Graft-versus-host disease (GVHD) is an immune disorder caused by the reaction of histoincompatible, immunocompetent donor cells against the tissues of an immunoincompetent host (graft-versus-host reaction, GVHR), characterized by acute cutaneous changes ranging from maculopapular eruption to toxic epidermal necrolysis, diarrhea, and liver dysfunction, as well as chronic changes comprising lichenoid eruptions and sclerodermatous changes.
Acute GVHD
Causes of Graft Versus Host Disease
GVHR associated with inflammatory reaction mounted by the donor cells against specific host organs-skin, liver, or GI tract. Severity of GVHD related to histocompatibility match between donor and recipient and preparatory regimen used. With successful engraftment, there is replacement of host marrow by immunocompetent donor cells capable of reacting against the “foreign” tissue antigens of the host.
Symptoms of Acute Graft Versus Host Disease
- Skin rash
- Abnormal liver function test
- Spots may coalesce to form widespread red rash
- Fever may be present
Diagnosis
Clinical findings confirmed by skin biopsy.
Treatment
Topical Glucocorticoids Potent glucocorticoid ointment gives symptomatic relief and adequate control in cases of mild to moderate cutaneous GVHD.
Prednisone 80 to 100 mg/d for mild to moderate cutaneous GVHD.
Cyclosporine Added to prednisone for severe cutaneous disease, ±GI or liver GVHD. Once cutaneous as well as GI and liver manifestations of GVHD have been controlled, cyclosporine and prednisone can be tapered and eventually discontinued.
PUVA Effective for subacute and chronic GVHD. Extracorporeal photopheresis is being evaluated.
Chronic GVHD
History
> 100 days after BMT. Either evolving from acute GVHD or arising de novo. Acute GVHD is not always followed by chronic GVHD. Clinical classification thus distinguishes between quiescent onset, progressive onset, and de novo chronic cutaneous GVHD. Chronic GVHD occurs in 25% of recipients of marrow from an HLA-identical sibling who survive > 100 days.
Physical examination
Skin Lesions Flat-topped (lichen planus-like) papules of violaceous color, initially on distal extremities but later generalized. Confluent areas of dermal sclerosis with overlying scale resembling scleroderma mainly on trunk, buttocks, hips, and thighs. With more severe disease, severe generalized sclerodermoid changes with necrosis and ulceration on acral and pressure sites. Hair loss; anhidrosis, vitiligo-like hypopigmentation.
General Findings Chronic liver disease, general wasting.
Differential diagnosis
Lichen planus, lichenoid drug reaction, scleroderma, poikiloderma.
Laboratory examinations
Chemistry Elevated transaminases, gammaGT
Dermatopathology Hyperkeratosis, mild hypergranulosis, mild irregular acanthosis or atrophy, moderate basal vacuolization; rare individual cell necrosis, mild perivascular mononuclear cell infiltrate, melanin incontinence; loss of hair follicles, entrapment of sweat glands; dense dermal sclerosis.
Course and prognosis
Sclerodermoid GVHD with tight skin/joint contracture may result in impaired mobility ulcerations. Permanent hair loss; xerostomia, xerophthalmia, corneal ulcers, blindness. Malabsorption. Mild chronic cutaneous GVHD may resolve spontaneously. Chronic GVHD may be associated with recurrent and occasionally fatal bacterial infections.
Symptoms of Chronic Graft Versus Host Disease
- Dry, itchy raised rash develops over whole body
- Hair loss or premature greying
- Skin thickening, scaling, hyper- or hypopigmentation (resembling lichen planus)
Treatment
Topical corticosteroids and PUVA are very effective. Systemic immunosuppression with prednisone, cyclosporine and azathioprine, in various combinations. Thalidomide. Extracorporeal photopheresis is being evaluated.
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