Itching to prescribe the right treatment for scabies: Topical permethrin or oral ivermectin?

By Warren R. Heymann, MD
Feb. 1, 2018

Three weeks after confirming the diagnosis of crusted scabies on an HIV-positive patient, I started to scratch while driving in the parking lot at Cooper University Hospital. I didn’t give it much thought until the next day, when this stinging-itching sensation wouldn’t relent (interestingly the scratching felt soooo gooood). I realized that I probably had acquired scabies. After a colleague identified the mite, the hardest part of this process was telling my wife and daughters that they needed treatment too. The family episode of permethrin application undoubtedly led to my preference for prescribing oral ivermectin whenever possible — it is so much easier to take pills. Have I been recommending substandard therapy?

Scabies is an infestation of the skin by the mite Sarcoptes scabiei. Transmission is by direct skin-to-skin contact or indirectly through fomites. Symptoms typically appear 3 to 6 weeks after an infestation. In patients with a prior exposure to the mite, symptoms can appear as early as 24 hours post exposure. Lesions consist of pruritic erythematous papules with excoriations. They’re usually symmetrical and involve the interdigital webs, the flexural aspect of wrists, the axillae, the peri-umbilical area, elbows, buttocks, feet, genital area in men, and the peri-areolar area in women. The entire integument, including the face and the scalp, can be involved in infants, the elderly, and immunosuppressed patients. The pathognomonic sign is the burrow, representing the tunnel that the female mite digs to lay its eggs. Crusted scabies (CS) is a severe form that occurs in immunosuppressed individuals such as patients with AIDS, manifesting with extensive hyperkeratosis, predominantly over the scalp and the extremities. (1)
 
The two first-line treatments for scabies are topical permethrin 5% cream and oral ivermectin. According to Powell and Tucker, “oral ivermectin in single doses of 200 microgm/kg has been shown to be very effective in a number of studies, although it is not more effective than properly applied permethrin…Its safety in children under 15 kg in weight is unknown. Oral ivermectin should therefore be reserved for when appropriate application of a topical antiscabetic is not possible or practicable—for example, compliance, severe eczematization, or as a part of a treatment regimen in crusted/hyperkeratotic and resistant cases. However, randomized controlled trials examining oral ivermectin in crusted scabies are lacking. Treatment with permethrin is repeated after 1 week, as it may not be effective against scabies mite eggs. This repeat treatment allows time for any such eggs not destroyed by the first treatment to hatch so the hatchlings may then be killed. Similarly oral ivermectin may not be effective against the ova, hence the reason why repeat dosing is often needed in practice and shows improved cure rates in studies.” (2)

Searching PubMed utilizing “permethrin versus ivermectin for scabies”, I found two relevant studies. Manjhi et al conducted a study on four groups including 60 scabetic patients in each group by simple random sampling. Treatment given in each group was: Group 1: Ivermectin (200 microgm/kg body weight) oral in a single dose, Group 2: Topical Permethrin 5% cream single application, Group 3: Topical gamma benzene hexachloride (GBHC) lotion 1% single application and Group 4: Topical Benzyl benzoate (BB) lotion 25% single application. All of the patients were followed for improvement in terms of severity of disease and severity of pruritus at the end of the first week and sixth week. The efficacy of ivermectin, permethrin, GBHC and BB lotion, using improvement in severity of pruritus as a parameter, was 85%, 90%, 75% and 68.33% respectively at second follow-up. Similarly, considering improvement in severity of lesion as parameter, results were 80%, 88.33%, 71.66% and 65% respectively at second follow up. Topical permethrin (5%) was more effective as compared to topical BB lotion and topical GBHC lotion (p<0.05, significant) but statistical difference between efficacy of topical permethrin and oral ivermectin was non-significant (p>0.05). This suggested that oral ivermectin and topical permethrin (5%) were equally efficacious. (3)
 
Goldust et al evaluated 242 patients with scabies who were divided into two groups randomly. The first group and their family contacts received 5% permethrin cream and the other received oral ivermectin. Treatment was evaluated at intervals of 2 and 4 weeks. A single dose of ivermectin provided a cure rate of 85.9% at a 2-week interval, which increased to 100% after crossing over to the permethrin group at a 4-week interval. Twice application of permethrin with a 1-week interval was effective in 92.5% of patients, which increased to 94.2% after crossing over to the ivermectin group at a 4-week interval. Permethrin-treated patients recovered earlier. The authors concluded that twice application of permethrin with a 1-week interval is superior to a single dose of ivermectin, however, it must be noted that this difference was not significant (P = 0.42). (4)

In a systematic review of 15 randomized controlled trials, which contained 2172 patients (several with variable dosing schedules — please read reference 5 for details), Dhana et al found that oral ivermectin was associated with a significantly increased risk of treatment failure compared with topical permethrin (RR 1.33), treatment failure rate: 14% [122/860] vs 10% [85/831]. (5) Dressler et al, in their systematic review of 16 studies, found 3 comparisons of topical and systemic therapies. A total of 6 trials reported findings after 2 and/or 4 weeks on the efficacy of topical permethrin versus systemic ivermectin. Efficacy was comparable, although the trials differed in terms of their outcome parameter and other factors. Frequency of repeat treatment was inadequately reported. (6)

In conclusion, I am not yet convinced that there is any significant therapeutic advantage of either oral ivermectin or topical permethrin. Certainly, there will be times when topical permethrin will indicated over ivermectin, most notably in children under 15 kg or during pregnancy. (7) In severe cases, if without contraindication, it may make sense to use both oral ivermectin and permethrin simultaneously. Recommendations may change over time based on drug resistance patterns. In the meanwhile, should I get scabies again, I’m taking the pill.

1. Khalil S, et al. Scabies in the age of increasing drug resistance. PLoS Negl Trop Dis 2017: 11 (11): e0005920.
2. Powell JB, Tucker WFB. Scabies. In Lebowohl MG, Heymann WR, Berth-Jones J, Coulson I (eds). Treatment of Skin Disease, fifth edition, 2018, Elsevier, Ch. 223.
3. Manjhi PK, et al. Comparative study of efficacy of oral ivermectin versus some topical antiscabies drugs in the treatment of scabies. J Clin Diagn Res 2014; 8: HC01-4.
4. Goldust M, et al. Treatment of scabies: Comparison of permethrin 5% versus ivermectin. J Dermatol 2012; 39:545-7.
5. Dhana A, et al. Ivermectin versus permethrin in the treatment of scabies: A systematic review and meta-analysis of randomized controlled trials. J Am Acad Dermatol 2018; 78: 194-8.
6. 7. Dressler C, et al. The treatment of scabies. Dtsch Arzebl Int 2016; 113: 757-62.
Hill TA, Cohen B. Scabies in babies. Pediatr Dermatol 2017; 34: 690-4.

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