RESUMO
CARD11-associated diseases are monogenic inborn errors of immunity involving immunodeficiency, predisposition to malignancy and immune dysregulation such as lymphoproliferation, inflammation, atopic and autoimmune manifestations. Defects in CARD11 can present as mutations that confer a complete or a partial loss of function (LOF) or contrarily, a gain of function (GOF) of the affected gene product. We report clinical characteristics, immunophenotypes and genotypes of 15 patients from our center presenting with CARD11-associated diseases. Index cases are pediatric patients followed in our immunology division who had access to next generation sequencing studies. Variant significance was defined by functional analysis in cultured cells transfected with a wild type and/or with mutated hCARD11 constructs. Cytoplasmic aggregation of CARD11 products was evaluated by immunofluorescence. Nine index patients with 9 unique heterozygous CARD11 variants were identified. At the time of the identification, 7 variants previously unreported required functional validation. Altogether, four variants showed a GOF effect as well a spontaneous aggregation in the cytoplasm, leading to B cell expansion with NF-κB and T cell anergy (BENTA) diagnosis. Additional four variants showing a LOF activity were considered as causative of CARD11-associated atopy with dominant interference of NF-kB signaling (CADINS). The remaining variant exhibited a neutral functional assay excluding its carrier from further analysis. Family segregation studies expanded to 15 individuals the number of patients presenting CARD11-associated disease. A thorough clinical, immunophenotypical, and therapeutic management evaluation was performed on these patients (5 BENTA and 10 CADINS). A remarkable variability of disease expression was clearly noted among BENTA as well as in CADINS patients, even within multiplex families. Identification of novel CARD11 variants required functional studies to validate their pathogenic activity. In our cohort BENTA phenotype exhibited a more severe and expanded clinical spectrum than previously reported, e.g., severe hematological and extra hematological autoimmunity and 3 fatal outcomes. The growing number of patients with dysmorphic facial features strengthen the inclusion of extra-immune characteristics as part of the CADINS spectrum. CARD11-associated diseases represent a challenging group of disorders from the diagnostic and therapeutic standpoint, especially BENTA cases that can undergo a more severe progression than previously described.
Assuntos
Proteínas Adaptadoras de Sinalização CARD , Síndromes de Imunodeficiência , Humanos , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Guanilato Ciclase/metabolismo , Heterozigoto , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/terapia , NF-kappa B/metabolismoRESUMO
La rosácea es una dermatosis crónica que se manifiesta clínicamente con eritema, telangiectasias, pápulas y pústulas en la parte central de la cara. Afecta, sobre todo, a los adultos y, en raras ocasiones, a los niños. La rosácea puede también presentar afección ocular y preceder, aparecer en forma simultánea o con posterioridad a las lesiones cutáneas; es mayor el riesgo de complicaciones oculares en los niños. La baja prevalencia de esta patología en la infancia origina demoras en el diagnóstico. Se presenta a un paciente de 1 año de edad con rosácea ocular y cutánea que desarrolló opacidades corneales con compromiso de la agudeza visual. Se destaca la importancia del diagnóstico y del tratamiento precoz para evitar el desarrollo de secuelas.
Rosacea is a chronic skin disease characterized by erythema, telangiectasia, papules and pustules in the central facial region. It most often affects adults and is rare in children. Rosacea can also present ocular involvement. Symptoms can precede cutaneous findings, appear simultaneously or after them, with a higher risk of ocular complications in children. Because of low prevalence of rosacea in childhood, the diagnosis is frequently delayed. We report a 1-year-old boy with ocular and cutaneous rosacea who developed corneal opacities and visual impairment. Early diagnosis and treatment is considerable to avoid sequels.
Assuntos
Humanos , Masculino , Lactente , Criança , Traumatismos Oculares , RosáceaRESUMO
Rosacea is a chronic skin disease characterized by erythema, telangiectasia, papules and pustules in the central facial region. It most often affects adults and is rare in children. Rosacea can also present ocular involvement. Symptoms can precede cutaneous findings, appear simultaneously or after them, with a higher risk of ocular complications in children. Because of low prevalence of rosacea in childhood, the diagnosis is frequently delayed. We report a 1-year-old boy with ocular and cutaneous rosacea who developed corneal opacities and visual impairment. Early diagnosis and treatment is considerable to avoid sequels.
La rosácea es una dermatosis crónica que se manifiesta clínicamente con eritema, telangiectasias, pápulas y pústulas en la parte central de la cara. Afecta, sobre todo, a los adultos y, en raras ocasiones, a los niños. La rosácea puede también presentar afección ocular y preceder, aparecer en forma simultánea o con posterioridad a las lesiones cutáneas; es mayor el riesgo de complicaciones oculares en los niños. La baja prevalencia de esta patología en la infancia origina demoras en el diagnóstico. Se presenta a un paciente de 1 año de edad con rosácea ocular y cutánea que desarrolló opacidades corneales con compromiso de la agudeza visual. Se destaca la importancia del diagnóstico y del tratamiento precoz para evitar el desarrollo de secuelas.
Assuntos
Opacidade da Córnea/etiologia , Oftalmopatias/diagnóstico , Rosácea/diagnóstico , Transtornos da Visão/etiologia , Oftalmopatias/etiologia , Humanos , Lactente , Masculino , Rosácea/complicaçõesRESUMO
El xantogranulomajuvenil es una patología benigna y representa la forma más común de histiocitosis de células no Langerhans. Está caracterizado por la presencia de pápulas o nodulos firmes de coloración rosada o amarillo amarronada, que comprometen, principalmente, la piel y, de forma excepcional, otros órganos. Es una entidad autolimitada con una involución espontánea en los primeros 5 años de vida. Presentamos a una paciente de 1 mes de vida con una lesión congénita en el abdomen, cuya histopatología mostró la presencia de células gigantes multinucleadas de Touton, características de esta patología. Destacamos la presentación infrecuente de este tipo de lesión y la importancia de los múltiples diagnósticos diferenciales que se deben tener en cuenta debido a la edad de la paciente y a sus características.
Juvenile xanthogranuloma is a bening pathology and it represents the most common form of non-Langerhans cell histiocytosis. It is characterized by the presence of papules or firm nodules of a pinkish or yellow-brownish nature, which mainly compromise the skin and, exceptionally, other organs. It is a self-limited entity having a spontaneous regression during the first five years of life. We report the case of a one-month-old patient who presented a congenital tumor in the abdomen, whose histopathology showed the presence of multinucleated giant Touton cells, which are typical of this pathology. We emphasize the rare occurrence of this type of lesion and the importance of the multiple differential diagnosis to be taken into account due to the age of the patient and the characteristics of the lesion.
Assuntos
Humanos , Feminino , Lactente , Xantogranuloma Juvenil/congênito , Xantogranuloma Juvenil/diagnósticoRESUMO
Juvenile xanthogranuloma is a bening pathology and it represents the most common form of non-Langerhans cell histiocytosis. It is characterized by the presence of papules or firm nodules of a pinkish or yellow-brownish nature, which mainly compromise the skin and, exceptionally, other organs. It is a self-limited entity having a spontaneous regression during the first five years of life. We report the case of a one-month-old patient who presented a congenital tumor in the abdomen, whose histopathology showed the presence of multinucleated giant Touton cells, which are typical of this pathology. We emphasize the rare occurrence of this type of lesion and the importance of the multiple differential diagnosis to be taken into account due to the age of the patient and the characteristics of the lesion.
El xantogranuloma juvenil es una patología benigna y representa la forma más común de histiocitosis de células no Langerhans. Está caracterizado por la presencia de pápulas o nódulos firmes de coloración rosada o amarillo amarronada, que comprometen, principalmente, la piel y, de forma excepcional, otros órganos. Es una entidad autolimitada con una involución espontánea en los primeros 5 años de vida. Presentamos a una paciente de 1 mes de vida con una lesión congénita en el abdomen, cuya histopatología mostró la presencia de células gigantes multinucleadas de Touton, características de esta patología. Destacamos la presentación infrecuente de este tipo de lesión y la importancia de los múltiples diagnósticos diferenciales que se deben tener en cuenta debido a la edad de la paciente y a sus características.
Assuntos
Xantogranuloma Juvenil/congênito , Feminino , Humanos , Lactente , Xantogranuloma Juvenil/diagnósticoRESUMO
Polyarteritis nodosa is a rare vasculitis in children characterized by necrotizing inflammation in small and medium size arteries. It is classified into systemic and cutaneous PAN according to the presence of systemic symptoms or visceral involvement. We describe the case of a 14-year-old girl with cutaneous Polyarteritis nodosa with an atypical clinical presentation.
Assuntos
Poliarterite Nodosa/patologia , Pele/patologia , Adolescente , Biópsia , Feminino , Humanos , Necrose , Gordura Subcutânea/patologiaRESUMO
Polyarteritis nodosa is a rare vasculitis in children characterized by necrotizing inflammation in small and medium size arteries. It is classified into systemic and cutaneous PAN according to the presence of systemic symptoms or visceral involvement. We describe the case of a 14-year-old girl with cutaneous Polyarteritis nodosa with an atypical clinical presentation.
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