Uso de PCR digital para definir terapéuticas específicas y seguimiento en enfermedades autoinflamatorias / Use of digital PCR to define specific therapeutics and follow-up in autoinflammatory diseases

Las enfermedades autoinflamatorias (AIDs) son un grupo heterogéneo de desórdenes monogénicos o poligénicos, con características de disregulación inmune innata y/o adaptativa, cuyo mecanismo central es la autoinflamación pero también pueden presentarse con autoinmunidad e inmunodeficiencia. En estos últimos años el desarrollo de las tecnologías de secuenciación masiva han provocado una explosión en el descubrimiento de nuevos genes responsables de AIDs monogénicas. Esto remarca la importancia de implementar este tipo de estudios para llegar a un diagnóstico definitivo sobre todo en este grupo de patologías genéticamente muy diversas donde los fenotipos clínicos se solapan. Sin embargo, dada la presencia de variantes de significación incierta (VUS), los resultados pueden no ser concluyentes planteándose la necesidad de desarrollar pruebas funcionales para determinar la patogenicidad de dichas variantes genéticas. En nuestro grupo de trabajo estamos aplicando la PCR digital en gotas (ddPCR), una técnica cuantitativa de 3era generación altamente sensible, especifica y reproducible que no necesita de curvas de calibración, para desarrollar pruebas funcionales que permitan no sólo reclasificar variantes VUS para lograr diagnósticos definitivos sino también estudiar los mecanismos responsables de las principales AIDs que permitan una estratificación de las terapéuticas especificas a aplicar y de esta manera poder contribuir al diagnóstico, tratamiento y seguimiento de nuestros pacientes en forma personalizada. (AU)

Autoinflammatory diseases (AIDs) are a heterogeneous group of monogenic or polygenic disorders, with characteristics of inborn and/or adaptive immune dysregulation, whose central mechanism is autoinflammation but may also present with autoimmunity and immunodeficiency. In recent years the development of massive sequencing technologies has led to an exponential increase in the discovery of new genes responsible for monogenic AIDs. This emphasizes the importance of the implementation of this type of studies to make a definitive diagnosis, especially in this group of genetically very diverse diseases with overlapping clinical phenotypes. However, given the presence of variants of uncertain significance (VUS), the results may not be conclusive, raising the need to develop functional tests to determine the pathogenicity of these genetic variants. In our working group we are applying droplet digital PCR (ddPCR), a highly sensitive, specific and reproducible third generation quantitative technique that does not require calibration curves, to develop functional tests that allow not only to reclassify VUS variants to achieve definitive diagnoses but also to study the mechanisms responsible for the main AIDs that allow for the stratification of specific treatments to be used and thereby contribute to the individualized diagnosis, treatment, and follow-up of our patients (AU)

Enfermedades autoinflamatorias sistémicas, entidades en auge: generalidades, principales síndromes monogénicos y aproximación al manejo terapéutico / Systemic autoinflammatory diseases, entities on the rise: basic concepts, main monogenic syndromes and approach to therapeutic management

Systemic autoinflammatory diseases are relatively recent entities caused by dysregulation of the innate immune system. They are mainly caused by monogenic mutations, although there are entities produced by polygenic mutations or of multifactorial origin. Traditionally, they have been classified based on the presence or absence of fever, however, thanks to the advancement of knowledge of their Pathogenic mechanisms and the signaling pathways involved, recently it has been advocated to classify them based on the latter. The three more important groups of monogenic autoinflammatory diseases are type 1 interferonopathies, inflammasomopathies and dysregulation in the nuclear factor kappa light chain enhancer of activated B cells [NFkB] pathway (relopahies). In this review, the main pathways involved, the main syndromes of each of these groups and the therapeutic approach are addressed. (AU)

Las enfermedades autoinflamatorias sistémicas son entidades relativamente recientes ocasionadas por disregulación del sistema inmune innato. Están ocasionadas fundamentalmente por mutaciones monogénicas, aunque existen entidades producidas por mutaciones poligénicas o de origen multifactorial. Tradicionalmente se han clasificadoen función de la presencia o ausencia de fiebre, sin embargo, con el avance en el conocimiento de sus mecanismos patogénicos y de las vías de señalización involucradas, recientemente se aboga por clasificarlas en base a esto último, siendo los tres grupos más importantes de entidades autoinflamatorias monogénicas las interferonopatías tipo 1,las inflamasomopatías y las ocasionadas por disregulación en la vía del factor nuclear potenciador de las cadenas ligeras kappa de las células B activadas [NF-KB] (relopatías). En la presente revisión se aborda de forma general las principales vías implicadas, los principales síndromes de cada uno de estos grupos y el abordaje terapéutico. (AU)

Hidradenitis supurativa: reporte de un caso / Hidradenitis suppurativa: a case report

Resumen La hidradenitis supurativa (HS) es una enfermedad dolorosa y crónica, que afecta en especial la unidad folículo-pilosebácea de la piel ubicada en ingle, axilas, región perianal, perineo, genitales y submamaria,regiones anatómicas donde se encuentran glándulas sudoríparas apocrinas. El curso clínico de la HS es heterogéneo pues varía desde formas muy graves con abscesos fluctuantes profundos y drenajes eventuales; concicatricesresiduales graves, hasta otra forma de enfermedad comparativamente leve caracterizada por la aparición de algunos nódulos inflamatorios,pústulas ypápulas,de manera recidivante. Comunicamos el caso de un niño de 12 añosde edad, con diagnóstico de hidradenitis supurativa,quien fue tratado con Adalimumab. Realizamos la revisión del estado de arte de esta patología, describimos sus características clínicas, criterios diagnósticos, diagnósticos diferenciales y los posibles tratamientos. Nuestra presentación, tiene por objeto relatar nuestra experiencia en el seguimiento del caso del paciente, y las vicisitudes diagnósticas al respecto, que variaron desde acné inflamatorio grave hasta finalmente arribar al diagnóstico de certeza de hidradenitis supurativa, basándonos en criterios clínicos y ecográficos.Consideramos de interés haber podido emplear el "agente biológico" inhibidordel factor de necrosis tumoral (FNT) que hemos mencionado, con excelente respuesta.

Abstract Hidradenitis suppurativa (HS) is a painful and chronic disease that particularlyaffects the follicle-pilosebaceous unit of the skin located in the groins, armpits, perianal region, perineum, genitals, and submammary glands, which areanatomical regions whereapocrine sweat glands are found. The clinical course of HS is heterogeneous as it varies from very severe forms with deep fluctuating abscesses and eventual drainage; with severe residual scars, to another form ofacomparatively mild condition characterized by the presence of some recurrent inflammatory nodules, pustules and papules as well. We report the case of a 12-year-old boy, diagnosed with hidradenitis suppurativa, who was treated with Adalimumab. We reviewed the state of the art of this pathology, described its clinical characteristics, diagnostic criteria, differential diagnoses and carried out possible treatments. The purpose of our presentation is to report our experience in monitoring the patient's case, along with the diagnostic vicissitudes in this regard, which ranged from severe inflammatory acne to finally arriving at a certain diagnosis of hidradenitis suppurativa, based on clinical and ultrasound criteria. We consider of interest the possibility of having been able to use the "biological agent" inhibitor of the tumor necrosis factor (TNF) that we have mentioned, with an excellent response.

Cambio de paradigma en las enfermedades autoinflamatorias monogénicas y las vasculitis sistémicas: el síndrome VEXAS / Paradigm shift in monogenic autoinflammatory diseases and systemic vasculitis: The VEXAS syndrome

A finales de 2020 se describió el síndrome VEXAS, como una enfermedad autoinflamatoria causada por variantes poscigóticas en el gen UBA1. Se presenta en varones adultos con fiebre recurrente, artralgias/artritis, condritis auricular/nasal, dermatosis neutrofílica, inflamación pulmonar, trombosis venosas y diferentes tipos de vasculitis. Los análisis muestran una respuesta de fase aguda elevada y anemia macrocítica. Es frecuente la coexistencia de mielodisplasia, y son características las vacuolas citoplasmáticas en precursores mieloides y eritroides en médula ósea. Los glucocorticoides a dosis medias-altas son eficaces, pero el resto de fármacos inmunodepresores, convencionales o biológicos, muestran una eficacia limitada o ausente. Azacitidina se ha asociado con una buena respuesta, sobre todo en pacientes con síndrome mielodisplásico acompañante. El trasplante alogénico de progenitores hematopoyéticos parece ser la única terapia curativa hasta el momento. El síndrome VEXAS ha supuesto un cambio de paradigma en el diagnóstico y tratamiento de las enfermedades autoinflamatorias y las vasculitis sistémicas. (AU)

VEXAS syndrome was described by the end of 2020 as an autoinflammatory disease caused by post-zygotic variants in the UBA1 gene. VEXAS syndrome occurs in adult males with recurrent fever, arthralgia/arthritis, ear/nose chondritis, neutrophilic dermatosis, lung inflammation, venous thrombosis, and different types of vasculitis. Common laboratory changes include raised acute phase reactants and macrocytic anemia. The coexistence of myelodysplasia is frequent, and bone marrow vacuolization of myeloid and erythroid precursors is characteristic. Glucocorticoids are effective at medium-high doses, but the remaining immunosuppressive drugs, either conventional or biological, have showed limited or absent efficacy. Azacitidine has been associated with a good response, especially in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation appears to be the only curative therapy by now. VEXAS syndrome has become a paradigm shift in the diagnosis and treatment of autoinflammatory diseases and systemic vasculitis. (AU)

Acute recurrent autoinflammatory myopericarditis: from pathophysiology to practice / Miopericarditis autoinflamatoria aguda recurrente: de la fisiopatología a la clínica

Recurrent myopericarditis is the acute inflammation of the pericardium and myocardium that relapses after a symptom-free interval of 4 to 6 weeks. A thorough differential diagnosis is necessary to identify uncommon causes that may have therapeutic and prognostic importance. These include autoinflammatory diseases, which can present as recurrent myopericarditis in genetically predisposed or impaired-immunity individuals.We present a 33-year-old male with polyclonal hypogammaglobulinemia and six episodes of myopericarditis, in which the diagnosis of a probable autoinflammatory syndrome was established. Targeted treatment based on the pathophysiological mechanismswas started with immunoglobulins and anakinra, with favourable clinical and serological outcome with no relapses.Organ-specific autoinflammatory diseases with myocardial involvement may be associated with life-threatening complications. The role of multidisciplinary care and a diagnostic approach focused on the pathophysiology of the disease could be the most important thing for early treatment to improve the prognosis and quality of life of our patients. (AU)

La miopericarditis recurrente es la inflamación aguda del pericardio yel miocardio que recidiva tras un periodo libre de síntomas de 4 a 6semanas. Es necesario realizar un diagnóstico diferencial exhaustivopara identificar causas poco comunes que puedan tener importanciaterapéutica y pronóstica. Entre ellas se encuentran las enfermedadesautoinflamatorias, que pueden presentarse como miopericarditis recurrente en individuos genéticamente predispuestos o una inmunidadalterada.Presentamos el caso de un varón de 33 años con hipogammaglobulinemia policlonal y seis episodios de miopericarditis, en el que seestableció el diagnóstico de un probable síndrome autoinflamatorio.Se inició un tratamiento dirigido con inmunoglobulinas y anakinra basado en los mecanismos fisiopatológicos de la enfermedad, con unresultado clínico y serológico favorable en ausencia de recaídas.Las enfermedades autoinflamatorias con afectación cardíaca órgano-específica pueden asociarse a complicaciones potencialmentemortales. El papel de la atención multidisciplinar y un enfoque diagnóstico centrado en la fisiopatología de la enfermedad, resultan devital importancia para instaurar un tratamiento precoz que mejore elpronóstico y la calidad de vida de nuestros pacientes. (AU)

Paradigm shift in monogenic autoinflammatory diseases and systemic vasculitis: The VEXAS syndrome. / Cambio de paradigma en las enfermedades autoinflamatorias monogénicas y las vasculitis sistémicas: el síndrome VEXAS.

VEXAS syndrome was described by the end of 2020 as an autoinflammatory disease caused by post-zygotic variants in the UBA1 gene. VEXAS syndrome occurs in adult males with recurrent fever, arthralgia/arthritis, ear/nose chondritis, neutrophilic dermatosis, lung inflammation, venous thrombosis, and different types of vasculitis. Common laboratory changes include raised acute phase reactants and macrocytic anemia. The coexistence of myelodysplasia is frequent, and bone marrow vacuolization of myeloid and erythroid precursors is characteristic. Glucocorticoids are effective at medium-high doses, but the remaining immunosuppressive drugs, either conventional or biological, have showed limited or absent efficacy. Azacitidine has been associated with a good response, especially in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation appears to be the only curative therapy by now. VEXAS syndrome has become a paradigm shift in the diagnosis and treatment of autoinflammatory diseases and systemic vasculitis.

Signo de Spodick: ¿aliado o enemigo? / Spodick's sign: ally or enemy?

La pericarditis se refiere a la inflamación de las capas del pericardio y es la forma más común de enfermedad pericárdica. Puede estar asociada a derrame pericárdico y resultar en un taponamiento. La enfermedad puede ser una condición aislada o una manifestación cardíaca de un trastorno sistémico (por ejemplo, enfermedades autoinmunes o autoinflamatorias). La pericarditis se categoriza como aguda, incesante, recurrente o crónica, pero se debe tener en cuenta que también se clasifica como de etiología infecciosa y no infecciosa, siendo la presentación idiopática la más común

Pericarditis refers to inflammation of the layers of the pericardium and is the most common form of pericardial disease. It may be associated with pericardial effusion and result in tamponade. The disease may be an isolated condition or a cardiac manifestation of a systemic disorder (e.g., autoimmune or autoinflammatory diseases). Pericarditis is categorized as acute, incessant, recurrent, or chronic, but it should be noted that it is also classified as being of infectious and noninfectious etiology, with the idiopathic presentation being the most common

Descripción de un caso de Fiebre Mediterránea Familiar / Family Mediterranean Fever: a case report

La Fiebre Mediterránea Familiar (FMF) es un trastorno autoinflamatorio hereditario de herencia autosómica recesiva, producida por mutaciones en el gen MEFV. La aparición de la enfermedad se produce antes de los 30 años de edad y se caracteriza por ataques recurrentes de fiebre y serositis con una duración de 1-4 días y de curación espontánea. Presentamos el caso de una familia que cumple criterios clínicos de FMF y presenta únicamente una mutación heterocigota en el gen MEFV lo cual viene a corroborar la posibilidad de un patrón de expresividad dominante en la FMF. (AU)

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disorder with an autosomal recessive inheritance pattern, due to mutations in the MEFV gene. The onset of the disease occurs before the age of 30 and is characterized by recurrent attacks of fever and serositis lasting 1-4 days and spontaneously healing. We present the case of a family that meets clinical criteria for FMF and presents only one heterozygous mutation in the MEFV gene, which corroborates the possibility of a dominant expressiveness pattern in FMF. (AU)

Characteristics and Disease Course in a Cohort of Children With PFAPA Syndrome in the Community of Madrid, Spain. / Características y evolución de una cohorte de niños con síndrome PFAPA en la Comunidad de Madrid.

INTRODUCTION: PFAPA syndrome is an autoinflammatory disease whose diagnosis is mainly clinical. Several treatments have been proposed; among them, tonsillectomy could be an effective one. MATERIAL AND METHODS: Retrospective multicenter study. Patients included were diagnosed with PFAPA syndrome, according to the Thomas criteria, in 3 hospitals in Madrid between 2009-2013. RESULTS: Thirty-two cases were included. Median age at onset and at diagnosis were 32 months (IQR 24-44) and 47.5 months (IQR 37-60), respectively. There were increases in leukocytes (13,580/µL [IQR 8,200-16,600] vs. 8,300/µL [IQR 7,130-9,650], P=.005), neutrophils (9,340/µL [IQR 5,900-11,620] vs. 3,660/µL [IQR 2,950-4,580], P=.002) and C-reactive protein (11.0mg/dL [IQR 6.6-12.7] vs. 0.2mg/dL [IQR 0.1-0.6], P=.003) during febrile episodes. In all, 80.8% of patients reported remission of symptoms within 24h after oral corticosteroid therapy. Fourteen patients were tonsillectomized. In 11, the febrile episodes stopped while, in 3, the frequency was reduced; there were 2 cases of postoperative bleeding. The disease was resolved in 56.3% of the patients, at a median age of 60 months (IQR 47-95), with similar duration in patients who were tonsillectomized and those who were not. CONCLUSIONS: We present a large cohort of children with PFAPA syndrome, with clinical and analytical features similar to those described in the literature, and a good response to corticosteroids and a high resolution rate of symptoms after tonsillectomy.

Osteomielitis Crónica Multifocal Recurrente: presentación de caso / Chronic Recurrent Multifocal Osteomyelitis: presentation of case

Los síndromes autoinflamatorios son un grupo de enfermedades caracterizadas por episodios espontáneos, recurrentes o persistentes de inflamación multisistémica. En ellos no se evidencia una etiología infecciosa, neoplásica o autoinmune. Están causadas por alteraciones de la inmunidad innata, lo que ocasiona una desregulación del sistema inflamatorio a nivel del inflamosoma. Estos síndromes se subdividen en dos grandes grupos los síndromes hereditarios de fiebre periódica y las enfermedades autoinflamatorias persistentes, dentro de este último se ubican las enfermedades inflamatorias óseas donde se incluye la osteomielitis multifocal crónica recurrente. Presentamos un caso de una niña de 9 años que ingresa en nuestro hospital por un síndrome febril prolongado y después de múltiples investigaciones se concluye como una osteomielitis multifocal crónica recurrente.

Autoinflammatory syndromes are a group of diseases characterized by spontaneous, recurrent or persistent episodes of multisystem inflammation. They do not show an infectious, neoplastic or autoimmune etiology. They are caused by alterations of the innate immunity, which causes a dysregulation of the inflammatory system at the level of the inflammasome. These syndromes are subdivided into two major groups, the hereditary syndromes of periodic fever and the persistent autoinflammatory diseases; within the latter are the inflammatory bone diseases which chronic recurrent multifocal osteomyelitis. We present a case of a 9-year-old girl who enters our hospital due to a prolonged febrile syndrome and after multiple investigations, it concludes as a Chronic Recurrent Multifocal Osteomyelitis.

Monogenic autoinflammatory diseases: General concepts and presentation in adult patients. / Enfermedades autoinflamatorias monogénicas: conceptos generales y presentación en pacientes adultos.

Monogenic autoinflammatory diseases (AIFD) are rare disorders characterized by an uncontrolled increase of the systemic inflammatory response, which is caused by mutations in genes involved in inflammatory pathways. Over the last few years, new genes and proteins responsible for new monogenic AIFD have been identified and a substantial improvement in their treatment has been achieved. Monogenic AIFD manifestations typically begin during childhood, but they can also occur in adults. Compared to pediatric patients, adults usually present with a less severe disease and fewer long-term complications. In addition, patients with adult-onset disease carry low-penetrance mutations more often than pathogenic variants. A late-onset of AIFD may be occasionally associated with the presence of somatic mutations. In this study, we review the most frequent monogenic AIFD, and others recently described, which may occur during adulthood.

Autoinflammatory Diseases in Pediatric Dermatology-Part 1: Urticaria-like Syndromes, Pustular Syndromes, and Mucocutaneous Ulceration Syndromes. / Enfermedades autoinflamatorias en dermatología pediátrica. Parte 1: síndromes urticariformes, síndromes pustulosos y síndromes con ulceraciones cutáneo-mucosas.

Monogenic autoinflammatory diseases are a heterogeneous emergent group of conditions that are currently under intensive study. We review the etiopathogenesis of these syndromes and their principal manifestations. Our aim is to propose a classification system based on the clinicopathologic features of typical skin lesions for routine clinical use in dermatology. Our focus is on diagnosis in pediatric practice given that this is the period when the signs and symptoms of these syndromes first appear. In Part 1 we discuss the course of urticaria-like syndromes, which include cryopyrin-associated periodic conditions and hereditary periodic fever syndromes. Pustular syndromes are also covered in this part. Finally, we review the range of therapies available as well as the genetic mutations associated with these autoinflammatory diseases.

Autoinflammatory Diseases in Pediatric Dermatology-Part 2: Histiocytic, Macrophage Activation, and Vasculitis Syndromes. / Enfermedades autoinflamatorias en dermatología pediátrica. Parte 2: síndromes histiocítico-macrofágicos y síndromes vasculopáticos.

The discovery of new autoinflammatory syndromes and novel mutations has advanced at breakneck speed in recent years. Part 2 of this review focuses on vasculitis syndromes and the group of histiocytic and macrophage activation syndromes. We also include a table showing the mutations associated with these autoinflammatory syndromes and treatment alternatives.

Autoinflammatory diseases in adults. Clinical characteristics and prognostic implications. / Enfermedades autoinflamatorias en el adulto. Características clínicas e implicaciones pronósticas.

Autoinflammatory diseases are clinical conditions with inflammatory manifestations that present in a periodic or persistent manner and are caused by acquired or hereditary disorders of the innate immune response. In general, these diseases are more common in childhood, but cases have been reported in adults and are therefore important for all specialists. There are few references on these diseases in adults due to their low prevalence and underdiagnosis. The aim of this study is to review the scientific literature on these disorders to systematise their clinical, prognostic and treatment response characteristics in adults.

Psoriasis pustulosa generalizada / Generalized pustular psoriasis

Introducción: la psoriasis pustulosa generalizada (PPG) es una forma grave de psoriasis asociada a manifestaciones sistémicas. Es una enfermedad infrecuente y potencialmente letal. En las últimas décadas, se ha avanzado mucho en la comprensión de su fisiopatología, gracias a estudios inmunológicos y genéticos. Objetivo y método: El objetivo de esta revisión es actualizar los conceptos respecto a la fisiopatología, diagnóstico y tratamiento de la PPG. Se realizó una revisión del tema mediante una búsqueda bibliográfica en Pubmed y LILACS en los últimos 10 años, y además se agregaron referencias relevantes que no se encontraran en los resultados. Resultados: La PPG podría comprenderse como una enfermedad del grupo de las enfermedades autoinflamatorias, cuya causa es una mutación en el gen IL36RN, que produciría una falla estructural o una secreción inadecuada del antagonista del receptor de IL36, lo que conduciría a un desbalance en la contra-regulación de las citoquinas pro-inflamatorias de la familia IL-1. Su gatillante más frecuente es la interrupción abrupta del uso de corticoides, aunque existen numerosos factores reportados. El tratamiento de primera línea es la hospitalización, manejo con terapia tópica y sistémica con retinoides o terapia biológica, para luego continuar con un esquema de mantención. Conclusión: Dado los avances en su investigación, la PPG podría considerarse una entidad etiológicamente distinta a la psoriasis común.

Introduction: generalized pustular psoriasis (GPP) is a severe form of psoriasis associated with systemic manifestations. It is a rare and potentially lethal disease. In recent decades, much progress has been made in understanding its pathophysiology, thanks to immunological and genetic studies. Objective and Methods: The aim of this review is to update the concepts regarding the pathophysiology, diagnosis and treatment of GPP. A review was performed by searching in PubMed and LILACS databases in the last 10 years, also relevant references that were not in the results were aggregated. Results: GPP could be understood as a disease of the group of autoinflammatory diseases, caused by a mutation in the gene IL36RN that produce structural failure or an inadequate secretion of IL36 receptor antagonist, leading to an imbalance in the counter-regulation of the pro-inflammatory cytokines from the IL-1 family. Its most common trigger is the abrupt discontinuation of corticosteroids, although there are numerous factors reported. The first line treatment is hospitalization, management with topical and systemic retinoid therapy or biological therapy, and continue with a scheme of maintenance afterwards. Conclusion: Due to the progress in its investigation, GPP could be regarded as an etiologically distinct entity to psoriasis vulgaris.

Hidradenitis supurativa / Hidradenitis suppurativa

Se comunican tres casos de hidradenitis supurativa, que respondieron con relativo éxito al adalimumab sub-cutáneo. Revisamos el tema y proponemos la hipótesis de su futura inclusión, en el amplio espectro de las enfermedades autoinflamatorias.(AU)

Three cases of hidradenitis suppurativa with a relative good response to the adalimumab sub cutaneous, are reported. A comprehensive review of the subject is made. The hypothesis of hidradenitis suppurativa as an autoinflammatory diseases, is proposed.(AU)

Hidradenitis supurativa / Hidradenitis suppurativa

Se comunican tres casos de hidradenitis supurativa, que respondieron con relativo éxito al adalimumab sub-cutáneo. Revisamos el tema y proponemos la hipótesis de su futura inclusión, en el amplio espectro de las enfermedades autoinflamatorias.

Three cases of hidradenitis suppurativa with a relative good response to the adalimumab sub cutaneous, are reported. A comprehensive review of the subject is made. The hypothesis of hidradenitis suppurativa as an autoinflammatory diseases, is proposed.

Descripción de un caso de fiebre mediterránea familiar / Family Mediterranean Fever - case description

RESUMEN: Arch Med Interna 2013 - 35(3):101-104 La fiebre mediterránea familiar es una enfermedad autosómica recesiva, causada por mutaciones en el gen MEFV, el cual codifica una proteína denominada pirina. Esta proteína interviene en la formación del inflamasoma que estimula la activación de la IL-1β a través de la activación de la caspasa-1. Esta proteína tendría un efecto inhibitorio sobre la activación de la IL-1 β, por lo que las mutaciones de pérdida de función de ésta causarían una regulación en más de la inflamación. Forma parte de los síndromes hereditarios de fiebre periódica, caracterizados por episodios inflamatorios recurrentes autolimitados que cursan con fiebre, poliserositis, sinovitis y manifestaciones cutáneas. Es más frecuente en determinados grupos étnicos como es el caso que se presenta en este trabajo, se considera de interés por la dificultad en su diagnóstico. Es opinión de los autores que esta enfermedad es subdiagnosticada en Uruguay.

ABSTRACT: Arch Med Interna 2013 - 35(3):101-104 Familial Mediterranean fever is an autosomal recessive disease caused by mutations in the gene MEFV, which encodes a protein called pirin. This protein is involved in the formation of stimulating inflamasome activation of IL-1β through activation of caspase-1. This protein would have an inhibitory effect on activation of IL-1β, so loss of function mutations cause an up-regulation of the inflammatory response. It is part of the hereditary periodic fever syndromes which characterized by recurrent episodes of fever, polyserositis, synovitis, and cutaneous manifestations. 
It is more common in certain ethnic groups such as this case, which is presented because of the difficulty in its diagnosis. It is the opinion of the authors that this disease is underdiagnosed in Uruguay.

Advances in the diagnosis and treatment of tumor necrosis factor receptor-associated periodic syndrome.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominant disease included in the group of autoinflammatory syndromes. It is characterized by recurrent episodes of fever and inflammation in different regions of the body. The main clinical manifestations are myalgia, migratory erythematous rash, periorbital edema, and abdominal pain. The diagnosis is reached using gene analysis and prognosis depends on the appearance of amyloidosis secondary to the recurrent episodes of inflammation. Tumor necrosis factor inhibitors and corticosteroids are the most widely used treatments. In recent years, significant advances have been made in the diagnosis and treatment of TRAPS, thanks to a better understanding of its pathogenesis. Dermatologists must be aware that the skin manifestations of TRAPS are particularly important, as they are often diagnostic.

Síndrome PFAPA / PFAPA syndrome

Introducción: PFAPA es una enfermedad pediátrica caracterizada por fiebre recurrente asociada a síntomas de cabeza y cuello. La etiopatogenia es desconocida. Se han usado diferentes tratamientos, incluyendo corticoides, cimetidina y tonsilectomía. Objetivos: describir la epidemiología, presentación clínica, hallazgos de laboratorio, diagnóstico diferencial y tratamiento. Métodos: se realizó una revisión sistemática de reportes de casos y ensayos clínicos de PFAPA en las bases de datos Lilacs, Medline, Scielo y Biblioteca Cochrane. Fueron utilizados como descriptores DeCS/MeSH las palabras clave:PFAPA syndrome, periodic fever in children. Resultados: se revisaron 23 publicaciones con 379 casos. La edad promedio al inicio fue de 3.2 años (0.05 a 37) y habían transcurrido 3.5 años (0.08 a 20) desde el diagnóstico. Las crisis febriles duraban 4.4 días (2 a 14), con periodicidad de 29.5 días (7 a 70). Conclusión: el síndrome PFAPA es una entidad de descripción relativamente reciente, necesitándose mayor información para un diagnóstico rápido y un abordaje terapéutico. (AU)