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LETTER

Treatment of Cyclosporine-Induced Gingival Hypertrophy

right arrow Emanuela Cecchin, MD; Fabrizia Zanello, MD; and Sergio De Marchi, MD

1 March 1997 | Volume 126 Issue 5 | Pages 409-410


TO THE EDITOR:

Gingival hypertrophy is a complication of cyclosporine therapy that affects one fourth to one third of patients receiving renal or cardiac transplants who receive traditional therapy [1]. The incidence of this adverse effect is lower with the new formulation of cyclosporine, which is based on a microemulsion technology [2]. The improvement of cyclosporine-associated gingival hypertrophy has been reported with metronidazole in transplant recipients [3, 4]. Cyclosporine is effective in the treatment of rheumatoid arthritis, but little is known about the prevalence of gingival hypertrophy and the treatment of this condition in patients with rheumatoid arthritis.

A 40-year-old woman who had rheumatoid arthritis according to the criteria of the American Rheumatism Association began receiving cyclosporine in December 1995. She had had rheumatoid arthritis for less than 5 years and had previously received prednisone. The initial daily dose was 2.5 mg of the new oral formulation of cyclosporine (Sandimmun Neoral, Sandoz-Wonder Pharma, SA, Switzerland) per kg of body weight and was cautiously increased until serum trough levels of 120 to 150 ng/mL were reached. Cyclosporine improved the clinical symptoms and signs of rheumatoid arthritis. However, substantial gingival hypertrophy was noted 3 months after the beginning of therapy, when the patient was receiving the stabilization dosage of 3.5 mg/kg per day. Grading of gingival hypertrophy before and after metronidazole was done according to the method of Matarasso, which provides four grades (0 to 3) of increasing severity. The patient received a 14-day course of metronidazole, 750 mg three times daily. At the end of therapy, the grade of gingival hypertrophy had changed from grade 3 to grade 2. Over the next 2 weeks, the condition remitted completely (grade 0). Six months later, it had not recurred. We saw no increase in serum cyclosporine and creatinine levels during metronidazole therapy.

We suggest that a course of metronidazole should be tried in patients with rheumatoid arthritis and cyclosporine-induced gingival hypertrophy. This treatment may be effective and safe. Distinct anaerobic gram-negative bacteria, such as Porphyromonas gingivalis, are involved in the pathogenesis of various forms of chronic periodontal disease [5]. Cyclosporine affects T lymphocytes, which play a pivotal role in the periodontal antibacterial immune response [5]. It is not known whether the response of cyclosporine-induced gum hypertrophy to metronidazole in patients with rheumatoid arthritis is mediated through the antibacterial effect of metronidazole or through another mechanism.


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University of Udine Medical School, 33100 Udine, Italy


References
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1. Pernu HE, Pernu LM, Knuuttilia ML, Huttunen KR. Gingival overgrowth among renal transplant recipients and uraemic patients. Nephrol Dial Transplant. 1993; 8:1254-8.

2. Milanes CL, Arminio A, Barrios Y, Garcia-Ramirez R, Herrera J, Leon I, et al. Safety in the switching traditional cyclosporin to microemulsion cyclosporin in stable renal transplant patients: cooperative study. Invest Clin. 1995; 36:183-96.

3. Wong W, Hodge MG, Lewis A, Sharpstone P, Kingswood JC. Resolution of cyclosporin-induced gingival hypertrophy with metronidazole. Lancet. 1994; 343:986.

4. Seymour HR, Goldsmith D, Sharpstone PS, Kingswood JC. Treatment of cyclosporin-induced gum hypertrophy. Nephrol Dial Transplant. 1996; 11:1434.

5. Yamazaki K, Nakajima T, Hara K. Immunohistological analysis of T cell functional subsets in chronic inflammatory periodontal disease. Clin Exp Immunol. 1995; 99:384-91.

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