Albert Selva-O’Callaghan

Anti-PL-7 (Anti-Threonyl-tRNA synthetase) Antisynthetase syndrome: Clinical manifestations in a series of patients from a european multicenter study (EUMYONET) and review of the literature

AbstractAutoantibodies against several aminoacyl-transfer-RNA synthetases have been described in patients with myositis; anti-threonyl-tRNA synthetase (anti-PL-7) is one of the rarest. We describe the clinical and laboratory characteristics of a cohort of European anti-PL-7 patients, and compare them with previously reported cases. This multicenter study of patients positive for anti-PL-7, identified between 1984 and 2011, derives from the EUMYONET cohort. Clinical and serologic data were obtained by retrospective laboratory and medical record review, and statistical analyses were performed with chi-squared and Fisher exact tests.Eighteen patients, 15 women, were anti-PL-7 antibody positive. Median follow-up was 5.25 years (interquartile range, 2.8–10.7 yr), and 4 patients died. All patients had myositis (12 polymyositis, 5 dermatomyositis, and 1 amyopathic dermatomyositis), 10 (55.6%) had interstitial lung disease, and 9 (50%) had pericardial effusion. Occupational exposure to organic/inorganic particles was more frequent in patients with interstitial lung disease than in the remaining patients (5 of 10 vs. 1 of 7; p = 0.152), although the difference was not significant. Concurrent autoantibodies against Ro60 and Ro52 were seen in 8 of 14 (57%) patients studied. In the literature review the most common manifestations of anti-PL-7 antisynthetase syndrome were interstitial lung disease (77%), myositis (75%), and arthritis (56%). As in other subsets of the antisynthetase syndrome, myositis and interstitial lung disease are common features of the anti-PL-7 antisynthetase syndrome. In addition, we can add pericarditis as a possible manifestation related to anti-PL-7 antibodies.

Polimiositis y dermatomiositis: incidencia en España (1997-2004)

Fundamento y objetivo: No existen estudios epidemiologicos sobre la incidencia de miopatia inflamatoria en Espana. El objetivo de este estudio fue determinar las tasas de incidencia de dermatomiositis y polimiositis y su distribucion en el territorio espanol. Material y metodo: Estudio descriptivo observacional a partir de los datos del Conjunto Minimo Basico de Datos de Altas Hospitalarias en el periodo 1997-2004. Se analizaron las variables sexo, comunidad autonoma y edad. Se calcularon las tasas de incidencia de hospitalizacion en casos por millon de habitantes y ano brutas y estandarizadas y su intervalo de confianza (IC) del 95%, en total y por comunidad autonoma. Para el analisis de tendencia del periodo estudiado, se calculo la odds ratio (OR) de tendencia mediante regresion logistica. Resultados: La tasa de incidencia total del conjunto de dermatomiositis y polimiositis fue de 8,9 (IC del 95%, 8,6-9,2) nuevos casos por millon de habitantes y ano; la de polimiositis, 3,9 (IC del 95%, 3,7-4,1), y la dermatomiositis, 4,9 (IC del 95%, 4,7-5,2). La diferencia entre las tasas de ambas enfermedades fue estadisticamente significativa (p < 0,001). La tasa de incidencia anual de ambas enfermedades disminuyo de forma significativa durante el periodo (dermatomiositis, OR de tendencia = 0,95; IC del 95%, 0,93-0,97; p < 0,001; polimiositis, OR = 0,96; IC del 95%, 0,93-0,97; p < 0,001). La incidencia de ambas enfermedades fue significativamente superior en mujeres. Las tasas de incidencia de polimiositis oscilaban en las diferentes comunidades autonomas entre 2,2 y 10,6 casos por millon de habitantes y ano y las de la dermatomiositis, entre 2,9 y 8,6 casos por habitantes y ano. Conclusiones: La incidencia de dermatomiositis y polimiositis en Espana es similar a la observada en otras zonas del mundo. La disminucion de la incidencia mantenida a lo largo del periodo y la incidencia mas alta de dermatomiositis podrian explicarse por una mejor categorizacion de estas enfermedades

Clinical manifestations and long-term outcome of anti-Jo1 antisynthetase patients in a large cohort of Spanish patients from the GEAS-IIM group

OBJECTIVE To evaluate the clinical manifestations, long-term clinical outcome and longitudinal pulmonary function in a large cohort of Spanish patients with anti-Jo1 antibodies. METHODS We retrospectively analyzed the clinical data and lung function parameters of 148 anti-Jo1 patients recruited from a multicentre registry including 18 Spanish hospitals. A composite endpoint was defined, comprising death due to respiratory failure directly related to antisynthetase syndrome (ASS), the need for long-term oxygen therapy or lung transplantation. RESULTS Median follow-up was 78.3 months. Clinical presentation patterns at onset are as follows: isolated interstitial lung disease (ILD) (32.4%), isolated myositis (26.9%), concomitant myositis and ILD (22.8%), and isolated polyarthritis (17.9%). Myositis with ILD was the most frequent final clinical phenotype (67.6%). In most ASS patients, ILD was a non-progressive disease, tending to stabilize with therapy. The endpoint was reached in a significantly larger number of ILD patients with dyspnea at onset than those with paucisymptomatic or asymptomatic forms (p = 0.01). A steady FVC decrease was the hallmark of patients with end-stage lung disease. Estimated survival rates were 87.7% and 75.4% at 5 and 10 years, respectively. Cancer (p = 0.02) and advanced age at ASS diagnosis (p < 0.0001) were related to poorer survival. Mortality was significantly higher than in the general Spanish population, with a standardised mortality ratio (95% CI) of 4.03 (2.79-5.64). CONCLUSIONS Anti-Jo1 ASS is a heterogeneous syndrome. ILD in ASS under immunosuppressive therapy is mainly a non-progressive disease. Dyspnea at ILD onset and a steady FVC decrease over time were related to a poorer respiratory prognosis.

Síndrome de Sjögren primario: características clínicas e inmunológicas de 114 pacientes

Fundamento Analizar las caracteristicas clinicas, evolutivas e inmunologicas de una serie de 114 pacientes diagnosticados de sindrome de Sjogren primario. Evaluar las diferencias clinicas en funcion de los criterios diagnosticos utilizados y la asociacion del sindrome de Sjogren primario con procesos linfoproliferativos. Pacientes y metodo Se incluyeron 114 pacientes (108 mujeres y 6 varones) diagnosticados de sindrome de Sjogren primario. Todos cumplian los criterios diagnosticos propuestos por el Grupo de Estudio de la Comunidad Europea, y 76 cumplian los criterios de San Diego. Resultados La edad media de los pacientes fue de 51 anos, con un tiempo medio de seguimiento clinico de 7,3 anos. El sintoma mas frecuente de inicio de la enfermedad (70%) fue la xerostomia/xeroftalmia (sindrome seco). Entre las manifestaciones extraglandulares, se observo afeccion articular en un 42% de los pacientes, neurologica en un 35%, pulmonar en el 21% y hepatica en el 13%. Once pacientes (9%) presentaron fenomenos vasculiticos y 3 (2%), un proceso linfoproliferativo. No se apreciaron diferencias estadisticamente significativas en los sintomas de inicio de la enfermedad, en la frecuencia de afeccion glandular y extraglandular, ni en la gravedad de la enfermedad entre los pacientes diagnosticados segun los criterios europeos frente a los de San Diego. La presencia del virus de la hepatitis C (VHC) se asocio de forma significativa con la vasculitis (p Conclusiones El curso clinico del sindrome de Sjogren no varia en funcion de los criterios diagnosticos. Existe asociacion entre la vasculitis y los procesos linfoproliferativos con el VHC, lo que confiere unas caracteristicas diferenciales a este subgrupo de pacientes.

Síndrome por anticuerpos antisintetasa

En 1984, Hochberg et al y posteriormente otros investigadores describieron un sı́ndrome clı́nico que reconocı́a un tipo peculiar de miositis, asociado principalmente a artritis y neumopatı́a intersticial. La identificación en estos pacientes de autoanticuerpos dirigidos frente a enzimas citoplasmáticas que participan en la sı́ntesis proteica, los llamados anticuerpos antisintetasa (anticuerpos que reconocen la sintetasa que cataliza la unión de cada aminoácido con su correspondiente ARN de transferencia) (fig. 1), dio una mayor personalidad a este sı́ndrome clı́nico. El antı́geno frente al que con mayor frecuencia se dirigen estos autoanticuerpos es la histidil-ARNt sintetasa, el primer anticuerpo antisintetasa descrito y el más frecuente, denominado antiJo-1, por las iniciales del nombre del paciente en el que se describió por primera vez. Desde entonces se han ido publicando en la bibliografı́a médica numerosos casos clı́nicos y algunas series de pacientes con este sı́ndrome clı́nico inmunológico, conocido como sı́ndrome por anticuerpos antisintetasa. A lo largo de este artı́culo se describirán aquellos aspectos más relevantes para su diagnóstico, ası́ como las recomendaciones terapéuticas actuales sobre las diferentes manifestaciones de este sı́ndrome.

Good outcome of interstitial lung disease in patients with scleroderma associated to anti-PM/Scl antibody.

OBJECTIVE The objective of this article was to establish the clinical course of interstitial lung disease (ILD) in scleroderma related to the presence of anti-PM/Scl antibody compared with anti-Scl-70 in a Spanish cohort. Furthermore, no study has thoroughly investigated the outcome of pulmonary function test in the first group of patients. METHODS A total of 63 Spanish patients with scleroderma and ILD were selected in a retrospective observational study. Among them, 14 were positive for anti-PM/Scl antibodies and 49 for anti-Scl-70. Clinical assessments, including pulmonary function test, were collected. Variations equal or greater than 10% in forced vital capacity (FVC) were considered significant. Progression-free survival of disease was defined as the period of stable illness since pulmonary fibrosis diagnosis. RESULTS Anti-Scl-70 patients had a higher frequency of diffuse SSc subset, peripheral vasculopathy, and gastrointestinal involvement. Inflammatory myopathy was associated to anti-PM/Scl antibody. Anti-PM/Scl patients presented more improvement in FVC during follow-up, 30.8% compared to a 7.1% in Scl-70 group (P = 0.04), with less worsening of this parameter (15.4% vs 52.4% in Scl-70 patients, P = 0.01), and secondary less frequency of severe restrictive pattern (FVC < 50%) (7.7% compared to 42.9% in the other group, P = 0.02). Regarding treatment, more anticalcineurinics were used in anti-PM/Scl patients, while cyclophosphamide and mycophenolate were mainly used in anti-Scl-70 patients. The progression-free survival of disease was higher in anti-PM/Scl patients, with 76% at 10 years from diagnosis of ILD against a 29% in the Scl-70 group. CONCLUSIONS Several features and prognosis of ILD in SSc may be modified depending on the identified immunological profile.

Fascitis eosinofílica: estudio de 10 pacientes

BACKGROUND AND OBJECTIVE: Eosinophilic fasciitis is an uncommon scleroderma-like syndrome with unknown etiology and pathogenesis. We report the clinical manifestations and response to therapy in a series of patients diagnosed with eosinophilic fasciitis. PATIENTS AND METHOD: The records of 10 eosinophilic fasciitis patients seen at our hospital between 1996-2004 were reviewed. RESULTS: Five patients were males, ages ranged from 20 years to 67 years, with a mean of 59 years. Patients were followed for 33.4 (27.1) months (SD). Nailfold capillaroscopy was near normal in all patients. Only one patient had antinuclear antibody positivity, and another had an autoimmune thyroiditis. No significant relationship was detected between the eosinophil count and the extent of skin induration. The clinical course was inadequate and the treatment response poor in patients with spreading cutaneous induration (p = 0.008). These patients had more often ventilatory restriction and perimyositis. CONCLUSIONS: Eosinophilic fasciitis does not always have a good prognosis. Ventilatory restriction, perimyositis and poor treatment response are not infrequent in a series of patients attended in a general hospital.

Mutations of activin-receptor-like kinase 1 (ALK-1) are not found in patients with pulmonary hypertension and underlying connective tissue disease

Pulmonary arterial hypertension is a recognized clinical component of systemic autoimmune diseases, especially systemic sclerosis. Mutations in the bone morphogenetic protein receptor 2 gene reported in sporadic and familial primary pulmonary arterial hypertension have failed to be detected in patients with either scleroderma spectrum disease or underlying connective tissue diseases. Activin receptor-like kinase 1 (ALK-1) gene has recently been linked to the pathogenesis of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia, which has some resemblance with the CREST syndrome. The presence of mutations in the ALK-1 gene in ten patients with underlying connective tissue diseases was investigated.

Polymyositis, a very uncommon isolated disease: clinical and histological re-evaluation after long-term follow-up

The aim of the present study was to explore whether polymyositis may be considered as an isolated, organ-specific disease or more suitably as a secondary or associated entity. A retrospective re-evaluation of all the muscle biopsies performed at the Hospital Clínic of Barcelona showing histopathological pattern of polymyositis from January 1997 to May 2012 was carried out. The medical records of the patients with the aforementioned pathological pattern were also reviewed. From 1.290 muscle biopsies performed during the period evaluated, 36 with polymyositis pattern were identified. At the time of muscle biopsy, polymyositis pattern was secondary or associated with other disease in 26 patients and was classified as isolated in the remaining ten patients. After pathological re-evaluation and long-term clinical follow-up, only one patient remained with this diagnosis. Overall, the main final diagnosis related to the initial polymyositis pattern was inflammatory myopathy associated with connective tissue disease. Several other associated conditions were also identified. Isolated polymyositis is highly uncommon. Ruling out potential associated or confusing entities, like inclusion body myositis, overlap syndromes, infections, and cancer, is mandatory.

Miopatías inflamatorias. Dermatomiositis, polimiositis y miositis con cuerpos de inclusión

Las miopatias inflamatorias idiopaticas son un grupo heterogeneo de enfermedades cuya principal caracteristica es la debilidad muscular y la identificacion de una inflamacion subyacente en la biopsia muscular. Se incluyen en este grupo la dermatomiositis, la polimiositis y recientemente la miositis con cuerpos de inclusion, con toda probabilidad la menos inflamatoria y tambien la miopatia adquirida mas frecuentemente a partir de los 50 anos. Aunque el principal organo diana es el musculo, la piel y el pulmon, entre otros organos internos, se afectan con frecuencia, por lo que las miopatias inflamatorias se consideran enfermedades sistemicas. En ocasiones pueden asociarse a cancer y la presencia de autoanticuerpos especificos y asociados a estas enfermedades sustenta la etiologia autoinmune del proceso y ayuda a categorizar a los pacientes. El tratamiento incluye la administracion de glucocorticoides, inmunodepresores y puntualmente terapias biologicas, sin descuidar la rehabilitacion incluso en la fase aguda de la enfermedadIdiopathic inflammatory myopathies are a group of heterogeneous, acquired systemic diseases characterized by progressive symmetrical muscle weakness, elevated serum levels of muscle enzymes, electromyographic abnormalities, and inflammatory infiltrates on muscle biopsy. Characteristic histopathologic features allow classification of idiopathic inflammatory myopathies into polymyositis, dermatomyositis, and sporadic inclusion-body myositis. These are commonly regarded as autoimmune disorders, and various autoantibodies directed to specific nuclear and cytoplasmic antigens are found. Other organs besides the muscle can be involved being the skin and lung the most frequent. Occasionally dermatomyositis and polymyositis can be associated with cancer in a paraneoplastic manner. Corticosteroids and immunosuppressive agents are the mainstay therapy, although in refractory cases biologic therapy can be used. Physical therapy can not be forgotten.Idiopathic inflammatory myopathies are a group of heterogeneous, acquired systemic diseases characterized by progressive symmetrical muscle weakness, elevated serum levels of muscle enzymes, electromyographic abnormalities, and inflammatory infiltrates on muscle biopsy. Characteristic histopathologic features allow classification of idiopathic inflammatory myopathies into polymyositis, dermatomyositis, and sporadic inclusion-body myositis. These are commonly regarded as autoimmune disorders, and various autoantibodies directed to specific nuclear and cytoplasmic antigens are found. Other organs besides the muscle can be involved being the skin and lung the most frequent. Occasionally dermatomyositis and polymyositis can be associated with cancer in a paraneoplastic manner. Corticosteroids and immunosuppressive agents are the mainstay therapy, although in refractory cases biologic therapy can be used. Physical therapy can not be forgotten.