Vesna Branković,
Svetlana Orlov,
Branislava Mirković,
Draginja Kojović,
Ljiljana Kesić,
Sonja Martinović,
Ana Pejčić,
Ivana Grigorov

Dental clinic, department of oral medicine and periodontology, Niš

Introduction 

Oral mucositis appears although preventive measures were applied, in patients with che-motherapy, with or without additional components of radiation. Besides pain, which unables adequate nutrition, those oral changes lead to dehydratation and malnutrition the risk of infection is increased, as well as the risk of hepato-vein occlusions.
During the last two decades, there were numerous attempts to determine medicaments which would do prevention, (described in the first article) or at least, alleviate the difficulty of mucositis, but with changeable results. Patho-physiology of mucositis is the complex of pro-cesses, which perform in four phases:
The first phase is inflammable or vasculous, in which tumor necrosis factor is released, Interleukin from 1-6 and C reactive protein.
The second phase is epithelial in which the proper division ceases, which leads to epithelium atrophy.
The third phase is ulcerous or infective one, where ulcuses appear as a consequence of cyto-kine activity and local trauma, which represent an ideal spot for microorganisms entrance, which appear in a great number in the mouth.
The fourth phase is the phase of recovery, in which anew proper cells division begins.
In the therapy of oral mucositis, when they appear, the following procedure is recomme-nded; the maintenance of ideal oral hygiena, the drugs which are protectors of oral mucosa, anesthetics and analgetics, medicaments which act on healing up oral changings i.e. they accelerate healing and also act on adequate diet during disease.^1,2       

 Oral  hygiena 

Oral hygiena is an important factor in the therapy of oral mucosa.Tooth brushing is ceased, until granulocytes and thrombocytes are under 0,5 x 109 / lit and 20 x 109/ lit, and then patients or dental hygienists  do washing up teeth by cottonwool soaked into 0,5% of hydrogen solution 4 times a day. For toilet and pseudomembranae taking down there are special small spongues (toothettes) by which teeth and soft tissue in oral mucosa are wiped. Saline solutions complete the care of oral health, as well as various expediences for mouth washing can be used, which contain pleasant supplements (mentha), because it clears unpleasant odor away. Besides adequate brush usage and aid expediences for teeth hygienic maintenance, there are various additional expediences for washing which are used.³ 

NATRIUM BICARBONATE is used for oral cavity washing, several times a day. One teaspoon of natriumbicarbonate is dissolved in a glass of moderate warm water, with which a patient washes his mouth. Because of its alkali characteristics, it prevents the progress of fungi of Candida gender, which multiply well in acid conditions, but also has a good mucous activity.³ 

HYDROGEN PEROXIDE (H₂O₂) is mostly recommended as a good disinfectant and deodorant for oral hygiene. Oral cavity should be washed several times a day with 0,5% of H₂O₂  solution. If stronger solutions, they can act irritable. Very long use is not recommended, because hydrogen is an acid solution and it can disorder the growth of new granulated tissue in the period of healing of erodent and ulcerous surfaces. Besides that, normal flora of oral cavity can be disturbed.³ 

CHLOHEXIDIN or 1,6 (chlorphe-nolguanid)  hexan, is used in the shape of gluconat, because in that shape it is perfectly dissolved. It efficiently functions on numerous Gram positive, but also on some Gram negative microorganisms. The application is based on bacterial activity, but also on resumption of activity at presence of organ materials, necrotic parts of epithelium and fibrin exudation. It has the characteristic to eliminate the activity of dental plaque, which is the bearer of infective materials in oral cavity. In mucositis treatment, it is ordinated in the form of  0,1 to 0,2 percent water solution. It is often used in combination with fungical expediences, especially Nistatin.³ 

Protectors of oral mucositis 

SUCRALPHATE (salt of aluminium hydroxid with sucrose-8-sulphat) was firstly introduced as a mucoprotector in therapy of ulcus disease, but as well as in mucositis therapy grade II and III. It is given in the shape of solu-tion for oral cavity washing, because it possesses numerous biological effects, such as prostagla-ndin production and mucosa production, incre-asing of blood circulation through mucous mem-branae and connection epithelial growth factor and basic fibroblast growth factor in tissues.^3,4,5 

COALIN-PECTIN in combination with Diphenhydramin syrup has local radio-prote-ctive effect. It is given as an expedient for oral cavity washing, because it reduces pain, impro-ves food possibility and avoids losing body weight.³ 

MAGNESIUM-PEROXID (MgO2) magnesium peroxidatum in the form of suspension as an alkalic expedient, is often used for oral cavity washing during mucositis, because it reduces acidity and alleviated the pain during nutrition. It makes solid mucous prote-ction over erodent and ulcerative surface. Other magnesium preparations have similar chara-cteristics. ³ 

HYDROXIPROPIL-CELULOSE  ( HPC ) is usually combined with some anesthetics because it reduces pain at serious mucositis grade III and IV and makes nutrition possible. It can be ordinated like gel for smearing mucous membranae or in a form of solution for washing.³ 

CYTOKINES belong to a group of cytopro-tectors and are given in mucositis therapy.³ 

IMMUNOGLOBULINES alleviate di-fficulty and duration of mucositis. They are gi-ven intramuscular, usually once a week. There are some authors, who disprove these thera-peutic effects.³ 

AMIFOSTINE (WR-R721) is ordinated in combination with manytol, in the form of infussion, 30 minutes before chemotherapy starts, as a good cytoprotector. It protects tissues from toxic effects of radio and polychemio therapy, because it reduces the duration of mucositis and opiates ordination.³

 Anesthetics and analgetics 

Anesthetics are symptomatic expedients and are used as the additional therapy with some other medicament, especially in some serious mucositis. Lidokain and morfin are ordinated locally, in the form of gel or aerosol, to reduce pain and alleviate nutrition and also reduce body losing weight. In our experience, there are numerous made preparations, as local anesthe-tics, but they can also be magisterially made in the form of various viscose gels with Lidokain, then Anestezin in combination with olive-oil for smearing erodont surfaces, as well as mixture of Anestezin with the same parts of glycerols. 

CAPSAICINA is ordinated in the form of candies which are suckled. Its function is to hyperstimulate receptors to pain until losing their function.³  

DOXEPRIN is triciklin antidepressive, which functions on the level of CNS and reduces pain and depression.³ 

Medicaments which act on healing 

HELIUM-NEON LASER has a good analgetic effect, because they accelerate wounds healing, reduces inflammation and edema, but also influence on alleviation of oral dryness. Low energy Helium-Neon- Laser were performed daily from d-5 to d-1 on five ana-tomic sites of oral mucosa.^3,6 

VITAMIN E is ordinated like a good direct cytoprotector and antioxident. At chemist,s there are numerous variations of this vitamin in the form (alfa tokoferol nikotinat and tokoferol acetat) and in combination with vitamin C, in the form of tablets and capsules for oral use.³  

TRETIOCIN is derivation of vitamin A, which accelerates wounds healing and has antiinflammable effect. It is also ordinated in therapy of acute promyelocyte leukemia in the period of 30 to 90 days.³ 

DIET 

The diet in such kind of patients, must be of high calorie values, and if patients can ,t take food in normal way, infusion should be applied. In the case of mucositis grade I and II, salty food should be avoided, then sour and peppery food, fizzy drinks alcohol, hot drinks, as well as the food which can damage mucous, such as biscuits, toast, tough meat.³ 

Conclusion

The prevention and therapy of mucositis is a very difficult challenge for oncologists and stomatologists. It is the most important before cytostatic  therapy and especially before radio therapy in head and neck area, to do sanation of oral cavity, which means, the extradition of caries-destuctive teeth, the caries and parodontopathy sanation. Patients shoul be motivated about good oral hygiena as well as their hospital and outhospital surrounding.

Small trials with various medicaments, show good results with antiholinergicin, prosta-glandin and local antibiotics, but hardly can drugs be found which can cease the appearance of serious mucositis in patients with tran-splanted bone marrow.

The solution of fungicid fluconazol is good in mucositis therapy, especially in those patients who are not able to swallow capsules or in small children.

Fungicides which are resorbed from dige-stive tract or those with partly absorption are very useful in prevention and treatment of oral Candida because it is most frequently isolated from changes.

Aminofostine, pilocarpin, local application of tretinoin, oral glutamin, interleukin 11 and  preparates which stimulate hematopoesa, are those which promise a lot, in prevention and therapy of  mucositis, as complications which become more expensive in patients treatment, because it prolong treatment duration, as well as the time spent at hospital conditions.  

REFERENCE LIST 

1.    DORR W, DOLLING-JOCHEM J, BAUMANN M, HERMANN T.The therapeutic management of radiogenic oral mucositis. Strahlenther Onkol 1997 April 173 (4):183-192.2.       MEAD GM . Manegement of oral mucositis  associated with cancer chemotherapy. Lancet 2002, 359: 815-816

3.   DEMAROSI F, BEZ C, CARRASSI A. prevenzione e trattamento della mucosite orale do chemio e radioterapia. Minerva Stomatol 2002;51:173-186.

4.   CAMPISI G, SPADARI F, SALVATO A: Sucralfate in odontostomatology. Clinical experience. Minerva Stomatol 1997, Jun 46(6):297-305.

5.   BARKER G, LOFTUS L, CUDDY P, BARKER B. The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy- induced mucositis. Oral Surg, Oral Med, Oral Pathol 1991;71:288-293.

6.   COWEN D, TARDIEN C, SCHUBERT M, PETERSON D, RESBENT M, FAUCHER C, FRANGUIN JC. Low energy  Helium-Neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant; results of a double blind randomized trial. Int J Radiat Oncol. Biol Phys 1997 Jul 1;38  (4):697- 703.

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