Patients who have received allogeneic or matched unrelated transplants are at risk for graft-versus-host disease (GVHD).[1-3] A related condition referred to as pseudo-GVHD is occasionally reported in autologous hematopoietic stem cell transplant recipients. The lesion can affect oral tissues and often mimics naturally occurring autoimmune diseases such as erosive lichen planus, lupus erythematosus, scleroderma, and Sjögren syndrome. Oral GVHD has also been linked with oral precancerous and malignant lesions.[4]

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.[5] The pattern and types of lesions seen in acute GVHD are also seen in chronic GVHD, but manifestations can also include raised white 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).

Biopsy of oral mucosa including both surface epithelium and minor labial salivary glands may be of value in establishing a final diagnosis.[6,7] 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 evolvement.

Topical management of mucosal lesions may include steroids, azathioprine, and/or oral psoralen and ultraviolet A (PUVA) (refer to the list on Management of Oral Chronic GVHD below).[5,8] While topical cyclosporin has been suggested as being therapeutically beneficial, its effectiveness is less than 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, cyclosporine, and other immunosuppressive agents) is routinely necessary primarily to treat the condition. 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.

Management of Oral Chronic GVHD

• Topical steroids:
  • Rinses: dexamethasone elixir (Decadron).
  • Gels, creams:
    • fluocinonide (Fluonex)
    • clobetasol (Temovate)
    • halobetasol (Ultravate)
    • betamethasone (Celestone)
  • Powders: beclomethasone (Beclovent) (inhalers applied to mucosa).



• Other topical immunosuppressants:
  • azathioprine rinse (Imuran; 5–8 mg/mL)
  • cyclosporin (Neoral)



• Antifungals:
  • Topical preparations:
    • nystatin (Mycostatin)
    • clotrimazole (Mycelex)
    • amphotericin (Amphocin)
  • Systemic agents:
    • fluconazole (Diflucan)
    • itraconazole (Sporanox)



• PUVA: Psoralen and ultraviolet irradiation.



• Sialogogues:
  • pilocarpine (Salagen)
  • bethanechol
  • cevimeline (Evoxac)



• Topical anesthetics:
  • lidocaine (Xylocaine)
  • dyclonine (Dyclone)
  • diphenhydramine (Benadryl)
  • doxepin (Zonalon)



• Dental caries prevention:
  • Oral hygiene (dental plaque removal)
  • Fluorides:
    • Adult patients: brush-on, rinses, home-use trays
    • Pediatric patients: brush-on

     [Note: If drinking water does not have adequate fluoride content to prevent tooth decay, oral fluoride (e.g., drops, vitamins) should be provided to children younger than 12 years.]

  • Remineralizing solution.

References

1. Schubert MM, Sullivan KM: Recognition, incidence, and management of oral graft-versus-host disease. NCI Monogr (9): 135-43, 1990.  [PUBMED Abstract]
   
   
2. Woo SB, Lee SJ, Schubert MM: Graft-vs.-host disease. Crit Rev Oral Biol Med 8 (2): 201-16, 1997.  [PUBMED Abstract]
   
   
3. Demarosi F, Bez C, Sardella A, et al.: Oral involvement in chronic graft-vs-host disease following allogenic bone marrow transplantation. Arch Dermatol 138 (6): 842-3, 2002.  [PUBMED Abstract]
   
   
4. Abdelsayed RA, Sumner T, Allen CM, et al.: Oral precancerous and malignant lesions associated with graft-versus-host disease: report of 2 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93 (1): 75-80, 2002.  [PUBMED Abstract]
   
   
5. Schubert MM, Peterson DE, Lloid ME: Oral complications. In: Thomas ED, Blume KG, Forman SJ, eds.: Hematopoietic Cell Transplantation. 2nd ed. Malden, Mass: Blackwell Science Inc, 1999, pp 751-63. 
   
   
6. Loughran TP Jr, Sullivan K, Morton T, et al.: Value of day 100 screening studies for predicting the development of chronic graft-versus-host disease after allogeneic bone marrow transplantation. Blood 76 (1): 228-34, 1990.  [PUBMED Abstract]
   
   
7. Yamada H, Chihara J, Hamada K, et al.: Immunohistology of skin and oral biopsies in graft-versus-host disease after bone marrow transplantation and cytokine therapy. J Allergy Clin Immunol 100 (6 Pt 2): S73-6, 1997.  [PUBMED Abstract]
   
   
8. Epstein JB, Nantel S, Sheoltch SM: Topical azathioprine in the combined treatment of chronic oral graft-versus-host disease. Bone Marrow Transplant 25 (6): 683-7, 2000.  [PUBMED Abstract]
   
   

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