Cutaneous graft-versus-host disease after hematopoietic stem cell transplant - a review

Villarreal, Cesar Daniel Villarreal; Alanis, Julio Cesar Salas; Pérez, Jose Carlos Jaime; Candiani, Jorge Ocampo

doi:10.1590/abd1806-4841.20164180

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Review • An. Bras. Dermatol. 91 (3) • May-Jun 2016 • https://doi.org/10.1590/abd1806-4841.20164180 copy

Cutaneous graft-versus-host disease after hematopoietic stem cell transplant - a review^* * Work performed at the Department of Dermatology, "Dr. Jose E. Gonzalez" University Hospital of the School of Medicine of the ''Universidad Autanoma de Nuevo León'', - Nuevo León, Mexico.

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Abstract

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplants (allo-HSCT) associated with significant morbidity and mortality. The earliest and most common manifestation is cutaneous graft-versus-host disease. This review focuses on the pathophysiology, clinical features, prevention and treatment of cutaneous graft-versus-host disease. We discuss various insights into the disease's mechanisms and the different treatments for acute and chronic skin graft-versus-host disease.

Keywords:
Graft vs host disease; Hematopoietic stem cell transplantation; Hematopoietic stem cells

Histopathology described by Lerner et al. for diagnosing GVHD (27)		1994 Consensus Conference on Acute GVHD Grading. (54)		International Bone Marrow Transplant Registry (IBMTR)
Grade	Skin	Stage	Skin	Grade	GVHD
0	Normal skin	0	No GVHD rash	I	Skin stage 1–2
1	Mild vacuolization of epidermal cells	1	Maculopapular rash< 25% BSA	II	Skin stage 3 or liver/gut stage I
2	Diffuse vacuolization of basal cells with scattered dyskeratotic bodies	2	Maculopapular rash 25 – 50% BSA
3	Sub-epidermal cleft formation	3	Maculopapular rash > 50% BSA	III	Skin Stage 3 or liver stage 2-3/ gut stage 2-4
4	Complete epidermal separation	4	Generalized erythroderma plus bullous formation	IV	Skin stage 4 or liver stage 4

Treatment	General characteristics
Steroids	• Immunosuppressive medications, used to prevent acute GVHD alone or in combination with other agents such as ATG, CSA, tacrolimus, MMF or monoclonal antibodies.
	• Only 20-40% of patients show a durable response.
	• Side effects: Increased risk of infection and of relapse of the underlying malignancy, skin atrophy.
	• Sort by potency:
		I. Mild (lower-potency steroid): Hydrocortisone 0.1–14
		II. Moderate (mid-potency steroid): Triamcinolone acetonide 0.05–0.1%
		III. Potent (high-potency steroid): Mometasone furoate 0.1%
		IV. Very potent (ultra-high-potency steroid): Clobetasol propionate 0.05%
Extracorporeal photopheresis	• Glucocorticoid-refractory acute and chronic GVHD
	• Peripheral blood leucocytes are isolated from the patient and irradiated with UVA light in combination with a photo-sensitizing agent such as psoralens.
	• Cytokine release and changes in Th1/Th2 ratios might explain some of its therapeutic benefits.
	• Side effects: hypotension during the procedure, post-reinfusion fever and erythema and nausea related to oral psoralen ingestion.
UVA-l phototherapy	• Induces apoptosis of skin-infiltrating T cells, thereby causing a gradual reduction of the inflammatory infiltrate.
	• Dose-dependent up-regulation of collagenase activity.
	• Highly effective in treating acute cutaneous GVHD with an overall response rate of 94.3%.
	• Feasible, well-tolerated and effective in treating chronic as well as acute GVHD.
	• This form of phototherapy is currently not widely available.
	• Few side effects: Erythema, tanning, polymorphic light eruptions, recrudescence of herpes simplex infection.
	• Potential long-term adverse effect: carcinogenic.
Skin transplantation	• Alternative in cases of skin ulceration due to refractory chronic cutaneous GVHD.
Skin transplantation	• Split-thickness transplantation from the HLA-identical donor.

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E-mail: revista@sbd.org.br

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[1] Mailing address: Cesar Daniel Villarreal Villarreal, Hematology, "Dr. Rodrigo Barragán Villarreal" Building, 2nd floor. Ave. Madero y Ave. Gonzalitos s/n, Colonia Mitras, Centro, C.P. 64460, Monterrey, N.L. Mexico. E-mail: cesardvv@gmail.com

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Cutaneous graft-versus-host disease after hematopoietic stem cell transplant - a review* * Work performed at the Department of Dermatology, "Dr. Jose E. Gonzalez" University Hospital of the School of Medicine of the ''Universidad Autanoma de Nuevo León'', - Nuevo León, Mexico.

Abstract

Cutaneous graft-versus-host disease after hematopoietic stem cell transplant - a review^* * Work performed at the Department of Dermatology, "Dr. Jose E. Gonzalez" University Hospital of the School of Medicine of the ''Universidad Autanoma de Nuevo León'', - Nuevo León, Mexico.