Dermatologic manifestations of chronic graft-versus-host reaction

Reakcija transplantata protiv primatelja je kompleksna multisistemna bolest koja se razvija kao komplikacija u pacijenata nakon alogene transplantacije hematopoetskih matičnih stanica. Transplantacija hematopoetskih matičnih stanica rabi se kao oblik liječenja u brojnim malignim i nemalignim bolestima, a reakcija transplantata protiv primatelja predstavlja jedan od najčešćih uzroka morbiditeta i mortaliteta u tih bolesnika. Do razvoja GVHD-a dolazi kada donorovi aloreaktivni imunkompetentni limfociti T prepoznaju i napadnu strane antigene na stanicama primatelja. Najčešće zahvaćen organ je koža. Reakcija transplantata protiv primatelja može se očitovati u dva oblika – akutnom i kroničnom. Akutni GVHD možemo podijeliti na klasični, te kasni akutni GVHD koji obuhvaća prezistentni, rekurentni i aGVHD odgođenog početka, dok se kronični GVHD može podijeliti na klasični cGVHD i preklapajući sindrom. Akutni GVHD primarno se očituje kožnim osipom, povišenjem bilirubina i proljevom, a liječenje se temelji na uporabi sistemnih kortikosteroida i imunosupresiva. Patogeneza kroničnog oblika GVHD-a i dalje je nedovoljno razjašnjena, ali se smatra kako su u podlozi aloreaktivnost te autoimuni mehanizmi. Kronični kožni oblik GVHD-a može se očitovati sklerodermiformnim i nesklerodermiformnim manifestacijama. Nesklerodermiformni oblik manifestira se papulama i plakovima nalik lichen planusu, dok se sklerodermiformni oblik očituje površinskom ili dubokom sklerozom. Kronični GVHD kože može se liječiti lokalno – pretežito kortikosteroidima ili inhibitorima kalcineurina; te fototerapijom (UVB, PUVA, UVA1). Kao druga linija terapije rabe se sistemni kortikosteroidi i ekstrakorporalna fotofereza. Cilj ovog rada je sustavan pregled epidemioloških faktora, klasifikacije, patofiziologije, kliničkih manifestacija akutnog i kroničnog GVHD-a, kao i lokalne, fizikalne i sistemne terapije koja se rabi u liječenju pacijenata oboljelih od GVHD-a.Graft-versus-host disease (GVHD) is a complex multisystem disease which mainly occurs as a complication in patients after allogenic hematopoetic stem cell transplantation. Hematopoetic cell transplantation is a potentially curative therapy for a variety of malignant and non-malignant conditions, and the graft-versus-host reaction is one of the most frequent causes of long-term morbidity and mortality. Graft-versus-host disease occurs when donor alloreactive immunocompetent T cells identify foreign antigens on recipient cells and attack them. The most commonly affected organ is the skin. Graft-versus-host disease can be acute or chronic. It is currently divided into classic acute GVHD, a persistent, recurrent or delayed onset acute GVHD, as well as classic chronic GVHD and overlap syndrome. Acute GVHD presents with three primary clinical features – skin rash, bilirubin elevation and diarrhoea, and treatment is based on systemic corticosteroids and immunosuppressant therapy. The pathogenesis of chronic GVHD remains poorly understood, but likely involves components of alloreactivity and autoimmunity. Chronic cutaneous GVHD may present with many different sclerotic and nonsclerotic manifestations. Nonsclerotic chronic GVHD manifests with lichen-planus-like papules and plaques, and sclerotic chronic GVHD may manifest with superficial or deep sclerosis. Chronic GVHD of the skin may be treated with topical therapies – generally steroids or calcineurin inhibitors; also phototherapy (ultraviolet B, PUVA, and UVA1 therapy) may be used. Systemic steroids combined with extracorporeal photopheresis are used as a second-line therapy. The following paper tries to give an overview of the epidemiologic factors, classification, pathogenesis, clinical manifestations of acute and chronic GVHD, as well as topical, physical and systemic treatment options available to patients with graft-versus-host disease