ABSTRACT
El síndrome de VEXAS (Vacuolas, enzima E1, ligado al X, Autoinflamatorio, Somático) es un síndrome autoinflamatorio de inicio en la edad adulta que se caracteriza por mutaciones somáticas en el gen UBA1 y se considera el prototipo de enfermedad hematoinflamatoria. Los pacientes con síndrome de VEXAS exhiben manifestaciones inflamatorias y hematológicas que pueden conducir a diagnósticos clínicos como policondritis recidivante, poliarteritis nodosa, síndrome de Sweet y síndrome mielodisplásico. El diagnóstico requiere la evaluación de la médula ósea en búsqueda de vacuolas citoplásmicas en precursores mieloides y eritroides. Sin embargo, la confirmación genética de las mutaciones en UBA1 es necesaria. El tratamiento es un desafío y a menudo incluye glucocorticoides e inmunosupresores, con respuestas variables. Las terapias hipometilantes y el trasplante alogénico de células progenitoras hematopoyéticas se consideran terapias prometedoras. El pronóstico es influido por factores genéticos y clínicos. El objetivo de esta revisión es proporcionar una visión general sobre la patogénesis, la presentación clínica, el tratamiento y el pronóstico del síndrome de VEXAS para la comunidad médica latinoamericana.(AU)
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory syndrome characterized by somatic mutations in the UBA1 gene and is considered the prototype of hematoinflammatory diseases. Patients with VEXAS syndrome exhibit inflammatory and hematological manifestations that can lead to clinical diagnoses such as relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, and myelodysplastic syndrome. Diagnosis requires bone marrow evaluation to identify cytoplasmic vacuoles in myeloid and erythroid precursors. However, genetic confirmation of mutations in UBA1 is necessary. Treatment is challenging and often involves glucocorticoids and immunosuppressants with variable responses. Hypomethylating agents and allogenic haemopoietic stem cell transplant are considered promising therapies. Prognosis is influenced by genetic and clinical factors. The aim of this review is to provide an overview of the pathogenesis, clinical presentation, treatment, and prognosis of VEXAS syndrome for the Latin American medical community.(AU)
Subject(s)
Humans , Male , Female , Exanthema/drug therapy , Vacuoles , Sweet Syndrome , Polychondritis, Relapsing , VasculitisABSTRACT
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory syndrome characterized by somatic mutations in the UBA1 gene and is considered the prototype of hematoinflammatory diseases. Patients with VEXAS syndrome exhibit inflammatory and hematological manifestations that can lead to clinical diagnoses such as relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, and myelodysplastic syndrome. Diagnosis requires bone marrow evaluation to identify cytoplasmic vacuoles in myeloid and erythroid precursors. However, genetic confirmation of mutations in UBA1 is necessary. Treatment is challenging and often involves glucocorticoids and immunosuppressants with variable responses. Hypomethylating agents and allogenic haemopoietic stem cell transplant are considered promising therapies. Prognosis is influenced by genetic and clinical factors. The aim of this review is to provide an overview of the pathogenesis, clinical presentation, treatment, and prognosis of VEXAS syndrome for the Latin American medical community.
Subject(s)
Myelodysplastic Syndromes , Skin Diseases, Genetic , Adult , Humans , Glucocorticoids , Immunosuppressive Agents , MutationABSTRACT
La enfermedad autoinflamatoria de la queratización (AiKD, por sus siglas en inglés) es un concepto clínico novedoso que engloba a las enfermedades que presentan antecedentes genéticos, así como mecanismos patogénicos mixtos de autoinflamación y autoinmunidad, lo que en su conjunto se traducirá en una queratinización aberrante de la piel. Los recientes avances han revelado causas genéticas y/o factores predisponentes para una serie de AiKD, dentro de los que se pueden enumerar la presencia de las mutaciones en el IL36RN, en relación con la psoriasis pustulosa, la acrodermatitis continua y la hidradenitis supurativa; en el CARD14, en relación con la pitiriasis rubra pilaris tipo V y algunas formas de psoriasis pustulosa, y en el NLRP1 en relación con la queratosis liquenoide crónica familiar (KLC, por sus siglas en inglés). Se sospecha que la fisiopatología de la AiKD también estaría presente en algunos trastornos no monogénicos. Se debe de comprender que existe una relación bidireccional entre la inflamación y la queratinización para poder determinar un tratamiento óptimo; así mismo para poder desarrollar nuevos fármacos ambos factores deben de tenerse en cuenta. Probablemente en los próximos años nuevas enfermedades inflamatorias de la queratinización serán incluidas dentro del grupo de las AiKD (AU)
Autoinflammatory keratinization disease (AiKD) is a novel clinical concept encompassing diseases with a genetic background and mixed pathogenic mechanisms of autoinflammation and autoimmunity, leading to an aberrant keratinization of the skin. Recent advances in medical genetics have revealed genetic causes and/or predisposing factors for a number of AiKD's, such as mutations in IL36RN related with pustular psoriasis, acrodermatitis continua and hidradenitis suppurativa, in CARD14 in pityriasis rubra pilaris type V and some forms of pustular psoriasis, and in NLRP1 related with familial keratosis lichenoides chronica (KLC). It is suspected that AiKD pathophysiology would also be involved in non-monogenic disorders. The bidirectional relationship between inflammation and keratinization should be understood in order to outline optimal management, and new drug development should take both targets into account. We assume that new inflammatory keratinization diseases may be recognized as AiKDs in the coming years (AU)
Subject(s)
Humans , Skin Diseases/diagnosis , Inflammation/diagnosis , Keratins , Pityriasis Lichenoides/diagnosis , Hidradenitis/diagnosis , Psoriasis/diagnosis , Keratosis/diagnosisABSTRACT
Autoinflammatory keratinization disease (AiKD) is a novel clinical concept encompassing diseases with a genetic background and mixed pathogenic mechanisms of autoinflammation and autoimmunity, leading to an aberrant keratinization of the skin. Recent advances in medical genetics have revealed genetic causes and/or predisposing factors for a number of AiKD's, such as mutations in IL36RN related with pustular psoriasis, acrodermatitis continua and hidradenitis suppurativa, in CARD14 in pityriasis rubra pilaris type V and some forms of pustular psoriasis, and in NLRP1 related with familial keratosis lichenoides chronica (KLC). It is suspected that AiKD pathophysiology would also be involved in non-monogenic disorders. The bidirectional relationship between inflammation and keratinization should be understood in order to outline optimal management, and new drug development should take both targets into account. We assume that new inflammatory keratinization diseases may be recognized as AiKDs in the coming years.
