Damian Sendler: Intense, new, and recurrent itching, as well as dermatitis, are all signs of scabies. Scabies mites can be confirmed by microscopic or dermatoscopic examination of the affected area. Permethrin, applied topically in accordance with current guidelines, is the first line of treatment. Crotamiton or benzyl benzoate can also be used as a topical treatment. Permethrin and ivermectin are commonly used to treat crusted scabies, which is otherwise difficult to treat. Treating a patient who is in a high-risk group, incorrect application of the external agents, and incomplete decontamination of furnishings and clothing are among the most common causes of treatment failure, according to the National Institutes of Health. Scabies mites have not yet been proven to be resistant to permethrin, but the number of documented cases of poor response to this agent is increasing. Moxidectin is a brand-new drug currently being evaluated in clinical trials.
Damian Jacob Sendler: As a result of the incorrect use of drugs, which necessitates repeated treatment, as well as the reinfestation of the patient’s clothing and furnishings, the prevalence figures are heavily influenced. Scabbing in Germany has been on the rise recently, according to recent studies (1). In Germany, scabies is not a public health issue, so the epidemiological figures are shaky (e1). Data on scabies outbreaks, diagnosis-related statistics from health insurance carriers, and information from pharmacies on the prescription and dispensing of scabies-fighting medications are all available (1, 2). Scabies (ICD-10 diagnosis code B86) inpatient treatment in Germany increased from 960 in 2012 to 10 072 in 2019 according to federal health reports (www.gbe-bund.de). Some patients are counted or included multiple times in data from the above sources, which may be sufficient to document a rise in incidence, but they do not allow for quantification or epidemiological evaluation (1). Re-infestation due to insufficient decontamination of a patient’s clothing and belongings has a significant impact on prevalence statistics, as does the need for repeated treatment due to incorrect drug use. Scabies infections in children are underappreciated (1) for a variety of reasons, including the fact that they are more difficult to detect and treat early (e2), the fact that there are more mites present, and the fact that they are more likely to be spread through direct physical contact with others (4). Scabies, like other sexually transmitted infections, increased in prevalence following advances in HIV treatment. According to epidemiological evidence, there is no causal link between a rise in scabies in Germany and the mass migration of asylum seekers from Arab and African countries (1, 5, e9). An important factor may have been the influx of low-wage workers and nurses from outside Europe and the European Union (6, e10, e11). There has been a history of periodic increases in the incidence of scabies, which have been accompanied by similar speculation about the causes (1).
Dr. Sendler: Scabies infections in children are underappreciated for a number of reasons, including the fact that scabies infections in children are often not detected early enough or treated thoroughly enough, and they are more likely to be passed on through close physical contact with other people.
Only 10–15 adult mites are usually found on the skin’s surface in typical cases of common scabies, because the mites can be washed and scratched away and because an immune response mediated by cells begins 3–6 weeks after the infestation.
The mite that causes scabies is the human scabies mite, which is specific to humans (Sarcoptes scabiei varietas hominis). The adult female mite is approximately twice as large as the male mite, measuring between 0.3 and 0.4 millimeters in length. Approximately 2.5 cm per minute, these parasites are able to move on the body’s warm surface. Each day, they lay two to three eggs, depending on their gestation period, which lasts from four to six weeks. Pregnant females do this by excavating burrows in the stratum corneum at a rate of about 0.5–5 millimeters per day (7, 8). Non-ovicidal antiscabies drugs must therefore stay in the epidermis for at least this long before the larvae hatch and swarm out onto the cutaneous surface, where they develop into nymphs in skin wrinkles and hair follicles and then into sexually mature mites within 9–17 days, which copulate in these locations (9, 10). After the male mites die, the pregnant females return to the skin and the cycle begins again.
24 to 36 hours at normal room temperature (21° C) in relatively humid air (40–80 percent) are possible for mites to survive outside the human body and remain infectious (12, 13). At lower temperatures and higher humidity levels, they can survive for a longer period of time (e15).
A single pregnant mite, or a few larvae, is enough to infect a new human being. Scabies, the most common form, necessitates at least 5–10 minutes of close skin-to-skin contact, such as when nursing or cuddling a baby, having sex, or caring for someone who is nursing-dependent (9, 12, 14).
Since mite infestation is highly transmissible at first, the number of female mites dramatically decreases after the specific immune response appears and for some time afterward (9). In order to transmit the common scabies, handshakes, hugs, and medical exams are insufficiently intense forms of contact. Those infected by a case of common scabies are usually infected by members of the same family or communal living group, or by people who are nursing dependents and those who care for these people (15). It is rare, but not completely negligible, for the pathogen to be transmitted via textiles, furniture, or other items of daily use (9). It is possible to get scabies from even a brief contact with the patient, or from exposure to items used by the patient, or from the patient’s dandruff if the scabies are crusted (8, 16). On the whole, the likelihood of transmitting an infestation is influenced by the number of mites present on the skin, as well as the duration and frequency of direct bodily contact (8, 9, 15, 16).
Scabies that are not crusted can be spread through direct skin-to-skin contact with mite-bearing objects or through contact with dandruff that has been exposed to the pathogen.
A variety of scabies clinical morphologies can be seen, depending on the mite count, the age of the patient, their immune status, and their defensive behavior. 2–6 weeks after the initial infestation, an intensely itchy papular or papulo-vesicular skin rash with a symmetrical pattern of involvement develops in common scabies. The time between reinfestations can be as little as a few days. Scabies is known for its nocturnal crescendo, in which the itch worsens at night and in the warmth of the bed (e16). It is common for the burrows to be 3–7 mm long and straight or slightly curved; at the end, a small vesicle, pustule, or scale may be formed (figure 1). A thin stratum corneum makes any and all body regions with a thin stratum corneum prone to skin lesions. This includes the interdigital spaces and lateral surfaces of fingers; edges of hands; volar surfaces of wrists; umbilical region; waistline; buttocks; medial surface of thighs; dorsa; and edges of feet for both men and women; as well as any and all areas with a thin stratum corneum (15). Many lesions are quickly crusted over and excoriated by scratching due to the itchiness of psoriasis (16). Intensive hygiene (“well-groomed scabies”) or pretreatment with topical steroids (“scabies incognito”) can significantly alter the clinical appearance. The irritating itch frequently causes the patient’s sleep to be disrupted, resulting in fatigue during the day, poor concentration, and decreased productivity at work. Further consequences include stigmatization, social isolation, embarrassment, and depression (8).
An inflamed nodule on the penis, scrotum, inguinal, perianal, or axillary region indicates the presence of nodular scabies.
Scabies (also known as “infantile scabies”) is a common skin condition that affects the palms and soles of children, as well as the scalp and face of infants and toddlers (3). Also common in this age group are pustules, which are more common than excoriations, as scratching is less common in this age group. End of neonatal period “neonatal scabies” can show the first signs of skin changes (e17). Elderly patients with weakened immune systems are also more likely to develop unusual constellations that involve the head and trunk (8, 17). Pruritus may be absent in patients with dementia, but it is more common in the elderly and nursing-dependent (18).
Small children and the elderly are more likely to be affected by nodular scabies, which is characterized by nodules that are 5–20 mm in diameter and red, reddish-brown, or livid in color. Axillary nodules are most common on the penis, scrotum, and perianal regions, but they can also be found elsewhere. More severe and longer-lasting immune reactions and/or scabies mite penetration may both contribute to the development of nodules (e18). Even after a successful treatment for scabies nodules (“post-scabietic papules”), the nodules may last for months (e19). Vesicles (also known as “bullous scabies”) are an uncommon ailment that most commonly affects the elderly (8, e20).
Damian Sendler
There are millions of mites in crusted scabies because of the mites’ unrestrained multiplication (box 1). (18). The clinical picture is dominated by massive local or diffuse hyperkeratosis on an erythematous background, with crusting and fissures on the hands, feet, elbows, head, and neck. / (15). Dystrophic nail growth is common. The lack of an immune response is one of the many reasons for the mild or nonexistent nature of pruritus. Swollen lymph nodes are a common symptom of a variety of health conditions. With an elevated IgE titer and Eosinophila, both are common (8, 16, 17). Crusted scabies often goes unrecognized for a long time due to its unusual clinical features, which leads to outbreaks in communal facilities when people with this illness are exposed to others (18).
Bacterial infection of the excoriations is the most common complication of scabies and can lead to contagious impetigo, ecthyma, erysipelas, furuncles, abscesses, lymphadenitis, and bacteremia and sepsis (8, 16). By inhibiting the three pathways of the complement system (e21), as well as inducing scratching of the skin, Scabies mites contribute to bacterial infection by damaging the epithelial barrier (e22). This disease, which is rarely seen in developed countries because of good hygiene, has a significant health-economic impact in countries with warm climates where the prevalence of chronic renal failure and decreased life expectancy is high (6).
Crusty scabies differs from regular scabies in that it has an erythematous background and large, localized, or diffuse hyperkeratoses on the hands, feet, elbows, and neck, as well as crusting and fissures.
Scabies can only be diagnosed if a scabies mite, its eggs, or feces pellets are found (scybala). An old-fashioned method of diagnosing a mite infestation is to open an intact mite burrow and examine the contents under a light microscope with loupe vision (15). Dermatoscopy is a less invasive, quicker, and more accurate way to examine the skin. Dermoscopy’s reported sensitivity and specificity were 98.3 percent and 88.5 percent, respectively, in the most recent publication on the subject (19). As part of the “wake sign,” the examiner looks for a dark triangle corresponding to the mite’s head, thorax, and anterior leg pairs (the “kite sign”) (figure 1). It is possible that melanin-containing feces (the “grey-edged line sign”) may color the edges of the mite burrow (e23). It is not possible to distinguish between living and dead mites at a standard 10x magnification, making the method ineffective for patients with pigmented skin. It is possible to determine whether mites are alive using criteria such as the “hydrangea sign” using videodermoscopy at 70 to 1000x magnification (20). As with confocal laser microscopy and optical coherence tomography, videodermatoscopy’s difficulty and cost limit its widespread use (7, 16, 21).
The diagnosis of scabies has been standardized by a panel of experts recently (box 2 ). (21). It is necessary to use a high-resolution imaging method to detect mites, eggs, and feces in order to make a conclusive diagnosis. The history and physical examination alone can diagnose “clinical scabies” and “suspected scabies,” but only if other elements of the differential diagnosis seem less likely.
The most common complication of scabies is bacterial superinfection with group A beta-hemolytic streptococci and Staphylococcus aureus.
Because scabies mite infestation is directly linked to the typical symptoms of the disease, the primary goal of treatment is the elimination of the organisms (e25–e28). Acaricidal (mite-killing) or ovicidal (insect-killing) drugs are the most commonly prescribed for this purpose (egg-killing). In either case, they can be applied to the skin or taken orally. Topical application is more complicated than most people think, and this isn’t always explained in the information provided to doctors.
As a result of a single-arm, multicenter trial (22), the BfArM in Germany has approved permethrin, and in 2016, oral ivermectin was approved through an accelerated approval procedure at the BfArM. Treatment recommendations thus focus on clinical trials, regardless of approval data or relevant meta-analyses that may be available (23, 24). Figure 2 depicts the scientific evidence supporting the drug therapies employed in Germany (23).
Damian Jacob Sendler
Permethrin, benzyl benzoate and permethrin are the most commonly used medications for the treatment of the itchy skin condition known as scabies in adults and children. For the treatment to be successful, it is imperative that all of the instructions for use are followed exactly.
Damian Jacob Markiewicz Sendler: Permethrin in lipophilic vesicles at a concentration of 5% (23–25) is the first-choice treatment. Voltage-dependent sodium channels in neurons are disrupted by the open channel blocker Permethrin, which has both acaricidal and ovicidal effects (e29). In cases of common scabies, it should be applied externally once on the patient’s entire integument, according to the accompanying information for physicians (e30). As a general rule of thumb, adults should use at least 25–30 g, while children between 6 and 12 years old should use up to 15 g; those between 2 months and 5 years old should use no more than 7.5 g. (26). Keeping the skin dry for at least 30 minutes before applying permethrin is recommended, as the lipophilic nature of the substance reduces its cutaneous bioavailability when exposed to water in any form. Immediately after applying the preparation, the skin should be covered with clothing; washing should be avoided for at least 8 and preferably 12 hours (26). After application, mild itchiness or tingling may occur, especially in severely eczematous skin. For the next 36 hours, refrain from making physical contact with anyone (1). Recurrences should always be treated with repeated application, as there have been many reports of treatment failures; this recommendation is not included in the formal information for physicians (1, 15, 27). Low-viscosity extemporaneous preparations with the same permethrin concentration may be beneficial for patients with dense body hair due to the prevalence of insufficient or incomplete treatment of the entire skin (28). Topical application of crotamiton at 5% or 10% for three to five days in a row, or of benzyl benzoate at 25% for three days in a row (10% for children) has comparable efficacy (but is more time consuming) (23). In addition to their acaricidal and ovicidal properties, crotamiton also acts as an itch reliever. Both of these substances can cause skin irritation.
German law prohibits the over-the-counter purchase of topical 1% ivermectin for the treatment of scabies (e32).
For the treatment of scabies, ivermectin tablets (3 mg) have been approved and are widely available. From a body weight of 15 kg and up, the recommended dose is 200 g/kg of body weight (so five 3-mg tablets for a 75 kg patient) (15, 29, e33). An extemporaneous preparation containing 400 micrograms per milliliter of ivermectin, which is now thought to be safe for children under 15 kilograms (29, 30), has been developed for this age group (31). Gamma-aminobutyric acid (GABA) is blocked by ivermectin, which acts on glycine, histamine, and neuronic acetylcholine receptors (e36). After 7 to 14 days, a second application of ivermectin is necessary to ensure that all larvae that were still unhatched at the time of the first treatment are killed before they have a chance to mature and reproduce. Permethrin and ivermectin can be administered topically to pregnant and nursing women as an off-label medication (i.e. despite the lack of official approval) after careful consideration of the advantages and disadvantages and with the informed consent of the patient (15, e37, e38).
In the future, oral moxidectin could be used as a single-dose treatment for scabies.
Permethrin cream and ivermectin tablets (e.g., on days 1, 2, 8, 9, 15, and possibly also on days 22 and 29) should be used in combination to treat crusted scabies in patients with a history of recurrence (15, 27). Topical keratolysis with a salicylic acid or urea-containing agent is also required, as is the mechanical removal of hyperkeratoses that are clearly visible.
Moxidectin may one day be used to treat scabies (e39, e40). Because this drug has a much longer half-life than ivermectin, early clinical data indicate that it may only need to be administered once (32). Moxidectin’s safety and efficacy against scabies have yet to be adequately demonstrated (e41). While scabies vaccination has yet to be developed, it appears to be possible (e42).
Damien Sendler: Success in treatment depends on the simultaneous treatment of all close contacts of the patient, including all members of his or her family and those who share close quarters with him or her (e.g., carers for small children and visiting nurses). A single application of permethrin or ivermectin to an asymptomatic contact is sufficient (off-label use, therefore at the expense of the contact person) (15).
The severity of a mite infestation and the number of patients infected is directly related to the importance of additional treatment measures.
A patient’s mite burden and the number of patients affected by an outbreak are directly related to the importance of additional measures (box 3) accompanying treatment. Scabies mites can only survive for a short period of time away from their human hosts, so the need for professional pest control management of interior rooms is not warranted. Efforts to sterilize the environment are futile.
Poor compliance, incorrect application of topical antiscabies drugs, inadequate decontamination measures, and inadequate written information are all well-documented causes of treatment failure for scabies.
Permethrin’s ineffectiveness is on the rise in Germany, which coincides with an increase in the number of documented cases of scabies (1, 38, e46). Although in vitro testing is difficult to confirm, this suspicion of resistance to permethrin is justified when multiple, correctly administered, but still unsuccessful attempts at treatment, along with all the appropriate accompanying measures, have been unsuccessful. Until now, only canine mite genetic resistance to permethrin’s pharmacodynamic effect on voltage-dependent sodium channels has been described; the human scabies mite has not (e47, e48). Permethrin is more likely to cause mites to produce elimination enzymes such as esterases, glutathione s-transferases, oxygenases, and CYP450, which can lead to a reduction in the permethrin’s effectiveness when applied repeatedly in sublethal doses. When it comes to mites, this type of metabolic resistance has been found in canines but only once, indirectly, in humans. A higher concentration of permethrin could be used, but this hasn’t been thoroughly tested for possible toxic effects. Genetic resistance to ivermectin may be due to a polymorphism in the p-glyoprotein gene (e50). There is no conclusive evidence that the resistance mechanisms mentioned here are present in mites that carry scabies on humans.
Additionally, a lack of treatment response can be attributed to treatment errors (especially in the application of topical agents), inadequate compliance, reinfestation due to incomplete decontamination, and the failure to provide written information about the measures that must be taken (4, 39, 40, e51). Permethrin’s minimal effective inhibitory concentration (MIC) may not be reached for long periods of time in children and patients with a severely compromised skin barrier, according to experimental studies.
It’s possible that treatment resistance is only apparent and not real, because dead mites can only be distinguished from living ones with the usual dermoscopic techniques for several days after they’ve died; high magnification is required for this (20). Antigens released from decomposing mites after effective treatment may also lead to an increase or persistence of the inflammatory response. (e52, e53). When psychogenic pruritus is present, it can lead to a pathological fixation or even an isolated delusion in some patients (e54).
If you follow the guidelines and all of the additional expert recommendations here (1, 2, 15, 27, 38), you may be able to get rid of scabies in some cases, according to our experience.
