| Abstract|| |
Background: The optimal treatment for cutaneous leishmaniasis (CL) is not known. Topical paromomycin is one of the many drugs that have been suggested for the treatment of CL caused by Leishmania major. Recently, topical photodynamic therapy (PDT) has been reported to be effective in the treatment of CL. This study aimed to compare the parasitological and clinical efficacy of PDT versus topical paromomycin in patients with old world CL caused by L. major in Iran. Materials and Methods: In this trial, sixty patients with the clinical and parasitological diagnosis of CL were recruited and were randomly divided into three treatment groups with twenty subjects in each group. Group 1 was treated with weekly topical PDT and groups 2 and 3 received twice daily topical paromomycin and placebo, respectively. The duration of treatment was four weeks for all groups. These groups were followed up for 2 months after the end of treatment. Results: 57 patients with 95 lesions completed the study. At the end of the study, complete improvement was seen in 29 of 31 (93.5%), 14 of 34 (41.2%) and 4 of 30 (13.3%) of the lesions in group 1, 2 and 3 respectively ( P <0.001). At the same time point, 100%, 64.7 and 20% of the lesions had parasitological cure in group 1, 2 and 3, respectively ( P <0.001). Conclusion: Topical PDT can be used safely as a rapid and highly effective alternative choice for treatment of old world CL in the selected patients.
Keywords: Cutaneous leishmaniasis, photodynamic therapy, paromomycin, topical therapy
|How to cite this article:|
Asilian A, Davami M. Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of old world cutaneous leishmaniasis: A placebo-controlled, randomized clinical trial. Indian J Dermatol 2006;51:182-5
|How to cite this URL:|
Asilian A, Davami M. Comparison between the efficacy of photodynamic therapy and topical paromomycin in the treatment of old world cutaneous leishmaniasis: A placebo-controlled, randomized clinical trial. Indian J Dermatol [serial online] 2006 [cited 2020 Aug 3];51:182-5. Available from: http://www.e-ijd.org/text.asp?2006/51/3/182/27980
| Introduction|| |
Isfahan province is an endemic area for cutaneous leishmaniasis (CL) in Iran, where the most prevalent infectious agent is Leishmania major. Although CL is a self-healing disease, the resulting disfigurement and the duration of the disease require an effective treatment. The optimal treatment for CL is not known. Among the topical preparations, paromomycin ointment has been advised as a first line treatment in uncomplicated CL. Recently, efficacy of PDT in the treatment of CL has been reported in a few case reports and case series.,,
| Materials and Methods|| |
This randomized, placebo-controlled clinical trial was performed in the Department of Dermatology, Isfahan University of Medical Sciences, between September 2004 and May 2005. Subjects in both paromomycin and placebo groups and clinicians treating them were blinded with respect to the identity of the topical treatment that they received. However, it was not possible to blind subjects in PDT group. The study protocol and informed consent form were approved by Isfahan University of Medical Research Committee. Sample size determination was obtained from this formula:
I confidence limits = 95% (a=0.05), power = 80%, P1= 97% (cure rate of CL lesions with PDT (4), P2=61% (an estimation of cure rate of CL lesions with topical paromomycin (pilot study) and drop out = 15%, n (sample size) and number of lesions will be twenty patients and forty lesions, respectively, for each group, at maximum.
People were excluded for any of the following reasons: number of the lesions more than 2 or lesions with greater than 2 cm of induration diameter, duration of the disease more than 2 months, previous use of any antileishmanial treatments, pregnant or nursing women, children under 5 years of age, serious concomitant medical problems, history of seizure and photosensitivity. So, 60 patients with clinically typical CL confirmed by positive Giemsa-stained direct smear for Leishman-Donovan body were included. All of them were new cases. The patients were divided into three twenty-subject groups randomly: Group 1, which included 31 lesions, was treated with PDT. In this group ten percent 5-ALA (5-aminolevulinic acid hydrochloride GMP, Biosynth AG, Switzerland) in a water in oil cream was applied topically on the lesion(s) with a 5 mm margin of perilesional normal skin by the physician and the area covered with an occlusive dressing for 4 hours. After being sure of accumulation of 5-ALA in the leishmaniasis lesion(s), as revealed by fluorescence of the lesions on exposure to Wood's light, we irradiated them using visible red l = 633 nm light (Omnilux PDT, phototherapeutics, UK) at 100J/cm 2sub per treatment session. Treatments were repeated every week for 4 weeks. Group 2, with 35 lesions, was treated with 15% paromomycin sulfate plus 12% methylbenzethonium chloride (MBCL) in a soft white paraffin-based ointment, produced in Isfahan Pharmacy College Research Laboratory. It was applied topically twice daily at 1 mm thickness over the total surface of the lesion(s) for 28 days. Similarly, patients in group 3 with 33 lesions used the ointment containing soft white paraffin.
The soft greatest diameter of induration, and the size were measured by a dermatologist, using a transparent ruler, before treatment and at weekly intervals during the treatment course and monthly thereafter for 2 months after the treatment ended. He was not aware of the type of the treatment that the patient was receiving. Any problems that the patients encountered with were recorded in a checklist form.
"Complete improvement" was defined as loss of induration and other signs of inflammation, complete re-epithelialization and return to normal skin texture as well as "parasitological cure", i.e., a negative Giemsa-stained direct smear. "Partial improvement" was considered when flattening, reduction in size and induration without complete re-epithelialization occured. All lesions which did not show any decrease in size and induration were regarded as "treatment failure". The statistical methods of analysis included Kruskal Wallis test and Chi-square test.
| Results|| |
One patient in group 2 and two patients in group 3 did not complete the study. The most common sites of involvement in all groups were extremities. Other demographic characteristics of the patients who completed the trial are shown in [Table - 1]. Statistical analysis showed no significant differences with respect to gender, age, duration and location of the lesions between the three groups. On day 90 the clinical results were as follows: In group 1, 29 (93.5%) lesions were completely improved, 2 (6.5%) lesions were partially improved and none of them failed to improve. In group 2, 14 (41.2%) lesions were completely improved and 10 (29.4%) lesions were partially improved while 10 (29.4%) failed to respond to twice daily application of paromomycin for four weeks. In group 3 that received placebo, 4 (13.3%) lesions were completely improved, 12 (40%) partially improved and 14 (46.7%) failed to respond [Figure - 1][Figure - 2]. Statistical analysis showed that the difference between these three groups was significant ( P <0.001).
At the end of the study, assessment of the completely improved lesions showed that deep or ugly scars were seen in none of the lesions in PDT group, 8 lesions in group 2 and 3 lesions in group 3 ( P <0.001).
With respect to parasitological cure, on day 28, 100% of lesions treated with PDT were amastigote-free and they also remained so until the end of the study; whereas, on day 90, only 64.7% (22 of 34) and 20% (6 of 30) of lesions treated with paromomycin or placebo were amastigote-free, respectively ( P <0.001).
Adverse side effects seen in some patients in all groups were pruritus, burning, redness, discharge, edema and pain, but all of them were generally mild and tolerable.
| Discussion|| |
The present study is the first randomized, placebo-controlled clinical trial that compares the effectiveness of PDT with a topical agent that is routinely used in the treatment of CL, i.e., paromomycin. Since the last 20 years, various topical formulations of paromomycin have been used for clinical studies with very variable results, ranging from ineffective to very effective (cure rate = 93.1%).
Currently, PDT is used in the treatment of superficial nonmelanoma skin cancers and benign diseases, such as recalcitrant viral warts, acne, psoriasis and cutaneous T-cell lymphoma. In a recent open study, 11 Israeli CL patients with a total of 32 lesions caused by L.major were treated with weekly PDT using ten percent d-aminolevulinic acid (d-ALA) and red light. All but one lesion became amastigote negative after only two treatments, at which time the mean reduction in lesion size was 67%. The cosmetic results were excellent, and no relapses were noted within the 6-month follow-up period. In another study, topical PDT used for treatment of CL lesions, including lesions with poor response to topical paromomycin sulfate. All of the lesions were leishmania-free histologically and cured clinically with excellent cosmetic results. Gardlo et al , reported a patient who presented with CL that PDT resulted in healing of the lesion with slight hypopigmentation.
Early in vitro investigations showed that porphyrins in combination with menadione induced a selective destruction of amastigotes in the macrophages. PDT has also some activities against other microorganisms. Antimicrobial activity of porphyrins might be on the basis of their ability to catalyze different light-dependent chemical reactions, which generate reactive oxygen species, which interfere with the bacterial membrane and lead to lipid peroxidation, oxidation of aminoacids in proteins and nucleotides, and protein cross-linking. Antiviral activity of PDT has been shown in the treatment of recalcitrant foot and hand warts. The effects of PDT on yeasts and dermatophytes bring attention to the fast that PDT is not only cost-effective, but also has the advantages of being highly selective, nongenotoxic and nonmutagenic. It seems a fundamental promise for the long-term safety of the treatment that avoids the occurrence of drug resistant strains.
Although the results of our study showed that both treatment modalities, PDT and topical paromomycin, are effective and superior to placebo, PDT was much more effective than paromomycin and caused a higher rate of complete improvement in CL lesions. In addition, PDT led to amastigote-free lesions in an earlier time in all the treated lesions compared to topical paromomycin. In our study, 100% of lesions were amastigote-free on day 28, however, Enk et al found that 31 lesions out of 32 were amastigote-free after one or two sessions of weekly PDT. Partial improvement in 74.2% of the lesions treated with PDT were seen as early as day 7, while at the same point of time only 26.5% of lesions treated with topical paromomycin and none of the placebo group had partial improvement [Figure - 1]. This finding also indicates that PDT affects the lesions rapidly and its clinical consequences can be revealed as flattening and reduction in size and induration. The results of our study demonstrated a very good response of CL caused by L. major to topical PDT. Most of the lesions treated with PDT healed with acceptable superficial or minimal scarring and none of them left an ugly scar.
However, the real place of PDT between the various treatment options remained to be determined by further randomized trials with a longer follow-up period and demonstration of its effect on other Leishmania species.
| Conclusion|| |
Topical PDT can be used safely as a rapid and highly effective alternative choice for treatment of old world CL in the selected patients in Isfahan region.
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[Figure - 1], [Figure - 2]
[Table - 1]