Recurrent aphthous ulcers (RAS).pptx

The term “aphthous” is derived from a Greek word “aphtha” which means ulceration. Recurrent aphthous stomatitis (RAS) is one of the most common painful oral mucosal conditions seen among patients.

1. Recurrent Aphthous Stomatitis Presented by Dr. Rahul Srivastava Professor Rama Dental College Hospital & Research Centre Kanpur

2. Recurrent Aphthous Stomatitis (RAS) Recurrent aphthous stomatitis is a disorder characterized by recurring ulcers in the oral mucosa in the patient with no other signs of disease. The term “ aphthous ” is derived from a Greek word “ aphtha ” which means ulceration.

3. Classification of Recurrent Aphthous Stomatitis (RAS) Based on nature of recurrence as follows: 1- Simple aphthosis – Here the recurrence occurs two to four times in a year. 2- Complex aphthosis - Associated with systemic disease and activity of disease continues throughout the year and as older lesions heal newer lesion develops.

4. Classification for determining the management strategies: 1- Type A: RAS episodes lasting a few days with tolerable pain and a few occurrences in a year. 2- Type B: Painful RAS lasting 3 to 10 days recurrence every month. 3- Type C: Chronic painful course with disease activity almost continuous throughout the year.

5.   Recurrent aphthous ulcers can also be divided in to: 1- Major recurrent aphthous stomatitis . 2- Minor recurrent aphthous stomatitis . 3- Herpetiform ulcers.

6. Etiology of recurrent aphthous stomatitis 1- Local: Trauma Smoking Dysregulated saliva composition 2- Microbial: Bacterial: Streptococci Viral: Varicella zoster, Cytomegalovirus

7. 3- Systemic: Behçet’s disease. Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome. Crohn’s disease. Ulcerative colitis. HIV infection. Periodic fever, aphthosis , pharyngitis , and adenitis (PFAPA) or Marshall’s syndrome. Cyclic neutropenia .

8. 4- Stress: Psychological imbalance. Menstrual cycle. 5- Nutritional: Gluten sensitive enteropathy Iron, folic acid, zinc deficiencies Vitamin B1, B2, B6 and B12 deficiencies

9. 6- Genetic: Ethnicity. HLA haplotypes : Certain genetically specific HLAs have been identified in RAS patients as HLA-A2, HLA-B5, HLA-B12, HLA-B44, HLA-B51, HLA-B52, HLA-DR2, HLA-DR7 and HLA-DQ series.

10. Allergic/Immunologic: Local T-lymphocyte cytotoxicity . Abnormal CD4:CD8 ratio. Dysregulated cytokine levels. Microbe-induced hypersensitivity. Sodium lauryl sulfate (SLS) sensitivity. Food sensitivity.

11. Others: Antioxidants. Non-steroidal anti-inflammatory drugs (NSAIDS). Beta blockers. Immunosuppressive drugs.

12. Pathogenesis of RAS It is cell mediated immune response in which TNF- alpha plays a major role. A mononuclear (lymphocyte cell) infiltrate in the epithelium in pre ulcerative stage followed by a localized papular swelling due to keratinocyte vacuolation surrounded by a reactive erythmatous halo representing vasculitis .

13. The painful papule then turns in to a vesicle which ulcerates and fibrinous membrane covers the ulcer that is infiltrated by neutrophils , lymphocytes and plasma cells. Finally there is healing with epithelial regeneration.

14. Clinical features of major recurrent aphthous Also known as Periadenitis mucosa necrotica recurrens , Sutton’s disease Rare and severe form. Sex ratio :M= F Age of onset (yrs): 10-19 Number of ulcers: 1-10 Size of ulcers: (mm) > 10 Duration (days):> 30

15. Rate of recurrence (months): < Monthly. Sites: lips, cheeks, tongue, palate, pharynx. Permanent scarring: Common Lesions are oval in shape and painful.

16. Giant aphthae , relapsing aphthae or refractory aphthae Rarely major aphthae may present as numerous ulcers affecting a large area or several giant lesions that persists for months. These lesions are referred as giant aphthae , relapsing aphthae or refractory aphthae .

17. Clinical features of Minor recurrent aphthous stomatitis Also known as mild aphthae or Mikulicz’s aphthae Sex ratio: M= F Age of onset (yrs): 5-19 Number of ulcers: 1-5 Size of ulcers: (mm) < 10 Duration (days): 4-14 Rate of recurrence(months): 1-4 Permanent scarring: uncommon

18. These ulcers are usually oval or round in shape enveloped by thin eryhematous halo with grey-white pseudomembrane . The labial and buccal mucosa and the floor of the mouth. Gingiva , palate, or dorsum of the tongue is rarely affected.

19. Prodromal symptoms like localized burning sensation and pain may occur before the appearance of ulcers. Ulceration and pain lasts for about 3 to 4 days, and then re- epithelialization begins after which pain starts subsiding.

20. Clinical features of herpetiform ulcers Sex ratio : F > M Age of onset (yrs): 20-29 Number of ulcers: 10-100 Size of ulcers: (mm) > 1-2 Duration (days): < 30 Rate of recurrence (months): < Monthly. Sites: Lips, cheeks, tongue, palate, pharynx, palate, gingiva , floor of mouth. Permanent scarring: uncommon Rare presentation.

21. Accounts for 5 to 10 % of all RAS cases. Characterized by multiple recurrent crops of small, painful ulcers (5-100) that are widespread and may be distributed throughout the oral cavity. They tend to fuse, producing large irregular ulcers. These ulcers have later age of onset with more predisposition for women.

22. Investigations for RAS Blood investigations- Serum iron, folate , vitamin B12 and ferritin levels. Immuno Histochemistry - The epithelial basalcells in pre-ulcerative RAS lesions and epithelium at the ulcer stage contain Class I and Class II MHC antigens, both being consistent with active cell mediated inflammation. RAS biopsy tissue on immunological study reveals numerous cells with variable ratios of CD4+:CD8+T lymphocytes depending on ulcer duration.

23. Treatment of RAS Topical preparation Topical corticosteroid such as: 1- Clobetasol proprionate 0.05% in Orabase , Clobetasol proprinate 0.05% or fluocinonide 0.05% in Orabase (1:1). 2- Hyaluronic acid gel 0.2 %. 3- Lidocaine 5% ointment and lidocaine 10% spray is also effective for temporary analgesia.

24. Systemic Therapy- Oral antimicrobials , such as penicillin G (50mg QIDx 4 days), decrease ulcer size and pain . Clofazimine , an antimicrobial, in combination with rifampin and dapsone , has been shown to prevent the formation of new lesions.  Zinc at 50mg/day has also produced beneficial effects on wound reepitheliazation and healing.

25. Pentoxifylline has shown promising results in reducing severity of outbreaks, but has little effect in preventing new outbreaks and has numerous GI side effects. Low-dose oral tetracyclines may also be helpful due to their anti-inflammatory properties .  

26. Oral prednisone (initial dose of 25mg/day with taper) is the first-line systemic therapy and is typically reserved for the acute treatment of severe RAS outbreaks . Steroid-sparing agents, such as colchicine at starting at 0.5mg/day and gradually increasing to 1.5mg/day or dapsone 25mg/day and gradually increasing to 100mg/day may also be effective.

27. Thalidomide at a dose of 50 to 100mg/day is considered the most effective immunomodulator for RAS, but is obviously limited by its side-effect profile . Daily ascorbic acid 2000mg/m 2 /day for minor RAS shows reduction in oral ulcer outbreaks and a significant reduction in pain level.   Bioadhesive Patches – Bio-adhesive hydrogel patches.

28. Reference S.R . Porter C. Scully Recurrent aphthous stomatitis Crit Rev Oral Biol Med 1998;9:306-321 . S Jurge , R Kuffer , C Scully, SR Recurrent aphthous stomatitis Porter Oral Diseases 2006;12 : 1–21 . doi:10.1111/j.1601-0825.2005.01143.x Edgar NR,   Saleh D,   Miller   R A . Recurrent Aphthous Stomatitis : A Review . J Clin Aesthet Dermatol 2017;10:26-36.

29. Akintoye SO, Greenberg MS , Recurrent Aphthous Stomatitis Dent Clin North Am. 2014;58: 281–297 . De Gallo CB, Mimura MA, Sugaya NN. Psychological stress and recurrent aphthous stomatitis . Clinics (Sao Paulo)  2009;64:645–648 .