Trophic skin ulceration in leprosy: evaluation of the efficacy of topical phenytoin sodium zinc oxide paste.

BACKGROUND: The trophic or chronic plantar ulcer of leprosy is one of the principle causes of disability and deformity in the disease and has been given due importance in the evolution of its classification. In view of the diversity of its clinical implications, the World Health Organization was obliged to bring this entity under its remit in order to develop uniform guidelines to be applied around the globe. Despite relentless endeavor, its management continues to represent a dilemma. OBJECTIVES: The role of topical phenytoin sodium in wound healing led this group to evaluate its efficacy in the healing of trophic or chronic plantar ulcers. The success of the therapy was assessed according to the extent of regression in the size of the ulcer(s) following the formation of granulation tissue. METHODS: Forty patients released from leprosy control were recruited. A retrospective diagnosis was made in each case, and patients were grouped accordingly. Demographic data were recorded after the provision of informed consent. Bacterial cultures before and after treatment, and radiography were performed in each case. A phenytoin sodium fine powder zinc oxide paste dressing was applied every day for four weeks. Granulation was graded according to its appearance in order to evaluate the success of the topical therapy. RESULTS: Of the 40 patients, 26 (65.0%) borderline lepromatous leprosy patients had trophic ulcers, with the ball of the great toe being the most common site. Twelve (30.0%) patients had bone involvement. A total of 22 (55.0%) patients achieved complete resolution of the ulcer, and evidence of granulation formation was seen in 33 (82.5%) patients. The clearance of bacterial load after treatment was a significant finding. Zinc oxide paste per se was not effective, but its role as a vehicle was an asset. CONCLUSIONS: Phenytoin sodium zinc oxide paste was found to be an efficacious, cost-effective, and well-tolerated alternative therapy. Patient compliance was good. Bone involvement contributed to poor wound healing, but the clearance of bacterial load was significant.

Topical phenytoin suspension and normal saline in the treatment of leprosy trophic ulcers: a randomized, double-blind, comparative study.

OBJECTIVE: To evaluate and compare two strengths of topical phenytoin sodium suspension (2% and 4%) with normal saline in the healing of acute trophic ulcers in leprosy patients. METHODS: A prospective, parallel, double-blind, randomized study was conducted in 45 leprosy inpatients with acute trophic ulcers. Patients were randomized to receive 2%, 4% or normal saline dressing on their ulcers once daily for 4 weeks. Efficacy parameters such as a reduction in the surface area of the ulcer, bacterial culture of the ulcer swab, appearance of healthy granulation tissue, cessation of ulcer discharge and overall gradation of clinical healing and safety were assessed at weekly intervals. RESULTS: The ulcer area reduction was greater in the 2% and 4% phenytoin groups compared with the normal saline group (p<0.001). Appearance of healthy granulation tissue and cessation of ulcer discharge was also observed earlier in the two phenytoin groups. At the end of 4 weeks, 11 ulcers each had healed completely in both the 2% and 4% phenytoin groups compared with none in the control group. There were no statistical differences between the 2% and 4% phenytoin groups. No side effects were reported by any patient. CONCLUSION: Topical phenytoin appears to be an effective, safe and cheap therapeutic option for the healing of trophic ulcers in leprosy patients.

Topical phenytoin for wound healing.

Oral phenytoin is used widely for the treatment of convulsive disorders and about half the patients treated develop gingival overgrowth as a side effect. The apparent stimulatory effect has prompted its assessment in wound healing. Studies have shown topical phenytoin to promote healing of decubitus ulcers, venous stasis ulcers, diabetic ulcers, traumatic wounds, burns, and leprosy trophic ulcers. The mechanism of action has been postulated to be multifactorial. The present literature indicates that topical phenytoin deserves further investigation as a wound-healing agent in controlled dose-finding clinical trials.

The use of topical phenytoin as an adjunct to immobilization in the treatment of trophic leprosy ulcers.

A total of 30 leprosy patients (controls n = 16; topical phenytoin n = 14) with trophic ulcers on the feet were investigated to ascertain the efficacy of topical phenytoin powder in the healing of ulcers. The ulcers in the two groups were matched for initial size. Healing patterns were assessed by determining changes in depth and planar (surface) dimensions at weekly intervals over a three week study period. Results indicate that while immobilization of the ulcer site is effective in promoting ulcer healing, additional use of topical phenytoin accelerates the healing process. There may however be non-responders to topical phenytoin.

Comparison of topical phenytoin with normal saline in the treatment of chronic trophic ulcers in leprosy.

BACKGROUND: Trophic ulceration, one of the most common complications of leprosy, is disabling, distressing, and demoralizing for the patient. METHODS: The wound healing effects of topical phenytoin powder were compared with those of normal saline in a controlled in-patient study of 100 patients with 110 trophic leprosy ulcers of varying chronicity, over a 4-week study period. Fifty patients were assigned to the topical phenytoin group and 50 to saline therapy group. Ten patients had two ulcers each, and, in these cases, one ulcer was treated with phenytoin and the other with saline. RESULTS: Over the 4-week treatment period healthy granulation tissue appeared earlier, and mean percentage of ulcer volume reduction was greater, in the phenytoin group (72.1 +/- 19.9% versus 55.5 +/- 21.6%) compared with the control group. CONCLUSIONS: This difference was statistically significant at the level of P < 0.001. Phenytoin appears to be a useful agent for the promotion of healing of trophic leprosy ulcers.

Effect of route of administration on phenytoin teratogenicity in A/J mice.

Acute administration of the anticonvulsant drug, phenytoin (PHT) has been shown to result in embryotoxicity and teratogenicity in several strains of mice. The A/J strain is reported to be most susceptible to the effects of the drug including an increased incidence of resorptions and orofacial clefts in treated animals. When administered chronically, the drug has been shown to be teratogenic in the absence of maternal toxicity and embryolethality in Swiss Webster mice [Hansen and Billings, 1985]. In this paper, we have compared the embryopathic effects of chronic and acute administrations of PHT to A/J mice. PHT was administered to pregnant females by intraperitoneal (i.p.) injection on day 10 of gestation at a dose of either 60 or 75 mg/kg body weight. Alternatively, PHT was added to ground chow and fed to animals prior to and throughout gestation; animals received a daily dose of either 60 or 75 mg/kg body weight. Pregnant animals were sacrificed on day 18 or 19 of gestation, and fetuses were examined for the presence of orofacial clefts and other anomalies. There was a significant increase in the frequency of cleft lip and palate in animals receiving the drug by i.p. administration, but there was no increase in the incidence of clefts if the drug were added to the diet. The results of this study reiterate the importance of the route of administration of a drug in determining its embryopathic effect.