Leila Soares Ferreira1 and Daiane Thais Meneguzzo2
1 Biodentistry Master Program, School of Dentistry, Ibirapuera University (UNIB), São Paulo, SP, Brazil2 São Leopoldo Mandic Dental Research Center, Campinas, SP, Brazil
ChapteR 36
Introduction
The recurrent aphthous ulcer (RAU) is the most common ulcerative lesion found in the oral cavity. It is characterized by the appearance of single or multiple ulcerative lesions in the oral mucosa; typically painful, recurrent, small, round or ovoid with circumscribed margins and erythematous haloes.1 It is usually first observed in adolescence, but it is in adulthood that patients face periods of increased pain and discomfort. Manifestations of RAU impair feeding, swallowing, and speaking, reducing a patient’s self-image and quality of life.2 RAU occurs worldwide and affects 2–66% of the international population. The cause of RAU is unknown, but are thought to be multifactorial with many triggers or precipitating factors.3 Among patient factors are genetic predisposition, local trauma, medications, allergy, hormonal changes, stress, and immunological abnormalities.4
RAU lesions follow a sequence of stages that can be described as: (1) prodromal – presence of symptoms but without any visible clinical signs; (2) preulcerative – initial presentation usu-ally with erythema and slight edema; (3) ulcerative – formation of the epithelial defect; (4) healing – symptom abatement and progressive healing; and (5) remission – no evidence of lesions.5 Also, RAU has three clinical presentations: minor aphthous ulcers (Fig. 36.1a), major aphthous ulcers (Fig. 36.1b), and herpetiform ulcers (Fig. 36.1c).
Minor RAU is the most common variety and involves every non-keratinized mucosa of the oral cavity. It appears as discrete and painful lesions, covered by a yellow–grey pseudomembrane surrounded by an erythematous halo (Fig. 36.1a). The ulcers are usually smaller than 8–10 mm in diameter and tend to heal within 10–14 days without scarring, but healing is slower than for other oral wounds, possibly because of intense lymphocytic infiltratration.6,7
Major RAU is a rare and severe form of RAU. It often pro-duces coalescent ulcers and tends to involve mucosa overlying the minor salivary glands. The lesions are oval, painful, with raised clear defined margins, usually larger than 1 cm in diam-eter, and tend to involve the mucosa of the lips, soft palate, and
throat (Fig. 36.1b). The prodromal symptoms are more intense, and the ulcers usually deeper, larger, and longer lasting than those seen in minor RAU. Fever, dysphagia, and malaise some-times occur early in the disease process.6
Herpetiform aphthous ulcer is the least common variety of RAU. It is characterized by painful ulcers, 1–3 mm in diameter and occurring in crops of 5–100 ulcers at any given time any-where on the mucosa (Fig. 36.1c). They tend to fuse and pro-duce larger ulcers that last 10–14 days.7
The treatment is palliative, since most existing therapies only reduce the symptoms and sometimes the duration of the lesion. Local corticosteroids, antiseptic and antibacterial drugs are used singly or in various combinations.7 Systemic medication is also used in severe cases or those resistant to topical therapies such as steroids and immunosuppressive systemic agents. However, none of the conventional treatments has been shown to be effective in preventing or even decreasing the incidence of lesions. Low level laser therapy (LLLT), on the other hand, has shown excellent results in the treatment and prevention of RAU.8
Low level laser therapy
LLLT is known to modulate the inflammatory process, promote analgesia, and accelerate wound healing (see Chapters 5 and 6),9–11 and these effects can be expected in the treatment of aph-thous ulcers. Zand et al. performed a randomized controlled clinical trial to evaluate the efficacy of a single session of non-ablative CO2 laser irradiation in reducing pain in minor RAU.12 The results showed that a low power, non-thermal, single-ses-sion of CO2 laser irradiation reduced pain in RAU immediately and dramatically, with no visible side effects. Another clinical evaluation comparing LLLT and a topical corticosteroid agent demonstrated that 75% of the patients treated with LLLT reported a reduction in pain after LLLT and total regression of the lesion after 4 days, while lesion regression took 5–7 days in the corticosteroid group.8 Also, LLLT was described to be an
286 Chapter 36
alternative treatment for primary herpes simplex infection in children, with an immediate positive outcome in severe painful gengivostomatitis lesions.13
The immediate analgesic response of phototherapy can be explained by blockage of the neuronal action potential.10 In addition, the anti-inflammatory response to laser irradiation contributes to the long-term analgesic effects, such as acceleration of the microcirculation, increased natural opioid peptides14,15; decreased release of histamine, interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ)16; blockage of acetylcholine15; and reduction of the synthesis of bradykinin14,15 and prostaglandin E2.
9 Since the acute inflammatory phase of the lesion is controlled, the tissue is ready to start healing.
The effectiveness of LLLT in the prevention of RAU lesions has not been established yet. However, RAU can be prevented by
treatments that promote the inhibition of endogenous TNF-α, such as thalidomide and pentoxifylline,17 and the same effect can be achieved by laser irradiation, with no side effects. Therefore, LLLT can be considered a promising approach to the prevention of RAU manifestations.
Laser protocol
The primary goals of therapy of RAU are relief of pain, reduction of ulcer duration, and restoration of normal oral function. The secondary goals include reduction in frequency and severity of recurrences and maintenance of remission.18,19 Therefore, there are three types of LLLT protocols for RAU management.
Figure 36.1 Clinical presentation of recurrent aphthous ulcers (RAU): (a) Minor RAU, (b) major RAU, (c) herpetiform aphthous ulcer.
(a) (b)
(c)
Recurrent aphthous ulcers 287
pain reliefAs the lesion starts to heal, there are a few days (3–5 days) when the main symptom is severe pain. At this time the patient seeks pain relief. LLLT is the only therapy capable of promoting immediate analgesia with no side effects, being a great clinical
differential for dentists and improving patient’s perception. Also, when LLLT is performed at this time, the duration of the RAU cycle will also be reduced. The LLLT protocol is daily infrared laser irradiation (2.0–3.0 J per point) until remission of symptoms (Fig. 36.2).
Figure 36.2 LLLT treatment of a patient presenting with RAU with traumatic factor: (a) Initial lesion (b) schematic of LLLT irradiation points.
(a) (b)
Clinical cases 36.1 Pain in the premolar area
A 22-year-old male patient presented to the Sao Leopoldo Mandic University Laser Center complaining of monthly recurrence of RAU with severe pain in the upper right premolar area (Fig. 36.3a). For pain control treatment, LLLT was applied using the following protocol: red laser irradiation (660 nm) in continuous mode, 100 mW of power, 3 J of energy per point at four points. The patient reported immediate pain relief of about
60%. A second irradiation with the same parameters was applied and 100% pain control was achieved in this session. After 24 hours, the patient returned reporting mild pain and the same LLLT protocol was repeated (Fig. 36.3b). On the following day, the patient reported no more pain and an LLLT protocol was proposed to accelerate healing: red laser, 1 J per point at four points. Complete remission occurred after 7 days (Fig. 36.3c).
Figure 36.3 Patient with a major RAU in the area of the upper right premolars: (a) Initial lesion (b) appearance of the lesion after 3 days of LLLT (c) complete healing 7 days after the first LLLT session.
(a) (b) (c)
288 Chapter 36
acceleration of wound healingAfter pain remission, LLLT can also be performed to accelerate ulcer healing. The LLLT protocol is daily red laser irradiation (0.5–1.0 J per point) until complete lesion healing.
RaU preventionLLLT can be also used when the patient has no RAU manifesta-tions. LLLT stimulates the immune system and increases the resistance of the mucosa to ulcer formation. The LLLT protocol is weekly infrared or red laser irradiation (2.0–3.0 J per point)
for 10 weeks in all regions of high incidence of RAU manifesta-tions (the patient should be asked to indicate the more critical areas).
The following are useful tips for LLLT:• An anti-inflammatory and analgesic effect dose should be
used on and around the lesion;• The number of points of irradiation can be increased until the
patient reports pain relief of at least 90% (the patient should be asked to rate their perception of pain from 0% to 100% before and after irradiation);
Clinical case 36.2 Pain in the lip
LLLT was used to treat a 14-year-old female patient who wore braces and complained of severe pain in the upper right lip (Fig. 36.4a). LLLT was applied using the following protocol: red laser emission (660 nm) in continuous mode, 100 mW of power, 3 J of energy per point in four points
(Fig. 36.4b,c). Immediately after laser irradiation, the patient reported pain relief of about 80%. The use of a protective wax on the brackets was recommended to avoid trauma. After 4 days, the lesion had healed completely (Fig. 36.4d).
Figure 36.4 LLLT of an RAU lesion: (a) Initial appearance of the aphthous lesion (b) red laser irradiation at the center of the ulcer, showing light scattering around the lesion (observe that the laser handpiece is not in contact with the tissue) (c) schematic of the LLLT irradiation points: one point in the center and four points around the ulcer (d) remission of the lesion after 4 days.
(a) (b)
(c) (d)
Recurrent aphthous ulcers 289
• As radiation scatters around the lesion, while performing the analgesic protocol this lower scattered energy will also improve the healing process (see Fig. 36.4b);
• Whenever possible, laser irradiation must be perpendicular to avoid loss of energy.
2 Mumcu G, Hayran O, Ozalp DO, et al. The assessment of oral health-related quality of life by factor analysis in patients with Behcet’s disease and recurrent aphthous stomatitis. J Oral Pathol Med 2007; 36(3): 147–152.
3 Wardhana, Datau EA. Recurrent aphthous stomatitis caused by food allergy. Acta Med Indones 2010; 42(4): 236–240.
9 Bjordal JM, Johnson MI, Iversen V, et al. Low-level laser therapy in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials. Photomed Laser Surg 2006; 24(2): 158–168.
10 Chow RT, Heller GZ, Barnsley L. The effect of 300mW, 830 nm laser on chronic neck pain: a double-blind, randomized, placebo- controlled study. Pain 2006; 124: 201–210.
11 Demidova-Rice TN, Salomatina EV, Yaroslavsky AN, et al. Low-level light stimulates excisional wound healing in mice. Lasers Surg Med 2007; 39(9): 706–715.
12 Zand N, Ataie-Fashtami L, Djavid GE, et al. Relieving pain in minor aphthous stomatitis by a single session of non-thermal carbon dioxide laser irradiation. Lasers Med Sci 2009; 24(4): 515–520.
13 Navarro R, Marquezan M, Cerqueira DF, et al. Low-level-laser therapy as an alternative treatment for primary herpes simplex infection: a case report. J Clin Pediatr Dent 2007; 31(4): 225–228.
14 Ohshiro T. An overview of pain. In: Oshiro T, ed. Low Reactive- Level Laser Therapy: Practical Application. Chichester: Wiley, 1991: 13–21.
15 Simunovic Z. Pain and practical aspects of its management. In: Simunovic Z (eds). Lasers in medicine and dentistry. Zagreb: AKD, 2000: 269–301.
16 Safavi SM, Kazemi B, Esmaeili M, et al. Effects of low-level He-Ne laser irradiation on the gene expression of IL-1beta, TNF-alpha, IFN-gamma, TGF-beta, bFGF, and PDGF in rat’s gingiva. Lasers Med Sci 2008; 23(3): 331–335.
17 Natah SS, Häyrinen-Immonen R, Hietanen J, et al. Immuno-localization of tumor necrosis factor-alpha expressing cells in recur-rent aphthous ulcer lesions (RAU). J Oral Pathol Med 2000; 29(1): 19–25.
