10.1. Background
10.1.1. Epidemiology
Scabies is a parasitic infection of the skin that is caused by the mite of sarcoptes scabiei var. hominis. It occurs throughout the world, with an estimated 150 million cases (Hay et al., 2013), but is particularly problematic in areas of poor sanitation, overcrowding and social disruption. The prevalence of scabies in children is estimated to be 0.2% to 24% globally, and 1.3% to 17% in sub-Saharan Africa (WHO, 2005). In HIV-infected populations, prevalence has been reported as between 0.5% to 6% in adults and 2% to 10% in children (Patton et al., 2002). Scabies has been described as occurring both endemically and epidemically. In industrialized countries, it occurs epidemically in institutional settings, such as in nursing homes and prisons.
Scabies transmission occurs by direct skin-to-skin contact with an infected person; the higher the parasite burden, the greater the likelihood of transmission. Transmission via inanimate objects, such as shared clothing, is rare, but occurs in immunocompromised individuals (Chosidow, 2006; Hay et al., 2004; Arlian et al., 1988).
10.1.2. Clinical features
Scabies infection is characterized by intensely pruritic and erythematous papules and papulovesicles. The classical sites of infestation are in the interdigital web spaces of the fingers, the wrists, axillary areas, female breasts (particularly the skin of the nipples), peri-umbilical area, penis, scrotum and buttocks (Chosidow, 2000). The average number of mites reported per patient is approximately five to 15. The female mite burrows downwards into the skin, consuming the horny layer of the epidermis and the sera that seeps into the burrow from the dermis. The burrows are often undetectable, but can be seen as greyish, short, wavy lines in affected areas. Atypical presentations are common in immunosuppressed patients, such as the HIV-infected, or in those with chronic infection. Nodules can occur in some cases, and these take several months to disappear after successful treatment (Walton & Currie, 2007). Papules can develop into secondary lesions with infection, crusting and excoriations.
Secondary infection with Staphyocccus and Streptococcus can occur, causing complications including impetigo, abscess, cellulitis and septicaemia, as well as immunologic diseases including glomerulonephritis.
10.1.3. HIV infection
A broad spectrum of presentations of scabies occurs in the HIV-infected population. Scabies may present in atypical or crusted forms (Portu et al., 1996).
Crusted scabies is a severe, debilitating disease. It is an uncommon condition, most often presenting in immunocompromised individuals, such as those with HIV infection, especially in association with a low CD4 cell count (Funkhouser et al., 1993), as well as the elderly. The infection is characterized by considerably high numbers of mites where multiplication continues unhindered, producing thousands to millions of mites. The clinical picture shows hyperkeratotic skin crusts that may be loose, scaly and flaky, or thick and adherent. The crusts contain high numbers of mites. The distribution may be localized or extensive, and often in atypical patterns including the neck, face, scalp, eyelids and under the nails (Chosidow, 2000 & 2006).
10.1.4. Diagnosis
Diagnosis of scabies is usually made on clinical findings. Confirmatory tests include microscopic identification of the mites, eggs or mite faeces. Secondary bacterial infection of the skin lesions may occur.
10.3. Review question and summary of evidence
A systematic review (Vekic et al., in preparation) was based on the PICO question: in children and adults living with HIV infection (receiving and not receiving ART) (P), does any anti-scabies treatment (including topical permethrin, benzyl benzoate, oral ivermectin and/or ART) (I) compared to another treatment, no intervention or placebo (C) result in a clinical cure, reduction of itch or disappearance of mites on scrapings (O).
The review carried out for these guidelines (Vekic et al., in preparation) identified a total of 36 relevant studies. It found very little evidence to support any particular intervention for scabies in HIV-infected individuals. However, the review suggested that treatments should be based on severity with separate recommendations for the severe form of scabies with a very high mite burden including crusted scabies, and for the classic mild/moderate type.
For mild/moderate disease in association with HIV infection, treatment efficacy appears to be similar to individuals in the HIV-negative population (Vekic et al., in preparation). A Cochrane review (Strong & Johnstone, 2007) included 22 studies involving 2676 people without HIV (both children and adults). Only one study was a controlled trial with a placebo, and six studies included only children, three included only adults, and 13 included both children and adults. In HIV-negative study subjects with non-crusted scabies, topical permethrin appeared more effective than oral ivermectin (140 participants, two trials, RR 4.61, 95% CI 2.07 to 10.26, fixed-effect model), topical crotamiton (194 participants, two trials, RR 0.24, 95% CI 0.10 to 0.55, fixed-effect analysis) and topical lindane (RR 0.59, 95% CI 0.37 to 0.95, fixed-effect model; 554 participants, the pooled effect for the three trials). Permethrin appeared to be the most effective topical treatment for scabies, and ivermectin appeared to be an effective oral treatment.
Because of the scarcity of articles on the treatment of HIV and scabies, an additional review was undertaken, looking at the treatment of crusted scabies, as this was identified as occurring commonly in immunocompromised hosts, particularly in association with HIV infection. No RCTs for HIV and scabies and no randomized trials for crusted scabies were identified. Currently there are no data on the best treatment for scabies in association with HIV. There is also no evidence that treatment of HIV-associated crusted scabies is different from treatment of non HIV-associated crusted scabies. The use of oral ivermectin (200 µg/kg in two doses, one to two weeks apart) was found to be successful in several reviews (Nofal, 2009; Dourmishev et al., 1998; Leppard & Naburi, 2000; Sullivan et al., 1997; Larralde et al., 1999). Keratolytics were shown to be useful in reducing the mite burden of scabies in all cases.
Use of ART
The use of ART in HIV-infected patients with reconstitution of the immune system will probably reduce the frequency of crusted scabies.
Considerations in choice of drug
Ivermectin is the only oral treatment available for scabies. It is not recommended for pregnant or lactating women and children under 15 kg due to its potential adverse effects including hepatotoxicity, tachycardia and hypotension (Golant & Levitt, 2012). Permethrin 5% cream is recognized as the most effective treatment for scabies in immunocompetent hosts (Strong & Johnstone, 2007). Benzyl benzoate can be used in a diluted form for children, infants and breastfeeding mothers. Topical treatments with benzyl benzoate and permethrin for scabies during pregnancy have shown no increase in adverse pregnancy outcomes in the second and third trimesters of pregnancy (Mytton, 2007). Benzyl benzoate and permethrin are both categorized as drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformations or other direct or indirect harmful effects on the human fetus.
Although previously effective in treating scabies, lindane is no longer recommended due to the risk of neurotoxicity, especially in children.
Children
No good quality data exist on the treatment of children under the age of two months. There have been three case reports of permethrin being used safely in neonates (Subramaniam et al., 2013; Quarterman & Lesher, 1994; Guerci et al., 2010). Permethrin has a good safety profile and should be well tolerated in neonates as its absorbance is very low. The risk of untreated scabies was considered and valued higher. Safety of the use of crotamiton in newborns and infants has not been well established, and results from a double-blind randomized trial proved that crotamiton cream is significantly less efficacious than permethrin (Meinking et al., 1995).
Sulphur-containing preparations are used extensively, especially in resource-limited countries, but there is little literature to support it. Comparison trials between sulphur and permethrin or benzyl benzoate are not available. Sulphur preparations require compounding, are messy in application and have an unpleasant smell (Mounsey & McCarthy, 2013; Ly et al., 2009).The efficacy of sulphur for three days at 8% to 10% has recently been confirmed for the treatment of adult scabies (Sharquie et al., 2012). Neonates are able to have sulphur preparations applied onto their skin, as for various other skin conditions including seborrhoeic dermatitis, without evidence of harm being reported in its very widespread use (Elish & Silverberg, 2006; Janniger & Schwartz, 1995).
10.4. Rationale for recommendations
Scabies, and especially crusted scabies, is associated with considerable patient distress due to itching and potential stigma, as well as being an entry point for secondary bacterial infection of the skin, which is a significant risk for morbidity and even mortality. Therefore, prompt resolution of the skin manifestations is a priority to patients and their families.
The group considered that permethrin appears to be the most effective treatment for scabies infection. It has been tested against topical crotamiton and oral ivermectin in RCTs, and it appears to be superior in terms of minimizing treatment failure in participants with a clinical diagnosis of scabies. A few trials show no difference in cure rates between permethrin and topical benzyl benzoate. No serious adverse events leading to death or permanent disability were reported.
Ivermectin is currently the only oral treatment for scabies that is in routine use. It appears to be more effective than both placebo and lindane, but less effective than permethrin.
The limited data on crusted scabies in HIV-infected patients suggest a good effect of oral ivermectin. Local ivermectin resistance needs to be assessed and considered.
Currently, there is no evidence of the effects of prophylaxis, either beneficial or adverse, when used for contacts of people with scabies (FitzGerald et al., 2014). However, the GDG considered it important and recommended that contact tracing and treatment are necessary to prevent spread of disease and ensure treatment success. The group also recommended that all family members and close contacts should be treated simultaneously. In close-contact communities such as nursing homes, hospitals, schools and prisons, all patients and staff are required to have treatment.
The community effect of the different options is considered to be similar. On balance, the panel made a strong recommendation with low quality evidence for treatment of classic scabies and a conditional recommendation with very low quality evidence for treatment of severe scabies. The benefits of the recommended treatments outweigh any possible harms of the medication.
Adverse effects, costs, availability and other implementation considerations
Reported adverse reactions with the use of permethrin are rare in both adults and children (Coleman et al., 2005).
Ivermectin has been used extensively in the treatment of onchocerciasis and serious adverse effects have been rare even with repeated doses (DeSole et al., 1989; Pacque et al., 1990). However, minor adverse effects such as aggravation of symptoms as well as headache, hypotension, abdominal pain and vomiting have been reported in some studies.
There are several advantages of oral treatment over topical treatment, most importantly, the ease of use. Ivermectin is easier to use, and proper administration of both permethrin and benzyl benzoate can be challenging. Despite ivermectin being an effective treatment for scabies, it is not presently licensed for this purpose in most countries. It lacks safety data on use in small children and pregnant women.
Considerable variation exists in the price of treatments, especially ivermectin, but in low- and middle-income countries the price is relatively low. A course of permethrin costs about US$ 0.50, 25% benzyl benzoate less than US$ 0.10 and 5% salicylic acid around US$ 0.10.
