Gingival enlargement due to Cyclosporine A therapy in aplastic anaemia.

Sir,

Cyclosporine A, an immunosuppressant belonging to the class of calcineurin inhibitors, is an effective component in the treatment of aplastic anaemia (AA). The important side effects of chronic cyclosporine treatment include nephrotoxicity, hypertension, hyperglycemia, seizures, and opportunistic infections.[1] Gingival enlargement is a complication of cyclosporine therapy that is known to affect one fourth to one third of renal or cardiac transplant patients who receive traditional therapy with this drug.[2] However, data in the context of AA is limited; an American study describes an odds ratio of 27 for the development of this complication.[3]

A 32 year old male was admitted with pneumonia, sepsis with pancytopenia and absolute neutrophil count of 126/mm3. He had been diagnosed with severe AA one year back and responded to a course of anti-thymocyte globulin. Thereafter, he was maintained on oral cyclosporine capsules at a dose of 10 mg/kg/day for six months, with monthly monitoring to ensure trough serum levels between 150 and 200 ng/mL. He remained asymptomatic and transfusion-free till the present admission. On examination, marked enlargement of both upper and lower gingiva was noted, with enlarged tissue engulfing the teeth [Figures 1 and 2]. There was presence dental plaque poor oral hygiene. These were incidental findings, with no specific complaints from the patient. There were no associated petechiae, bleeding, herpetic lesions, tenderness or halitosis. Unfortunately, the patient rapidly succumbed to septic complications despite intensive therapy with appropriate antimicrobials, blood products and mechanical ventilation.

Figure 1

Enlarged upper and lower gingival tissue engulfing plaque-affected teeth

Figure 2

Another view of the lower gums showing extent of enlargement on lingual aspect of the teeth and poor oral hygiene

Cyclosporine A has been suggested to alter the metabolic function of gingival fibroblasts by increasing interleukin-6 secretion, which enhances collagen and glycosaminoglycan synthesis and reduces collagen breakdown.[1] It also affects T lymphocytes, which play a pivotal role in the periodontal antibacterial immune response.[4] The severity of gingival enlargement correlates with the degree of oral hygiene and concomitant use of drugs such as the calcium channel blocker, nifedipine; contrasting findings exist however, regarding correlation with duration of therapy or serum levels of the drug.[1] Notably, our patient was maintaining recommended drug levels and had in fact, presented with treatment failure. Also, neutropenia itself is contributory and gum overgrowth may be the presenting feature of AA.[5]

The incidence of enlarged gums is reported to be lower with the newer formulation of cyclosporine based on microemulsion technology.[6] Different therapeutic approaches have been proposed. Use of specific oral hygiene programs, psychosocial support, surgery (laser excision over conventional gingivectomy) and/or alternative pharmacological therapy (metronidazole, azithromycin, roxithromycin) have been reported.[17-10] If left untreated, patients may develop severe periodontal disease and even lose teeth.