RESUMEN
A patient with leukocyte adhesion deficiency type 1 (LAD1) had severe periodontitis and an intractable, deep, nonhealing sacral wound. We had previously found a dominant interleukin-23-interleukin-17 signature at inflamed sites in humans with LAD1 and in mouse models of the disorder. Blockade of this pathway in mouse models has resulted in resolution of the immunopathologic condition. We treated our patient with ustekinumab, an antibody that binds the p40 subunit of interleukin-23 and interleukin-12 and thereby blocks the activity of these cytokines, inhibiting interleukin-23-dependent production of interleukin-17. After 1 year of therapy, our patient had resolution of his inflammatory lesions without serious infections or adverse reactions. Inhibition of interleukin-23 and interleukin-17 may have a role in the management of LAD1. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
Asunto(s)
Interleucina-12/antagonistas & inhibidores , Interleucina-23/antagonistas & inhibidores , Síndrome de Deficiencia de Adhesión del Leucocito/tratamiento farmacológico , Ustekinumab/uso terapéutico , Encía/patología , Humanos , Inyecciones Subcutáneas , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Síndrome de Deficiencia de Adhesión del Leucocito/complicaciones , Masculino , Enfermedades Periodontales/tratamiento farmacológico , Enfermedades Periodontales/etiología , Enfermedades Periodontales/patología , ARN Mensajero/metabolismo , Úlcera Cutánea/tratamiento farmacológico , Úlcera Cutánea/etiología , Úlcera Cutánea/patología , Ustekinumab/efectos adversos , Adulto JovenRESUMEN
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.