eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa

Chemotherapy-Induced Oral Mucositis: Differential Diagnoses & Workup

Author: Nathaniel S Treister, DMD, DMSc, Assistant Professor, Harvard School of Dental Medicine; Consulting Staff, Division of Oral and Maxillofacial Surgery, Oral Medicine And Dentistry, Brigham and Women's Hospital and Dana Farber Cancer Institute
Coauthor(s): Sook-Bin Woo, DMD, MS, BDS, MMSc, Associate Professor, Chief, Division of Oral Medicine, Department of Oral Medicine and Diagnostic Services, Harvard School of Dental Medicine; Consulting Staff, Brigham and Women's Hospital, Dana Farber Cancer Institute, Beth Israel/Deaconess Medical Center
Contributor Information and Disclosures

Updated: Oct 31, 2008

Differential Diagnoses

Candidiasis, Cutaneous
Graft Versus Host Disease
Herpes Simplex
Herpes Zoster

Other Problems to Be Considered

Chemotherapy and bone marrow transplantation–induced mucositis

Overall, candidiasis is the most frequent oral infection in patients who are myelosuppressed (see Media File 7), whereas recurrent herpes simplex virus 1 (HSV-1) is the most frequent oral viral infection in these patients (see Media Files 8-9). Consider other viral infections, including human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7), and cytomegalovirus (CMV).

Acute GVHD occurs within the first 100 days after transplantation and involves the skin; the liver; and the mucosa of the eye, the mouth, and the GI tract. Acute GVHD lesions in the oral cavity occur 3-4 weeks after HCT, following engraftment and restoration of the white cell count.  Acute GVHD typically presents well after the resolution of oral mucositis (OM) lesions, although in some cases, they may manifest as a continuation or exacerbation of oral mucositis. An important difference is that lesions of acute GVHD may affect the keratinized mucosa, which is not a feature of oral mucositis (see Media File 10). Risk factors include HLA disparity, sex mismatching, multiple donor pregnancies, and advanced age. Management includes controlling systemic acute GVHD with systemic immunosuppressive therapy, controlling pain, and providing local palliative measures.

Workup

Laboratory Studies

• Diagnosis is primarily based on the clinical findings and the chronology of the development of lesions.
• WBC count with differential (absolute neutrophil count in particular) is a helpful test. Oral mucositis usually occurs when the absolute neutrophil count is less than 500 cells/µL.
• Cultures (particularly for herpetic infection) should be performed if erythema and ulcers (or vesicles) are located on the keratinized tissues of the hard palate, the attached gingiva, or the dorsum of the tongue or if lesions persist after the period of profound neutropenia has passed. If the patient is on prophylactic antiviral agents, the possibility of breakthrough infection or the development of resistant strains must be considered.
• Biopsy is indicated, especially if a deep fungal infection is suspected. Infection may present as a rapidly growing discrete ulcer on either the keratinized mucosa or the nonkeratinized mucosa (see Procedures). Biopsy should be considered when oral ulcerations are exacerbated with engraftment and restoration of the white cell count, especially when skin changes are absent, as this is suggestive of emerging acute GVHD.  However, biopsy is not routinely necessary for oral mucositis.

Other Tests

• The severity of oral mucositis can be evaluated using several different instruments. The 2 most commonly used are the World Health Organization (WHO) Oral Toxicity score and the National Cancer Institute (NCI) Common Toxicity Criteria for oral mucositis. While the NCI system has separate scores for objective (erythema and ulceration) and functional (pain and ability to eat solids, liquids, or nothing by mouth) components, the WHO score combines both elements into a single score that is useful for measuring severity over time. The Oral Mucositis Daily Questionnaire (OMDQ), which evaluates mouth and throat soreness and its impact on daily activities, has been recently validated and shown to correlate with oral mucositis severity based on the WHO score.³ Of note, symptoms have been found to precede objective findings by 1-3 days.

Procedures

• A biopsy may be necessary, particularly to rule out a deep fungal infection or CMV infection (although CMV infection usually occurs as a later event).
  • The patient should have a minimum of 50,000-80,000 platelets/µL. Antibiotic coverage may be necessary if the patient has less than 1000 neutrophils/µL. The antibiotics should be administered 30 minutes to 1 hour prior to the biopsy to reduce bacteremia and the possibility of a central venous line infection, if such a line is present, and should continue for 5-7 days after the biopsy. Infectious disease physicians should be consulted for their recommendation for the most appropriate antibiotic if the patient is already on a variety of antimicrobial agents.
  • The biopsy is performed under local anesthesia. If indicated, a portion of the tissue should be submitted fresh for fungal culture (for speciation) and viral culture. The wound should be primarily closed with sutures.

Histologic Findings

Routine biopsies are not performed on oral mucositis lesions unless other pathology is suspected, such as a deep fungal infection. In banal oral mucositis, the oral mucosa exhibits ulceration that unlike other ulcerative conditions shows a paucity of neutrophils in the fibrin clot. Granulation tissue is present at the base of the ulcer with chronic inflammatory cells. Stains for fungi and viruses may be necessary to identify organisms.

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