Chemotherapy-induced oral cc in a patient with acute lymphoblastic leukaemia.
Abstract: BACKGROUND: Oral mucositis is the main complication of chemotherapy and radiotherapy used in the treatment of cancer. Phototherapy has proven effective in the treatment of mucositis, as it accelerates the tissue healing process and has both analgesic and anti-inflammatory properties. CASE REPORT: This paper reports the case of a paediatric patient with oral mucositis stemming from chemotherapy employed for the treatment of acute lymphoblastic leukaemia. TREATMENT: The lesions were treated daily with a light-emitting diode (LED). FOLLOW-UP: Remission of the lesions occurred after 10 days of treatment. CONCLUSIONS: LED was effective in the treatment of mucositis, as it diminished pain symptoms and accelerated the tissue repair process.

Key words: acute lymphoblastic leukaemia, children, chemotherapy, oral mucositis, phototherapy.
Article Type: Clinical report
Subject: Acute lymphocytic leukemia (Care and treatment)
Chemotherapy (Complications and side effects)
Mucositis (Risk factors)
Cancer (Chemotherapy)
Cancer (Complications and side effects)
Authors: Rimulo, A.L.
Ferreira, M.C.
Abreu, M.H.
Aguirre-Neto, J.C.
Paiva, S.M.
Pub Date: 04/01/2011
Publication: Name: European Archives of Paediatric Dentistry Publisher: European Academy of Paediatric Dentistry Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 European Academy of Paediatric Dentistry ISSN: 1818-6300
Issue: Date: April, 2011 Source Volume: 12 Source Issue: 2
Geographic: Geographic Scope: Brazil Geographic Code: 3BRAZ Brazil
Accession Number: 277106755
Full Text: Introduction

Acute lymphoblastic leukaemia accounts for 80% of all leukaemia cases in children and young adults [Ziegler et al., 2005]. Chemotherapy is one of the main forms of treatment for leukaemia and consists of the use of different drugs that act on malignant cells as well as normal cells in constant division, such as hair, mucosa and the haemopoietic system [Nikoui and Lalonde, 1996]. Oral mucositis is the most frequent and debilitating stomatological complication in patients undergoing chemotherapy for leukaemia and other cancers [Kostler et al., 2001; Epstein and Schubert, 2004].

Mucositis is clinically manifested as erythema, ulcerations, oedema and bleeding. In the oral mucosa, this condition involves the ventral portion of the tongue, floor of the mouth and soft palate [Scully et al., 2004]. With the evolution of the lesion, there is an increased risk of infection, pain, compromised food intake and impaired speech--all of which exert a significant impact on quality of life. Depending on the severity of the process, the cancer treatment may need to be altered or even interrupted, which affects the remission of the disease, cure rates and treatment costs [Sonis et al., 2000; Hejna et al., 2001; Epstein and Schubert, 2004; Scully et al., 2004; Sonis, 2004; Brown and Wingard, 2004; Glenny et al., 2010].

Among the different therapies tested for reducing the impact of oral mucositis, low-level laser therapy has proven effective in accelerating the tissue healing process and has both analgesic and anti-inflammatory properties [Barasch et al., 1995; Bensadoun et al., 1999; Epstein and Schubert, 2004; Scully et al., 2004; Silva et al., 2010; Cauwels and Martens, 2011]. Originally developed by the American National Aeronautics and Space Administration, the light-emitting diode (LED) is a light source that is differentiated from laser for exhibiting a cheaper non-coherent light with a larger spread, making it an alternative to laser [Bensadoun et al., 1999; Whelan et al., 2001; Corti et al., 2006; Sacono et al., 2008]. LED can act in both a preventive and curative fashion [Whelan et al., 2001; Whelan et al., 2002].

This paper describes a clinical case of a paediatric patient in chemotherapy for the treatment of acute lymphoblastic leukaemia who developed oral mucositis, the lesions of which were treated with LED.

Case report

Medical history and examination. A five-year-old female patient undergoing in chemotherapy for the treatment of acute lymphoblastic leukaemia at the Santa Casa de Misericordia in the city of Belo Horizonte (Brazil), developed oral mucositis (Fig. 1a) as well as cellulitis on the palm side of the ring finger of the left hand. Chemotherapy was employed for the remission of the leukaemia, consisting of the administration of prednisone, vincristine, daunorubicin, L-asparaginase and methotrexate/ara-C/dexamethasone IT. The patient experienced febrile neutropaenia following the second dose of anthracycline, together with oral mucositis and cellulitis on the left ring finger. Infection was determined, the resolution of which occurred after haematological recovery associated with antibiotic therapy with meropenem and vancomycin.

Treatment. LED (FisioLED[R], MMOptics, Sao Carlos, SP, Brazil) emitted in the red band with a wavelength of 630 nm, 100 mW output power and point applications of 6.0 J/[cm.sup.2] was used for the treatment of the mucositis and cellulitis on a daily basis for ten consecutive days. For bio-safety purposes, the patient wore protective glasses (Uvex, Furth, Germany) and the device was covered with a polyvinyl chloride wrap (Delta Pack, Taboao da Serra, SP, Brazil). The clinical involution of the lesions was monitored daily using the Oral Mucositis Toxicity Scale [WHO, 1979]. A Visual Analogue Scale was used for the assessment of pain [Sung et al., 2007]. The procedure, possible discomfort and possible benefits were fully explained to the family, whose authorisation was obtained prior to treatment.

Prior to LED therapy, the patient had Grade 3 mucositis [WHO, 1979] and Grade 5 pain [Sung et al., 2007]. Mucositis was present in the form of ulcers on the lower lip, upper lip, labial commissure and side of the tongue as well as erythema on the dorsum of the tongue and oedema in the lips (Fig. 1a).

[FIGURE 1a OMITTED]

Follow-up. On the sixth day of treatment, the pain had reduced to Grade 2 and mucositis had reduced to Grade 1 (Fig. 1b). The following lesions were found: erythema on the upper lip as well as the dorsum, ventrum and side of the tongue and a scab aspect on the finger previously affected by cellulitis (Fig. 1c). On the tenth day, there was remission of the mucositis lesions (Figs 1d-e) and the lesion on ring finger of the left hand was healed (Fig. 1f). Despite the initial debilitating state of the patient, the treatment of the lesions was successful. LED therapy caused no pain, as the equipment did not come into contact with the lesion. At the end of treatment, the patient reported the alleviation of symptoms from the lesions.

[FIGURE 1b OMITTED]

[FIGURE 1c OMITTED]

[FIGURE 1d OMITTED]

[FIGURE 1e OMITTED]

[FIGURE 1f OMITTED]

Discussion

In the present case, oral mucositis developed on the fifth day of chemotherapy instituted for the treatment of acute lymphoblastic leukaemia. Mucositis commonly appears between 5 and 7 days after the beginning of medication. The most affected regions in the present case were the dorsum, ventrum and side of the tongue. The ventrum of the tongue is one of the most vulnerable sites to direct stomatoxicity, together with the soft palate, floor of the mouth and oral mucosa. In most cases, mucositis is limited to non-keratinised mucosa, as occurred in the present case [Kostler et al., 2001; Scully et al., 2004].

The cancer therapy agents vincristine and daunorubicin have a toxic effect on the mucosa [Kostler et al., 2001]. Either the use of these drugs or the cancer itself leads to neutropaenia, which predisposes the mucosa to mucostitis lesions and also enables bacterial invasion of the submucosa and vascular walls, leading to bacteraemia and septicaemia [Sonis, 2004; Brown and Wingard, 2004]. The patient in the case described here initially exhibited bacteraemia, the remission of which occurred following haematological recovery associated to the use of meropenem and vancomycin.

Prior to cancer therapy, the patient was submitted to an assessment of the oral cavity. Dental caries or periodontal disease associated with inadequate oral hygiene may lead to a greater risk for oral complications during the course of cytotoxic therapy. Odontogenic and gingival infections are a considerable source of bacteria, which aggravate oral mucositis lesions. These risk factors underscore the importance of an inspection of the oral environment before and during treatment that has a potentially toxic effect on the mucosa, as prior assessment allows differentiating oral mucositis from other pre-existing lesions as well as the elimination of potential sources of infection and sites of chronic irritation [Stevenson-Moore, 1990; Pajari et al., 1995; Brown and Wingard, 2004]. This conduct is part of the protocol for patients at the Oncology Clinic at which the present case was treated.

The patient and guardian were instructed with regard to the practice and benefits of oral hygiene. During the time the child was hospitalised, oral hygiene was performed by the a carer accompanying her. Oral hygiene contributes to the prevention and treatment of biofilm-dependent diseases, reducing the bacterial load and assisting in the treatment of complications stemming from oral mucositis. Even in patients with neutropaenia, the risk of bacteremia is reduced when oral hygiene is instituted on a regular basis [Kostler et al., 2001; Epstein and Schubert, 2004; Coulson, 2007]. Gargling with 0.12% chlorhexidine gluconate (5 ml) every 12 hours was also part of the treatment instituted for this patient, as evidence indicated that the use of this agent associated to oral hygiene was effective in the treatment of oral mucositis [Pereira Pinto et al., 2006].

Oral mucositis and associated pain are among the heaviest burdens experienced by patients receiving aggressive chemotherapy [Borbasi et al., 2002]. Immediate pain relief and improved wound healing has been reported using LLLT in children [Cauwels and Martens, 2011]. Pain stems from the exposure of nerve endings due to the breakdown of the mucosa. In the case reported here, a pain scale was used to assess the intensity of the pain associated to oral mucositis. This use of this scale assists in the determination of progress in the treatment of mucositis, as pain is the main symptom of the condition. At the beginning of treatment, the patient exhibited Grade 5 pain [Sung et al., 2007], which had diminished to Grade 2 by the sixth day of LED therapy. There was also a regression in mucositis, which went from Grade 3 [WHO, 1979] at the beginning of treatment to Grade 1 by the sixth day. This demonstrates that, as with laser therapy, LED has a curative effect on mucosa lesions [Whelan et al., 2001] and accelerates the healing process.

The effectiveness of LED is further demonstrated by the remission of the lesions after 10 days of treatment. The resolution of the initial clinical condition corroborates findings reported in the literature [Whelan et al., 2001; Corti et al., 2006; Sacono et al., 2008]. Unlike the study carried out by Corti et al. [2006], in which LED therapy was performed three times a day for seven consecutive days, in the present case, LED was applied once a day for 10 consecutive days. However, in both situations, the daily application of chlorhexidine gluconate was part of the treatment used. Regarding the indices used for the assessment of mucositis, the first study employed the Daily Mucositis Index (DMI) [Tardieu et al., 1996], the gradation of which ranges from 0 to 3 and assesses different aspects in the lips, gums, oral mucosa and tongue. In the present case, the WHO scale [1979] was employed, which ranges from 0 to 4 and does not measure different aspects in the different sites analysed. Moreover, the aforementioned study assessed the lesions only on the first and last days of treatment, whereas the assessment was performed on a daily basis in the present case.

It should be stressed that, regardless of the therapy instituted to treat oral mucositis, the maintenance of oral hygiene is essential to the prevention/treatment of complications stemming from this condition as well as a reduction in the duration and severity of the lesions and, consequently, the pain. Education in oral health with a particular emphasis on oral hygiene should be part of the daily routine of patients in an oncological program. Dentists should collaborate in the establishment of an oral health protocol as well as assess the patient prior to and during treatment for cancer. Thus, the inclusion of a dentist to the oncological team is fundamental. Moreover, the institution of guidelines should be based on clinical evidence that sustains and stimulates the maintenance of oral health.

Preventive and treatment strategies for mucositis have provided patients in treatment for cancer with a better quality of life. In the present case, LED therapy proved effective in the treatment of oral mucositis, as it diminished pain symptoms with each therapy session and accelerated the tissue repair process. The choice of LED was based on the characteristics attributed to this light source, such as a lower cost and greater spreading of light in comparison to low-level laser therapy. This enables a larger tissue area to be reached and consequently reducing the application time. These characteristics are incentives for carrying out randomised clinical trials that can either confirm or refute the effectiveness of the treatment instituted in the present case.

Conclusion

LED was effective in the treatment of mucositis, as it diminished pain symptoms and accelerated the tissue repair process.

Acknowledgments

This study was supported by the State of Minas Gerais Research Foundation (FAPEMIG), Brazil.

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A.L. Rimulo *, M.C. Ferreira **, M.H. Abreu ***, J.C. Aguirre-Neto ****, S.M. Paiva **

* School of Dentistry, Itauna University, Minas Gerais, Brazil, ** Department of Paediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Minas Gerais, Brazil, *** Department of Preventive and Social Dentistry, School of Dentistry, Federal University of Minas Gerais, Brazil, **** Service of Clinic Oncology of the Santa Casa de Misericordia de Belo Horizonte, Minas Gerais, Brazil.

Postal address: Meire Coelho Ferreira. Dept Paediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil.

Email: meirecofe@ig.com.br
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