By Christeebella O. Akpala and Philip R. Fischer, MD, DTM&H
Christeebella Akpala is a student at the Mayo Clinic Alix School of Medicine in Rochester, MN. Dr. Fischer is Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.
SYNOPSIS: With increasing concern about reduced effectiveness of topical 5% permethrin cream against scabies, new data show that topical therapy with 25% benzyl benzoate is significantly more effective than permethrin.
SOURCE: Meyersburg D, Hoellwerth M, Brandlmaier M, et al. Comparison of topical permethrin 5% vs. benzyl benzoate 25% treatment in scabies: A double-blinded randomized controlled trial. Br J Dermatol 2024;190:486-491.
Scabies, an itchy skin infection caused by Sarcoptes scabiei var. hominis, affects 200 million people worldwide and is considered by the World Health Organization to be a “neglected tropical disease.” While scabies is most problematic in resource-limited areas of the world, it also is seen in high-income countries, including those in Europe and North America.
Topical 5% permethrin and oral ivermectin are the most commonly used treatments for scabies. However, there have been reports in recent years of reduced effectiveness of topical permethrin. The research team, based in Austria, wanted to determine if topical treatment with something other than 5% permethrin would be a better primary treatment choice.
Thus, during 2022 and 2023, Meyersburg and colleagues performed a single-institution, double-blinded, randomized controlled trial comparing 5% permethrin cream and 25% benzyl benzoate emulsion in the treatment of scabies in 110 individuals aged 12 years and older. The initial diagnosis was confirmed by dermoscopy. Patients were not included in the study if they were pregnant or breastfeeding, if they had received anti-scabies medication during the three weeks prior to study enrollment, or if they had crusted/Norwegian scabies. A maximum of 60 grams of the treatment was used once daily (after bathing) over the entire skin other than the scalp for a total of three days. (Patients tended to use only half to two-thirds of the available doses.) Symptoms were followed, and dermoscopic exams were performed three to four weeks after treatment.
With treatment, 87% of study subjects receiving 25% benzyl benzoate and 27% of those receiving 5% permethrin resolved their scabies infection (P < 0.001). Treatment with 5% permethrin was well-tolerated, with only 6% of patients reporting mild itching following topical application of the medication; 43% of patients receiving benzyl benzoate had a mild to moderate burning or stinging skin sensation immediately after the application of the medication; this sensation resolved spontaneously within two to 60 minutes, and no patients decided to discontinue treatment based on the reaction.
Aware of recent clinical reports of reduced response to 5% permethrin among European patients with scabies, the authors were not surprised by the low response to 5% permethrin in this study. They also noted a recent finding that there is a mutation in the permethrin-binding site of the voltage-sensitive sodium channel in some scabies parasites in Austria. Other investigators have postulated that poor responses to 5% permethrin relate to incomplete application, and some patients, despite clear instructions, do treat only itchy areas; nonetheless, there seemed to be reasonably good compliance with medication application in this controlled study. In addition, both permethrin and benzyl benzoate kill both mites and eggs, making repeat treatment a week later (after eggs hatch) unnecessary.
Based on these results, the authors suggest that 25% benzyl benzoate could replace 5% permethrin as a first-line treatment for classic scabies. (Patients with crusted scabies were not included in this study, so conclusions about treatment of that condition are beyond the scope of this investigation.)
COMMENTARY
For years, 5% permethrin cream has been a reliable treatment for scabies, effectively eliminating both mites and their eggs. Oral ivermectin, traditionally reserved for cases of crusted (Norwegian) scabies, provides an alternative and is administered in two doses spaced a week apart to target newly hatched mites from eggs unaffected by the initial treatment.1
In recent years, there have been reports citing treatment failures with permethrin, particularly in Europe.2,3 The cause remains ambiguous, shifting between the possibility of permethrin resistance within the parasite, inconsistencies in cream application, and non-standard treatment approaches by healthcare providers.4 It has been suggested that there is potentially improved efficacy of dual therapy, employing oral ivermectin alongside topical 25% benzyl benzoate.4 An Italian study observed a resolution rate of 100% among a cohort of 63 patients (with resolution defined as absence of mites on dermoscopy and lack of itching and visible lesions), indicating that dual therapy may be as effective, if not more effective, than the monotherapy advocated by Meyersburg and colleagues.4
Some physicians propose using a two-dose treatment regimen (with doses separated by one week) with permethrin, hoping to either combat partially resistant parasites or simply afford patients an extended opportunity for thorough skin coverage, but definitive comparative dosing studies are lacking.5 Notably, recent findings, as noted by Meyersburg, revealed genetically rooted permethrin resistance in scabies parasites in Austria, thus heightening concerns and potentially accounting for escalating treatment setbacks in at least some parts of the world.6 Contrastingly, benzyl benzoate, a longstanding treatment used outside North America for decades, is emerging with promising efficacy, often administered across three consecutive nights. Meyersburg’s comparative study reveals benzyl benzoate’s superiority to 5% permethrin cream, with tolerable local side effects. With benzyl benzoate already available over the counter in the United States, it beckons consideration as a first-line substitute for scabies treatment.
At the same time, Meyersburg’s convincing study did not include centers in regions where scabies resistance patterns might be different, nor did it include young children or women who were pregnant or breastfeeding. Further studies of the effectiveness of benzyl benzoate in the treatment of scabies are warranted.
Beyond its nuisance as a parasitic infection, scabies poses graver risks, particularly in predisposing children to secondary skin infections with group A streptococci. This vulnerability increases the probability of developing post-streptococcal glomerulonephritis and chronic kidney disease over the long term.7
REFERENCES
- Rosumeck S, Nast A, Dressler C. Ivermectin and permethrin for treating scabies. Cochrane Database Syst Rev 2018;4:CD012994.
- Mbuagbaw L, Sadeghirad B, Morgan RL, et al. Failure of scabies treatment: A systematic review and meta-analysis. Br J Dermatol 2024;190:163-173.
- Broster B, Clarke A, Iwuji C, Soni S. Scratching beneath the surface: An evaluation of the management of scabies 2017-2023. Int J STD AIDS 2024; Mar 27:9564624241242167. doi: 10.1177/09564624241242167. [Online ahead of print].
- Bassi A, Piccolo V, Mazzatenta C. “One-shot” combined therapy with oral ivermectin and local benzyl benzoate: Is the current best therapeutic option in the era of permethrin resistant scabies? Travel Med Infect Dis 2023;53:102585.
- Committee on Infectious Diseases. Scabies. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, editors. Red Book: 2021-2024 Report of the Committee on Infectious Diseases, Committee on Infectious Diseases, American Academy of Pediatrics; 2021.
- Riebenbauer K, Purkhauser K, Walochnik J, et al. Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites. J Eur Acad Dermatol Venereol 2023;37:2355-2361.
- Dowler J, Wilson A. Acute post-streptococcal glomerulonephritis in Central Australia. Aust J Rural Health 2020;28:74-80.
