Asunto(s)
Dedos/patología , Poliarteritis Nudosa/diagnóstico , Inmunodeficiencia Combinada Grave/diagnóstico , Anemia Hemolítica/etiología , Azatioprina/uso terapéutico , Preescolar , Consanguinidad , Ciclofosfamida/uso terapéutico , Errores Diagnósticos , Glucocorticoides/uso terapéutico , Hemoptisis/etiología , Hemorragia/etiología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Lactante , Enfermedades Pulmonares/etiología , Masculino , Necrosis , Inmunodeficiencia Combinada Grave/complicaciones , Inmunodeficiencia Combinada Grave/terapia , Grasa Subcutánea/patología , Vasculitis/etiologíaRESUMEN
Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.3 years (1.3-47.7) spanning 1693 patient years, were enrolled. Eczema, recurrent respiratory tract infections, allergies, abscesses, viral infections and mucocutaneous candidiasis were the most frequent clinical manifestations. Overall survival probability in this cohort [censored for hematopoietic stem cell transplantation (HSCT)] was 87 % at 10, 47 % at 20, and 33 % at 30 years of age, respectively. Event free survival was 44, 18 and 4 % at the same time points if events were defined as death, life-threatening infections, malignancy or cerebral complications such as CNS vasculitis or stroke. Malignancy was diagnosed in 23/136 (17 %) patients (11 hematological and 9 epithelial cancers, 5 other malignancies) at a median age of 12 years. Eight of these patients died from cancer. Severe, life-threatening infections were observed in 79/136 (58 %); severe non-infectious cerebral events occurred in 14/136 (10 %). Therapeutic measures included antiviral and antibacterial prophylaxis, immunoglobulin replacement and HSCT. This study provides a comprehensive evaluation of the clinical phenotype of DOCK8 deficiency in the largest cohort reported so far and demonstrates the severity of the disease with relatively poor prognosis. Early HSCT should be strongly considered as a potential curative measure.
Asunto(s)
Estudios de Asociación Genética , Factores de Intercambio de Guanina Nucleótido/deficiencia , Factores de Intercambio de Guanina Nucleótido/genética , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Incidencia , Lactante , Infecciones/diagnóstico , Infecciones/epidemiología , Infecciones/etiología , Síndrome de Job/complicaciones , Síndrome de Job/diagnóstico , Síndrome de Job/genética , Síndrome de Job/inmunología , Síndrome de Job/mortalidad , Síndrome de Job/terapia , Recuento de Linfocitos , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Neoplasias/epidemiología , Neoplasias/etiología , Fenotipo , Adulto JovenRESUMEN
Myasthenia gravis is among the rare complications after allogeneic hematopoietic stem cell transplantation and is usually associated with chronic GVHD. Herein, we report a 2-year and 10 months of age female with Griscelli syndrome, who developed severe myasthenia gravis at post-transplant +22nd month and required respiratory support with mechanical ventilation. She was unresponsive to cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate mofetil and the symptoms could only be controlled after plasma exchange and subsequent use of rituximab, in addition to cyclosporine A and mycophenolate mofetil maintenance. She is currently asymptomatic on the 6th month of follow-up.
