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Skin-nontumor / Clinical Dermatology

Other dermatoses

Skin graft rejection


Reviewer: Mowafak Hamodat, MB.CH.B, MSc., FRCPC (see Reviewers page)
Revised: 5 September 2011, last major update August 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

General
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● Clinically, rejection appears as maculopapular rash at mean 8 weeks after transplant

Proposed grading system for rejection of full-thickness cadaver skin transplant for large abdominal defects:
● Grade 0: no rejection; no perivascular infiltrates; normal skin
● Grade 1: indeterminate for rejection; 1-10% of vessels have infiltrates of small lymphocytes; no eosinophils, large lymphocytes, spongiosis, epidermis or stromal inflammation; basal vacuolar change
● Grade 2: mild rejection; 11-50% of vessels have infiltrates of small lymphocytes, variable eosinophils or mild spongiosis; no epidermal or stromal infiltrates or large lymphocytes; basal vacuolar change
● Grade 3: moderate rejection: 51%+ of vessels have infiltrates of small lymphocytes, variable epidermal and stromal inflammation, at most mild spongiosis, possible endothelial plumping, eosinophils and large lymphocytes; fusion of basilar vacuoles to form clefts and microvesicles
● Grade 4: severe rejection; 51% of vessels have infiltrates of small lymphocytes, but also dyskeratosis, epidermis has heavier lymphocytic infiltrates and moderate to severe spongiosis; stroma shows infiltrates extending into base of epidermis; also endothelial plumping, eosinophils and large lymphocytes; separation of epidermis from dermis
Am J Surg Pathol 2004;28:670

● Another grading system:
● Grade 0: normal skin
● Grade 1: basal vacuolar change
● Grade 2: dyskeratotic cells in the epidermis and/or follicle, dermal lymphocytic infiltrate
● Grade 3: fusion of basilar vacuoles to form clefts and microvesicles
● Grade 4: separation of epidermis from dermis

● Acute GVHD develops in one-third of HLA-matched recipients of allogeneic bone marrow; also follows stem cell transplantation; is seen only rarely after solid organ transplantation

Treatment
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● Chronic cutaneous GVHD has been treated with corticosteroids and immunosuppressants such as cyclosporine and extracorporeal photopheresis (ECP)

Clinical description
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● Early acute GVHD has vomiting, diarrhea, hepatic manifestations and erythematous macular rash; rarely it is confined to the flexures, there are follicular papules or blisters, or toxic epidermal necrolysis ensues
● In one case, just two erythematous nodules were the presenting features
● A pustular acral erythema with associated eccrine squamous syringometaplasia has also been reported
● Ichthyosiform features may occur in both the acute and chronic forms
● Chronic GVHD has an early lichenoid phase which resembles lichen planus and includes oral lesions
● Sclerodermatous GVHD has a 3% prevalence in patients receiving allogeneic bone marrow transplants
● Other late manifestations include alopecia, a lupus erythematosus-like eruption, cicatrizing conjunctivitis, pyogenic granuloma and angiomatous lesions, wasting, diffuse melanoderma, leukoderma and leukotrichia, esophagitis, liver disease and the sicca syndrome

Micro description
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● Acute GVHD: focal or diffuse basal cell hydropic changes
● Apoptotic and dyskeratotic keratinocytes at all levels of the epidermis and associated with adjacent lymphocytes (satellite cell necrosis) are characterstic
● Isolated cytoid bodies are also evident
● Lymphocytic exocytosis and spongiosis is sometimes a feature
● Also microvesiculation at the epidermodermal junction, follicular involvement. endothelial cell swelling and intimal and perivascular lymphocytic infiltrate, perivascular edema and nuclear dust

● Chronic GVHD is typically lichenoid, resembles lichen planus
● Hyperkeratosis, hypergranulosis, irregular acanthosis, basal cell hydropic changes, cytoid body formation, pigment incontinence and band like lymphohistiocytic infiltrate
● In contrast to idiopathic lichen planus, satellite cell necrosis is often present in the early phase of Chronic GVHD, and the infiltrate sometimes contain plasma cells and eosinophils
● Squamous metaplasia of eccrine sweat ducts have been described
● The late stage of chronic GVHD is charaterized by epidermal atrophy, with abolition of ridge pattern and scarring of superficial and deep dermis, with loss of adnexal structures

Micro images
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Moderate acute rejection (right: CD3 stain), courtesy of Dr. Bejarano, Univ of Miami, Florida

Differential diagnosis
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Acute contact dermatitis: more severe spongiosis, often intraepidermal vesicles and inflammatory cells in epidermis; also affects areas other than transplanted skin
● Drug, viral infection, chemotherapy effect: the use of skin biopsies to differentiate between drug reaction, chemotherapy effect, viral infection and GVHD has no real practical value; the presence of eosinophils is generally taken to favor a drug reaction, but this is not a correct assumption as eosinophils are occasionally seen in GVHD; the presence of more than five apoptotic keratinocytes, predominantly involving adnexal keratinocytes, is said to favor GVHD

Additional references
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eMedicine-Skin grafting

End of Skin-nontumor / Clinical Dermatology > Other dermatoses > Skin graft rejection


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