HASAN HATİPOĞLU, MÜJGAN GÜNGÖR HATİPOĞLU

Tekrarlayan Aftöz Ülserler: Güncel Yaklaşımlar ve Kavramlar

Tekrarlayan aftöz ülserler toplumda oldukça sık izlenmektedir. Etyolojisi günümüzde henüz tam olarak bilinmemekle birlikte genetik, immünolojik, hematolojik ve mikrobiyolojik nedenlerin klinik tablonun gelişiminde rol aldığı düşünülmektedir. Lokal travma, stres, hormonal değişiklikler gibi faktörlerin de bu tablonun oluşumunda etkili olduğu ileri sürülmektedir. Tekrarlayan aftöz ülserlerin tedavi yaklaşımında birçok yöntem önerilmektedir. Ancak günümüzde tedavinin temeli ağrının kontrol edilmesi, iyileşmeyi hızlandırmak ve ortaya çıkış sıklığını azaltmaya çalışmaktır. Bu derlemede güncel literatür çerçevesinde tekrarlayan aftöz ülserlerin klinik bulguları, nedenleri ve tedavi seçenekleri gözden geçirilmiş ve tartışılmıştır.

RECURRENT APHTHOUS ULCERS: CURRENT APPROACHES AND CONCEPTS

Recurrent aphthous ulcers are one of the most common oral mucosal disorders. Etiology of recurrent aphthous ulcers remains unknown. Genetic, immunologic, hematological and microbial factors are potential etiologic factors. Local trauma, stress and hormonal changes are suggested to be responsible in the formation of recurrent aphthous ulcers. Many treatment modalities are proposed for the management of aphthous ulsers. Treatment goals include pain control, promote healing, duration and reduce frequency of the ulcerative lesions. In this article of current literature, clinical aspects, causes and treatment options of recurrent aphthous ulcers are reviewed and discussed.

PDF

___

1. Lehner T. Autoimmunity in oral diseases, with special reference to recurrent oral ulceration. Proc R Soc Med 1968; 61:515-524.
2. Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg 1997;16:278-283.
3. Scully C, Porter S. Recurrent aphthous stomatitis: current concepts of etiology, pathogenesis and management J Oral Pathol Med 1989;18: 21-27.
4. Ship JA, Chavez EM, Doerr PA, Henson BS, Sarmadi M. Recurrent aphthous stomatitis. Quintessence Int 2000; 31:95-112.
5. Shashy RG, Ridley MB. Aphthous ulcers: a difficult clinical entity. Am J Otolaryngol 2000;21:389-393.
6. Embil JA, Stephens RG, Manuel FR. Prevalence of recurrent herpes labialis and aphthous ulcers among young adults on six continents. Can Med Assoc J 1975; 113: 627-630.
7. Axéll T, Henricsson V. The occurrence of recurrent aphthous ulcers in an adult Swedish population. Acta Odontol Scand 1985;43:121-125.
8. Kovac-Kovacic M, Skaleric U. The prevalence of oral mucosal lesions in a population in Ljubljana, Slovenia. J Oral Pathol Med 2000;29:331-335.
9. Zain RB. Oral recurrent aphthous ulcers/stomatitis: prevalence in Malaysia and an epidemiological update. J Oral Sci 2000; 42:15-19.
10. Mumcu G, Cimilli H, Sur H, Hayran O, Atalay T. Prevalence and distribution of oral lesions: a crosssectional study in Turkey. Oral Dis 2005;11:81-87.
11. Cebeci AR, Gülşahi A, Kamburoglu K, Orhan BK, Oztaş B. Prevalence and distribution of oral mucosal lesions in an adult Turkish population. Med Oral Patol Oral Cir Bucal 2009;14:E272-277.
12. Castellanos JL, Díaz-Guzmán L. Lesions of the oral mucosa: an epidemiological study of 23785 Mexican patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105:79-85.
13. Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc 2003; 134: 200-207.
14. Kleinman DV, Swango PA, Pindborg JJ. Epidemiology of oral mucosal lesions in United States school children: 1986-87.Community Dent Oral Epidemiol 1994; 22: 243- 253.
15. Majorana A, Bardellini E, Flocchini P, Amadori F, Conti G, Campus G. Oral mucosal lesions in children from 0 to 12 years old: ten years' experience. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:13-18.
16. Parlak AH, Koybasi S, Yavuz T, et al. Prevalence of oral lesions in 13- to 16-year-old students in Duzce, Turkey. Oral Dis 2006;12:553-558.
17. Yilmaz AE, Gorpelioglu C, Sarifakioglu E, Dogan DG, Bilici M, Celik N. Prevalence of oral mucosal lesions from birth to two years. Niger J Clin Pract 2011; 14: 349-353.
18. Miller MF, Garfunkel AA, Ram CA, Ship II. The inheritance of recurrent aphthous stomatitis. Observations on susceptibility. Oral Surg Oral Med Oral Pathol 1980; 49: 409-412.
19. Kılıç SS, Demirbaş T. Tekrarlayan Aftöz Stomatit. Güncel Pediatri 2005; 4: 107-111.
20. Axéll T. A preliminary report on prevalences of oral mucosal lesions in a Swedish population. Community Dent Oral Epidemiol 1975;3:143-145.
21. Crivelli MR, Aguas S, Adler I, Quarracino C, Bazerque P. Influence of socioeconomic status on oral mucosa lesion prevalence in schoolchildren. Community Dent Oral Epidemiol 1988;16: 58-60.
22. Özeç I, Taşveren S, Yeler D, Kılıç E. Sivas'ta 40 Yaş Üzeri Bireylerde Ağız Mukozası Lezyonlarının Yaygınlı- ğının Değerlendirilmesi Cumhuriyet Üniversitesi Diş Hekimliği Fakültesi Dergisi 2008; 11: 10-15.
23. Jainkittivong A, Aneksuk V, Langlais RP. Oral mucosal conditions in elderly dental patients. Oral Dis 2002; 8: 218-223.
24. Ship II. Epidemiologic aspects of recurrent aphthous ulcerations. Oral Surg Oral Med Oral Pathol 1972; 33: 400-406.
25. Scully C. Aphthae (Aphtous Stomatitis). In: Scully C, editor. Oral and Maxillofacial Medicine. The Basis of Diagnosis and Treatment. 1 st ed.China: Elsevier 2004; 194-202.
26. Furlanetto DL, Crighton A, Topping GV. Differences in methodologies of measuring the prevalence of oral mucosal lesions in children and adolescents. Int J Paediatr Dent 2006;16:31-39.
27. Ship II. Inheritance of aphthous ulcers of the mouth. J Dent Res 1965; 44: 837-844.
28. Albanidou-Farmaki E, Deligiannidis A, Markopoulos AK, Katsares V, Farmakis K, Parapanissiou E. HLA haplotypes in recurrent aphthous stomatitis: a mode of inheritance? Int J Immunogenet 2008; 35: 427-432.
29. Landesberg R, Fallon M, Insel R. Alterations of T helper/inducer and T suppressor/inducer cells in patients with recurrent aphthous ulcers. Oral Surg Oral Med Oral Pathol 1990; 69: 205-208.
30. Abdel All M, Ayoub A, el Refai M. Phenotypic identification of T lymphocytes subset in recurrent aphthous stomatitis. Egypt Dent J 1990; 36: 33-46.
31. Bachtiar EW, Cornain S, Siregar B, Raharjo TW. Decreased CD4+/CD8+ ratio in major type of recurrent aphthous ulcers: comparing major to minor types of ulcers. Asian Pac J Allergy Immunol 1998;16:75-79.
32. Sistig S, Cekic-Arambasin A, Rabatic S, Vucicevic-Boras V, Kleinheinz J, Piffko J. Natural immunity in recurrent aphthous ulceration. J Oral Pathol Med 2001;30:275-280.
33. Hietanen J, Häyrinen-Immonen R, Al-Samadi A, Trokovic N, Koskenpato K, Konttinen YT. Recurrent aphthous ulcers--a Toll-like receptor-mediated disease? J Oral Pathol Med 2012; 41:158-164.
34. Borra RC, de Mesquita Barros F, de Andrade Lotufo M, Villanova FE, Andrade PM. Toll-like receptor activity in recurrent aphthous ulceration. J Oral Pathol Med 2009; 38:289-298.
35. Taylor LJ, Bagg J, Walker DM, Peters TJ. Increased production of tumour necrosis factor by peripheral blood leukocytes in patients with recurrent oral aphthous ulceration. J Oral Pathol Med 1992; 21: 21-25.
36. Eguia-del Valle A, Martinez-Conde-Llamosas R, LópezVicente J, Uribarri-Etxebarria A, Aguirre-Urizar JM. Salivary levels of Tumour Necrosis Factor-alpha in patients with recurrent aphthous stomatitis. Med Oral Patol Oral Cir Bucal 2011; 16: 33-36.
37. Buño IJ, Huff JC, Weston WL, Cook DT, Brice SL. Elevated levels of interferon gamma, tumor necrosis factor alpha, interleukins 2, 4, and 5, but not interleukin 10, are present in recurrent aphthous stomatitis. Arch Dermatol 1998; 134: 827-831.
38. Jurge S, Kuffer R, Scully C, Porter SR. Mucosal disease series. Number VI. Recurrent aphthous stomatitis. Oral Dis 2006; 12:1-21.
39. Piskin S, Sayan C, Durukan N, Senol M. Serum iron, ferritin, folic acid, and vitamin B12 levels in recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol 2002; 16: 66-67.
40. Burgan SZ, Sawair FA, Amarin ZO. Hematologic status in patients with recurrent aphthous stomatitis in Jordan. Saudi Med J 2006; 27:381- 384.
41. Nolan A, McIntosh WB, Allam BF, Lamey PJ. Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy. J Oral Pathol Med 1991; 20: 389-391.
42. Thongprasom K, Youngnak P, Aneksuk V. Hematologic abnormalities in recurrent oral ulceration. Southeast Asian J Trop Med Public Health 2002; 33: 872-877.
43. Porter SR, Scully C, Flint S. Hematologic status in recurrent aphthous stomatitis compared with other oral disease. Oral Surg Oral Med Oral Pathol 1988; 66: 41- 44.
44. Compilato D, Carroccio A, Calvino F, Di Fede G, Campisi G. Haematological deficiencies in patients with recurrent aphthosis. J Eur Acad Dermatol Venereol 2010; 24: 667-673.
45. Koybasi S, Parlak AH, Serin E, Yilmaz F, Serin D. Recurrent aphthous stomatitis: investigation of possible etiologic factors. Am J Otolaryngol 2006; 27: 229-232.
46. Francis TC, Oppenheim JJ. Impaired lymphocyte stimulation by some streptococcal antigens in patients with recurrent aphthous stomatitis and rheumatic heart disease. Clin Exp Immunol 1970; 6: 573-586.
47. Donatsky O. A leucocyte migration study on the cellmediated immunity against adult human oral mucosa and streptococcal antigens in patients with recurrent aphthous stomatitis. Acta Pathol Microbiol Scand C 1976; 84: 227-234.
48. Hoover CI, Olson JA, Greenspan JS. Humoral responses and cross-reactivity to viridans streptococci in recurrent aphthous ulceration. J Dent Res 1986; 65: 1101-1104.
49. Gadol N, Greenspan JS, Hoover CI, Olson JA. Leukocyte migration inhibition in recurrent aphthous ulceration. J Oral Pathol 1985; 14: 121-132.
50. Birek C, Grandhi R, McNeill K, Singer D, Ficarra G, Bowden G. Detection of Helicobacter pylori in oral aphthous ulcers. J Oral Pathol Med 1999; 28:197-203.
51. Mansour-Ghanaei F, Asmar M, Bagherzadeh AH, Ekbataninezhad S. Helicobacter pylori infection in oral lesions of patients with recurrent aphthous stomatitis. Med Sci Monit 2005; 11: 576-579.
52. Fritscher AM, Cherubini K, Chies J, Dias AC. Association between Helicobacter pylori and recurrent aphthous stomatitis in children and adolescents. J Oral Pathol Med 2004; 33:129-132.
53. Eglin RP, Lehner T, Subak-Sharpe JH. Detection of RNA complementary to herpes-simplex virus in mononuclear cells from patients with Behçet's syndrome and recurrent oral ulcers. Lancet 1982; 2: 1356-1361.
54. Pedersen A, Hornsleth A. Recurrent aphthous ulceration: a possible clinical manifestation of reactivation of varicella zoster or cytomegalovirus infection. J Oral Pathol Med 1993; 22: 64-68.
55. Sun A, Chang JG, Chu CT, Liu BY, Yuan JH, Chiang CP. Preliminary evidence for an association of EpsteinBarr virus with pre-ulcerative oral lesions in patients with recurrent aphthous ulcers or Behçet's disease. J Oral Pathol Med 1998; 27: 168-175.
56. Güncü GN, Tözüm TF, Cağlayan F. Effects of endogenous sex hormones on the periodontium-review of literature. Aust Dent J 2005; 50:138-145.
57. Ferguson MM, Carter J, Boyle P. An epidemiological study of factors associated with recurrent aphthae in woman. J Oral Med 1984; 39:212-217.
58. McCartan BE, Sullivan A. The association of menstrual cycle, pregnancy, and menopause with recurrent oral aphthous stomatitis: a review and critique. Obstet Gynecol 1992; 80:455-458.
59. Preeti L, Magesh K, Rajkumar K, Karthik R. Recurrent aphthous stomatitis. J Oral Maxillofac Pathol 2011;15: 252-256.
60. Mahmoud K. AL-Omiri, J. Karasneh, E. Lynch. Psychological profiles in patients with recurrent aphthous ulcers. Int J Oral Maxillofac Surg 2012; 41: 384-388.
61. Huling LB, Baccaglini L, Choquette L, Feinn RS, Lalla RV. Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis. J Oral Pathol Med 2012; 41:149-152.
62. Sawair FA. Does smoking really protect from recurrent aphthous stomatitis? Ther Clin Risk Manag 2010;6:573- 577.
63. Marakoğlu K, Sezer RE, Toker HC, Marakoğlu I. The recurrent aphthous stomatitis frequency in the smoking cessation people. Clin Oral Investig 2007; 11: 149-153.
64. Healy CM, Thornhill MH. An association between recurrent oro-genital ulceration and non-steroidal antiinflammatory drugs. J Oral Pathol Med 1995; 24: 46-48.
65. Hasan AA, Ciancio S. Association between ingestion of nonsteroidal anti-inflammatory drugs and the emergence of aphthous-like ulcers. J Int Acad Periodontol 2009; 11:155-159.
66. Boulinguez S, Reix S, Bedane C et al. Role of drug exposure in aphthous ulcers: a case-control study. Br J Dermatol 2000;143: 1261-1265.
67. Gupta A, Morris G. Major aphthous ulcers induced by nicorandil. Age Ageing 2000; 29: 372-373.
68. Shotts RH, Scully C, Avery CM, Porter SR. Nicorandilinduced severe oral ulceration: a newly recognized drug reaction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999; 87: 706-707.
69. Agbo-Godeau S, Joly P, Lauret P, Szpirglas R, Szpirglas H. Association of major aphthous ulcers and nicorandil. Lancet 1998; 352: 1598-1599.
70. Wright A, Ryan FP, Willingham SE, et al. Food allergy or intolerance in severe recurrent aphthous ulceration of the mouth. Br Med J (Clin Res Ed) 1986; 292:1237-1238.
71. Nolan A, Lamey PJ, Milligan KA, Forsyth A. Recurrent aphthous ulceration and food sensitivity. J Oral Pathol Med 1991; 20: 473-475.
72. Gönül M, Gül U, Cakmak SK, Kiliç A. The role of the diet in patients with recurrent aphthous stomatitis. Eur J Dermatol 2007; 17: 97-98.
73. Herlofson BB, Barkvoll P. Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study. Acta Odontol Scand 1994; 52: 257-259.
74. Chahine L, Sempson N, Wagoner C. The effect of sodium lauryl sulfate on recurrent aphthous ulcers: a clinical study. Compend Contin Educ Dent 1997;18: 1238-1240.
75. Healy CM, Paterson M, Joyston-Bechal S, Williams DM, Thornhill MH. The effect of a sodium lauryl sulfate-free dentifrice on patients with recurrent oral ulceration. Oral Dis 1999; 5: 39-43.
76. Shim Y, Choi JH, Ahn HJ, Kwon JS. Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: a randomized controlled clinical trial. Oral Dis 2012;18: 655-660.
77. Talacko AA, Gordon AK, Aldred MJ. The patient with recurrent oral ulceration. Aust Dent J 2010; 55: 14-22.
78. Orme RL, Nordlund JJ, Barich L, Brown T. The MAGIC syndrome (mouth and genital ulcers with inflamed cartilage). Arch Dermatol 1990; 126: 940-944.
79. Femiano F, Gombos F, Scully C. Sweet's syndrome: recurrent oral ulceration, pyrexia, thrombophlebitis, and cutaneous lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003; 95: 324-327.
80. Marshall GS, Edwards KM, Butler J, Lawton AR. Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr 1987; 110: 43-46.
81. Scully C, MacFadyen E, Campbell A. Oral manifestations in cyclic neutropenia. Br J Oral Surg 1982; 20: 96-101.
82. MacPhail LA, Greenspan D, Feigal DW, Lennette ET, Greenspan JS. Recurrent aphthous ulcers in association with HIV infection. Description of ulcer types and analysis of T-lymphocyte subsets. Oral Surg Oral Med Oral Pathol 1991; 71: 678-683.
83. Muzyka BC, Glick M. Major aphthous ulcers in patients with HIV disease. Oral Surg Oral Med Oral Pathol 1994; 77: 116-120.
84. Livneh A, Zaks N, Katz J, Langevitz P, Shemer J, Pras M. Increased prevalence of joint manifestations in patients with recurrent aphthous stomatitis (RAS). Clin Exp Rheumatol 1996; 14: 407-412.
85. Altenburg A, Abdel-Naser MB, Seeber H, Abdallah M, Zouboulis CC. Practical aspects of management of recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol 2007; 21:1019-1026.
86. Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA, Häyrinen-Immonen R. Recurrent aphthous ulcers today: a review of the growing knowledge. Int J Oral Maxillofac Surg 2004; 33: 221-234.
87. Seymour RA, Heasman PA. Anti Plaque And Anticalculus Agents. In: Seymour RA, Heasman PA, editors. Drugs, Diseases and the Periodontium.1 st ed. Hong Kong: Oxford Medical Publications 1992;153-179.
88. Matthews RW, Scully CM, Levers BG, Hislop WS. Clinical evaluation of benzydamine, chlorhexidine, and placebo mouthwashes in the management of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1987; 63: 189-191.
89. Graykowski EA, Kingman A. Double-blind trial of tetracycline in recurrent aphthous ulceration. J Oral Pathol 1978; 7: 376-382.
90. Gorsky M, Epstein J, Rabenstein S, Elishoov H, Yarom N. Topical minocycline and tetracycline rinses in treatment of recurrent aphthous stomatitis: a randomized cross-over study. Dermatol Online J 2007; 13: 1.
91. Sharquie KE, Al-Tammimy SM, Al-Mashhadani S, Hayani RK, Al-Nuaimy AA. Lactic acid 5 percent mouthwash is an effective mode of therapy in treatment of recurrent aphthous ulcerations. Dermatol Online J 2006; 12: 2.
92. Fridh G, Koch G. Effect of a mouth rinse containing amyloglucosidase and glucose oxidase on recurrent aphthous ulcers in children and adolescents. Swed Dent J 1999; 23: 49-57.
93. Hoseinpour H, Peel SA, Rakhshandeh H, et al. Evaluation of Rosa damascena mouthwash in the treatment of recurrent aphthous stomatitis: a randomized, double-blinded, placebo-controlled clinical trial. Quintessence Int 2011; 42: 483-491.
94. Eisen D, Ellis CN. Topical cyclosporin for oral mucosal disorders. J Am Acad Dermatol 1990; 23: 1259-1264.
95. Miles DA, Bricker SL, Razmus TF, Potter RH. Triamcinolone acetonide versus chlorhexidine for treatment of recurrent stomatitis. Oral Surg Oral Med Oral Pathol 1993; 75: 397-402.
96. Browne RM, Fox EC, Anderson RJ. Topical triamcinolone acetonide in recurrent aphthous stomatitis. A clinical trial. Lancet 1968; 1: 565-567.
97. Kutcher M. Evaluating the efficacy of 2-octyl cyanoacrylate bioadhesive for treatment of oral ulcerations. Compend Contin Educ Dent Suppl 2001; 12-16.
98. Narang U. Cyanoacrylate medical adhesives-a new era Colgate ORABASE Soothe. N.Seal Liquid Protectant for canker sore relief. Compend Contin Educ Dent Suppl 2001; 7-11.
99. Al-Na'mah ZM, Carson R, Thanoon IA. Dexamucobase: a novel treatment for oral aphthous ulceration. Quintessence Int 2009; 40: 399-404.
100. Skaare AB, Herlofson BB, Barkvoll P. Mouthrinses containing triclosan reduce the incidence of recurrent aphthous ulcers (RAU). J Clin Periodontol 1996;23:778- 781.
101. Taylor LJ, Walker DM, Bagg J. A clinical trial of prostaglandin E2 in recurrent aphthous ulceration. Br Dent J 1993; 175: 125-129.
102. Ueta E, Osaki T, Yoneda K, Yamamoto T, Kato I. A clinical trial of Azelastine in recurrent aphthous ulceration, with an analysis of its actions on leukocytes. J Oral Pathol Med 1994; 23:123-129.
103. De Souza TO, Martins MA, Bussadori SK, et al. Clinical evaluation of low-level laser treatment for recurring aphthous stomatitis. Photomed Laser Surg 2010;28:85- 88.
104. Tezel A, Kara C, Balkaya V, Orbak R. An evaluation of different treatments for recurrent aphthous stomatitis and patient perceptions: Nd: AG laser versus medication. Photomed Laser Surg 2009; 27:101-106.
105. Rhodus NL, Bereuter J. An evaluation of a chemical cautery agent and an anti-inflammatory ointment for the treatment of recurrent aphthous stomatitis: a pilot study. Quintessence Int 1998; 29: 769-773.
106. Alidaee MR, Taheri A, Mansoori P, Ghodsi SZ. Silver nitrate cautery in aphthous stomatitis: a randomized controlled trial. Br J Dermatol 2005; 153: 521-525.
107. Arikan OK, Birol A, Tuncez F, Erkek E, Koc C. A prospective randomized controlled trial to determine if cryotherapy can reduce the pain of patients with minor form of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 101: 1-5.
108. Orbak R, Cicek Y, Tezel A, Dogru Y. Effects of zinc treatment in patients with recurrent aphthous stomatitis. Dent Mater J 2003; 22: 21-29.
109. Volkov I, Rudoy I, Freud T et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam Med 2009; 22: 9-16.
110. Gulcan E, Toker S, Hatipoğlu H, Gulcan A, Toker A. Cyanocobalamin may be beneficial in the treatment of recurrent aphthous ulcers even when vitamin B12 levels are normal. Am J Med Sci 2008; 336: 379-382.
111. Lalla RV, Choquette LE, Feinn RS, et al. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc 2012; 143: 370-376.
112. Sun A, Wang JT, Chia JS, Chiang CP. Levamisole can modulate the serum tumor necrosis factor-alpha level in patients with recurrent aphthous ulcerations. J Oral Pathol Med 2006; 35:111-116.
113. Miller MF. Use of levamisole in recurrent aphthous stomatitis. Drugs 1980; 20:131-136.
114. De Cree J, Verhaegen H, De Cock W, Verbruggen F. A randomized double-blind trial of levamisole in the therapy of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1978; 45: 378-384.
115. Pakfetrat A, Mansourian A, Momen-Heravi F, et al. Comparison of colchicine versus prednisolone in recurrent aphthous stomatitis: A double-blind randomized clinical trial. Clin Invest Med 2010; 33: 189-195.
116. Altinor S, Oztürkcan S, Hah MM. The effects of colchicine on neutrophil function in subjects with recurrent aphthous stomatitis. J Eur Acad Dermatol Venereol 2003; 17: 469-470.
117. Hello M, Barbarot S, Bastuji-Garin S, Revuz J, Chosidow O. Use of thalidomide for severe recurrent aphthous stomatitis: a multicenter cohort analysis. Medicine (Baltimore) 2010; 89: 176-182.
118. Cheng S, Murphy R. Refractory aphthous ulceration treated with thalidomide: a report of 10 years' clinical experience. Clin Exp Dermatol 2012; 37:132-135.
119. Thornhill MH, Baccaglini L, Theaker E, Pemberton MN. A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis. Arch Dermatol 2007; 143: 463-470.
120. Chandrasekhar J, Liem AA, Cox NH, Paterson AW. Oxypentoxifylline in the management of recurrent aphthous oral ulcers: an open clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:564- 567.
121. Hamuryudan V, Ozyazgan Y, Hizli N, et al. Azathioprine in Behçet's syndrome: effects on long-term prognosis. Arthritis Rheum 1997; 40: 769-774.
122. Sharquie KE, Najim RA, Abu-Raghif AR. Dapsone in Behçet's disease: a double-blind, placebo-controlled, cross-over study. J Dermatol 2002; 29: 267-279.
123. Melikoglu M, Fresko I, Mat C, et al. Short-term trial of etanercept in Behçet's disease: a double blind, placebo controlled study. J Rheumatol 2005; 32: 98-105.