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Review
. 2023 Dec;58(12):1298-1313.
doi: 10.1038/s41409-023-02109-x. Epub 2023 Sep 20.

Understanding and treatment of cutaneous graft-versus-host-disease

Junshik Hong #  1   2   3 , Johnathan Fraebel #  3 , Yenny Yang  3 , Eric Tkacyk  4   5 , Carrie Kitko  6   7 , Tae Kon Kim  8   9   10   11
Affiliations
Review

Understanding and treatment of cutaneous graft-versus-host-disease

Junshik Hong et al. Bone Marrow Transplant. 2023 Dec.

Abstract

The skin is the outermost mechanical barrier where dynamic immune reactions take place and is the most commonly affected site in both acute and chronic graft-versus-host disease (GVHD). If not properly treated, pain and pruritis resulting from cutaneous GVHD can increase the risk of secondary infection due to erosions, ulcerations, and damage of underlying tissues. Furthermore, resulting disfiguration can cause distress and significantly impact patients' quality of life. Thus, a deeper understanding of skin-specific findings of GVHD is needed. This review will highlight some promising results of recent pre-clinical studies on the pathophysiology of skin GVHD and summarize the diagnostic and staging/grading procedures according to the clinical manifestations of skin GVHD. In addition, we will summarize outcomes of various GVHD treatments, including skin-specific response rates.

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Conflict of interest statement

TKK has received a research funding from Nextcure, that is not relevant to this manuscript. TKK is a consultant for Agenus and Immunobiome. ERT has previously received as a consultant for Incyte. CLK has serviced on an advisory board for Horizon Therapeutics.

Other authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.. Pathophysiology of acute cutaneous graft vs host disease.
Tissue injury (e.g. chemotherapy) initiates the process (1) with activation of innate immunity, release of pro-inflammatory cytokines (2), and antigen presenting cell (APC) activation (3) which recruit alloreactive T cells (4). CD4+ alloreactive T cells amplify the immune response (5) leading expansion and activation of CD8+ effector T cells that mediate host tissue injury (6).
Figure 2.
Figure 2.. Pathophysiology of chronic cutaneous grafts vs host disease.
Preceding skin injury (e.g. chemotherapy, acute GVHD, etc.) (1) initiates an innate immune response (2) with release of pro-inflammatory cytokines that recruit alloreactive T cells (3) originating from the graft and through escape of negative selection due to thymic injury and impaired central tolerance during immune reconstitution (4). CD4+ T cells facilitate survival and proliferation of alloreactive B cells (5) leading to alloantibody production (6). Chronic inflammation mediated by alloreactive T and B cells are further promoted through decreased survival of Tregs with impairment of peripheral tolerance (7) leading ultimately to tissue fibrosis (8).
Figure 3.
Figure 3.. Typical clinical features of acute cutaneous graft-versus-host disease (GVHD).
a Ill-defined morbilliform eruption with greatest intensity in cephalic regions. b Exfoliative acute GVHD with a superficial epidermal split mimicking Stevens-Johnson Syndrome / toxic epidermal necrolysis. c Acral hemorrhagic bullae and violaceous papules. Reprinted from Am J Clin Dermatol. 2018; 19(1): 33–50. Published online 2017 Jun 27. doi: 10.1007/s40257-017-0306-9
Figure 4.
Figure 4.. Stevens-Johnson Syndrome/toxic epidermal necrolysis-like presentation of acute cutaneous graft-versus-host disease.
a Blisters on right auricle. b total separation of the epidermis, resembling the symptoms of toxic epidermal necrolysis. Reprinted from Am J Clin Dermatol. 2018; 19(1): 33–50. Published online 2017 Jun 27. doi: 10.1007/s40257-017-0306-9
Figure 5.
Figure 5.. Chronic graft-versus-host disease presenting with lichen-planus like violaceous thin papules.
Morbilliform eruption can also be seen here.
Figure 6.
Figure 6.
Body surface area estimation according to the ‘Rule of Nines’ in adults and children.
Figure 7.
Figure 7.. Chronic graft-versus-host disease with deep sclerosis.
Overlying mottled hyper and hypopigmentation also seen here are characteristic of poikiloderma.
Figure 8.
Figure 8.. Lichen sclerosus-like epidermal chronic graft-versus-host disease with mild erythema.
On left upper chest, neck near clavicle, and some of the left biceps. Increased skin markings are the clue to dermal atrophy.
See this image and copyright information in PMC

References

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