Scabies

Updated April, 2009

Dr Andrew Redmond,  Professor James McCarthy

Life Cycle

               Scabies is caused by infestation with the mite, Sarcoptes scabiei. It has been estimated to affect 300 million people annually (115). Known in animals as mange, the disease has been described since ancient times. A disease not unlike human scabies was described in the Old Testament and also by Aristotle in the fourth century BC (58, 104). Celsus, a physician of ancient Rome, is credited with coining the term scabies to describe a pruritic rash (31). Avenzoar (1070-1162 AD), an Arabian physician, and St Hildegar, Abbess of Bingam (1089-1179 AD) are reported to have described the mite but not the connection to human disease (100, 104). That link was made by Bonomo, who, with the aid of microscopy, saw the mite in fluid expressed from the lesions of infested patients (100,). His description is notable for being the first accurate description of parasitic etiology of disease. A treatise by Hebra in 1844 is said to have settled debate about the veracity of Bonomo’s discovery (23, 57, 100,).

Wisniewski B.  A Brief History of Scabies.  2008.

               The mite is transmitted by direct skin to skin contact and the disease occurs most commonly in children. Infestation induces intense pruritis, but sepsis from secondary skin infections, typically Streptococcus pyogenes and postinfective glomerulonephritis, especially in communities where the disease is endemic, are becoming increasingly appreciated (68). An atypical, more severe presentation of the disease, crusted scabies, is associated with mortality as high as 50% (38).

Hengge UR, Currie BJ, et al. Scabies: a ubiquitous neglected skin disease. Lancet Infect Dis. 2006 Dec;6:769-79.
 

Parasitology Guided Medline Search

               The mite, Sarcoptes scabiei var. hominis, is an obligate ectoparasite of humans. It is an arthropod of the class Arachnida, subclass Acari, order Astigmata and family Sarcoptidae (46). Sarcoptoid mites burrow into the skin of mammals and birds. The parasite spends most of its lifecycle within the stratum corneum of the host. The adult male and female mate with the male believed to die after this. The female lays eggs at a rate of two to three eggs per day for a lifespan of four to seven weeks. It is reported that less than 1% of laid eggs mature into adult mites (78). Over a two week period larvae develop into protonymph and tritonymph instars before becoming adults (19), at which time they emerge on the skin and ready for mating. Females will then reinfect the skin of the host or pass on to a new host.

               The adult female measures 0.4 x 0.3 mm, the male is smaller at 0.2 x 0.15 mm. Larvae have six legs, while adults and nymph stages have eight legs.

Epidemiology Guided Medline Search

               Scabies is ubiquitous. It causes episodic outbreaks in industrialized countries and is endemic in some tropical and subtropical regions (65, 90, 99, 124). It is able to affect people of all ages, ethnic groups and socioeconomic status. In industrialized countries the disease occurs sporadically in the community or in outbreaks in residential settings, such as prisons, army barracks, nursing homes or hospitals (9, 25, 51, 69, 83, 102, 106, 121). The disease is endemic in some developing countries and in economically deprived regions of some industrialized countries (65, 90, 99, 124).

               While the prevalence of scabies was previously thought to relate to poor hygiene, nosocomial outbreaks (54, 106, 121) and the high incidence in communities where children spend significant time in sea water (72) argue against this. Further, mites can survive bathing, even with soapy water (79). Endemicity thus appears to relate to overcrowding, rather than conditions of poor hygiene, per se (39, 62).  Poverty generally accompanies overcrowding and malnutrition, and associated immune dysfunction may in addition contribute to disease distribution and expression (122). Detailed epidemiologic data on the worldwide distribution are not available. While it has been proposed that the epidemiology of scabies has a cyclical pattern of infection over several years, this theory is not well supported by data.

Clinical Manifestations Guided Medline Search

               Classical scabies presents three to four weeks after infestation as a severely pruritic rash that is worse at night. The distribution of the rash is usually characteristic, affecting the interdigital webs of the hands, flexor surface of the wrists, anterior axillary folds, periumbilical skin, groin, ankles and at the periareolar region in women, and on the penis and scrotum in men. In young children and the elderly wider regions including the scalp, face, neck and soles of the feet may be involved. The initial skin lesions are papular and erythematous and are associated with mite burrows. Subsequently, more generalized papules and excoriations may occur, likely related to type-IV delayed hypersensitivity (59).

               Nodular scabies is characterized by extremely pruritic, firm, ruddy brown nodules in the pelvic or axillary regions. These are reported not to contain mites, and may persist for some weeks after successful treatment (59). They are likely to represent immune-mediated hypersensitivity. Supporting this hypothesis is the observation that topical pimecrolimus has been reported to be efficacious in achieving resolution of steroid resistant-disease after effective treatment with an acaricide (3).

               Crusted scabies, previously known as Norwegian scabies, is a more severe atypical form of the disease (114). The patient with crusted scabies may harbor millions of mites instead of the 10-12 present in classical disease (78, 103). This presentation has been associated with diseases affecting T cell function such as HIV or HTLV-I infection, T cell lymphoma, leukemia and solid-organ transplantation (26, 53, 103, 112). However, in a ten year series from the Royal Darwin Hospital in Australia it was most common to find no predisposing factor. Important risk factors that were identified in this study included chronic substance abuse, past leprosy, diabetes, malnutrition, chronic liver disease and immunosuppressive therapy (103). The affected areas of skin become hyperkeratotic with deep cracking. Any area may be involved but the peripheries and buttocks are the most common sites. The nails may become dystrophic and harbor thick deposits of skin debris (Figure 1). Empiric treatment of unrecognized scabetic pruritis with topical corticosteroids can alter the appearance and natural history of the disease. The clinical appearance of scabies may be altered by absence of scratch marks and diminution of rash. Failure to diagnose and treat the infestation may result in spreading of the infestation to others (119), or to the development of crusted scabies (35, 73, 75, 82).

               Secondary infection is a significant problem in classical scabies but even more so with crusted scabies. Streptococcus pyogenes is the most common pathogen, giving rise to pyoderma or lymphangitis. Post-streptococcal glomerulonephritis and possibly rheumatic heart disease are potential consequences of secondary infection of scabies (77, 113). Staphylococcus aureus may also cause secondary infection.

               Reinfestation presents differently from the initial infestation, in that pruritis generally develops within 2-3 days of infestation, rather than after 3-4 weeks. The generalized rash may also present earlier in the course and the localized rash may fail to occur.

               Endemic Scabies. In regions where scabies is endemic, clinical presentation may be altered. Priming of the host immune response by previous episodes of scabies is the likely mechanism. Lesions are generally present in multiple regions simultaneously, with the most commonly involved areas being the abdomen, inguinal/thigh region, axillae, wrists, interdigital spaces, legs, thorax, back, elbows, buttocks and arms (65).  It has been observed that burrows may not be detectable in infestations in tropical latitudes (124).  In adults with a degree of acquired immunity to clinical disease, pregnancy may be associated with development of limited areas of crusted disease, especially in the groin.

Delusional Parasitosis and Factitious Dermatitis. Infect Med. 2009: 84-88.

Laboratory Diagnosis Guided Medline Search

               Clinical diagnosis of scabies is straightforward when the typical syndrome of acute onset of widespread pruritis, worse at night occurring in several family members after contact with a known case of scabies. However, such pathognomic presentations are not universal.

               Laboratory diagnosis is therefore an important adjunct to history and clinical examination. It relies on demonstration of the mites or their products. Microscopy is performed on skin scrapings in 10% KOH with a light microscope under a low power objective. As well as mites, eggs, eggshell fragments or mite fecal pellets may be seen. While this method is highly specific its, sensitivity is reported to be poor (32, 122). Formal evaluation of the performance of microscopy of skin scrapings is hampered by lack of a gold standard test; however, a comparative study of skin scrapings with dermatoscopy undertaken in a specialist dermatology clinic is informative (44). In this study 238 patients were evaluated by skin scrapings and dermatoscopy. In the case of positive dermatoscopy and negative skin scrapings, repeat skin scrapings oriented by dermatoscopy were performed. According to this matrix 72% of patients evaluated were clinically assessed as being likely or very likely to have scabies; 52% had positive skin scrapings and 5% had been negative on initial scrapings but were positive on repeated scraping after revelation of positive dermatoscopy result. Thus, in this setting, the sensitivity of skin scrapings was high (90%). However, the test may not perform as well in other settings, depending on the number of mites infesting the patient, the number of sampling occasions, the sites sampled and the experience of the sampler (122). Skin biopsy may be undertaken when the diagnosis is uncertain. Features include perivascular monocytic and eosinophilic cell infiltration, papillary edema and epidermal spongiosis (47). While consistent with a hypersensitivity-type reaction, these features are not specific for scabies. A biopsy technique utilizing cyanoacrylate has been reported to facilitate diagnosis and to assist with differentiation between living and dead mites in assessment of treatment response (91).  Epiluminescence microscopy utilizes a stereomicroscope to examine the skin, and, as with videodermatoscopy, enables more detailed inspection than is possible with the naked eye. Recognition of mite anatomy and of the mite and burrow appearing as a “jet-with-contrail” has been reported (7, 56). Both techniques involve little risk, but again require expensive equipment and neither has been subjected to systemic evaluation (7, 29, 71, 80, 81). Dermatoscopy with a handheld device was found to be easy to use and as sensitive as microscopy of skin scrapings, with acceptable specificity (85%) (44).

               Polymerase chain reaction (PCR) targeting highly conserved sequences of the scabies genome, combined with competitive enzyme-linked immunosorbent assay detection of the PCR product (PCR ELISA) has been reported to assist with diagnosis of infestation. However the assay is not standardized and requires substantial time, expertise and specialized equipment (24). The low burden of mites and geographic location of most infestations provide challenges to the use of this technique (Figure 2).

Pathogenesis Guided Medline Search 

               Mites move slowly on warm skin and can survive for 24-36 hours away from human contact (17). If dislodged, mites are thought to seek odor and heat in order to find a new host (61). Mites are able to penetrate intact epidermis by secretion of enzymes capable of dissolving skin (77). In animal studies, mites induce migration of dendritic cells, T cells, neutrophils and plasma cells into the stratum corneum (16, 109). In subsequent infestations neutrophil migration is more rapid, of greater magnitude, and is associated with lower intensity of infestations compared to primary infestation. Study of the immune response in rabbits has demonstrated an antibody response but the titer of this response does not correlate with the severity of subsequent infestations. It is likely that cell mediated immunity (CMI) mediates the observed reduction in severity of subsequent infestations (15).

               Animal and human cell culture systems have been used to evaluate the CMI response to a crude extract of S. scabiei var. canis. It is characterized by stimulation of a variety of cytokines including TNF-α, IL-6, IL-8, G-CSF and VEGF, and stimulation of type-1 T regulatory cells (11-13, 15,  16). How these factors interact in the host in scabies have not been elucidated, but they are likely to be informative in efforts to produce a vaccine against scabies. It has been shown that a degree of immunity to disease arises in humans (78), but it is not clear how robust or durable it is.

               Patients with crusted scabies have been found to have eosinophilia and high circulating levels of IgE and IgG, of the IgG subclasses 1, 3 and 4 (103). Preliminary data reported by the same investigators indicated that there was an elevation of IL-4 mRNA level in peripheral blood mononuclear cells of patients with crusted scabies. It may be that host Th-2 predilection has a role in the development of crusted scabies. In two cross-sectional studies an overrepresentation of people with the MHC haplotype HLA-A11 was observed among people with scabies infestation, but the significance of this is uncertain (48, 86). Gene discovery in scabies has been underway since the mid 1990s (49, 63, 123). It has provided insights into a range of clinically relevant biologic questions including mechanisms of invasion, immune response, and drug resistance mutations such as kdr mutations ATP-binding cassette transporter genes (76, 87, 88). Such work may assist in development of novel diagnostics and therapeutic agents, and to prolong the utility of current acaricides.

SUSCEPTIBILITY IN VITRO AND IN VIVO Guided Medline Search In Vitro and In Vivo  

               There is no established culture system for S. scabiei var. hominis; so traditional susceptibility tests cannot be performed. Ex vivo mite survival assays using varying methods have been reported. In one mites are exposed to acaricides in an emulsion and motility monitored. Serial use of this method in Northern Australia demonstrated apparent increased tolerance to permethrin (50, 125). Comparative assessment of acaricides by direct application to mites has also been reported (93).

               Animal studies have been performed with varieties of S. scabiei other than var. hominis. Experimental infestation of rabbits and dogs with S. scabiei var. canis has provided information about the parasitic life cycle and the immunological response of the host (8, 10, 14-16, 18, 19, 84). Studies of varying design have evaluated treatment of sarcoptic mange in dogs and livestock and have demonstrated efficacy of avermectins (ivermectin etc.), chloronicotinyl insecticides, amitraz and a variety of plant-derived oils (22, 42, 43, 66, 70, 85, 108). Of these compounds, only ivermectin and tea tree oil have reached human use at this time. An animal model would be expected to have utility in evaluation of novel therapies and of development of acaricide resistance.

ANTIPARASITIC THERAPY

Drug of Choice Guided Medline Search

               There is a paucity of high quality data from randomized controlled trials comparing different therapies for classical scabies. Permethrin 5% is the preferred agent for topical treatment. It is a synthetic pyrethroid insecticide that is well tolerated, poorly absorbed across the skin and the small amount that is absorbed is rapidly metabolized. It is superior to crotamiton, (4, 110, 115) equivalent or superior to lindane, (4, 107, 110, 116, 129) and equivalent to synergized natural pyrethrins (5, 110).  Ivermectin, a macrocyclic lactone antibiotic of the avermectin group is active against a broad variety of nematodes and arthropods. It is the only oral medication with useful activity against scabies. It is superior to lindane (33, 74, 110) and at least as effective as benzyl benzoate (28, 52, 92, 111). Published data comparing ivermectin and permethrin is limited to two trials (2, 120). Comparison of these studies is impeded by lack of standardization of diagnosis and follow-up.

               As scabies is readily transmitted by close personal contact, it is recommended to treat simultaneously all members of a family unit and recent sexual partners, in order to avoid rapid reinfestation.

Special Forms of Scabies Endemic Infestation of a Community and Crusted Disease

               Effective management of scabies in a community where infestation is endemic requires simultaneous treatment of the whole community; otherwise treated individuals will be rapidly reinfested. A successful program in the Northern Territory of Australia employed a multifaceted approach, involving the community with education, diagnosis, treatment, adjunctive measures, follow up and retreatment (127). A report of a program in the Solomon Islands demonstrated a reduction in rates of scabies in children from 25% to less than 1% out to 32 months with a program of education, screening, treatment with ivermectin and retreatment on rescreening (72). When supply of medication for retreatment was interrupted in Panama, disease rates rose from ~1.5% to 12% within three months (117). As can be seen from these examples, there are no examples where the disease has been able to be eradicated.

               Treatment of recurrent or crusted scabies has not been subjected to systematic evaluation. Reinfection may be more likely than treatment failure. A reported treatment protocol for recalcitrant crusted scabies from Currie et al entails the administration of up to seven doses of ivermectin (at least 200 micrograms/kg/dose on days 0, 1, 7, 8, 14, 21 and 28) together with benzyl benzoate (every 2-3 days) and topical keratolytic creams (e.g. urea 10% and lactic acid 5% creams) (34, 64, 77) (Table 1).

Underlying Diseases

               While immune suppression may lead to altered disease expression, (6, 45, 95-97) treatment is dictated by clinical disease characteristics rather than host factors.

Alternative Therapy

               Ivermectin and permethrin are more expensive than some other treatments. Lindane 1%, benzyl benzoate and sulfur 6% are alternative topical therapies. However each has disadvantages.

               No acaricides have been shown to be safe in pregnancy. Animal studies have suggested toxicity of permethrin and benzyl benzoate (21, 30, 89). Lindane has demonstrated human toxicity (1, 27, 67, 128) and ivermectin has demonstrated embryotoxicity in rats (98). Ivermectin is being used in large quantities against filarial infection and substantial data about its use in humans should be forthcoming (55).

               Toxicity is a significant factor in choice of therapy. Permethrin may cause burning, and erythema, and dystonic reactions have been reported (36, 59). Pruritis is commonly reported after use of ivermectin, although this may represent hypersensitivity to released mite antigens rather than a reaction to the drug itself (94). Reported transient and mild reactions include anorexia, headache, asthenia, arthralgia, myalgia, fever and rash (59). There is one report of apparent excess mortality after use of ivermectin where the drug was used in a nursing home with an epidemic of scabies (20). While the report has been subject to criticism on epidemiologic criteria (37, 41, 101) and no similar reports have occurred, this should be taken into account when planning eradication treatment in elderly people. Benzyl benzoate can cause local irritation and may cause a disulfiram-like reaction if alcohol is consumed within 48 hours of application (32, 59). Lindane has been associated with neurotoxicity in babies (1). While a variety of dermatological adverse effects and aplastic anemia have also been reported, the strength of this association is not clear (27, 67). Crotamiton may cause conjunctivitis and erythema, and sulphur has local irritant effects and may be absorbed, and cause interstitial nephritis (59).  Drug resistance is an emerging concern with acaricides. Clinical resistance to lindane (60, 105), crotamiton (105) and ivermectin has been described, (40) and in vitro studies have shown reduced susceptibility to permethrin and ivermectin (40, 125).

Combination Therapy

               As outlined in the table, combination therapy is used in treatment of crusted disease. This approach has not been subjected to a randomized controlled trial, but has been developed in a setting where extensive crusted disease is seen regularly. (Personal communication Professor Bart Currie.)

ADJUNCTIVE THERAPY Guided Medline Search  

               As scabies spreads easily through personal contact, it is important to treat people with whom an index case has been in close contact. Machine-washing at 600C of clothes and bed linen with which the patient and his or her close contacts have been in contact within the last 48-72 hours is recommended on the day after the first treatment (32). As mentioned above, the use of keratolytic creams has been recommended in crusted scabies.

ENDPOINTS FOR MONITORING THERAPY Guided Medline Search

               Clinical response is the usual endpoint for monitoring therapy. Nodules may persist for some time after otherwise successful therapy. Persistent itch after therapy may be caused by treatment failure, reinfestation, reaction to therapy, postinfectious hypersensitivity/eczema or an incorrect initial diagnosis. Differential diagnoses for scabies include inflammatory conditions such as atopic eczema, contact dermatitis, bullous pemphigoid, dermatitis herpetiformis and urticaria; infections such as folliculitis, tinea corporis, herpes gestationis, eczema herpeticum, secondary syphilis, viral exanthemata and zoonotic scabies; or other causes, such as bites from insects or other mites, and delusional parasitosis. Currently available diagnostic methods do not permit the differentiation of dead from living mites, so a positive skin scraping soon after treatment may overestimate treatment failure. Some of the novel diagnostic methods referred to above may allow this distinction.

VACCINES Guided Medline Search

               There are no vaccines against scabies licensed for use. The observations that infestation is generally self-limiting and that significant protective immunity develops after primary infestation indicate that the development of a vaccine may be possible. Further, there is an available vaccine for cattle tick, another ectoparasite, (126). Of note, limited efforts to develop a vaccine against S. scabiei var. hominis have been unsuccessful to date. A recently published study examined response to caprine mite antigens adjuvanted with incomplete Freund’s adjuvant for the 1st and 2nd doses, and with Quil A for the 3rd and 4th doses. While a rise in IgG but not IgE was observed, no protection against disease was induced (118).

PREVENTION OR INFECTION CONTROL MEASURES Guided Medline Search

               Case management is a critical infection control measure for scabies. Isolation is not necessary except in cases of crusted scabies, as these patients can act as potential “super-spreaders” (103). Early diagnosis is essential for prevention of local epidemics in residential care settings, such as hospitals and nursing homes. Consideration should be given to treatment of all patients, employees and families in an institutional care setting if even one patient is confirmed to have scabies (106).

CONTROVERSIES, CAVEATS, OR COMMENTS

               The most urgent research goals for scabies are (i) development of a safe and effective vaccine, in order to prevent the disease and its complications, (ii) the development of more sensitive diagnostic tools for both primary diagnosis and test of cure, and (iii) clarification of optimal treatment for both classic and crusted scabies.

TABLE AND FIGURES

Figure 1: Examples of Crusted Scabies

Figure 2. Magnified Photograph of a Skin Scraping from a Patient with Crusted Scabies.

Table 1: Recommended Treatment of Scabies

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