Cutaneous Chronic Graft-Versus-Host Disease: Clinical Manifestations, Diagnosis, Management, and Supportive Care

Abstract

Cutaneous chronic graft-versus-host disease (cGVHD) is associated with morbidity, mortality, and impaired quality of life after hematopoietic stem cell transplantation. The clinical features of cutaneous cGVHD are heterogeneous but can be broadly classified into nonsclerotic or sclerotic presentations. This review provides an overview of clinical presentation, diagnosis and differential diagnosis, grading, and treatment of cutaneous cGVHD. Particular attention is given to cutaneous cGVHD in skin of color, which can have unique features and is generally underrepresented in the literature leading to delays in diagnosis. Finally, an overview of long-term skin care for patients with cutaneous cGVHD is provided in order to support patients from a dermatologic perspective as they recover from cGVHD. Multidisciplinary care with frequent communication between transplant specialists and dermatologists is critical to effectively managing cutaneous cGVHD.

Keywords: Cutaneous graft versus host disease.

Figure 1.

Acute GVHD. (A) Dusky red papules symmetrically distributed on acral skin. (B) Diffuse areas of dusky erythema have coalesced with bullae formation and epidermal sloughing resembling toxic epidermal necrolysis in severe disease. (C) Folliculocentric appearance of macules and papules on the trunk.

Figure 2.

Lichen Planus-like lesions both in skin of color and white skin. (A) Violaceous papules on the penile shaft with erythema and scaling of the glans penis mimic idiopathic lichen planus. (B) White papules on the lips. (C) Periorbital violaceous papules and (D) similar lesions on the lips. Prominent pigmentation often results, particularly in patients with skin of color.

Figure 3.

Poikiloderma. Reticulate hyperpigmentation and hypopigmentation on the chest and neck.

Figure 4.

Postinflammatory hyperpigmentation and hypopigmentation (following nonsclerotic involvement). (A) Mottled neck hypopigmentation and follicular hyperpigmentation on the chest in a male with a history of epidermal cGVHD. (B) Extensive mottled pigmentation in a girl. Both hyperpigmentation and hypopigmentation are often present in heavily pigmented individuals.

Figure 5.

Alopecia. (A) Diffuse loss of scalp density and (B) focal areas of complete loss consistent with alopecia areata in a pediatric patient after allogeneic stem cell transplantation.

Figure 6.

Nail changes. Nail abnormalities range from prominent longitudinal ridging (onychorrhexis, 3rd digit) thin nail plate with nail splitting (2nd digit) to complete nail loss with scarring (anonychia, 4th and 5th digits).

Figure 7.

Lichen sclerosus-like lesions. Small guttate white/gray plaques with characteristic shiny appearance and cigarette paper-like scale.

Figure 8.

Morphea-like lesions. Hyperpigmented, thickened areas of fibrosis demonstrate a shiny, taut appearance. Note the preferential involvement of skin changes in the brassiere and waistband areas, consistent with isomorphic involvement.

Figure 9.

Scleroderma versus sclerotic cGVHD. (A) Scleroderma is characterized by progressive fibrosis which begins on acral surfaces resulting in sclerodactyly with a taut, shiny appearance of digits (Courtesy: Victoria Werth MD, University of Pennsylvania). (B) Sclerotic cGVHD often involves the proximal dorsal hands and forearms but usually spares the skin on the fingers.

Figure 10.

Pipestem appearance of lower extremities. Bound-down fibrotic white plaques on the feet and circumferential involvement of the lower legs leading to a ‘pipestem’ appearance. Note prominent hair loss in areas of skin fibrosis. (A) White patient with vascular appearing papules on the left dorsal foot consistent with GVHD-associated angiomatosis. (B) Similar presentation in skin of color.

Figure 11.

Subcutaneous fibrosis in cGVHD. Subtle rippling with cellulite-like appearance. The overlying skin may appear clinically normal, as in this case, or may develop pigmentary changes.

Figure 12.

Fascial cGVHD. Prominent linear grooving may be seen along the path of superficial vessels or demarcating muscle/fascial groups, as in the popliteal fossae in this patient with subcutaneous sclerotic disease.

Figure 13.

Histopathology of sclerotic cGVHD. Homogenization and thickening of collagen are seen primarily in the adipose tissue in the deep portion of the specimen (hematoxylin and eosin 2×, inset 10×). *Image courtesy of Ruth Ann Vleugels, MD (Brigham and Women’s Hospital, Department of Dermatology).

Figure 14.

Differential diagnosis of chronic skin graft-versus-host disease (GVHD) according to clinical presentation.

Figure 15.

Lichen planus-like cutaneous GVHD on the dorsal hands.

Figure 16.

(A) Melanoma in situ presenting as an asymmetrically pigmented patch on the shoulder, (B) Squamous cell carcinoma presenting as a crusted, nonhealing hyperkeratotic papule on the forearm, both in patients who had undergone HSCT.

Figure 17.

(A) Ulceration on the medial malleolus of a patient with sclerotic and myofascial GVHD and concomitant venous stasis. (B) Traumatic injury on the lower leg resulting in a difficult-to-heal ulceration in a patient with sclerotic GVHD.

Figure 18.

GVHD-associated angiomatosis. Multiple vascular-appearing nodules on the medial aspects of the plantar feet in a patient with long-standing lower extremity skin sclerosis.