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• W2775154448 abstract "To the Editor: Scabies, an intensely pruritic ectoparasitic skin infestation, affects over 130 million people and hampers quality of life.1Currie B.J. Scabies and global control of neglected tropical diseases.New Engl J Med. 2015; 373: 2371-2372Crossref PubMed Scopus (25) Google Scholar, 2Jackson A. Heukelbach J. Filho A.F. et al.Clinical features and associated morbidity of scabies in a rural community in Alagoas, Brazil.Trop Med Int Health. 2007; 12: 493-502Crossref PubMed Scopus (55) Google Scholar Permethrin is considered the most effective topical treatment for scabies.3Strong M. Johnstone P.W. Interventions for treating scabies (update).Cochrane Database of Systematic Reviews. 2010; (Available at: http://onlinelibrary.wiley.com/doi/10.1002/ebch.861/full. Accessed October 2, 2017)Google Scholar Ivermectin is the only oral alternative and can also be applied topically. Because randomized controlled trials comparing oral or topical ivermectin with topical permethrin have been inconclusive, we performed a meta-analysis. On March 21, 2017, we searched PubMed, Embase, Cochrane Library, and references of included articles using the terms “scabies” and “permethrin” and “ivermectin” for peer-reviewed randomized controlled trials comparing oral or topical ivermectin with topical permethrin in patients with scabies. Two authors independently selected studies, extracted data, and assessed study quality using the Cochrane Risk of Bias Tool. The primary outcome was treatment failure as defined in the individual studies, although we required that the definition include persistent lesions, new lesions, or confirmation of a live mite. Secondary outcomes were persistence of itch and adverse effects. We calculated pooled risk ratios (RRs) and 95% confidence intervals (CIs) using a random effects model. Our search identified 461 potential articles. We ultimately included 15 randomized controlled trials, which contained 2172 patients. Table I summarizes the main study characteristics. In terms of dose regimens, oral ivermectin (200 μg/kg) was given as a single dose in 5 trials and repeat doses in 9 trials. Topical ivermectin (1%) was given as repeat applications in 2 trials. Topical permethrin (5%) was given as a single application in 5 trials and repeat applications in 9 trials, while topical permethrin (2.5%) was given as repeat applications in 1 trial.Table IMain characteristics of studies comparing oral or topical ivermectin with topical permethrinAuthor, countryNumber of subjectsInterventionsPrimary outcome, treatment failureSecondary outcomesCointerventionsImportant additional exclusion criteriaUsha et al, India, J Amer Acad Dermatol. 2000;42:236-40.85Group A: OI, single dose, repeated at week 2 for nonrespondersGroup B: Pa, applied overnight, repeated at week 2 for nonrespondersI+PNL+LMAdverse effectsTreated family and/or close contacts + washed clothes and bedding + antibiotic if infectioni)Age <5 yearsii)Pregnant and lactating womenBachewar et al, India, Indian J Pharmacol. 2009;41:9-14.55Group A: OI, single dose, repeated at week 1 for nonrespondersGroup B: Pa, applied overnight, repeated at week 1 for nonrespondersPNLNoneTreated family and/or close contacts + antibiotic if infectioni)Age <12 yearsii)Pregnant and lactating womeniii)Immunocompromisediv)Crusted scabiesMushtaq et al, Pakistan, Journal of Pakistan Association of Dermatologists. 2010;20:227-31.86Group A: OI, single dose, repeated at week 2 for nonrespondersGroup B: Pa, applied over 12 hours, repeated at week 2 for nonrespondersI+PNL+LMAdverse effectsItch persistenceNonei)Age <2 and >60 yearsii)Pregnant and lactating womeniii)ImmunocompromisedSharma et al, India,∗Results for both ivermectin groups were combined in the final pooled estimate. Indian J Dermatol Venereol Leprol. 2011;77:581-6.117Group A: OI, single doseGroup B: OI, single dose, repeated at week 2Group C: Pa, applied overnightI+PNL+LMAdverse effectsItch persistenceTreated family and/or close contacts + washed clothes and beddingi)Age <5 yearsii)Pregnant and lactating womeniii)Immunocompromisediv)Crusted scabiesGoldust et al, Iran, Journal of Dermatology. 2012;39:545-7.242Group A: OI, single doseGroup B: Pa, applied over 12 hours, repeated at week 1PNL+LMAdverse effectsNonei)Age <2 yearsii)Pregnant and lactating womeniii)Immunocompromisediv)Crusted scabiesSaqib et al, Pakistan, Journal of Pakistan Association of Dermatologists. 2012;22:45-9.120Group A: OI, single doseGroup B: Pa, applied over 10-12 hoursI+PNL+LMNoneTreated family and/or close contacts + washed clothes and bedding + antihistamine + antibiotic if infectioni)Age <18 and >60 yearsii)Pregnant and lactating womenChhaiya et al, India, Indian J Dermatol Venereol Leprol. 2012;78:605-10.300Group A: OI, single dose, repeated at week 1 and 2 for nonrespondersGroup B: TI, applied for at least 8 hours, repeated at week 1 and 2 for nonrespondersGroup C: Pa, applied for at least 8 hours, repeated at week 1 and 2 for nonrespondersPNLAdverse effectsItch persistenceAntihistaminei) Age <5 and >80 yearsii) Pregnant and lactating womeniii) Immunocompromisediv) Crusted scabiesRanjkesh et al, Iran, Ann Parasitol. 2013;59:189-94.60Group A: OI, single dose, repeated at week 2 for nonrespondersGroup B: Pa, 2 applications 1 week apart, repeated at week 2 for nonrespondersPNL+LMAdverse effectsTreated family and/or close contactsi)Age <2 yearsii)Pregnant and lactating womeniii)Immunocompromisediv)Crusted scabiesGoldust et al, Iran, Ann Parasitol. 2013;59:79-84.380Group A: TI, 2 applications 1 week apart, repeated at week 2 for nonrespondersGroup B: Pb, 2 applications 1 week apart, repeated at week 2 for nonrespondersPNL+LMAdverse effectsTreated family and/or close contactsi)Age <2 yearsii)Pregnant and lactating womeniii)Immunocompromisediv)Crusted scabiesAggarwal et al, India, Natl J Integr Res Med. 2014;5:57-60.88Group A: OI, single doseGroup B: Pa, applied overnightI+PNL+LMNoneTreated family and/or close contactsi)Age <10 and >60 yearsii)Pregnant and lactating womeniii)Immunocompromisediv)Crusted scabiesManjhi et al, India, J Clin Diagn Res. 2014;8:HC01-4.120Group A: OI, single doseGroup B: Pa, applied overnightPNLItch persistenceNonei)Age <5 and >60 yearsii)Pregnant and lactating womenMaurya et al, India, International Journal of Pharmacology and Clinical Sciences. 2014;5:15-21.120Group A: OI, single dose, repeated at week 1Group B: Pa applied over 12 hours, repeated at week 1I+PNLAdverse effectsTreated family and/or close contacts + washed clothes and beddingi)Age <12 yearsii)Pregnant and lactating womenKanwar et al, India, Int J Basic Clin Pharmacol. 2016;5:1234-8.199Group A: OI, single doseGroup B: Pa, applied overnightPNLItch persistenceNonei)Age <5 and >60 yearsii)Pregnant and lactating womenWankhade et al, India, Indian J Pharmacol. 2013;45:S202.100Group A: OI, single dose, repeated at week 1 for nonrespondersGroup B: Pa, applied overnight, repeated at week 1 for nonrespondersI+PNLAdverse effectsNonei)Age <5 and >60 yearsii)Pregnant and lactating womeniii)Immunocompromisediv)Crusted scabiesAbdel-Raheem et al, Egypt,†Pb used for children <10 years.J Dermatolog Treat. 2016;27:473-9.100Group A: OI, single dose, repeated at week 1 for nonrespondersGroup B: Pa for adults, applied overnight for 5 consecutive nights, repeated at week 1 for nonrespondersPNL+LMAdverse effectsItch persistenceTreated family and/or close contacts + washed clothes and bedding + antibiotic if infectioni)Age <2 and >50 yearsii)Pregnant and lactating womeniii)Immunocompromisediv)Crusted scabiesI, Itching; LM, live mite confirmed on microscopy; OI, oral ivermectin 200 μg/kg; Pa, 5% permethrin cream; Pb, 2.5% permethrin cream; PNL, persistent or new lesions; TI, 1% topical ivermectin cream.∗ Results for both ivermectin groups were combined in the final pooled estimate.† Pb used for children <10 years. Open table in a new tab I, Itching; LM, live mite confirmed on microscopy; OI, oral ivermectin 200 μg/kg; Pa, 5% permethrin cream; Pb, 2.5% permethrin cream; PNL, persistent or new lesions; TI, 1% topical ivermectin cream. Oral ivermectin was associated with a significantly increased risk of treatment failure compared with topical permethrin (RR 1.33, 95% CI 1.04-1.72, I2 = 0%, treatment failure rate: 14% [122/860] vs 10% [85/831], n = 1691) (Fig 1). Meta-regression revealed no significant heterogeneity by various study characteristics: length of follow-up, treatment of family or close contacts, repetition of ivermectin dose, itch in definition of treatment failure, and microscopy in definition of treatment failure. Visual inspection of the funnel plot and Egger's test (P = .19) revealed no evidence of small-study effect. Oral ivermectin was associated with a nonsignificant increased risk of persistent itch compared with topical permethrin (RR 1.32, 95% CI 0.91-1.93, I2 = 0%, persistent itch rate: 13% [57/432] vs 10% [39/389], n = 821). Topical ivermectin was associated with a nonsignificant increased risk of treatment failure compared with topical permethrin (RR 1.49, 95% CI 0.88-2.51, treatment failure rate: 10% [30/291] vs 7% [20/289], I2 = 0%, n = 580). One trial by Chhaiya et al found no significant difference in itch persistence between both agents.4Chhaiya S.B. Patel V.J. Dave J.N. Mehta D.S. Shah H.A. Comparative efficacy and safety of topical permethrin, topical ivermectin, and oral ivermectin in patients of uncomplicated scabies.Indian J Dermatol Venereol Leprol. 2012; 78: 605-610Crossref PubMed Scopus (43) Google Scholar The number of adverse effects were few: 4.3% (26/604) for oral ivermectin, 4.6% (35/758) for topical permethrin, and 6.9% (20/291) for topical ivermectin. There were no serious adverse effects. Several other topical treatments are available for scabies: benzyl benzoate, lindane, crotamiton, malathion, and sulfur. A previous systematic review found topical permethrin to be the most effective current scabicide.3Strong M. Johnstone P.W. Interventions for treating scabies (update).Cochrane Database of Systematic Reviews. 2010; (Available at: http://onlinelibrary.wiley.com/doi/10.1002/ebch.861/full. Accessed October 2, 2017)Google Scholar Although the authors found much higher treatment failures with oral ivermectin compared with topical permethrin than in our study, the review only included two small trials (n = 140) and data from the earliest follow-up visit. Indeed, several studies have noted a slower response with oral ivermectin.5Mounsey K.E. McCarthy J.S. Treatment and control of scabies.Curr Opin Infect Dis. 2013; 26: 133-139Crossref PubMed Scopus (35) Google Scholar Of note, our meta-regression analyses found no significant difference between trials using single and multiple doses of oral ivermectin (Pheterogeneity = .46). However, given ivermectin's limited ovicidal activity and short half-life, it would be prudent to administer 2 doses at least 4 days apart.6Golant A.K. Levitt J.O. Scabies: a review of diagnosis and management based on mite biology.Pediatr Rev. 2012; 33: e1-e59Crossref PubMed Scopus (33) Google Scholar Other factors could also affect choice of agent. Ivermectin is cheaper, and oral administration might improve adherence.5Mounsey K.E. McCarthy J.S. Treatment and control of scabies.Curr Opin Infect Dis. 2013; 26: 133-139Crossref PubMed Scopus (35) Google Scholar However, oral ivermectin is not approved for use in young children and pregnant or lactating women–key groups that most trials excluded. It should be noted that the basis for therapeutic recommendations should not be made solely on a meta-analysis. Our study was limited by the lack of patient-level data; potential performance bias (assessment of study quality revealed absence of blinding in most trials); and trial exclusion of subjects with crusted scabies, which generally requires combination therapy. Our findings, however, suggest that combination therapy with oral ivermectin and topical permethrin is presumably safe and, in typical scabies, might potentially enhance efficacy. In summary, oral ivermectin is less effective than topical permethrin. Topical ivermectin may have a similar efficacy to topical permethrin, but further trials are warranted given the small sample size used for this comparison. All 3 agents, however, have low treatment failure rates and are well tolerated." @default.
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• W2775154448 title "Ivermectin versus permethrin in the treatment of scabies: A systematic review and meta-analysis of randomized controlled trials" @default.
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