Abscesos cerebrales por Dermacoccus nishinomiyaensis como primera manifestación de enfermedad granulomatosa crónica / Dermacoccus nishinomiyaensis brain abscesses as the first manifestation of chronic granulomatous disease

La enfermedad granulomatosa crónica es una inmunodeficiencia primaria poco frecuente, que secaracteriza por defectos en alguna de las subunidades del complejo enzimático nicotinamida adeninadinucleótido fosfato oxidasa, que ocasiona un déficit en la generación de anión superóxido por losfagocitos. Dentro de este grupo, la forma ligada al X es la más frecuente. Se reporta el caso de una paciente de sexo femenino de 2 años con enfermedad granulomatosa crónica autosómica recesiva, con mutación en gen CYBA, quien presentó manifestación inicial de la enfermedad con abscesos cerebrales ocasionados por un germen oportunista (Dermacoccus nishinomiyaensis). Esta infección permitió la sospecha diagnóstica temprana, por lo que recibió el tratamiento y la profilaxis en forma oportuna. Actualmente, se encuentra libre de infecciones, a la espera del trasplante de células progenitoras hematopoyéticas.

Chronic granulomatous disease is a rare primary immunodeficiency characterized by defects in one of the subunits of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex, which causes a deficiency in the capacity of phagocytes to generate superoxide anion. Within this group, the X-linked form is the most frequent. Here we report the case of a 2-year-old female patient with autosomal recessive chronic granulomatous disease, with a mutation in the CYBA gene, whose initial manifestation was brain abscesses caused by an opportunistic microorganism (Dermacoccus nishinomiyaensis). The infection led to an early diagnostic suspicion, so treatment and prophylaxis were administered in a timely manner. Currently, she is infectionfree, awaiting hematopoietic progenitor cell transplantation.

Osteomielitis multifocal por Serratia marcescens en un niño con enfermedad granulomatosa crónica / Serratia marcescens multifocal osteomyelitis in a child with chronic granulomatous disease

Resumen La enfermedad granulomatosa crónica (EGC) es una inmunode-ficiencia primaria poco frecuente. Se caracteriza por una alteración en la función de los fagocitos, causando infecciones recurrentes bacterianas y fúngicas. Presentamos el caso clínico de un niño con una osteomielitis multifocal por Serratia marcescens , microorganismo infrecuente como causa de infecciones óseas en niños, aunque asociado a la EGC. El estudio de infecciones con presentación clínica y agentes inhabituales deben hacer sospechar una EGC. Su diagnóstico precoz en la vida, así como el tratamiento antimicrobiano oportuno y el uso posterior de una profilaxis antimicrobiana adecuada logrará evitar recurrencias infecciosas y secuelas.

Abstract Chronic granulomatous disease (CGD) is a rare primary immuno-deficiency. It is characterized by an alteration in the function of phagocytes causing recurrent bacterial and fungal infections. This is a case report of a child with multifocal osteomyelitis by Serratia marcescens, an infrequent as a cause of bone infections, although associated with CGD. The study of infections with clinical presentation and unusual agents should lead to suspicion of CGD. The diagnosis early in life, as well as timely antimicrobial treatment and the subsequent antimicrobial prophylaxis will avoid infectious recurrences and sequelae.

Infección pulmonar por Arthrographis kalrae en un paciente con enfermedad granulomatosa crónica / Pulmonary infection by Arthrographis kalrae in patient with chronic granulomatous disease

Antecedentes: Arthrographis kalrae es un hongo hialino de crecimiento lento que, en su desarrollo, forma artroconidios. Es un patógeno oportunista que causa infecciones en personas inmunocomprometidas e inmunocompetentes, y ha sido aislado muy raramente en muestras clínicas de seres humanos. Caso clínico: Se describe el caso de un paciente con inmunodeficiencia primaria y afectación pulmonar con evolución tórpida. Presentó compromiso de ambos pulmones a pesar del tratamiento antibiótico y antifúngico instaurado. Durante su seguimiento, se realizaron múltiples biopsias pulmonares y se aisló A. kalrae en el cultivo de tejido pulmonar. Recibió tratamiento con posaconazol, con buena respuesta y remisión de las lesiones. Conclusión: Este es el primer caso reportado de infección pulmonar por A. kalrae en un paciente pediátrico con enfermedad granulomatosa crónica en Argentina.

Background: Arthrographis kalrae is a hyaline fungus that grows forming arthroconidia. It is an opportunistic pathogen that causes infections in immunocompromised as in immunocompetent people and has been rarely isolated from human clinical samples. Case report: We describe the case of a male child with primary immunodeficiency who initially presented unilateral pneumonia and progressed to bilateral involvement despite antibiotic, antifungal treatment. A. kalrae was diagnosed by pulmonary biopsy. He received posaconazole with resolution of disease. Conclusions: This is the first case of A. kalrae pulmonary infection in a pediatric patient with chronic granulomatous disease in Argentina.

Infecciones por Serratia, ¿debemos pensar en mmunodeficienaas primarias? / Serratia infections, should we think about primary immunodeficiencies?

La enfermedad granulomatosa crónica es una inmunodeficiencia primaria, con una incidencia de 1/200 000-250 000recién nacidos vivos. Afecta, principalmente, a varones; la mayoría de las mutaciones son ligadas al cromosoma X y las formas autosómicas recesivas ocurren, con más frecuencia, en comunidades con mayor número de matrimonios consanguíneos. Se caracteriza por sensibilidad a infecciones recurrentes y graves, bacterianas y fúngicas, con formación de granulomas, debido a la incapacidad de los fagocitos para generar compuestos reactivos de oxígeno, necesarios para la muerte intracelular de microorganismos fagocitados. Se presentan tres casos de enfermedad granulomatosa crónica en los que se aisló Serratia marcescens y, tras una anamnesis minuciosa y obtener resultados de pruebas de funcionalidad de neutrófilos, se llegó a un diagnóstico molecular de la enfermedad. La enfermedad granulomatosa crónica puede manifestarse de formas muy variadas, por lo que el alto índice de sospecha y una buena anamnesis son fundamentales para alcanzar un diagnóstico.

Chronic granulomatous disease (CGD) is a primary immunodeficiency with an incidence of 1/200,000-250,000 live births. CGD affects mainly male patients, most of the mutations being X-linked, and autosomal recessive forms occur more frequently in communities with greater numbers of consanguineous marriages. CGD is characterized by sensitivity to recurrent and severe bacterial and fungal infections, with formation of granulomas due to the inability of phagocytes to generate reactive oxygen compounds, necessary for the intracellular death of phagocytic microorganisms. We report three cases of CGD in which Serratia marcescens was isolated, and after detailed anamnesis and performance of neutrophil function tests, a molecular diagnosis of the disease was reached. CGD can be manifested in a wide variety of ways, so that high suspicion and a meticulous anamnesis are essential to reach a diagnosis.

A propósito de un caso: micosis pulmonar en paciente pediátrico con enfermedad granulomatosa crónica / Case report: pulmonary mycosis in children with chronic granulomatous diseaseSE

A 8-year-old girl, born and resident of Guárico state, was referred to our Department because of a history of recurrent pneumonia and a history of deceased sister by unspecified lung disease. At the age of 4 years she had suffered several episodes of pneumonia requiring hospitalization. These episodes were no-responsive to antibiotic therapy and treatment for tuberculosis. Subsequently, At the age of 8 years she was hospitalized again for an episode of left lower lobe pneumonia that did not improve. Studies were performed to rule out pulmonary pathology disease: Cystic Fibrosis was discarded and also Pulmonary Tuberculosis. Serology for HIV and Fungi were negative. Because serological studies were inconclusive, a videobronchoscopy plus Bronchoalveolar lavage and lung tissue biopsy were performed, which reported bronchitis and chronic granulomatous and caseous necrosis. Special stains were observed that suggest fungus infection. Primary immunodeficiency was suspected in the patient, because the presence of recurrent pneumonia of different etiologies. The presence of the granuloma observed by the videobronchoscopy. A positive culture for Histoplasma and Aspergillus fungi, and the result of the oxidative capacity test, where the deficiency was observed in the microbicidal activity of macrophages. They were strong evidence that corroborated the immunodeficiency called Chronic Granulomatous Disease.

Escolar femenino de 8 años de edad, natural y procedente del Estado Guárico, con antecedente de hospitalizaciones por neumonías recurrente desde los 4, recibió antibioticoterapia endovenosa y cumplió tratamiento antifímico en dos oportunidades, persistiendo con sintomatología respiratoria. A los 8 años precisó nueva hospitalización por diagnóstico de neumonía del lóbulo inferior izquierdo. Por no presentar mejoría y antecedente de hermana fallecida por patología pulmonar no precisada fue referida a nuestro centro. Se realizaron estudios por patología pulmonar crónica: se descartó Fibrosis Quística y Tuberculosis Pulmonar. Serología para HIV y Hongos Negativa. Por no ser concluyentes los estudios serológicos se realizó Videobroncoscopia más lavado y biopsia, la cual reportó bronquitis crónica granulomatosa y necrosis caseosa. Coloraciones especiales: hongos intracitoplasmáticos sugestivos de Histoplasma Sp. y en el cultivo presentó crecimiento de Aspergillus fumigatus. Ante la presencia de paciente con neumonía recurrente por diferentes etiologías se sospechó la presencia de Inmunodeficiencia Primaria, planteando en base al reporte de la videobroncoscopia de granuloma y la confirmación de Infección por Histoplasma y Aspergillus una Enfermedad Granulomatosa Crónica que fue documentada al medir la deficiencia en la actividad microbicida dependiente de oxigeno evaluada a través del Test de Capacidad Oxidativa.

BCGiosis as a presenting feature of a child with chronic granulomatous disease

Bacillus Calmette Guerin (BCG) vaccine, which is administered to all newborns in some regions, could lead to serious complication ranging from local disease (known as BCGitis) to disseminated disease (BCGosis) in a group of patients with primary immunodeficiency diseases. We are reporting here a 3.5 year-old girl with a history of prolonged BCGitis, which developed to disseminated disease without any other special features. Immunological studies with nitro-blue tetrazolium test confirmed the diagnosis of chronic granulomatous disease in this patient. Chronic granulomatous disease should be considered in the list of differential diagnosis in all children with BCGosis, even in the absence of any other manifestations related to immunodeficiency.

A novel mutation of the CYBB gene resulting in severe form of X-linked chronic granulomatous disease.

We evaluated a boy who had multiple Salmonella septicemia, Aspergillus pneumonia and brain abscesses. His nitroblue tetrazolium (NBT) test was reportedly abnormal. The dihydrorhodamine (DHR) flow cytometry assay was compatible with typical X-linked chronic granulomatous disease (X-CGD). CYBB analysis revealed a novel complex mutation atggacg --> ttca in exon 12 (base pairs 1532-1538). As a result, 3 amino acids Tyr 511, Gly 512 and Arg 513 were deleted and replaced by 2 amino acids, Phe and Gln. The DHR and mutation analysis of his mother showed normal DHR pattern and no mutations in exon 12 of CYBB gene. In conclusion, any children with multiple Salmonella and Aspergillus infection should be suspected of CGD. NBT test, DHR assay and gene analysis are helpful toolsto confirm the diagnosis e v en i n the case of de novo mutation.

Malakoplakia of colon in a child with celiac disease and chronic granulomatous disease.

Malakoplakia is a rare pseudotumoral inflammatory disease known to affect immunocompromised subjects. We report a 4-year-old boy with malakoplakia of colon who was diagnosed with celiac disease in late infancy; despite aggressive nutritional and medical management for celiac disease, symptoms did not resolve. His nitro-blue-tetrazolium test was compatible with chronic granulomatous disease. In colonic biopsy Michaelis-Gutmann bodies were seen.

Acremonium kiliense infection in a child with chronic granulomatous disease

Infection by unusual microorganisms can be one of the clinical manifestations of primary immunodeficiency (PID). We report on a four-month-old child with pneumonia caused by the fungus Acremonium kiliense as the first clinical manifestation of chronic granulomatous disease. We emphasize the importance of an active search for unusual organisms in immunodeficient patients, and a precise diagnosis and early institution of specific treatment against such microorganisms for the reduction of the morbidity and mortality of these patients.

Fatal granulomatous disease of childhood: presenting as acute abdomen.

Fatal granulomatous disease of childhood is a rare disorder of phagocytic function. We report a 6-year-old boy who presented with acute abdomen. The diagnosis was established by mesenteric lymph node biopsy obtained at laparotomy. The boy succumbed within hours of surgery.

Granulomatose septique chronique chez une fillette revelee par une aspergilose pulmonaire invasive et une paraplegie flasque

The invasive Pulmonary Aspergillosis [lPA] is the principal cause of death in patients with chronic granulomatosis disease [CGD]. It can happen before age of one and can reveal the [CGD]. Usually, the transmission of GSD is linked to in 65% of cases. We report, the case of a girl aged 3 years issued from consanguine mariage referred to hospital for hemoptysia. We note that at 40 days she presents an suppurate adenitis. She is hypotrophic at 3DS without respiratory problem, she has a splenomegaly. The radiography chest note an alveolar and interstitiel opacity bilateral, apical right and basal left. There is a biological inflammatory syndrome. During the evolution, the child presents a paraplegia secondary to cornpression myelitis. A D5 laminectomy in urgency was done. The vertebral Biopsia, the serology and the culture isolate fumigatus aspergillus the GCD is evoqued confirmed by the NBT test who was negatif. In We have to look for GCD in front of pulmonary aspergillus The vertebra lesion is secondary to pulmonary lesion. Our observation is noticeable by the recessive autosomal transmission who was seen in 35% of cases, and by the neurologic complication rarely reported

Manifestaciones otorrinolaringológicas de las enfermedades granulomatosas: Experiencia en el Hospital Universitario de Caracas, Venezuela / Otorhinolaryngologic manifestation of granulomatose diseases: Experience at Hospital Universitario de Caracas, Venezuela

Las enfermedades granulomatosas representan un grupo heterogeneo de afecciones de evolucion cronica, caracterizadas por su tendencia a persistir y a progresar. En la esfera otorrinolaringologica, causan lesiones mucosas granulomatosas necrotizantes, que se manifiestan por un variado espectro de formas clinicas, afectando todos los organos del tracto respiratorio superior, ocasionando graves defectos anatomicos y severos trastornos funcionales. En el Servicio de Otorrinolaringologia del Hospital Universitario de Caracas se presentan con mayor frecuencia la tuberculosis, leishmaniasis, paracoccidioidomicosis e histoplasmosis. Se realiza una revision de las manifestaciones clinicas más frecuentes y se hacen consideraciones diagnosticas, ya que son enfermedades que requieren un alto indice de sospecha y representan un reto a la terapeutica otorrinolaringologica, debido a lo prolongado, costoso y mal tolerado del tratamiento, asi como por la tendencia natural a recidivar

Chronic granulomatous disease in two Chinese families.

Two Chinese families with X-linked chronic granulomatous disease (CGD) are reported. The first case was an 11-month-old male baby and the second a 2-month-old male baby. Both patients presented with persistent infections caused by Staphylococcus and Candida since birth. Neutrophil functions were studied in patients and a number of family members. Chemotaxis and phagocytosis were normal in every subject. Slide and spectrophotometric nitroblue tetrazolium (NBT) tests of both patients were abnormal and remained unchanged in spite of treatment with ascorbic acid, levamisole, sulfamethoxazole, trimethoprim and isoniazide. Mothers were proved to be carriers as evidenced by the presence of both normal and CGD phagocytes in the slide NBT test. During the 2-month follow-up period, the percentage of normal phagocytes from the mother of case 1 varied from 12% to 73%, which correlated with the fluctuation of spectrophotometric NBT value. The slide NBT test of the mother of case 2 was nearly normal in face of the presence of CGD phagocytes. Both carrier mothers were healthy and asymptomatic.

Pericardite constritiva como complicaçäo de doença granulomatosa crônica na infância / Constrictive pericarditis as a complication of chronic granulomatous disease in infancy

Apresenta-se um paciente de 11 meses de idade, do sexo masculino, acompanhado na Unidade de Imunopatologia do infstituto da Criança "Prof. Pedro de Alcantara" do Hospital das Clínicas da Faculdade de Medicina da Universidade de Paulo, portador de doença granulomatosa crônica da infância, que evoluiu com pericardite constrictiva, manifestaçäo rara nesta imunodeficiência. Discutem-se alguns aspectos desta entidade, dando ênfase ao diagnóstico precoce e à terapêutica de suporte