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CLINICAL REPORT ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Cutaneous Chronic Graft Versus Host Disease Following Allogeneic Haematopoietic Stem Cell Transplantation in Children: A Retrospective Study
Rony SHREBERK-HASSIDIM 1 #, Michal NEUMARK 1 #, Shoshana GREENBERGER 2, Gal GOLDSTEIN 3, Ayal HASSIDIM 4, Yuval DUKLER 5, Alexander MALY 6, Polina STEPENSKY 7 and Vered MOLHO-PESSACH 1 Departments of 1 Dermatology, 4 Plastic Surgery, 6 Pathology and 7 Pediatric Hemato-Oncology and Bone Marrow Transplantation, Pediatric Division, Hadassah-Hebrew University Medical Center, Jerusalem, Departments of 2 Dermatology and 3 Pediatric Hemato-Oncology and Bone Marrow Transplantation, The Edmond and Lily Safra Children Hospital, Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv and 5 Hadassah-Hebrew University Faculty of Medicine, Jerusalem, Israel
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These authors contributed equally to this study.
Chronic graft versus host disease( cGVHD) is a complication of allogeneic haematopoietic stem cell transplantation( HSCT). The aim of this study was to clinically characterize childhood cutaneous cGVHD. A retrospective study of children treated with HSCT at 2 tertiary medical centres in Israel between 2011 and 2014 was performed. A total of 112 children were included. Cutaneous cGVHD developed in 18 % of subjects. Risk factors were older age, HSCT from peripheral blood and acute lymphoblastic leukaemia. The eruption was lichenoid in 90 % of subjects, of whom onethird progressed to sclerosis. Topical treatments were usually sufficient in localized disease. Widespread eruption necessitated phototherapy, extracorporeal photopheresis and / or systemic immunosuppressants. Patients presenting with palmoplantar keratoderma, developed sclerosis. To the best of our knowledge, this is the first study describing childhood cutaneous cGV- HD. Lichenoid eruption is the most common cutaneous pattern of cGVHD in children. Sclerotic changes may be associated with prior keratoderma. cGVHD poses a therapeutic challenge and better treatments should be sought.
Key words: allogeneic haematopoietic cell transplantation; graft versus host disease; chronic cutaneous graft versus host disease; children; lichenoid; sclerotic.
Accepted Oct 19, 2017; Epub ahead of print Oct 23, 2017 Acta Derm Venereol 2018; 98: 206 – 211.
Corr: Vered Molho-Pessach, Department of Dermatology, Hadassah-Hebrew University Medical Center, Kiryat Hadassah, POB 12000, Jerusalem, 9112001, Israel. E-mail: Rverem @ hadassah. org. il
Allogeneic haematopoietic stem cell transplantation
( HSCT) is a life-saving treatment for haematooncological malignancies, hereditary disorders and primary immuno-deficiencies. The use of allogeneic HSCT in children has been expanding in recent years. Conditioning by chemotherapy with or without irradiation is given to destroy the immune system. This is followed by transplantation of haematopoietic stem cells harvested from the donor’ s peripheral blood stem cells( PBSC), bone marrow or using umbilical cord blood( 1). The donor can be a family member or an unrelated donor, and the degree of matching is classified according to the human leukocyte antigen( HLA) system( 2).
Excluding infections, graft versus host disease( GVHD) is the most common complication following allogeneic HSCT, and is a major cause of morbidity and mortality. GVHD can affect any body organ, but the skin is most commonly involved( 1). GVHD occurs when the donor’ s immune cells recognize the recipient’ s tissues as foreign due to an interaction between the recipient’ s antigen-presenting cells and the donor’ s mature T cells, leading to immune dysregulation( 3). Nevertheless, GVHD is also considered beneficial in haematological malignancies, due to an immunological effect of the donor’ s immune system against the tumour cells( 4). GVHD is divided into acute and chronic reactions, traditionally distinguished by a cut-off of 100 days following HSCT. Nowadays, the distinction is defined by specific clinical features and by different pathophysiology( 5). Acute GVHD( aGVHD) is caused by reaction of the host’ s dendritic cells to the graft, which results in activation of donor-derived T cells, activation of type 1 helper T( Th) cells and tissue damage( 6). Clinically there is a triad of skin eruption, hyperbilirubinaemia and diarrhoea( 7). Chronic GVHD( cGVHD) involves allogeneic and autoimmune-like reactions. The conditioning regimen and / or aGVHD damages the thymus and impairs self-tolerance. CD4 and CD8 T cells, regulatory T cells and B cells participate in the production of autoantibodies. Activation of Th1, Th2 and Th17 cells results in tissue inflammation, leading eventually to fibrosis( 8 – 10). Cutaneous involvement is observed in 75 % of cases, followed by hepatic, oral, ophthalmic or lung involvement( 11). Recognized risk factors are: older age of the patient or donor, former aGVHD, unrelated donor with low HLA matching, use of progenitor haematopoietic cells derived from PBSC, a diagnosis of chronic myeloid leukaemia, and infusion of donor white blood cells( 6, 12). Cutaneous features of cGVHD are pleomorphic. Typically non-sclerotic and sclerotic forms are distinguished( 1). The non-sclerotic form is usually lichenoid( simulating lichen planus), but other less common morphologies have been described, such as keratosis pilaris-like, ichthyotic-like, poikilodermatous, doi: 10.2340 / 00015555-2824 Acta Derm Venereol 2018; 98: 206 – 211
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica.