Enfermedades autoinflamatorias / Autoinflammatory diseases

Las enfermedades autoinflamatorias monogénicas son desórdenes raros que resultan en defectos del sistema inmune innato, originando excesiva respuesta a señales de peligro, activación espontánea de vías inflamatorias o pérdida de reguladores inhibitorios. En los últimos 15 años un creciente número de enfermedades inflamatorias monogénicas han sido descriptas y sus respectivos genes responsables identificados. Las proteínas codificadas por estos genes están involucradas en las vías regulatorias de la inflamación y están expresadas fundamentalmente en las células del sistema inmune innato. Si bien un grupo de pacientes exhibe inflamación sistémica episódica (fiebres periódicas), estos desórdenes están mediados por una continua sobreproducción y liberación de mediadores pro-inflamatorios -especialmente la interleucina 1beta- y su conceptualización como enfermedades autoinflamatorias es preferible por sobre la de fiebres periódicas. Las enfermedades más frecuentes son fiebre mediterránea familiar (FMF), TRAPS, deficiencia de mevalonatocinasa/síndrome de hiper IgD (MKD/HIDS) y los síndromes periódicos asociados a criopirina (CAPS). Sus características clínicas frecuentemente incluyen fiebre, erupciones cutáneas, compromiso de serosas y reactantes de fase aguda. Los autoanticuerpos están usualmente ausentes pero pueden observarse en ciertos síndromes. El diagnóstico es clínico y se basa en las características fenotípicas. El diagnóstico genético es muy importante pero debe ser realizado de manera juiciosa e interpretado con cautela. El tratamiento con agentes biológicos que bloquean citocinas pro-inflamatorias, particularmente IL-1, ha demostrado ser efectivo en muchos pacientes. Sin embargo, en otros tantos casos no se descubren anormalidades genéticas y el tratamiento es subóptimo, planteando la posibilidad de mutaciones patogénicas en genes y vías aún no explorados.

The monogenic autoinflammatory diseases are rare, genetic disorders resulting in constitutive innate immune defects leading to excessive response to danger signals, spontaneous activation of inflammatory mediators or loss of inhibitory regulators. During the past 15 years, a growing number of monogenic inflammatory diseases have been described and their respective responsible genes identified. The proteins encoded by these genes are involved in the regulatory pathways of inflammation and are mostly expressed in cells of the innate immune system. Although a group of patients exhibit episodic systemic inflammation (periodic fevers), these disorders are mediated by continuous overproduction and release of pro-inflammatory mediators, notably IL-1β, and are best considered as autoinflammatory diseases rather than periodic fevers. The most common autoinflammatory diseases are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS) and the cryopyrin-associated periodic syndromes (CAPS). Clinical features often include fever, cutaneous rash, serosal involvement and acute phase reactants. Autoantibodies are usually absent but may accompany certain syndromes. Diagnosis remains clinical and is based on the different phenotypic features. Genetic diagnosis is of utmost importance, but must be performed judiciously and interpreted cautiously. Treatment with biologic agents that block proinflammatory cytokines, particularly IL-1, has proved to be dramatically effective in many patients. Still, in many cases of autoinflammation no genetic abnormalities are detected and treatment remains suboptimal, raising the question of novel pathogenic mutations in unexplored genes and pathways.

Rapid detection of methicillin resistant staphylococcus aureus bacteraemia in bactec blood culture bottles of ICU patients

Methicillin resistance and infections caused by methicillin-resistant Staphylococcus aureus [MRSA] represent a growing problem and a challenge for health-care institutions. Resistance to methicillin is primarily associated with acquisition of mecA gene. The aim of the current study was to find out the incidence of MRSA bacteraemia among ICU bacteraemic patients and evaluate direct mecA gene detection from blood culture bottles and the oxacillin [methicillin] disk diffusion method commonly used in hospitals to identify MRSA using PCR for mecA detection in isolates as the golden. The study was conducted on 300 ICU patients with pyrexia of unknown origin. Blood samples were collected under complete aseptic precautions for blood culture onto BACTEC blood culture bottles. Detection of mecA gene by Polymerase Chain Reaction [PCR] was carried directly on any bottle showing Gram-positive cocci in clusters in film. Isolates of all positive blood culture bottles were identified. For Staph aureus isolates oxacillin disk diffusion and mecA gene detection was carried. Out of 300 samples included in the study, 190 [63.3%] yielded growth. Methicillin resistant Staph aureus was isolated from 88/190 patients [46.3%]. The agreement between the results of mecA gene detection among isolates and those among blood culture bottles was found to be 100% [Kappa = 1] and the sensitivity 100%. Disk diffusion method detected 79 cases out of the 88 MRSA strains The agreement between the results of oxacillin disk diffusion sensitivity method and mecA detection either in isolates or blood culture bottles was found to be 94% [Kappa= 0.87] and the sensitivity was 89. 8%.Methicillin resistant Staph. aureus bacteraemia is a major problem in ICU. Detection of mecA gene by PCR from blood culture bottles is a good tool for rapid detection of methicillin resistance in staph aureus bacteremia. To confirm the specificity of this test, more samples from patients with Enterococcus and Streptococcus species bacteraemias need to be studied

Displasia ectodérmica hipohidrótica: caso clínico y revisión de la literatura / Hypohydrotic ectodermal dysplasia: a clinical case and review of the literature

La displasia ectodérmica hipohidrótica (DEH) es un trastorno genético que se caracteriza por hipohidrosis, hipotricosis e hipodoncia. Comúnmente afecta a varones con una herencia recesiva ligada al X, aunque existen otras formas con herencia autosómica dominante y recesiva. Los pacientes afectados pueden presentar intolerancia al calor, fiebre, hipertermia grave e incluso muerte súbita. Objetivo: Presentan el caso clínico de un paciente portador de DEH, y actualizar el conocimiento de la etiología y medidas terapéuticas de esta patología. Caso clínico: Se reporta el caso de una niña de 7 años de edad, que presenta escaso vello, alteraciones dentarias, amastia y escasa sudoración, compatible con una DEH y una probable herencia autosómica recesiva. Se comenta su evolución y manejo clínico, junto a aspectos embriológicos, genéticos, diagnósticos y el consejo genético de esta enfermedad.