Comparative study of elderly-onset rheumatoid arthritis and young-onset rheumatoid arthritis in a Colombian population: clinical, laboratory and HLA-DRB1 findings.

OBJECTIVES: Elderly-onset rheumatoid arthritis (EORA) is considered to have different features in relation to young-onset rheumatoid arthritis (YORA). However, results from different evaluated populations worldwide have been inconsistent and in Colombia there are no known descriptions of the differences between these pathologies. The aim of this paper is to compare the clinical, laboratory and immunogenetic features in a Colombian population suffering with EORA and YORA. METHODS: EORA (≥65, n=104) and YORA (<65, n=96) patients were compared regarding clinical, laboratory and HLA-DRB1 alleles features. A control group without rheumatoid arthritis over 65 (n=179) was used to compare the HLA-DRB1 alleles. All patients met the ACR/1987 criteria for rheumatoid arthritis and the clinimetric index was calculated. RESULTS: The gender ratio (female/male) was 1.8:1 in EORA. In both groups, the main onset pattern of disease was an insidious polyarticular onset (p=0.35). EORA was characterised by more distal-proximal joint involvement in comparison to YORA (p=0.0007). In EORA, the rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies frequency was close to 50%, lower than in YORA (63%). In both groups, the DAS28 and HAQ-DI score was higher than 6 and 1, respectively. The HLA-DRB1*0403 and *1402 frequency was significantly higher in EORA than in YORA. Also, the shared epitope (p=0.0392), HLA-DRB1*01 (p=0.0068) and *0101 (p=0.0151) were associated with an anti-CCP positivity and the HLA-DRB1*0403 is protective for the anti-CCP presence in EORA (p=0.0201). CONCLUSIONS: EORA is characterised by a different clinical presentation and HLA-DRB1 alleles with respect to YORA. HLA-DRB1*0403 and *1402 are significantly more frequent in EORA compared to YORA.

The PTPN22 C1858T variant as a risk factor for rheumatoid arthritis and systemic lupus erythematosus but not for systemic sclerosis in the Colombian population.

OBJECTIVES: C1858T single nucleotide polymorphism in PTPN22 encoding the R620W allele variant of Lyp-PTPN22 (a protein phosphatase negatively regulating T-cell activation) has been associated with autoimmunity. This work has investigated the possible association between PTPN22 C1858T (rs2476601) polymorphism and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in a Colombian population. METHODS: A case-control study included 1,042 samples from 413 RA, 94 SLE and 101 SSc patients and 434 healthy controls. The TaqMan allele discrimination assay was used for genotyping. RESULTS: The case-control study provided robust evidence of association between allele 1858T and RA (p=5E-05), as well as between 1858T and SLE (p=0.004). These observations were confirmed for both diseases by meta-analysis (p=2E-04, pooled OR 1.9; 1.3-2.7 95% CI for RA; p<0.0001, pooled OR 2.8, 1.8-4.5 95% CI for SLE). No significant association was observed between 1858T and SSc (p=0.98, OR 1.11, 0.46-2.65 95% CI). CONCLUSIONS: The study suggested that the PTPN22 1858T variant influences RA and SLE genetic background but not that of SSc in the Colombian population.

Panniculitis: another clinical expression of gout.

Gouty panniculitis is an unusual clinical manifestation of gout, characterized by the deposition of monosodium urate crystals in the lobular hypodermis. Its pathogenesis is poorly understood but is associated with hyperuricemia, and the clinical presence of indurate subcutaneous plaques, which may precede or appear subsequently to the articular clinical expression of tophaceous gout. The aim of this report is to describe the clinical characteristics and potential risk factors for the development of lobular panniculitis secondary to chronic tophaceous gout. This is a retrospective clinical review of 6 patients with gouty panniculitis seen at the rheumatology service at the National University of Colombia. All cases fulfill diagnostic criteria for gout. The presenting clinical characteristics of each case were analyzed. All 6 patients were men, with an average age of 26 years. Two patients initially presented with cutaneous manifestations, and in the remainder 4 joint involvements preceded the cutaneous manifestations. Articular involvement first developed in lower extremities, of intermittent nature, and subsequent occurrence of polyarthritis of upper and lower extremities. A positive family history of gout was observed in half of the patients. Smoking and high alcohol intake were relevant risk factors. On physical examination, all exhibited the presence of erythematous, irregular surface, deep indurate subcutaneous plaques. Biopsy of skin and deep dermis including panniculus revealed the presence of granulomatous inflammatory changes with deposition of amorphous eosinophilic material surrounded by palisading histocytes and lymphocytes. Characteristic negative birefringent monosodium urate crystals were observed in the synovial fluid of patients with arthritis. All patients exhibited high levels of serum uric acid and were non-complaint to treatment with allopurinol, NSAIDs, and colchicine. Gouty panniculitis should be considered in the differential diagnosis of panniculitis, especially in the presence of high levels of uric acid. It is usually observed in the third decade of life and may appear prior to the inflammatory articular manifestations of tophaceous gout.

Potential biomarkers for detecting pulmonary arterial hypertension in patients with systemic sclerosis.

Pulmonary arterial hypertension (PAH) is the major complication of systemic sclerosis (SSc) and the main cause of morbi-mortality. It is important to find predictors for this vascular problem. The objective of this study was to determine the serum levels of different biomarkers in patients with SSc and secondary PAH and to compare them with those of healthy control subjects to define their potential role as predictors of PAH. Cross-section study in which 20 patients with SSc were included. PAH was diagnosed by echocardiogram. The optical densities of endoglin (Eng), endothelin-1 (ET-1), platelet-derived growth factor (PDGF), tumoral necrosis factor alpha (TNF-alpha), Transforming growth factor beta 2 (TGF-beta2) and Interleukin 8 (IL-8) were measured in 20 patients with SSc and 20 healthy controls matched by sex. The differences found between the group of patients with PAH and the control group were (mean or median and range): ET-1 (0.20; 0.10-0.35 vs. 0.16; 0.10-0.24; P = 0.0276), IL-8 (195.7; 45.5-504 vs. 118.9; 23-299.5; P = 0.0364), TNF-alpha (0.70; 0.50-0.96 vs. 0.48; 0.38-0.65; P = 1 x 10(-8)) and Eng (0.95; 0.57-1.72 vs. 0.75; 0.57-0.89; P = 0.0028). A correlation was found between the progression of the disease and the development of Raynaud's phenomenon (Rho: 0.67 and P = 0.0011), ET-1 and Eng (Rho: 0.53 and P = 0.0196), and between IL-8 and Eng (Rho: 0.68 and P = 0.0019). In conclusions, the elevation of the serum levels of Eng and ET-1 could represent a useful tool as PAH biomarkers. Nevertheless, the diagnostic value of these markers needs to be determined by prospective studies.

The use of procalcitonin determinations in evaluation of systemic lupus erythematosus.

BACKGROUND: Procalcitonin (PCT), the precursor of the calcitonin, is synthesized in the parafollicular C-cells of the thyroid. It has been used to detect and to differentiate systemic bacterial infections from flares of systemic lupus erythematosus (SLE). PCT in serum increases in severe bacterial and fungal infections, but not, or only slightly in viral infections. OBJECTIVE: To measure PCT levels in patients with active SLE and to compare them with patients without lupus activity and to determine the possible association between activity and elevation of the PCT. DESIGN: Prospective case control study. PATIENT AND METHODS: Measurements were made of PCT (METHOD: Essay immunoluminometric--and ultrasensitive--BRAHMS Diagnostika, Berlin, Germany), C-reactive protein, erythrocyte sedimentation rate, and blood and urine cultures. The index of activity of SLE was determined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of a serial group of patients seen by our rheumatology service. Samples from 53 patients were analyzed. The patients were divided in 2 groups: group I (n = 21) with little or no activity for SLE; group II (n = 32) with activity for SLE (SLEDAI >5). None of the patients had severe bacterial infection, sepsis, or systemic multiorgan failure. RESULTS: Group I had a SLEDAI score of 1.8 [95% confidence interval (CI) 1.09-2.51] with mean levels of PCT 0. 08 ng/mL (Negative smaller than 0. 5 ng/mL). Group II SLEDAI score was 14.6 (95% CI 11.95-17.23) with mean levels of PCT 0.418 ng/mL with standard deviation 1.0021 (95% CI 0.0628-0.773). The measure of association calculated by Fisher method was not significant (1.927) (P = 0. 282). In the group II, 3 patients had frankly positive PCT (3.18, 3.42, and 3.95 ng/mL) and high activity indices (14, 13, and 24). None presented with severe infection, sepsis, or systemic multiorgan failure. They had pneumonia, renal failure (PCT 3.42 ng/mL) and urinary tract infection without systemic symptoms (3.95 ng/mL). Infection was not detected in the other patient (3.18 ng/mL) that was interpreted as a false positive. CONCLUSIONS: This study demonstrates that there is no association between the activity of SLE and PCT levels. The utility of the PCT resides is in raising suspicion of a concurrent bacterial or mycotic infection in the evaluation of patients with active autoimmune diseases.

Lupus arthropathy: a case series of patients with rhupus.

Among the clinical manifestations of systemic lupus erythematosus (SLE) is an arthropathy, which is usually nonerosive. In many cases the joint involvement is mild. A subset of patients have deforming, nonerosive Jaccoud's arthropathy, and a minority have an arthropathy with clinical findings similar to rheumatoid arthritis (RA) that has been called "rhupus." We report our series of eight patients (seven female, one male) with rhupus arthropathy. Patients were between the ages of 17 and 38 years (average: 30.3 years) at disease onset. All had deforming or Jaccoud's arthropathy, and three had erosive disease. The arthritis was typically the first disease manifestation. Other symptoms of lupus including vasculitis and glomerulonephritis appeared after an average of 2.8 years. All had positive antinuclear antibody and rheumatoid factor. Rhupus arthritis is not a combination of RA and SLE, but should be regarded as a variant of the arthropathy of lupus.

Neumonía intersticial linfocítica en una paciente con lupus eritematoso sistémico y síndrome de Sjögren secundario: reporte de caso y revisión de la literatura / Lymphocytic interstitial pneumonia in a patient with systemic lupus erythematosus and secondary Sjögren's syndrome: Case report and literature review

RESUMEN La neumonía intersticial linfocítica es una complicación, poco frecuente, asociada con el lupus eritematoso sistémico, sin embargo, con gran impacto en la calidad de vida. Se asocia con la presencia de anti Ro/SSA, anti La/SSB y con el diagnóstico de síndrome de Sjögren secundario. No es clara la estrategia terapéutica y la información existente está basada en reportes de caso sin disponibilidad de estudios adecuadamente diseñados. En el presente documento se expone el caso de una paciente con lupus eritematoso sistémico y síndrome de Sjögren secundario, que presentó una enfermedad pulmonar intersticial con características de neumonía intersticial linfocítica.

ABSTRACT Lymphocytic interstitial pneumonia is an infrequent complication associated with systemic lupus erythematosus and has a great impact on quality of life. It is associated with the presence of anti-Ro/SSA, anti-La/SSB, and the diagnosis of secondary Sjögren Syndrome. Its therapeutic strategy is not clear, and the existing information is based on case reports, with there being no properly designed studies available. The case is presented here of a patient with systemic lupus erythematosus and secondary Sjögren's syndrome, who also presented with interstitial lung disease with characteristics of lymphocytic interstitial pneumonia.

Medición de la percepción global de salud mediante diferentes escalas en pacientes con artritis reumatoide: propuesta de una escala combinada / Measurement of overall perceived health using different scales in patients with rheumatoid arthritis and a proposal of a combined scale

RESUMEN Introducción: La percepción global de la salud (PGA) es una parte de los instrumentos compuestos utilizados para determinar la actividad de la artritis reumatoide (AR). Por lo general, se mide por medio de la escala visual análoga (EVA). En nuestra práctica clínica y en la literatura se han observado dificultades en la aplicación de la EVA. Este estudio se llevó a cabo luego de considerar la necesidad de definir el desempeño de las diferentes escalas usadas para evaluar la PGA, determinar la facilidad de su uso y proponer una nueva escala. Métodos: Se trata de un estudio basado en desenlace de pacientes con diagnóstico de AR a los que se aplicaron cuatro tipos de escalas para evaluar la PGA: escala 1 (EVA), escala 2 (escala de rostros) y una propuesta de escala visual en dos versiones: escala 3 (escala visual compuesta en orientación horizontal) y escala 4 (similar a la escala 3, pero en orientación vertical). Se analizó su correlación y la frecuencia con la que los pacientes las entendieron. Resultados: Se incluyeron 198 pacientes, 169 mujeres (85,3%) y 29 hombres (14,6%), y la edad media fue de 54,2 anos. El 59,6% de los pacientes no entendió la escala 1. La mayoría de los pacientes entendió las escalas 2, 3 y 4. Aproximadamente el 80% de los pacientes prefirió las escalas 2 (43,4%) y 3 (36,3%) (p < 0,00). Ninguna variable clínica predijo la selección de la escala. Se observó una buena correlación y una aceptable reproducibilidad de las escalas 2, 3 y 4. Conclusiones: La mayoría de los pacientes no entendió la EVA; la mayoría de nuestros pacientes entendió y prefirió las escalas propuestas, que podrían ser útiles en la práctica clínica de los pacientes con AR.

ABSTRACT Introduction: The overall perceived health (OPH) is part of the composite tools used to determine the activity of Rheumatoid Arthritis (RA). It is usually measured using a Visual Analogue Scale (VAS). Difficulties in applying the VAS have been observed in clinical practice and in the literature. This study was carried out after considering the need to define the performance of the different scales used to evaluate OPH, and determine their ease of use, as well as to propose a new scale. Methods: The study based on the outcome of patients, subjects diagnosed with RA, to whom 4 types of scales were applied to evaluate OPH: Scale 1 (VAS), Scale 2 (face scale), a proposal of a visual scale in two versions: Scale 3 (composite visual scale in horizontal orientation), and Scale 4, similar to 3 in vertical orientation. Results: Of the 198 patients included, 169 (85.3%) were women, and 29 (14.6%) were men. The mean age was 54.2 years, and 59.6% of the patients did not understand the Scale 1. The majority of the patients understood the Scales 2,3, and 4. Approximately 80% of the patients preferred the Scales 2 (43.4%) and 3 (36.3%) (P< .00), but no clinical variable predicted the selection of the scale. A good correlation and an acceptable reproducibility were observed for scales 2, 3, and 4. Conclusions: Although the majority of patients did not understand the VAS, the majority of our patients understood and preferred the proposed scales that could be useful in the clinical practice of RA patients.

Lupus arthropathy: historical evolution from deforming arthritis to rhupus.

Systemic lupus erythematosus is an autoimmune and inflammatory disease with multiple clinical manifestations, including arthropathy. The clinical presentation of articular involvement is variable, ranging from arthralgia without erosions or deformity to an erosive arthropathy and severe functional disability. A subset of patients with this articular involvement have Jaccoud's arthropathy, and others have an arthropathy with clinical findings similar to rheumatoid arthritis that has been called "rhupus." In this paper we review the historical evolution of concepts of lupus arthropathy, from deforming arthritis to rhupus, and conclude that rhupus is not a combination of rheumatoid arthritis and lupus. Instead, rhupus arthropathy should be regarded as a variant of the arthropathy of systemic lupus erythematosus.

Pannus y artritis reumatoide: evolución histórica y fisiopatológica / Pannus and rheumatoid arthritis: Historic and pathophysiological evolution

RESUMEN La proliferación del tejido sinovial, que es llamada pannus, se ha considerado como una manifestación tardía, inactiva e irreversible de la artritis reumatoide (AR), contrario a lo que históricamente se ha estudiado. Se realizó una búsqueda de la literatura para realizar una revisión narrativa e histórica respecto al surgimiento del término pannus y su papel en la artritis reumatoide. Estudios de microscopia de luz han mostrado el carácter destructivo de este tejido con hallazgos característicos de la AR, corroborados con microscopia electrónica arios más tarde. Estos hallazgos llevaron a caracterizar el componente celular del pannus con gran número de células inmunológicas y de líneas celulares específicas con propiedades especiales como los sinoviocitos similares a fibroblastos. Este componente celular es el origen de una gran cantidad de citoquinas y proteinasas que perpetúan y causan el daño óseo y del cartílago. Este componente inflamatorio ha sido evidente también con el desarrollo de técnicas de imágenes, como la resonancia magnética y la ultrasonografía, que muestran un papel activo del tejido sinovial engrosado, junto a la hipervascularización en el daño articular y la reversibilidad de estos cambios tras el tratamiento. Las evidencias contempladas permiten concluir que el pannus como evidencia histológica (más que clínica) se refiere a la proliferación del tejido sinovial e incluye un gran componente celular activo que genera y perpetúa la inflamación y, por tanto, la enfermedad.

ABSTRACT Pannus refers to synovial tissue proliferation, and has been considered a late, inactive and irreversible manifestation of rheumatoid arthritis (RA), contrary to historical findings. A literature search was performed on terminology about pannus and its historical role in the pathophysiology of RA. Light microscopy studies have shown the destructive impact of pannus tissue with very specific abnormalities, corroborated a year later with electronic microscopy. Some of these findings are the isolation of the immunological cells inside the tissue, especially one cell line with particular capacities, called synoviocytes similar to fibroblasts. This cellular component is the source a large quantity of cytokines and proteinases that perpetuate and cause bone and cartilage damage. Inflammation has been seen in many image techniques, such as magnetic resonance and ultrasound. These show the role of tissue widening and hyper-vascularization in tissue damage, and some reversibility after treatment of RA. With the evidence presented it is possible to conclude that pannus refers to a histological (more than clinical) term for synovial hypertrophy, and includes a large component of cell activity that generates and perpetuates inflammation and thus the disease.

Clinical and immunological features of post-chikungunya virus chronic arthritis and its effect on functional ability and quality of life in a cohort of Colombian patients / Caracterización clínica e inmunológica de la artropatía crónica por virus chikungunya y su relación con discapacidad funcional y afectación de la calidad de vida en una cohorte de pacientes colombianos

ABSTRACT Introduction: Post-chikungunya virus (CHIKV) chronic arthritis is a common complication of the acute infection caused by this virus, with high risk of progression to functional and quality of life sequelae. Objective: To identify the clinical and immunological characteristics, functional disabilities, and quality of life decline in a sample of Colombian patients with chronic arthropathy associated with chikungunya virus (CHIKV). Methods: A group of 94 patients was evaluated in a City in Colombia during the CHIKV epidemics from 2014 to 2015. Results: The mean age of the 94 patients was 57 years; 76% were women, and 100% came from low socioeconomic groups. Typically, the joint disease was symmetrical, with joint swelling present in 30% of the cases, mostly involving the small and large joints of the upper limbs. Rheumatoid factor was positive in 1.06% and anti-citrulline antibodies in 0%. There were detectable levels of IL6 in 64.9%, and IL 17 in 7.45% of the patients. The severity of disease activity was determined using the DAS28 score, identifying 55.3% with moderate activity, 40.4% with mild activity, and 4.2% with high activity. The HAQ-DI identified a moderate functional limitation in 45.7% of the cases, with a mean score of 1.02. The quality of life measured with the SF-36 scale showed that all of the domains evaluated were affected but pain and the physical and emotional domains were significantly more affected. Conclusions: Patients with post-chikungunya chronic arthritis, presented in most cases arthralgia, arthritis, functional impairment, and poor quality of life. It is then necessary to adopt comprehensive therapeutic measures for a sound intervention of this pathology.

RESUMEN Introducción: La artropatía por virus de chikungunya (CHIKV) es una complicación frecuente secundaria a la infección inicial por este virus con un alto riesgo de progresión a secuelas funcionales y de calidad de vida. Objetivo: Identificar las características clínicas, inmunológicas, de discapacidad funcional y de deterioro de la calidad de vida en una muestra de pacientes colombianos con artropatía crónica por CHIKV. Métodos: Se evaluó un grupo de 94 pacientes en una ciudad colombiana durante la epidemia por CHIKV en el periodo 2014-2015. Resultados: En los 94 pacientes la edad media fue de 57 años, siendo el 76% mujeres y el 100% de la población afectada perteneció a estratos socioeconómicos bajos. El cuadro articular característicamente fue simétrico con inflamación articular en el 30%, mayor compromiso de articulaciones grandes y pequeñas de miembros superiores. Se identificó positividad para factor reumatoide en el 1,06%, anticuerpos anticitrulina en el 0%, niveles detectables de IL-6 en el 64,9% y de IL-17 en el 7,45% de los pacientes. La severidad de la actividad articular se exploró con la escala DAS28, identificando un 55,3% con actividad moderada, un 40,4% actividad leve y un 4,2% con actividad alta. El HAQ-DI identificó un compromiso funcional moderado en el 45,7%, con puntaje medio de 1,02. La calidad de vida medida con la escala SF-36 mostró que todos los dominios evaluados fueron afectados con mayor compromiso de los dominios dolor, rol físico y rol emocional. Conclusiones: En los pacientes afectados por artropatía crónica por CHIKV se observó artralgias, artritis, deterioro funcional y de la calidad de vida en la mayoría de la población estudiada, por lo que es necesario adoptar medidas terapéuticas en todos estos niveles para una intervención adecuada en esta patología.

Tiroiditis y pancreatitis como presentación simultánea en una paciente con nefritis lúpica. Reporte de caso / Thyroiditis and pancreatitis as a simultaneous presentation in a patient with lupus nephritis. Case report

RESUMEN El lupus eritematoso sistémico se puede presentar con un amplio espectro de síntomas que en algunas ocasiones pueden enmascarar complicaciones graves asociadas a la misma enfermedad. Dentro de estas la pancreatitis es una causa poco común, y sin embargo de alta mortalidad, especialmente en pacientes con un tratamiento no oportuno. Reportamos el caso de una paciente que cursa con lupus eritematoso sistémico con compromiso renal y de sistema nervioso central, de reciente aparición, que se asocia a la aparición de pancreatitis y tiroiditis, presentando evolución satisfactoria con esquema terapéutico de ciclofosfamida y prednisolona.

ABSTRACT Systemic lupus erythematosus can present with a broad spectrum of symptoms that on some occasions may mask serious complications associated with the same disease. Within these, pancreatitis is an uncommon but high-mortality cause, especially in patients with non-oportune treatment. We report the case of a patient with systemic lupus eryt-hematosus with recent renal and central nervous system involvement that is associated with the onset of pancreatitis and thyroiditis. A satisfactory outcome was obtained with a cyclophosphamide and prednisolone therapeutic regimen.

Methotrexate-induced pulmonary toxicity in psoriatic arthritis (PsA): case presentation and literature review.

A 45-year-old female with a 4-week history of psoriatic arthritis developed cough, fever, and progressive shortness of breath 2 weeks following initiation of methotrexate therapy. High resolution CT of chest revealed bilateral basal interstitial involvement and diffuse ground glass opacities. Patient, though, died despite immediate discontinuation of methotrexate and initiation of treatment with IV methylprednisolone and cyclophosphamide. Post-mortem examination showed diffuse interstitial pulmonary fibrosis. Methotrexate-induced pulmonary toxicity is a serious event, unpredictable, and unusual, especially in patients with psoriatic arthritis, and although reversible, it may be fatal.

Necrotizing lymphocytic vasculitis limited to the peripheral nerves: report of six cases and review.

Background. The systemic vasculitides are syndromes characterized by inflammation and injury (necrosis or thrombosis) of blood vessels, resulting in clinical manifestations according to the affected vascular bed, but not classically in stocking-glove neuropathy. Objective. To describe a form of primary vasculitis affecting strictly peripheral nerves manifesting as stocking-glove neuropathy. Methods. Case series of 110 patients seen in three centers in Bogotá who presented with symptoms and signs of polyneuropathy and/or were identified with vasculitis affecting only the peripheral nerves, and who underwent sural nerve biopsy. Results. Six patients had a vasculitis affecting only the peripheral nerves diagnosed on sural nerve biopsy which demonstrated a mixed infiltrate of monocytes/macrophages and lymphocytes especially in the small epineurial blood vessels. Over time, all had worsening of symptoms, with grip weakness and motor deficits in the hand and feet. Serologies and acute phase reactants were normal in all patients. Treatment response to immunosuppression was satisfactory in 5 patients; 1 patient had progressive neurologic damage. Conclusions. There is a distinct form of primary vasculitis of the peripheral nervous system characterized by distal sensory polyneuropathy with stocking-glove distribution with good prognosis, few and minor relapses and good response to treatment even after delayed diagnosis.

Are classification criteria for vasculitis useful in clinical practice? Observations and lessons from Colombia.

INTRODUCTION: Idiopathic systemic vasculitis represents a group of clinical entities having non-specific etiology with the common characteristic of acute or chronic inflammatory compromise of the small and large vessels walls, associated with fibrinoid necrosis. OBJECTIVES: To describe the most common inflammatory vascular diseases in a long historical cohort of patients from San Juan de Dios Hospital located in Bogota, Colombia using two different systems and a clinical histopathological correlation format, and to make a comparison between them. METHODS: We reviewed all previously ascertained cases of vasculitis confirmed by biopsy processed between 1953 and 1990, and systematically collected data on all new cases of vasculitis from 1991 to 1997 at the Hospital San Juan de Dios (Bogota-Colombia). The cases were classified in accordance with the Chapel Hill Consensus criteria, and the system proposed by J.T. Lie. RESULTS: Of 165,556 biopsy tissue specimens obtained during this period from our hospital, 0.18% had vasculitis, perivasculitis or vasculopathy. These included 304 histopathological biopsies from 292 patients. Cutaneous leukocytoclastic vasculitis (64 histological specimens) was the most frequently encountered type of "primary" vasculitis followed by thromboangiitis obliterans (38 specimens), and polyarteritis nodosa (24 specimens). Vasculitis associated with connective tissue diseases (33 specimens) and infection (20 specimens) were the main forms of secondary vasculitis, a category that was omitted from the Chapel Hill consensus report. We found that 65.8% of our histopathological diagnoses could not be classified according to the Chapel Hill classification, and 35.2% could not be classified according to the classification of Lie. Only 8.9% of cases remained unclassified by our system after clinical and histological correlation. CONCLUSION: Current vasculitis classification schemes are designed for classification, rather that diagnosis of disease and do not adequately address some common forms of inflammatory vascular diseases, including those of infectious etiology and unusual etiology seen in clinical practice. Based on our clinical experience, we suggest a classification outline which practitioners can use which emphasizes correlation of the clinical picture to the histopathology findings for diagnosis and therapy, which may promote better clinical practice and standardization for clinical trials.

Risk factors associated with pulmonary arterial hypertension in Colombian patients with systemic sclerosis: review of the literature.

OBJECTIVE: Considering the significant morbidity and mortality of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc) and the lack of precise information on disease in Latin America, we investigated the clinical and laboratory characteristics associated with PAH in Colombian patients with SSc and review the literature. METHODS: This multicenter study included patients followed at 5 rheumatology units that were systematically assessed using a pretested questionnaire on clinical and immunological variables, focusing on PAH. Conditional logistic regression was employed to assess association between PAH and specific clinical characteristics. A systematic review of the literature was performed through electronic databases. RESULTS: Of a total of 349 patients with SSc, 61 (17%) met the criteria for PAH. Pulmonary fibrosis [adjusted odds ratio (AOR) 7.37, 95% CI 3.67-14.81, p < 0.0001], microstomia (AOR 3.3, 95% CI 1.70-6.28, p < 0.0001), gastroesophageal reflux (AOR 2.41, 95% CI 1.31-4.43, p = 0.005), dysphagia (AOR 2.7, 95% CI 1.49-4.77, p = 0.001), hyperpigmentation (AOR 2.15, 95% CI 1.11-4.16, p = 0.02), and hypopigmentation (AOR 2.4, 95% CI 1.26-4.64, p = 0.008) were the most prevalent clinical characteristics associated with PAH, while anemia (AOR 5.4, 95% CI 1.98-14.93, p = 0.001) was observed as the unique laboratory risk factor. Association between subtypes of SSc and PAH was not observed. Significant differences in both clinical and laboratory data were observed among different series. CONCLUSION: PAH may be a frequent complication of SSc in the Colombian population regardless of disease subtype. The identified clinical and laboratory risk factors might assist earlier diagnosis and guide decisions on therapeutic interventions on this critical complication of SSc. The reasons underlying the reported divergences among patients from different ethnicities are not fully understood, but it is most likely that both genetic and environmental factors are responsible for them.

Artropatía de Jaccoud y fibrosis pulmonar en síndrome CREST / Jaccoud’s arthropathy and pulmonary fibrosis in CREST syndrome

Se describe el caso de una paciente de 48 años de edad con diagnóstico de síndrome CREST incompleto (variante de esclerosis sistémica limitada), en quien se documenta la presencia de artropatía de Jaccoud de las manos y compromiso pulmonar intersticial por fibrosis pulmonar tipo neumonía intersticial usual, con positividad para factor reumatoide y anticuerpos contra el péptido citrulinado.Palabras clave: síndrome CREST, artropatía, enfermedad pulmonar intersticial, fibrosis pulmonar.

We report a case of a 48 years old patient with diagnosis of incomplete CREST syndrome (variant limited systemic sclerosis) in who we documented the presence of Jaccoud’s arthropathy of the hands and pulmonary involvement by pulmonary fibrosis type usual interstitial pneumonia, with positivity for rheumatoid factor and anti-cyclic citrullinated peptide antibody.Key words: CREST syndrome, joint disease, interstitial lung disease, pulmonary fibrosis.

Osteomalacia inducida por tumor / Tumor-induced osteomalacia

La osteomalacia inducida por tumor es un síndrome paraneoplásico secundario en la mayoría de los casos a tumores de origen mesenquimal. Se caracteriza por pérdida aumentada de fosfato a nivel urinario por el efecto inhibidor que ejerce el factor de crecimiento fibroblástico 23 sobre el transporte de fósforo en el túbulo renal proximal. Debe sospecharse en un paciente con debilidad y dolor osteomuscular generalizado que se presente con hipofosfatemia, normocalcemia, fosfatasa alcalina elevada y niveles de 25 hidroxivitamina D y PTH normales. El tratamiento definitivo de la enfermedad es la resección quirúrgica del tumor. Cuando se desconozca la neoplasia primaria o no sea posible el tratamiento quirúrgico debe iniciarse reposición de fósforo y calcitriol. En este artículo se presenta el primer caso de una paciente con osteomalacia inducida por tumor asociada a un carcinoma lobulillar infiltrante de seno.

The tumor-induced osteomalacia is a paraneoplastic syndrome secondary in most cases to tumors of mesenchymal origin. It is characterized by increased lost of urinary phosphate by the inhibitory effect exerted by the fibroblast growth factor 23 on phosphorus transport in the proximal renal tubule. Should be suspected in a patient with weakness and generalized muscle in addition to hypophosphatemia, normocalcemia, elevated alkaline phosphatase and normal serum 25-hydroxyvitamin D and PTH. The definitive treatment of the disease is surgical resection of the tumor. When the primary tumor is unknown or is not possible the surgical treatment should be initiated replacement of phosphorus and calcitriol. This paper presents the first case of a patient with tumor-induced osteomalacia associated with lobular breast cancer.

Defectos en la síntesis de cadena ζ en el linfocito T, generando señales intracelulares equivocadas, responsables de lupus eritematoso sistémico / Defects in the synthesis of ζ chain in T lymphocytes, generating wrong intracellular signals, responsible for systemic lupus erythematosus

La expresión anormal de moléculas claves en señalización y la función defectuosa de los linfocitos T cumplen un papel significativo en la patogénesis de la enfermedad autoinmune. Las células T muestran numerosas anormalidades en la señalización del complejo TCRζ¹, estas aberraciones resultan en la alteración de la expresión de citoquinas. Mientras algunas de estas anormalidades explican el aumento de la actividad de células B por células T con incremento de los anticuerpos, la disminución en la producción de IL-2 resulta en un aumento en la susceptibilidad a las infecciones, reducción en la activación de las células T, inducción de la muerte celular y prolongada sobrevida de las células T autorreactivas².

The abnormal expression of key molecules in signaling and the malfunction of the T cell T have a significant activity in the pathogenesis of the autoimmune disease. The cells T exhibit numerous abnormalities in the signaling of the complex TCRζ¹, these aberrations result in the alteration of the citoquines. While some of these abnormalities explain the increase of the activity of cells B for cells T with increment of the antibodies production, the decrease in the production of IL-2 induces an increase in the susceptibility to the infections, diminishing in the activation of the cells T, and expansion of the lifespan of the autorreactive cells².