1. ROLE OF AMLEXANOX AND REBAMIPIDE IN RECURRENT APHTHOUS STOMATITIS - CASE SERIES AND REVIEW OF LITERATURE
DR. SHAMIMUL HASAN (MDS)
ASSISTANT PROFESSOR
DEPARTMENT OF ORAL MEDICINE AND RADIOLOGY
FACULTY OF DENTISTRY JAMIA MILLIA ISLAMIA
NEW DELHI
INDIA

2. INTRODUCTION
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3. Oral ulcer is defined as a break in the continuity of epithelium of oral mucosa covered by granulation tissue.
The etiology for oral ulcers is multifactorial like trauma, infections caused by bacteria, virus and fungi, immunologically mediated diseases, allergy, nutritional deficiency, blood dyscrasias and malignancy.
The most common oral ulcer is traumatic ulcer followed by recurrent aphthous ulcer (RAS).

4. The word “Aphthous” comes from the greek word “Aphthae” which means ulcer.
Aphthous ulcers are among the most common oral lesions in the general population, with a frequency of 5-25% and three month recurrence rate as high as 50%.
RAS is characterized by multiple, recurrent, small, round, or ovoid ulcers with circumscribed margins, erythematous haloes, and yellow-grey floors that presents first in childhood and adolescence.

5. The term “recurrent aphthous stomatitis” should be reserved for recurrent ulcers confined to the mouth and seen in the absence of systemic disease.
The first use of the term “aphthae” in relation to mouth is credited to Hippocrates as far back as BC.
Von Mikulicz and Kummel (1888) are given the credit of the first valid clinical description of RAS.

6. ETIOPATHOGENESIS

7. The exact etiology of RAS is not clear, but genetic predisposition and immune mechanism may be involved in majority of cases.
PREDISPOSING ETIOLOGICAL FACTORS
-LOCAL FACTORS :
Oral trauma, smoking cessation.
-MICROBIAL FACTORS :
Bacterial: Streptocci- S. viridans, S. mitis, S. sanguis, S. oralis, H.pylori
Viral: Varicella Zoster, Cytomegalovirus, Ebstein Barr virus

8. SYSTEMIC CONDITIONS : (Aphthous like oral ulcers)
Behchet’s syndrome
Reiter’s syndrome
Sweet syndrome
Mouth and genital ulcers with inflamed cartilage (MAGIC SYNDROME)
Inflammatory bowel diseases: Crohn’s disease, ulcerative colitis
HIV infection
Periodic Fever, Apthosis, Pharyngitis and Adenitis (PFAPA syndrome) or Marshal’s syndrome
Cyclic neutropenia
Stress and psychologic imbalance
Hormonal changes- menstrual cycle disturbances
Drugs: NSAID’s, Nicorandril

9. NUTRITIONAL FACTORS:
Iron , folic acid, zinc deficiencies
Vitamin B1 , B2, B6 and Vit B12 deficiencies
GENETIC FACTORS:
Ethnicity
HLA antigens
ALLERGIC/ IMMUNOLOGICAL FACTORS :
Local T- lymphocyte cytotoxity
Abnormal CD4: CD8 ratio
Food sensitivity (to preservatives and agents such as benzoic acid cinnamaldehyde)
Hypersensitivity to toothpastes containing sodium lauryl sulphate.

10. CLINICAL FEATURES

11. Aphthous ulcer presents as one or more rounded ulcers with a clearly defined margins, a floor of yellowish-grey slough, and an edematous halo of inflamed mucosa.
For hours preceding the appearance of an ulcer, most patients have a pricking or burning sensation in the affected area.
They generally occur on non-keratinized surfaces such as the labial and the buccal mucosa, tongue and the floor of the mouth.
It is more common in patients between years of age, and predominantly affects women and individuals of higher socioeconomic levels.

12. MINOR APHTHAE (Cancer sores) MAJOR APHTHAE (Sutton’s Disease)
STANLEY’S CLASSIFICATION- BASED ON SIZE, DISTRIBUTION AND HEALING OF ULCERS
CHARACTERSTICS
MINOR APHTHAE (Cancer sores)
MAJOR APHTHAE (Sutton’s Disease)
HERPETIFORM
GENDER (M:F)
M=F
F> M
AGE OF ONSET (YRS)
5-19
10-19
20-29
NO. OF ULCERS
1-5
1-10
10-100
SIZE OF ULCERS (MM)
<10
>10
1-2(large if fused)
DURATION (DAYS)
4-14
>30
<30
RECURRENCE (MONTHS)
1-4
<1
SITE PREDILICTION
Lips, cheeks, tongue, floor of mouth
Lips, cheeks, tongue, palate, pharynx
Lips, cheeks, tongue, palate, pharynx, gingiva, floor of mouth
HEALING WITH SCAR
Unusual
Common

13. A.MINOR APHTHAE
B.MAJOR APHTHAE
C.HERPETIFORM APHTHAE

14. TREATMENT MODALITIES

15. Treatment of RAS is symptomatic and based mainly on empirical basis.
It is mainly directed at relieving pain and diminishing functional disability, inhibition of the acute inflammatory reaction as well as the frequency and the degree of severity of the recurrences.
Topical therapy is effective in most cases, although, systemic therapy is reserved for major RAS patients or those with large number of minor lesions.
Despite the many therapeutic options available, no treatment is specific and definitive.

16. In order to facilitate definition of the best treatment option, the patients can be classified according to their clinical characteristics as follows:
Type A: Brief episodes occurring only a few times during the year, and characterized by tolerable pain levels.
Type B: Episodes develop on a monthly basis, lasting 3-10 days, and the pain causes the patient to modify habits of hygiene and diet.
Type C: The episodes are very painful, with chronic aphthae.

17. REPORTED TREATMENT MODALITIES OF APHTHOUS STOMATITIS
Drug Classification
Drugs
MOUTH RINSES
Chlorhexidine gluconate, Benzydamine hydrochloride, Carbenoxolone disodium,
Betadine
TOPICAL STEROIDS
Hydrocortisone hemisuccinate ,Triamcinolone acetonide, Betamethasone valerate, Beclomethasone dipropionate, Sucralphate
ANTIBIOTICS
Tetracyclines, Minocycline
IMMUNOMODULATORS
Systemic steroids, Levamisole, Colchicine, Azathioprine, Dapsone ,
Thalidomide, Pentoxifylline , Cyclosporine , Amlexonox
OTHERS
Systemic zinc sulphate , Monoamineoxidase inhibitors, Sodium cromoglycate , Etretinate,
Low-energy laser

18. AMLEXANOX

19. Amlexanox (C16H14N2O4) is one of the most extensively studied topical agents available for treatment of RAU.
It is the only clinically proven product approved by the US FDA for the treatment of aphthous stomatitis.
It is an anti‑inflammatory, anti‑allergic drug, can inhibit the formation and release of histamine and leukotrienes from mast cells, neutrophils and mononuclear cells.
Various studies have demonstrated that 5% amlexanox paste accelerates ulcer healing and resolution of erythema, pain and lesion size of RAU.
It was noted that 5% amlexanox paste might be beneficial if commenced during the prodromal stage of ulceration.

20. It is the only agent that has a “triple action” –
Preventing Recurrences
Decreasing Healing Time
Accelerating Pain Resolution.
It has been available in India by the trade name of LEXENOX (Macleods Pharmaceuticals).
Amlexanox 5% paste applied to ulcers 3-4 times daily may considerably reduce their size and pain, and speed up healing.
Few patients complained of a transient “stinging” sensation that was mild in severity, metallic taste in the oral cavity soon after application of the paste and “cooling” sensation at the application site.

21. REBAPIMIDE

22. Rebamipide 2‑(4‑chlorobenzoylamine)‑3‑[2‑(1H)‑quinolinon‑4‑yl] is a new mucoprotective agent which enhances preservation of existing epithelial cells and replacement of lost tissue through stimulation of PGs release and inhibition of free radicals.
Rebamipide is often used to treat Behcet's disease, an inflammatory disease involving chronic recurrent oral aphthous ulcers (aphthae), uveitis, skin lesions and genital ulcers. But, it might also be useful in preventing and treating frequently recurrent oral aphthous ulcers.
Dosage- 100 mg rebagen tab TDS x 7-14 days.
Common side-effects- Gastrointestinal like constipation, bloating, diarrhea, nausea and vomiting.
Hypersensitivity and rash was seen in less than 1% of patients.

23. CASE SERIES

24. Case 1: 28 years, Male, 1 ulcer
Pre Treatment
Post Treatment

25. Case 2: 24 years, Female, 2 ulcers
Pre Treatment
Post Treatment

26. Case 3: 34 years, Male, 3 ulcers
Pre Treatment
Post Treatment

27. Case 4: 34 years, Male, 4 ulcers
Pre Treatment
Post Treatment

28. Age and Sex Distribution of Patients
No. of patients
No. of patients
Sex distribution
Age group

29. Number of ulcers and the Site predilection
No. of patients
No. of patients
Site predilection
Number of ulcers

30. CONCLUSION

31. Extensive researches have encertained that RAS has a multifactorial etiology.
Due to multivaried etiopathogenesis, there is no defined and accurate treatment modality for the condition.
The present study has enhanced the knowledge about the efficacy of 5% amlexanox oral paste and rebapimide tablets as the emerging treatment modalities for aphthous ulcers.

32. THANK YOU