Chemotherapy-Induced Oral Mucositis Clinical Presentation

Oral pain contributes to patient morbidity. Difficulty with eating, drinking, speaking, and maintenance of oral hygiene regimens typifies morbidity. A dry mouth from decreased salivary flow (hyposalivation) secondary to chemotherapy reduces natural lubrication and contributes to the accumulation of debris in the mouth, to the ease of trauma-induced ulceration, and to difficulty in eating and swallowing (dysphagia). A hairy tongue and superficial mucoceles may develop as a result (see the images below).

Dysgeusia, or altered taste sensation, may further reduce the patient's appetite contributing to poor oral intake, requiring parenteral nutrition. Additionally, oropharyngeal and esophageal involvement is common and may precede the onset of oral ulcers.

The earliest changes in chemotherapy-induced oral mucositis are those of leukoedema, although these changes cannot always be appreciated. These changes present as diffuse, poorly defined areas of pallor or milky-white opalescence most noticeable on the buccal mucosa. These areas disappear if the mucosa is stretched.

Oral mucositis begins 5-10 days following the initiation of chemotherapy and lasts 7-14 days. Therefore, the whole process lasts 2-3 weeks in more than 90% of patients. Resolution (in the case of HCT) coincides with recovery of the WBC count, specifically when the absolute neutrophil count becomes greater than 500 cells/µL. In patients being treated for solid tumors, the duration of oral mucositis depends on the type, dose, and course of treatment.

Oral mucositis begins as areas of erythema (see image below) and atrophy on the mucosa that may then break down to form ulcers that are covered by a yellowish-white fibrin clot (the pseudomembrane). Peripheral erythema is usually present. Ulcers may range from 0.5 cm to greater than 4 cm in maximum dimension. At the height of oral mucositis, patients experience marked pain, difficulty opening the mouth, difficulty with any form of oral intake, and difficulty with mouth care regimens.

The mouth is a trauma-intense environment. When the oral mucosa becomes atrophic from chemotherapy and renewal of oral epithelium has been slowed by chemotherapy, local trauma leads to ulceration, with nonkeratinized sites being the most vulnerable. Therefore, lesions occur bilaterally, mainly on the nonkeratinized sites in the mouth, namely the buccal mucosa, the ventral and lateral parts of the tongue, the labial mucosa, the floor of the mouth, the soft palate, and the oropharyngeal fauces (see images below).

Spontaneous healing (from the occurrence of erythema to resolution) without scar formation occurs within 2-3 weeks. Healing of ulcers usually takes 7-10 days. Because many patients (especially those undergoing HCT) are profoundly thrombocytopenic, bleeding may occur from sites of ulcerative oral mucositis.

In patients undergoing HCT, those who are conditioned with total body irradiation in preparation for allogenic transplantation are at a somewhat higher risk of experiencing more severe and prolonged oral mucositis. Patients treated with methotrexate as part of their graft versus host disease (GVHD) prophylaxis are also at increased risk; non–methotrexate-containing regimens have been associated with lower rates of mucositis.^[8]

With decreased salivary flow, debris that is normally washed away by saliva builds up in the oral cavity. One major manifestation of this is hairy tongue. Hairy tongue is not a candidal infection; retention of keratin on the filiform papillae of the tongue from hyposalivation, alteration of constituents of the saliva, and eating a soft diet or not eating at all causes hairy tongue. The retention of keratin on other sites, such as the gingiva and hard palate, may also be mistaken for oral candidiasis; however, hyposalivation changes the intraoral milieu and predisposes to candidiasis so that the conditions may coexist. Candidiasis is less likely when patients are on antifungal prophylaxis.

The underlying malignancy and the intensity and duration of the chemotherapy regimen are the 2 most important factors in determining the occurrence and the severity of oral mucositis. Hematologic malignancies and highly myelotoxic regimens lead to more severe oral mucositis, but many factors can modify the occurrence and the degree of oral mucositis.

Other factors that modify the occurrence and the severity of oral mucositis include age, level of pretreatment oral health, oral care during treatment, and salivary flow. Young age, poor oral health before and during treatment, and hyposalivation all contribute to an increased risk and increased severity of mucositis. The use of methotrexate for long-term GVHD prophylaxis may exacerbate lesions of oral mucositis, and use of non–methotrexate-containing regimens have been shown to reduce the overall severity of mucositis. Nevertheless, as mentioned earlier, other factors, including underlying genetic predisposition, likely also play an important role in determining risk.

• Generally, patients with hematologic malignancies have an increased rate of oral mucositis compared with those with solid tumors. This is to some extent related to the treatment regimens.
• Great variability exists in the stomatotoxicity of different treatment regimens. Some of the most stomatotoxic agents include the antimetabolites 5-fluorouracil, methotrexate, and cytarabine.
• Concomitant radiation therapy (especially to the head and neck region) increases the risk of oral mucositis because of synergistic effects with the chemotherapeutic agents.
• Younger age is associated with more severe oral mucositis.
• Chronic irritation from ill-fitting prostheses or faulty restorations predisposes patients to the development of oral mucositis due to local irritation and trauma.
• Hyposalivation prior to and during treatment is associated with an increased risk of oral mucositis.
• Oral mucositis occurs independently of oral mucosal infections of viral and fungal etiology, but it may be exacerbated by such concomitant infections.
• Better pretreatment oral health is probably associated with a reduced incidence of and less severe oral mucositis; however, this has never been proven.