{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:00:42Z","timestamp":1790654442817,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T00:00:00Z","timestamp":1593734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cutaneous leishmaniasis (CL) is one of the major neglected disease worldwide. Although many drugs have been used, the pentavalent antimonials (PA) remain as the first\u2010line choice despite their toxicity and limited efficacy. The combination of two drugs has risen as a potential alternative to increase the cure rate while lowering the side\u2010effects caused by pentavalent antimonials (PA). The objective of this study was to critically review and appraise the potential synergism of the adjuvant therapies of PA with other drugs\/interventions previously used in the literature. We carried out a search of literature from PubMed, MEDLINE, Embase, Cochrane and clinicaltrials.gov. Articles that described a two\u2010arm or three\u2010arm design in which one of the arms consisted in a combination of a drug\/intervention with intralesional or systemic PA were selected. The primary outcome was proportion of complete clearance of the lesions defined as complete re\u2010epithelization and\/or negative direct smear. Our literature search identified 554 references. Thirty\u2010one records with a total sample size of 2668 participants met the eligibility criteria. The studies investigated the association of PA with the following: cryotherapy (five studies), allopurinol, imiquimod, pentoxifylline (four studies each), trichloroacetic acid 50% (three studies) and other additional interventions (eleven studies). Overall, the combined therapy of PA with a supplementary intervention was superior to PA monotherapy (RR: 1.23 95% CI: 1.11\u20131.35, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a064%). In association with PA, the comparator\u2010specific stratified analysis showed that cryotherapy (RR: 1.50 95% CI: 1.25\u20131.81, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a057%) and allopurinol (RR: 1.70 95% CI: 1.37\u20132.12, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a028%) were superior to PA in monotherapy. On the contrary, the combined therapy with imiquimod (RR: 1.08 95% CI: 0.88\u20131.32, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a040%) and pentoxifylline (RR: 1.14 95% CI: 0.94\u20131.40, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a041%) revealed a non\u2010significant result. The application of TCA along with PA did not show significant differences in the clearance rate, although it was close to it (RR: 1.31 95% CI: 0.99\u20131.73, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a084%). The present work represents an attempt to find new and reliable treatment modalities to enhance the efficacy based on the adjuvant therapy of pre\u2010existing drugs\/interventions with PA. According to our results, the combination of allopurinol\u2010PA is the most effective adjuvant therapy. The application of cryotherapy and TCA stand as useful and encouraging supplementary interventions. The combination of imiquimod\u2010PA and pentoxifylline adds no additional benefit. The results of this work may be helpful in devising and modifying the current guidelines for CL which face major remaining evidence gaps. Triple therapies consisting in cryotherapy\u2010PA\u2010TCA or allopurinol\u2010PA\u2010cryotherapy or allopurinol\u2010PA\u2010TCA can represent promising treatments yet to be confirmed in future trials.<\/jats:p>","DOI":"10.1111\/jdv.16333","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T11:49:57Z","timestamp":1583149797000},"page":"2216-2228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Evidence supporting the enhanced efficacy of pentavalent antimonials with adjuvant therapy for cutaneous leishmaniasis: a systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"34","author":[{"given":"H.","family":"Husein\u2010ElAhmed","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology Hospital de Baza Granada Spain"},{"name":"Translational Research Institute Academic Health System Medical School Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Gieler","sequence":"additional","affiliation":[{"name":"Translational Research Institute Academic Health System Medical School Hamad Medical Corporation Doha Qatar"},{"name":"Department of Dermatology and Venereology Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Steinhoff","sequence":"additional","affiliation":[{"name":"Translational Research Institute Academic Health System Medical School Hamad Medical Corporation Doha Qatar"},{"name":"Department of Dermatology and Venereology Hamad Medical Corporation Doha Qatar"},{"name":"College of Medicine Weill Cornell Medicine\u2010Qatar Doha Qatar"},{"name":"Medical School Qatar University Doha Qatar"},{"name":"College of Medicine Weill Cornell University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,3]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"https:\/\/www.who.int\/features\/qa\/58\/en\/."},{"key":"e_1_2_7_3_1","unstructured":"https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/leishmaniasis. 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