Low level light therapy in the management of paediatric oral and oropharyngeal mucositis

Oral and oropharyngeal mucositis

Oral and oropharyngeal mucositis occurs in 52–80% of children undergoing treatment for cancer.¹ Mucositis is a debilitating condition which can be so severe that it can delay or stop oncology treatment. The mucositis disease process is initiated by chemotherapy or radiotherapy at 0–2 days, followed by cell damage at 2–10 days. Frank ulceration and mucosal damage occurs at 10–15 days, finally healing after 2–3 weeks. The clinical presentation is a combination of erythema and ulceration; and as healing begins, mucosal sloughing affects the intra-oral tissues and oesophageal tract (Figure 1). Maintaining adequate oral hygiene is difficult due to oral discomfort which may further exacerbate the condition and increase a patient's vulnerability to developing infection. The consequences for paediatric patients are significant: eating, drinking, speaking and engaging with those around them can be significantly restricted. This presents concerns regarding recovery and physical and mental wellbeing. Psychological distress has been described by parents of children suffering from mucositis at a time when stress and anxiety of the parent and child is already amplified by many other factors.²

Mucositis can be graded using the ‘World Health Organization (WHO) Grading,’ which comprises gradings zero to four (Table 1).³ Both the clinical presentation and functional outcomes form the basis for this grading system.

Management of mucositis

General management of mucositis often involves a mixture of preventive and symptomatic control measures such as: oral hygiene instruction, soft diet, cryotherapy, protective gels, analgesics (ranging from paracetamol and non-steroidal analgesia to narcotic analgesia), topical anaesthetics, benzydamine hydrochloride sprays or mouthwashes and chlorhexidine and calcium phosphate mouthrinses. Many of these, for example mouthwashes, require a certain degree of co-operation and maturity which not all paediatric patients will have.

Mucositis is such a common and significant problem in oncology that many different guidelines have been developed to assist practitioners. Guidelines published in 2012 by the The Royal College of Surgeons of England and The British Society for Disability and Oral Health⁴ recommend benzydamine hydrochloride mouthwash, cryotherapy, intravenous keratinocyte growth factor-1 (palifermin), anaesthetic mouthwash and analgesia as options to consider in the management of mucositis. More recent guidelines published in 2014 by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) similarly advise most of the afore-mentioned interventions, along with other weaker evidence for options such as doxepin mouthwash and zinc supplements.⁵ A guideline by Sung et al in 2015 included a weak recommendation for cryotherapy to prevent mucositis.⁶ Both MASCC/ISOO⁵ and Sung et al⁶ also recommend LLLT as an option for managing mucositis. It is anticipated with new evidence emerging that all future guideline revisions will also soon advocate low level light therapy.

Low level light therapy

Low level light therapy (LLLT) is emerging as an effective treatment modality in both medicine and dentistry for a range of conditions. LLLT involves the use of a low power laser emitting less than 500 mW on the red or near infra-red spectrum with light wavelengths of 600–1000 nm. On applying the light to areas of the body, cells are stimulated, thereby reducing inflammation, increasing cell metabolism and inducing endorphins. A Dental Update article by Milward et al in 2014⁷ described the mechanism of action, including wound repair, analgesia and anti-inflammatory effects. The combination of cellular effects has led to this therapy becoming a widely studied topic and gathering increasing attention from the medical and dental professions. Despite the growing body of evidence, a recent systematic review by Hadis et al⁸ found inadequacies in the reporting of LLLT studies, with incomplete information available on wavelength, light source type, power, pulse frequency, beam area, irradiance, exposure time, radiant energy and fluence.

As mentioned, LLLT can be considered for a number of different conditions. Research in medical patients has resulted in a Cochrane review on the use of LLLT in rheumatoid arthritis, providing evidence that it reduces pain and stiffness.⁹ Systematic reviews on its use in treating trigeminal neuralgia¹⁰ and recurrent aphthous ulceration¹¹ are also available in the literature. Ayyildiz et al discuss LLLT for use on patients suffering from temporomandibular joint dysfunction (TMD) with limited mouth opening.¹² There has also been research involving orthodontic patients concerning the potential for LLLT to accelerate tooth movement and also reduce orthodontic-related pain.^13,14

Low level light therapy and mucositis

In the literature there have been many studies involving LLLT as a treatment modality for oral and oro-pharyngeal mucositis. In a systematic review with meta-analysis by Bjordal et al,¹⁵ low level light therapy was shown to reduce pain, severity and duration of mucositis. This paper included 11 randomized placebo-controlled trials with a total of 415 patients. The relative risk of developing mucositis was found to be significantly reduced after LLLT when compared to a placebo (RR = 2.03, p value = 0.02). In patients with mucositis, the number of days patients had mucositis was found to be reduced for severity gradings 2 or more from 4.38 days to 1.33 days compared with a placebo.

A randomized controlled study by Khun et al,¹⁶ in 2009, recommended LLLT as a first-line option in paediatric patients with chemotherapy-induced oropharyngeal mucositis. The trial compared treatment for mucositis with a placebo for 5 days with LLLT for the same duration of time. Twenty-one patients were included in the study, with the number of days in which patients had mucositis decreasing from a mean duration of 8.9 days with a placebo to a mean duration of 5.8 days with LLLT.

The benefits that LLLT can offer to the paediatric patient appear to be significant. As this is often a patient group where co-operation may be limited; quick, efficient and effective treatment is necessary. In addition, paediatric oncology patients in particular are a group where the prevention of infection and pain are of paramount importance.

Low level light therapy use for paediatric patients in Glasgow

Currently in the Royal Hospital for Children (previously The Royal Hospital for Sick Children) in Glasgow, LLLT is used daily in the management of oro-pharyngeal mucositis by the Paediatric Dentistry Department. It is often used in conjunction with previously described measures such as mouthrinses, analgesia and protective gels. The paediatric dental team makes regular visits to the oncology ward and has a good relationship with the ward staff, allowing a team approach to the provision of LLLT. LLLT is delivered using a Diobeam 830 laser (830 nm) with an output of 150 mW (Figure 2). Bensadoun and Nair recommended that wavelengths of 633–685nm or 780–830nm and power output between 10 and 150mW are used to treat mucositis.¹⁷

Initially, an extra- and intra-oral examination by a qualified dentist determines the areas affected by mucositis and a WHO mucositis grading is assigned. An administered dose (J/cm²) is then delivered according to the severity of mucositis.³ The paperwork completed for each treatment episode used can be seen in Figure 3. Although in Glasgow the ’laser’ is primarily used for symptomatic mucositis, a lower joules/cm² setting is available for use on healthy mucosa, which would allow for prophylactic treatment. The Diobeam laser is classed as a 3B laser, which means that it carries an ocular hazard. Local laser safety precautions are employed, such as using safety glasses to protect the patient, parent's and user's eyes. The laser is used in an approved room which has blinds on the windows, a locked door and safety signs displayed outside. LLLT is not visible but has a red guide light to help the user to visualize the target area and an auditory guide for when the laser is active. Treatment is painless. Similar to radiographic regulations, there are also local laser rules which have to be followed and training must be completed prior to any clinician delivering treatment.

A pilot study completed in 2012 involving 15 patients demonstrated a statistically significant reduction in self-reported pain levels for children who had treatment with LLLT for mucositis. A larger, retrospective case note analysis was then undertaken, comprising 319 separate LLLT sessions in 39 patients undergoing LLLT treatment from January 2013 to July 2014. Paediatric patients with symptomatic oropharyngeal mucositis were included (aged 4–17 years-old). Patients were excluded from this analysis if they were not able to communicate their pain score due to communication ability or age. The Diobeam 830 Laser was used for all treatment, with administered dose (J/cm²) varying according to the severity of mucositis (WHO scale 1–4). The pain scores (0–10) were recorded prior to and immediately post-treatment on a visual/faces analogue scale, along with daily neutrophil counts. Neutrophils are the most common white blood cell and, in this group of patients, the counts vary greatly depending upon their stage of disease and type of treatment.

Results

The results are summarized in Tables 2 and 3 and Figures 4 and 5. The most common WHO grade for mucositis was Grade 3 (extensive erythema and ulceration and cannot swallow a solid diet). A statistically significant change in pain score was noted with the median change of pain score being 2 (P-value <0.0005). No statistically significant relationship between neutrophil count and pain response was found (P-value = 0.263), or indeed between pain response and type of tumour (blood/solid) (P-value = 0.121).

Parents, staff and patients have embraced LLLT, finding it easy and beneficial, with regular requests for treatment and many positive reports. The ward and dental team work closely to ensure that LLLT is available to those patients who need it and it has been widely accepted by the medical team as an effective management tool for mucositis.

Currently in Glasgow, due to resources and staff availability, LLLT is mainly provided when patients develop symptomatic mucositis. Our research has shown the ability to reduce pain in this patient group and this theoretically should reduce the need for narcotic analgesia and allow patients to maintain oral diets. This has been supported, with one of the pain nurses in Glasgow stating that, ‘the laser provides better pain relief than ketamine.’

A patient explained when asked about LLLT, ‘my mouth was a 10/10, now it's a 0/10.’ Figueiredo et al, in 2013,¹⁸ conducted a meta-analysis of the prophylactic use of LLLT to prevent mucositis and showed a significant positive effect. This research may extend our provision of LLLT, utilizing the lowest setting on the laser to provide this.

Conclusion

As with all new technologies, availability and cost naturally become less of a consideration over time. Access to LLLT across medical and dental services will no doubt improve, alongside cost-effectiveness. A study by Bezinelli et al (2014) has already demonstrated that oncology patients with mucositis not treated with LLLT had 30% higher hospitalization costs,¹⁹ an important finding for NHS hospitals under mounting financial pressures. Provision of LLLT is straightforward, quick and effective for many conditions. LLLT use within the specialist dental services continues to expand throughout the UK, transforming the care we are able to provide routinely. Its use is also expanding in other areas of dental health and it will be interesting to see what the future holds for this remarkable technology.