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Review
. 2024 Jan;90(1):1-16.
doi: 10.1016/j.jaad.2022.12.024. Epub 2022 Dec 23.

Chronic graft-versus-host disease. Part I: Epidemiology, pathogenesis, and clinical manifestations

Emily Baumrin  1 , Alison W Loren  2 , Sandy J Falk  3 , Jacqueline W Mays  4 , Edward W Cowen  5
Affiliations
Review

Chronic graft-versus-host disease. Part I: Epidemiology, pathogenesis, and clinical manifestations

Emily Baumrin et al. J Am Acad Dermatol. 2024 Jan.

Abstract

Chronic graft-versus-host disease is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 U.S. Food and Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of chronic graft-versus-host disease. Part II discusses disease grading and therapeutic management.

Keywords: graft-versus-host disease; medical dermatology; transplantation.

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Conflict of interest statement

Conflicts of interest None disclosed.

Figures

Figure 1.
Figure 1.. Graft-versus-host disease classification.
Acute GVHD is defined by characteristic clinical features of the skin, liver, and gastrointestinal tract and can occur as classic acute GVHD (prior to day 100) or late acute GVHD (after day 100). Chronic GVHD is defined by 2014 NIH Diagnostic Criteria of involved organs and can occur as classic chronic GVHD (without acute GVHD features) or chronic overlap GVHD (with acute GVHD features). Adapted from Lee SJ Classification systems for chronic graft-versus-host disease, Blood, 2017. 129(1): 30-37
Figure 2:
Figure 2:. Histologic features of chronic skin graft-versus-host disease.
A) Nonsclerotic-type in a patient with lichen planus-like involvement (see Figure 3B for clinical pathologic correlation) demonstrating vacuolar interface changes at the dermal-epidermal junction, with scattered apoptotic basal epidermal keratinocytes, and focal detachment of the epidermis from the subjacent dermis (hematoxylin and eosin, 20x). B) Sclerotic-type in a patient with deep-seated involvement resembling eosinophilic fasciitis demonstrating thickening of collagen bundles in the deep reticular dermis near the border with the subcutaneous fat and marked thickening of the fat septae. The epidermis and papillary dermis appear relatively normal (hematoxylin and eosin, 2x).
Figure 2:
Figure 2:. Histologic features of chronic skin graft-versus-host disease.
A) Nonsclerotic-type in a patient with lichen planus-like involvement (see Figure 3B for clinical pathologic correlation) demonstrating vacuolar interface changes at the dermal-epidermal junction, with scattered apoptotic basal epidermal keratinocytes, and focal detachment of the epidermis from the subjacent dermis (hematoxylin and eosin, 20x). B) Sclerotic-type in a patient with deep-seated involvement resembling eosinophilic fasciitis demonstrating thickening of collagen bundles in the deep reticular dermis near the border with the subcutaneous fat and marked thickening of the fat septae. The epidermis and papillary dermis appear relatively normal (hematoxylin and eosin, 2x).
Figure 3.
Figure 3.. Nonsclerotic features of chronic skin graft-versus-host disease.
A) Lichen planus-like, back, B) Lichen planus-like, forehead, C) Dyspigmentation, D) Nail dystrophy, pterygium
Figure 3.
Figure 3.. Nonsclerotic features of chronic skin graft-versus-host disease.
A) Lichen planus-like, back, B) Lichen planus-like, forehead, C) Dyspigmentation, D) Nail dystrophy, pterygium
Figure 3.
Figure 3.. Nonsclerotic features of chronic skin graft-versus-host disease.
A) Lichen planus-like, back, B) Lichen planus-like, forehead, C) Dyspigmentation, D) Nail dystrophy, pterygium
Figure 3.
Figure 3.. Nonsclerotic features of chronic skin graft-versus-host disease.
A) Lichen planus-like, back, B) Lichen planus-like, forehead, C) Dyspigmentation, D) Nail dystrophy, pterygium
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 4.
Figure 4.. Sclerotic features of chronic skin graft-versus-host disease.
A) Lichen sclerosus-like, B) Morphea-like, overlying joint causing contracture, C) Isomorphic (lichen planus-like and morphea-like), buttocks at area of pressure, D) Fasciitis groove sign, E) Sclerosis causing hand contracture, F) Sclerosis causing chest wall restriction, G) Leg ulcers, H) GVHD-associated angiomatosis, I) Cutaneous calcifications
Figure 5.
Figure 5.. Chronic oral graft-versus-host disease
A) Lichen planus-like, vermillion lips, B) Lichen planus-like, buccal mucosa, C) mucosal erythema, gingiva, D) Patchy hyperkeratosis with associated erythema, E) Papillary atrophy and hyperkeratosis of the dorsal tongue, F) Palatal mucoceles
Figure 5.
Figure 5.. Chronic oral graft-versus-host disease
A) Lichen planus-like, vermillion lips, B) Lichen planus-like, buccal mucosa, C) mucosal erythema, gingiva, D) Patchy hyperkeratosis with associated erythema, E) Papillary atrophy and hyperkeratosis of the dorsal tongue, F) Palatal mucoceles
Figure 5.
Figure 5.. Chronic oral graft-versus-host disease
A) Lichen planus-like, vermillion lips, B) Lichen planus-like, buccal mucosa, C) mucosal erythema, gingiva, D) Patchy hyperkeratosis with associated erythema, E) Papillary atrophy and hyperkeratosis of the dorsal tongue, F) Palatal mucoceles
Figure 5.
Figure 5.. Chronic oral graft-versus-host disease
A) Lichen planus-like, vermillion lips, B) Lichen planus-like, buccal mucosa, C) mucosal erythema, gingiva, D) Patchy hyperkeratosis with associated erythema, E) Papillary atrophy and hyperkeratosis of the dorsal tongue, F) Palatal mucoceles
Figure 5.
Figure 5.. Chronic oral graft-versus-host disease
A) Lichen planus-like, vermillion lips, B) Lichen planus-like, buccal mucosa, C) mucosal erythema, gingiva, D) Patchy hyperkeratosis with associated erythema, E) Papillary atrophy and hyperkeratosis of the dorsal tongue, F) Palatal mucoceles
Figure 5.
Figure 5.. Chronic oral graft-versus-host disease
A) Lichen planus-like, vermillion lips, B) Lichen planus-like, buccal mucosa, C) mucosal erythema, gingiva, D) Patchy hyperkeratosis with associated erythema, E) Papillary atrophy and hyperkeratosis of the dorsal tongue, F) Palatal mucoceles
Figure 6.
Figure 6.. Chronic vulvovaginal graft-versus-host disease
A) Lichen sclerosus-like with hypopigmented, thickened, adhesed left labium minus; fissures at right labium minus and posterior fourchette, B) Vulvar patchy erythema and erosions.
Figure 6.
Figure 6.. Chronic vulvovaginal graft-versus-host disease
A) Lichen sclerosus-like with hypopigmented, thickened, adhesed left labium minus; fissures at right labium minus and posterior fourchette, B) Vulvar patchy erythema and erosions.
Figure 7.
Figure 7.. Chronic male genital graft-versus-host disease.
A) Noninfectious balanitis with erythema and erosion of the coronal sulcus, B) Lichen planus-like with flat-topped papules with overlying scale
Figure 7.
Figure 7.. Chronic male genital graft-versus-host disease.
A) Noninfectious balanitis with erythema and erosion of the coronal sulcus, B) Lichen planus-like with flat-topped papules with overlying scale
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