Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®): Supportive care - Health Professional Information [NCI] - Graft-versus-Host Disease
Patients who have received allogeneic or matched unrelated transplants are at risk of developing graft-versus-host disease (GVHD).[1,2] A related condition referred to as pseudo-GVHD is occasionally reported in autologous hematopoietic stem cell transplant recipients. GVHD can affect oral tissues and often mimics naturally occurring autoimmune diseases such as erosive lichen planus, pemphigus, scleroderma, and Sjögren syndrome. Oral GVHD has also been linked to oral precancerous and malignant lesions.
Acute GVHD can occur as early as 2 to 3 weeks posttransplant; mucosal erythema and erosion/ulceration are typical manifestations. Chronic oral GVHD changes can be recognized as early as day 70 posttransplant. The pattern and types of lesions seen in acute GVHD are also seen in chronic GVHD, but manifestations can also include raised white hyperkeratotic plaques and striae and persistent reduced salivary function. Oral symptoms of oral GVHD include xerostomia and increased sensitivity and pain with spices, alcohols, and flavoring agents (especially mint flavors in toothpaste and oral care products). Patients may also suffer from odynophagia and dysphagia due to gastrointestinal involvement. All of these symptoms of GVHD may lead to weight loss and malnutrition.
Biopsy of oral mucosa, including both surface epithelium and minor labial salivary glands, may be of value in establishing a final diagnosis.[7,8] Presence of a lymphocytic infiltrate (grade I) with epithelial cell necrosis (grade II) provides the diagnostic basis for oral GVHD. As clinical criteria for recognition of oral signs and symptoms of GVHD have become more established, dependance on the oral biopsy to diagnose oral involvement has lessened. In cases of equivocal examination findings, the biopsy can improve the recognition of oral involvement.
Topical management of mucosal lesions may include steroids, azathioprine, and/or oral psoralen and ultraviolet A (PUVA) therapy (refer to the list on Management of Oral Chronic GVHD).[4,9] While topical cyclosporin has been suggested as therapeutically beneficial, its effectiveness is less predictable than that of other treatments—which, when coupled with increased cost of care, usually decreases its utility. The use of FK506 and mycophenolate mofetil to topically treat oral GVHD remains anecdotal and of uncertain efficacy. Systemic therapy (e.g., prednisone, budesonide, cyclosporine, mycophenolate mofetil, and other immunosuppressive agents) is routinely necessary, primarily to treat the condition. Topical treatment can be used to specifically manage oral sensitivity and help heal ulcerations. Patients with clinically significant xerostomia may benefit from pilocarpine (5 mg 3 or 4 times a day) or cevimeline (10 mg 4 times a day) if native salivary gland function remains partially intact.
Submucosal and/or dermal fibrosis can occur in persistent cases of chronic GVHD. This scleroderma-like complication can be subtle and appear as slight mucosal or skin tightness, or it can progress to skin thickening and fibrosis. Intraoral submucosal fibrotic bands have been noted to significantly restrict the oral opening. Successful management of GVHD with systemic therapy will usually see resolution and/or significant resolution of this problem. However, in rare instances, surgical or chemical techniques to disrupt fibrotic bands can be required to improve the oral opening.