integrate the best available evidence for the treatment and follow-up of patients with these conditions.

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions.

Efficacy and tolerability of rituximab in patients with rhupus.

Rhupus in an infrequent disease in which an overlap between lupus eritematosus and rheumatoid arthritis exists. Joint manifestations are prominent and treatment with non biological DMARDs is not always satisfactory, so immunosupressors and biological agents have been tried. A prospective, open clinical study was done to evaluate efficacy and tolerability of rituximab in patients with Rhupus. The main objective was a change in DAS28 at 6 months and secondary objectives were a change in MEX-SLEDAI at 6 months, change in DAS28 and MEX-SLEDAI during follow up, steroid requirements and detection of adverse events. We included 9 women with a mean age of 43 years and disease duration of 10 years. A significant reduction in DAS28 was observed (from 5.73 at baseline to 3.02 at 6 months, P<.001). Improvement in DAS28 was maintained during follow up. At 6 months, 3 patients were in remission and 3 had low disease activity. MEX-SLEDAI diminished from 5 points at baseline to 1.22 at 6 months (P<.001). There was a negative correlation between clinical improvement and anti-CCP levels (r=-0,794, P=.011). Mean prednisone dose was reduced from 11.66mg/day at baseline to 0,55 and 1.11mg/day at 12 and 24 months. Treatment was well tolerated. In this study rituximab was effective not only for joint affection but also for other manifestations of the disease. We consider that this biological agent can be a good therapeutic option for patients with rhupus.

Implications in the difference of anti-Mi-2 and -p155/140 autoantibody prevalence in two dermatomyositis cohorts from Mexico City and Guadalajara.

INTRODUCTION: Autoantibodies and clinical manifestations in polymyositis/dermatomyositis (PM/DM) are affected by both genetic and environmental factors. The high prevalence of DM and anti-Mi-2 in Central America is thought to be associated with the high UV index of the area. The prevalences of autoantibodies and the clinical manifestations of PM/DM were evaluated comparing two cohorts in Mexico. METHODS: Ninety-five Mexican patients with PM/DM (66 DM, 29 PM; 67 Mexico City, 28 Guadalajara) were studied. Autoantibodies were characterized by immunoprecipitation using 35S-methionine labeled K562 cell extract. Clinical information was obtained from medical records. RESULTS: DM represented 69% of PM/DM and anti-Mi-2 was the most common autoantibody (35%), followed by anti-p155/140 (11%); however, anti-Jo-1 was only 4%. The autoantibody profile in adult-onset DM in Mexico City versus Guadalajara showed striking differences: anti-Mi-2 was 59% versus 12% (P = 0.0012) whereas anti-p155/140 was 9% versus 35% (P = 0.02), respectively. A strong association of anti-Mi-2 with DM was confirmed and when clinical features of anti-Mi-2 (+) DM (n = 30) versus anti-Mi-2 (-) DM (n = 36) were compared, the shawl sign (86% versus 64%, P < 0.05) was more common in the anti-Mi-2 (+) group (P = 0.0001). Levels of creatine phosphokinase (CPK) were higher in those who were anti-Mi-2 (+) but they responded well to therapy. CONCLUSIONS: Anti-Mi-2 has a high prevalence in Mexican DM and is associated with the shawl sign and high CPK. The prevalence of anti-Mi-2 and anti-p155/140 was significantly different in Mexico City versus Guadalajara, which have a similar UV index. This suggests roles of factors other than UV in anti-Mi-2 antibody production.

[Efficacy of rituximab versus cyclophosphamide in lupus patients with severe manifestations. A randomized and multicenter study]. / Eficacia de rituximab comparado con ciclofosfamida en pacientes con manifestaciones graves de lupus eritematoso generalizado. Estudio aleatorizado y multicéntrico.

UNLABELLED: There are no controlled studies that compare the efficacy of RTX with standard treatment, such as cyclophosphamide, in patients with systemic lupus erythematosus (SLE). OBJECTIVE: The objective of this study was to compare the efficacy of rituximab to that of cyclophosphamide in patients with severe manifestations of SLE. MATERIALS AND METHOD: This is a multicenter, randomized open and controlled trial in adults with a diagnosis of active SLE. Patients were randomized into two groups; group 1: treated with RTX and group 2: cyclophosphamide pulses with the same steroid scheme. We registered MEX-SLEDAI, steroid requirements and adverse events for 12 months. Descriptive and comparative statistic analysis was performed. RESULTS: 19 patients were included, 17 females, mean age 35.7±12.1 years and duration of disease 5.6 years (range 0.35 to 30.8 years). There were no differences at baseline regarding gender, age, duration of disease, previous treatments or disease activity between both groups. MEX-SLEDAI was reduced from 12 to 3 in group 1 and from 9 to 2 in group 2 (p=0.80). Nevertheless, patients treated with RTX had a faster improvement. There was no difference in the cumulative steroid dose. Both groups had significant reduction in antinuclear antibody levels and similar increase in C3 levels. Adverse events were similar in both groups. CONCLUSION: This comparative clinical study in patients with SLE shows that rituximab can be as useful as cyclophosphamide for severe manifestations, maybe showing a faster response. Adverse events were no different. Rituximab should be considered as an adequate alternative for this group of patients.

[Outcome measures]. / Instrumentos de evaluación.

Inflammatory myositis are rare and heterogeneous diseases. Most clinical and therapeutic studies differ in diagnostic and inclusion criteria as well as in improvement measures. Several collaborative study groups have recently developed and validated outcome measures for both activity and damage of these diseases. The broad use of these core set measures will result in standardized clinical studies, with more reliable results that will allow comparing between individual studies.

[Myopathies and malignancy]. / Miopatías y relación con el cáncer.

There is a greater risk of developing cancer among patients with inflammatory myositis, specifically dermatomyositis. This relationship was first described in 1916 by Sterz and has been corroborated in population based studies. This chapter describes clinical and serological characteristics of patients with myositis and cancer, as well as the most common malignancies and diagnostic and prognostic considerations in this group of patients.