medigraphic.com

2025, Number 1

<< Back Next >>

Rev Hematol Mex 2025; 26 (1)

Graft-versus-host disease: A focus on skin.

Guzmán MZ, Morales PA, Ordoñez AAG, Chávez ÁS, Colunga PPR

Language: English
References: 49
Page: 1-14
PDF size: 505.62 Kb.


ABSTRACT

Background: Graft-versus-host disease (GVHD) remains a significant complication of allogeneic hematopoietic stem cell transplantation, with cutaneous manifestations being the most prevalent and early presenting. Both acute and chronic forms of cutaneous GVHD impose substantial morbidity and mortality risks.
Objective: To provide a comprehensive overview of graft-versus-host disease’s pathophysiology, clinical presentation, differential diagnosis, and therapeutic approaches, highlighting its impact on patient outcomes and quality of life.
Methodology: A bibliographic search in PubMed was done using the terms “cutaneous graft versus host disease”, “acute cutaneous graft versus host disease”, “chronic cutaneous graft versus host disease”, “acute GVHD”, “chronic GVHD”, “diagnosis” and “treatment”. The articles were selected based on the most recent published ones, text availability, citation frequency, and relevance.
Results: While acute cutaneous GVHD often presents with a characteristic rash, chronic GVHD exhibits a diverse clinical spectrum. Accurate diagnosis can be challenging and frequently necessitates histopathological confirmation. Management requires a multidisciplinary approach, incorporating pharmacological, phototherapeutic, and emerging immunomodulatory interventions. Given the complexity of the disease, personalized treatment plans, regular monitoring, and ongoing research are essential to optimize patient outcomes.
Conclusions: Cutaneous graft-versus-host disease remains a common and challenging complication of allogeneic bone marrow and hematopoietic cell transplantation.


REFERENCES

  1. Johnson ML, Farmer ER. Graft-versus-host reactions indermatology. J Am Acad Dermatol 1998; 38 (3): 369-92.doi: 10.1016/s0190-9622(98)70495-5

  2. Inamoto Y, Storer BE, Petersdorf EW, Nelson JL, et al. Incidence,risk factors, and outcomes of sclerosis in patientswith chronic graft-versus-host disease. Blood 2013; 121(25): 5098-103. doi: 10.1182/blood-2012-10-464198

  3. Vargas-Díez E, Fernández-Herrera J, Marin A, Cámara R,García-Díez A. Analysis of risk factors for acute cutaneousgraft-versus-host disease after allogeneic stem celltransplantation. Br J Dermatol 2003; 148 (6): 1129-34. doi:10.1046/j.1365-2133.2003.05336.x

  4. Cohen-Sors R, Arnault JP, Attencourt C, Charbonnier A, etal. Iatrogenic cutaneous graft versus host disease. DermatolOnline J 2020; 26 (11): 13030/qt16z1159

  5. Department of Clinical Haematology. http://nssg.oxfordhaematology.org.uk/bmt/gvhd/B-2-7c-diagnosis-andmanagement-cutaneous-gvhd.pdf . 2017. Guidelines fordiagnosis and management of cutaneous graft versus hostdisease Oxford university hospitals.

  6. Mawardi H, Hashmi SK, Elad S, Aljurf M, Treister N. Chronicgraft-versus-host disease: Current management paradigmand future perspectives. Oral Dis 2019; 25 (4): 931-48. doi:10.1111/odi.12936

  7. Ramachandran V, Kolli SS, Strowd LC. Review of graftversus-host disease. Dermatol Clin 2019; 37 (4): 569-82.doi: 10.1016/j.det.2019.05.014

  8. Martin PJ, Rizzo JD, Wingard JR, Ballen K, et al. First- andsecond-line systemic treatment of acute graft-versus-hostdisease: Recommendations of the American Society ofBlood and Marrow Transplantation. Biol Blood MarrowTransplant 2012; 18 (8): 1150-63. doi: 10.1016/j.bbmt.2012.04.005

  9. Naymagon S, Naymagon L, Wong SY, Ko HM, et al. Acutegraft-versus-host disease of the gut: considerations for thegastroenterologist. Nat Rev Gastroenterol Hepatol. 2017;14 (12): 711-26. doi: 10.1038/nrgastro.2017.126

  10. Hacisalihoglu UP, Sahin D. Incidence, histopathologicalfeatures and differential diagnosis of cutaneous graft versushost disease in allogeneic bone marrow transplantation.SiSli Etfal Hastan Tip Bul 2021; 55 (1): 68-75. doi: 10.14744/SEMB.2019.86729

  11. Zeiser R, Blazar BR. Acute graft-versus-host disease —biologic process, prevention, and therapy. N Engl J Med2017; 377 (22): 2167-79. DOI: 10.1056/NEJMra1609337

  12. Hong J, Fraebel J, Yang Y, Tkacyk E, et al. Understandingand treatment of cutaneous graft-versus-host-disease.Bone Marrow Transplant 2023; 58 (12): 1298-313. doi.org/10.1038/s41409-023-02109-x

  13. Link-Rachner CS, Sockel K, Schuetz C Established andemerging treatments of skin GvHD. Front Immunol2022; 13.

  14. Berhan A, Damtie S, Almaw A, Legesse B, et al. The role ofextracorporeal photopheresis in the management of graftversus host disease: Narrative review. Immunotargets Ther2024; 13: 235-46. doi: 10.2147/ITT.S457366

  15. Strong Rodrigues K, Oliveira-Ribeiro C, de Abreu FiuzaGomes S, Knobler R. Cutaneous graft-versus-host disease:diagnosis and treatment. Am J Clin Dermatol 2018; 19 (1):33-50. doi: 10.1007/s40257-017-0306-9

  16. Kavand S, Lehman JS, Hashmi S, Gibson LE, El-Azhary RA.Cutaneous manifestations of graft-versus-host disease: roleof the dermatologist. Int J Dermatol 2017; 56 (2): 131-40.doi: 10.1111/ijd.13381

  17. Hymes SR, Alousi AM, Cowen EW. Graft-versus-hostdisease: part I. Pathogenesis and clinical manifestationsof graft-versus-host disease. J Am Acad Dermatol 2012;66 (4): 515.e1-515.e18. doi: 10.1016/j.jaad.2011.11.960

  18. Aractingi S, Chosidow O. Cutaneous graft-versus-hostdisease. Arch Dermatol 1998; 134 (5). doi: 10.1001/archderm.134.5.602

  19. Garbutcheon-Singh KB, Fernández-Peñas P. Phototherapy forthe treatment of cutaneous graft versus host disease. AustralasJ Dermatol 2015; 56 (2): 93-9. doi: 10.1111/ajd.12191

  20. Kim YJ, Lee GH, Kwong BY, Martires KJ. Evidence-based,skin-directed treatments for cutaneous chronic graft-versus-host disease. Cureus 2019; 11 (12): e6462. doi:10.7759/cureus.6462

  21. Häusermann P, Walter RB, Halter J, Biedermann BC, etal. Cutaneous graft-versus-host disease: A guide for thedermatologist. Dermatology 2008; 216 (4): 287-304. doi:10.1159/000113941

  22. Schaffer JV., McNiff JM, Seropian S, Cooper DL, BologniaJL. Lichen sclerosus and eosinophilic fasciitis as manifestationsof chronic graft-versus-host disease: Expanding thesclerodermoid spectrum. J Am Acad Dermatol 2005; 53(4): 591-601. doi: 10.1016/j.jaad.2005.06.015

  23. Wu PA, Cowen EW. Cutaneous graft-versus-host disease– Clinical considerations and management. Curr ProblDermatol 2012: 43: 101-15. doi: 10.1159/000335270

  24. Marks DH, Naftulin JS, Penzi LR, Manatis-Lornell A, et al.Histologic and clinical cross-sectional study of chronic hairloss in patients with cutaneous chronic graft-versus-hostdisease. J Am Acad Dermatol 2019; 81 (5): 1134-41. doi:10.1016/j.jaad.2019.03.031

  25. Kohler S, Hendrickson MR, Chao NJ, Smoller BR. Value ofskin biopsies in assessing prognosis and progression ofacute graft-versus-host disease. Am J Surg Pathol 1997;21 (9): 988-96. doi: 10.1097/00000478-199709000-00002

  26. Ji H, Feng S, Liu Y, Cao Y, Lou H, Li Z. Effect of GVHD on thegut and intestinal microflora. Transpl Immunol 2024; 82:101977. doi: 10.1016/j.trim.2023.101977

  27. Blaise D, Vey N, Faucher C, Mohty M. Current status ofreduced intensity conditioning allogeneic stem cell transplantationfor acute myeloid leukemia. Haematologica.2007; 92 (4): 533-41. doi: 10.3324/haematol.10867

  28. Lerner KG, Kao GF, Storb R, Buckner CD, et al. Histopathologyof graft-vs.-host reaction (GvHR) in human recipientsof marrow from HL-A-matched sibling donors. TransplantProc 1974; 6 (4): 367-71.

  29. Ziemer M, Haeusermann P, Janin A, Massi D, et al. Histopathologicaldiagnosis of graft-versus-host disease of theskin – an interobserver comparison. J Eur Acad DermatolVenereol 2014; 28 (7): 915-24. doi: 10.1111/jdv.12215

  30. Pidala J, Onstad L, Martin PJ, Hamilton BK, et al. Initialtherapy for chronic graft-versus-host disease: analysis ofpractice variation and failure-free survival. Blood Adv 2021;5 (22): 4549-59. doi: 10.1182/bloodadvances.2021005286

  31. Kadri N, Amu S, Iacobaeus E, Boberg E, Le Blanc K. Currentperspectives on mesenchymal stromal cell therapy for graftversus host disease. Cell Mol Immunol 2023; 20 (6): 613-25.https://doi.org/10.1038/s41423-023-01022-z

  32. Rashidi A, DeFor TE, Holtan SG, Blazar BR, et al. Outcomesand predictors of response in steroid-refractory acutegraft-versus-host disease. Biol Blood Marrow Transplant2019; 25 (11): 2297-302. doi: 10.1016/j.bbmt.2019.07.017

  33. Hill GR, Koyama M. Cytokines and costimulation in acutegraft-versus-host disease. Blood 2020; 136 (4): 418-28. doi:10.1182/blood.2019000952

  34. Carpenter PA, Kitko CL, Elad S, Flowers MED, et al. NationalInstitutes of Health Consensus Development Project on Criteriafor Clinical Trials in Chronic Graft-versus-Host Disease:V. The 2014 Ancillary Therapy and Supportive Care WorkingGroup Report. Biol Blood Marrow Transplant 2015; 21 (7):1167-87. doi: 10.1016/j.bbmt.2015.03.024

  35. Marks C, Stadler M, Häusermann P, Wolff D, et al. German-Austrian-Swiss Consensus Conference on clinical practicein chronic graft-versus-host disease (GVHD): guidance forsupportive therapy of chronic cutaneous and musculoskeletalGVHD. Br J Dermatol 2011; 165 (1): 18-29. doi:10.1111/j.1365-2133.2011.10360.x

  36. Rao A, Luo C, Hogan PG. Transcription factors of the NFATfamily: Regulation and function. Annu Rev Immunol 1997;15 (1): 707-47. doi: 10.1146/annurev.immunol.15.1.707

  37. Choi CJ, Nghiem P. Tacrolimus ointment in the treatmentof chronic cutaneous graft-vs-host disease. Arch Dermatol2001; 137 (9). doi:10.1001/archderm.137.9.1202

  38. Elad S, Or R, Resnick I, Shapira MY. Topical tacrolimus? Anovel treatment alternative for cutaneous chronic graftversus-host disease. Transplant Int 2003; 16 (9): 665-70.doi: 10.1007/s00147-003-0594-2

  39. Olson KA, West K, McCarthy PL. Toxic tacrolimus levelsafter application of topical tacrolimus and use of occlusivedressings in two bone marrow transplant recipients withcutaneous graft-versus-host disease. Pharmacotherapy2014;34 (6). doi: 10.1002/phar.1418

  40. Vaidya TS, Menzer C, Ponce DM, Markova A. Inpatientmanagement of mucocutaneous GVHD. Curr DermatolRep 2019; 8 (4): 258-78. doi: 10.1007/s13671-019-00280-3

  41. Ballester-Sánchez R, Navarro-Mira MÁ, de Unamuno-BustosB, Pujol-Marco C, et al. Análisis retrospectivo del papelde la fototerapia en la enfermedad injerto contra huéspedcrónica cutánea. Revisión de la literatura. Actas Dermosifiliogr2015; 106 (8): 651-7. https://doi.org/10.1016/j.ad.2015.04.009

  42. Baumrin E, Loren AW, Falk SJ, Mays JW, Cowen EW. Chronicgraft-versus-host disease. Part II: Disease activity gradingand therapeutic management. J Am Acad Dermatol 2024;90 (1): 19-36. doi: 10.1016/j.jaad.2022.12.023

  43. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, et al.1994 consensus conference on acute GVHD grading. BoneMarrow Transplant 1995; 15 (6): 825-8.

  44. Malagola M, Cancelli V, Skert C, Leali PF, et al. Extracorporealphotopheresis for treatment of acute and chronicgraft versus host disease. Transplantation 2016; 100 (12):e147-55. doi: 10.1097/TP.0000000000001466

  45. Assal A, Mapara MY. Janus kinase inhibitors and celltherapy. Front Immunol 2021; 12.

  46. Mohty M, Holler E, Jagasia M, Jenq R, et al. Refractoryacute graft-versus-host disease: a new working definitionbeyond corticosteroid refractoriness. Blood 2020; 136 (17):1903-6. doi: 10.1182/blood.2020007336

  47. Guo W Wen, Su X Hua, Wang M Yang, Han M Zhe, et al.Regulatory T cells in GVHD therapy. Front Immunol 2021;12. doi: 10.3389/fimmu.2021.697854

  48. Inamoto Y, Zeiser R, Chan GCF. Novel treatment for graftversus-host disease. Blood Cell Ther 2021; 4 (4). doi:10.31547/bct-2021-022

  49. Canninga-van Dijk MR, Sanders CJ, Verdonck LF, FijnheerR, van den Tweel JG. Differential diagnosis of skin lesionsafter allogeneic haematopoietic stem cell transplantation.Histopathology 2003; 42 (4): 313-30. doi:10.1046/j.1365-2559.2003.01591.x




2020     |     www.medigraphic.com