RESUMEN Existe una relación compleja, dinámica y bidireccional entre la autoinmunidad y el cáncer. Si bien los mecanismos carcinogénicos y fisiopatológicos de las enfermedades autoinmunes no están claramente dilucidados, existe una base inmunológica común relacionada con la expresión de autoantígenos por parte de las células tumorales que desencadenan una respuesta antitumoral, facilitando el desarrollo de síndromes paraneoplásicos reumáticos y enfermedades autoinmunes reumáticas en población genéticamente susceptible. Se presenta un caso de un hombre que debutó con un síndrome pulmón riñón y se diagnosticó cáncer de pulmón y lupus eritematoso sistémico de forma simultánea.

A B S T R A C T There is a complex, dynamic, and bidirectional connection between autoimmunity and cancer. The underlying mechanisms of carcinogenesis and physiopathological aspects of autoimmune diseases are not fully understood. However, there is a common immunological base related to expression of autoantigens by tumour cells that cause an anti-cancer immune response, thereby, triggering the development of paraneoplastic rheumatic syndromes and autoimmune rheumatic diseases in a genetically predisposed population. The case is reported of a 57 year-old man presenting with pulmonary renal syndrome, and who was diagnosed lung cancer and systemic lupus erythematosus at the same time.

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.

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 Introducción: La validación de cuestionarios es fundamental en el proceso de medición de cualquier estudio de investigación. El cuestionario Community Oriented Program for Control of Rheumatic Diseases (COPCORD) es útil como tamizaje para la detección de enfermedades reumáticas. Objetivo: Adecuar y validar la metodología y el cuestionario COPCORD en población colom biana. Materiales y métodos: Se realizó un estudio de validación de metodología COPCORD que incluyó: 1) adecuación transcultural del cuestionario COPCORD del español mexicano, y 2) validación de los cuestionarios: COPCORD, cuestionario de nivel socioeconómico, uso de servicios de salud y un instrumento de calidad de vida (EQ-5D-3L), siguiendo las guías internacionales. Resultados: Participaron 329 sujetos de 6 ciudades de Colombia, 10 en la primera fase del estudio y 309 en la segunda; un 67,3% fueron mujeres, con una edad promedio de 46,4 años, con una escolaridad entre básica y media (77%). Los participantes residían en Bogotá (29,4%), Barranquilla (22%), Cali (20,3%), Medellín (15,2%), Bucaramanga (6,4%) y Cúcuta (6,4%). Repor taron dolor musculoesquelético en los últimos 7 días el 43,6% y dolor histórico el 68,9%. En 127 (41,1%) se estableció un diagnóstico reumatológico: osteoartrosis (9,3%), síndrome de dolor regional (5,5%), lumbalgia (5,1%) y artritis reumatoide (0,9%). La validez interna fue de 0,70. Al comparar el cuestionario COPCORD con la revisión por el reumatólogo, tuvo una sensibilidad del 70,8%, una especificidad del 35%, una razón de verosimilitud positiva de 1,09 y un área bajo la curva de 0,53. Conclusiones: El cuestionario COPCORD es válido como prueba de tamizaje de detección de malestares musculoesqueléticos y enfermedades reumáticas en población colombiana.

ABSTRACT Introduction: The validation of questionnaires is fundamental in the measurement process of any research study. The Community Oriented Program for Control of Rheumatic Dis eases (COPCORD) questionnaire is useful as a screening tool for the detection of rheumatic diseases. Objective: To adapt and validate the methodology and the COPCORD questionnaire in the Colombian population. Materials and methods: A validation study of the COPCORD methodology was carried out that included: (1) transcultural adaptation of the COPCORD questionnaire of Mexican Spanish, and (2) validation of the questionnaires: COPCORD, socioeconomic level questionnaire, use of health services and a quality of life questionnaire (EQ-5D-3L), following international guidelines. Results: A total of 329 subjects of 6 cities in Colombia participated in the process, with 10 in the first phase and 309 in the second. Approximately two-thirds (67.3%) were women. The mean age was 46.4±18.4 years, with an educational level between basic and medium (77%). Participants resided in Bogota (29.4%), Barranquilla (22%), Cali (20.3%), Medellin (15.2%), Bucaramanga (6.4%), and Cucuta (6.4%). Musculoskeletal pain in the previous 7 days was reported by 43.6%, and historical pain was reported by 68.9%. A rheumatological diagnosis was established in 127 (41.1%) cases: osteoarthrosis (9.3%), regional pain syndromes (5.5%), low back pain (5.1%), and rheumatoid arthritis (0.9%). The internal validity was 0.70. When comparing the COPCORD questionnaire with the diagnosis made by the rheumatologist, it had a sensitivity of 70.8%, specificity 35%, positive likelihood ratio of 1.09 m and area under the curve of 0.53. Conclusions: The COPCORD questionnaire is valid as a screening test to detect musculoskeletal complaints and rheumatic diseases in the Colombian population.

Resumen La paquimeningitis es el compromiso fibrosante de las leptomeninges poco común y de múltiple etiología. Una de ellas, la enfermedad relacionada a inmunoglobulina IgG4. Las manifestaciones clínicas más frecuentes son la cefalea crónica de difícil tratamiento y el déficit neurológico focal. Se presenta el caso de un hombre de 31 años, con cefalea crónica localizada en el hemicráneo izquierdo y disimetría izquierda, resonancia nuclear magnética con imagen hiperintensa y edema perilesional ubicada a nivel infratentorial y parieto-occipital izquierda, angiografía cerebral y estudio de líquido cefalorraquídeo normales. La biopsia del sistema nervioso central (SNC) descartó lesiones neoplásicas, granulomatosas, infección y malformación arteriovenosa, y reportó fragmentos meníngeos engrosados. A nivel sérico se encontraron altos niéveles de IgG4. ANA, ENA, anti-DNA, SCL-70, CCp y FR, negativos. Con el diagnóstico presuntivo inicial de paquimeningitis craneal hipertrófica idiopática, recibió tratamiento con dosis elevadas de glucocorticoides por espacio de 2 anos, sin buena respuesta y el desarrollo de síndrome de Cushing iatrogénico, cataratas y osteoporosis. Durante el seguimiento se documentó dactilitis, esclerosis distal de miembros superiores, síndrome de Raynaud y con capilaroscopia con asas dilatadas, microhemorragia, desorganización de la arquitectura capilar y megacapilares, configurándose el diagnóstico de esclerodermia sistémica limitada. Aunque se propuso inicialmente la asociación entre estas 2 condiciones, la revisión de la literatura indica que se trata de 2 entidades fisiopa-tológicamente diferentes. El tratamiento con metotrexato a dosis de 25 mg semanal permitió el retiro de los glucocorticoides y la resolución completa de los síntomas neurológicos.

Abstract Pachymeningitis is an uncommon disease with multiple etiologies with fibrosis of leptomeninges. One type of this disease is related to immunoglobulin G4 (IgG4). The most frequent manifestations include chronic cephalgia and focal neurological deficits. The case of a 31-year-old man with chronic cephalgia localized to the left hemicranium and left dysmetria is presented. Nuclear magnetic resonance imaging showed image hyperintensity and perilesional edema located at the infratentorial and left parietal occipital levels. The results of cerebral angiography and a cerebrospinal fluid examination were normal. A biopsy of the central nervous system (CNS) ruled out neoplastic lesions, granulomatous lesions, infection, and arteriovenous malformation and indicated thickened meningeal fragments. Elevated serum IgG4 levels were found. The antinuclear antibodies (ANAs), antibodies to extractable nuclear antigens (ENAs), anti-native DNA antibodies (anti-DNA), topoisomerase I antibodies (Scl-70), antibodies to cyclic citrullinated peptides (anti-CCP), and rheumatoid factor (RF) were negative. After an initial diagnosis of idiopathic hypertrophic cranial pachymeningi-tis, the patient received treatment with high doses of glucocorticosteroids for two years, without response, and developed Cushing's syndrome, cataracts, and osteoporosis. During the follow-up, dactylitis, distal upper limb sclerosis, and Raynaud's phenomenon occurred. A capillaroscopy indicated capillaries with dilated loops, microhemorrhaging, disorganization of the capillary architecture, and megacapillaries, which led to a diagnosis of limited systemic scleroderma. Although an association between scleroderma and pachymeningitis was originally proposed, review of the literature suggests that these are two different entities. Treatment with methotrexate, 25 mg weekly, allowed the withdrawal of glucocorticoids and resolution of neurological symptoms.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, inflamatoria, crónica, que se desarrolla en individuos genéticamente predispuestos. La interacción de un factor detonante en conjunto con la falla de los mecanismos de depuración de potenciales autoantígenos reactivos, dará lugar a la formación de complejos inmunes responsables del daño tisular de los órganos blanco. En la fisiopatología han sido implicados una variedad de elementos pertenecientes a la inmunidad innata y adaptativa. Una población celular descrita recientemente es la de linfocitos Th17, designados así por la producción de la IL-17; citosina que media procesos fisiológicos y fisiopatológicos; estos últimos responsables del desarrollo de condiciones inflamatorias como las del LES. Dada la heterogeneidad de esta enfermedad, en la actualidad no se cuenta con un biomarcador de actividad lo suficientemente sensible, específico y con un grado de predicción, que permita una confiable toma de decisiones clínicas. Con la intención de suplir dicha carencia, se ha postulado que los niveles séricos de IL-17, pueden ser un biomarcador que cumpla con dichos parámetros. Sin embargo, la información al respecto no es conclusiva. A continuación se presenta una revisión sobre los mecanismos ontogénicos de los linfocitos Th17, la argumentación de su rol fisiopatológico en LES y los estudios clínicos que apoyan y debaten el protagonismo de las citosinas relacionadas con linfocitos Th17 como biomarcadores de actividad de la enfermedad en LES.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease expressed in genetically predisposed individuals. The interaction of a trigger factor together with the failure of the mechanisms for handling potential reactive autoantigens leads to the development of immune complex responsible for the damage of the target organs. Elements of both innate and adaptive immunity have been implicated in the pathophysiology of the disease, but given the heterogeneity of the SLE, we still do not have a biological marker of activity of the disease with high sensitivity, specificity and predictive value. Recently, a cell population was described as lymphocytes T helper 17 (Th17), so called because of their production of Interleukin 17 (IL-17), cytokine that mediates physiological and pathophysiological processes implicated in the development of inflammatory conditions such as SLE. It has been postulated that serum IL-17 may be a biomarker that meets these parameters; however, data on this topic is still incomplete. We present a review of the ontogenetic mechanisms of Th17 lymphocytes, an explanation of its pathophysiological role in SLE and clinical studies that support and discuss the role of Th17 lymphocytes related cytokines as biomarkers of disease activity in SLE.

INTRODUÇÃO: A combinação de metotrexato (MTX) + leflunomida (LFN) demonstrou ser efetiva no tratamento da artrite reumatoide (AR), mas sua segurança tem sido questionada. OBJETIVO: Avaliar a eficácia e a segurança terapêutica da combinação de MTX + LFN em pacientes com AR ativa. MÉTODOS: Estudo multicêntrico com 24 semanas de duração envolvendo 88 pacientes com doença ativa, apesar do tratamento regular com MTX e prednisolona. RESULTADOS: Participaram do estudo 78 mulheres (88%) e 10 homens. A idade foi de 51,3 ± 12,4 anos, e o tempo de evolução da doença, 8,0 ± 6,8 anos. Os pacientes tinham doença ativa evidenciada por IQR média de 10 (7,0-13,0) nas articulações inflamadas e 14,0 (18,0-10,0) nas articulações dolorosas. As respostas ACR obtidas na semana 24 foram: ACR20: 76%; ACR50: 67,1%; e ACR70: 23,9%. Houve melhora na atividade da doença, medida pelo escore DAS-28: 5,8 ± 1,2 no início do estudo vs. 3,8 ± 1,6 na semana 24 (P = 0,000). O evento adverso mais significativo foi elevação das transaminases, ocorrida em oito (26%) pacientes. Oito pacientes descontinuaram o estudo devido a eventos adversos: quatro por elevação das transaminases, um por diabetes insípido, um por erupção cutânea, um por diabetes mellitus e um por dor osteomuscular. CONCLUSÃO: A combinação de MTX + LFN é efetiva para o tratamento de AR em pacientes que não obtiveram sucesso com o tratamento convencional. Há necessidade de rígido controle médico e laboratorial para segurança terapêutica.

INTRODUCTION: The combination of methotrexate (MTX) + leflunomide (LFN) has been shown to be effective in the treatment of RA. Its safety has been questioned. OBJECTIVE: To evaluate the effectiveness and safety of the combination of MTX + LFN in patients with active RA. METHODS: This was a 24-week multicenter study, which included 88 patients with active disease despite consistent treatment with methotrexate and prednisolone. RESULTS: We included 78 women (88%) and 10 men. The age was 51.3 ± 12.4 years, and the evolution of disease was 8 ± 6.8 years. Patients had active disease, which was indicated by a median of IQR of 10.0 (7.0-13.0) for swollen and of 14.0 (18.0-10.0) for tender joints for the whole group. The ACR responses achieved at week 24 were: ACR20: 76.0%; ACR50: 67.1%; ACR70: 23.9%. There was improvement in the activity of disease: DAS-28 score: 5.8 ± 1.2 at baseline vs. 3.8 ± 1.6 at week 24 (P = 0.000). The most significant adverse event was elevation of transaminases in eight patients (26%). Eight patients were withdrawn due to adverse events: four due to the elevation of transaminases, and one each due to diabetes insipidus, rash, diabetes mellitus and osteomuscular pain. CONCLUSION: The combination of MTX + LFN is effective for treating RA in patients for whom conventional treatment has failed. Strict medical and laboratory control is to be enforced for safety.

INTRODUÇÃO: Biomarcadores séricos, tradicionalmente associados à atividade inflamatória e mau prognóstico em doenças reumáticas, não apresentam a mesma relação nas espondiloartrites. OBJETIVO: Estabelecer uma associação entre os níveis séricos de biomarcadores com a presença de fatores associados com a atividade clínica e com o mau prognóstico nas espondiloartropatias. MÉTODOS: Sessenta e dois pacientes (13 com artrite reativa, 19 com espondilite anquilosante e 30 com espondiloartropatia indiferenciada) foram comparados a 46 controles sadios. Foram realizadas avaliações clínicas, radiológicas e laboratoriais. Os resultados foram analisados de acordo com a presença de uveíte, entesite, lombalgia inflamatória, artrite, HLA-B27 e comprometimento das articulações sacroilíacas. Os biomarcadores utilizados foram: VHS, PCRus, SAA, LBP, FSC-M e MMP-3, além da dosagem dos níveis séricos das citocinas: IL-17, IL-6, IL-1α , TNF-α , IFN-γ, e IL-23. RESULTADOS: Quarenta e três (69,4%) pacientes eram homens. A média de idades foi de 31,9 ± 9,9 anos, enquanto a idade média para o aparecimento dos sintomas foi de 26,9 ± 7,3 anos. HLA-B27 foi positivo em 26 (41,9%) dos pacientes, lombalgia inflamatória esteve presente em 42 (67,7%), artrite em 44 (71,0%) e entesite em 34 (54,8%) pacientes. Os níveis séricos de IL-17, IL-23, TNF-α , IL-6, IL-1α e PCRus foram mais elevados em pacientes com espondiloartropatia em comparação com os controles. Os valores de PCRus (P = 0,04), IL-6 (P = 0,003), IL-1α (P = 0,03), e LBP (P = 0,03) se associaram de maneira significativa com presença de HLA-B27, dor lombar inflamatória e artrite. CONCLUSÃO: O aumento dos níveis séricos de PCRus, IL-6, IL-1α e LBP apresentaram associação com fatores relacionados a atividade clínica e mau prognóstico em pacientes com espondiloartrites.

BACKGROUND: Serum biomarkers traditionally associated with inflammatory activity and a poor prognosis in rheumatic diseases do not show the same relationship in spondyloarthritis. OBJECTIVE: To establish the association between serum levels of potential biomarkers with the presence of factors related to clinical activity and poor prognosis in spondyloarthritis. METHODS: Sixty-two patients were included: 13 with reactive arthritis, 19 with ankylosing spondylitis, and 30 with undifferentiated spondyloarthritis. The results were compared with those from 46 healthy controls. Clinical, radiological, and laboratory characteristics were assessed. The results were analyzed based on the presence of uveitis, enthesitis, inflammatory back pain, arthritis, HLA-B27 and sacroiliac involvement. The analyzed biomarkers included ESR, US-CRP, SAA, LBP, FSC-M, and MMP-3; and cytokine serum levels measured were: IL-17, IL-6, IL-1α , TNF-α , IFN-γ, and IL-23. RESULTS: Forty-three (69.4%) patients were male. The average age was 31.9 ± 9.9 years and the age at the onset of symptoms was 26.9 ± 7.3 years. HLA-B27 was positive in 26 (41.9%) patients, inflammatory back pain in 42 (67.7%), arthritis in 44 (71.0%), and enthesitis in 34 (54.8%). IL-17, IL-23, TNF-α , IL-6, IL-1α , and US-CRP levels were significantly higher in patients with SpA when compared to controls. US-CRP (P = 0.04), IL-6 (P = 0.003), IL-1α (P = 0.03), and LBP (P = 0.03) levels were associated with presence of HLA-B27, inflammatory back pain, and arthritis. CONCLUSION: An increase in serum levels of US-CRP, IL-6, IL-1α , and LBP was correlated with factors associated with clinical activity and poor prognosis in spondyloarthritis.