Treatment Options for Scabies
Scabies treatment has typically entailed the application of a topical acaricide, although oral administration of ivermectin is being increasingly used. For all topical treatments, patients are advised to cover the entire body from the neck down and leave the cream on for a prolonged period (usually overnight), before washing off. In pediatric and geriatric patients, the face is also treated due to more generalized skin involvement in these groups. The treatment of contacts is emphasized to prevent possible reinfestation, as patients can remain asymptomatic for several weeks following infestation.
Topical acaricides include longstanding formulations, such as 8–10% sulphur, 10–25% benzyl benzoate, 1% lindane, 10% crotamiton, 5% permethrin, or 0.5% malathion. The choice depends on local availability, cost and practitioner preference.
Permethrin
The synthetic pyrethroid 5% permethrin is a first-line acaricide in many countries, including the United States, Australia and the United Kingdom. It has an excellent record for safety and low toxicity. In a Cochrane review it was concluded that it was the most effective scabies treatment currently available. Recent findings concur, with all studies reporting more than 90% 14 or 28 day cure (Table 1). While in many reports its effectiveness when applied as a single dose has been satisfactory, its efficacy as an ovicide remains unresolved, and therefore a second treatment after 1 week to kill residual hatched eggs is prudent. A significant limitation to more widespread use of permethrin is its cost, which is significantly higher than other topical treatments, and the fact that it is not available in some areas, especially in the developing world where the burden of scabies is likely higher. In addition, there are suggestions of emerging resistance (see below).
Benzyl Benzoate
Benzyl benzoate is used at a concentration of 25% in adults, and 10% or 12.5% in children. It advantages include: its high efficacy, especially at 25%; that no resistance has been reported; and its low cost. It is therefore a very popular treatment in Africa and parts of Europe, although it is not available in the United States. A limitation is that the drug is prone to cause significant immediate skin irritation, thereby limiting its tolerance; dilution to reduce this may reduce efficacy. For example, in a recent trial 17.6 and 37.5% of patients reported irritation with one or two doses of benzyl benzoate, respectively. Treatment guidelines recommend that benzyl benzoate be left on for 24 hours and/or used on repeated consecutive days, an application regime that is more intensive than recommended for permethrin for example. The rationale for this recommendation is not clear, as compared to other commercially available acaricides, 25% benzyl benzoate is an extremely rapidly acting acaricide in vitro, with death of mites occurring within 30 min. There is a paucity of studies comparing different treatment regimens for benzyl benzoate, with the exception of a study by Ly et al., who reported that that the difference between one or two doses was modest ( Table 1 ). Trials comparing the efficacy of short versus long application times would be beneficial, as reduction in application time could reduce adverse effects and increase acceptability of an otherwise effective and affordable drug.
Controversies Over Lindane
1% Lindane ([gamma] benzene hexachloride), an organochloride insecticide and formerly the treatment mainstay, has been withdrawn from many regions worldwide due to concerns regarding neurotoxicity. In some countries however, it remains utilised as a first or second-line treatment. Although some proponents have attributed adverse events (including ataxia, tremors, seizures) to inappropriate or excessive application, a recent review of lindane adverse events showed that 43% of serious adverse events occurred when the drug was used as labelled. Due to the potential risks, these authors recommended that lindane be removed from other markets. The merit of continuing to recommend use of lindane is further weakened by evidence suggesting that it is less effective than available alternatives (Table 1).
Other Topical Agents
Topical application of 8–10% precipitated sulphur, although effective, is rarely a popular choice due to its messy application and odour. It is still used in some areas due to its low cost and its wide margin of safety in infancy and in pregnant women. In a recent study, it was confirmed that application for three consecutive days was required for optimal efficacy (Table 1). Crotamiton, another old drug that has not been evaluated recently, when used at a concentration of 10% has a wide margin of safety and is suitable for infants. Although crotamiton has good acaricidal properties in vitro, clinical efficacy is variable, with multiple applications advised. Nonetheless, it remains an option when responses to other acaricides are deemed inadequate. In addition, it may also be a good adjunct therapy due to its antipruritic activity.
Malathion is an organophosphate insecticide, reported to be effective for scabies at a concentration of 0.5%. Although it is currently recommended as a second-line treatment in the United Kingdom, there is a paucity of published clinical trial data to support its use.
Oral Ivermectin
Although the utility of ivermectin for the treatment of scabies is now widely recognized, its use remains off-label in most countries. It is most commonly administered at a weight-based dose of 200 μg/kg, although lower doses have been used in some trials. The principal indication for oral ivermectin therapy has been for the treatment of the most severe form of infection, namely crusted scabies. In addition, it has been used in mass treatment settings, and for control of institutional outbreaks in which topical application is less practical. The obvious advantage of an oral medication over topical therapy is that correct drug administration and compliance with treatment is more likely, not a trivial consideration. A disadvantage is that ivermectin is not approved for use in children below 15 kg, or in pregnant or lactating women. As these groups often carry a high burden of scabies in the community, this represents a significant obstacle to its use in mass treatment.
Despite early hopes that this drug would revolutionize the treatment of scabies, in a meta-analysis of published trials it was concluded that single dose ivermectin was not as effective as single-dose permethrin; the administration of a second dose of ivermectin resulted in efficacy similar to permethrin. In one recent trial in which two doses of permethrin were compared with a single dose of ivermectin, only a small and nonsignificant advantage was observed with permethrin (93 vs. 86%). These results are in contrast to other trials in which day 14 efficacy was reported to range from 26 to 100% (Table 1). Chhaiya et al. also examined topical application of 1% ivermectin, and found it to be more effective than a single dose of oral ivermectin. Strangely, the investigators advised patients to only apply the cream to affected sites, which goes against principles for the topical treatment of scabies. Thus, results should be interpreted with some caution.
It is important to recognize as a general comment that the contrasting outcomes reported in clinical trials likely reflect major differences in definition of cure. For some, this is defined as the absence of new lesions, whereas others require complete disappearance of all lesions. In this respect, it is well recognized that the pruritus caused by scabies frequently persists for some time after the administration of curative therapy (see below).
Despite heterogeneity between trials, it is worth noting that several studies report slower responses to ivermectin compared with permethrin, with relatively lower cure at days 7 and 14, but increasing at day 28 (Table 1). Reasons for this difference are difficult to explain, but could relate to the rate of mite killing in vivo, the mechanism of action, or individual differences in the distribution and retention of ivermectin in skin and tissues. The latter factor, although potentially of importance, has received little attention. Regardless, it is now generally accepted that single-dose ivermectin may be suboptimal due to its relatively short half-life in human plasma and its lack of ovicidal properties. Thus, some authors have recommended that a second dose 7 days later be administered.