Comparison of efficacy of intralesional meglumine antimoniate vs. combination of 50% trichloroacetic acid and intralesional meglumine antimoniate in patients of cutaneous leishmaniasis.
Keywords: Cutaneous leishmaniasis, intralesional injection, meglumine antimoniate, trichloroacetic acid, topical therapy.
Cutaneous leishmaniasis (CL) is an endemic disease in 88 countries. The estimated annual incidence of new cases is 1.5 to 2 million cases per year globally. More than 350 million people are at risk world wide.1
Pakistan is one of the countries where CL is becoming an epidemic disease. And because of its morbidity and disfiguring scars, it is emerging as a major public health problem especially alongside regions bordering the neighboring Afghanistan and cities that have had the maximum influx of Afghan refugees.2
Treatment of leishmaniasis is often difficult. Many physical, topical, intralesional and systemic modalities have been suggested for cutaneous leishmaniasis. Although pentavalent antimonial compounds are still considered the standard treatment, their side effects and increasing rate of resistance have motivated researchers to seek safer and alternative modalities.3
Trichloroacetic acid (TCA) peeling is a long utilized procedure in dermatology. TCA is an analogue of acetic acid. It works by precipitating proteins and inducing coagulative necrosis of epidermis and/or papillary dermis followed by sloughing off of necrotic layers and re-epithelization, and promotes dermal collagen remodeling.4 Topical TCA is not significantly absorbed and, therefore, does not produce systemic complications. Considering the TCA potential to induce collagen synthesis, it can be used as an adjuvant in treatment of CL.5
Different studies have shown variable effectiveness of TCA and meglumine antimoniate (MA) in treatment of CL. A study done in Iran showed an accelerated resolution rate with combination therapy of intralesional meglumine plus topical TCA, with 85.7% showing complete resolution in 8 weeks time as compared to 79.2%3 of with intralesional meglumine alone. In another similar study success of MA alone was 70.9%.6
The present study was designed to evaluate the efficacy of intralesional meglumine antimoniate versus combination of 50% TCA and intralesional meglumine antimoniate (GlucantimeA(r)) in patients of CL. If found effective, then in future, topical 50% TCA could be suggested as an adjuvant therapy to accelerate the healing process and decrease the healing time of the lesions in patients of CL.
This study was a randomized controlled trial done in department of dermatology, Military Hospital, Rawalpindi, over a period of six months from August 2016 to February 2017. Sample size was calculated by using WHO sample size calculator for two proportions based on outcome variables, level of significance 5%, power of test 80%, anticipated population proportion (P1) 85.7%,1 anticipated population proportion (P2) 70.9%.6
Considering 10% for loss to follow-up total sample size of 210 (105 in each group) was calculated. Patients in group A received intralesional MA twice weekly for 8 weeks and topical 50% TCA applied by cotton swab fortnightly for 8 weeks. Patients in group B received intralesional MA alone twice weekly for 8 weeks.
Efficacy was calculated in terms of clinical response (more than 75% reduction in size and induration of lesion) achieved at 8 weeks' time, which was measured by palpation and ruler using two largest perpendicular diameters. Measurements done before treatment and weekly till the end of eighth week.
Non probability consecutive sampling was done. Patients included in the study were clinically and histopathologically confirmed cases of CL from either gender, aged 15-40 years, with no visceral involvement and no previous history of systemic or topical therapy for CL. Patients with less than 5 skin lesions and less than 3cm diameter and of less than 12 weeks duration with no superimposed bacterial infection (culture negative) were included. Patients having any major concomitant illnesses like hepatic, renal or cardiac diseases and immunocompromised patients were excluded. Similarly, pregnant or nursing women were not included in the study group as well. Lesions located within 2cm distance of palpebral margin were excluded.
Patients of CL fulfilling the inclusion criteria were admitted in dermatology inpatient department (ward) at Military Hospital Rawalpindi after informed consent and permission from Hospital Ethical Committee. Random allocation of patients was done into two groups: those reporting on even dates fallen in first group and those reporting on odd dates fallen in second group.
Response to treatment was graded as complete cure (complete re-epithelization of lesion, lack of induration and size reduction more than 75%), partial cure (partial improvement in erythema, induration and size reduction 50% to 75%), and non-cure (no significant improvement in lesion and size reduction less than 50%). All data was recorded on a proforma.
SPSS version 20 was used for analysis of the data. Qualitative variables like gender, efficacy, site of lesion were measured by frequency and percentage. Quantitative variables like age, number of lesions and duration of lesions were measured as mean+-SD. Chi square test was applied to compare efficacy between two groups. P value a$?0.05 was taken as significant. Effect modifiers like age, gender, site, duration of lesion and number of lesions were controlled by stratification.
Table 1 Comparison of efficacy of intralesional meglumine antimoniate (MA) with trichloroacetic acid (TCA) vs. intralesional MA alone.
Efficacy###Group A###Group B
###50% TCA with MA###MA alone
Mean age of the patients was 31.38+-4.64 years and 31.48+-3.92 years in group A and B, respectively. There were 102 (97.2%) males in group A and 100 (95.2%) males in group B. Only 3 females (2.8%) were in group A and 5 (4.8%) in group B. Mean number of lesions in group A was 1.06+-0.23 and in group B 1.08+-0.26. In group-A mean size of lesion was 3.08+-1.19cm2 and in group-B mean size of lesion was 2.99+-1.30cm2. Mean duration of lesion was 8.87+-1.77 weeks in group A and 7.87+-1.72 weeks in group B. Sites of upper extremity were involved in 61 (58.1%) patients of group A and 55 (52.4%) patients in group B while sites of lower extremity were involved in 44 patients (41.9%) of group-A and 50 patients (47.6%) of group-B. Efficacy was observed in 91 (86.7%) patients of group A and in 78 (74.3%) patients of group B (Table 1).
Stratification was carried out with regard to age, gender, site of lesion, duration of lesion, size of lesion and number of lesions.
Majority of leishmaniasis cases are more geographically concentrated, as 90% cases of visceral leishmaniasis (the most severe form of leishmaniasis) occur in six countries. 90% of CL cases (the most common type of leishmaniasis) occur in seven countries. It is very prevalent in Pakistan and has been reported from all provinces and almost all major cities. It is endemic in Baluchistan, Interior Sindh, North West Pakistan and Multan.7
CL has a huge social and economic burden.8 Different treatment strategies have been described. The choice of treatment is often determined by the characteristics of the patient (age, gender, location of lesion, and immunity) and parasite (species variation). The treatment efficacy is also dependent on the geographical area.
The pentavalent antimonial meglumine antimonate (GlucantimeA(r), Aventis, France, 85 mg Sb5+/mL) for intramuscular and intralesional administration and sodium stibogluconate (PentostamA(r), 100 mg Sb5+/mL) for intravenous and intramuscular administration have been used for decades for the treatment of CL, and are the gold standard for other new investigational drugs.10
The World Health Organization (WHO) recommendations for the treatment of CL are intralesional or systemic antimonials, according to the species and the clinical features.11
Topical TCA has different indications in dermatology. It is reported as a safe and effective treatment for benign pigmented lesions such as seborrheic keratosis, solar lentigines, melasma, and freckles with no significant complications.12 El-Domyati et al.13 reported epidermal and dermal rejuvenation in four patients with photodamaged skin treated with TCA.13 Yug et al.14 reported the treatment of three patients with acne scars by topical application of TCA 95%, resulting in cosmetic and histologic improvement of the depth of acne scars. Treatment of atrophic scars with TCA was associated with activation of dermal fibroblasts and increased collagen contents.14 The same mechanism of new collagen formation and elastic fibers degradation might contribute to the accelerated healing process of CL lesions after topical application of TCA in combination therapy group.
Results: of present study showed that combining topical TCA treatment with intralesional MA improves the efficacy of intralesional alone (86.7% vs. 74.3%). Topical application of TCA 50% have advantages when used as an adjuvant therapy to accelerate the healing process and decrease the healing time of the lesions in patients with CL. Further studies to assess the mechanism of action of TCA in the treatment of CL, its possible efficacy as combination therapy with other treatment modalities of CL, and assessment of its long-term usage side effects are warranted.
Combination therapy with TCA 50% and intralesional MA accelerated the resolution of CL lesions with significant difference in complete resolution rate in comparison to the patients treated with intralesional MA alone. Topical application of TCA 50% as an adjuvant therapy have advantages in decreasing the resolution time of the lesions in patients with CL.
1. Mohammadzadeh M, Behnaz F, Golshan Z. Efficacy of glucantime for treatment of cutaneous leishmaniasis in Central Iran. J Infect Public Health. 2013;6:120-4.
2. Afghan AL, Kassi M, Kasi PM, Ayub A, Kakar N, Marri SM. Clinical manifestations and distribution of cutaneous leishmaniasis in Pakistan. J Trop Med. 2011;2011:359145.
3. Nilforoushzadeh MA, Jaffary F, Derakhshan R, Haftbaradaran E. Comparison between intralesional meglumine antimoniate and combination of trichloroacetic acid 50% and intralesional meglumine antimoniate in the treatment of acute cutaneous leishmaniasis: a randomized clinical trial. J Skin Stem Cell. 2014;1:e16633.
4. Ali NM, Fariba J, Elaheh H, Ali N. The efficacy of 5% trichloroacetic acid cream in the treatment of cutaneous leishmaniasis lesions. J Dermatolog Treat. 2012;23:136-9.
5. Banihashemi M, Yazdanpanah MJ, Amirsolymani H, Yousefzadeh H. Comparison of lesion improvement in lupoid leishmaniasis patients with two treatment approaches: trichloroacetic acid and intralesional meglumine antimoniate. J Cutan Med Surg. 2015;19:35-9.
6. Silva RE, Toledo A Junior, Senna MC, Rabello A, Cota G. Intralesional meglumine antimoniate for the treatment of localised cutaneous leishmaniasis: a retrospective review of a Brazilian referral centre. Mem Inst Oswaldo Cruz. 2016;111:512-6.
7. Khan SJ, Muneeb S. Cutaneous leishmaniasis in Pakistan. Dermatol Online J. 2005;11:1-4.
8. Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7:e35671.
9. Gonzalez U, Pinart M, Reveiz L, Alvar J. Interventions for Old World cutaneous leishmaniasis. Cochrane Database Syst Rev. 2008;4:CD005067.
10. Blum J, Desjeux P, Schwartz E, Beck B, Hatz C. Treatment of cutaneous leishmaniasis among travellers. J Antimicrob Chemother. 2004;53:158-66.
11. World Health Organization. The leishmaniases. WHO technical report series, vol. 701. Geneva: WHO; 1984.
12. Garrett SJ, Robinson JK, Roenigk HH Jr. Trichloroacetic acid peel of molluscum contagiosum in immunocompromised patients. J Dermatol Surg Oncol. 1992;18:855-8.
13. El-Domyati MB, Attia SK, Saleh FY, Ahmad HM, Uitto JJ. Trichloroacetic acid peeling versus dermabrasion: a histometric, immunohistochemical, and ultrastructural comparison. Dermatol Surg. 2004;30:179-88.
14. Yug A, Lane JE, Howard MS, Kent DE. Histologic study of depressed acne scars treated with serial high-concentration (95%) trichloroacetic acid. Dermatol Surg. 2006;32:985-90.
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|Publication:||Journal of Pakistan Association of Dermatologists|
|Date:||Dec 31, 2018|
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