RESUMEN
Multisystem inflammatory syndrome in children (MIS-C) affects a small percentage of pediatric patients infected with COVID-19 and is characterized by fever, laboratory evidence of inflammation, multisystem involvement, and severe illness necessitating hospitalization. Skin findings are often present in these patients, and when initially compared with Kawasaki disease, they likely represent distinct phenomena and overall remain poorly characterized. In this retrospective review of 34 case reports and series, we identified cutaneous manifestations documented in 417 of 736 patients (57%) with MIS-C associated with COVID-19. "Rash" was the sole descriptor of skin findings in nearly half of patients. Case reports and smaller case series provided more detail, outlining a broad range of lesion morphologies (polymorphic, maculopapular, morbilliform, erythrodermic, urticarial, reticular, petechial, purpuric) in variable anatomic distribution. More thorough descriptions of dermatologic manifestations in patients with MIS-C are warranted to better characterize this syndrome, as they may lend important insight into pathogenic mechanisms of disease.
Asunto(s)
COVID-19/complicaciones , Enfermedades de la Piel/etiología , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , COVID-19/diagnóstico , Niño , Humanos , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/diagnósticoAsunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Antihipertensivos/efectos adversos , Edema/diagnóstico , Hidralazina/efectos adversos , Enfermedades Cutáneas Vasculares/diagnóstico , Úlcera Cutánea/diagnóstico , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inducido químicamente , Biopsia , Nalgas , Criptococosis/diagnóstico , Diagnóstico Diferencial , Edema/inducido químicamente , Edema/patología , Cara , Femenino , Granulomatosis con Poliangitis/diagnóstico , Humanos , Hipertensión/tratamiento farmacológico , Pierna , Mucosa Bucal/patología , Piel/patología , Enfermedades Cutáneas Vasculares/inducido químicamente , Enfermedades Cutáneas Vasculares/patología , Úlcera Cutánea/inducido químicamente , Úlcera Cutánea/patología , Síndrome de Sweet/diagnósticoRESUMEN
BACKGROUND: One of the promises in regenerative medicine is to regenerate or replace damaged tissues. The embryonic chick can regenerate its retina by transdifferentiation of the retinal pigmented epithelium (RPE) and by activation of stem/progenitor cells present in the ciliary margin. These two ways of regeneration occur concomitantly when an external source of fibroblast growth factor 2 (FGF2) is present after injury (retinectomy). During the process of transdifferentiation, the RPE loses its pigmentation and is reprogrammed to become neuroepithelium, which differentiates to reconstitute the different cell types of the neural retina. Somatic mammalian cells can be reprogrammed to become induced pluripotent stem cells by ectopic expression of pluripotency-inducing factors such as Oct4, Sox2, Klf4, c-Myc and in some cases Nanog and Lin-28. However, there is limited information concerning the expression of these factors during natural regenerative processes. Organisms that are able to regenerate their organs could share similar mechanisms and factors with the reprogramming process of somatic cells. Herein, we investigate the expression of pluripotency-inducing factors in the RPE after retinectomy (injury) and during transdifferentiation in the presence of FGF2. RESULTS: We present evidence that upon injury, the quiescent (p27(Kip1)+/BrdU-) RPE cells transiently dedifferentiate and express sox2, c-myc and klf4 along with eye field transcriptional factors and display a differential up-regulation of alternative splice variants of pax6. However, this transient process of dedifferentiation is not sustained unless FGF2 is present. We have identified lin-28 as a downstream target of FGF2 during the process of retina regeneration. Moreover, we show that overexpression of lin-28 after retinectomy was sufficient to induce transdifferentiation of the RPE in the absence of FGF2. CONCLUSION: These findings delineate in detail the molecular changes that take place in the RPE during the process of transdifferentiation in the embryonic chick, and specifically identify Lin-28 as an important factor in this process. We propose a novel model in which injury signals initiate RPE dedifferentiation, while FGF2 up-regulates Lin-28, allowing for RPE transdifferentiation to proceed.