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CASE REPORT Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 3  |  Page : 365-369
Rehabilitation of exacerbated case of oral mucositis associated with renal failure following bone marrow transplantation


Department of Rehabilitation Science, Post- Graduation Program, Nove de Julho University - UNINOVE, São Paulo - SP, Brazil

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Date of Submission14-Nov-2007
Date of Decision25-Apr-2008
Date of Acceptance22-May-2008
Date of Web Publication30-Oct-2009
 

   Abstract 

Inflammation of oral mucosa induced by anti neoplastic drugs is an important, dose limiting and costly side effect of cancer therapy. Here is presented an exacerbated case of oral mucositis associated with renal failure in a patient who underwent bone marrow transplantation. The clinical aspects and an integrated rehabilitation program are discussed below.

Keywords: Bone marrow transplantation, chemotherapy, mucositis, renal failure

How to cite this article:
Pavesi V, Martins M, Seneda L M, Massumoto C, Fernandes K, Bussadori S K, Martins M D. Rehabilitation of exacerbated case of oral mucositis associated with renal failure following bone marrow transplantation. Indian J Dent Res 2009;20:365-9

How to cite this URL:
Pavesi V, Martins M, Seneda L M, Massumoto C, Fernandes K, Bussadori S K, Martins M D. Rehabilitation of exacerbated case of oral mucositis associated with renal failure following bone marrow transplantation. Indian J Dent Res [serial online] 2009 [cited 2019 Aug 24];20:365-9. Available from: http://www.ijdr.in/text.asp?2009/20/3/365/57373
Mucositis is a common and debilitating complication for patients undergoing anti neoplastic therapy characterized by inflammation of oral and gastrointestinal mucosa. Its incidence ranges from 70-80% among patients receiving high dose chemotherapy with total body irradiation and 30- 50% of patients receiving high dose chemotherapy alone. [1],[2],[3]

According to the pathogenic model of mucositis, chemotherapy and radiation treatment cause DNA damage which leads to the generation and amplification of an inflammatory process, resulting in loss of mucosal integrity and painful lesions. It primarily affects the non-keratinized surface of oral mucosa, probably due to the smaller rate of cell renewal in these areas. Lesions tend to recur at the same site in each episode of mucositis. [4]

Some factors contributing to the occurrence and intensity of mucositis include type of tumor and type of drug used. Patients with hematological tumors generally develop more mucositis than those with solid tumors. Other interfering factors include the patient's general health status, age, nutritional state and oral hygiene. [5],[6]

The first signs of oral mucositis include edema and erythema of mucosa, and as symptoms, patients report increased sensitivity to warm and seasoned food. Erythematous zones may evolve into foci of ulceration with whitish pseudo membrane formation which when removed leave a bloody and painful layer. [4]

Clinically, mucositis is graded in a simpler grading system determined by the World Health Organization in which both objective and subjective criteria are taken into account. It is divided into grade 0-no symptom; 1- sore mouth, no ulcers; 2- sore mouth with ulcers, but able to eat normally; 3-oral ulcer with liquid diet only; and 4-oral ulcer and patient unable to eat or drink. [7]

Mucositis presents a broad range of issues with financial, clinical, and personal consequences. Patients with severe mucositis may experience pain requiring opioid analgesics, a higher risk of infection, total parenteral nutrition (TPN), increased hospital charges, and decreased quality of life. [8]

Prophylaxis and treatment of mucositis refer to measures taken prior to and after the onset of this complication, respectively. Many agents have been tested for this purpose. However, they are mostly based on palliation of symptoms (topical anesthetics, anti-inflammatory agents, systemic analgesics) and prevention of secondary infections (antimicrobial agents). The most promising procedure seems to be use of low-energy laser. [9],[10]

Current recommendations for the prevention of oral mucositis include cryotherapy only with 5 FU bolus, benzydamine only in head and neck radiation patients and low-level laser therapy. Many other agents for treatment of oral mucositis have been reported in literature but there is insufficient evidence to support their use. Recently, keratinocyte growth factor (Palifermin) was reported to reduce the duration and incidence of oral mucositis. However, it was only approved for oral mucositis after intensive chemotherapy and radiotherapy in autologous hematopoietic stem cell transplantation (HSCT). [11],[12]

The purpose of this work is to report clinical and rehabilitation aspects of an exacerbated case of oral mucositis associated with renal failure in a patient who underwent Bone Marrow Transplantation (BMT).


   Case Report Top


The patient, a 53-year-old pediatrician from Sao Paulo, sought a medical nephrologist following increased urinary volume and abundant foam in urine. Laboratorial tests gave the following results: Hb 9.3 mg/dL; Platelet count 191,000/mm 3 ; Creatinine 2.0 mL/dL; Hyper gammaglobulinemia 1.7 g/dL.

The nephrologist referred the patient to a hematologist who performed a myelogram by puncture of the iliac crest. The findings: Increased number of typical mature plasma cells and Bence Jones proteinuria positive, as well as 1690 mg/dL serum immunoglobulin (IgM) (RR 50- 300 mg/dL), indicating multiple myeloma. To confirm the diagnosis a bone marrow biopsy was performed and sent for immunohistochemical study. The result confirmed the diagnostic hypothesis of light chain Kappa IgM-type Multiple Myeloma.

The patient then underwent cycles of chemotherapy with VAD (vincristine, adriamycin, and dexamethasone) associated with a Bisphosphonate (Aredia® ). Conditioning of the marrow was performed using Melphalan 200 mg/m 2 .

Five days (D-5) prior to BMT the patient was referred to a group of dental surgeons (oral medicine team) for pre- transplant evaluation and follow-up. An intra-oral physical exam was conducted in which the mucosa was found intact. The general dental and gingival health status evaluation showed no need for dental intervention.

As per protocol, in patients undergoing autologous BMT, dental surgeons conducted preventive sessions for mucositis with laser diode applications at 780 nM, 60W power output and 2.5 J/cm, 2 point-to-point, for conditioning the mucosa from D-5 until D+2.

By day three post-BMT (D+3), the patient developed Grade 2 mucositis and supportive treatment was initiated with topical corticoid (Celestone elixir) associated with an antifungal agent (Mycostatin), through mouthwashes three times a day, in addition to oral antiseptics (Cariax), lip moisturizer (Ceralip), artificial saliva (Oral Balance) and topical lidocaine prepared with gelatin and taken prior to meals. Daily laser application with the same parameters used earlier was done.

Five days post-BMT (D+5), the patient developed an ulcerated lesion on the upper lip diagnosed as recurring labial Herpes [Figure 1], in addition to pseudo membranous candidiasis at the back of the tongue [Figure 1]a, grade 3 mucositis with countless erosive erythematous areas and ulcerated lesions on the lower labial mucosa, and right and left edges of the tongue [Figure 1]b-d.

By D+8, the patient showed renal failure and exacerbation of oral lesions, leading to grade 4 mucositis [Figure 2], depriving the patient of oral food intake.

From D+8, through D+35, she had two hemodialysis sessions performed. From the thirty-fifth day on, she showed significant gradual improvement of mucositis lesions [Figure 3] with only one lesion at the back of the tongue [Figure 3]a from which material was collected for a PCR assay, for detection of Cytomegalovirus (CMV) and herpes simplex virus (HSV), which turned out negative for both.

The patient reported a significant relief in pain after daily laser application. Forty-five days following BMT, mucositis had completely resolved without leaving any marks or scars.


   Discussion Top


Multiple myeloma (MM) is a hematological malignancy characterized by abnormal proliferation of immunoglobulin-secreting plasma cells. Manifestations of MM may include anemia, osteolytic lesions, and renal dysfunction. Renal insufficiency is often associated with this pathology due to the urinary system overload as a result of the metabolism of this immunoglobulin in excess. Treatment for this disease chiefly consists of corticosteroids, bisphosphonates, chemotherapy, and hematopoietic stem-cell transplantation. [13]

In this case, in accordance with literature, [13] the patient had MM and underwent aggressive chemotherapy sessions that cause complete bone marrow aplasia and after that was done the substitution with healthy marrow from the patient (autologous transplant).

High doses of chemotherapy affect mucosal integrity, resulting in pain, increased risk of infection and an impaired nutritional state. [2],[14],[15] The present case presented with mucositis, fungal and viral infection as side effects of chemotherapy and BMT treatment. These sequelae and others such as nausea, vomiting, diarrhea, weight loss, hypo salivation, and taste alterations have been described. [16]

The mucositis was the most severe complication of oncologic treatment in this case. This was awaited since patients treated with Melphalan had been associated with severe mucositis. Usually mucosal injury associated with oral mucositis results in the development of diffuse, painful ulcerative lesions typically within two weeks of receipt of conditioning regimens. However, the mucositis presented here had a long time course based on the fact that the patient developed renal failure and the chemotherapy agents could not be eliminated and the mucositis was maintained.

In patients undergoing BMT, with mucositis, an increased risk of developing fever and systemic infection is seen. This is due to the marrow aplasia, and subsequent state of immunosuppression. At the same time, the need for PN, analgesia with narcotic drugs, the length of hospital stay also increases. [2],[15]

According to Brennan et al. there is a growing body of evidence that supports the benefits of consistently applied oral care protocols. [16] Maintaining optimal oral health to minimize oral complications such as infection, bleeding, pain, and dryness are important. An interdisciplinary team approach, nursing, medicine, and dentistry, is vital to prevent oral complications during chemotherapy treatment. The nursery team must be in contact with the medical and dental professionals because they check prescriptions daily and orient the patient. On other side, the medical and dental professionals need to know of the effects of the treatment on oral mucosa because some of these complications could lead to the interruption of the oncologic treatment. However, even under preventive and integrated protocols the patients could develop complications.

The dental team protocol used in this case to prevent and minimize oral complications was based on three key components described by the foundations [8] of supportive care in cancer patients that includes: Basic oral care, oral care protocols and patient education, and palliative care including pain management.

Prior to transplantation (daily follow-up visits and dental interventions as needed), maintenance of good oral heath to minimize the risk of local or disseminated infection from an oral source were done. At present, there is no clinically appropriate prophylaxis efficacious antidote for mucositis. To prevent oral mucositis we used low intensity laser. In some cases, like in this one, it is palliative. However, they could reduce severity of oral mucositis and improve oral health status and quality of life.

The patient developed the oral mucositis on D+3 and the supportive treatment was initiated with topical corticosteroid, anti fungal and anti septic mouthwashes, associated with lip moisturizer, artificial saliva and topical lidocaine. As described prior in the literature, current treatments such as oral hygiene and patient-controlled analgesia are not successful in preventing or treating severe oral mucositis. [17] In an attempt to diminish discomfort in this patient and promote healing of the oral ulcers, we used the daily application of low intensity laser on the oral mucosa. It has been proposed that lasers have anti-inflammatory effect and are effective in controlling mucositis-associated pain. This therapeutic modality seems to influence the healing of the mucous membrane through the acceleration or the replication of myofibroblasts of the oral cavity, without, apparently, presenting any side effect. [18],[19] A few trials have demonstrated the clinical effects of low intensity laser therapy on the prevention and reduction of severity of oral mucositis. [10],[20],[21] The MASCC/ISOO mucositis guidelines propose that laser therapy, although expensive and requiring specific training for its utilization, seems to have beneficial effects in the prevention and treatment of oral mucositis.

Antunes et al. randomized 38 patients undergoing autologous or allogenic hematopoietic stem cell transplantation. [10] In the low intensity laser therapy group, 94.7% of patients had grade less than or equal to 2 oral mucositis, including 63.2% with grade 0 and 1, whereas in the controls group, 31.5% of patients had grade 2 oral mucositis. The results of ulcer area and grade of oral mucositis indicate that the use of prior low laser therapy in BMT patients is a powerful instrument in reducing the incidence of oral mucositis. Sandoval et al. observed that low energy laser was well tolerated, and showed beneficial effects on the management of oral mucositis, improving quality of life during the oncologic treatment of patients undergoing chemo- and radiotherapy. [22]

The patient treated in this study, even under a strict prevention and treatment protocol of oral complications associated with chemotherapy, did develop a very long (35 days) episode of severe mucositis. This was because the patient had evidence of renal failure prior to transplant, with exacerbation by D+8. From D+8 through D+35, the patient underwent two hemodialysis sessions, a fact reflected in a significant improvement of mucositis. Therefore, apart from the palliative and supportive care to minimize the complications of the anti neoplastic treatment, the dental surgeon should keep close contact with the interdisciplinary team treating the patient to better perceive eventual changes in the clinical course of the disease or the treatment.

 
   References Top

1.Scully C, Epstein J, Sonis S. Oral mucositis: A challenging complication of radiotherapy, chemotherapy, and radiochemotherapy: Part 1, pathogenesis and prophylaxis of mucositis. Head Neck 2003;25:1057- 70.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy induced mucosal injury: Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004;100:1995-2025.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Wardley AM, Jayson GC, Swindell R, Morgenstern GR, Chang J, Bloor R, et al. Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol 2000;110:292-9.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Kostler WJ, Hejna M, Wenzel C, Zielinski CC. Oral mucositis complicating chemotherapy and/or radiotherapy: Options for prevention and treatment. CA Cancer J Clin 2001:51:290-315.  Back to cited text no. 4      
5.Hoffmann T. Oral Mucositis: A Challenging Comlication of Radiotherapy, Chemotherapy and Radiochemotherapy: Part 1 pathogenis and prophylaxis of mucositis. Head Neck 2003;1057-70.  Back to cited text no. 5      
6.Avritscher EB, Cooksley CD, Elting LS. Scope and epidemiology of cancer therapy-induced oral and gastrointestinal mucositis. Semin Oncol Nurs 2004;20:3-10.  Back to cited text no. 6      
7.Parulekar W, Mackenzie R, Bjarnason G, Jordan RC. Scoring oral mucositis. Oral Oncol 1998;34:63-71.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 2004;100:2026-46.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Antunes HS, de Azevedo AM, da Silva Bouzas LF, Adao CA, Pinheiro CT, Mayhe R, et al. Low-power laser in the prevention of induced oral mucositis in bone marrow transplantation patients: A randomized trial. Blood 2007;109:2250-5.  Back to cited text no. 9      
10.Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE, et al. Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 2007;109:820-31.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Beaven AW, Shea TC. Recombinant human keratinocyte growth factor palifermin reduces oral mucositis and improves patient outcomes after stem cell transplant. Drugs Today (Barc) 2007;43:461-73.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Fliedner M, Baguet B, Blankart J, Davies M, Henriques E, Leather A, et al. Palifermin for patients with haematological malignancies: shifting nursing practice from symptom relief to prevention of oral mucositis. Eur J Oncol Nurs 2007;11:S19-26.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Molassiotis A. Managing oral mucositis in patients with haematological malignancies: The progress in European centres. Eur J Oncol Nurs 2007;11:S1-2.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]  
14.Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy: Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 2003;98:1531-9.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]  
15.Sonis ST, Oster G, Fuchs H. Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol 2001;19:2201-5.  Back to cited text no. 15      
16.Brennan MT, von Bultzingslowen I, Schubert MM, Keefe D. Alimentary mucositis: Putting the guidelines into practice. Support Care Cancer 2006;14:573-9.  Back to cited text no. 16      
17.Barasch A, Peterson DE. Risk factors for ulcerative oral mucositis in cancer patients: Unanswered questions. Oral Oncol 2003;3:91-100.  Back to cited text no. 17      
18.Bensadoun RJ, Franquin JC, Cias G. Low-energy He/Ne laser in the prevention of radiation-induced mucositis: A multicenter phase III randomized study in patients with head and neck cancer. Support Care Center 1999;7:217-8.  Back to cited text no. 18      
19.Karu TI. Photobiological fundamentals of low-power laser therapy. J Quantum Electronics 1987;23:1703-17.  Back to cited text no. 19      
20.Barasch A, Peterson DE, Tanzer JM, D'Ambrosio JA, Nuki K, Shubert MM, et al. Helion-neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients. Cancer 1995;76:2550-6.  Back to cited text no. 20      
21.Cowen D, Tardieu C, Schubert M, Peterson D, Resbeut M, Faucher C, et al. Low energy Helium-Neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: Results of a double blind randomized trial. Int J Radiat Oncol Biol Phys 1997;38:697-703.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]  
22.Sandoval RL, Koga DH, Buloto LS, Suzuki R, Dib LL. Manejo da mucosite oral induzida por quimioterapia e radioterapia com laser de baixa potência: Resultados iniciais do Hospital A C Camargo. J Appl Oral Sci 2003;11:337-41.  Back to cited text no. 22      

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Correspondence Address:
M D Martins
Department of Rehabilitation Science, Post- Graduation Program, Nove de Julho University - UNINOVE, São Paulo - SP
Brazil
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.57373

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