Clinical Diagnosis of Chikungunya Infection: An Essential Aid in a Primary Care Setting Where Serological Confirmation Is Not Available.

BACKGROUND: Chikungunya virus (CHIKV) diagnosis has become a challenge for primary care physicians in areas where the Zika virus and/or Dengue virus are present. Case definitions for the three arboviral infections overlap. METHODS: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in a multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. RESULTS: 295 patients with confirmed CHIKV infection were included. A screening tool was created using symmetric arthritis (4 points), fatigue (3 points), rash (2 points), and ankle joint pain (1 point). The ROC curve identified a cut-off value, and a score ≥ 5.5 was considered positive for identifying CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. CONCLUSION: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.

The burden of the most common rheumatic disease in Colombia.

BACKGROUND: Estimating the burden of rheumatic diseases (RDs) requires proper evaluation of its lethal and nonlethal consequences. In Colombia, it is possible to find local data and Global Burden of Disease (GBD) reports that collect information from varied contexts and apply complex statistical models, but no on-site estimations are available. METHODS: This was a descriptive study on the burden of RD based on occurrence and mortality data in the general population during 2015, including information and prevalence estimations from the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) study. Disability-adjusted life years (DALYs) were estimated by combining measures of years of life lost (YLL) and years lived with disability (YLDs). For disability weight estimations among cases, different COPCORD responses were mapped using flowcharts to show the severity distribution according to GBD. All model parameters and results were validated through an expert consensus panel. RESULTS: Low back pain (LBP) was the RD with the greatest burden of disease, costing 606.05 (95% CI 502.76-716.58) DALYs per 100,000 inhabitants, followed by osteoarthritis (292.11; 95% CI 205.76-386.85) and rheumatoid arthritis (192.46, 95% CI 109.7-239.69). CONCLUSIONS: The burden of RD is as high in Colombia as in other countries of the region. The results offer an interesting tool for optimizing healthcare system design as well as for planning the distribution of human and economic resources to achieve early diagnosis and adequate care of these diseases.

Can presence of HLA type I and II alleles be associated with clinical spectrum of CHIKV infection?

Host immune response and virulence factors are key to disease susceptibility. However, there are no known association studies of human leukocyte antigen (HLA) class I and II alleles with chikungunya virus (CHIKV) infection in the Latin American population. Here, we aimed to identify HLA alleles present in patients with CHIKV infection versus healthy controls as well as the allelic association with the clinical spectrum of the disease. We conducted a cross-sectional analysis of a community cohort and included patients aged 18 years and older with serologically confirmed CHIKV infection. HLA typing of HLA-A, HLA-B, and HLA-DRB1 alleles was performed. Two-by-two tables were used to establish associations between allele presence and clinical characteristics. Data from 65 patients with confirmed CHIKV infection were analyzed for HLA typing. CHIKV infection was significantly associated with the presence of HLA-A*68 [p = .005; odds ratio (OR): 8.90; 95% confidence interval (CI): 1.88-42.13], HLA-B*35 (p = .03; OR: 2.01; 95% CI: 1.06-3.86), HLA-DRB*01 (p <.001; OR: 5.70; 95% CI: 1.95-16.59), HLA-DRB1*04 (p <.001; OR: 7.37; 95% CI: 3.33-16.30), and HLA-DRB1*13 (p = .004; OR: 3.75; 95% CI: 1.50-9.39) alleles in patients versus healthy subjects. A statistically significant relationship was found between the presence of a rash on the face or abdomen and the presence of HLA-DRB1*04 (p = .028; OR: 3.2; 95% CI: 1.11-9.15 and p = .007; OR: 4.33; 95% CI: 1.45-12.88, respectively). Our study demonstrated that, in our cohort, HLA type I and type II alleles are associated with CHIKV infection, and an HLA type II allele is associated with dermatological symptoms. Further research is needed to establish a path for future investigation of genes outside the HLA system to improve knowledge of the pathophysiology of CHIKV infection and its host-pathogen interaction.

Pharmacogenetic aspects of methotrexate in a cohort of Colombian patients with rheumatoid arthritis.

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). However, over time, ~40% of patients may experience therapeutic failure or drug toxicity. The genetic variability of the enzymes involved in the MTX metabolic pathway seem to serve an important role in the eventual therapeutic failure or drug toxicity. Depending on the enzymes affected, the toxicity or the therapeutic response may change. The present study reports some of the polymorphisms identified in enzymes in the MTX metabolic pathway that are present in a group of Colombian patients with RA, and assesses the associations of these polymorphisms with toxicity or therapeutic response to the medication. A total of 400 patients with RA were evaluated, of which 76% were women. the average age was 60.7±13.9 years and the duration of the disease was 13.2±10.9 years. The disease activity scoring method, DAS28-CRP, was used to evaluate the therapeutic response. Toxicity was determined based on reports of adverse events during the evaluation of the patients. The single nucleotide polymorphisms (SNPs) assessed using reverse transcription-PCR in the present study were MTHFR C677T, A1298C, ATIC C347G, RFC-1-G80A, FPGS-AG and DHFR-CT. The SNPs of MTHFR C677T (P=0.05) and A1298C (P=0.048) were significantly associated with the efficacy of MTX, and DHFR-CT (P=0.01) and ATIC C347 (P=0.005) were significantly associated with documented toxicity. Haematological, hepatic or renal toxicity was not associated with any of the SNPs. The results obtained in Colombian patients with RA receiving MTX are similar to those reported in other populations; however, the SNPs associated with a lack of response previously reported in the literature were not observed in our data. The SNPs identified in the present study may be used as biomarkers to predict response to MTX in terms of efficacy and toxicity in Colombian patients with RA.

Demographic and clinical characteristics of chikungunya patients from six Colombian cities, 2014-2015.

In 2014, the chikungunya virus reached Colombia for the first time, resulting in a nationwide epidemic. The objective of this study was to describe the demographics and clinical characteristics of suspected chikungunya cases. Chikungunya infection was confirmed by enzyme-linked immunosorbent assay and 548 patients where included in the study. Of these patients, 295 were positive for antibodies against chikungunya (53.8%), and 27.6% (151/295) were symptomatic for chikungunya infection, with a symptomatic:asymptomatic ratio of 1.04:1. Factors associated with infection included low income and low socio-economic strata (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.0-3.2, p = 0.003 and OR: 2.1; CI: 1.3-3.4, p = 0.002, respectively). Confirmed symptomatic cases were associated with symmetric arthritis (OR: 11.7; CI: 6.0-23.0, p < 0.001) of ankles (OR: 8.5; CI: 3.5-20.9, p < 0.001), hands (OR: 8.5; CI: 3.5-20.9, p < 0.001), feet (OR: 6.5; CI: 2.8-15.3, p < 0.001), and wrists (OR: 17.3; CI: 2.3-130.5, p < 0.001). Our study showed that poverty is associated with chikungunya infection. Public health strategies to prevent and control chikungunya should focus on poorer communities that are more vulnerable to infection. The rate of asymptomatic infections among confirmed cases was 48.8%. However, those with symptoms displayed a characteristic rheumatic clinical picture, which could help differentiate chikungunya infection from other endemic viral diseases.

Dickkopf 1 protein circulating levels as a possible biomarker of functional disability and chronic damage in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease characterized by joint destruction, deformity, lower functionality, and decrease in life expectancy. Wingless signaling pathway (Wnt) has been recently involved in bone homeostasis. Studies suggest that overexpression of the pathway inhibitors, like the Dickkopf 1 protein (DKK1), has been implicated in bone destruction. The objective of this study is to compare circulating levels of DKK1 in different groups of patients with disease activity (remission, low, moderate, high activity,) and functionality status. Three hundred seventy-nine patients with RA were evaluated between March 2015 and November 2016. Disease activity was evaluated by disease activity score 28 with C-reactive protein (DAS28CPR), simplified and clinical disease activity scores (SDAI, CDAI), routine assessment of patient index data 3 (RAPID3), functional status using Multidimensional Health Assessment Questionnaire (MD-HAQ), and the Steinbrocker functional classification. DKK1 levels were measured by ELISA. The mean age was 60.7 ± 13.9 years. Disease duration was 13.2 ± 10.9 years. Higher levels of DKK1 were not associated with disease activity by CDAI (p = 0.70), SDAI (p = 0.84), DAS28CRP (p = 0.80), or RAPID3 (p = 0.70). Interestingly higher levels of DKK1 were significantly associated to lower functional status evaluating by the Steinbrocker classification (p = 0,013), severe disability by MD-HAQ (p = 0,004), and variables associated with joint destruction like osteoporosis, higher titles of rheumatoid factor, smoking, and increased hospital admissions related to RA. Higher levels of DKK1 were found in patients with lower functional status. This association was not found in patients with greater disease activity by CDAI, SDAI, DAS28, and RAPID3. This could be explained by more structural damage; DKK1 could be used as a biomarker of joint destruction in RA.

Association of human leukocyte A, B, and DR antigens in Colombian patients with diagnosis of spondyloarthritis.

There is substantial evidence that non-B27 major histocompatibility complex (MHC) genes are associated with spondyloarthritis (SpA). Studies in Mexican and Tunisian populations demonstrated the association of SpA and human leukocyte antigen (HLA) B15. The purpose of this study was to evaluate the association of HLA-A, B, and DR antigens in a group of Colombian patients with a diagnosis of SpA. A total of 189 patients and 100 healthy subjects were included in the present study. All subjects underwent a complete characterization of HLA alleles A, B, and DR. Of the 189 studied patients, 35 were reactive arthritis (ReA), 87 were ankylosing spondylitis (AS), and 67 undifferentiated SpA (uSpA). According to the Assessment of Spondyloarthritis International Society (ASAS) criteria, 167 were axial SpA (axSpA) and 171 were peripheral SpA (pSpA). 63.8% were men, with a mean age of 35.9 ± 12.7 years. 40.7% (77/189) of patients were HLA-B27 positive of which 52.9% had AS and 42.5% axSpA. 23.2% (44/189) of patients were HLA-B15 positive: 23.8% were uSpA, 12.57% were axSpA, and 11.7% were pSpA. In addition, HLA-DRB1*01 was associated with AS (58.6%) and axSpA (42.5%). Also, HLA-DRB1*04 was present in 62 patients with AS (71.2%) and in 26 with axSpA (15.5%). In this population, we found a strong association between the presence of HLA-B27 and the diagnosis of axSpA and AS, but the HLA-B15 is also significantly associated with all subtypes of the disease, predominantly with pSpA. Additionally, HLA-DR1 and DR4 were associated in a cohort of patients with SpA from Colombia.

Interobserver Agreement in Magnetic Resonance of the Sacroiliac Joints in Patients with Spondyloarthritis.

Background. Clinical, laboratory, and radiologic parameters are used for diagnosis and classification of spondyloarthritis (SpA). Magnetic resonance imaging (MRI) of sacroiliac (SI) joints is being increasingly used to detect early sacroiliitis. We decided to evaluate the interobserver agreement in MRI findings of SI joints of SpA patients between a local radiologist, a rheumatologist, and an expert radiologist in musculoskeletal diseases. Methods. 66 MRI images of the SI joints of patients with established diagnosis of SpA were evaluated. Agreement was expressed in Cohen's kappa. Results. Interobserver agreement between a local radiologist and an expert radiologist was fair (κ = 0.37). Only acute findings showed a moderate agreement (κ = 0.45), while chronic findings revealed 76.5% of disagreement (κ = 0.31). A fair agreement was observed in acute findings (κ = 0.38) as well as chronic findings (κ = 0.38) between a local radiologist and a rheumatologist. There was a substantial agreement between an expert radiologist and a rheumatologist (κ = 0.73). In acute findings, a 100% agreement was achieved. Also chronic and acute plus chronic findings showed high levels of agreement (κ = 0.73 and 0.62, resp.). Conclusions. Our study shows that rheumatologists may have similar MRI interpretations of SI joints in SpA patients as an expert radiologist.

Correlation between rapid-3, DAS28, CDAI and SDAI as a measure of disease activity in a cohort of Colombian patients with rheumatoid arthritis.

The objective of this study is to correlate the patient-driven tool Routine Assessment of Patient Index Data 3 (RAPID-3) with other common tools used in daily practice to measure disease activity in rheumatoid arthritis (RA).One hundred nineteen RA patients according to 1987 American College of Rheumatology criteria who consecutively attended a RA outpatient clinic between August and December 2015 were evaluated. Data was stored in an electronic form that included demographic information, comorbidities, concomitant medication, and laboratory results. The disease activity was determined by tender and swollen joint count, pain and disease activity visual analog scales (VAS), disease activity score 28 (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and multidimensional health assessment questionnaire (MDHAQ). Correlations between RAPID-3 and other disease activity tools were assessed. Mean age was 61 ± 13.8 years with a median disease duration of 14 years (IQR 5-21), 77% were females. Median scores were MDHAQ 0.5 (IQR 0.1-1.2), DAS 28 3.8 (IQR 2.7-5.1), and RAPID-3 12.3 (IQR 6-19). A strong correlation was obtained between RAPID-3 and DAS 28 (r 0.719, p < 0.001), CDAI (r 0.752, p < 0.001), and SDAI (r 0.758, p < 0.001). RAPID-3 had a high correlation with tools regularly used for disease activity assessment of RA patients in daily practice. The ease of its application favors routine use as it does not require laboratory results and joint counts.

Comparison of quality of life in patients with musculoskeletal symptoms, those with other comorbidities, and healthy people, in a Colombian open population study / Comparación de la calidad de vida de pacientes con síntomas musculoesqueléticos, comorbilidades asociadas y personas sanas en un estudio abierto de población colombiano

A b s t r a c t Purpose: To describe health-related QOL (HRQOL) in patients with musculoskeletal symptoms, compared to a population with other comorbidities, and a healthy population. Methods: A cross-sectional study was carried out on an open population involved in a community-oriented program for control of rheumatic diseases (COPCORD) study in Colombia, using EQ-5D-3L for estimating QOL, and the health assessment questionnaire disability index (HAQ-DI) for functional capacity. Results: Out of the total 4020 individuals evaluated, 2274 had rheumatic diseases, 642 had non-rheumatic diseases, and 1104 were healthy subjects. Spondyloarthritis (SpA) and rheumatoid arthritis (RA) patients had more complaints regarding pain/discomfort and mobility. As for daily activities, the diseases that mostly affected them were systemic lupus erythematosus (SLE) and RA. RA and fibromyalgia (FM) patients had the worst scores as regards anxiety/depression and self-care dimensions. FM patients had the lowest QOL measured by EQ-VAS (57.7 ± 26.2). The most frequent non-rheumatic diseases were cardiovascular and mental disorders, with 20% of these patients having a moderate level of pain/discomfort and anxiety/depression. The rheumatic patients reported a decrease in functional capacity (HAQ: 0.49), in contrast to the healthy population (0.01), and the population having other diseases (0.06). Conclusion: Rheumatic disease patients in Colombia had the worst QOL compared to the healthy population and patients with other comorbidities. Rheumatic patients had greater functional limitations, even more so when having comorbidities. This study revealed potential factors of interest requiring the attention of public health authorities, and for improving patients' QOL.

RESUMEN Objetivo: Describir la calidad de vida relacionada con la salud en pacientes con síntomas musculoesqueléticos, en comparación con pacientes con enfermedades no reumáticas y una población sana. Métodos: Se realizó un estudio transversal en comunidad abierta, en personas involucradas en un programa orientado a la comunidad para el control de enfermedades reumáticas (COP-CORD) en Colombia, utilizando el EQ-5D-3L para estimar la calidad de vida y el cuestionario de evaluación de la salud (HAQ- DI) para la capacidad funcional. Resultados: Se evaluaron 4.020 individuos; 2.274 tenían enfermedades reumáticas, 642 tenían enfermedades no reumáticas y 1.104 eran sujetos sanos. Los pacientes con espondiloartritis (SpA) y artritis reumatoide (AR) tuvieron mayores quejas con respecto al dolor/malestar y la movilidad. En cuanto a las actividades diarias, los enfermos con lupus eritematoso sistémico (LES) y AR fueron los más afectados. Los pacientes con AR y fibromialgia (FM) tuvieron las peores puntuaciones en ansiedad/depresión en las dimensiones de cuidado personal. Los pacientes con FM tuvieron la calidad de vida más baja medida por EQ-VAS (57,7 ± 26,2). Las enfermedades no reumáticas más frecuentes fueron los trastornos cardiovasculares y mentales; el 20% de estos pacientes tenía un nivel moderado de dolor/malestar y ansiedad/depresión. Los pacientes reumáticos reportaron una disminución de la capacidad funcional (HAQ: 0,49); en contraste con la población sana (0,01) y la población con otras enfermedades (0,06). Conclusión: Los pacientes con enfermedades reumáticas en Colombia tuvieron la peor calidad de vida en comparación con la población sana y los pacientes con otras enfermedades. Los pacientes reumáticos tuvieron una mayor limitación funcional, incluso más que los que tenían otras enfermedades. Este estudio reveló posibles factores relacionados con las enfermedades reumáticas que requieren la atención de las autoridades de salud pública con el objetivo de mejorar la calidad de vida de los pacientes.