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Graft versus host disease

Nov. 1, 2010
Mrs. Jones has been referred to your office by her surgeon and general physician. Mrs. Jones had a bone marrow transplant 15 months ago due to leukemia and has been diagnosed with chronic graft versus host disease (GVHD).
by Nancy W. Burkhart, RDH, EdD[email protected]Mrs. Jones has been referred to your office by her surgeon and general physician. Mrs. Jones had a bone marrow transplant 15 months ago due to leukemia and has been diagnosed with chronic graft versus host disease (GVHD).

Bone marrow transplants were performed because the patient developed a malignancy in the blood-forming system. Chemotherapy and whole body radiation was performed with replacement cells then returned to the patient.

GVHD has developed in Mrs. Jones, and she has very evident oral lesions, as well as extensive lesions on her lips. The skin is affected with pigmentation in various areas on her extremities.

The general physician has noted in his comments that eating has been difficult for the patient, and her oral lesions need improvement. The patient reports dryness, difficulty in opening her mouth (the similar scarring that is found in scleroderma is related to restricted oral tissue opening), and the pain is very intense at times. Because of these factors, Mrs. Jones has been consuming liquids with some soft foods (see Figure1).

Figure 1: This slide depicts the GVHD patient's ulcerative lesions. Lesions are noted on the lips and tongue. Candida is evident on the central dorsal surface of the tongue (Courtesy of Dr. T.D. Rees).

The patient was prescribed clobetasol 0.05%, chlorhexidine in water, nystatin oral suspension, and Biotene toothpaste. After a period of six weeks, much improvement was noted, and the patient exhibited only some candidiasis with mild hyperkeratotic lichenoid lesions (see Figures 2, 3, 4).

The term desquamative gingivitis is often used to describe chronic gingival lesions that may have multiple etiologies. This term is used as a descriptor of the tissue, usually noting persistent ulcerative tissue. Classifying the etiology of a specific mucocutaneous condition often involves extensive, encompassing biopsies, thorough health histories, and consultations. Mucocutaneous diseases exhibit similar oral lesions, including lichen planus, pemphigus vulgaris, pemphigoid, lupus erythematosus, linear IgA disease, erythema multiforme, and chronic ulcerative stomatitis, as well as GVHD (Toscano et al. 2010).

Clinically, many of the above mentioned disease states do appear similar. Therefore, a correct diagnosis is important for the future treatment of the patient. Additionally, sometimes a patient may have combinations of these mucocutaneous diseases at the same time or intermittently. For example, a patient who is prescribed certain medications may have what is considered a "lichenoid reaction" and have lichen type lesions.

GVHD occurs after hematopoietic stem cell transplantation. Oral lesions relating to this disease appear frequently as being clinically similar to the disease states mentioned above. Engrafted cells recognize the host cells as foreign, and a rejection process begins to occur. GVHD is a hypersensitivity reaction and results from an immune response to major histocompatibility complexes (MHC) that are present on the surface of the cells.

The exact mechanisms are not clearly understood and may vary with each individual. No matter how closely the MHCs are matched, they will not be identical (except in identical twins), which is termed syngeneic donor cells (Delong, Burkhart 2008). In most cases, the cells are autologous, meaning the donor and the recipient are the same person.

GVHD may be acute or chronic in nature. The acute form occurs within the first 100 days after the transplant, or infusion of T cells. The acute form usually affects the skin, liver, and gastrointestinal tract.

Figures 2, 3, 4: Top slide depicts ulcerative areas on the lateral border of the patient's tongue. Center slide depicts dorsal tongue after treatment. The bottom slide notes improvement of the lip region after treatment. (Courtesy of Dr. T.D. Rees)

The chronic form can occur after the first 100 days and may be intermittent for several years. A version of GVHD occurs within 80 days after transplantation (cGVHD). In recent years, there is a shift to base the acute or chronic forms on more clinical observations rather than on specific time points (Imangulo et al. 2007). Both the severity and incidence of GVHD vary depending on the mismatch of major histocompatibility antigens of the host and donor. The buccal and labial mucosa along with the tongue are most often affected.

  • Treatment protocols: Multiple medications are needed to sustain the individual, such as immunosuppressant medications, and there may be multiple organ systems involved. Because of the medications involved in patient care, there may be as much as a two- to eightfold greater chance of developing secondary hematologic malignancies than the general population (Toscano et al. 2010).

Dental caries, periodontal disease, and oral infections may be more pronounced in patients with GVHD. Xerostomia in hematopoietic stem cell transplantation is a common problem for the patient, as well as inflammation with scarring of the masticatory muscles that may restrict the oral opening (Brand et al. 2009).

Additionally, candida may be an ongoing problem for a patient who has a mucocutaneous disorder since these patients frequently use both systemic steroids and oral corticosteroids. Oral corticosteroids suppress the immune system and the xerostomia assists in promoting the candida growth. Antifungal medications such as nystatin rinses are needed for the treatment of candidiasis. Toothbrushes may be infected with candida and need to be replaced frequently. Recent studies also support the use of devices such as the Violight in sanitizing the brush and keeping counts of bacteria and colony forming units at low levels (Boylan et al. 2008).

Biotene products, chlorhexidine in water, and various corticosteroids such as clobetasol 0.05% are used in supportive care of these patients. Because of the tendency to develop candidiasis, there is a need for balance in treating the candidiasis, as well as trying to keep the oral lesions under control.

Although there is no prevention for GVHD, there are some tips that can help to diminish many of the problems associated with GVHD. There is no way to predict the severity in the individual's development of GVHD since each case will vary considerably. The careful evaluation by the physician and oral health-care provider will determine the course of action in each case. Below are suggested considerations for the patient with GVHD.

Recommended Links from the Academy of Oral Medicine

References

  • Boylan R, Yihong L, Simeonova L, Sherwin G, Kreismann J, Craig RG, Ship JA, McCutcheon JA. Reduction in bacterial contamination of toothbrushes using the Violight ultraviolet light activated toothbrush sanitizer. Am J Dent 2008:21:313-317.
  • Brand HS, Bots CP, Raber-Durlacher JE. Xerostomia and chronic oral complications among patients treated with haematopoietic stem cell transplantation. Br Dent J 2009 Nov;207(9): E17;discussion 428-9.
  • DeLong L, Burkhart NW. General and Oral Pathology for the Dental Hygienist. Lippincott Williams & Wilkins, Baltimore, 2008.
  • Imanguli MM, Pavletic SZ, Guadagnini JP, Brahim JS, Atkinson JC. Chronic graft versus host disease of oral mucosa:Review of available therapies. Oral Med Oral Pathol Oral Radiol Endod 2006;101:177-85.
  • Toscano NJ, Holtzclaw DJ, Shumaker ND, Stokes SM, Meehan SC, Rees TD. Surgical considerations and management of patients with mucocutaneous disorders. Compend Contin Educ Denat 31:5 June 2010, 344-59.

Nancy W. Burkhart, BSDH, EdD, is an adjunct associate professor in the department of periodontics, Baylor College of Dentistry and the Texas A & M Health Science Center, Dallas. Dr. Burkhart is founder and co-host of the International Oral Lichen Planus Support Group http://www.bcd.tamhsc.edu/outreach/lichen/ and coauthor of General and Oral Pathology for the Dental Hygienist. Her Web site for seminars is www.nancywburkhart.com.

Graft versus host disease suggestions

  • Carefully follow the directions, dosage, and use of any medications that are prescribed by the health-care provider.
  • Adhere to specific diet guidelines that have been recommended, such as avoiding spicy, rough or acidic foods. Alcohol and caffeine may cause dehydration of the skin and oral tissues.
  • Monitor any skin lesions and frequently clean the skin in general.
  • Avoid hot showers that may irritate the skin. Use of a shower filter that removes unhealthy contaminants may help the skin surface.
  • Instruct the patient to avoid scratching skin surfaces.
  • Avoid sun exposure, and wear a sunscreen daily.
  • Maintain a healthy environment in the home and workplace.
  • Stay away from potential health risks such as sick people.
  • Be alert to any signs or changes within your body.
  • Oral changes can often be managed with medications and good oral hygiene.
  • Change toothbrushes frequently and try the Violight to sanitize toothbrushes after each use. Studies show a dramatic decrease in bacterial counts with the use of the device (Boylan et al. 2008).
  • Xerostomia is a major problem for patients with GVHD. Xerostomia can be decreased with products sold over the counter or those recommended by the oral health provider. Frequent consumption of water, oral moisture products, and medications such as Salagen may be prescribed.
  • Practice relaxation techniques daily. Breathing exercises, yoga, tai chi, meditation or prayer are all beneficial.
  • GVHD is not contagious, and the patient cannot transfer the condition to a family member. However, chronic candida in couples should be evaluated and both people may need to be treated.
  • Maintain good oral hygiene and request frequent dental examinations with oral cancer screenings at each appointment.

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