Combine permethrin and check alternative if therapy fails

Although an increasing development of resistance to permethrin has been reported in recent years, this topical therapeutic agent is still the first choice for the treatment of common scabies due to its favorable side effect profile. If the prescribed use of permethrin in combination with ivermectin does not lead to healing, alternative treatment options can be used. This approach has proved successful at Zurich Children’s Hospital to date.

Also known as scabies (from the Latin scabere for “to scratch”), the contagious and extremely itchy parasitic skin disease scabies is primarily caused in humans by Sarcoptes scabiei variatio hominis [1]. Children are disproportionately affected by ectoparasitosis. The clinical picture shows blisters, vesicles and pustules. The mites are easy to see dermoscopically, usually in the area of the hands. “You often see a lot of mites,” reported PD Dr. med. Martin Theiler Pang, Head Physician, Dermatology, Children’s Skin Center – Dermatology, University Children’s Hospital Zurich [2]. Babies have a particularly large number of mites. A whole-body infestation usually manifests itself in infants and small children. The feet, including the soles of the feet, ankle region, scalp and face, but also the axillae, popliteal fossae and lower legs are frequently affected [3]. In the case of common scabies, the risk of infection generally affects family members or members of a shared flat. The first symptoms appear after 2-5 weeks of initial infection. In the case of reinfestation, the eczematous skin changes appear after 1-4 days due to the already existing sensitization. According to the speaker, a questionnaire study showed that, in contrast to dermatologists, only around two thirds of general practitioners also treat close contacts [2].

Permethrin plus ivermectin as a first line

The treatment options for adults and children recommended in the European guidelines for the management of scabies are permethrin or ivermectin (p.o.) 200 μg/kg [4]. Permethrin 5% cream (Scabi-med®) and ivermectin (Subvectin®) are approved in Switzerland; benzyl benzoate (Antiscabiosum®) and crotamiton (Crotamitex®) are also used in everyday clinical practice [5]. If a combination of permethrin 5% plus ivermectin does not prove effective, ivermectin can be combined with crotamiton (in infants) or benzyl benzoate (over 1-year-olds) instead, explained Dr. Theiler and illustrated the therapeutic procedure practiced at the Children’s Hospital Zurich as follows (Fig. 1) [2]: In families with infants affected by scabies, a combination of permethrin 5% once plus ivermectin 0.2-0.3 mg/kg/d is used and repeated after 7-10 days. In cases that have already been pre-treated several times with permethrin, this step is skipped. The permethrin is left for 12 hours (instead of 8 hours as previously recommended). If the hands and feet are clearly infested, the speaker recommends continuing to treat them with permethrin overnight for the following 2-3 days. Ivermectin is used in children ≥5 kg, which mostly applies to infants over 2 months of age, and care should be taken to ensure that it is taken on an empty stomach. Close contacts should also be treated if they are asymptomatic, if necessary with ivermectin therapy alone. “If that doesn’t work, then we usually go on two treatment tracks,” said the speaker, explaining the procedure anchored in the treatment regimen [2].

You can switch to benzyl benzoate or crotamiton

As an alternative to permethrin, crotamiton can be used in infants for 5 consecutive days in combination with ivermectin 0.2-0.3 mg/kg/d, which is also repeated after 7-10 days. In children aged ≥1 year, benzyl benzoate** is used and combined with ivermectin for three days. Benzyl benzoate can cause neurological problems in infants, which is why the use of this medication is not recommended for this subpopulation.

** Children: benzyl benzoate 10%, adults: benzyl benzoate 25%

In the past, they sometimes took an intermediate step at the children’s hospital: permethrin was used all over the body in combination with ivermectin. This is rarely done today, as it rarely brings much additional benefit. It is at best an option to be considered in individual cases if benzyl benzoate is poorly tolerated.

For pregnant mothers, the use of permethrin or benzyl benzoate is actually considered to be unproblematic. Ivermectin is probably also safe in pregnancy. Permethrin and ivermectin are considered safe for breastfeeding mothers. However, they recommend discarding or expressing milk or switching to infant milk during the 12-hour period when permethrin is applied. “Benzyl benzoate should not be used during breastfeeding,” the speaker added [2].

Educate and inform patients
In Switzerland, the treatment costs for affected families can be relatively high, as only permethrin (Scabi-med®) of the scabies drugs mentioned is on the list of specifics (SL), whereas ivermectin is not [5]. However, the latter is considered a “pharmaceutical with a tariff (ALT)”, which means that the health insurance company must cover the costs of extemporaneous prescriptions. The cantonal medical service has compiled a list of pharmacies for the canton of Zurich. The remaining medication must be paid for by the patient. The follow-up check of the children 2 weeks after treatment is very important, emphasized PD Dr. med. Martin Theiler Pang and added: “Simply examine them from top to bottom with a dermatoscope” [2]. If you find a mite somewhere, you can start all over again, says the speaker. With regard to the decontamination of furnishings, he pointed out that this is a particularly important aspect for infants who are heavily infested with mites. This and other information relevant to everyday life can also be found in scabies patient brochures, which are now available in numerous languages.

Ivermectin is considered safe from a body weight of 5 kg

The official approval for ivermectin is limited to children and adults weighing at least 15 kg body weight (bw). But millions of children under 15 kg bw have been treated with ivermectin worldwide and a look at the data shows that ivermectin can be considered safe in children over 4 kg bw, explained Dr. Theiler Pang [2]. For example, a study conducted between 2012 and 2015 in the dermatology departments of 28 centers in France showed that out of 170 infants and children treated with oral ivermectin for scabies whose KG <15 kg, mild side effects were reported in only 4% (n=7) and no serious adverse events were recorded [6]. This was a questionnaire study in which the treating physicians filled out a standardized questionnaire anonymously. At follow-up, 85% (n=139) of patients had achieved a cure. Analyses showed that a higher efficacy could be achieved with a dose exceeding 200 μg ^kg-1 (p<0.001) and if the time interval between the two doses was <10 days (p=0.025). The study included infants and children aged 1-64 months with a body weight of 4-14.5 kg. The mean dose administered was 223 μg ^kg-1, and 89% of patients systematically received a second dose. Concomitant topical treatment was carried out in 73% of patients.

Much-discussed permethrin resistance

Recently, several reports of treatment failure under permethrin treatment have been published. In a study of 55 scabies patients, monotherapy with permethrin resulted in healing rates of only 29-31% [7]. One possible explanation for permethrin resistance is a mutation (M918L) in voltage-dependent sodium channels. This mutation has been associated with a reduced response (“knockdown resistance”) in various arthropod species [8]. However, there is also an interesting study finding that indicates that the permethrin regimen used plays a role: in the retrospective analysis published in 2022, 85 infants and young children were treated with topical permethrin 5% in different treatment regimens [9]. Intensified treatment with permethrin on the whole body on days 1/8/15 and on the hands and feet on days 2/3/4/9/10/11 led to healing of the scabies in 73.5% of cases, while healing was achieved with whole-body permethrin on days 1/8 and days 1/8/15 in only 44% and 53.8% respectively. This meant that the success of the treatment could be significantly increased by treating the whole body and applying permethrin to the hands and feet in the meantime. The interdigital areas of the hands and feet typically have a particularly high number of mites.

Congress: Swiss Derma Day and STI reviews and updates

Literature:

“Scabies”, https://tropeninstitut.de/krankheiten-a-z/kraetze,(last accessed 18.03.2024)
“Scabies: Management in infancy and childhood”, PD Dr. med. M. Theiler Pang, Swiss Derma Day and STI reviews and updates, 11.01.2024.
RKI: Scabies fact sheet, www.rki.de,(last accessed 18.03.2024).
Salavastru CM, et al: European guideline for the management of scabies. JEADV 2017; 31(8): 1248-1253.
Swissmedic: Medicinal product information, www.swissmedicinfo.ch,(last accessed 18.03.2024)
Levy M, et al: Groupe de Recherche de la Société Française de Dermatologie Pédiatrique. Ivermectin safety in infants and children under 15 kg treated for scabies: a multicentric observational study. Br J Dermatol 2020; 182(4): 1003-1006.
Meyersburg D, Kaiser A, Bauer JW: Loss of efficacy of topical 5% permethrin for treating scabies: an Austrian single-center study. J Dermatolog Treat 2022; 33(2): 774-777.
Riebenbauer K, et al: Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites. JEADV 2023; 37(11): 2355-2361.
Riebenbauer K, et al: Comparison of Permethrin-Based Treatment Strategies against Scabies in Infants and Young Children. J Pediatr 2022; 245: 184-189.