Abstract
Graft-versus-host disease (GVHD) is one of the most challenging diseases to diagnose and manage in both children and adults. Despite significant research and advances, GVHD remains a significant cause of morbidity and mortality in the post-hematopoietic stem cell transplant population. Given that skin is the most common organ affected in both acute and chronic forms of GVHD, it is imperative for dermatologists not only to recognize cutaneous manifestations but also to familiarize themselves with first-line therapies for these conditions. In this chapter, we describe four unique cases of acute and chronic GVHD, and discuss the differential diagnosis, diagnostic pearls, and therapeutic approach to these diseases. We begin with a case of classic acute GVHD, and review characteristic clinical features, risk factors, differential diagnosis, and first-line therapies. We then move on to a rare case of toxic epidermal necrolysis-like acute GVHD and discuss second- and third-line agents for treatment-refractory disease, including interventions that saved the patient’s life. In case 3, we transition to a discussion of chronic GVHD, and present a patient with sclerotic disease, reviewing clinical features, risk factors, and first-line therapies for this condition. Lastly, we conclude our chapter with a discussion of an atypical nonsclerotic form cutaneous chronic GVHD associated with a good prognosis.
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References
Jacobsohn DA. Acute graft-versus-host disease in children. Bone Marrow Transplant. 2008;41(2):215–21.
Eisner MD, August CS. Impact of donor and recipient characteristics on the development of acute and chronic graft-versus-host disease following pediatric bone marrow transplantation. Bone Marrow Transplant. 1995;15(5):663–8.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56.
Hymes SR, Alousi AM, Cowen EW. Graft-versus-host disease: part II. Management of cutaneous graft-versus-host disease. J Am Acad Dermatol. 2012;66(4):535.e1–16.
Dignan FL, Clark A, Amrolia P, et al. Diagnosis and management of acute graft-versus-host disease. Br J Haematol. 2012;158(1):30–45.
Hu SW, Cotliar J. Acute graft-versus-host disease following hematopoietic stem-cell transplantation. Dermatol Ther. 2011;24(4):411–23.
Firoz BF, Lee SJ, Nghiem P, Qureshi AA. Role of skin biopsy to confirm suspected acute graft-vs-host disease: results of decision analysis. Arch Dermatol. 2006;142(2):175–82.
Kuykendall TD, Smoller BR. Lack of specificity in skin biopsy specimens to assess for acute graft-versus-host disease in initial 3 weeks after bone-marrow transplantation. J Am Acad Dermatol. 2003;49(6):1081–5.
Zhou Y, Barnett MJ, Rivers JK. Clinical significance of skin biopsies in the diagnosis and management of graft-vs-host disease in early postallogeneic bone marrow transplantation. Arch Dermatol. 2000;136(6):717–21.
Byun HJ, Yang JI, Kim BK, Cho KH. Clinical differentiation of acute cutaneous graft-versus-host disease from drug hypersensitivity reactions. J Am Acad Dermatol. 2011;65(4):726–32.
Frankel HC, Qureshi AA. Comparative effectiveness of topical calcineurin inhibitors in adult patients with atopic dermatitis. Am J Clin Dermatol. 2012;13(2):113–23.
Olson KA, West K, Mccarthy PL. Toxic tacrolimus levels after application of topical tacrolimus and use of occlusive dressings in two bone marrow transplant recipients with cutaneous graft-versus-host disease. Pharmacotherapy. 2014;34(6):e60–4.
Gratwohl A, Hermans J, Apperley J, et al. Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation. Blood. 1995;86(2):813–8.
Baird K, Cooke K, Schultz KR. Chronic graft-versus-host disease (GVHD) in children. Pediatr Clin North Am. 2010;57(1):297–322.
Rowlings PA, Przepiorka D, Klein JP, et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol. 1997;97(4):855–64.
Goiriz R, Peñas P, Pérez-gala S, et al. Stage IV cutaneous acute graft-versus-host disease. Clinical and histological study of 15 cases. J Eur Acad Dermatol Venereol. 2009;23(12):1398–404.
Irvine AD, Hoeger PH, Yan AC. Harper’s textbook of pediatric dermatology. West Sussex: Wiley-Blackwell; 2011.
Calore E, Marson P, Pillon M, et al. Treatment of acute graft-versus-host disease in childhood with extracorporeal photochemotherapy/photopheresis: the Padova experience. Biol Blood Marrow Transplant. 2015;21(11):1963–72.
Couriel D, Hosing C, Saliba R, et al. Extracorporeal photopheresis for acute and chronic graft-versus-host disease: does it work? Biol Blood Marrow Transplant. 2006;12(1 Suppl 2):37–40.
Abu-dalle I, Reljic T, Nishihori T, et al. Extracorporeal photopheresis in steroid-refractory acute or chronic graft-versus-host disease: results of a systematic review of prospective studies. Biol Blood Marrow Transplant. 2014;20(11):1677–86.
Hymes SR, Alousi AM, Cowen EW. Graft-versus-host disease: part I. Pathogenesis and clinical manifestations of graft-versus-host disease. J Am Acad Dermatol. 2012;66(4):515.e1–18.
Holtick U, Albrecht M, Chemnitz JM, et al. Bone marrow versus peripheral blood allogeneic haematopoietic stem cell transplantation for haematological malignancies in adults. Cochrane Database Syst Rev. 2014;4:CD010189.
Rocha V, Wagner JE, Sobocinski KA, et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med. 2000;342(25):1846–54.
Wagner JE, Kernan NA, Steinbuch M, Broxmeyer HE, Gluckman E. Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease. Lancet. 1995;346(8969):214–9.
Jagasia MH, Greinix HT, Arora M, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015;21(3):389–401.e1.
Patel AR, Pavletic SZ, Turner ML, Cowen EW. The isomorphic response in morphea-like chronic graft-vs-host disease. Arch Dermatol. 2008;144(9):1229–31.
Arora M. Therapy of chronic graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21(2):271–9.
Wolff D, Schleuning M, Von harsdorf S, et al. Consensus conference on clinical practice in chronic GVHD: second-line treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2011;17(1):1–17.
Connolly KL, Griffith JL, Mcevoy M, Lim HW. Ultraviolet A1 phototherapy beyond morphea: experience in 83 patients. Photodermatol Photoimmunol Photomed. 2015;31(6):289–95.
Enk CD, Elad S, Vexler A, Kapelushnik J, Gorodetsky R, Kirschbaum M. Chronic graft-versus-host disease treated with UVB phototherapy. Bone Marrow Transplant. 1998;22(12):1179–83.
Brazzelli V, Grasso V, Muzio F, et al. Narrowband ultraviolet B phototherapy in the treatment of cutaneous graft-versus-host disease in oncohaematological paediatric patients. Br J Dermatol. 2010;162(2):404–9.
Apisarnthanarax N, Donato M, Körbling M, et al. Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results. Bone Marrow Transplant. 2003;31(6):459–65.
Foss FM, Divenuti GM, Chin K, et al. Prospective study of extracorporeal photopheresis in steroid-refractory or steroid-resistant extensive chronic graft-versus-host disease: analysis of response and survival incorporating prognostic factors. Bone Marrow Transplant. 2005;35(12):1187–93.
Greinix HT, Volc-platzer B, Rabitsch W, et al. Successful use of extracorporeal photochemotherapy in the treatment of severe acute and chronic graft-versus-host disease. Blood. 1998;92(9):3098–104.
Kennedy-nasser AA, Ku S, Castillo-caro P, et al. Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation mediates expansion of regulatory T cells without diminishing antiviral and antileukemic activity. Clin Cancer Res. 2014;20(8):2215–25.
Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365(22):2055–66.
Chakrabarti S, MacDonald D, Hale G, Holder K, Turner V, Czarnecka H, Thompson J, Fegan C, Waldmann H, Milligan DW. T-cell depletion with Campath-1H “in the bag” for matched related allogeneic peripheral blood stem cell transplantation is associated with reduced graft-versus-host disease, rapid immune constitution and improved survival. Br J Haematol. 2003;121:109–18.
Chosidow O, Bagot M, Vernant JP, Roujeau JC, Cordonnier C, Kuentz M, et al. Sclerodermatous chronic graft-versus-host disease. Analysis of seven cases. J Am Acad Dermatol. 1992;26:49–55.
Skert C, Patriarca F, Sperotto A, Cerno M, Fili C, Zaja F, et al. Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome. Haematologica. 2006;91:258–61.
Kim SJ, Choi JM, Kim JE, Cho BK, Kim DW, Park HJ. Clinicopathologic characteristics of cutaneous chronic graft-versus-host diseases: a retrospective study in Korean patients. Int J Dermatol. 2010;49(12):1386–92.
Huang JT, Duncan CN, Boyer D, Khosravi H, Lehmann LE, Saavedra A. Nail dystrophy, edema, and eosinophilia: harbingers of severe chronic GVHD of the skin in children. Bone Marrow Transplant. 2014;49(12):1521–7.
Creamer D, Martyn-simmons CL, Osborne G, et al. Eczematoid graft-vs-host disease: a novel form of chronic cutaneous graft-vs-host disease and its response to psoralen UV-A therapy. Arch Dermatol. 2007;143(9):1157–62.
Shulman HM, Cardona DM, Greenson JK, et al. NIH Consensus development project on criteria for clinical trials in chronic graft-versus-host disease: II. The 2014 Pathology Working Group Report. Biol Blood Marrow Transplant. 2015;21(4):589–603.
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Khosravi, H., Mikailov, A., Huang, J.T. (2016). Acute and Chronic Graft-Versus-Host Disease of the Skin. In: Hogeling, M. (eds) Case-Based Inpatient Pediatric Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-31569-0_6
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DOI: https://doi.org/10.1007/978-3-319-31569-0_6
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