Rheumatoid Arthritis: Mexico

Contreras-Ruiz J, Kresch-Tronik NS, de la Cruz-Garcia MI, Mercado-Ceja S, Lozano-Platonoff A. · Interdisciplinary Wound and Ostomy Care Center, Dr. Manuel Gea Gonzalez General Hospital, Mexico City, Mexico. · Ostomy Wound Manage. · Pubmed #19037135 No free full text.

Abstract: Pyoderma gangrenosum (PD) is a rare, chronic, relapsing, ulcerative, neutrophilic cutaneous disease and may be difficult to recognize. It is not uncommon for PD to be mistakenly diagnosed as vascular occlusive or venous disease, vasculitis, cancer, infection, exogenous tissue injury, or other inflammatory disorders. A 55-year-old woman with a 5-year history of a very painful and enlarging ulcer presented at the authors' clinic. Previously, based on an original diagnosis of venous ulcer, the wound had been surgically debrided and managed with saline-soaked gauze and compression therapy. After the authors secured a complete history (which included rheumatoid arthritis) and assessment, PD was suspected. A biopsy was performed for histological confirmation. Pyoderma gangrenosum treatment, including oral corticosteroids and topical 0.01% tacrolimus twice daily covered with nonadhesive gauze and compression wrapping, was started. After 4 weeks, the wound had improved noticeably and pain medications to manage wound pain were discontinued. The wound was completely healed after 4 months. The presence or absence of PD must be ascertained in all patients who present with a history of painful lower leg ulcers and PD risk factors, such as rheumatoid arthritis.

Jara LJ, Navarro C, Brito-Zerón Mdel P, García-Carrasco M, Escárcega RO, Ramos-Casals M. · Direction of Education and Research, Hospital de Especialidades, Centro Médico La Raza, IMSS, Seris y Zaachila s/n C.P., 02990, Mexico City, México. · Clin Rheumatol. · Pubmed #17558463 No free full text.

Abstract: From 1960 to 2007, an important number of patients with primary Sjögren's syndrome (pSS) along with thyroid disease diagnosed by laboratory data and clinical presentation were reported. The most common thyroid disorder found was autoimmune thyroiditis and the most common hormonal pattern was subclinical hypothyroidism. The coexistence of SS and thyroiditis is frequent and suggests a common genetic or environmental factor predisposition with similar pathogenic mechanisms. pSS was ten times more frequent in patients with autoimmune thyroid disease and autoimmune thyroiditis was nine times more frequent in pSS. Therefore, SS should be studied in patients with thyroid disease and vice versa. Antigens are shared by both thyroid and salivary glands, which could be responsible for the association between both diseases. Immunogenetic studies had suggested that both diseases have a common genetic predisposition. pSS and thyroid disease patients were mostly women with positive antithyroglobulin, antiparietal cell and antithyroid peroxidase antibodies. Thyroid dysfunction is frequent in pSS patients and those prone to develop thyroid disorders are identified by thyroid-related autoantibodies or by rheumatoid factor and anti-Ro/SSA activity. Patients with pSS have an increased tendency to develop other autoimmune diseases. Hypothyroidism was the most common autoimmune disease developed in pSS patients during follow-up of 10.5 years. Lymphomas are also associated with SS and thyroiditis and a 67-fold increased risk for thyroid mucosa-associated lymphoid tissue (MALT) lymphoma and a 44-fold increased risk for parotid lymphoma is being attributed to autoimmune thyroiditis and pSS. It is suggested that immune mechanism deficiency is a causal factor for B cell lymphoma in pSS and autoimmune thyroid disease. Other studies are necessary to clarify the shared pathogenesis mechanism in SS and autoimmune thyroid disease and to understand this fascinating autoimmune association.

Thompson-Chagoyán OC, Maldonado J, Gil A. · Department of Paediatrics, "Los Venados" General Hospital, Mexican Institute of Social Security, México City, Mexico. · Dig Dis Sci. · Pubmed #17420934 No free full text.

Abstract: The aim of this study was to review the process of microbial colonization and the environmental and host factors that influence colonization and microbial succession. The impact of some diseases on intestinal microbiota composition is also described. Microbial colonization of the gut by maternal vaginal and fecal bacteria begins during and after birth. During the first 2 years of life, specific microbes become established in a process designated microbial succession. Microbial succession in the gastrointestinal tract is influenced by numerous external and internal host-related factors, and by the second year of life, the intestinal microbiota composition is considered identical to that of adults. Nevertheless, intestinal microbiota in both infants and adults remain incompletely characterized and their diversity poorly defined. The main explanation is that many intestinal bacteria that live in an anaerobic environment are difficult or impossible to culture outside the intestine. However, recent advances in molecular biology techniques have initiated the description of new bacteria species. The composition of gut microbiota can be modulated by host, environmental, and bacterial factors, and strong evidence has emerged of substantial modifications during illness or exposure to threatening experiences. It has been postulated that improvements in hygienic measures have led to an increase in allergic diseases ("hygiene hypothesis"). Alterations in gut microbiota and their functions have been widely associated with many chronic and degenerative diseases, including inflammatory bowel disease, colon cancer, and rheumatoid arthritis.

Pardo A, Selman M. · Facultad de Ciencias, Universidad Nacional Autónoma de México and Instituto Nacional de Enfermedades Respiratorias, Apartado Postal 21-630, Coyoacan, México, DF, CP 04000, Mexico. · Int J Biochem Cell Biol. · Pubmed #15474975 No free full text.

Abstract: The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue remodeling. Human fibroblast collagenase (MMP-1) was the first vertebrate collagenase purified as a protein and cloned as a cDNA, and is considered the prototype for all the interstitial collagenases. It is synthesized as a zymogen where N-terminal residues are removed by proteolysis and shares with other MMPs a catalytic domain and a carboxy terminal domain with sequence similarity to hemopexin. Importantly, MMP-1 should be considered a multifunctional molecule since it participates not only in the turnover of collagen fibrils in the extracellular space but also in the cleavage of a number of non-matrix substrates and cell surface molecules suggesting a role in the regulation of cellular behaviour. Furthermore, an extensive body of evidence indicates that MMP-1 plays an important role in diverse physiologic processes such as development, tissue morphogenesis, and wound repair. Likewise, it seems to be implicated in a variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders, suggesting that its inhibition or stimulation may open therapeutic avenues.

Richaud-Patin Y, Soto-Vega E, Jakez-Ocampo J, Llorente L. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga #15, Tlalpan, 14000 Mexico City, Mexico. · Autoimmun Rev. · Pubmed #15110230 No free full text.

Abstract: Multidrug resistance-1 (MDR-1) is characterized by overfunction of P-glycoprotein (P-gp), a pump molecule that decreases intracellular drug concentration by effluxing them from the intracellular space. Broad ranges of structurally unrelated compounds are transported by P-gp, including antineoplastic agents, HIV protease inhibitors, prednisone, gold salts, methotrexate, colchicine as well as several antibiotics. In contrast, many other compounds such as calcium channel blockers (verapamil) and immunosupressors (cyclosporine-A) are able to inhibit P-gp function. The P-gp role in therapeutic failures has been extensively studied in cancer; however, there is little information regarding MDR-1 phenotype in autoimmune disorders. It has been reported that an increased number of lymphocytes are able to extrude P-gp substrates in rheumatoid arthritis, immune thrombocytopenic purpura and systemic lupus erythematosus, the patients with poor response to treatment being the ones that exhibit the highest values. This may be due, at least in part, to a simultaneous long-term usage of several drugs that induce P-gp function. Since abnormally activated cell compartments characterize autoimmune diseases, it is possible that those cells are the ones that exhibit drug resistance. The study of drug resistance mechanisms in autoimmunity may be helpful for the optimization of the current therapeutic schemes through their combination with low doses of P-gp inhibitors.

Soto-Rojas AE, Kraus A. · Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Vasco de Quiroga #15, Tlalpan, 14000 México City, D.F., México. · Arch Med Res. · Pubmed #11886706 No free full text.

Abstract: Sjögren syndrome (SS) is an inflammatory disease of the exocrine glands. Although not always present, signs and symptoms of dry eyes and xerostomia are characteristic features of SS. Oral dryness is one of the most important data of patients with SS. Several sets of criteria have been published; however, there is no definitive agreement concerning which is the most useful. In addition to its various clinical manifestations, lack of understanding of the causes of SS delays prompt diagnosis. Histologically, the salivary gland shows a characteristic lymphocytic infiltrate, which is implicated in the destruction of gland cells. Saliva performs an important role in maintaining and protecting oral health. Deficient quality and quantity of saliva have a detrimental consequence for dental and oral health. In some patients, appropriate information regarding dry mouth care is not offered because most professionals either neglect or ignore adequate attention to oral health. Therefore, lack of treatment is frequent. Medical and dental studies that focus on the oral aspects of diagnosis, consequences, and treatment of SS are commented on. Diagnostic methods used for the oral component are also reviewed. The role of the oral tests developed to diagnose SS is assessed, especially tests used by the majority of criteria. Impairment of salivary secretion increases the risk of developing oral diseases; the therapeutic modalities designed to ameliorate these damages by increasing salivary output or by substitution of saliva are reviewed. We discuss published prevention techniques to diminish dental, periodontal, and soft tissue infections.

Miranda JM, Alvarez-Nemegyei J, Saavedra MA, Terán L, Galván-Villegas F, García-Figueroa J, Jara LJ, Barile L, Anonymous00012. · Departamento de Reumatología, Hospital de Especialidades, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico. · Arch Med Res. · Pubmed #15036798 No free full text.

Abstract: BACKGROUND: Our objective was to assess the efficacy and safety of cyclosporine-A (CsA) plus chloroquine (Clq) in early-onset rheumatoid arthritis (RA) compared to CsA plus placebo. METHODS: We conducted a prospective, 12-month follow-up, multicenter, double-blind, placebo-controlled study of CsA (2.5-5 mg/kg/day[d]) plus Clq (150 mg/d) vs. CsA plus placebo in active RA of <2 years of evolution. RESULTS: A total of 149 patients were included; 111 patients (74.4%) completed the 12-month follow-up period. Evaluation at 6 and 12 months showed improvement for all clinical disease parameters. In both groups there was a decrease in tender joint count, swollen joint count, pain, assessment of efficacy by both investigator and patient, functional assessment, and morning stiffness, all differences statistically significant. With an intention-to-treat analysis, there was 64% in the CsA plus Clq group (CsA/Clq) and 63% in the CsA plus placebo group (CsA/Plac) at 12 months in the American College of Rheumatology (ACR)-20 criteria of improvement. Response rate for ACR-50 was 48 and 47%, and for ACR-70 it was 29% in both groups; the difference was not statistically significant between study groups. Gastrointestinal complaints were common in both groups. Four patients in CsA/Clq group and five patients in CsA/placebo group increased creatinine levels; two patients in each group discontinued treatment due to this reason. CONCLUSIONS: There was no advantage to adding chloroquine to cyclosporine in patients with RA.

Furuzawa-Carballeda J, Cabral AR, Zapata-Zuñiga M, Alcocer-Varela J. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. · J Rheumatol. · Pubmed #12563677 No free full text.

Abstract: OBJECTIVE: To determine the efficacy, tolerance and safety of subcutaneous injections of porcine type I collagen-polyvinylpyrrolidone (PVP) in patients with rheumatoid arthritis (RA). METHODS: Eleven patients with active RA on stable therapy with methotrexate (MTX) were enrolled in a 3 month prospective and longitudinal study. Patients were treated weekly with subcutaneous injections of 0.2 ml of collagen-PVP (1.7 mg of collagen) in the 8 most painful joints. The primary endpoints included the Ritchie index (RI), swollen joint count, disease activity score (DAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The secondary endpoints included morning stiffness, pain intensity on a visual analog scale (VAS), and the Spanish-Health Assessment Questionnaire Disability Index (HAQ-DI). Improvement was determined using American College of Rheumatology (ACR) response criteria. RESULTS: Collagen-PVP was safe and well-tolerated and there were no adverse events. Patients had a statistically significant improvement (p < 0.05) in basal versus 3 month's treatment in morning stiffness (Delta -32.3, -68.6%), RI (Delta -10.2, -46.4%), swollen joint count (Delta -10.7, -71.8%), VAS (Delta -39.9, -63.8%), HAQ-DI (Delta -0.5, -48.5%), DAS (Delta -1.35, -70.5%) and ACR20, 50, and 70 (80.0%; 60.0% and 20.0% respectively). We found no differences in serologic or hematologic variables. CONCLUSION: Collagen-PVP was a safe and well-tolerated drug for the short term treatment of RA. The combination of collagen-PVP plus MTX was more efficacious than MTX alone. However, double-blind placebo-controlled phase II and III clinical trials are necessary to determine whether this drug could be useful in the longterm treatment of RA.

Tovar AR, Gómez E, Bourges H, Ortíz V, Kraus A, Torres N. · Department of Physiology of Nutrition, Instituto Nacional de Ciencias Médicas y Nutricion, México, México. · Eur J Clin Nutr. · Pubmed #12428174 links to  free full text

Abstract: BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjögren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.

Jakez-Ocampo J, Richaud-Patin Y, Simón JA, Llorente L. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. · Joint Bone Spine. · Pubmed #12102278 No free full text.

Abstract: AIMS: To assess the therapeutic effect of leflunomide in weekly dose of 100 mg in patients with refractory rheumatoid arthritis. MATERIAL AND METHODS: Sixteen patients were included (18-72 years, disease duration 2-32 years). Eight patients received a weekly dose of 100 mg of leflunomide and 8 the conventional dose. Current treatment was not modified. All patients underwent a monthly evaluation for one year, applying the 1995 ACR preliminary definition of improvement in rheumatoid arthritis. RESULTS: After 2 months, the group treated with the conventional leflunomide dose evidenced a remarkable improvement (7/8 patients achieving ACR 20), while the group receiving the weekly dose, the improvement was not as clearly evident (3/8 patients achieving ACR 20). By the fourth to sixth month, the response was comparable on both groups (6/6 and 6/8 patients achieving ACR 50 in the daily and weekly dose, respectively) and prevailed through the end of the study. There were no statistical differences between groups at any evaluation. Side effects made itself clear in 6 patients in the daily leflunomide group, and 2 patients withdrawn leflunomide because severe gastrointestinal symptoms and hepatotoxicity, respectively. In the group of weekly leflunomide 2 patients presented side effects which disappeared spontaneously. CONCLUSION: The use of leflunomide in a weekly dose of 100 mg proved to have similar therapeutic benefit as that of the conventional scheme and might represent a new option for the treatment of refractory rheumatoid arthritis patients.

Ramos-Remus C, Dorazco-Barragan G, Aceves-Avila FJ, Alcaraz-Lopez F, Fuentes-Ramirez F, Michel-Diaz J, Torres-Bugarin O, Ventura-Aguilar A, Zuñiga-González G. · Department of Rheumatology, Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara. · Clin Exp Rheumatol. · Pubmed #12051400 No free full text.

Abstract: OBJECTIVES: This study investigated whether: (i) rheumatoid arthritis (RA) patients have more micronuclei (MN) than healthy controls; (ii) methotrexate (MTX) treated RA patients have more MN than those not using MTX, and (iii) folic acid supplementation decreases the number of MN in MTX treated patients. METHODS: MN assays were performed in oral mucosa sweeps of 50 consecutive MTX treated RA patients, 30 consecutive RA patients not receiving MTX and 39 healthy controls. MTX treated RA patients were then randomly placed in a cross-over design to receive folic acid supplementation, and MN assays were repeated after 6 weeks. RESULTS: The MTX-RA patients had a mean age of 46 +/- 10 yrs and a mean disease duration of 12 +/- 9 yrs; 80% were women. The MTX dose range was 8.7 +/- 1.5 mg/week and the mean duration of use was 16 +/- 18 months. In the non-MTX RA group, the mean age was 48 +/- 14 yrs, the mean disease duration was 13 +/- 9 yrs, and 87% were women. At baseline, the number of MN were significantly higher in RA patients as compared with controls (3.31 +/- 2.3 vs 0.8 +/- 0.8, p <0.001). No difference in MN numbers was observed between users and non-users of MTX. Folic acid supplementation did not decrease the MN number in the MTX treated RA patients. CONCLUSIONS: Genotoxicity, as assessed by the MN assay, is increased in RA patients. These results suggest that genotoxicity is associated with RA itself and not with MTX use. Folic acid supplementation had no effect on the number of MN.

Luis M, Pacheco-Tena C, Cazarín-Barrientos J, Lino-Pérez L, Goycochea MV, Vazquez-Mellado J, Burgos-Vargas R. · Hospital General de México, Mexico City, Mexico. · Arthritis Rheum. · Pubmed #10524688 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy of 2 low-dose oral methotrexate (MTX) schedules in maintaining remission in patients with rheumatoid arthritis (RA). METHODS: Patients with RA were included if they were receiving treatment with weekly MTX for at least 9 months and the RA was in remission (defined by American College of Rheumatology [ACR] criteria) for at least 6 months. Patients were stratified by treatment and randomly assigned to weekly or every-other-weekly (EOW; reducing their monthly dose by half) treatment with MTX. Patients were evaluated by a rheumatologist (blinded to the treatment schedule) at baseline and at 6, 12, and 24 weeks. The evaluations included joint counts, Ritchie Articular Index, Health Assessment Questionnaire Disability Index, physician's and patient's global health assessments, visual analog scale for pain, and incidence of adverse effects. Laboratory evaluations were done at baseline and at week 24. RESULTS: Fifty-one patients were included (26 taking weekly MTX, 25 taking EOW MTX). Baseline comparisons showed no differences between the groups. The mean duration of RA was <3 years in both groups, and they had been started on weekly MTX treatment early after diagnosis. After 24 weeks, >90% of the patients in both groups continued in remission. Evaluations of disease activity at 6 and 12 weeks showed no between-group differences. EOW MTX patients who experienced relapse were switched back to weekly MTX, and after a few weeks, their RA was again controlled. The incidence of adverse effects was slightly higher in the weekly MTX group, although the difference did not reach statistical significance. The observed laboratory values were very similar for both groups, except for the serum aspartate aminotransferase and alanine aminotransferase levels, which decreased in the EOW MTX group and were statistically significant at week 24 (P = 0.04 and P = 0.006, respectively). CONCLUSION: EOW MTX represents a valid therapeutic alternative for a specific subgroup of RA patients, as outlined by the ACR remission criteria. Patients with a short disease duration who were treated early after disease onset with weekly MTX and who achieve sustained remission have a higher probability of success with the EOW MTX schedule.

Alpízar-Aguirre A, Lara-Cano JG, Rosales-Olivares LM, Miramontes-Martínez V, Reyes-Sánchez AA. · Servicio Cirugía de Columna Vertebral, Instituto Nacional de Rehabilitación y Ortopedia, México, D.F., Mexico. · Cir Cir. · Pubmed #19534859 No free full text.

Abstract: Background: Instability of the cervical spine is defined as an increase in flexibility farther than the physiological limits of one vertebra over another in some of its axes, conditioning symptoms for the patient. Traumatic, degenerative, metabolic and neoplastic causes have all been identified. Methods: A retrospective, longitudinal, observational and descriptive study was carried out on patients surgically intervened specifically for atlantoaxial instability from January 1993 to May 2002, with a minimum 5-year follow-up. Results: Eleven patients were evaluated. Ages ranged from 25 to 75 years (average age 56 years) with a female predominance. Etiology was iatrogenic in six cases, and there were four cases of rheumatoid arthritis and one case due to trauma. In all cases, fixation was accomplished with occipitocervical arthrodesis with posterior arch resection. Predominant preoperative neurologic deficit according to Ranawat was grade II and postoperatively was grade I. Conclusions: The average age of patients in our series was discreetly lower in regard to what has been reported in the literature. Female predominance was in accordance with previous publications. Eight of 11 patients showed improvement as in other series. A higher impact was observed in patients between 30 and 64 years of age. The occupational activity with the highest frequency was homemaker, and the neurologic deficit according to Ranawat showed improvement in 72% of the patients.

Jiménez-Morales S, Velázquez-Cruz R, Ramírez-Bello J, Bonilla-González E, Romero-Hidalgo S, Escamilla-Guerrero G, Cuevas F, Espinosa-Rosales F, Martínez-Aguilar NE, Gómez-Vera J, Baca V, Orozco L. · Genomic of Complex Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico. · Hum Immunol. · Pubmed #19480843 No free full text.

Abstract: There is a great deal of evidence that points to the association of the tumor necrosis factor-alpha (TNF-alpha) gene as a common genetic factor in the pathogenesis of diseases that are caused by inflammatory and/or autoimmune etiologies. Two single nucleotide polymorphisms (SNPs) identified in the TNF-alpha promoter region have been associated with disease susceptibility and severity. We investigated whether -308G/A and -238G/A TNF-alpha polymorphisms were associated with asthma, systemic lupus erythematosus (SLE), and juvenile rheumatoid arthritis (JRA) in a pediatric Mexican population. In a case-control study of 725 patients (asthma: 226, JRA: 171, and SLE: 328) and 400 control subjects, the participants were analyzed using the allelic discrimination technique. The genotype distribution of both TNF-alpha polymorphisms was in Hardy-Weinberg equilibrium in each group. However, there were significant differences in the allele frequency of TNF-alpha-308A between the patients and the healthy controls. This allele was detected in 2.9% of the controls, 6.0% of asthmatic and JRA patients (p = 0.002 and p = 0.0086), and 6.7% of SLE patients (p = 0.00049); statistical significance was maintained after ancestry stratification (asthma: p = 0.0143, JRA: p = 0.0083, and SLE: p = 0.0026). Stratification by gender showed that the risk for the -308A allele in asthma and JRA was greater in females (OR = 4.16, p = 0.0008 and OR = 4.4, p = 0.0002, respectively). The TNF-alpha -238A allele showed an association only with JRA in males (OR = 2.89, p = 0.004). These results support the concept that the TNF-alpha gene is a genetic risk factor for asthma, SLE, and JRA in the pediatric Mexican population.

Cabrera Pivaral CE, Gutiérrez González TY, Gámez Nava JI, Nava A, Villa Manzano AI, Luce González E. · Hospital de Especialidades, Centro Médico Nacional de Occidente, Guadalajara, México. · Rev Alerg Mex. · Pubmed #19374160 No free full text.

Abstract: OBJECTIVE: To evaluate the competence of the primary care physicians for the evaluation of rheumatic disorders. PARTICIPANTS AND METHODS: In a cross-sectional survey we included primary care physicians working at the official Mexican Social Security Institute that provides nation-wide health-care for salaried workers. Four hospitals from 23 potentially eligible primary-care hospitals in Guadalajara, Jalisco, Mexico, were randomly selected. From these hospitals the physicians who agree to participate were asked to answer a questionnaire for clinical competence. Using a Delphi modified approach; this questionnaire was elaborated by a group of rheumatologists and researchers working in continuous medical education. A Kuder-Richardson reliability index was computed in 0.94. The diseases included in the questionnaire were: (1) rheumatoid arthritis, (2) Sjogren syndrome, 3) gout, 4) osteoarthritis and 5) systemic lupus erythematosus and questions regarding to these were made using the technique of "representative patients". Domains included in the questionnaire were: assessment of risk factors, strategies for diagnosis, and treatment. According to the scores obtained in the questionnaire the ranges for clinical competence were: very high level 93-110 points, high level 75-92, moderate 57-74, low 39-56, very low 21-38 and <20 points was considered obtained by chance. RESULTS: One-hundred and four primary care physicians were interviewed. From the total, 60 (58%) physicians had the speciality of family physician. Only 11% (95% CI 5-17) of the interviewed had a high level of competence according to the instrument. Moderate competence was achieved by 20% (95% CI 13-27), whereas suboptimal levels had 51%: being low 31% (95% CI 22-40), very low 20% (95% CI 13-27). An additional 18% had scores obtained by chance (95% CI 11-25). There was no statistical difference in the scores between physicians with or without the specialty in family medicine. CONCLUSIONS: These results pointed-out a sub-optimal competence in a significant proportion of the primary care-physicians attending rheumatic disorders. Higher efforts need to be made to increase the levels of competence and improve the effectiveness of continuous medical education for these physicians.

Solano C, Martinez A, Becerril L, Vargas A, Figueroa J, Navarro C, Ramos-Remus C, Martinez-Lavin M. · National Institute of Cardiology, Mexico City, Mexico. · J Clin Rheumatol. · Pubmed #19342959 No free full text.

Abstract: BACKGROUND: It has been suggested that autonomic nervous system dysfunction may explain all of fibromyalgia (FM) multisystem features. Such proposal is based mostly on the results of diverse heart rate variability analyses. The Composite Autonomic Symptom Scale (COMPASS) is a different validated method to recognize dysautonomia. OBJECTIVES: The main objective of our study was to investigate symptoms of autonomic dysfunction in FM patients by means of COMPASS. A secondary objective was to define whether there is a correlation between COMPASS and Fibromyalgia Impact Questionnaire (FIQ) scores in FM patients. METHODS: Design, analytical cross-sectional study. Our study population included 3 different groups of women: 30 patients with FM, 30 patients with rheumatoid arthritis, and 30 women who considered themselves healthy. All participants filled out COMPASS and FIQ questionnaires. RESULTS: FM patients had significantly higher values in all COMPASS domains. COMPASS total score (54.6 +/- 20.9; mean +/- standard deviation) clearly differentiated FM patients from the other 2 groups (21.6 +/- 16.5 and 9.5 +/- 10.2, respectively). P < 0.0001. The majority of FM patients gave affirmative answers to questions related to orthostatic, digestive, sleep, sudomotor, or mucosal dysfunction. There was a significant correlation between COMPASS and FIQ scores (Spearman r = 0.5, P < 0.005). CONCLUSIONS: Patients with FM have multiple nonpain symptoms related to different expressions of autonomic dysfunction. There is a correlation between a questionnaire that measures FM severity (FIQ) and an autonomic dysfunction questionnaire (COMPASS). Such correlation suggests that autonomic dysfunction is inherent to FM.

Pascual-Ramos V, Contreras-Yañez I, Cabiedes-Contreras J, Rull-Gabayet M, Villa AR, Vázquez-Lamadrid J, Mendoza-Ruiz JJ. · Early Arthritis Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. · Ultrasound Q. · Pubmed #19276959 No free full text.

Abstract: To investigate if serial clinical and ultrasound evaluations differ between early rheumatoid arthritis patients who do or do not develop erosive disease and to identify predictors of erosions. METHODS: Patients with at least 7 consecutive 2-monthly clinical and 3 consecutive 6-monthly ultrasound evaluations were included. Ultrasound (gray scale and power Doppler) assessed synovitis, power Doppler-positive synovitis (PD+) and power Doppler-negative synovitis (PD-) in each of 14 joints of the dominant hand. After 1 and 2 years, erosive disease was defined according to digitized radiography. Areas under the curve (AUCs) for serial assessments were calculated. Multivariate logistic regression analysis was performed. RESULTS: Seventy-one and 38 patients completed 1- and 2-year consecutive assessments. After 2 years (21.5 +/- 6.2 months), 13 patients developed erosions. At baseline, nonerosive patients had shorter duration of symptoms to RA diagnosis, lower number of the American College of Rheumatology (ACR) classification criteria, lesser synovitis and PD+ synovitis than erosive patients. At follow-up, erosive and nonerosive patients showed similar AUC for clinical, serological, and treatment parameters; erosive patients had higher AUCs for synovitis and PD+ synovitis than nonerosive patients. In the multivariate model, the amount of PD+ synovitis (odds ratio, 1.3; 95% confidence interval, 1.11-1.51; P = 0.001) and more ACR classification criteria (odds ratio, 2.3; 95% confidence interval, 1.05-5.02; P = 0.04), both at baseline, predicted erosive disease. CONCLUSIONS: Serial Power Doppler ultrasonography-assessed synovitis was greater in patients who developed erosions than in those who did not. More power Doppler positive (hypervascular) synovitis and more ACR classification criteria, both at baseline, were the only predictors of erosions.

Simón-Campos JA, Padilla-Hernández RO. · Unidad de Investigación Médica, Centro Medico "Nacional El Fénix". · Rev Med Inst Mex Seguro Soc. · Pubmed #19263661 No free full text.

Abstract: OBJECTIVE: To compare the correlation between C reactive protein (CRP) and erythrosedimentation rate (ESR) with rheumatoid arthritis (RA) activity. METHODS: Cross-sectional study, in patients with RA. All were assessed by a rheumatologist who evaluated the RA disease activity according to the American College of Rheumatology score. Blood sample was dropped to test CRP and ESR levels. The correlation between CRP and ESR with RA disease activity was estimated using rho Spearman coefficient. RESULTS: We included 80 patients, mean age of 50.5 +/- 11.0 years. 62.5% had some degree of disease activity. We found that CRP had a high correlation with all parameters of disease activity included: number of tenders joins (r = 0.352, p = 0.001), number of painful joins (r = 0.327, p = 0.003), VAS of join pain (r = 0.385, p < 0.0001), VAS of global disease activity estimated by the patient (r = 0.325, p = 0.003), VAS of global disease activity estimated by the rheumatologist (r = 0.486, p < 0.0001), and HAQ score (r = 0.310, p= 0.005). In contrast the ESR only had correlation with the HAQ score (r = 0.310, p = 0.005). CONCLUSIONS: Our results suggest that CRP is a better test to support the clinical evaluation of disease activity in RA.

Alvarez-Nemegyei J, Bautista-Botello A, Dávila-Velázquez J. · Unidad Médica de Alta Especialidad, Instituto Mexicano del Seguro Social, Mérida, Yucatán, México. · Clin Rheumatol. · Pubmed #19139949 No free full text.

Abstract: Quality of life, functional status, or cumulated damage were compared between users and non-users of complementary and alternative medicine (CAM) in 445 rheumatic patients (rheumatoid arthritis [RA]: 64; systemic lupus erythematosus [SLE]: 192; fibromyalgia [FM]: 34; and knee osteoarthritis [KOA]: 155). CAM use was reported by 249 subjects (55.9%; 95%CI; 51.4-60.6). After a general linear model was applied, CAM use was associated with lower scores in the physical function (p = 0.02) and bodily pain (p = 0.03) domains of the SF-36 survey. In FM, RA and KOA, functional status was not different between users and non-users. CAM use was associated with higher cumulated damage (p = 0.04) in SLE. In patients with chronic rheumatic diseases, CAM use was not associated with better quality of life. Additionally, in SLE patients, CAM use was associated with higher cumulated damage. More research on CAM use in chronic rheumatic diseases is needed to better delineate its risk/benefit profile.

Mena-Ramírez JP, Salazar-Páramo M, Dávalos-Rodríguez IP. · CUCS Universidad de Guadalajara y División de Genética, Centro de Investigación Biomédica de Occidente, Guadalajara, Jalisco, México. · Gac Med Mex. · Pubmed #19043967 No free full text.

Abstract: Rheumatoid arthritis (RA) is a common rheumatic disease in Mexico. Methotrexate (MTX) is a drug frequently used in the treatment of this disease. However, treatment discontinuation due to side effects is also common. Inter-individual differences in effectiveness and occurrence of side effects in RA patients treated with MTX (RA-MTX) have been reported. Several studies analyzed the presence of MTHFR C677T and A1298C polymorphisms in RA-MTX patients associated with effectiveness, side effects and toxicity. Given the high frequency of the MTHFR C677T polymorphism in Mexico, it is of utmost interest to determine the allelic and genotypic frequency of these polymorphisms in patients with RA-MTX. The use of molecular techniques, feasible in our country, such as PCR/RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) can allow us to identify these MTHFR genotypes among RA-MTX patients in order to target patients at risk of developing drug toxicity, side effects or better MTX efficacy. The ultimate goal is to develop individualized treatment, as promised by the field of pharmacogenomics.

Herrera-Esparza R, Bollain-y-Goytia J, Ruvalcaba C, Ruvalcaba M, Pacheco-Tovar D, Avalos-Díaz E. · Centro de Biología Experimental (CBE), Universidad Autónoma de Zacatecas, Guadalupe, Zacatecas, Mexico. · Acta Reumatol Port. · Pubmed #18846009 links to  free full text

Abstract: AIM: To assess apoptosis and proliferation in salivary glands of patients with primary Sjögren's syndrome. METHODS: Studies were performed in twenty four minor salivary glands from patients with primary Sjögren's syndrome and an equal number of controls. Apoptosis was studied by immunohistochemistry using monoclonal antibodies anti-Fas FasL and Caspase 3 and apoptotic features by TUNEL. Proliferation was assessed with monoclonal anti-PCNA and anti-Ki67 antibodies. RESULTS: All salivary glands from Sjögren's display apoptotic molecules along the epithelia of salivary ducts and in a smaller amount in acinar tissue. The presence of Caspase 3 Fas FasL was concordant with the expression of apoptosis by TUNEL. Proliferation markers were encountered in inflammatory emigrant cells but not in ductal epithelia nor in acini. Control biopsies poorly expressed apoptotic or proliferation markers. CONCLUSION: Present data suggests that the ductal epithelial and acinar cells of salivary glands from Sjögren's disease patients exhibit increased apoptosis. Proliferation was mainly observed in infiltrating lymphoid cells. Both events constitute a biological paradox related to the inflammatory process of salivary glands in Sjögren's disease.

Furuzawa-Carballeda J, Macip-Rodríguez PM, Cabral AR. · Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico. · Clin Exp Rheumatol. · Pubmed #18799084 No free full text.

Abstract: OBJECTIVE: Pannus in osteoarthritis (OA) has only recently been characterized. Little is known, however, regarding the behavior of OA pannus in vitro compared to rheumatoid arthritis (RA) pannus. The purpose of our study was to compare OA with RA pannus. METHODS: Pannus and synovial tissue co-cultures from 5 patients with OA and 5 patients with RA obtained during arthroplasty were studied. Pannus was defined as the microscopic invasive granulation tissue covering the articular surface. Tissues were cultured for 7 days and stained with Alcian Blue technique. Interleukin-1beta (IL-1beta), IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were also determined in supernatants by ELISA. Cartilage oligomeric matrix protein (COMP), type II collagen, TNF-alpha, IL-10 and Ki-67 expression were also detected by immunohistochemistry. RESULTS: All patients had vascular or fibrous pannus. Synovial proliferation, inflammatory infiltrates and a decrease of extracellular matrix proteins were observed in all tissue samples. Chondrocyte proliferation was lower in OA than RA cartilage. OA synovial tissue expressed lower levels of proteoglycans than RA synoyium. Type II collagen levels were lower in OA than in RA cartilage. Significantly higher levels of IL-1beta were found in the supernatants of RA pannus compared to OA pannus (p<0.05). High but similar levels of TNF-alpha, IL-8 and TIMP-1 were detected in OA and RA pannus supernatants. IL-10, IL-12 and IFN-gamma were undetectable. CONCLUSION: RA and OA pannus had similar pro-inflammatory and anti-inflammatory cytokine profile expression. OA cartilage, synovial tissue and pannus had lower production of proteoglycans, type II collagen and IL-1beta. It remains to be elucidated why OA pannus invades the cartilage surface but does not cause the marginal erosions typically seen in RA.

Rojo Contreras W, Montoya Fuentes H, Gámez Nava JI, Suárez Rincón AE, Vázquez Salcedo J, Padilla Rosas M, Baltazar Rodríguez LM, Trujillo X, Ramírez Flores M, Trujillo Hernández B, González López L. · Unidad de Investigación Médica en Epidemiología Clínica, Unidad Médica de Alta Especialidad, Hospital de Especialidades, IMSS, Guadalajara, Jalisco, México. · Ginecol Obstet Mex. · Pubmed #18798391 No free full text.

Abstract: BACKGROUND: Nevertheless its association with cervicouterine cancer, there is no information about cervical human papillomavirus infection prevalence in patients with rheumatoid arthritis. OBJECTIVE: To evaluate human papillomavirus infection prevalence through molecular biology tests, and to analyze this infection related factors in patients with rheumatoid arthritis. MATERIAL AND METHOD: Analytic, transversal study to 250 patients: 61 women with rheumatoid arthritis selected from a rheumatologic external consult of a second level hospital, and 189 healthy women, with cervical cytology, of a first level hospital. They were polled to find infection risk factors. They were exfoliated to get cervix cells to extract its DNA and detect human papillomavirus (chain reaction of polymerase with specific consensus markers), and identification of restriction enzyme in high and low risks viruses. Prevalence was calculated, and adjusted factors analysis was performed through logistic regression with odds ratio and confidence intervals of 95%. RESULTS: Prevalence of papillomavirus infection in patients with rheumatoid arthritis was 30%, and in control group was 24%, with an odds ratio of 0.8 (CI 95% 0.42-1.6, p = 0.5). Ninety-four percent of the most frequent viral types in women with rheumatoid arthritis were high risk (mainly types 16, 58, and 18). Factors associated with higher human papillomavirus adjusted to rheumatoid arthritis were: more than one sexual partner (OR = 5.8 CI 95% 1.1-31.1, p = 0.04), more than one sexual intercourse weekly (OR = 6.7, CI 95% 0.9-51.6, p = 0.06), circumcised sexual partner (OR = 9.0, CI 95% 1.2-64.4, p = 0.02). Patients and controls had same values of marital status. Seventy-four percent of controls worked, compared to 44% of women with rheumatoid arthritis (p < 0.01). CONCLUSION: One out of three women with rheumatoid arthritis has human papillomavirus infection and 94% has the high-risk viral type. Infection associated factors mainly includes sexual partner ones; due to high risk of cervical dysplasia, it is necessary the early detection of the infection and surveillance.

Aceves-Avila FJ, Benites-Godínez V. · Hospital General Regional No. 46, IMSS, Guadalajara, Jalisco, México. · J Clin Rheumatol. · Pubmed #18679134 No free full text.

Abstract: OBJECTIVE: To measure the frequency of drug allergies in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and register the causal drug, the type, and severity of the reaction. MATERIAL AND METHODS: Direct interview and chart review in patients with RA and SLE were conducted. We registered demographic data, drug allergies, the causal drug, how causality was assessed, and the type and severity of the allergic reaction. We include as drug allergies only those cases in which the result of exposure and re-exposure was known or in which a physician evaluating the original event established the causality link with the suspected drug. Differences between groups were assessed by chi test. RESULTS: Two hundred ninety-three RA and 58 patients with SLE were included. Fifty-three of the patients with RA (18%) and 20 of the patients with SLE (34.3%, P = 0.049) reported drug allergies. Most of them presented skin rash as their clinical expression of allergy (73%); anaphylaxis was reported in 4 cases (5%). Allergy to sulfa drugs is found more frequently in SLE (P = 0.0079). No differences were found when comparing the frequency of other drug allergies, such as penicillin and metamizole. DISCUSSION: Drug allergies are more frequent in SLE than in RA. Sulfa drugs are still the most frequent cause of drug allergies in SLE. Allergies because of drugs forbidden in the United States but easily available in specific ethnic groups are frequent in patients with SLE and RA. Their specific consumption must be intentionally assessed in cases of suspected drug allergies.

Salinas-Carmona MC, de la Cruz-Galicia G, Pérez-Rivera I, Solís-Soto JM, Segoviano-Ramirez JC, Vázquez AV, Garza MA. · Department of Immunology, Faculty of Medicine and University Hospital, Monterrey, Mexico. · Autoimmunity. · Pubmed #18608175 No free full text.

Abstract: Rheumatoid arthritis is an autoimmune disease that affects human beings worldwide. Infections have been associated to autoimmune diseases because their ability to induce a dominant cytokine response. Joint inflammation has been related to Th1 response because they induce high expression of proinflammatory cytokines TNF-alpha, IL-1, IFN-gamma. MRL/lpr mice spontaneously develop an autoimmune disease affecting joints, kidneys, etc. We compared incidence and severity of arthritis, antibody response, cytokine production, in mice infected with bacteria or helminthes in the Murphy Roths Large (MRL)lpr mice. Infections with helminthes Heligmosomoides polygyrus, Nippostrongylus brasiliensis or bacteria Nocardia brasiliensis and Staphylococcus aureus were studied. IL-4, IFN-gamma and IgG1, IgG2a antibody productions were determined. IFN-gamma was increased in all groups, the highest production was observed after bacterial infection; IL-4 production was higher after helminthes infection. IgG1 sera levels were increased in the helminthes infected group. IgG2a sera concentration was stimulated by bacterial infection. The histopathology showed that 100% of bacterial infected mice developed arthritis and severe tissue damage such as cartilage erosion and bone destruction. Animals infected with parasites showed a decreased incidence and severity of arthritis. Severity of tissue damage in joints is correlated with increased numbers of lymphocytes and macrophages immunoreactive to proinflammatory cytokines.