Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast.

Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.

Calcinosis is associated with digital ischaemia in systemic sclerosis-a longitudinal study.

OBJECTIVE: To determine if ischaemia is a causal factor in the development of calcinosis in SSc. METHODS: Patients with SSc were assessed yearly. Physicians reported the presence of calcinosis, digital ischaemia (digital ulcers, digital necrosis/gangrene, loss of digital pulp on any digits and/or auto- or surgical digital amputation) and nailfold capillary dropout assessed using a dermatoscope. The number of digits with digital ischaemia was used as an assessment of the severity of digital ischaemia. SSc specific antibodies were detected with a line immunoassay. Multiple logistic regression and Cox proportional hazards models were generated to determine associations between calcinosis, digital ischaemia and capillary dropout. RESULTS: One thousand three hundred and five patients were included in this study, of whom 300 (23.0%) had calcinosis at study entry. In a cross-sectional multivariate analysis, at baseline, calcinosis was associated with digital ischaemia (odds ratio (OR) = 2.37, 95% CI: 1.66, 3.39), severity of ischaemia (OR = 1.12, 95% CI: 1.06, 1.18), capillary dropout (OR = 1.41, 95% CI: 1.05, 1.89), ACAs (OR = 1.68, 95% CI: 1.17, 2.43) and anti-RNA polymerase III antibodies (OR = 1.77, 95% CI: 1.08, 2.89). Current use of calcium channel blockers was inversely associated with the presence of calcinosis (OR = 0.70, 95% CI: 0.52, 0.96). Of the 805 patients with no calcinosis at study entry and at least one follow-up visit, 215 (26.7%) developed calcinosis during follow-up. Significant baseline predictors of the development of calcinosis in follow-up were digital ischaemia (hazard ratio (HR) = 1.82, 95% CI: 1.30, 2.54), capillary dropout (HR = 1.46, 95% CI: 1.08, 1.99), dcSSc (HR = 1.57, 95% CI: 1.11, 2.21), ACA (HR = 2.18, 95% CI: 1.50, 3.17) and anti-RNA polymerase III antibodies (HR = 2.58, 95% CI: 1.65, 4.04). CONCLUSION: Ischaemia may play a role in the development of calcinosis in SSc.

Guías de práctica clínica para la atención del embarazo en mujeres con enfermedades reumáticas autoinmunes del Colegio Mexicano de Reumatología. Parte I / Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part I

Antecedentes. El embarazo en mujeres con enfermedades reumáticas autoinmunes se asocia a diversas complicaciones maternofetales. El desarrollo de guías de práctica clínica con la mejor evidencia científica disponible puede ayudar a homogeneizar la atención en estas pacientes. Objetivos. Proporcionar recomendaciones respecto al control prenatal, el tratamiento y el seguimiento más efectivo de la mujer embarazada con lupus eritematoso (LES), artritis reumatoide (AR) y síndrome por anticuerpos antifosfolípidos (SAF). Metodología. Para la elaboración de las recomendaciones se conformaron grupos nominales de expertos y se realizaron consensos formales, búsqueda sistematizada de la información, elaboración de preguntas clínicas, elaboración y calificación de las recomendaciones, fase de validación interna por pares y validación externa del documento final teniendo en cuenta los criterios de calidad del instrumento AGREE II. Resultados. Los grupos de trabajo contestaron las 37 preguntas relacionadas con la atención maternofetal en LES, AR y SAF, así como de fármacos antirreumáticos durante el embarazo y la lactancia. Las recomendaciones fueron discutidas e integradas en un manuscrito final y se elaboraron los algoritmos correspondientes. En esta primera parte se presentan las recomendaciones para mujeres embarazadas con LES. Conclusiones. La guía mexicana de práctica clínica para la atención del embarazo en mujeres con LES proporciona recomendaciones e integra la mejor evidencia disponible para el tratamiento y el seguimiento de estas pacientes (AU)

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 (AU)

Guías de práctica clínica para la atención del embarazo en mujeres con enfermedades reumáticas autoinmunes del Colegio Mexicano de Reumatología. Parte II / Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II

Antecedentes. El embarazo en mujeres con enfermedades reumáticas autoinmunes se asocia a diversas complicaciones materno-fetales. El desarrollo de guías de práctica clínica con la mejor evidencia científica disponible puede ayudar a homogeneizar la atención en estas pacientes. Objetivos. Proporcionar recomendaciones respecto al control prenatal, el tratamiento y el seguimiento más efectivo de la mujer embarazada con lupus eritematoso sistémico, artritis reumatoide (AR) y síndrome por anticuerpos antifosfolípidos (SAF). Metodología. Para la elaboración de las recomendaciones se conformaron grupos nominales de expertos y se realizaron consensos formales, búsqueda sistematizada de la información, elaboración de preguntas clínicas, elaboración y calificación de las recomendaciones, fase de validación interna por pares y validación externa del documento final teniendo en cuenta los criterios de calidad del instrumento AGREE II. Resultados. Los grupos de trabajo contestaron las 37 preguntas relacionadas con la atención materno-fetal en lupus eritematoso sistémico, AR y SAF, así como de fármacos antirreumáticos durante el embarazo y lactancia. Las recomendaciones fueron discutidas e integradas en un manuscrito final y se elaboraron los algoritmos correspondientes. En esta segunda parte se presentan las recomendaciones para mujeres embarazas con AR, SAF y el uso de fármacos antirreumáticos durante el embarazo y lactancia. Conclusiones. La guía mexicana de práctica clínica para la atención del embarazo en mujeres con AR y SAF integra la mejor evidencia disponible para el tratamiento y el seguimiento de estas pacientes (AU)

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 (AU)

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.

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.

Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies.

INTRODUCTION: Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA-protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein-Barr virus in the pathogenesis has been suggested. Similar to Epstein-Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1-70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. METHODS: Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein-Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1-70 k, P peptide, rheumatoid factor, dsDNA, beta2-glycoprotein I). RESULTS: IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV+ group (n = 20) versus the IgM anti-CMV(-)IgG+ (n = 39) group were compared. Most (19/20) of the IgM anti-CMV+ cases were IgG anti-CMV+, consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein-Barr virus-viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV+ group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1-70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA-protein complex (P = 0.0077). CONCLUSIONS: Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis.

[Informed consent in clinical practice and medical research]. / El consentimiento informado en la práctica clínica y en la investigación médica.

The present paper deals with the basic aspects, influences and elements that constitute Informed Consent seeing it as a process and not only as an administrative format. Both the patient-physician relationship, as well as the research subject-investigator relationship, should be seen in the same manner, in spite of recognizing specific objectives for each one. For this reason, Informed Consent should not be different regarding both clinical as well as research activities. The patient-physician relationship presents a disbalance of power within the relationship in favor of the physician; this adds to the moral considerations that take place within both participants. Informed Consent should be defined in a broad sense as all those actions that promote a process of communication and dialogue which facilitates a person in order to make decisions with respect of an action, practice or product that have an impact on his/her body, intimacy or other vital spaces. Informed Consent has influences that originate in basic bioethical principles (autonomy, beneficience, non-maleficence, justice), professional and international declarations (Hippocratic Oath, Declaration of Helsinki), as well as legal considerations pertinent to each country. In our country legality emmanates from the General Health Law which, unfortunately, only contemplates Informed Consent as part of the relation established in clinical research. However, the Official Medican Norm on the Clinical Record establishes the conditions where Informed Consent must be obtained during clinical as well as research activities. Primary components of Informed Consent (revelation, capacity to understand and voluntariness), can be better understood when divided into several elements: information, voluntariness, risks and benefits, confidentiality, return of information, utility of the process and management of fragility. Informed Consent should be legally instrumented in an explicit written manner (administrative formats). However, it is important to recognize the limitations of these formats when used outside the context of a continuous communication process with the patient. For this reason, ultimate instrumentation is through continuous dialogue between patient and physician. Finally, Informed Consent might help improve the patient-physician relationship which, in the end, might be the best way to counteract the influence of the establishment of health management services.