主要目标是排除严重疾病和/或全身性疾病,并提供治疗,以缓解疼痛、缩短溃疡持续时间和降低发作频率。
局部用皮质类固醇仍然是主要的治疗手段,可联合局部抗微生物药物辅助治疗,以减轻炎性反应。然而,如果局部治疗对 RAU 无效,可能需要进行系统性免疫调节治疗。[3]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.http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com[32]Letsinger JA, McCarty MA, Jorizzo JL. Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide. J Am Acad Dermatol. 2005;52:500-508.http://www.ncbi.nlm.nih.gov/pubmed/15761429?tool=bestpractice.com
对于所有患者,应考虑局部创伤(如尖锐牙和/或断牙、义齿和矫治器、以及咀嚼时咬伤)的可能性,并应采取适当的口腔科治疗。[3]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.http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com有一些证据表明,即使没有任何缺乏,口服维生素 B12 仍有益处;研究显示,无论血清中维生素 B12 水平如何,口服维生素 B12(氰钴维生素)对该病都是有效的。[33]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.http://www.jabfm.org/content/22/1/9.fullhttp://www.ncbi.nlm.nih.gov/pubmed/19124628?tool=bestpractice.com[34]Gulcan E, Toker S, Hatipoğlu H, et al. 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.http://www.ncbi.nlm.nih.gov/pubmed/19011392?tool=bestpractice.com[35]Liu HL, Chiu S, Chen KH. Effectiveness of vitamin B12 on recurrent aphthous stomatitis in long term care: a systematic review. JBI Database System Rev Implement Rep. 2013;11:281-307.
局部治疗
局部用皮质类固醇是 RAU 的主要治疗方法,通常作为首选。可以使用各种不同的药物。[36]Liu C, Zhou Z, Liu G, et al. Efficacy and safety of dexamethasone ointment on recurrent aphthous ulceration. Am J Med. 2012;125:292-301.http://www.ncbi.nlm.nih.gov/pubmed/22340928?tool=bestpractice.com常用药物包括曲安奈德乳膏、氢化可的松丸剂和倍他米松含漱液。同样可以使用更强效的局部用皮质类固醇(如二丙酸倍他米松、氯倍他索或氟轻松醋酸酯)。[3]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.http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com治疗持续时间因人而异,但没有证据表明低效激素可引起肾上腺功能抑制。
缓解症状的局部疗法可能是有效的。这包括局麻药(如利多卡因)、局部用抗炎药(如苄达明、[37]Matthews RW, Scully CM, Levers BG, et al. 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.http://www.ncbi.nlm.nih.gov/pubmed/3469601?tool=bestpractice.com溃疡疼痛减轻:有低质量的证据显示,相比安慰剂,苄达明在减轻口腔溃疡患者的疼痛方面并没有明显疗效。然而,由于具有短暂的局部止痛效果,使用苄达明还是有益的。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。氨来呫诺糊剂)。[38]Greer RO Jr, Lindenmuth JE, Juarez T, et al. A double-blind study of topically applied 5% amlexanox in the treatment of aphthous ulcers. J Oral Maxillofac Surg. 1993;51:243-248.http://www.ncbi.nlm.nih.gov/pubmed/8445464?tool=bestpractice.com[39]Murray B, MacGuinness N, Biagioni P, et al. A comparative study of the efficacy of Aphtheal in the management of recurrent minor aphthous ulceration. J Oral Pathol Med. 2005;34:413-419.http://www.ncbi.nlm.nih.gov/pubmed/16011610?tool=bestpractice.com[40]Murray B, Biagioni A, Lamey PJ. The efficacy of amelxanox OraDisc on the prevention of recurrent minor aphthous ulceration. J Oral Pathol Med. 2006;35:117-122.http://www.ncbi.nlm.nih.gov/pubmed/16430743?tool=bestpractice.com抗微生物药物辅助治疗也可能有一定效果,部分是通过减少继发性感染。这些药物可减轻溃疡的疼痛和严重程度。随机对照试验(RCT)显示葡萄糖酸氯己定含漱液可缩短 RAU 的持续时间,延长间歇期。[41]Addy M, Tapper-Jones L, Seal M. Trial of astringent and antibacterial mouthwashes in the management of recurrent aphthous ulceration. Br Dent J. 1974;136:452-455.http://www.ncbi.nlm.nih.gov/pubmed/4531936?tool=bestpractice.com[42]Addy M, Carpenter R, Roberts WR. Management of recurrent aphthous ulceration: a trial of chlorhexidine gluconate gel. Br Dent J. 1976;141:118-120.http://www.ncbi.nlm.nih.gov/pubmed/786339?tool=bestpractice.com[43]Addy M. Hibitane in the treatment of aphthous ulceration. J Clin Periodontol. 1977;4:108-116.http://www.ncbi.nlm.nih.gov/pubmed/350904?tool=bestpractice.com[44]Hunter L, Addy M. Chlorhexidine gluconate mouthwash in the management of minor aphthous ulceration: a double-blind, placebo controlled cross-over trial. Br Dent J. 1987;162:106-110.http://www.ncbi.nlm.nih.gov/pubmed/3545267?tool=bestpractice.com溃疡症状减轻:有低质量的证据显示,相比安慰剂,氯己定含漱液在减轻口腔溃疡症状方面更有效。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。四环素类药物局部含漱可能同样有效,[45]Graykowski EA, Kingman A. Double-blind trial of tetracycline in recurrent aphthous ulceration. J Oral Pathol. 1978;7:376-382.http://www.ncbi.nlm.nih.gov/pubmed/105096?tool=bestpractice.com[46]Hayrinen-Immonen R, Sorsa T, Pettila J, et al. Effect of tetracyclines on collagenase activity in patients with recurrent aphthous ulcers. J Oral Pathol Med. 1994;23:269-272.http://www.ncbi.nlm.nih.gov/pubmed/7932246?tool=bestpractice.com溃疡疼痛减轻:有低质量的证据显示,相比安慰剂,四环素漱口水在减轻阿弗他溃疡患者的疼痛方面更有效。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。然而,此类药物必须进行调配,并且由于其可能导致牙齿变色,因此禁用于 8 岁以下儿童。
系统治疗
如果局部治疗 RAU 无效,可能需要进行系统性免疫调节治疗。然而,目前仍然缺乏评估其有效性(或不良反应)的研究。[47]Brocklehurst P, Tickle M, Glenny AM, et al. Systemic interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database Syst Rev. 2012;(9):CD005411.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005411.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22972085?tool=bestpractice.com对于病情严重的 RAU 患者,可用系统性皮质类固醇或沙利度胺进行治疗。[1]Scully C. Clinical practice: aphthous ulceration. N Engl J Med. 2006;355:165-172.http://www.ncbi.nlm.nih.gov/pubmed/16837680?tool=bestpractice.com[3]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.http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com[32]Letsinger JA, McCarty MA, Jorizzo JL. Complex aphthosis: a large case series with evaluation algorithm and therapeutic ladder from topicals to thalidomide. J Am Acad Dermatol. 2005;52:500-508.http://www.ncbi.nlm.nih.gov/pubmed/15761429?tool=bestpractice.com[48]Hello M, Barbarot S, Bastuji-Garin S, et al. Use of thalidomide for severe recurrent aphthous stomatitis: a multicenter cohort analysis. Medicine (Baltimore). 2010;89:176-182.http://www.ncbi.nlm.nih.gov/pubmed/20453604?tool=bestpractice.com
一种可行的治疗方案是口服泼尼松(泼尼松龙)一周,第二周逐渐减量。[3]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.http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com
目前已有研究数据支持沙利度胺用于 RAU[49]Revuz J, Guillaume JC, Janier M, et al. Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis. Arch Dermatol. 1990;126:923-927.http://www.ncbi.nlm.nih.gov/pubmed/2193629?tool=bestpractice.com 和 HIV 感染相关的 ALU 的治疗。[50]Nicolau DP, West TE. Thalidomide: treatment of severe recurrent aphthous stomatitis in patients with AIDS. DICP. 1990;24:1054-1056.http://www.ncbi.nlm.nih.gov/pubmed/2275226?tool=bestpractice.com对这些患者进行的开放性和双盲研究显示,在严重、难治性 RAU 的可选药物中,沙利度胺是最有效的。[13]Jurge S, Kuffer R, Scully C, et al. Mucosal disease series. Number VI. Recurrent aphthous stomatitis. Oral Dis. 2006;12:1-21.http://www.ncbi.nlm.nih.gov/pubmed/16390463?tool=bestpractice.com但是,其使用需十分谨慎,建议由口腔黏膜病专家进行诊治和开具处方。[1]Scully C. Clinical practice: aphthous ulceration. N Engl J Med. 2006;355:165-172.http://www.ncbi.nlm.nih.gov/pubmed/16837680?tool=bestpractice.com[3]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.http://www.ncbi.nlm.nih.gov/pubmed/12636124?tool=bestpractice.com
使用其他免疫调节剂(如秋水仙碱、左旋咪唑或己酮可可碱)治疗严重或难治性 RAU 的结果并不理想,不是疗效差,就是不良反应的发生率高。[13]Jurge S, Kuffer R, Scully C, et al. Mucosal disease series. Number VI. Recurrent aphthous stomatitis. Oral Dis. 2006;12:1-21.http://www.ncbi.nlm.nih.gov/pubmed/16390463?tool=bestpractice.com然而,有证据表明这些生物制剂可能有作用。[51]O'Neill ID, Scully C. Biologics in oral medicine: principles of use and practical considerations. Oral Dis. 2012;18:525-536.http://onlinelibrary.wiley.com/doi/10.1111/j.1601-0825.2012.01919.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22420757?tool=bestpractice.com[52]O'Neill ID, Scully C. Biologics in oral medicine: ulcerative disorders. Oral Dis. 2013;19:37-45.http://www.ncbi.nlm.nih.gov/pubmed/22471882?tool=bestpractice.com