With the ever-increasing number of bone marrow transplantations and increasing survival rates of patients undergoing these procedures, graft-versus-host disease (GVHD) is becoming more prevalent. Two distinct clinical cutaneous forms exist, acute and chronic, each with its own manifestations and treatment options. Acute GVHD is often manifested by mucocutaneous eruptions that can range from a mild macular rash to life-threatening blistering of the skin. Chronic cutaneous GVHD is entirely different in clinical manifestation than its acute counterpart. The two forms are also seen during specific time frames: Acute GVHD is most likely to occur within the first 3 months after transplantation, whereas chronic GVHD occurs later, typically 4 months or longer after transplantation.
GVHD can be seen not only after bone marrow transplantation but in any immunosuppressed patient who has receives antigenically and immunologically viable cells from a donor. This may occur during organ transplantation or, rarely, during blood transfusion. The use of leuko-poor blood has helped decrease the chance of GVHD after blood transfusions.
Clinical Findings: Acute GVHD is a common complication after bone marrow transplantation. The incidence has been reported to be as high as 90%. The degree of involvement is variable. GVHD affects males and females equally, and there is no racial preference. Patients who develop acute GVHD typically begin having symptoms soon after their cell counts recover, usually 1 to 2 weeks after transplantation. Skin rashes that develop within the first week after transplantation are usually not from GVHD. The skin, upper and lower digestive tract, and liver are frequently involved, and these organ systems are evaluated to help make the diagnosis of GVHD. The rash of acute GVHD can range from a fine maculopapular rash to severe blistering of the skin that can resemble toxic epidermal necrolysis and can be life-threatening. It is difficult, if not impossible, to predict the development and course of acute GVHD. These patients are always taking multiple medications, and the differential diagnosis includes a drug rash. Histological evaluation of a skin biopsy cannot differentiate the two. The coexistence of mucositis, diarrhea, and elevated liver enzymes makes the diagnosis of acute GVHD more plausible. The constellation of all these symptoms leads one to make the diagnosis.
Chronic GVHD has entirely different clinical manifestations. This form of GVHD typically begins 3 to 6 months after transplantation. The skin is the organ system most commonly involved. Two distinct forms of chronic cutaneous GVHD occur, lichenoid and sclerodermatous. The lichenoid variant manifests as red papules, patches, and plaques. They can occur anywhere on the surface of the skin. There is a slight resemblance to lichen planus. The sclerodermatous variant is less common and manifests as thickened, firm skin with poikilodermatous changes. The surface of the skin is shiny, and the loss of adnexal structures is variable. This variant of chronic GVHD can be localized to a small area, or it can be generalized and may include the entire surface area of the skin. The amount of surface area involved is directly related to the morbidity the patient experiences.
Histology: Histological evaluation of skin biopsy specimens cannot differentiate acute GVHD from drug exanthems. Acute GVHD has been graded on a histological scale of 1 to 4. Grade 1 shows basal layer vacuolar and interface changes; grade 2 shows signs of keratinocyte death; grade 3 shows clefting within the subepidermal space; and grade 4 is full bulla formation with epidermal parting.
Lichenoid chronic GVHD shows a lichenoid dermatitis with a predominantly lymphocytic infiltrate. The sclerodermatous form of chronic GVHD shows abnormally thick dermal collagen, much like that seen in scleroderma.
Treatment: The treatment of acute GVHD is based on the clinical symptoms and the type of skin lesions.
Corticosteroids are commonly used in cases of GVHD, both acute and chronic. The acute form has also been treated with FK506 and cyclosporine. Many other immunosuppressants have been used.
Chronic GVHD is difficult to manage. There is no cure for GVHD, and treatment is directed at stabilizing and improving skin function and increasing the patient’s functional capabilities. Phototherapy has been use successfully, as has extracorporeal photopheresis.