Mucositis oral

Author: Prof. Dr. med. Peter Altmeyer

Last updated on: 29.10.2020

Synonym(s)

mucositis enoralis; oral mucositis

Definition
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Frequent, early (usually in the course of the 1st week of treatment), reactive, painful, inflammatory, complex side effect of the oral mucosa on mucotoxic oncological therapy procedures of the head and neck region (see also ANUG = acute necrotizing ulcerative gingivitis) with phased course (enanthema - focal pseudomembranous mucosal lesions - localized or even confluent ulcers). Frequently also occurring as a side effect of radio(chemo)-therapy (see also cytostatics, supportive therapy). Oral mucositis represents a dose-limiting factor for cytostatic therapy and, due to the disruption of the mucosal barrier, represents an increased risk of systemic infection.

Classification
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The severity of mucositis is classified as follows:

Grade 0: normal oral mucosa without changes.
Grade 1: redness, soreness and burning; occasional and minor pain; difficulty with solid food.
Grade 2: Redness, minor inflammation; temporary and bearable pain; difficulties with soft food.
Grade 3: Major inflammation; severe and persistent pain.
Grade 3 and above is called severe mucositis. Even drinking causes increasing problems. Pain also occurs when speaking.
Grade 4: most severe form of the disease; deep ulcers, excruciating pain; artificial nutrition.

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Occurrence/Epidemiology
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A variety of cytostatic substances can cause stomatitis, esophagitis and oral ulcerations. The frequency and severity of mucositis depend on the substance, dose, type of application and the combination chosen with other cytostatic drugs or with radiotherapy. Mucositis is particularly observed when methotrexate, antracyclines, 5-fluorouracil, capecitabine and etoposide are used. Other particularly mucotoxic chemotherapeutic agents are:

Actinomycin
Bleomycin
Chlorambucil
Cisplatin
Cytarabine
Daunorubicin
docetaxel
Doxorubicin
Fluorouracil
Mitoxantrone
Vinblastine
Vindesin

Etiopathogenesis
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The pathogenesis of mucositis/stomatitis is a complex process. Stomatotoxic chemotherapeutics and radiotherapy generate oxygen radicals with resulting DNA damage to the epithelium. This leads to early changes in both the endothelium of submucous blood vessels and the connective tissue, although mucositis is interpreted as an epithelial process.

Clinical features
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Acute reactions manifest themselves in different forms (depending on the agent, type and extent of radiation therapy): A characteristic feature is the occurrence of a burning sensation of the oral mucosa which occurs 3-10 days after administration of the cytostatic drugs. At this time, objective signs such as redness or ulceration are not yet visible. 3-5 days after the appearance of the first symptoms, erythema and extensive erosions (mucositis enoralis) appear which can develop into extensive ulcers. In severe cases a hemorrhagic stomatitis develops. The oral mucositis can develop as:

manifest as smooth-surface mucositis (inflammation of the cheeks, palate, tongue, floor of the mouth, oropharynx) or as
Gingivitis, the maximum variant of which is ANUG (acute, necrotizing, ulcerative gingivitis)
Furthermore, xerostomia with taste disorders is regularly observed.

The disturbance of the barrier function of the oral mucosa leads to the danger of local and systemic infection up to sepsis. Late reactions can occur after months or years in the form of mucosal atrophies, ulcers, radiation caries, permanent xerostomia and taste disorders, trismus (jaw clamp). The damage is usually reversible and heals 1-2 weeks after the end of therapy.

Complication(s)
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Secondary infections caused by various bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Streptococcus viridans) and fungi (Candida albicans), which can lead to localised but also septic infections Further complicative infections, especially in immunosuppressed patients, are herpes simplex virus type I and varicella zoster virus infections. The majority of HSV infections are caused by reactivation of the latent virus.

Therapy
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Chlorhexidine: Chlorhexidine digluconate (0.12% to 0.2%) is effective against gram-positive bacteria. Side effects include altered taste sensation, tooth discoloration and colonization of the oral cavity by gram negative bacteria [Foote RL 1994].
For the other topical disinfectants (hydrogen peroxide 3%, polyvidone iodide, cetylpyridinium chloride, silver nitrate) there are no data available which support a general recommendation.
PTA lozenges: contain polymyxin E, tobramycin and amphotericin B to suppress oral and pharyngeal infections.
Benzydamine HCl: The use of 0.15% flushing solution before and after radiotherapy showed superiority in a placebo-controlled study
Traumeel S: A smaller randomized study in children who received a stem cell transplantation showed a reduced rate of chemotherapy-induced stomatitis.
Oral cryotherapy: Randomized studies have shown that 30-minute oral cryotherapy with bolus 5-Flourouracil or melphalan-containing chemotherapy has a beneficial effect on the frequency of oral mucositis. Application mainly for substances with a short half-life and bolus application.
Sucralfat: Sucralfat is used in patients with radiotherapy. The preparation is dissolved in water as granules and forms a protective film on the mucosa.
Anti-inflammatory: plant extracts (chamomile or ointment solutions): chamomile had no proven influence on 5-fluorouracil induced stomatitis despite known anti-inflammatory, antibacterial and spasmolytic properties. The positive effect of sage tea and myrrh tinctures is also not proven.

Prophylaxis
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Radiation therapy: Expose as small a mucosal surface as possible to radiation therapy with the lowest possible doses.
Optimal oral hygiene, frequent rinsing with tap water or antiphlogistic preparations (see below)
Abstention from alcohol or cigarette consumption
Dietary measures (low salt, low spice)
Symptomatic pain treatment
In case of infection signs, targeted antibiogram - controlled antibiotic or antifungal system - or local therapy
Prosthesis leave

Note(s)
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The oral cavity must be considered as a whole organ for oncological therapy, with a complex interaction of different structures such as: mucous membrane, gustatory papillae, teeth, periodontium, soft tissue, muscles, jaw joints, salivary glands.

Literature
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Awidi A et al (2001) Double-blind, placebo-controlled cross-over study of oral pilocarpine for the prevention of chemotherapy-induced oral mucositis in adult patients with cancer. Eur J Cancer 37:2010-2014
Bleyer WA (1978) The clinical pharmacology of methotrexate: new applications of an old drug. Cancer 41:36-51
Dodd MJ et al (2000) Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to treat chemotherapy-induced mucositis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:39-47
Meropol NJ et al (2003) Randomized phase I trial of recombinant human keratinocyte growth factor plus chemotherapy: potential role as mucosal protector. J Clin Oncol 21:1452-1458.