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Dermatologic Conditions of the Early Post-Transplant Period in Hematopoietic Stem Cell Transplant Recipients

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Abstract

Hematopoietic stem cell transplants (HSCTs) are used to treat a variety of conditions, including hematologic malignancies, bone marrow failure syndromes, and immunodeficiencies. Over 60,000 HSCTs are performed annually worldwide, and the numbers continue to increase. Indeed, as new conditioning regimens develop, more and more individuals, including those of older age, will be eligible for transplants. Nevertheless, although HSCTs are clearly a life-saving and necessary treatment for thousands of patients per year, there is still substantial morbidity and mortality associated with the procedure. Of note, skin eruptions in the post-HSCT period are frequent and often significantly reduce quality of life in recipients. Moreover, these cutaneous findings sometimes herald an underlying systemic condition, presenting possible opportunities for timelier intervention. Dermatologists therefore play a vital role in distinguishing life-threatening conditions from benign issues and prompting recognition of critical complications earlier in their course. This article aims to review the major dermatologic conditions occurring in the early post-HSCT period.

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References

  1. Niederwieser D, Baldomero H, Szer J, Gratwohl M, Aljurf M, Atsuta Y, et al. Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey. Bone Marrow Transpl. 2016;51(6):778–85.

    Article  CAS  Google Scholar 

  2. Champlain A, Bach D, West D, Mehta J, Cotliar J. Dermatology consultation and change in diagnosis and/or management of patients after allogeneic hematopoietic stem cell transplantation. J Am Acad Dermatol. 2014;70(5):AB115.

    Google Scholar 

  3. Zulu S, Kenyon M. Principles of Conditioning Therapy and Cell Infusion. In: Kenyon M, Babic A, editors. The European blood and marrow transplantation textbook for nurses: under the auspices of EBMT. Cham: Springer International Publishing; 2018. p. 89–96.

    Chapter  Google Scholar 

  4. Blaise D, Vey N, Faucher C, Mohty M. Current status of reduced-intensity-conditioning allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica. 2007;92(4):533–41.

    Article  PubMed  Google Scholar 

  5. Kebriaei P, Bassett R, Lyons G, Valdez B, Ledesma C, Rondon G, et al. Clofarabine plus busulfan is an effective conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia: long-term study results. Biol Blood Marrow Transpl. 2017;23(2):285–92.

    Article  CAS  Google Scholar 

  6. Sengsayadeth S, Savani BN, Blaise D, Mohty M. Haploidentical transplantation: selecting optimal conditioning regimen and stem cell source. Semin Hematol. 2016;53(2):111–4.

    Article  PubMed  Google Scholar 

  7. Valadkhani B, Kargar M, Ashouri A, Hadjibabaie M, Gholami K, Ghavamzadeh A. The risk factors for cytomegalovirus reactivation following stem cell transplantation. J Res Pharm Pract. 2016;5(1):63–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Danby R, Rocha V. Improving engraftment and immune reconstitution in umbilical cord blood transplantation. Front Immunol. 2014;5:68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sahin U, Toprak SK, Atilla PA, Atilla E, Demirer T. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. J Infect Chemother. 2016;22(8):505–14.

    Article  PubMed  Google Scholar 

  10. Jaing T-H. Complications of haematopoietic stem cell transplantation. ISBT Sci Ser. 2011;6(2):332–6.

    Article  CAS  Google Scholar 

  11. Spitzer TR. Engraftment syndrome: double-edged sword of hematopoietic cell transplants. Bone Marrow Transpl. 2015;50(4):469–75.

    Article  CAS  Google Scholar 

  12. Chen Y, Xu LP, Liu KY, Chen H, Chen YH, Zhang XH, et al. High incidence of engraftment syndrome after haploidentical allogeneic stem cell transplantation. Eur J Haematol. 2016;96(5):517–26.

    Article  CAS  PubMed  Google Scholar 

  13. Takatsuka H, Takemoto Y, Yamada S, Wada H, Tamura S, Fujimori Y, et al. Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome. Bone Marrow Transpl. 2000;26(4):419–26.

    Article  CAS  Google Scholar 

  14. Oyama Y, Cohen B, Traynor A, Brush M, Rodriguez J, Burt RK. Engraftment syndrome: a common cause for rash and fever following autologous hematopoietic stem cell transplantation for multiple sclerosis. Bone Marrow Transpl. 2002;29(1):81–5.

    Article  CAS  Google Scholar 

  15. Ravoet C, Feremans W, Husson B, Majois F, Kentos A, Lambermont M, et al. Clinical evidence for an engraftment syndrome associated with early and steep neutrophil recovery after autologous blood stem cell transplantation. Bone Marrow Transpl. 1996;18(5):943–7.

    CAS  Google Scholar 

  16. Cornell RF, Hari P, Zhang MJ, Zhong X, Thompson J, Fenske TS, et al. Divergent effects of novel immunomodulatory agents and cyclophosphamide on the risk of engraftment syndrome after autologous peripheral blood stem cell transplantation for multiple myeloma. Biol Blood Marrow Transpl. 2013;19(9):1368–73.

    Article  CAS  Google Scholar 

  17. Gutierrez-Garcia G, Rovira M, Magnano L, Rosinol L, Bataller A, Suarez-Lledo M, et al. Innovative strategies minimize engraftment syndrome in multiple myeloma patients with novel induction therapy following autologous hematopoietic stem cell transplantation. Bone Marrow Transpl. 2018. https://doi.org/10.1038/s41409-018-0189-2

    Article  Google Scholar 

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

    CAS  Google Scholar 

  19. Madero L, Vicent MG, Sevilla J, Prudencio M, Rodriguez F, Diaz MA. Engraftment syndrome in children undergoing autologous peripheral blood progenitor cell transplantation. Bone Marrow Transpl. 2002;30(6):355–8.

    Article  CAS  Google Scholar 

  20. Koreth J, Biernacki M, Aldridge J, Kim HT, Alyea EP 3rd, Armand P, et al. Syngeneic donor hematopoietic stem cell transplantation is associated with high rates of engraftment syndrome. Biol Blood Marrow Transpl. 2011;17(3):421–8.

    Article  Google Scholar 

  21. Gorak E, Geller N, Srinivasan R, Espinoza-Delgado I, Donohue T, Barrett AJ, et al. Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation: incidence and effects on survival. Biol Blood Marrow Transpl. 2005;11(7):542–50.

    Article  Google Scholar 

  22. Ileri T, Unal Ince E, Cakmakli H, Uysal Z, Gencturk Z, Ertem M. Evaluation of engraftment syndrome in children following full-matched related donor hematopoietic stem cell transplantations. Pediatr Transpl. 2016;20(4):581–9.

    Article  Google Scholar 

  23. Omer AK, Kim HT, Yalamarti B, McAfee SL, Dey BR, Ballen KK, et al. Engraftment syndrome after allogeneic hematopoietic cell transplantation in adults. Am J Hematol. 2014;89(7):698–705.

    Article  PubMed  Google Scholar 

  24. Chang L, Frame D, Braun T, Gatza E, Hanauer DA, Zhao S, et al. Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes. Biol Blood Marrow Transpl. 2014;20(9):1407–17.

    Article  Google Scholar 

  25. Moreb JS, Kubilis PS, Mullins DL, Myers L, Youngblood M, Hutcheson C. Increased frequency of autoaggression syndrome associated with autologous stem cell transplantation in breast cancer patients. Bone Marrow Transpl. 1997;19(2):101–6.

    Article  CAS  Google Scholar 

  26. Rapoport AP, Stadtmauer EA, Aqui N, Vogl D, Chew A, Fang HB, et al. Rapid immune recovery and graft-versus-host disease-like engraftment syndrome following adoptive transfer of Costimulated autologous T cells. Clin Cancer Res. 2009;15(13):4499–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Morishima M, Nobeyama Y, Kamiyama Y, Nakagawa H. Case of engraftment syndrome appearing as scratch dermatitis. J Dermatol. 2018;45(2):e25–6.

    Article  PubMed  Google Scholar 

  28. Champlain A, Frankfurt O, West D, Gerami P, Guitart J, Mehta J, et al. Clinical features of cutaneous pre-engraftment syndrome in patients receiving umbilical cord blood stem cell transplantation. Biol Blood Marrow Transpl. 2014;20(2):S263.

    Article  Google Scholar 

  29. Mossad S, Kalaycio M, Sobecks R, Pohlman B, Andresen S, Avery R, et al. Steroids prevent engraftment syndrome after autologous hematopoietic stem cell transplantation without increasing the risk of infection. Bone Marrow Transpl. 2005;35(4):375–81.

    Article  CAS  Google Scholar 

  30. Kanda J, Kaynar L, Kanda Y, Prasad VK, Parikh SH, Lan L, et al. Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment. Bone Marrow Transpl. 2013;48(7):926–31.

    Article  CAS  Google Scholar 

  31. Jang KT, Song KY, Kim BK. Histological features and immune cell changes in skin lesions of engraftment syndrome of children undergoing hematopoietic stem cell transplantation. Histol Histopathol. 2012;27(2):235–40.

    PubMed  Google Scholar 

  32. Horn TD, Redd JV, Karp JE, Beschorner WE, Burke PJ, Hood AF. Cutaneous eruptions of lymphocyte recovery. Arch Dermatol. 1989;125(11):1512–7.

    Article  CAS  PubMed  Google Scholar 

  33. Horn TD. Acute cutaneous eruptions after marrow ablation: roses by other names? J Cutan Pathol. 1994;21(5):385–92.

    Article  CAS  PubMed  Google Scholar 

  34. Horn T, Lehmkuhle MA, Gore S, Hood A, Burke P. Systemic cytokine administration alters the histology of the eruption of lymphocyte recovery. J Cutan Pathol. 1996;23(3):242–6.

    Article  CAS  PubMed  Google Scholar 

  35. Hurabielle C, Sbidian E, Beltraminelli H, Bouchindhomme B, Chassagne-Clement C, Balme B, et al. Eruption of lymphocyte recovery with atypical lymphocytes mimicking a primary cutaneous T-cell lymphoma: a series of 12 patients. Hum Pathol. 2018;71:100–8.

    Article  PubMed  Google Scholar 

  36. Bauer DJ, Hood AF, Horn TD. Histologic comparison of autologous graft-vs-host reaction and cutaneous eruption of lymphocyte recovery. Arch Dermatol. 1993;129(7):855–8.

    Article  CAS  PubMed  Google Scholar 

  37. Gibney MD, Penneys NS, Nelson-Adesokan P. Cutaneous eruption of lymphocyte recovery mimicking mycosis fungoides in a patient with acute myelocytic leukemia. J Cutan Pathol. 1995;22(5):472–5.

    Article  CAS  PubMed  Google Scholar 

  38. Nellen RG, van Marion AM, Frank J, Poblete-Gutierrez P, Steijlen PM. Eruption of lymphocyte recovery or autologous graft-versus-host disease? Int J Dermatol. 2008;47(Suppl 1):32–4.

    Article  PubMed  Google Scholar 

  39. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, 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 Transpl. 2015;21(3):389–401.

    Article  Google Scholar 

  40. Sun Y, Tawara I, Toubai T, Reddy P. Pathophysiology of acute graft-versus-host disease: recent advances. Transl Res. 2007;150(4):197–214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C, et al. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transpl. 2012;18(8):1150–63.

    Article  Google Scholar 

  42. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. Consensus conference on acute GVHD grading. Bone Marrow Transpl. 1995;15(6):825–8.

    CAS  Google Scholar 

  43. Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ, 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.

    Article  CAS  PubMed  Google Scholar 

  44. Ringden O, Hermans J, Labopin M, Apperley J, Gorin NC, Gratwohl A. The highest leukaemia-free survival after allogeneic bone marrow transplantation is seen in patients with grade I acute graft-versus-host disease. Acute and Chronic Leukaemia Working Parties of the European Group for blood and marrow transplantation (EBMT). Leuk Lymphoma. 1996;24(1–2):71–9.

    Article  CAS  PubMed  Google Scholar 

  45. 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 

  46. Friedman KJ, LeBoit PE, Farmer ER. Acute follicular graft-vs-host reaction. A distinct clinicopathologic presentation. Arch Dermatol. 1988;124(5):688–91.

    Article  CAS  PubMed  Google Scholar 

  47. 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 

  48. Aractingi S, Chosidow O. Cutaneous graft-versus-host disease. Arch Dermatol. 1998;134(5):602–12.

    Article  CAS  PubMed  Google Scholar 

  49. Lehman JS, Gibson LE, el-Azhary RA, Chavan RN, Hashmi SK, Lohse CM, 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 

  50. Jacobsohn DA, Vogelsang GB. Acute graft versus host disease. Orphanet J Rare Dis. 2007;2:35.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Sullivan KM, Deeg HJ, Sanders J, Klosterman A, Amos D, Shulman H, et al. Hyperacute graft-v-host disease in patients not given immunosuppression after allogeneic marrow transplantation. Blood. 1986;67(4):1172–5.

    CAS  PubMed  Google Scholar 

  52. Saliba RM, de Lima M, Giralt S, Andersson B, Khouri IF, Hosing C, et al. Hyperacute GVHD: risk factors, outcomes, and clinical implications. Blood. 2007;109(7):2751–8.

    CAS  PubMed  Google Scholar 

  53. Shiohara J, Takata M, Shiohara M, Ito T, Ishida F. Hyperacute graft-versus-host disease: histological assessment of skin biopsy specimens from 19 cases. Clin Exp Dermatol. 2012;37(4):335–40.

    Article  CAS  PubMed  Google Scholar 

  54. Kim DH, Sohn SK, Kim JG, Suh JS, Lee KS, Lee KB. Clinical impact of hyperacute graft-versus-host disease on results of allogeneic stem cell transplantation. Bone Marrow Transpl. 2004;33(10):1025–30.

    Article  CAS  Google Scholar 

  55. Deeg HJ, Antin JH. The clinical spectrum of acute graft-versus-host disease. Semin Hematol. 2006;43(1):24–31.

    Article  PubMed  Google Scholar 

  56. Bigby M. Rates of cutaneous reactions to drugs. Arch Dermatol. 2001;137(6):765–70.

    CAS  PubMed  Google Scholar 

  57. Weyers W, Metze D. Histopathology of drug eruptions—general criteria, common patterns, and differential diagnosis. Dermatol Pract Concept. 2011;1(1):33–47.

    PubMed  PubMed Central  Google Scholar 

  58. Stern RS. Clinical practice. Exanthematous drug eruptions. N Engl J Med. 2012;366(26):2492–501.

    Article  CAS  PubMed  Google Scholar 

  59. Mays SR, Kunishige JH, Truong E, Kontoyiannis DP, Hymes SR. Approach to the morbilliform eruption in the hematopoietic transplant patient. Semin Cutan Med Surg. 2007;26(3):155–62.

    Article  CAS  PubMed  Google Scholar 

  60. Cices AD, Carneiro C, Majewski S, et al. Differentiating skin rash after stem cell transplantation: graft versus host disease, cutaneous reactions to drugs and viral exanthema. Curr Dermatol Rep. 2016;5(1):12–7.

    Article  Google Scholar 

  61. Cetkovska P, Pizinger K, Cetkovsky P. High-dose cytosine arabinoside-induced cutaneous reactions. J Eur Acad Dermatol Venereol. 2002;16(5):481–5.

    Article  CAS  PubMed  Google Scholar 

  62. Gerson D, Sriganeshan V, Alexis JB. Cutaneous drug eruptions: a 5-year experience. J Am Acad Dermatol. 2008;59(6):995–9.

    Article  PubMed  Google Scholar 

  63. Weaver J, Bergfeld WF. Quantitative analysis of eosinophils in acute graft-versus-host disease compared with drug hypersensitivity reactions. Am J Dermatopathol. 2010;32(1):31–4.

    Article  PubMed  Google Scholar 

  64. 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 

  65. Bircher AJ. Exanthematous (maculopapular) drug eruption. In: UpToDate. Waltham. http://www.uptodate.com/contents/exanthematous-maculopapular-drug-eruption. Accessed 27 June 2018.

  66. Mockenhaupt M. The current understanding of Stevens-Johnson syndrome and toxic epidermal necrolysis. Expert Rev Clin Immunol. 2011;7(6):803–13 (quiz 14-5).

    Article  PubMed  Google Scholar 

  67. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993;129(1):92–6.

    Article  CAS  PubMed  Google Scholar 

  68. Downey A, Jackson C, Harun N, Cooper A. Toxic epidermal necrolysis: review of pathogenesis and management. J Am Acad Dermatol. 2012;66(6):995–1003.

    Article  CAS  PubMed  Google Scholar 

  69. Boull CL, Hylwa SA, Sajic D, Wagner JE, Tolar J, Hook KP. Toxic epidermal necrolysis in recessive dystrophic epidermolysis bullosa following bone marrow transplantation. J Pediatr. 2016;173:242–4.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Schaich M, Schakel K, Illmer T, Ehninger G, Bornhauser M. Severe epidermal necrolysis after treatment with imatinib and consecutive allogeneic hematopoietic stem cell transplantation. Ann Hematol. 2003;82(5):303–4.

    CAS  PubMed  Google Scholar 

  71. Gomulka J, Wilson BD, Joyce JC. Toxic epidermal necrolysis due to voriconazole: case report and review. Dermatol Online J. 2014;20(9).

  72. McDonald BJ, Singer JW, Bianco JA. Toxic epidermal necrolysis possibly linked to aztreonam in bone marrow transplant patients. Ann Pharmacother. 1992;26(1):34–5.

    Article  CAS  PubMed  Google Scholar 

  73. Takeda H, Mitsuhashi Y, Kondo S, Kato Y, Tajima K. Toxic epidermal necrolysis possibly linked to hyperacute graft-versus-host disease after allogeneic bone marrow transplantation. J Dermatol. 1997;24(10):635–41.

    Article  CAS  PubMed  Google Scholar 

  74. Birch J, Chamlin S, Duerst R, Jacobsohn D. Mycoplasma pneumoniae and atypical Stevens-Johnson syndrome in a hematopoietic stem cell transplant recipient. Pediatr Blood Cancer. 2008;50(6):1278–9.

    Article  PubMed  Google Scholar 

  75. Zakrzewski JL, Lentini G, Such U, Duerr A, Tran V, Guenzelmann S, et al. Toxic epidermal necrolysis: differential diagnosis of an epidermolytic dermopathy in a hematopoietic stem cell transplant recipient. Bone Marrow Transpl. 2002;30(5):331–3.

    Article  CAS  Google Scholar 

  76. Friedman HZ, Arias AM, Catchatourian R, Fretzin DF. Toxic epidermal necrolysis following bone marrow transplantation. Cutis. 1984;34(2):158–62.

    CAS  PubMed  Google Scholar 

  77. Villada G, Roujeau JC, Cordonnier C, Bagot M, Kuentz M, Wechsler J, et al. Toxic epidermal necrolysis after bone marrow transplantation: study of nine cases. J Am Acad Dermatol. 1990;23(5 Pt 1):870–5.

    Article  CAS  PubMed  Google Scholar 

  78. Hilgendorf I, Casper J, Sviland L, Prall F, Junghanss C, Freund M, et al. Toxic epidermal necrolysis after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transpl. 2007;39(4):245–6.

    Article  CAS  Google Scholar 

  79. Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000;136(3):323–7.

    Article  CAS  PubMed  Google Scholar 

  80. Roujeau JC, Bastuji-Garin S. Systematic review of treatments for Stevens-Johnson syndrome and toxic epidermal necrolysis using the SCORTEN score as a tool for evaluating mortality. Ther Adv Drug Saf. 2011;2(3):87–94.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Kim KJ, Lee DP, Suh HS, Lee MW, Choi JH, Moon KC, et al. Toxic epidermal necrolysis: analysis of clinical course and SCORTEN-based comparison of mortality rate and treatment modalities in Korean patients. Acta Derm Venereol. 2005;85(6):497–502.

    CAS  PubMed  Google Scholar 

  82. Kelemen JJ 3rd, Cioffi WG, McManus WF, Mason AD Jr, Pruitt BA Jr. Burn center care for patients with toxic epidermal necrolysis. J Am Coll Surg. 1995;180(3):273–8.

    PubMed  Google Scholar 

  83. Halebian PH, Corder VJ, Madden MR, Finklestein JL, Shires GT. Improved burn center survival of patients with toxic epidermal necrolysis managed without corticosteroids. Ann Surg. 1986;204(5):503–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Zimmermann S, Sekula P, Venhoff M, Motschall E, Knaus J, Schumacher M, et al. Systemic immunomodulating therapies for Stevens-Johnson syndrome and Toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol. 2017;153(6):514–22.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR Study. J Am Acad Dermatol. 2008;58(1):33–40.

    Article  PubMed  Google Scholar 

  86. Kardaun SH, Jonkman MF. Dexamethasone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis. Acta Derm Venereol. 2007;87(2):144–8.

    Article  CAS  PubMed  Google Scholar 

  87. Liu W, Nie X, Zhang L. A retrospective analysis of Stevens-Johnson syndrome/toxic epidermal necrolysis treated with corticosteroids. Int J Dermatol. 2016;55(12):1408–13.

    Article  CAS  PubMed  Google Scholar 

  88. Hirahara K, Kano Y, Sato Y, Horie C, Okazaki A, Ishida T, et al. Methylprednisolone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis: clinical evaluation and analysis of biomarkers. J Am Acad Dermatol. 2013;69(3):496–8.

    Article  CAS  PubMed  Google Scholar 

  89. Bolognia JL, Cooper DL, Glusac EJ. Toxic erythema of chemotherapy: a useful clinical term. J Am Acad Dermatol. 2008;59(3):524–9.

    Article  PubMed  Google Scholar 

  90. Jacobi U, Waibler E, Schulze P, Sehouli J, Oskay-Ozcelik G, Schmook T, et al. Release of doxorubicin in sweat: first step to induce the palmar-plantar erythrodysesthesia syndrome? Ann Oncol. 2005;16(7):1210–1.

    Article  CAS  PubMed  Google Scholar 

  91. Baack BR, Burgdorf WH. Chemotherapy-induced acral erythema. J Am Acad Dermatol. 1991;24(3):457–61.

    Article  CAS  PubMed  Google Scholar 

  92. Demircay Z, Gurbuz O, Alpdogan TB, Yucelten D, Alpdogan O, Kurtkaya O, et al. Chemotherapy-induced acral erythema in leukemic patients: a report of 15 cases. Int J Dermatol. 1997;36(8):593–8.

    Article  CAS  PubMed  Google Scholar 

  93. Parker TL, Cooper DL, Seropian SE, Bolognia JL. Toxic erythema of chemotherapy following i.v. BU plus fludarabine for allogeneic PBSC transplant. Bone Marrow Transpl. 2013;48(5):646–50.

    Article  CAS  Google Scholar 

  94. Martorell-Calatayud A, Sanmartin O, Botella-Estrada R, Balmer NN, Serra-Guillen C, Gomez-Moyano E, et al. Chemotherapy-related bilateral dermatitis associated with eccrine squamous syringometaplasia: reappraisal of epidemiological, clinical, and pathological features. J Am Acad Dermatol. 2011;64(6):1092–103.

    Article  PubMed  Google Scholar 

  95. Reyes-Habito CM, Roh EK. Cutaneous reactions to chemotherapeutic drugs and targeted therapies for cancer: part I. Conventional chemotherapeutic drugs. J Am Acad Dermatol. 2014;71(2):203.e1–12 (quiz 15-6).

    Article  CAS  Google Scholar 

  96. Bandini G, Belardinelli A, Rosti G, Calori E, Motta MR, Rizzi S, et al. Toxicity of high-dose busulphan and cyclophosphamide as conditioning therapy for allogeneic bone marrow transplantation in adults with haematological malignancies. Bone Marrow Transpl. 1994;13(5):577–81.

    CAS  Google Scholar 

  97. Robert C, Sibaud V, Mateus C, Verschoore M, Charles C, Lanoy E, et al. Nail toxicities induced by systemic anticancer treatments. Lancet Oncol. 2015;16(4):e181–9.

    Article  CAS  PubMed  Google Scholar 

  98. Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. Am J Clin Dermatol. 2001;2(4):253–62.

    Article  CAS  PubMed  Google Scholar 

  99. Vaiman M, Lazarovitch T, Heller L, Lotan G. Ecthyma gangrenosum and ecthyma-like lesions: review article. Eur J Clin Microbiol Infect Dis. 2015;34(4):633–9.

    Article  CAS  PubMed  Google Scholar 

  100. Koo SH, Lee JH, Shin H, Lee JI. Ecthyma gangrenosum in a previously healthy infant. Arch Plastic Surg. 2012;39(6):673–5.

    Article  Google Scholar 

  101. Vaiman M, Lasarovitch T, Heller L, Lotan G. Ecthyma gangrenosum versus ecthyma-like lesions: should we separate these conditions? Acta Dermatovenerol Alp Pannonica Adriat. 2015;24(4):69–72.

    PubMed  Google Scholar 

  102. Greene SL, Su WP, Muller SA. Ecthyma gangrenosum: report of clinical, histopathologic, and bacteriologic aspects of eight cases. J Am Acad Dermatol. 1984;11(5 Pt 1):781–7.

    Article  CAS  PubMed  Google Scholar 

  103. Martinez-Longoria CA, Rosales-Solis GM, Ocampo-Garza J, Guerrero-Gonzalez GA, Ocampo-Candiani J. Ecthyma gangrenosum: a report of eight cases. An Bras Dermatol. 2017;92(5):698–700.

    Article  PubMed  PubMed Central  Google Scholar 

  104. McManus AT, Mason AD Jr, McManus WF, Pruitt BA Jr. Twenty-five year review of Pseudomonas aeruginosa bacteremia in a burn center. Eur J Clin Microbiol. 1985;4(2):219–23.

    Article  CAS  PubMed  Google Scholar 

  105. Abdelkefi A, Torjman L, Ladeb S, Sghaier Z, Jeddi R, Lakhal A, et al. Isolated extramedullary relapse in the breast of a patient with acute myeloid leukemia following allogeneic stem cell transplantation: case report and review of the literature. Int J Hematol. 2007;85(2):149–53.

    Article  PubMed  Google Scholar 

  106. Wingard JR, Hsu J, Hiemenz JW. Hematopoietic stem cell transplantation: an overview of infection risks and epidemiology. Hematol Oncol Clin North Am. 2011;25(1):101–16.

    Article  PubMed  Google Scholar 

  107. Mays SR, Bogle MA, Bodey GP. Cutaneous fungal infections in the oncology patient: recognition and management. Am J Clin Dermatol. 2006;7(1):31–43.

    Article  PubMed  Google Scholar 

  108. Nucci M, Anaissie E. Revisiting the source of candidemia: skin or gut? Clin Infect Dis. 2001;33(12):1959–67.

    Article  CAS  PubMed  Google Scholar 

  109. Burke VE, Lopez FA. Approach to skin and soft tissue infections in non-HIV immunocompromised hosts. Curr Opin Infect Dis. 2017;30(4):354–63.

    Article  PubMed  Google Scholar 

  110. Guarana M, Nucci M. Acute disseminated candidiasis with skin lesions: a systematic review. Clin Microbiol Infect. 2018;24(3):246–50.

    Article  CAS  PubMed  Google Scholar 

  111. Kauffman CA. Clinical manifestations and diagnosis of candidemia and invasive candidiasis in adults. In: UpToDate. http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-candidemia-andinvasive-candidiasis-in-adults. Accessed 27 June 2018.

  112. Singh N, Paterson DL. Aspergillus infections in transplant recipients. Clin Microbiol Rev. 2005;18(1):44–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Steinbach WJ, Marr KA, Anaissie EJ, Azie N, Quan SP, Meier-Kriesche HU, et al. Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH Alliance registry. J Infect. 2012;65(5):453–64.

    Article  PubMed  Google Scholar 

  114. van Burik JA, Colven R, Spach DH. Cutaneous aspergillosis. J Clin Microbiol. 1998;36(11):3115–21.

    PubMed  PubMed Central  Google Scholar 

  115. Allo MD, Miller J, Townsend T, Tan C. Primary cutaneous aspergillosis associated with Hickman intravenous catheters. N Engl J Med. 1987;317(18):1105–8.

    Article  CAS  PubMed  Google Scholar 

  116. Johnson AS, Ranson M, Scarffe JH, Morgenstern GR, Shaw AJ, Oppenheim BA. Cutaneous infection with Rhizopus oryzae and Aspergillus niger following bone marrow transplantation. J Hosp Infect. 1993;25(4):293–6.

    Article  CAS  PubMed  Google Scholar 

  117. Bernardeschi C, Foulet F, Ingen-Housz-Oro S, Ortonne N, Sitbon K, Quereux G, et al. Cutaneous invasive aspergillosis: retrospective multicenter study of the french invasive-aspergillosis registry and literature review. Medicine (Baltimore). 2015;94(26):e1018.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Chakrabarti A, Gupta V, Biswas G, Kumar B, Sakhuja VK. Primary cutaneous aspergillosis: our experience in 10 years. J Infect. 1998;37(1):24–7.

    Article  CAS  PubMed  Google Scholar 

  119. Reischies F, Hoenigl M. The role of surgical debridement in different clinical manifestations of invasive aspergillosis. Mycoses. 2014;57(Suppl 2):1–14.

    Article  PubMed  Google Scholar 

  120. Bodey GP, Boktour M, Mays S, Duvic M, Kontoyiannis D, Hachem R, et al. Skin lesions associated with Fusarium infection. J Am Acad Dermatol. 2002;47(5):659–66.

    Article  PubMed  Google Scholar 

  121. Nucci M, Marr KA, Queiroz-Telles F, Martins CA, Trabasso P, Costa S, et al. Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2004;38(9):1237–42.

    Article  PubMed  Google Scholar 

  122. Zimmerli W, Zarth A, Gratwohl A, Speck B. Neutrophil function and pyogenic infections in bone marrow transplant recipients. Blood. 1991;77(2):393–9.

    CAS  PubMed  Google Scholar 

  123. Chakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O’Gorman P, et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood. 2002;99(12):4357–63.

    Article  CAS  PubMed  Google Scholar 

  124. Xuan L, Huang F, Fan Z, Zhou H, Zhang X, Yu G, et al. Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies. J Hematol Oncol. 2012;5:46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Lin R, Liu Q. Diagnosis and treatment of viral diseases in recipients of allogeneic hematopoietic stem cell transplantation. J Hematol Oncol. 2013;6:94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Lewis DJ, Schlichte MJ, Dao H Jr. Atypical disseminated herpes zoster: management guidelines in immunocompromised patients. Cutis. 2017;100(5):321 (324, 330).

    PubMed  Google Scholar 

  127. Kadakia MP, Rybka WB, Stewart JA, Patton JL, Stamey FR, Elsawy M, et al. Human herpesvirus 6: infection and disease following autologous and allogeneic bone marrow transplantation. Blood. 1996;87(12):5341–54.

    CAS  PubMed  Google Scholar 

  128. Ogata M, Kikuchi H, Satou T, Kawano R, Ikewaki J, Kohno K, et al. Human herpesvirus 6 DNA in plasma after allogeneic stem cell transplantation: incidence and clinical significance. J Infect Dis. 2006;193(1):68–79.

    Article  CAS  PubMed  Google Scholar 

  129. Gotoh M, Yoshizawa S, Katagiri S, Suguro T, Asano M, Kitahara T, et al. Human herpesvirus 6 reactivation on the 30th day after allogeneic hematopoietic stem cell transplantation can predict grade 2-4 acute graft-versus-host disease. Transpl Infect Dis. 2014;16(3):440–9.

    Article  CAS  PubMed  Google Scholar 

  130. Drago F, Ciccarese G, Broccolo F, Cozzani E, Parodi A. Atypical exanthems associated with HHV-6 reactivation after hematopoietic cell transplantation. J Clin Virol. 2015;72:119–21.

    Article  PubMed  Google Scholar 

  131. de Pagter PJ, Schuurman R, Visscher H, de Vos M, Bierings M, van Loon AM, et al. Human herpes virus 6 plasma DNA positivity after hematopoietic stem cell transplantation in children: an important risk factor for clinical outcome. Biol Blood Marrow Transpl. 2008;14(7):831–9.

    Article  CAS  Google Scholar 

  132. Betts BC, Young JA, Ustun C, Cao Q, Weisdorf DJ. Human herpesvirus 6 infection after hematopoietic cell transplantation: is routine surveillance necessary? Biol Blood Marrow Transpl. 2011;17(10):1562–8.

    Article  Google Scholar 

  133. Zerr DM, Corey L, Kim HW, Huang ML, Nguy L, Boeckh M. Clinical outcomes of human herpesvirus 6 reactivation after hematopoietic stem cell transplantation. Clin Infect Dis. 2005;40(7):932–40.

    Article  PubMed  Google Scholar 

  134. Breuer S, Rauch M, Matthes-Martin S, Lion T. Molecular diagnosis and management of viral infections in hematopoietic stem cell transplant recipients. Mol Diagn Ther. 2012;16(2):63–77.

    Article  CAS  PubMed  Google Scholar 

  135. Wingard JR, Majhail NS, Brazauskas R, Wang Z, Sobocinski KA, Jacobsohn D, et al. Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011;29(16):2230–9.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Flowers ME, Inamoto Y, Carpenter PA, Lee SJ, Kiem HP, Petersdorf EW, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011;117(11):3214–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Min CK. The pathophysiology of chronic graft-versus-host disease: the unveiling of an enigma. Korean J Hematol. 2011;46(2):80–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Socie G, Ritz J. Current issues in chronic graft-versus-host disease. Blood. 2014;124(3):374–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Jacobsohn DA, Kurland BF, Pidala J, Inamoto Y, Chai X, Palmer JM, et al. Correlation between NIH composite skin score, patient-reported skin score, and outcome: results from the Chronic GVHD Consortium. Blood. 2012;120(13):2545–52 (quiz 774).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Strong Rodrigues K, Oliveira-Ribeiro C, de Abreu Fiuza Gomes S, Knobler R. Cutaneous graft-versus-host disease: diagnosis and treatment. Am J Clin Dermatol. 2018;19(1):33–50.

    Article  PubMed  Google Scholar 

  141. Pinney SS, Alousi AM, Hymes SR. Clinical presentation of nonsclerotic epidermal chronic graft-versus-host disease and hair and nail changes. In: Cotliar JA, editor. Atlas of graft-versus-host disease: approaches to diagnosis and treatment. Cham: Springer International Publishing; 2017. p. 69–91.

    Chapter  Google Scholar 

  142. Penas PF, Fernandez-Herrera J, Garcia-Diez A. Dermatologic treatment of cutaneous graft versus host disease. Am J Clin Dermatol. 2004;5(6):403–16.

    Article  PubMed  Google Scholar 

  143. Zuo RC, Naik HB, Steinberg SM, Baird K, Mitchell SA, Kuzmina Z, et al. Risk factors and characterization of vitiligo and alopecia areata in patients with chronic graft-vs-host disease. JAMA Dermatol. 2015;151(1):23–32.

    Article  PubMed  Google Scholar 

  144. Ceovic R, Desnica L, Pulanic D, Serventi Seiwerth R, Ilic I, Grce M, et al. High frequency of cutaneous manifestations including vitiligo and alopecia areata in a prospective cohort of patients with chronic graft-vs-host disease. Croat Med J. 2016;57(3):229–38.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Huang JT, Song JS, Hawryluk EB, London WB, Guo D, Sridharan M, et al. Nonmalignant late cutaneous changes after allogeneic hematopoietic stem cell transplant in children. J Am Acad Dermatol. 2018;79(2):230–7.

    Article  PubMed  Google Scholar 

  146. Nadeem S, Hymes S, Kebriaei P, Abruzzo L, Curry JL, Duvic M. Alopecia areata after HLA-identical BMT from an affected, sibling donor. Bone Marrow Transpl. 2014;49(4):592–4.

    Article  CAS  Google Scholar 

  147. DePry JL, Vyas R, Lazarus HM, Caimi PF, Gerstenblith MR, Bordeaux JS. Cutaneous malignant neoplasms in hematopoietic cell transplant recipients: a systematic review. JAMA Dermatol. 2015;151(7):775–82.

    Article  PubMed  Google Scholar 

  148. Omland SH, Gniadecki R, Haedersdal M, Helweg-Larsen J, Omland LH. Skin cancer risk in hematopoietic stem-cell transplant recipients compared with background population and renal transplant recipients: a population-based cohort study. JAMA Dermatol. 2016;152(2):177–83.

    Article  PubMed  Google Scholar 

  149. Rambhia PH, Conic RZ, Atanaskova-Mesinkovska N, Piliang M, Bergfeld WF. Role of graft versus host disease in the development of secondary skin cancers in hematopoietic stem cell transplant recipients: a meta-analysis. J Am Acad Dermatol. 2018;79(2):378–80.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank Dr. Leo Shmuylovich, MD/PhD, and Dr. Douglas Laurain, MD, for assisting with select photographs in this review.

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Authors and Affiliations

  1. Washington University School of Medicine, St. Louis, MO, USA

    Cynthia X. Wang, Milan J. Anadkat & Amy C. Musiek

  2. Division of Dermatology, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8123, St. Louis, MO, 63110, USA

    Milan J. Anadkat & Amy C. Musiek

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  1. Cynthia X. Wang
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Correspondence to Amy C. Musiek.

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CXW, MJA, and ACM have no conflicts of interest that are directly relevant to the content of this review.

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Wang, C.X., Anadkat, M.J. & Musiek, A.C. Dermatologic Conditions of the Early Post-Transplant Period in Hematopoietic Stem Cell Transplant Recipients. Am J Clin Dermatol 20, 55–73 (2019). https://doi.org/10.1007/s40257-018-0391-4

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