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Wild Chamomile (Matricaria Recutita L.) Mouthwashes in Methotrexate- Induced Oral Mucositis

Posted on: Sunday, 20 March 2005, 03:00 CST

Abstract

Oral mucositis is a known complication of methotrexate (MTX) therapy, but a single efficacious intervention or agent for prophylaxis or management of this side effect has not yet been identified. We report a case of MTX-induced oral mucositis in a patient with rheumatoid arthritis, who was successfully treated with Wild chamomile mouthwashes.

2004 Elsevier GmbH. All rights reserved.

Keywords: Wild chamomile; Matricaria recutita L; Methotrexate; Oral mucositis; Aplastic anaemia

Introduction

Methotrexate (MTX), a broad-spectrum anti-cancer agent, is used to treat a number of autoimmune diseases, including rheumatoid arthritis. Oral mucositis is a known complication of MTX therapy, reducing the quality of life of the affected patients, and a significant risk factor for systemic infections, particularly in neutropenic patients (Kostler et al., 2001).

The dried flower heads of the plant Chamomile have been widely used in traditional and herbal medicine for centuries because of its anti-inflammatory, spasmolytic, antipeptic, sedative, antibacterial and antifungal properties (Avallone et al., 2000; Zanoli et al., 2000; Fidler et al., 1996). In this report we describe an interesting case of MTX-induced oral mucositis in a patient with rheumatoid arthritis, who was successfully treated with Wild chamomile (Matricaria chamomilla L. [= Chamomilla recutita (L.) Rauschert], Asteraceae) mouthwashes.

Case report

A 76 year-old woman was presented with a 48-h history of high- grade fever (up to 39 C) and a progressively worsening odynophagia and dysfagia. In her previous medical history she had rheumatoid arthritis. This disease had been diagnosed eleven years previously, and a combination of corticosteroids (prednizolone 5 mg/day), MTX (10 mg/week), and folic acid (5 mg/week) having been prescribed ten days prior to admittance. Unfortunately, the patient had mistakenly taken MTX 10 mg/daily instead of the prescribed 10 mg weekly dose. On examination she had a temperature of 38.6C, a pulse rate of 78/ min, respiratory rate 15/min, and blood pressure 120/80 mmHg. On examination of the mouth there was grade 3 mucositis (oral ulcers, liquid diet only), according to World Health Organization (WHO) criteria (WHO, 1979), secondary to overdose of MTX. The initial investigations showed: haematocrit 33%; haemoglobin (Hb) 11 gr/dl (normal range, female: 12-16gr/dl), white cell count (WBC) 3.0 10^sup 9^/1 (neutrophils 1.4 10^sup 9^/l, lymphocytes 1.5 10^sup 9^/1, monocytes 0.1 10^sup 9^/1); platelet count 131 10^sup 9^/1; erythrocyte sedimentation rate 73 mm/lh; normal biochemical parameters and urinalysis. An electrocardiogram and a chest X-ray were both within normal limits. The MTX was discontinued, calcium folinate was commenced and the dose of corticosteroids was increased. The patient refused to receive the suggested combination of chlorhexidine and nystatin or allopurinol mouthwashes (Kostler et al., 2001; Montecucco et al., 1994). Instead the patient was administered a liquid preparation of Wild chamomile (adding 8 gr of the dried flowers into 1000 ml of boiling water, covering and leaving to steep for 15min) for mouthwashes. The chamomile mouthwashes (gargles) were well tolerated and repeated 4 times daily; the suggested amount and duration of each mouthwash was 20 ml of the preparation for 1-2 min. On the 9th day of hospitalization the laboratory tests showed: Hb 8 gr/dl; WBC 1.5 10^sup 9^/l (neutrophils 0.1 10^sup 9^/l, lymphocytes 1.2 10^sup 9^/l, monocytes 0.2 10^sup 9^/l); platelet count 19 10^sup 9^/l (normal- sized platelets in peripheral blood smear); corrected reticulocyte index 0.6% (absolute reticulocyte count 4 10^sup 9^/l). The bone marrow aspiration showed severe hypocellularity secondary to a marked decrease in megacaryocytes, granulocytes, and erythroid cells; the morphology of the marrow elements was normal. Serological tests for bacteria and viruses were negative, and multiple blood cultures were also repeatedly negative. MTX serum levels were not determined and a gastroscopy was not performed. Based on the International Aplastic Anemia Study Group criteria (Camitta et al., 1983; Rozman et al., 1987), a diagnosis of very severe aplastic anaemia due to an overdose of MTX was defined. Two packed leukocyte- depleted red cells transfusions and haematopoietic growth factor [three doses of 300 meg subcutaneously filgrastim: recombinant human granulocyte colony stimulating factor (G-CSF)] were administered with rapid response. On the 13th day of hospitalization the oral mucositis was moderate (grade 2: oral erythema, ulcers, able to eat solids) (WHO, 1979), and was completely healed within four weeks of admittance.

Discussion

The term oral mucositis emerged in the late 1980s to describe the chemotherapy- and radiotherapy-induced inflammation of the oral mucosal cells (Kostler et al., 2001). Although the pathogenesis of oral mucositis is not fully understood, it is thought to involve direct or indirect mechanisms, but more recent pathophysiologic concepts have emerged characterizing oral mucositis as having four phases (inflammatory/vascular, epithelial, pseud omembraneous ulcerative/bacteriological, and healing phase) (Kostler et al., 2001). Moreover, a linear relationship between the occurrence of oral mucositis, oral and systemic granulocyte counts, and a coincidence of resolution of mucositis with neutrophil recovery has been demonstrated (Kostler et al., 2001).

The efficacy of Wild chamomile as a mucosa protective agent has only been evaluated in two studies, and their results are controversial (Carl and Emrich, 1991; Fidler et al., 1996). The Chamomile plant contains many different substances with anti- inflammatory, anti-bactrerial, and antifungal properties, as chamazulene; alpha bisabolol, bisabol oxides, spiroethers, and flavonoids (Fidler et al., 1996). Considering the local microbial colonization of damaged mucosal surfaces which occurs in the pseudomembraneous/ulcerative phase of oral mucositis and is exacerbated by concomitant neutropenia (Kostler et al., 2001), the intervention with chamomile mouthwashes and the effects of the above components might be responsible for the reduction of oral mucositis in our patient.

A single efficacious intervention or agent for prophylaxis or management of chemotherapy-induced oral mucositis has not yet been identified (Kostler et al., 2001). Chamomile is inexpensive and readily available. Some, generally mild, side effects have been reported (Kostler et al., 2001), but close monitoring is recommended for patients who are taking anticoagulants such as warfarin (Heck et al., 2000). Further well-designed studies are needed to confirm the clinical efficacy of this plant.

References

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Camitta, B., O'Reilly, R.J., Sensenbrenner, L., Rappeport, J., Champlin, R., Doney, K., August, C., Hoffmann, R.G., Kirkpatrick, D., Stuart, R., Santos, G., Parkman, R., Gale, R.P., Storb, R., Nathan, D., 1983. Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia. Blood 62, 883-888.

Carl, W., Emrich, L.S., 1991. Management of oral mucositis during local radiation and systemic chemotherapy: a study of 98 patients. J. Prosthet. Dent. 66, 361-369.

Fidler, P., Loprinzi, C.L., O'Fallon, J.R., Leitch, J.M., Lee, J.K., Hayes, D.L., Novotny, P., Clemens-Schutjer, D., Bartel, J., Michalak, J.C., 1996. Prospective evaluation of a chamomile mouthwash for prevention of 5-FU-induced oral mucositis. Cancer 77, 522-525.

Heck, A.M., DeWitt, B.A., Lukes, A.L., 2000. Potential interactions between alternative therapies and warfarin. Am. J. Health Syst. Pharm. 57, 1221-1227.

Kostler, W.J., Hejna, M., Wenzel, C., Zielinski, C.C., 2001. Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment. CA Cancer J. Clin. 51, 290-315.

Montecucco, C., Caporali, R., Rossi, S., Porta, C., 1994. Allopurinol mouthwashes in methotrexate-induced stomatitis. Arthritis. Rheum. 37, 777-778.

Rozman, C., Marin, P., Nomdedeu, B., Montserrat, E., 1987. Criteria for severe aplastic anaemia. Lancet 2, 955-957.

WHO handbook for reporting the results of cancer treatment, 1979. WHO Offset Publications, Geneva, Series number 48. sold by WHO Publications Centre USA, Albany, NY.

Zanoli, P., Avallone, R., Baraldi, M., 2000. Behavioral characterisation of the flavonoids apigenin and chrysin. Fitoterapia 71, S117-S123.

E.E. Mazokopakis, G.E. Vrentzos, J.A. Papadakis, D.E. Babalis, E.S. Ganotakis*

Department of Internal Medicine, University General Hospital of Heraklion Crete, P.O. Box 1352, 71110 Heraklion, Crete, Greece

Received 4 September 2003; accepted 24 November 2003

* Corresponding author. Tel.: +281-0-392360; fax: +281-0-392847

E-mail address: ganotak@med.uoc.gr (E.S. Ganotakis).

Copyright Urban & Fischer Verlag Jan 2005

Source: Phytomedicine

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