Adjunctive use of antimicrobial photodynamic therapy ...

Case Report

Adjunctive use of antimicrobial photodynamic therapy in periodontal treatment of a patient susceptible to osteoradionecrosis Abdul Ahad, Shruti Tandon, Arundeep K. Lamba, Farrukh Faraz Department of Periodontics, Maulana Azad Institute of Dental Sciences, New Delhi, India

ABSTRACT Photodynamic therapy (PDT) has emerged as an adjunct to conventional periodontal therapy since its antimicrobial effect has been discovered. The oral health of patients with head and neck cancer undergoing radiotherapy or those who have completed such treatment deteriorates as oral tissues, including the periodontium, are adversely affected. Vascular changes, in particular, predispose the periodontium for degeneration and also reduce the potential of tissues to regenerate following periodontal surgery. Since periodontal surgical procedures or extraction of teeth carries the risk of osteoradionecrosis (ORN) in such cases, a conservative approach with nonsurgical measures is preferred for the treatment of periodontal diseases. This report highlights a case of treatment of localized chronic periodontitis around endodontically treated teeth in a patient with history of radiotherapy for the treatment of oral cancer. In addition to mechanical debridement, PDT was used to disinfect the moderately deep periodontal pockets, resulting in significant improvement. No complication was observed after therapy and good periodontal health has been maintained for the last 18 months. Keywords: Osteoradionecrosis, periodontitis, photodynamic therapy, radiotherapy

INTRODUCTION Photodynamic therapy (PDT), also known as photoradiation therapy, phototherapy, or photochemotherapy, is a treatment modality that has been developing rapidly within various medical specialties since the 1960s. It has been defined as “the light induced inactivation of cells, microorganisms, or molecules.” PDT has been used in the treatment of premalignant lesions and recurrent tumors after previous surgery or chemotherapy. It has also been used for superficial infections like candidiasis and Herpes simplex virus infections. Use of PDT as an Access this article online Quick Response Code: Website: www.craniomaxillary.com DOI: 10.4103/2278-9588.163267

antimicrobial therapy is based on the concept that an agent (photosensitizer), usually a phenothiazine compound, which absorbs light can be preferentially taken up by bacteria and subsequently activated by light of appropriate wavelength in the presence of oxygen to generate singlet oxygen and free radicals that are cytotoxic to bacteria. These cytotoxic species can damage plasma membranes and DNA, resulting in cell death. Other microorganisms such as fungi, viruses, and protozoa can also be killed by singlet oxygen species generated from PDT. PDT has been reported to provide additional benefits over scaling and root planing (SRP) in terms of reduction of the bleeding indices, reduction of probing depth, and improvement in clinical attachment level (CAL) if strict plaque control is maintained.[1‑3] The potential benefits of PDT in periodontal therapy can be best utilized in cases of deep pockets and

Correspondence to: Dr. Abdul Ahad, Department of Periodontics, Maulana Azad Institute of Dental Sciences, New Delhi - 110 002, India. E-mail: [email protected]

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other less accessible sites. However, it is also useful in shallower pockets as the bacteria that penetrate the gingival tissue cannot be eliminated by mechanical instrumentation alone. PDT can also be used in cases of recurrent or refractory periodontitis not responding to nonsurgical mechanical treatment and certain conditions where periodontal surgery is not feasible due to medical status of the patient. Radiotherapy is either an effective alternative or a valuable adjunct to surgery and/or chemotherapy in the treatment of malignant head and neck tumors. Care of the oral health of patients with head and neck cancer undergoing radiotherapy or who have completed treatment is important as oral tissues including the periodontium are adversely affected. Decreased cellularity and vascularity of the periodontal ligament, thickening and disorientation of Sharpey's fibers and widening of periodontal space have been observed.[4] Vascular changes, particularly obliterating endarteritis, predispose the periodontium to degeneration.[5] Osteoradionecrosis (ORN) is a bone ischemic necrosis that is one of the most serious consequences of radiotherapy, causing pain as well as substantial loss of bone structure.[6] Due to radiotherapy, bone cells and the vascularization of bone tissues may suffer irreversible injuries. ORN may occur spontaneously or more commonly after trauma. Periodontal infection of teeth at high dose‑radiated sites has been found to be the second most common precipitating factor for ORN after postradiation tooth extractions.[7] In addition, it reduces the potential of tissues to regenerate following periodontal surgery. Since inadequate healing and reduced potential of tissue regeneration following periodontal surgical procedures after radiotherapy carries the risk of ORN, a conservative approach with nonsurgical measures is preferred. Although antimicrobial photodynamic therapy (aPDT) has been used widely as an adjunctive modality in the treatment of chronic and aggressive periodontitis, its use in patients who are susceptible to ORN has not been reported. This report highlights the case of treatment of localized moderate periodontitis around endodontically treated maxillary premolars in a patient with history of hemimandibulectomy and 158

radiotherapy for the treatment of carcinoma on the floor of the mouth. In addition to mechanical debridement, PDT was used to disinfect the moderately deep periodontal pockets. Bleeding on probing, pocket depth, and mobility reduced significantly after treatment. No complication was observed after therapy and good periodontal health has been maintained for the last 18 months.

CASE REPORT A 60‑year‑old female was referred by an endodontist for the management of mobility in the right upper premolars. There was history of root canal therapy completed in the same teeth 3 weeks back. The patient also complained about reduced mouth opening, dryness of mouth, and difficulty in speech and chewing. She had undergone surgery and radiotherapy for malignancy on the floor of the mouth 5 months back. No other relevant medical history was reported. On examination, her face was found to be asymmetric and the lower jaw deviated to the right. Her mouth opening was significantly limited [Figure 1]. On intraoral examination, oral hygiene was found to be inadequate. The left part of the mandible distal to the canine was missing. There were multiple missing teeth as the patient reported extractions before the radiotherapy. Gingival recession was present in all the remaining maxillary teeth. Over-contoured bridge, impinging on buccal gingiva was found at teeth #44, #45, and #46. Mucosa and gingiva were found to be dry since salivary flow was reduced. Cervical restoration was found on the buccal aspect of teeth #14 and #15 with grade II mobility [Figure 2]. Bleeding was observed on probing and pocket depth of 6 mm was found on the palatal aspect of both premolars [Figures 3 and 4]. Panoramic radiograph was suggestive of left partial hemimandibulectomy, generalized moderate periodontal bone loss, widening of periodontal spaces, periapical rarefaction with root canal treated #14 and #15, and cantilever bridge at #44, #45, and #46 [Figure 5]. Periapical radiograph revealed the presence of angular bone defect around #14 and #15 [Figure 6].



Figure 1: Asymmetry of the face and reduced mouth opening

Figure 2: Dry gingiva and oral mucosa

Figure 3: Periodontal pocket on palatal aspect of #14. Bleeding on probing present

Figure 4: Periodontal pocket on palatal aspect of #15. Bleeding on probing present

Management Supragingival scaling was done on the first visit, along with oral hygiene instructions. The patient was educated about the importance of meticulous plaque control after radiotherapy. She was also explained about the chances of failure of periodontal therapy if strict oral hygiene was not maintained. Risk of ORN was also explained if the teeth needed to be extracted in case of failure of conservative treatment. Root planing followed by antimicrobial PDT were planned in the mobile right maxillary premolars. On the following visit, root planing was done in #14 and #15 with Gracey curettes (Hu-Friedy, Chicago, IL, USA). Pocket was irrigated with normal saline. After hemostasis was achieved, PDT was performed as per following steps:

• Injection of photosensitizer dye, i.e. phenothiazine chloride at concentration of 10 mg/mL (Helbo® Blue Photosensitizer, Bredent Medical, Senden, Bavaria, Germany) in the bottom of the pocket using a blunt cannula until it appeared flowing over the gingival margin [Figure 7] • Following the instructions of the manufacturer, the dye was left in the pocket for a duration of 3 minutes • The pocket was irrigated by normal saline to remove excess dye as it can act as an optical shield during laser irradiation [Figure 8] • Pocket was irradiated with a diode laser (Helbo® Theralite laser, Bredent Medical, Senden, Bavaria, Germany), circumferentially at six sites per tooth for 1 minute (10 seconds


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Figure 5: Panoramic view

Figure 6: Periapical radiograph showing root canal treated #14 and #15

Figure 7: Injection of photosensitizer dye in the periodontal pocket

Figure 8: Pockets irrigated with normal saline

Figure 9: Photosensitizer dye activated by diode laser

each for the mesiobuccal, buccal, distobuccal, mesiooral, oral, and distooral surfaces of tooth) 160

at a wavelength of 660 nm and power density of 100 mW/cm2 [Figure 9]



• Application times of both the photosensitizer and laser light were monitored by a time controller (Helbo® T-Controller, Bredent Medical, Senden, Bavaria, Germany) [Figure 10]. An interdental brush was advised to be used for cleaning the proximal surfaces of the teeth in addition to fluoridated toothpaste and sodium fluoride mouthwash. Threaded floss was advised for cleaning the undersurface of the bridge in the mandibular arch. The patient was recalled after 1 week to check her adherence to oral hygiene instructions. On the seventh postoperative day, inflammation was found to be resolved and no bleeding was observed. There was an improvement in oral hygiene while mobility reduced from grade II to grade I. The patient was put on supportive periodontal therapy. She was advised to adhere to the routine plaque control procedures and report every month for follow‑up. Supragingival scaling was repeated on every following visit. There was a continuous improvement in oral health throughout the past 1 year. After 3 months, periodontal pockets around the palatal aspect of #14 and #15 reduced to 3 mm from an initial depth of 6 mm. SRP and PDT were repeated at 6 months when mild bleeding was found on probing the pockets around #14 and #15. After 18 months of follow‑up, there was no bleeding on probing while the probing depth on the palatal aspect continues to be 3 mm [Figure 11].

DISCUSSION Radiotherapy may produce both acute and

Figure 10: Helbo® Photodynamic System

late complications in human tissues. Acute effects generally subside several weeks after the completion of treatment and are not a major problem. Late effects are a major concern because the tissue injury is progressive and permanent. The late effects of radiotherapy for head and neck cancers include damage to the salivary glands with resultant xerostomia, damage to the dentition, mucosal and muscular fibrosis, soft tissue ulceration, and ORN. ORN is a severe debilitating condition that may follow radiotherapy for head and neck malignancies. The maxilla and the mandible are particularly susceptible to this complication. Contrary to the common perception, risk of ORN continues indefinitely after undergoing radiotherapy.[8] Although not very common, periodontal disease sites have been reported to be susceptible to the development of ORN. Galler et al. (1992)[8] described three cases of development of ORN from the sites of periodontal disease activity. He suggested that despite the presence of a healthy periodontium present immediately after radiation, ORN may develop with fulminating severity when oral care deteriorates. Poor oral hygiene has been related to rapid onset of ORN.[9] The literature suggests that if strict periodontal management and follow‑up are planned, it is possible to avoid the development of ORN. In the present case, recent history of radiation therapy, periodontitis, stress, history of previous periodontal disease and tooth loss, reduced mouth opening leading to inadequate oral hygiene

Figure 11: Probing depth after 15 months. No bleeding on probing


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maintenance, and poor nutritional status due to inability to chew solid food were making the patient susceptible to the development of ORN. SRP may be adequately useful in mild‑to‑moderately deep pockets. In deeper pockets (≥6 mm), however, adjunctive treatment becomes necessary as complete debridement is not achieved by SRP alone. Galler et al. (1992) suggested various options for the treatment of periodontitis in patients at risk of ORN including subgingival irrigation with 2% chlorhexidine gluconate or local drug delivery as an adjunct to SRP.[8] However, PDT offers many advantages over irrigation with chlorhexidine or local delivery of antibiotics. These include localized, broad spectrum effect without any risk of development of resistance. It is easy to use without any adverse effect on the body cells. No repetition is required until gingival bleeding reappears. A plausible explanation for reduction in bleeding on probing could be bacterial load reduction and inactivation of bacterial virulence factors and cytokines when the photosensitizer dye is irradiated with laser.[10] Pinheiro et al. (2010) showed a significantly greater reduction in the percentage of viable bacteria in periodontal pockets treated with aPDT (96%) compared to those treated with SRP only (81%).[11] de Oliveira et al. (2009)[12] also observed reduction in crevicular proinflammatory cytokines, tumor necrosis factor‑alpha (TNF-α), and receptor activator of nuclear factor kappa‑b ligand (RANKL) levels in patients with periodontitis who were subjected to PDT. Although biofilms have been reported to reduce the effectiveness of PDT, it is not as much as reported in the case of antibiotics. Due to decreased vascularity of the periodontium, the option of surgical periodontal therapy is generally not feasible for patients who have undergone radiotherapy as it can hardly regenerate the lost alveolar bone. Additionally, extraction and periodontal surgical procedures carry the risk of developing ORN. Thus, antimicrobial PDT proved to be an effective means to control periodontal disease in the present case. Since after radiotherapy ORN can develop at the sites of periodontal disease activity and poor oral hygiene is associated with rapid development of ORN, strict periodontal maintenance program 162

can help in prevention. PDT may be added as an adjunctive modality to nonsurgical treatment of periodontitis in patients at risk of ORN. To establish it as an alternative to surgical periodontal treatment in patients of radiotherapy, controlled clinical studies need to be carried out.

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