Definition

Oral mucositis is an inflammatory-like reaction of the oral mucosa as a result of the cytotoxic effect of antineoplastic chemotherapy and head and neck radiotherapy.
It is one of the most debilitating side effects of antineoplastic therapy.

Incidence

It varies with the type of cancer therapy.
About 40% of patients receiving chemotherapy, 80% of patients receiving HSCT and almost all patients who undergo head and neck cancer radiotherapy will develop oral complications, including mucositis.
About 10% to 15% of patients who receive chemotherapy and about 35% to 43% or more of patients receiving head and neck RT will develop severe mucositis.

Clinical picture - Differential diagnosis

Oral mucositis is classified in 5 grades ( grade 0 to grade 4), according to its severity for communicating purposes among oncologists and for the administration of the appropriate treatment.

The severity of mucositis varies between redness to painful ulcerations, that may extent to all mucosa and are covered by fibrinous pseudomembranes, teeming with bacteria. Oral microbial load plays an important role in the development and severity of mucositis.

Severe mucositis grade 3 and 4, which is also reffered in the literature as pseudomembranous mucositis or ulcerative mucositis, should be differentiated from the pseudomembranous form of candidiasis and the ulcerations of herpes simplex virus-1 infection.
In the case of allogeneic HSCT, mucositis should also be differentiated from the lesions of GvHD.

Oral mucosal infections, mostly oral pseudomembranous candidiasis and herpes simplex virus -1 infection may complicate chemotherapy and radiation-induced mucositis, or may cause early initiation or may prevent healing.

The concomitant administration of chemotherapy, during head and neck radiotherapy may increase the severity of mucositis.

The administration of Cetuximab during head and neck radiotherapy has not been found to increase the severity of mucositis, of grade 3 or higher.

Treament of mucositis:

Oral mucositis is a panmucosal reaction.
The 5 phases of mucositis that have been described by Stephen Sonis offer a good model for the study of several therapeutic interventions.

In general:

• We can administer oral mucosal protectants
• The alcohol containing mouthwashes should be avoided
• A mouthwash made of water or chamomile, soda and salt is most appropriate Salt or soda may be removed, according to the condition of the mucosa
• Prophylactic antifungal or antiherpetic treatment may be administered
• Depending on the case, infection is treated upon its development
• The preservation of optimum oral care is important

The keratinocyte growth factor palifermin ( a cell resistant modifier) may reduce the incidence of severe, grade 3 and 4, mucositis.

Other medications such as Saforis, are in the final phase of
study for the treatment of mucositis

Selected references

1. Barash A et al. Antimicrobials, mucosal coating agents, anesthetics, analgesics, and nutritional supplements for alimentary tract mucositis. Support Care Cancer 2006;14:528-532.
2. Bensandoun R-J et al. Amifostine in the management of radiation-induced and chemo-induced mucositis. Support Care Cancer 2006;14:566-572.
3. Bonner JA et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-578.
4. Elad S et al. The dental management of patients prior to hematology cytotoxic therapy or hematopoietic stem cell transplantation. A dicision analysis. Support Care Cancer 2006;14:648, abstract.
5. McGuire DB et al. The role of basic oral care and good clinical practice principles in the management of oral mucositis. Support Care Cancer 2006;14:541-547.
6. McGuire DB et al. Promulgation of guidelines fro mucositis management: educating health care professionals and patients. Support Care Cancer 2006;14:548-557.
7. Migliorati CA et al. The role of alternative and natural agents, cryotherapy, and/or laser for management of alimentary mucositis. Support Care Cancer 2006;14:533-540.
8. Nicolatou-Galitis O et al. The oral manifestations of chronic graft-versus-host disease (cGVHD) in paediatric allogeneic bone marrow transplant recipents. J Oral Pathol Med 2001;30:148-153.
9. Nicolatou-Galitis O et al. Oral pseudomembranous candidiasis, herpes simplex virus-1 infection, and oral mucositis in head and neck cancer patients receiving radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash. J Oral Pathol Med 2001;30:471-480.
10. Nicolatou-Galitis O & FKL Spijkervet. Mucositis. 2004. www.eastman.ucl.ac.uk/-eaom.
11. Nicolatou-Galitis O et al. Effect of fluconazole antifungal prophylaxis on oral mucositis in head and neck cancer patients receiving radiotherapy. Support Care Cancer 2006;14:44-51.
12. Nicolatou-Galitis O et al. Herpes simplex virus-1 (HSV-1) infection in radiation-induced oral mucositis. Support Care Cancer 2006;14:753-762.
13. Sonis S et al. A biological approach to mucositis. J Support Oncol 2004;2:21-36.
14. Peterson DE et al. Alimentary tract mucositis in cancer patients: impact of terminology and assessment on research and clinical practice. Support Care Cancer 2006;14:499-504.
15. Stiff PJ et al. Palifermin reduces patient-reported mouth and throat soreness and improves patient functioning in the hematopoietic stem-cell transplantation setting. J Clin Oncol 2006; eprint, 10.1200/JCO.2005.02.8340.
16. Trotti A et al. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy : a systematic literature review. Radiother Oncol 2003;66:253-262.