Josep M. Grau-Junyent

Malignancy and myositis: novel autoantibodies and new insights.

Purpose of reviewCurrently available data support the idea that inflammatory myopathies, particularly dermatomyositis, are paraneoplastic diseases. Cancer screening is usually recommended in patients with these conditions, but there is no consensus regarding how and how often screening should be performed. This review will address recent advances in our understanding of the relationship between cancer and myositis and describe new data regarding the best approach for cancer screening in myositis patients. Recent findingsA newly described autoantibody to a 155-kDa nuclear protein, identified as transcription intermediary factor 1-gamma (TIF1-γ), has proven useful for cancer screening in patients with dermatomyositis. Occult tumor detection by PET/computed tomography (PET/CT) seems to be a good alternative to broad conventional screening. A combination of both methods, detection of autoantibodies against p155 and PET/CT study, may be the best approach to ascertain the presence of occult malignancy in patients with dermatomyositis. SummaryAdvances in immunology and imaging techniques are increasing the accuracy of occult malignant cancer detection in dermatomyositis patients. Nevertheless, the diagnosis of cancer in this population remains elusive in some cases. Further investigation is needed to improve our knowledge of the link between myositis and cancer.

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

CELIAC DISEASE AND ANTIBODIES ASSOCIATED WITH CELIAC DISEASE IN PATIENTS WITH INFLAMMATORY MYOPATHY

Celiac disease is usually associated with autoimmune disorders and has occasionally been reported in patients with inflammatory myopathies. Our aim was to determine the presence of celiac disease and antibodies associated with celiac disease in patients with inflammatory myopathies and to investigate their relationship. Serum antigliadin, anti–tissue transglutaminase, and antiendomysial antibodies were determined in 51 patients with inflammatory myopathies. HLA‐DQ2 and ‐DQ8 alleles were studied to assess their complementary diagnostic value. Jejunal biopsy was performed in patients with moderate to high levels of antigliadin antibodies. Patients with jejunal histology consistent with celiac disease initiated a gluten‐free diet. Seventeen patients (31%) were positive for antigliadin antibodies, which were significantly more frequent in patients with inclusion‐body myositis than dermatomyositis (P < 0.001). Positive status to HLA‐DQ2 and/or ‐DQ8 did not differ between antigliadin‐positive (75% and 12.5%) or ‐negative (60% and 15%) patients. Three of five jejunal biopsies were diagnostic for celiac disease with histological normalization after a gluten‐free diet. Thus, celiac disease is more prevalent in patients with inflammatory myopathies than in the general population. Positive status to HLA‐DQ2 allele, which is known to be more frequent in patients with inflammatory myopathies, could explain the high prevalence of antigliadin antibodies in this population. The diagnostic value of HLA‐DQ2 or ‐DQ8 haplotypes to detect celiac disease in patients with inflammatory myopathy is limited. Muscle Nerve, 2006

Muscle inflammation, autoimmune Addison's disease and sarcoidosis in a patient with dysferlin deficiency

Idiopathic inflammatory myopathies are a group of acquired, heterogeneous, systemic diseases commonly regarded as autoimmune disorders. Differential diagnosis includes muscular dystrophies, especially the dysferlin-deficiency myopathy. We report a case of a patient diagnosed with polymyositis and with associated autoimmune diseases that finally turned out to be a dysferlin deficiency (limb girdle muscular dystrophy type 2B). A possible link between dysferlin deficiency an autoimmunity is discussed.

Delayed diagnosis of late-onset Pompe disease in patients with myopathies of unknown origin and/or hyperCKemia

Pompe disease is a rare metabolic myopathy whose diagnosis is sometimes delayed despite being essential for improving clinical outcomes. We aimed to investigate the prevalence of late-onset Pompe disease among patients with a myopathy of unknown etiology, including polymyositis, or with idiopathic rise of creatine kinase (CK) levels, in a department of internal medicine. A cohort study was conducted in 241 subjects: 140 patients with myopathies of unknown origin or increased CK levels, 30 with polymyositis and 71 who constituted the control group of other myopathies. Acid α-glucosidase (GAA) activity was tested in dried blood spots. If a positive result was obtained, GAA activity in isolated lymphocytes and/or genetic testing was performed as a confirmatory diagnosis. Out of the 140 investigated patients, 2 patients with myopathies of unknown origin were confirmed to be positive for Pompe disease. Thus, late-onset Pompe disease should be considered among adult patients with myopathy of unknown origin.

Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories.

BACKGROUND AND OBJECTIVE Statin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies. PATIENTS AND METHODS Twenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls. RESULTS 21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95. CONCLUSIONS A new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.

Tumour TIF1 mutations and loss of heterozygosity related to cancer-associated myositis

Objectives To analyse the influence of genetic alterations and differential expression of transcription intermediary factor 1 (TIF1) genes in the pathophysiology of cancer-associated myositis (CAM). Methods Paired blood and tumour DNA samples from patients with anti-TIF1γ-positive CAM and from controls were analysed by whole-exome sequencing for the presence of somatic mutations and loss of heterozygosity (LOH) in their TIF1 genes. The genesis and maintenance of the autoimmune process were investigated immunohistochemically by studying TIF1γ expression in the different tissues involved in CAM (skin, muscle and tumour) based on the immunohistochemical H-score. Results From seven patients with anti-TIF1γ-positive CAM, we detected one somatic mutation and five cases of LOH in one or more of the four TIF1 genes compared with just one case of LOH in tumours from TIF1γ-negative myositis patients (86% vs 17%; P = 0.03). Compared with type-matched control tumours from non-myositis patients, TIF1γ staining was more intense in tumours from anti-TIF1γ-positive patients (H-score 255 vs 196; P = 0.01). Also, TIF1γ staining in muscle was slightly more intense in anti-TIF1γ-positive than in anti-TIF1γ-negative myositis (H-score 22 vs 5; P = 0.03). In contrast, intense TIF1γ staining was detected in the skin of both myositis and control patients. Conclusion Tumours from paraneoplastic anti-TIF1γ-positive patients showed an increased number of genetic alterations, such as mutations and LOH, in TIF1 genes. These genetic alterations, in the context of a high expression of TIF1γ in the tumour, muscle and skin of these patients may be key to understanding the genesis of paraneoplastic myositis.

El mini-CEX como instrumento de evaluación de la competencia clínica: estudio piloto en estudiantes de medicina

espanolIntroduccion. La evaluacion de la competencia clinica constituye un importante elemento de la formacion medica. En el presente articulo se presentan los resultados de un estudio piloto para evaluar la factibilidad del empleo del Mini-Clinical Evaluation Exercise (mini-CEX) en estudiantes de grado de medicina. Sujetos y metodos. Se utilizo el mini-CEX en estudiantes de tercer, cuarto y quinto cursos de la Facultad de Medicina de la Universitat de Barcelona durante las practicas clinicas de semiologia y propedeutica, neumologia/cirugia toracica y nefrologia/urologia en el curso academico 2013-2014. Los estudiantes completaron al menos una evaluacion y participaron diversos profesores de los departamentos correspondientes. Resultados. Participaron 13 tutores y 27 estudiantes, con un total de 64 observaciones y una media de 2,4 observaciones por estudiante. El tiempo medio empleado en cada una de ellas fue de 14 min (rango: 4-60 min) y en el periodo de feedback, de 8,4 min (rango: 3-30 min). La satisfaccion media de los estudiantes (9,2; rango: 6-10) fue superior a la de los tutores (8,8; rango: 7-10). Conclusiones. El estudio demostro la factibilidad del empleo del mini-CEX en estudiantes de medicina en cuanto al tiempo empleado para realizarlo y en la satisfaccion de los participantes. EnglishIntroduction. The evaluation of clinical skills is an important part of the medical training. The present article describes the results of a pilot study that was carried out to analyze the feasibility of the implementation of the Mini-Clinical Evaluation Exercise (mini-CEX) in medical students. Subjects and methods. Mini-CEX was used in students from third, fourth and fifth year of Medical School of the University of Barcelona during their clerkship in Internal Medicine, Pneumology/Thoracic surgery, Nephrology/Urology in the academic year 2013-2014. Students completed at least one encounter and several tutors from different departments participated in the study. Results. Thirteen tutors and 27 students participated, with 64 encounters and a mean of 2.4 encounters by student. The mean time of the encounters was 8.4 min (range: 4-60 min) and of the feedback period of 8.4 min (range: 3-30 min). The mean score of students’ satisfaction (9.2; range: 6-10) was higher than of the tutors (8.8; range: 7-10). Conclusions. The study showed the feasibility of mini-CEX in medical students regarding the time needed to perform it and the satisfaction of tutors and students with the experience.