Case series of low-level laser therapy for minor ulceration: Diverse outcomes related to predisposing factors

Ratna Kumala Indrastiti; Indriasti Indah Wardhany; Masita Mandasari; Yuniardini Septorini Wimardhani

doi:10.4103/SDJ.SDJ_21_23

CASE REPORTS

Year : 2023 | Volume : 7 | Issue : 1 | Page : 33-38

Case series of low-level laser therapy for minor ulceration: Diverse outcomes related to predisposing factors

Ratna Kumala Indrastiti, Indriasti Indah Wardhany, Masita Mandasari, Yuniardini Septorini Wimardhani
Department of Oral Medicine, Faculty of Dentistry, Universitas Indonesia, Jakarta, Indonesia

Date of Submission	07-Nov-2022
Date of Decision	11-Jan-2023
Date of Acceptance	03-Feb-2023
Date of Web Publication	17-May-2023

Correspondence Address:
Ratna Kumala Indrastiti
Department of Oral Medicine, Faculty of Dentistry, Universitas Indonesia, Jakarta 10430
Indonesia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/SDJ.SDJ_21_23

Abstract

Background: There are many strategies to alleviate the pain and suffering associated with oral mucosal ulcers. Low-level laser therapy (LLLT) has recently been widely used as a treatment for oral lesions because of its modalities in promoting ulcer healing and reducing pain and discomfort. Case Report: Three patients aged 22–24 years old came to the Universitas Indonesia Dental Hospital with the chief complaint of ulcers in the mouth. Two patients were diagnosed with minor recurrent aphthous ulceration and the third patient with aphthous ulceration. The visual analog scale (VAS) was used to assess the patients’ pain. The VAS scores of each patient were recorded before, immediately after, and 30 min after the application of LLLT. The patients were followed up on the second and third days after treatment. All patients reported a significant reduction of VAS, but there were dissimilar results in the ulcer healing process. Conclusion: Several factors (e.g., local and systemic conditions that may affect wound healing and the location of the lesions) must be considered in determining the success of LLLT.

Keywords: Alternative therapy, low-level laser therapy, oral ulceration

How to cite this article:
Indrastiti RK, Wardhany II, Mandasari M, Wimardhani YS. Case series of low-level laser therapy for minor ulceration: Diverse outcomes related to predisposing factors. Sci Dent J 2023;7:33-8

How to cite this URL:
Indrastiti RK, Wardhany II, Mandasari M, Wimardhani YS. Case series of low-level laser therapy for minor ulceration: Diverse outcomes related to predisposing factors. Sci Dent J [serial online] 2023 [cited 2023 Jun 2];7:33-8. Available from: https://www.scidentj.com/text.asp?2023/7/1/33/377188

Background

While many pathological disorders can induce both acute and long-lasting pain in the oral mucosa, ulcerated lesions brought on by a variety of etiologic factors, including infection, autoimmune diseases, trauma, or neoplasia, are one of the most frequent causes of oral mucosal pain.^[1] If an inciting trauma, condition, or medication can be identified, the duration of the lesion’s presence, the frequency of episodes in cases where it recurs, the presence or absence of pain, and the lesion’s growth over time should all be considered in a thorough patient history when evaluating ulcerative oral lesions.^[2] Many alternative therapies that can overcome pain that may be caused by lesions in the oral cavity have been developed. The main treatment strategies aim to relieve pain, reduce inflammation, and minimize symptoms.^[3]

Laser therapy has gained popularity as a way to supplement conventional dental treatment plans. High-power lasers employing carbon dioxide (CO₂), neodymium-doped yttrium aluminum garnet (Nd:YAG), or erbium-doped yttrium aluminum garnet (Er:YAG) have been utilized frequently in dental surgery and endodontic treatment.^[4] The use of light (often provided by a low-power laser or light-emitting diode) to promote tissue repair, reduce inflammation, or cause analgesia is known as low-level laser therapy (LLLT). In contrast to many other laser therapies, photosynthesis is likened to LLLT’s mode of action rather than ablating or heating. Additionally, LLLT is distinct from photodynamic treatment, which uses light to indirectly cause photosensitive dyes to create bactericidal chemicals that kill disease-causing bacteria.^[5],[6]

Several studies have investigated the effectiveness of LLLT in comparison to topical medications, such as anti-inflammatory medications, anesthetics, immune modulators, antibiotics, and herbal remedies. These studies suggest that laser therapy is effective in reducing the pain and size of lesions in comparison to topical medications. In general, the follow-up period was up to 7 days.^[7] While the exact mechanisms of LLLT are still debatable, notwithstanding all the benefits of LLLT, there are allegedly some limitations that could hinder the effectiveness of this therapy in the management of lesions in the oral cavity.

The aim of this article is to provide an overview of the efficacy of using LLLT as an alternative therapy in treating three patients with minor ulcerated lesions in their oral cavity who came to Oral Medicine Clinic, Universitas Indonesia Dental Hospital, and to bring perspective to a factor that may contribute to the delayed healing process of lesions.

Case Reports

The patients were treated with two times with irradiation by an 830-nm diode laser of BTL—4000 Topline LASER^® with irradiation times of 36 and 57 s/cm² sequentially. A 1–2-J/cm² dose, 80%–10% duty factor, was used with a frequency of 5.00 Hz in noncontact mode. The tip was moved in circular motions at 1 mm/s from the periphery toward the center of the lesion.

The first patient, a 22-year-old female individual, came to Oral Medicine Clinic, Universitas Indonesia Dental Hospital, with a chief complaint of painful ulcer in the mouth for 1 week and a visual analog scale (VAS) score of 3. She noted that the ulcer caused difficulty in eating, worsened when eating hot and spicy food, and felt relieved when drinking warm water. The ulcer arose spontaneously and was not preceded by trauma. A history of ulcers occurring 3–4 times a year was noted. Treatments of vitamin C consumption and antiseptic mouthwash were carried out by the patient herself, with which her ulcers recovered within a week. Extra-oral examination did not reveal anything noteworthy. The intra-oral examination revealed an ulcer on the right buccal area of the mouth at tooth regions 46 and 47 [Figure 1]A. Based on the patient’s history and the clinical presentation of the lesions, a diagnosis of recurrent aphthous ulceration was given. Following each irradiation, the VAS was used to ask the patient if she was still feeling pain. At the end of the treatment, the patient reported that the ulcer was free of pain and mildly sensitive to touch, and the VAS score subsided to 1. The patient was sent home without any prescriptions, and instructions to avoid hard and spicy foods were given. The patient was followed up over a period of 3–5 days after laser therapy and showed improvement with no signs of pain or discomfort [Figure 1]B and C.

Figure 1: (A) Clinical appearance of an ulcerated lesion at the first visit: a single ulcer with well-defined irregular margins, approximately 7 × 5 mm in size with a large erythematous area surrounding the lesion; (B) 24 h after LLLT, the ulcer was in the healing stage (ulceration and erythematous area were significantly reduced); (C) 48 h after LLLT, the ulceration was no longer visible; however, there was still a small area of faint redness

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The second patient, a 22-year-old female individual, came to Oral Medicine Clinic, Universitas Indonesia Dental Hospital, with a chief complaint of a painful ulcer in the mouth since 4 days ago and a VAS score of 2. She had a history of recurrent ulcers since age 11, which were often triggered by trauma and/or stress. No treatments were carried out by the patient and her ulcers usually healed within a week. Extra-oral examination revealed nothing noteworthy, and intra-oral examination revealed an ulcer on the right mucobuccal area at tooth regions 15 and 16 [Figure 2]A. A diagnosis of recurrent aphthous ulceration was given based on subjective and objective examinations. The patient was also treated with LLLT and stated that the VAS was 0 immediately after treatment. The patient was followed up over a period of 7 days after laser therapy and showed complete remission of the lesions with no signs of pain or discomfort within 3 days [Figure 2]B and C.

Figure 2: (A) Clinical appearance of an ulcerated lesion at the first visit: a single ovoid ulcer with well-defined regular margins, approximately 2 × 3 mm in size surrounded by an erythematous halo; (B) 24 h after LLLT, the ulcer was in the healing stage (ulceration and erythematous area were significantly reduced); (C) 48 h after LLLT, the ulceration was no longer visible; however, there was still a small area of redness

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The third patient, a 24-year-old female individual, came to Oral Medicine Clinic, Universitas Indonesia Dental Hospital, with a chief complaint of an ulcer preceded by trauma 3 days ago and a VAS score of 4. The patient experienced ulcers in the mouth one to two times a year, which were always caused by trauma, and no history of recurrent ulcers in the family. The patient was diagnosed with anemia six years ago and given an iron supplement prescription. No notable conditions were revealed upon extra-oral examination. The intra-oral examination revealed an ulcer on the left dorsolateral area of the tongue at tooth regions 35 and 36 [Figure 3]A. A diagnosis of aphthous ulcer was given based on the patient’s history and clinical examination. The patient was also treated with LLLT and stated that the VAS score was 0 without stimulation and 5 if the ulcer was touched by a tooth. The patient was followed up over a period of 10 days after laser therapy. After day 3, the ulcer persisted, but the VAS score upon stimulation had decreased to 3 [Figure 3]B and C. Complete remission occurred within 10 days.

Figure 3: (A) Clinical appearance of an ulcerated lesion at the first visit: a single ulcer with well-defined irregular margins, approximately 2 × 4 mm in size with an erythematous area surrounding the lesion; (B) 24 h after LLLT, the ulcer had increased in size, measuring approximately 8 × 5 mm and surrounded by redness; (C) 48 h after LLLT, the ulcer persisted but the erythematous area had slightly subsided

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Discussion

There are four stages of recurrent aphthous stomatitis (RAS) proposed by Stanley^[8]: premonitory, pre-ulcerative, ulcerative, and healing. The premonitory stage continues for the first 24 h of RAS development. Patients may experience burning or tingling where the RAS first appears. The pre-ulcerative stage occurs during the initial 18–72 h of the formation of a RAS lesion. Clinically, erythematous macules or papules with a faint indurated erythematous halo are the initial manifestations of aphthae, and pain might range in severity, but it is typically moderate to severe. The ulcerative stage lasts from 1 to 16 days. The papule or macule, which starts to dissolve in the second stage, enlarges and ulcerates clinically but still maintains a distinct lesion. After 2 or 3 days, there is cessation of pain. In most cases, the maximum size of the lesion is achieved 4–6 days after onset. The healing phase lasts between 4 and 35 days, and lesions usually heal without leaving scars in 10–21 days.^[9] In our study, the patients came to our clinic at the ulcerative stage, with pain VAS scores ranging between 2 and 4. The clinical appearance of the lesions was characterized by shallow ulceration surrounded by an erythematous halo.

Medical uses of lasers have existed for a very long time as an alternative therapy that has been widely used. These medical uses are in line with the development of knowledge and the requirement for a pleasant, effective therapy to be able to treat a condition that may lead to faster recovery and fewer adverse effects. They fit the description of high-powered, low-powered, surgical, or therapeutic. LLLT has been proven to have analgesic, anti-inflammatory, and biostimulatory effects on living tissue.^[10],[11] LLLT has been considered to promote wound healing through several mechanisms of fibroblast proliferation. One explanation is that lasers encourage the synthesis of basic fibroblast growth factor, a multifunctional polypeptide that stimulates fibroblast proliferation and differentiation, stimulates wound contraction, and promotes healing.^[12]

Recently, LLLT has been used as an alternative therapy in the management of lesions in the oral cavity. Some hypotheses state that the mechanisms of LLLT include modulation of natural substances (such as histamine, acetylcholine, opioid peptides, kinins, prostaglandin, interleukin, and tumor necrosis factor), alterations in the impulse conduction of nociceptors, and effects on lymphocyte metabolism. Additionally, laser therapy can increase the tissue’s microcirculation and oxygenation and promote the proliferation of epithelial, endothelial, and mesenchymal cells.^[13] Another theory stated that a rise in adenosine triphosphate (ATP) synthesis brought on by LLLT results in hyperpolarization and stimulus blockage, which lessens the induction of pain sensations. Enhanced photoreceptor absorption in mitochondrial components, specifically in the electron transport (respiratory) chain, is necessary for increased ATP production following LLLT. Additionally, interleukin-1 beta and prostaglandin E2 inhibition contribute to pain relief (prostaglandin enhances pain by sensitizing receptors and lowering their thresholds).^[14]

In a study by Anand et al.,^[15] the time needed for the complete healing of aphthous lesions was 3–4 days. LLLT not only immediately relieved pain and caused the lesion’s size to immediately decrease but also resulted in no recurrence even after a year of follow-up.^[15] There are several factors that must be considered to determine the success of LLLT in the management of oral lesions. A number of factors directly affect tissue healing by modifying it, slowing it down, and preventing complications associated with wound exposure. The main local and systemic elements that influence tissue wound healing are shown in [Table 1].^[16]

Table 1: Factors that influence healing^[16]

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There are three primary characteristics of tissue healing which can be impacted by LLLT. First, there is a rise in ATP production induced by laser. This increase in ATP production causes a rise in mitotic activity and protein synthesis by mitochondria which resulted in more tissue regeneration during the healing process. Second, increased microcirculation which speeds up the mitotic process and promotes cell division by increasing the delivery of nutrients such as protein, carbohydrate, and vitamins. Finally, laser stimulates new vessel formations. The development of new blood vessels which is essential for wound healing occurs concurrently during all phases of repair. The neutrophils, macrophages, platelet-derived growth factor (PDGF), and transforming growth factor 1 (TGF-1) that are released during the hemostatic phase stimulate angiogenesis in addition to drawing in other cell types. Acute granulation tissue is made up of proliferating fibroblasts, macrophages, vascularized stroma, collagen, fibrinogen, fibronectin, and hyaluronic acid. This tissue then replaced the fibrin-based provisional matrix that was created during the early stages of wound healing.^[17]

Tissue healing is directly impacted by a number of circumstances that affect the process, slow it down, and enable complications from wound exposure. In our study, the aphthous lesions of the first and second patients recovered within 3–7 days. A history of low iron levels was considered to be the cause of prolonged ulcer healing in the third patient. There are a number of ways iron deficiency may delay wound healing. According to recent research, hypoxia has a significant effect. Hypoxia-inducible factor-1 (HIF-1) and positive HIF-1 regulators, such as prolyl-4-hydroxylase inhibitors, play roles in all stages of wound healing. HIF-1 is involved in cell migration, hypoxic cell survival, cell division, growth factor release, and matrix formation.^[18] The effectiveness of LLLT must also be evaluated with respect to the application site, wavelength, duration, and dosage.^[19]

Nasry et al.^[3] demonstrated the application of 970-nm diode lasers for the treatment of RAS in noncontact mode. The laser beam was delivered using a fiber-optic tip with a 320-µm diameter. Then, 5–8 mm away from the lesion, the laser’s diode was started in a defocused mode, moved slowly toward the area, and finally stopped 2–3 mm away. It was then continuously moved from the lesion’s periphery to its center and moved away from the lesion if the patient felt warmth. The setting was maintained at 0.8 W for 30–45 s. The laser treatment consisted of one sitting which started at day 0. Each sitting consisted of a maximum of four sessions of applications. In this study, a significant reduction in ulcer size and pain—about 50% from the initial condition—was observed on days 2 and 5. In comparison, in our study, the patients were each treated two times with irradiation by an 830-nm diode laser (4000 Topline LASER, BTL, United Kingdom) with irradiation times of 36 and 57 s/cm² sequentially. All three patients reported a significant decrease in pain scores immediately after the application of LLLT. Over the following days, there was no repetition of the LLLT and 48 h after the application of LLLT, the pain VAS score was reduced to 0.

An increase in ATP synthesis brought on by LLLT results in hyperpolarization and stimulus blockage, which lessens the induction of pain stimuli. The mechanism of LLLT’s increased ATP synthesis is mostly based on the photoreceptors’ ability to absorb red and near-infrared wavelengths in specific subcellular mitochondrial components, especially in the electron transport (respiratory) chain.^[20] Suter et al.^[21] found that a wavelength of 830 nm had the most significant treatment effect on pain. A wavelength of 809 or 810 nm was favorable for reducing pain in RAS treatment using a laser. In contrast, a broader spectrum of LLLT wavelengths is effective in the reduction of pain: reduction of immediate pain occurs at 670, 810, and 940 nm, and reduction of late pain occurs at 658, 809, and 810 nm. However, there was no improvement in late pain with LLLT at 670 nm.^[21]

The energy of photons from LLLT is turned into photochemical, photophysical, and photobiological effects when administered with the proper dosage. These outcomes include mast cell activation, lymphocyte stimulation, and enhanced ATP synthesis. Other cell types, including fibroblasts and macrophages, have also been found to proliferate as a result of LLLT. Together, fibroblasts and macrophages encourage both biostimulatory and anti-inflammatory effects, which promote wound healing.^[16] Energy density seems to play an important role as photobiostimulation is favorable at low doses (<2 J/cm²), while at higher doses (>16 J/cm²), it has mostly been described as suppressive.^[21]

Further research is needed to assess the effectiveness of LLLT in various oral lesions, not only minor ulcerations. Katara et al.^[22] showed that the use of LLLT as a treatment for arteriovenous malformation, homogeneous leukoplakia, mucocele, traumatic fibroma, and erosive lichen planus offered promising results, although follow-up and thorough evaluation are needed to see if the lesions can be completely healed. A study on the efficacy of LLLT as a treatment for oral mucositis by Tarigan and Wimardhani^[23] showed that the severity of the lesions was reduced, and up to 70% of the patients claimed that their discomfort subsided immediately after receiving LLLT.

Kathuria et al.^[24] proposed that LLLT for treating herpes simplex labialis resulted in a significant reduction in pain immediately after the first session, and all signs and symptoms had disappeared by the fifth day. In addition, LLLT has been used effectively in mucositis therapy and has been able to reduce the incidence of inflammation and pain. Several mechanisms have been involved in pain reduction and the therapeutic effects of low-level laser effects on temporomandibular disorder. These mechanisms include promoting the release of endogenous opioids, enhancing cell respiration and tissue healing, increasing vasodilatation, increasing the pain threshold by affecting the cellular membrane potential, and decreasing inflammation, possibly due to the reduction of prostaglandin E2 and suppression of cyclooxygenase-2 levels.^[24]

LLLT is a safe and clinically effective method for treating oral lesions, and it also provides time benefits to patients, in terms of healing time reduction. The significant outcomes of the present study are immediate and lasting pain relief and accelerated ulcer healing. Limitations of this therapy include the subjective evaluation of pain perception and host immune responses that may interfere with the healing process. VAS is a method for evaluating patient-reported pain. Measurements using this method may vary depending on a number of factors, such as the patient’s pain thresholds. For instance, it is feasible for individuals who frequently encounter recurrent ulceration to have higher pain thresholds than those who have recently experienced recurrent ulceration. Immune cells modulate wound healing by promoting cellular cross-talk via secreting signaling molecules, including cytokines, chemokines, and growth factors. For successful wound healing, a delicate balance in this process needs to be maintained.^[25]

Conclusion

The utilization of LLLT as a treatment for lesions in the oral cavity is very promising; it may even end up being a primary form of ulcer therapy in the future, lessening the necessity for pharmacological therapy. All conditions that may interfere with the tissue-healing process must be considered to determine the success of LLLT as a management for oral lesions. Dentists must be able to determine whether LLLT can be applied to patients as an independent therapy or whether other modalities should be added to improve treatment outcomes.

Declaration of patient consent

The written consent from the patient/patient’s guardian was gained to publish the article which contains photographs or other materials from the patient in an issue of the Scientific Dental Journal.

Acknowledgements

We would like to express our gratitude to Prof. Armasastra Bahar, DDS, Ph.D., for his encouragement and thoughtful support. And, special thanks to Bold Technologies Leading Indonesia for the opportunity and kind assistance during the use of LLLT in our clinic.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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