The IL-2RG R328X nonsense mutation allows partial STAT-5 phosphorylation and defines a critical region involved in the leaky-SCID phenotype.

In addition to their detection in typical X-linked severe combined immunodeficiency, hypomorphic mutations in the interleukin (IL)-2 receptor common gamma chain gene (IL2RG) have been described in patients with atypical clinical and immunological phenotypes. In this leaky clinical phenotype the diagnosis is often delayed, limiting prompt therapy in these patients. Here, we report the biochemical and functional characterization of a nonsense mutation in exon 8 (p.R328X) of IL2RG in two siblings: a 4-year-old boy with lethal Epstein-Barr virus-related lymphoma and his asymptomatic 8-month-old brother with a Tlow B+ natural killer (NK)+ immunophenotype, dysgammaglobulinemia, abnormal lymphocyte proliferation and reduced levels of T cell receptor excision circles. After confirming normal IL-2RG expression (CD132) on T lymphocytes, signal transducer and activator of transcription-1 (STAT-5) phosphorylation was examined to evaluate the functionality of the common gamma chain (γc ), which showed partially preserved function. Co-immunoprecipitation experiments were performed to assess the interaction capacity of the R328X mutant with Janus kinase (JAK)3, concluding that R328X impairs JAK3 binding to γc . Here, we describe how the R328X mutation in IL-2RG may allow partial phosphorylation of STAT-5 through a JAK3-independent pathway. We identified a region of three amino acids in the γc intracellular domain that may be critical for receptor stabilization and allow this alternative signaling. Identification of the functional consequences of pathogenic IL2RG variants at the cellular level is important to enable clearer understanding of partial defects leading to leaky phenotypes.

¿Es útil el cribado familiar en el déficit selectivo de inmunoglobulina A? / Is familial screening useful in selective immunoglobulin A deficiency?

INTRODUCCIÓN: El déficit selectivo de IgA (DSIgA) es la inmunodeficiencia primaria más frecuente, siendo a menudo asintomática. Se ha descrito una elevada agregación familiar, sin conocerse el defecto genético causante ni su mecanismo hereditario. OBJETIVOS: Definir la utilidad del cribado de los familiares de primer grado de los pacientes con DSIgA valorando si los casos familiares presentan unas características clínicas e inmunológicas más graves que los casos esporádicos (CE) y si los familiares diagnosticados de DSIgA presentan sintomatología clínica significativa para justificar su cribado. PACIENTES Y MÉTODOS: Estudio transversal descriptivo (octubre del 2010-septiembre del 2011) de todos los pacientes con DSIgA controlados en nuestro centro, con revisión de datos demográficos, clínicos y analíticos. Se consideró como caso familiar (CF) todo aquel con al menos un familiar de primer grado (FPG) con DSIgA. RESULTADOS: De los 130 participantes, 42 eran pacientes con DSIgA y 88 FPG. Se diagnosticaron 13 CF (31%), 29 CE (69%) y 14 (16%) FPG enfermos (FPG-E). El número necesario a analizar para encontrar un FPG-E fue de 6 familiares. No hubo diferencias clínicas entre los pacientes. Hubo una proporción mayor de patología intestinal (p = 0,001, OR=9,57, IC del 95%, 2,59-35,3), ingresos (p = 0,045, OR=4,01; IC del 95%, 1,10-14,67) y necesidad de tratamiento crónico (p = 0,006, OR=5,5; IC del 95%, 1,57-19,54) en los FPG-E con respecto a los FPG sanos. CONCLUSIONES: A pesar de no encontrar más complicaciones clínicas en los CF de DSIgA, la elevada prevalencia de familiares afectados con afectación clínica significativa podría justificar la realización sistemática de estos programas de cribado

INTRODUCTION: Selective immunoglobulin A deficiency (SIgAD), the most common primary immunodeficiency, is often asymptomatic. High rates of familial clustering have been described in SIgAD, but the causative genetic defect and mechanism of inheritance are unknown. OBJECTIVES: To determine whether familial SIgAD cases show more severe clinical and immunological characteristics than sporadic ones; to investigate the utility of screening first-degree relatives (FDRs) of these patients, and to determine whether symptoms in affected family members are important enough to justify screening. PATIENTS AND METHODS: Descriptive, cross-sectional study (October 2010-September 2011) of all patients with SIgAD and followed up in our center. Demographic, clinical, and analytical data were reviewed. A familial case was defined as an SIgAD patient with at least one affected FDR. RESULTS: Of the 130 participants, 42 were SIgAD patients and 88 FDR. There were 13 (31%) familial cases and and 14 (16%) affected FDRs. Six family members had to be analyzed in order to detect one affected one. There were no clinical differences between familial and sporadic SIgAD cases. The percentages of intestinal disease (p=001, OR=9.57, 95%CI 2.59-35.3), hospitalizations (p=045, OR=4.01; 95%CI 1.10-14.67], and need for chronic treatment (p=006, OR=5.5; 95%CI 1.57-19.54) were higher in affected FDRs than in unaffected ones. CONCLUSIONS: The symptoms were not more severe in familial than sporadic SIgAD cases. Nonetheless, the elevated prevalence of affected FDRs with significant morbidity may justify routine screening of close family members of these patients

[Is familial screening useful in selective immunoglobulin A deficiency?]. / ¿Es útil el cribado familiar en el déficit selectivo de inmunoglobulina A?

INTRODUCTION: Selective immunoglobulin A deficiency (SIgAD), the most common primary immunodeficiency, is often asymptomatic. High rates of familial clustering have been described in SIgAD, but the causative genetic defect and mechanism of inheritance are unknown. OBJECTIVES: To determine whether familial SIgAD cases show more severe clinical and immunological characteristics than sporadic ones; to investigate the utility of screening first-degree relatives (FDRs) of these patients, and to determine whether symptoms in affected family members are important enough to justify screening. PATIENTS AND METHODS: Descriptive, cross-sectional study (October 2010-September 2011) of all patients with SIgAD and followed up in our center. Demographic, clinical, and analytical data were reviewed. A familial case was defined as an SIgAD patient with at least one affected FDR. RESULTS: Of the 130 participants, 42 were SIgAD patients and 88 FDR. There were 13 (31%) familial cases and and 14 (16%) affected FDRs. Six family members had to be analyzed in order to detect one affected one. There were no clinical differences between familial and sporadic SIgAD cases. The percentages of intestinal disease (p=001, OR=9.57, 95%CI 2.59-35.3), hospitalizations (p=045, OR=4.01; 95%CI 1.10-14.67], and need for chronic treatment (p=006, OR=5.5; 95%CI 1.57-19.54) were higher in affected FDRs than in unaffected ones. CONCLUSIONS: The symptoms were not more severe in familial than sporadic SIgAD cases. Nonetheless, the elevated prevalence of affected FDRs with significant morbidity may justify routine screening of close family members of these patients.

Actinomicosis apendicular como causa de masa ileocecal en la edad pediátrica: Caso clínico / Appendicular actinomycosis as a cause of ileocecal mass in children: Case report

Introducción. La actinomicosis apendicular es una patología rara producida por la invasión del apéndice cecal por bacterias del género Actinomyces al alterarse la barrera mucosa después de una causa predisponente, como podría ser una apendicitis aguda. Se presenta con mayor frecuencia en adultos, aunque en la literatura se han descrito algunos casos en edad pediátrica. En este artículo se presenta un nuevo caso pediátrico de actinomicosis apendicular de presentación atípica y se revisa la literatura al respecto. Caso clínico. Paciente varón de 10 años de edad derivado a nuestro hospital por el hallazgo intraoperatorio en otro centro de una tumoración en flanco derecho, sin identificación del apéndice cecal. Tras completar el estudio con pruebas de imagen, el paciente fue reintervenido bajo la orientación diagnóstica de apendicitis aguda complicada. Intraoperatoriamente, se identifica un plastrón organizado y con escasos signos inflamatorios agudos. La evolución postquirúrgica fue favorable con tratamiento antibiótico convencional. El estudio anatomopatológico de la pieza reveló una actinomicosis apendicular, por lo que se amplió el tratamiento antibiótico de forma ambulatoria y se descartó patología predisponente. Comentarios. La actinomicosis apendicular es una causa infrecuente de apendicitis que puede simular una tumoración intraabdominal en niños y adultos. Es necesario descartar patología predisponente y realizar un tratamiento antibiótico adecuado

Introduction. Appendicular actinomycosis is a rare disease produced by cecal appendix invasion by Actinomyces gender bacteria after a predisposing cause that disrupts mucosal barrier, such as acute appendicitis. The highest frequency appears in adults; however, there are cases in paediatric age described in literature. The aim of this article is to introduce a case of appendicular actinomycosis in a child with atypical presentation and to review the literature. Clinical case. 10-year-old boy transferred to our hospital due to intraoperative finding at a different centre of a right flank tumor, without identification of cecal appendix. After completing the study with image tests, the patient was re-intervened with the diagnosis of complicated acute appendicitis. Intraoperatively, an organized plastron lacking of acute inflammatory signs was found. Post-surgical evolution was positive with conventional antibiotic treatment. Histological study of the specimen revealed an appendicular actinomycosis, so antibiotic treatment was widened in an outpatient basis and predisposing diseases were ruled out. Comments. Appendicular actinomycosis is an infrequent cause of appendicitis that can simulate an intra-abdominal tumor in children and adults. It is necessary to rule out predisposing diseases and to administer an adequate antibiotic treatment

Meningitis recurrente por defectos anatómicos: la bacteria indica su origen / Recurrent meningitis due to anatomical defects: The bacteria indicates its origin

Introducción: La meningitis recurrente es una patología infrecuente. Los factores predisponentes son alteraciones anatómicas o situaciones de inmunodeficiencia. Presentamos 4 casos en los que, excluida una inmunodeficiencia, el microorganismo responsable orientó al defecto anatómico causante de las recurrencias. Pacientes y métodos: Revisión retrospectiva de 4 casos clínicos con diagnóstico de meningitis bacteriana recurrente. Resultados: Caso 1: niño de 30 meses con hipoacusia unilateral, diagnosticado por resonancia magnética (RM) de malformación de Mondini tras 2 episodios de meningitis por Haemophilus influenzae. Reparación quirúrgica tras tercera recurrencia. Caso 2: niña de 14 años diagnosticada por RM de defecto de lámina cribiforme posterior a 3 episodios de meningitis por Streptococcus pneumoniae. Se coloca válvula de derivación ventrículo-peritoneal. Caso 3: niña con meningitis por Staphylococcus aureus a los 2 y 7 meses. La RM muestra seno dérmico occipital que requiere exéresis. Complicación con abscesos cerebelosos por coexistencia de quiste dermoide. Caso 4: niño con meningitis por Streptococcus bovis a los 9 días y porEnterococcus faecium, Klebsiella pneumoniae y Escherichia coli a los 7 meses, con crecimiento de Citrobacter freundii y E. faecium posteriormente. RM compatible con síndrome de Currarino. Incluye fístula rectal de LCR, que se repara quirúrgicamente. A los 4 pacientes se les habían realizado pruebas de imagen durante los primeros episodios de meningitis, informadas como normales. Conclusiones: En los pacientes con meningitis recurrentes se debe valorar la posibilidad de un defecto anatómico; el microorganismo aislado debe ayudar a localizarlo. Es imprescindible conocer la flora normal de los potenciales focos. El tratamiento definitivo es habitualmente quirúrgico (AU)

Introduction: Recurrent meningitis is a rare disease. Anatomical abnormalities and immunodeficiency states are predisposing factors. Four cases, in which immunodeficiency was excluded, are presented. The causal microorganism led to the detection of the anatomical defect responsible for the recurrences. Patients and methods: Retrospective review of 4 cases with clinical diagnosis of recurrent bacterial meningitis. Results: Case 1: a thirty month-old boy with unilateral hearing loss, diagnosed with Mondini abnormality by magnetic resonance imaging (MRI) after 2 episodes of Haemophilus influenzae meningitis. Surgical repair after third recurrence. Case 2: fourteen year-old girl diagnosed by MRI with cribriform plate defect after 3 episodes of meningitis due toStreptococcus pneumoniae. Ventriculoperitoneal shunt was placed. Case 3: girl with meningitis due to Staphylococcus aureus at 2 and 7 months. MRI shows occipital dermal sinus requiring excision. Complication with cerebellar abscesses because of a coexisting dermoid cyst. Case 4: child with meningitis due to Streptococcus bovis at 9 days andEnterococcus faecium, Klebsiella pneumoniae and Escherichia coli at 7 months, with positive cultures to Citrobacter freundii and E. faecium later on. Spinal MRI led to the diagnosis of Currarino syndrome with CSF fistula, which was surgically repaired. The 4 patients had undergone image studies reported as normal during the first episodes. Conclusions: In patients with recurrent meningitis the possibility of an anatomical defect should be considered. The isolated microorganism should help to locate it. It is essential to know the normal flora of the different anatomical sites. The definitive treatment is usually surgical (AU)

[Appendicular actinomycosis as a cause of ileocecal mass in children: Case report]. / Actinomicosis apendicular como causa de masa ileocecal en la edad pediátrica: Caso clínico.

INTRODUCTION: Appendicular actinomycosis is a rare disease produced by cecal appendix invasion by Actinomyces gender bacteria after a predisposing cause that disrupts mucosal barrier, such as acute appendicitis. The highest frequency appears in adults; however, there are cases in paediatric age described in literature. The aim of this article is to introduce a case of appendicular actinomycosis in a child with atypical presentation and to review the literature. CLINICAL CASE: 10-year-old boy transferred to our hospital due to intraoperative finding at a different centre of a right flank tumor, without identification of cecal appendix. After completing the study with image tests, the patient was re-intervened with the diagnosis of complicated acute appendicitis. Intraoperatively, an organized plastron lacking of acute inflammatory signs was found. Post-surgical evolution was positive with conventional antibiotic treatment. Histological study of the specimen revealed an appendicular actinomycosis, so antibiotic treatment was widened in an outpatient basis and predisposing diseases were ruled out. COMMENTS: Appendicular actinomycosis is an infrequent cause of appendicitis that can simulate an intra-abdominal tumor in children and adults. It is necessary to rule out predisposing diseases and to administer an adequate antibiotic treatment.

INTRODUCCION: La actinomicosis apendicular es una patología rara producida por la invasión del apéndice cecal por bacterias del género Actinomyces al alterarse la barrera mucosa después de una causa predisponente, como podría ser una apendicitis aguda. Se presenta con mayor frecuencia en adultos, aunque en la literatura se han descrito algunos casos en edad pediátrica. En este artículo se presenta un nuevo caso pediátrico de actinomicosis apendicular de presentación atípica y se revisa la literatura al respecto. CASO CLINICO: Paciente varón de 10 años de edad derivado a nuestro hospital por el hallazgo intraoperatorio en otro centro de una tumoración en flanco derecho, sin identificación del apéndice cecal. Tras completar el estudio con pruebas de imagen, el paciente fue reintervenido bajo la orientación diagnóstica de apendicitis aguda complicada. Intraoperatoriamente, se identifica un plastrón organizado y con escasos signos inflamatorios agudos. La evolución postquirúrgica fue favorable con tratamiento antibiótico convencional. El estudio anatomopatológico de la pieza reveló una actinomicosis apendicular, por lo que se amplió el tratamiento antibiótico de forma ambulatoria y se descartó patología predisponente. COMENTARIOS: La actinomicosis apendicular es una causa infrecuente de apendicitis que puede simular una tumoración intraabdominal en niños y adultos. Es necesario descartar patología predisponente y realizar un tratamiento antibiótico adecuado.

[Recurrent meningitis due to anatomical defects: The bacteria indicates its origin]. / Meningitis recurrente por defectos anatómicos: la bacteria indica su origen.

INTRODUCTION: Recurrent meningitis is a rare disease. Anatomical abnormalities and immunodeficiency states are predisposing factors. Four cases, in which immunodeficiency was excluded, are presented. The causal microorganism led to the detection of the anatomical defect responsible for the recurrences. PATIENTS AND METHODS: Retrospective review of 4 cases with clinical diagnosis of recurrent bacterial meningitis. RESULTS: Case 1: a thirty month-old boy with unilateral hearing loss, diagnosed with Mondini abnormality by magnetic resonance imaging (MRI) after 2 episodes of Haemophilus influenzae meningitis. Surgical repair after third recurrence. Case 2: fourteen year-old girl diagnosed by MRI with cribriform plate defect after 3 episodes of meningitis due to Streptococcus pneumoniae. Ventriculoperitoneal shunt was placed. Case 3: girl with meningitis due to Staphylococcus aureus at 2 and 7 months. MRI shows occipital dermal sinus requiring excision. Complication with cerebellar abscesses because of a coexisting dermoid cyst. Case 4: child with meningitis due to Streptococcus bovis at 9 days and Enterococcus faecium, Klebsiella pneumoniae and Escherichia coli at 7 months, with positive cultures to Citrobacter freundii and E. faecium later on. Spinal MRI led to the diagnosis of Currarino syndrome with CSF fistula, which was surgically repaired. The 4 patients had undergone image studies reported as normal during the first episodes. CONCLUSIONS: In patients with recurrent meningitis the possibility of an anatomical defect should be considered. The isolated microorganism should help to locate it. It is essential to know the normal flora of the different anatomical sites. The definitive treatment is usually surgical.

Patología infecciosa importada en hospitales terciarios / Imported infectious diseases in tertiary hospital

INTRODUCCIÓN: En el ańo 2009 se crea en nuestro centro una Consulta de Patología Importada. El objetivo de este trabajo es conocer su aportación en cuanto a capacidad, calidad asistencial y docencia ofrecida. PACIENTES Y MÉTODOS: Estudio retrospectivo entre 2009 y 2011 donde se analizan: a) desarrollo del conocimiento mediante la valoración de protocolos y publicaciones realizadas, así como la docencia impartida; y b) capacidad y calidad asistencial ofrecida mediante el análisis de los pacientes atendidos, la adecuación a los protocolos y la accesibilidad a la consulta. Se clasifican los pacientes atendidos en 3 grupos: grupo 1 cribado del paciente inmigrante; grupo 2 consulta tras viaje a zona tropical o subtropical; grupo 3 cribado de enfermedad importada de transmisión vertical. RESULTADOS: Se han desarrollado y difundido en la web de la unidad 6 protocolos y 5 publicaciones científicas. Se han atendido 316 pacientes: 191 incluidos en el grupo 1 (29 adoptados y 162 inmigrantes); 57 en el grupo 2 (94,7% Visiting Friends and Relatives y 81,5% sin consulta previaje), que acudieron principalmente por clínica gastrointestinal (52,6%) y fiebre (43,8%); y 68 en el grupo 3 con riesgo de infección importada de transmisión vertical (62 Trypanosoma cruzi, 1 virus linfotrópico T humano y 5 Plasmodium spp.). La adecuación global a los protocolos disponibles fue del 77,1%. DISCUSIÓN: Las unidades de patología infecciosa deben adaptarse a la realidad de la población que atienden, siendo flexibles en su estructura. Es imprescindible la valoración periódica de la calidad asistencial ofrecida, así como la valoración en la rentabilidad de los estudios complementarios a realizar (AU) - es INTRODUCTION: An Imported Diseases Clinic was created in the hospital in 2009. The aim of this study was to asses its contribution in terms of capacity, quality of care and teaching offered. PATIENTS AND METHODS: A retrospective study was conducted from 2009 to 2011, analyzing: A) development of knowledge by means of protocols and publications created, and subject taught; B) capacity and quality of care offered by the analysis of patients seen, the adequacy of the protocols and accessibility.The patients were classified into 3 groups. Group 1: immigrant patient screening, group 2: patient consultation after tropical or sub-tropical travel, group 3: screening of vertical transmission of imported disease. RESULTS: Six protocols have been developed and disseminated on the unit website, as well as 5 scientific publications. A total of 316 patients were evaluated: 191 included in group 1 (29 Adopted and 162 Immigrants), 57 in group 2 (94.7% Visiting Friends and Relatives and 81.5% without a pre-travel consultation). They consulted due to, gastrointestinal symptoms (52.6%) and fever (43.8%), with 68 included in group 3 at risk of imported disease by vertical transmission (62 Trypanosoma cruzi, 1 Human T Lymphotropic Virus and 5 Plasmodium spp.). The overall adherence to the protocols was about 77.1%. DISCUSSION: Infectious Diseases Units must adapt to the reality of the population and be flexible in its structure. Periodic assessment of the quality of care offered is essential, as well as an evaluation on the need for additional studies

INTRODUCTION: An Imported Diseases Clinic was created in the hospital in 2009. The aim of this study was to asses its contribution in terms of capacity, quality of care and teaching offered. PATIENTS AND METHODS: A retrospective study was conducted from 2009 to 2011, analyzing: A) development of knowledge by means of protocols and publications created, and subject taught; B) capacity and quality of care offered by the analysis of patients seen, the adequacy of the protocols and accessibility.The patients were classified into 3 groups. Group 1: immigrant patient screening, group 2: patient consultation after tropical or sub-tropical travel, group 3: screening of vertical transmission of imported disease. RESULTS: Six protocols have been developed and disseminated on the unit website, as well as 5 scientific publications. A total of 316 patients were evaluated: 191 included in group 1 (29 Adopted and 162 Immigrants), 57 in group 2 (94.7% Visiting Friends and Relatives and 81.5% without a pre-travel consultation). They consulted due to, gastrointestinal symptoms (52.6%) and fever (43.8%), with 68 included in group 3 at risk of imported disease by vertical transmission (62 Trypanosoma cruzi, 1 Human T Lymphotropic Virus and 5 Plasmodium spp.). The overall adherence to the protocols was about 77.1%. DISCUSSION: Infectious Diseases Units must adapt to the reality of the population and be flexible in its structure. Periodic assessment of the quality of care offered is essential, as well as an evaluation on the need for additional studieS

Enfermedad invasora por Neisseria meningitidis serogrupo 29E y deficiencia de C5 / Invasive disease due to Neisseria meningitidis serogroup 29E and C5 deficiency

No disponible

Fiebre y lesiones cutáneas en un paciente con enfermedad granulomatosa crónica / Fever and skin lesions in a patient with chronic granulomatous disease

No disponible

[Imported infectious diseases in tertiary hospital]. / Patología infecciosa importada en hospitales terciarios.

INTRODUCTION: An Imported Diseases Clinic was created in the hospital in 2009. The aim of this study was to asses its contribution in terms of capacity, quality of care and teaching offered. PATIENTS AND METHODS: A retrospective study was conducted from 2009 to 2011, analyzing: A) development of knowledge by means of protocols and publications created, and subject taught; B) capacity and quality of care offered by the analysis of patients seen, the adequacy of the protocols and accessibility. The patients were classified into 3 groups. Group 1: immigrant patient screening, group 2: patient consultation after tropical or sub-tropical travel, group 3: screening of vertical transmission of imported disease. RESULTS: Six protocols have been developed and disseminated on the unit website, as well as 5 scientific publications. A total of 316 patients were evaluated: 191 included in group 1 (29 Adopted and 162 Immigrants), 57 in group 2 (94.7% Visiting Friends and Relatives and 81.5% without a pre-travel consultation). They consulted due to, gastrointestinal symptoms (52.6%) and fever (43.8%), with 68 included in group 3 at risk of imported disease by vertical transmission (62 Trypanosoma cruzi, 1 Human T Lymphotropic Virus and 5 Plasmodium spp.). The overall adherence to the protocols was about 77.1%. DISCUSSION: Infectious Diseases Units must adapt to the reality of the population and be flexible in its structure. Periodic assessment of the quality of care offered is essential, as well as an evaluation on the need for additional studies.

La infección en el paciente pediátrico inmunodeprimido / Infection in the immunodepressed pediatric patient

Desde 1996 la Unidad de Patología Infecciosa e Inmunode4ficiencias de Pediatría se ha adaptado a los camibos en las nuevas características de la infecciones en el paciente pediátrco, especialmente en el inmunodeprimido, compaginando la tarea asistencial, docente e investigadora, compaginando la tarea asitencial, docente e investigadora principalmente en 3 áreas: 1) inmunodeficiencias primarias (IDP), 2) infección por el VIH y 3) infecciones oportunistas, con especial dedicación a la infección fúngica invasiva. Actualmente se siguen más de 400 pacientes afectos de una IDP, se ha introducido el uso de gammaglobulina subcutánea en nuestro país y se colabora tanto con instituciones nacionales como internacionales parap romover el conocimiento de las IDP. La investigación en VIH se ha centrado en las complicaciones asociado a la infección y a la evaluación de la calidad asistencial ofrecida a estos pacientes y sus familias. Finalmente, debido a las características intrínsecas del paciente pediátrico, los esfuerzos en el campo de la infección fúngica se han dedicado al conocimiento de las propiedades farmacocinéticas y farmacodinámicas de los diferentes antifúngicos. Consideramos que en todo hospital pediátrico del tercer nivel se hace indispensable la presencia de un Sevicio de Infectología Pediátrica para avanzar en el campo de la racionalización del complejo y costoso tratamiento antiinfeccioso (AU)

Since 1996, the Pediatric Infectious Diseases Immunodeficiencies Unit has adapted itself to the changing features of infections in the pediatric patient, especially int he immunocompromised, combining health care, teaching and research mainly in 3 areas: 1) primary immunodeficiencies (PID), 2)HIV infection and 3) opportunistic infections, with special emphasis on invasive fungal infection. More than 400 patients with a PID are currently followed-up in our UNIT, we have introduced the use of subcutaneous immunoglobulin in Spain and collaborate with both national and international instituitonto promote awareness on PID, HIV research has focused on the complications associated with treatment, the chronic inflammatory process associated with infection and evaluationof the quality of care provided to these patients and their families. Finally, due to the intrinsic characteristics of pediatric patients, efforts in the field of fungal infection have been devoted to the understanding of the pharmacokinetic and pharmacodynamic properties of different antifungal drugs. We believe that in the any tertiary care pediatric hospital the presence of a Pediatric nfectious Diseases Departmetn is mandatory in order to optimize the rationalization ot the complex and expensive anti-infective treatment (AU)

Uso de derivados intravenosos de artemisinina en la malaria grave / Use of intravenous artemisinin derivatives in severe malaria

No disponible

Evaluación de un programa de valoración de adherencia al tratamiento antirretroviral / Evaluation of a program for assessing adherence to antiretroviral treatment

Introducción: Una baja adherencia al tratamiento antirretroviral (TARV) es la causa más frecuente de fracaso terapéutico tanto en niños como en adultos que viven con el VIH, siendo especialmente importante durante la adolescencia. En consecuencia, cualquier análisis de la efectividad del TARV deberá considerarse incompleto si no incluye una evaluación de la adherencia. El objetivo de este estudio es evaluar la utilidad de un programa de valoración de la adherencia al TARV en una población de pacientes pediátricos infectados por el VIH. Pacientes y métodos: Se trata de un estudio observacional y transversal, dentro del «Programa de educación sanitaria para la optimización de la adherencia en pacientes pediátricos con VIH», que forma parte del proyecto «No estoy solo». La adherencia se estudió simultáneamente mediante una combinación de diferentes métodos: entrevista personal, evolución de la carga viral y del recuento de linfocitos TCD4+, determinación de concentraciones plasmáticas de fármacos y registros de dispensación de farmacia. Resultados: Se incluyó un total de 20 pacientes (50% mujeres, edad mediana: 14,5 años). Se obtuvo un porcentaje de adherencia completa informada por el propio paciente o cuidador del 90% (IC 95%: 70-97,2%); sin embargo, el porcentaje medio de adherencia según los registros de dispensación fue significativamente inferior (83,3%; DE=32,88). La media de principios activos/día y de medicamentos/día fue de 3,5 (DE=0,83) y 5,5 (DE=2,72), respectivamente. Hubo una relación inversa entre el n.° de medicamentos/día y las puntuaciones de adherencia (F=13,8; p=0,002). Ninguno de los métodos de evaluación se relacionó de manera estadísticamente significativa con la adherencia, presentando la determinación de concentraciones plasmáticas una tendencia a la significación. Conclusiones: La adherencia global al TARV fue elevada y se vio favorecida por el uso de pautas posológicas sencillas. La adherencia informada por el paciente y/o el cuidador sobreestimó la verdadera adherencia al TARV. Recomendamos la utilización simultánea de diversos métodos de valoración de la adherencia en los niños y adolescentes que viven con el VIH (AU)

Introduction: Poor adherence to antiretroviral treatment (ART) is the commonest cause of treatment failure in children and adults living with HIV, and this is especially important during adolescence. Therefore, any analysis of ART effectiveness in children should include an evaluation of adherence to ART. The aim of this study is to assess the usefulness of an ART adherence monitoring program in an HIV-infected paediatric population. Patients and methods: An observational and cross-sectional study was performed, within the framework of the “Health Education Program for Optimising Adherence in Paediatric Patients with HIV”, which is part of the “I am not alone” project. Adherence was assessed simultaneously by different methods: personal interview, therapeutic drug monitoring, pharmacy dispensing records and evolution of viral load and T CD4+ lymphocyte count. Results: Twenty patients were included (50% female, median age 14.5 years). Percentage of self-reported full adherence was 90% (95% CI: 70-97.2%); however, the median adherence percentage according to pharmacy dispensing records was significantly lower (83.3%, SD=32.88). The average of drugs and dosage forms per day were 3.5 (SD=0.83) and 5.5 (SD=2.72), respectively. There was an inverse relationship between the number of dosage forms per day and adherence scores (F=13.8; P=0.002). No single method was statistically related to adherence, although therapeutic drug monitoring showed a trend towards significance. Conclusions: Global adherence to ART was high and was easier with simpler regimens. Self-reported adherence overestimated real adherence to ART in our cohort. The simultaneous use of different methods to assess adherence is recommended in HIV-infected children (AU)

[Evaluation of a program for assessing adherence to antiretroviral treatment]. / Evaluación de un programa de valoración de adherencia al tratamiento antirretroviral.

INTRODUCTION: Poor adherence to antiretroviral treatment (ART) is the commonest cause of treatment failure in children and adults living with HIV, and this is especially important during adolescence. Therefore, any analysis of ART effectiveness in children should include an evaluation of adherence to ART. The aim of this study is to assess the usefulness of an ART adherence monitoring program in an HIV-infected paediatric population. PATIENTS AND METHODS: An observational and cross-sectional study was performed, within the framework of the "Health Education Program for Optimising Adherence in Paediatric Patients with HIV", which is part of the "I am not alone" project. Adherence was assessed simultaneously by different methods: personal interview, therapeutic drug monitoring, pharmacy dispensing records and evolution of viral load and T CD4+ lymphocyte count. RESULTS: Twenty patients were included (50% female, median age 14.5 years). Percentage of self-reported full adherence was 90% (95% CI: 70-97.2%); however, the median adherence percentage according to pharmacy dispensing records was significantly lower (83.3%, SD=32.88). The average of drugs and dosage forms per day were 3.5 (SD=0.83) and 5.5 (SD=2.72), respectively. There was an inverse relationship between the number of dosage forms per day and adherence scores (F=13.8; P=.002). No single method was statistically related to adherence, although therapeutic drug monitoring showed a trend towards significance. CONCLUSIONS: Global adherence to ART was high and was easier with simpler regimens. Self-reported adherence overestimated real adherence to ART in our cohort. The simultaneous use of different methods to assess adherence is recommended in HIV-infected children.

Documento de Consenso de la Sociedad de Infectología Pediatrica y la Sociedad de Reumatología Pediatrica sobre el diagnóstico diferencial y el abordaje terapéutico de la fiebre recurrente / Consensus Document on the differential diagnosis and therapeutic approach to recurrent fever by the Paediatric Infectology Society and the Paediatric Rheumatology Society

La fiebre recurrente es un problema relativamente frecuente en la infancia. En la mayoría de las ocasiones es sencillo establecer su etiología generalmente asociada a episodios infecciosos banales. No obstante, en un pequeño porcentaje de casos estos episodios se deben a procesos de causa no infecciosa a menudo de complejo diagnóstico. En este documento se analiza el diagnóstico diferencial de la fiebre recurrente o periódica frente a otros procesos, con especial atención a las enfermedades autoinflamatorias (EA). Las EA son alteraciones de la inmunidad innata recientemente incluidas dentro de las inmunodeficiencias, sin embargo no se caracterizan por presentar infecciones lo que las diferencia de las inmunodeficiencias clásicas. Un importante número de las EA tienen una base genética conocida. La sintomatología que ocasionan se deriva de una inflamación sistémica que puede dar clínica y procesos muy variados. Uno de los grupos mejor conocidos es el formado por los síndromes hereditarios de fiebre periódica. Este grupo se caracteriza por presentar fiebre recurrente, asociada a diversos síntomas, con una relativa periodicidad y con intervalos libres o casi libres de síntomas. Para algunas de las entidades más frecuentes se dispone de criterios diagnósticos que son aquí recogidos, así como las características que deben hacernos iniciar el estudio genético. El tratamiento debe ser individualizado dada la complejidad de estos cuadros si bien se pueden dar algunas recomendaciones generales (AU)

Recurrent fever is a relatively common problem during childhood. Diagnosis is often easy and related to mild viral infections. However a small proportion of these cases originate from an underlying non-infectious process that is generally difficult to diagnose. In this paper we describe the differential diagnosis of recurrent or periodic fever versus other processes, with especial attention to autoinflammatory disorders (AD). AD are alterations of innate immunity, and they have been recently classified as an immunodeficiency. Anyhow, since infections are not present, these processes are different to the classic primary immunodeficiency. An important part of AD is of known genetic aetiology. The symptoms originate from an underlying inflammatory process and can have different clinical expressions. One of the most relevant groups is the hereditary syndromes of periodic fever. This group of diseases associates recurrent fever and several clinical symptoms with a relative periodicity, separated by intervals free or almost free of symptoms. We include the diagnostic criteria for some processes as well as the characteristics that should, eventually, lead to a genetic study. Although treatment should be individualised, we also include some general recommendations (AU)