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Early GVHD with Follicular Rash

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Pathology of Graft vs. Host Disease

Abstract

Van Bekkum and colleagues first described secondary disease following ablation or suppression of a recipients’ immune system followed by lymph-hematopoietic cell transplant from a genetically non-identical donor. The immune reaction by donor T lymphocytes, subsequently known as graft-versus-host disease (GVHD), is preceded by donor T cell activation with secretion of cytokines and expansion of host antigen-presenting cells. The acute form occurring early after transplantation most often presents with a rash ± gastrointestinal symptoms and elevated liver tests. Skin biopsies, in particular, are often first used to establish the diagnosis, but interpretation must consider a number of alternative conditions related to toxicity from pre-transplant conditioning, infectious causes, or reactions to drugs or transfused blood products. The initial site of the skin GVHD attack is against progenitor cell regions in the hair follicle and rete ridges in the epidermis. This chapter discusses the pathobiologic basis for the initial targeting of progenitor regions in skin GVHD, the key histologic findings, and the differential considerations.

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References

  1. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sale GE, Lerner KG, Barker EA, Shulman HM, Thomas ED. The skin biopsy in the diagnosis of acute graft-versus-host disease in man. Am J Pathol. 1977;89(3):621–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai acute GVHD international consortium. Biol Blood Marrow Transplant. 2016;22(1):4–10.

    Article  PubMed  Google Scholar 

  4. Dumler JS, Beschorner WE, Farmer ER, Di Gennaro KA, Saral R, Santos GW. Endothelial-cell injury in cutaneous acute graft-versus-host disease. Am J Pathol. 1989;135(6):1097–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Sale GE, Shulman HM, Gallucci BB, Thomas ED. Young rete ridge keratinocytes are preferred targets in cutaneous graft-versus-host disease. Am J Pathol. 1985;118(2):278–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Cotsarelis G, Sun TT, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990;61(7):1329–37.

    Article  CAS  PubMed  Google Scholar 

  7. Lyle S, Christofidou-Solomidou M, Liu Y, Elder DE, Albelda S, Cotsarelis G. The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. J Cell Sci. 1998;111(Pt 21):3179–88.

    CAS  PubMed  Google Scholar 

  8. Zhan Q, Signoretti S, Whitaker-Menezes D, Friedman TM, Korngold R, Murphy GF. Cytokeratin15-positive basal epithelial cells targeted in graft-versus-host disease express a constitutive antiapoptotic phenotype. J Invest Dermatol. 2007;127(1):106–15.

    Article  CAS  PubMed  Google Scholar 

  9. Zhan Q, Korngold R, Lezcano C, McKeon F, Murphy GF. Graft-versus-host disease-related cytokine-driven apoptosis depends on p73 in cytokeratin 15-positive target cells. Biol Blood Marrow Transplant. 2012;18(6):841–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang Y, Li D, Jones D, et al. Blocking LFA-1 activation with lovastatin prevents graft-versus-host disease in mouse bone marrow transplantation. Biol Blood Marrow Transplant. 2009;15(12):1513–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Giaccone L, Martin P, Carpenter P, et al. Safety and potential efficacy of low-dose methotrexate for treatment of chronic graft-versus-host disease. Bone Marrow Transplant. 2005;36(4):337–41.

    Article  CAS  PubMed  Google Scholar 

  12. Shulman H. Pathology of chronic GVHD. In: Burakoff SJ, Deeg HJ, Ferrara J, Atkinson K, editors. Graft-versus-host disease: immunology, pathophysiology and treatment. 1st ed. New York: Marcel Dekker, Inc.; 1990. p. 587–614.

    Google Scholar 

  13. Horn TD, Bauer DJ, Vogelsang GB, Hess AD. Reappraisal of histologic features of the acute cutaneous graft-versus-host reaction based on an allogeneic rodent model. J Invest Dermatol. 1994;103(2):206–10.

    Article  CAS  PubMed  Google Scholar 

  14. Bircher AJ, Scherer HK. Drug hypersensitivity reactions during hematopoietic stem cell transplantation. Curr Probl Dermatol. 2012;43:150–64.

    Article  PubMed  Google Scholar 

  15. Fischer A, Jakubowski AA, Lacouture ME, et al. Histopathologic features of cutaneous acute graft-versus-host disease in T-cell-depleted peripheral blood stem cell transplant recipients. Am J Dermatopathol. 2015;37(7):523–9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kreft A, Mottok A, Mesteri I, et al. Consensus diagnostic histopathological criteria for acute gastrointestinal graft versus host disease improve interobserver reproducibility. Virchows Arch. 2015;467(3):255–63.

    Article  PubMed  Google Scholar 

  17. Hammami MB, Al-Taee A, Meeks M, et al. Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease. Clin J Gastroenterol. 2017;10(2):142–6.

    Article  PubMed  Google Scholar 

  18. Keyes A, Mathias M, Boulad F, et al. Cutaneous involvement of disseminated adenovirus infection in an allogeneic stem cell transplant recipient. Br J Dermatol. 2016;174(4):885–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lee CK, Gingrich RD, Hohl RJ, Ajram KA. Engraftment syndrome in autologous bone marrow and peripheral stem cell transplantation. Bone Marrow Transplant. 1995;16(1):175–82.

    CAS  PubMed  Google Scholar 

  20. Lehman JS, Gibson LE, el-Azhary RA, et al. Acute cutaneous graft-vs.-host disease compared to drug hypersensitivity reaction with vacuolar interface changes: a blinded study of microscopic and immunohistochemical features. J Cutan Pathol. 2015;42(1):39–45.

    Article  PubMed  Google Scholar 

  21. Nishio N, Yagasaki H, Takahashi Y, et al. Engraftment syndrome following allogeneic hematopoietic stem cell transplantation in children. Pediatr Transplant. 2009;13(7):831–7.

    Article  CAS  PubMed  Google Scholar 

  22. Savolainen H, Lautenschlager I, Piiparinen H, Saarinen-Pihkala U, Hovi L, Vettenranta K. Human herpesvirus-6 and -7 in pediatric stem cell transplantation. Pediatr Blood Cancer. 2005;45(6):820–5.

    Article  PubMed  Google Scholar 

  23. Wang X, Liu H, Li L, et al. Pre-engraftment syndrome after unrelated donor umbilical cord blood transplantation in patients with hematologic malignancies. Eur J Haematol. 2012;88(1):39–45.

    Article  CAS  PubMed  Google Scholar 

  24. Wei J, Zhang Y, Xu H, Jin J, Zhang J. Atopic dermatitis-like presentation of graft-versus-host disease: a novel form of chronic cutaneous graft-versus-host disease. J Am Acad Dermatol. 2013;69(1):34–9.

    Article  PubMed  Google Scholar 

  25. Kohler S, Hendrickson MR, Chao NJ, Smoller BR. Value of skin biopsies in assessing prognosis and progression of acute graft-versus-host disease. Am J Surg Pathol. 1997;21(9):988–96.

    Article  CAS  PubMed  Google Scholar 

  26. Ali AM, DiPersio JF, Schroeder MA. A proposed biology- and biomarker-based algorithm for management of acute GvHD. Bone Marrow Transplant. 2017;52(2):337–40.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  PubMed  Google Scholar 

  28. Marra DE, McKee PH, Nghiem P. Tissue eosinophils and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft-versus-host disease. J Am Acad Dermatol. 2004;51(4):543–6.

    Article  PubMed  Google Scholar 

  29. 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.

    Article  PubMed  Google Scholar 

  30. Li N, Guthrie KA, Storer BE, et al. Keratinocyte dysplasia in hematopoietic stem cell transplantation recipients in the day-28-to-84 posttransplantation period. Biol Blood Marrow Transplant. 2012;18(8):1281–6.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Hymes SR, Simonton SC, Farmer ER, Beschorner WB, Tutschka PJ, Santos GW. Cutaneous busulfan effect in patients receiving bone-marrow transplantation. J Cutan Pathol. 1985;12(2):125–9.

    Article  CAS  PubMed  Google Scholar 

  32. Shimose L, Munoz-Price LS. Diagnosis, prevention, and treatment of scabies. Curr Infect Dis Rep. 2013;15(5):426–31.

    Article  PubMed  Google Scholar 

  33. Choi YL, Kim JA, Jang KT, et al. Characteristics of cutaneous cytomegalovirus infection in non-acquired immune deficiency syndrome, immunocompromised patients. Br J Dermatol. 2006;155(5):977–82.

    Article  PubMed  Google Scholar 

  34. Golden MP, Hammer SM, Wanke CA, Albrecht MA. Cytomegalovirus vasculitis. Case reports and review of the literature. Medicine (Baltimore). 1994;73(5):246–55.

    Article  CAS  Google Scholar 

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Correspondence to Cecilia C. S. Yeung .

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Yeung, C.C.S., Dinh, T.T., Shulman, H.M. (2019). Early GVHD with Follicular Rash. In: Yeung, C., Shulman, H. (eds) Pathology of Graft vs. Host Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-42099-8_3

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  • DOI: https://doi.org/10.1007/978-3-319-42099-8_3

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