Introduction

Years of experience with scabies patients and analysis of literature allowed us to systematize the reasons that contribute to the development of rare clinical variants of the disease. In Russian dermatological practice over the past 20 years, the Norwegian scabies (NS) has ceased to be a rare disease [1]. The importance of rare disease forms in clinical practice in term of scabies is indicated by the World Health Organization as a «forgotten skin disease» [2]. Foreign authors even proposed the term «surrepticius» (secret) to combine into one group of atypical clinical scabies’ varieties [3]. The causes of scabies pathomorphosis are numerous and they should be known not only by dermatologists but also by various doctors’ specialties in order to prevent diagnostic errors.

1. Diagnostic errors of scabies — one of the main reasons for the development of bullous scabies, NS, persistent skin scabious lymphoplasia (SLS), secondary pyoderma, etc. The use of drugs (systemic and topical) decreasing or eliminating the itching may contribute to uncontrolled increase in the number of pathogens in the skin and on its surface. An interesting fact was established that itching was weakened in alcohol abusers especially with alcoholic dementia [4]. Constant itching leads to a violation of the skin integrity that is a prerequisite for the introduction of bacterial flora and occurrence of secondary pyoderma. Scabies complicated by staphyloderma that represented by impetigo is considered an independent clinical form but not just a disease complication [5].

2. Scabies invasion in patients suffering from various dermatoses consequently leads to changes in the clinical picture of both diseases. The scabies features in patients with psoriasis, atopic dermatitis [6, 7], ichthyosis, dermatophytosis and rubromycosis of the feet upon infection with scabies [7], pseudolymphoma of the skin [8], NS at Deverji's disease [9], fungal mycosis [10] are described. Emphasis is placed on changing the clinical picture of these non-infectious dermatoses.

3. The clinical manifestations of scabies can mimic other skin diseases like eczema [11], bullous pemphigoid [3, 12], psoriasis [13—15], including rupioid [16], lichen rosacea [4, 17], Dühring's herpetiformis, urticaria, mastocytosis, histiocytosis [3], erythroderma of unknown etiology [18], systemic lupus erythematosus [19], seborrheic dermatitis [20], prurigo nodularis [19], epidermodysplasia veruciform [21] and even «graft versus host» reaction in recipients of hematopoietic cells [22].

4. Clinical manifestations of scabies often undergo pathomorphosis due to diseases’ comorbidity of various organs and systems that is most typical for elderly and senile people. Analysis of NS cases registered in the last century indicates that it arose in patients mainly based on monopathology of various comorbidities. However, in the last 30 years the cause of its development is polymorbidity of various origins pathology. NS occurs especially often at HIV infection with damage of various organs and systems [1, 13, 23-27].

5. Pathomorphosis of the scabies’ clinical manifestations was the reason for the new form of disease — scabious erythroderma that was first described by the authors [28, 29]. Later, other specialists began to register this form in clinical practice [30]. Erythroderma in scabies eliminates the main diagnostically significant clinical symptoms of the disease.

6. The presence of scabies on the head and neck in the adult can also be considered pathomorphosis. These skin areas are not the subject to scabicide treatment that can cause a disease relapse. At the same time, it can be assumed that a violation of treatment regimens for scabies, in particular, partial treatment of the skin, non-compliance with the drugs frequency, underestimated concentrations of scabicides, etc., that can contribute to the migration of the scabies mite to untreated areas — the head and neck. Scabies with a lesion of the «scalp» is even included in the list of rare variants of this dermatosis [4].

7. The development of resistance to scabicides in S. scabiei may also be the cause of the pathomorphosis. Mite resistance to lindane (the γ-isomer of hexachlorocyclohexane) was found in scabies treatment when repeated applications did not lead to patient recovery [31]. The term «lindane-resistant scabies» has even appeared in the literature [32]. Clinically identified resistance of S. scabiei to this drug was noted in different countries [33]. In Russia, the use of lindane is prohibited. Cases of S. scabiei resistance to ivermectin have also been described [34–36]. There have been reports recommending testing the sensitivity of ticks to ivermectin before administering it to a patient with scabies [37]. Multicenter randomized trials comparing the efficacy of various scabicides in scabies indicate that permethrin is an effective drug with a pronounced ovicidal effect [39]. There are no data on the resistance of the human scabies mite to permethrin and other pyrethroids in the literature although a case of resistance to permethrin has been reported in S. scabiei canis parasitizing on dogs [38].

In rare cases of scabies, the foci that form around the patients may have specific features. We have been studying the problem of scabies foci for many years [40–47]. The joint work of dermatologists and entomologists (A.B. Lange and Yu.V. Lopatin) made it possible to study various aspects of S. scabiei parasitism [47–49]. Examination of patients in the scabies foci made it possible to conclude that the epidemiology of scabies is due to the obligate-anthroponous nature of the disease, the constant type of parasitism and the predominance of the direct route of transmission of the invasion. The definition of the scabies focus is given like a group of people where a patient is a source of infection and conditions for pathogen transmission. The lesions are divided into potential (with one patient) and radiating (with two or more patients). The number of these foci depends on the level of contact between people that in parasitology is usually called invasive contact.

When studying the features of scabies focalization in families the main emphasis was noted on their development around patients with typical scabies. In these cases, the main route of pathogen transmission was considered like direct one — close bodily contact, more often in bed at night. Irradiating foci prevailed (²/₃) and the incidence in them depended on the children age. The indirect route of infection was rarely observed (up to 13%), mainly with a parasitic index (PI) of 40—60 in one patient or in total in the focus (in all patients) [40]. In this regard, the possibility of implementing an indirect route of infection was determined only clinically — by a complete count of scabies in all patients in the foci. The skin, bedding, underwear of the patients were not examined for the pathogen presence.

We did not find any works on scabies foci in patients with rare variants of the dermatoses course in the available literature. An analysis of numerous publications devoted to rare cases of scabies including NPs characterized by high contagiousness. When describing the local status it indicates often there is no data on the presence of the disease’s main clinical symptom— the scabies. Their visual identification and / or detection by dermatoscopy allows quickly confirm the diagnosis by a laboratory method. However, in some cases, NS was diagnosed only after histological examination of skin biopsies [14, 15, 19, 20].

From an epidemiological point of view, it is important to determine the number of itch tunnels. Only their calculation makes it possible to characterize the invasive potential of the focus in scabies and to answer the question of implementing possibility an indirect route of infection. It is clear that not every doctor considers it necessary to do this. However, even an indication in the medical history or outpatient card for the presence of «single» or «multiple» scabies makes it possible to assess the certain probability that contact persons are infected and decide on their treatment or preventive measures. In addition, in almost all publications describing rare variants of scabies there is no epidemiological history data: source of infection, route of infection, size of the focus (number of members and patients). There is no data on parasitological examination of underwear and bedding and, therefore, on the presence of ticks outside the patient.

Objective — to assess the epidemiological significance of family foci in rare scabies variants, to compare the effectiveness of various diagnostic methods and to adjust the treatment tactics.

Material and methods

Internet search engines Google Scholar, Cyberleninka, eLibrary, PubMed, Sigla were used for the selection of literature. The 29 family foci with rare variants of scabies’ patients were examined in 2012—2019. In most cases, the examination of the foci was carried out at the place of patients’ residence after applying to department by the patients themselves (8 / 27.6%) or their relatives (21 / 72.4%).

Among 29 patients with rare variants of scabies, NS was found in 8, scabious erythroderma — in 5, scabies with SLS misdiagnosed as other dermatoses — in 4, scabies complicated by secondary pyoderma in the places of typical localization of the tunnels — in 6, scabies with localization of scabies tunnels on the head — in 6. The age of patients varied from 50 to 93 years, men 17, women 12. Parasitic index (PI) was determined by visual counting of itch tunnels and using a dermatoscope.

The laboratory diagnosis of scabies was confirmed in all cases. We used the methods of removing the tick with a needle, scraping the scabies tunnel and individual sections of the epidermis using lactic acid, the method of adhesive tape tests and dermatoscopy that was performed using a DELTA 20 dermatoscope, USB microscopes of various modifications. This method also examined areas of the skin atypical for the localization of scabies, scrapings were performed from areas of the epidermis, and the resulting contents were studied in preparations made in lactic acid. The crusts removed from the skin of NS patients were examined after their layer-by-layer incision. To identify ticks the adhesive tape was also used (scotch-test method): a piece of transparent adhesive tape measuring 2×5 cm was glued several times to different areas of the patient's skin or to the layer on which the patient was lying. The used adhesive tape was glued to a glass slide, microscoped, counting ticks. Histological examination of a skin biopsy was carried out with additional cutting of material from blocks with a PAS reaction.

Results

The reasons analysis for the development of scabies rare clinical of is presented in Table 1.

Table 1. Reasons for rare variants of scabies development in family foci (n=29)

One of the important reasons for scabies foci development in families was mistakes in disease diagnosis. Both doctors of related specialties (100%) and dermatologists (62.1%) admitted them. There were 3.2 ± 0.9 mistakes in the diagnosis made by doctors for 1 patient. This led to the development of scabies rare variants. Long-term presence of the patient in the family focus contributed to dissemination of the skin process, an increase in the number of ticks on the patient and, as a rule, to the formation of severe forms of disease. Late diagnosis of scabies (from 3 months to 5 years) was noted in all patients. Topical glucocorticosteroids were prescribed in 100% of cases for the treatment of pruritic dermatosis. Elimination of itching as an important factor affecting the maintenance of the population of scabies mites at a certain level contributed to its growth and the development of a widespread process. The patients were characterized by comorbid pathology of various organs and systems — 89.7% of patients had 3 diseases or more that influenced the course of scabies. The weakening and/or elimination of itching was facilitated by the intake of systemic corticosteroids, immunosuppressants, antihistamines in connection with concomitant pathology treatment (55.2%). Non-compliance of treatment regimens for scabies was registered in 44.8% of cases.

Characteristics of scabies foci in patients with rare clinical variants in Table 2.

Table 2. Epidemiological characteristics of scabies foci in patients with rare clinical variants (n=29)

Scabies foci were 2.6 times more likely to form in patients aged 70 and older (72.4% versus 27.6%), 1.4 times more often in the presence of bedridden patients requiring constant care compared with patients who serve themselves independently (58.7% versus 41.3%). Irradiating foci 6.7 times prevailed over potential foci (86.2% versus 13.8%). From 2 to 4 people were ill in family foci. 45 contact persons were clinically and laboratory examined, 39 (86.7%) patients with typical scabies were identified. The reasons for the formation of radiating foci were the duration of their existence and mistakes in diagnosis (see Table 1). Unfortunately, it was not possible to identify the sources of infection the first patients in the foci were infected. The possibility of bringing scabies from family foci to non-dermatological hospitals was established in 1/4 (8/27.6%) of cases. All patients or their relatives noted the «ineffectiveness» of various scabicides (20% ointment and emulsion of benzyl benzoate, 5% concentrate of permethrin in ethanol, esbiol + piperonyl butoxide).

In radiating family foci (25/82.2%), its members did not have contact in bed, so the realization of direct route of scabies infection was minimal. This proved the rationales of assessing the invasive potential of 25 radiating foci taking into account the number of persons living together, the number of patients, the clinical form of scabies in the primary source, its PI, the results of dermatoscopy of skin lesions, skin examination by scotch-tape tests for the presence of the pathogen outside the patient. The results are presented in Table 3.

Table 3. Invasive potential of radiating scabies foci around patients with rare dermatosis variants (n=25)

Characteristics of radiating foci that have arisen around patients with NS, and their invasive potential

There were 8 such foci (32.0%). The age of patients that were the primary sources of infection ranged from 50 to 93 years. All had comorbidity of somatic pathology (3 diseases or more). The flats were mainly occupied by adults of three generations, all over 18 years old. There were only 2 foci with children under the age of 7 (1 and 2 children). The size of the foci (the number of people living together) is small — 2—5 people. The scabies were registered in all family members (2—4 persons) in 7 out of 8 foci. The existence of the foci ranged from 6 months to 5 years. It was not possible to determine the PI of the infection source due to the lesions of almost the entire skin.

In typical localization (hands, wrists, feet), itch tunnels were multiple and uncountable completely. The part of tunnels were destroyed. They were found behind the auricles (8 patients), on the face (8), buttocks (8), legs (5), shoulders (2), abdomen (2), back (1) by the method of skin dermatoscopy where the tunnels are usually absent. The invasiveness of the foci was determined by the scotch-tape samples from the patient's skin. After application to the skin, from 56 to 118 ticks (females, males, and larvae) were counted on the adhesive tape. Mites’ eggs were rarely detected.

The crusts contain the layer-by-layer scabies and many mites. It was possible to detect from 15 to 34 mites (females, males and larvae) using the scotch-tape tests when examining the bedding of patients. These data clearly indicate the risk of indirect infection the persons living together with NS patients and constantly care of them.

Clinical case 1

Patient E., 93 years old (Fig. 1). Diagnosis: NS. She was bedridden, operated on for colon cancer (colostomy introduced). Sick for about 6 months. She fell ill during her stay at the boarding house (August 2018). The dermatologist consulted the patient at home on 11.11.2018. Diagnosis: senile pruritus despite the presence of pruritus in daughter and her husband. Antihistamines were prescribed. For prophylactic purposes, it was recommended to treat the patient and family members with a scabicide. A 20% benzyl benzoate emulsion was used in violation of the treatment regimen (the drug was not rubbed into the perineum and soles). Itching and rashes persisted. They contacted the Skin and Venereal Dispensary at the place of residence, diagnosed with scabies, the mite was found. The patient and both family members received treatment with benzyl benzoate (again with a violation of the treatment regimen). In early December, the patient fell and broke her hip. She was admitted to the trauma department but the operation was not performed (the patient is elderly). After 4 days of hospitalization, massive crusts began to appear on the skin. She was consulted by 4 doctors and the scabies was not diagnosed. A week later, she was discharged home. Since then, the patient has been bedridden. At the end of December, a third course of treatment with 20% benzyl benzoate emulsion was carried out by dermatologist recommendation; it was recommended to treat all family members with the same scabicide. After examining the patient, the authors diagnosed with NS. The photographs taken on 01/23/2019 show the clinical manifestations of the disease (Fig. 1, a-e). The results of parasitological examination by the scotch-tape samples of the patient's skin and bedding are shown in Fig. 2, a-d. The study of the cross-section of the crusts made it possible to reveal their porous structure (Fig. 3, a), layered tunnels (Fig. 3, b), many mites (Fig. 3, c) including alive female (Fig. 3, d).

Fig. 1. Patient E., 93 years old. Diagnosis: Norwegian scabies.

a — forced position of the patient, diffuse erythema and multiple cortical layers in various areas of the skin; b — scabies burrows identified on the foot by dermatoscopy (marked with dots); c — massive crusts on the face; d — crusts on the scalp and auricles; e — crusted layering on the hands.

Fig. 2. Parasitological examination by the method of scotch-tape samples of the patient’s skin and bedding.

a — females, males and larvae (×30); b — mites from the forehead and cheeks; c — mites from bedding; d — mites from the scalp (circled with a marker).

Fig. 3. Study of a cross-section of crusts removed from the skin of a patient with Norwegian scabies.

a — porous structure of the crust (×3); b — multiple burrows, arranged in layers (×20); c — a set of mites in the crusts (indicated by red arrows, ×20); d — live female itch mite (×100).

Characteristics of irradiating foci and their invasive potential that have arisen around patients with scabious erythroderma

The proportion of such foci was 20% (5 patients). The primary sources of infection in the foci were patients aged 65 to 89 years. All had comorbidity of somatic pathology (3 diseases or more). Only adults of three generations lived in the flats where the foci were identified. The size of the foci is small (2-4 people). Scabies is registered in all family members living together. The foci existence is significant — from 5 to 8 months. Visually, in places of typical localization, from 50 to 310 itch burrows were fixed per anatomical area. By the method of dermatoscopy of the skin areas where there are usually no routs, they were found on the face of 5 patients, the neck (5), the scalp (5), and the pubis (1), in the inter-scapular region (3). In contrast to NS, many short metamorphic tunnels 2—3 mm long could be found in the skin. Females ticks were detected both in the affected skin and in externally unchanged skin (from 2 to 35 individuals per 1 cm2 of skin). Scrapings of the epidermis were carried out on the skin areas that atypical for the localization of scabies. Depending on the size area where the epidermis was scraped, from 9 to 25 mites were found. Females and males prevailed; less often, it was the found eggs of mites and, extremely rarely, larvae. On the adhesive tape after application to the skin (4 patients) from 2 to 12 mites (females, males and larvae, less often nymphs) were found, significantly less than in NS. Apparently, this can be explained by the peculiarities of the pathological process on the skin in scabious erythroderma — the presence of generalized erythema with infiltration and xerosis with minimal desquamation of the stratum corneum that created favorable conditions for the pathogen invasion into the skin. Examination of the patients’ bedding by the scotch-tape method made it possible to detect from 12 to 31 mites at different stages of development (females, males, larvae, very rarely nymphs). This indicates that there is an opportunity for indirect infection invasion to the persons living with the patient.

Clinical case 2

Patient S., 89 years old (Fig. 4). Diagnosis: scabious erythroderma. A detailed description of the case is given in publications (T.V. Sokolova et al., 2014; T.V. Sokolova, et al., 2018). Fig. 4 shows: a, c — generalized erythema with infiltration (erythroderma), dry skin, minimal desquamation, areas of hyperkeratosis in the buttocks, absence of crusts, b — itch burrows on the scalp. Parasitological examination results (d): scotch-test from the surface of bed linen, glass with adhesive tape and mites marked on it (circled with a fountain pen), ticks around (females and larvae) and eggs adhered to the tape.

Fig. 4. Patient S., 89 years old. Diagnosis: scabious erythroderma.

Detailed description of the case is given in the publications: Sokolova T.V., et al., 2014; Sokolova T.V., et al., 2018 [28, 29].

a — generalized erythema with infiltration (erythroderma), dry skin, minimal scaling; b — burrows on the scalp; c — generalized erythema with infiltration, scotch sample from the bedding, areas of hyperkeratosis in the buttocks, no crusts; d — mites are labeled with a marker, around it are mites (males, larvae) and eggs, adhered to the tape (pictures of mites with different magnifications).

Characteristics of irradiating foci around scabies patients with multiple SLS rashes

The share of irradiating foci was 16% in the structure. In all cases, mistakes were made in the diagnosis. Doctors' diagnoses: pruritus (2 patients), urticaria (1), toxicoderma (1). The age of the primary sources ranged from 56 to 87 years. All of them had 3 concomitant diseases or more. The 2—4 people lived in the flats; there were no children, 2—3 patients were found, in 3 out of 4 foci all persons were ill. The time existence of the foci was significant — from 4 to 7 months. It was impossible to count the number of itch tunnels due to the predominance of destroyed ones and heavily combed lenticular papules. The contents of itch tunnels were found not in all patients when scraping the epidermis from lenticular papules that are a variant of itch tunnels. It is explained by the fact that contents of the tunnels that associated with such papules can be detected only in the presence of fresh rashes. Severe itching leads to scratching and removal of the epidermis along with scabies routs. By the method of dermatoscopy, atypical skin localization of itch tunnels were found on the face (3 patients), neck (4), ears (1), behind the ears (3), on the scalp (3), buttocks (4). From 15 to 98 mites (females and larvae) were identified on the adhesive tape after application to the patients’ skin. Possibly, the mites were removed from the tunnels and they adhered to the tape because of unbearable itching in multifocal SLS. It was possible to detect from 3 to 12 mites (females, males, and rarely larvae) when examining the bedding by the scotch-tape method. It indicates the possibility of implementing an indirect route of infection in the foci.

Clinical case 3

Patient Ch., 87 years old (Fig. 5). Diagnosis: scabies, multiple SLS rashes. He has been ill since October 2019. He was caring for his «bedridden» wife (suffered a stroke). The woman was worried about severe itching and the presence of multiple rashes all over the skin. The neuropathologist interpreted this as an allergy to drugs. The wife died at the beginning of November 2019. The husband's rashes also appeared in October 2019. He had a history of spinal surgery that caused a decrease in the sensitivity of the skin below the IV thoracic vertebra and dysfunction of the bladder (permanent cystostomy and urine collection bag). After his wife died, the patient consulted a local dermatologist. He was diagnosed with «scabies by clinical signs» since mites were not found in the scrapings of the epidermis. Treatment with 20% benzyl benzoate emulsion with its rubbing on the 1^st and 4^th days into the entire skin except neck and head (as indicated in the directions to use) was prescribed. No treatment effect has been reported. Later he was treated by a dermatologist with a diagnosis of adult pruritus complicated by allergic dermatitis. Examination data: there are many lenticular highly itchy papules ranging from 0.5×0.5 to 0.7×0.7 cm that colored bright red with a bluish tinge and located focally on the skin of the abdomen, thighs, lower back, buttocks (Fig. 5 a, b, d). The skin of the face and auricles is affected (Fig. 5, c). Scabies tunnels were revealed on the lateral surfaces of the feet and on her toes (Fig. 5, e). The itch tunnel was revealed on the foot by the method of dermatoscopy; a mite-female was extracted from this tunnel by a needle (Fig. 5, f).

Fig. 5. Patient C., 87 years old. Diagnosis: scabies with lesions of scabious lymphoplasia.

a—d — multiple lenticular papules on the abdomen, thighs, lower back, buttocks, face and auricles; e — burrows on the foot (lateral surfaces and fingers); f — mite found on the foot by dermatoscopy and extracted from with the needle (preparation in lactic acid, ×30).

The contents of the Scabies tunnel were found when scraping the epidermis from the surface of uncombed lenticular papule (Fig. 6).

Fig. 6. Scraped epidermis from the surface of the unscratched lenticular papule (7 eggs with various stages of embryogenesis, feces).

Characteristics of radiating foci that have arisen around patients with scabies complicated by secondary pyoderma on the hands, wrists and feet — in the places of typical localization of scabies

Earlier, a classification of clinical variants of scabies was proposed on the basis of clinical and laboratory data [41]. It is based on the confinement to the tunnels of certain morphological elements and the results of its contents analysis. The 3 groups of tunnels including more than 15 varieties were identified. The importance of one group within others is the concomitant secondary infection to the exudate of cavity elements confined to the original tunnel type (the original type with a vesicle, a «chain» of vesicles, and a tunnel in the cap of a vesicle or bubble). In this case, the clinical manifestations are presented by staphylococcal impetigo. Analysis of the tunnels contents showed that in pus presence the female, as a rule, leaves it and most of the eggs die. In addition, patients, even with small abscesses, do not comb them. Thus, conditions for the migration of females along the skin and their introduction in other areas are created.

The proportion of radiating foci that arose around such patients was 12%. In all cases, mistakes were made by 3—6 doctors before the correct diagnosis was made. The age of the primary sources is 50—59 years, 2 of them had 3 concomitant diseases or more. These family foci existed for 3 to 5 months. Family size was 2—4 people, no children, and scabies reviled in 2—3 family members. PI at the primary source of infection is low due to the development of complicated tunnels variants (it is difficult to detect visually). The diagnosis in all cases was confirmed by dermatoscopy, scabies were found both on typical (hands and feet) and untypical (shin, shoulder) areas of the skin. In the epidermis scraping from lenticular papules (when fresh elements are presented), the contents of the scabies were found. From 2 to 8 mites were detected from the patients’ skin (only females), and from bedding — just 1–3 mites (only females) by the method of scotch-tape tests. In these foci, the infection of family members, most likely, occurred both directly (caring for the sick) and indirectly because of prolonged contact with the primary source.

Clinical case 4

Patient G., 50 years old (Fig. 7). Diagnosis: scabies complicated by secondary pyoderma. Complains of severe itching, mainly at night, the presence of rashes on the skin of the trunk and extremities. Patient has been ill for 5 months. Diagnostic mistakes of scabies made by 6 doctors (dermatologists, neuropathologist, traumatologist, phlebologist, infectious disease specialist). After an accidental fall, he broke both shinbones. An Ilizarov apparatus was installed for a fracture with displaced bones. In clinical manifestations of scabies he was twice treated in hospitals (neurological and trauma departments). Skin pathology was regarded as allergic dermatitis. He received glucocorticosteroids (methylprednisolone) intramuscularly for 3 weeks. The effect of the treatment is temporary. At the beginning the itching decreased somewhat, and then became very intensive with deep scratching development. Initially, pustules appeared on the hands, wrists and feet skin. Severe itching violating the integrity of the skin was the cause of the bacterial flora dissemination and the appearance of multiple foci of secondary pyoderma in various skin areas. Patient self-medicated the scabies used benzyl benzoate and rubbed it only on the affected areas. Objective examination data (Fig. 7): a deep pyoderma focus around wire of Ilizarov apparatus that rounded by bright red colored erythema with papules and folliculitis (Fig. 7, a). There are multiple deep (biopsy) scratches with purulent plaque on the surface (Fig. 7, b) and multiple pustules (impetigo and folliculitis) on the back of the foot. Erosion and purulent crusts located in the interdigital folds that treated with brilliant green (Fig. 7, c). In addition, lenticular papules in axillary region (Fig. 7, d), papules and pustules in the elbow area — a positive Ardi symptom were identified (Fig. 7, e). The 32 itch tunnels detected visually. The method of dermatoscopy revealed the tunnels in atypical skin localization: on the lower leg in 2 patients (Fig. 7, f), on the forearm in 1. Several mites-females were removed from the tunnels on the hands. The 8 mites were identified (only females) on the adhesive tape after application to the patient's skin; while examining the bedding — only 2. The female itch mite was removed from the itch tunnel on the lower leg that revealed by dermatoscopy (Fig. 7, g).

Fig. 7. Patient G., 50 years old. Diagnosis: scabies, complicated with secondary pyoderma.

a — a focus of deep pyoderma in place of the spokes from the Ilizarov apparatus; papules and folliculitis set against bright-red erythema; b — multiple deep (biopsy) scratches with purulent pellicle; c — multiple pustules (impetigo and folliculitis) on the back of the foot, erosions and purulent crusts in the interdigital folds, treated with brilliant green; d — lenticular papules in the axillary region; e — papules and pustules in the elbow area (positive Hardy’s symptom); f — burrow, detected with dermatoscopy on the lower leg; g — lactic acid preparation: female mite (×100).

Characteristics of radiating foci that have arisen around patients with scabies localized on the head

There were 5 such foci (20%) in the structure of irradiating foci. In all cases, when making a diagnosis, many doctors (5—8) made mistakes. The 2—4 people lived in the foci were no children and all family members fell ill (2—4). The primary sources in the foci were persons aged 62–78 years. The lifetime of foci is 5 months to 2.5 years. PI in patients is low (12—25) due to periodically treatment with various scabicides. The formation of irradiating foci in this case had specific features. Episodes of scabies «exacerbation» were associated with the not presence of high PI but with the migration of mites to areas of the skin (neck, face, scalp) that were atypical for adults (neck, face, scalp) with subsequent penetration the skin and scabies development that led to the preservation of a viable micro-population pathogen. The treatment of these skin areas in adult is not provided by actual direction from producers and is not included into Federal Clinical Recommendations of the Russian Society of Dermatologist-venerologists and Cosmetologists (2016). As a result, in the families the caregivers were re-infected. It is so-called ping-pong infection. The diagnosis in all cases was confirmed by dermatoscopy. Scabies were found on the ears and behind the auricles (3 patients), on the neck back (1), and on the scalp (2). Females, eggs, empty egg membranes were revealed by microscopic examination of epidermal scrapings from lenticular papules. The diagnosis was confirmed by a histological method in one patient. The results of scotch-test from the patient's skin and bedding were negative. In these foci, the infection of family members, most likely, occurred both directly (caring for the sick person) and indirectly because of prolonged contact with primary sources.

Clinical case 5

Patient S., 74 years old (Fig. 8). Diagnosis: scabies with head tunnels localization. She has been ill for 1.5 years. Her husband fell ill first in the family. He was under psychiatrist monitoring with severe form of schizophrenia and was constantly receiving tranquilizers and antipsychotics. The source of infection has not been identified. The man was treated with diagnoses of «senile itching», «drug toxicoderma», and «benign skin lymphoplasia». Prophylactic treatment of scabies was carried out twice. Piperonil butoxide + esbiol (Spregal) was prescribde to the patient only on skin areas with rashes. The effect of treatment is temporary. After 3 weeks, the itching began to bother the wife and the nurse. On the recommendation of a dermatologist friend, the patient and both women were prescribed treatment with 20% benzyl benzoate emulsion. After 3 months, the situation in the family was repeated. All persons living in the foci were treated once more. Again, piperonyl butoxide + esbiol was used. Similar episodes of «exacerbation» of scabies were observed 3 times. The source of infection in the foci (husband) died 3 months ago. The wife was admitted to the hospital N.N. Burdenko with complaints of excruciating itching and skin rashes. Physical examination data: the process is widespread; the rash is disseminated throughout the skin. Multiple follicular and single lenticular papules were found on the buttocks (Fig. 8, a). The 2 lenticular papules were localized on the groin area skin based on erythema, (Fig. 8, c). Two lenticular papules were found on the right auricle skin (Fig. 8, b). The diagnosis of scabies was confirmed by scraping the epidermis from the lenticular papules on the auricle. The typical contents of the itch tunnels were found. A biopsy of the lenticular papule under the mammary gland was performed (Fig. 8, d). An intradermal cystic cavity with a mite (PAS-positive) was found in the epidermis.

Fig. 8. Patient S., 74 years old. Diagnosis: scabies with localization of burrows on the head.

a — multiple follicular and single lenticular papules on the buttocks; b — erythema and lenticular papules, the place of biopsy labeled with arrow; c — two lenticular papules on the auricle; d — histological preparation of a skin bioptate: an intradermal cystic cavity with a cut of the mite in the epidermis (PAS-positive).

Diagnostic value assessment of various methods of scabies’ laboratory diagnosis

In accordance with the Order of the Ministry of Health of the Russian Federation of 24.04.2003 No. 162 «On the approval of the sectoral standard «Protocol for the patients’ care. Scabies» the diagnosis of the disease must necessarily be confirmed by laboratory methods (extraction of the mite with a needle, dermatoscopy and scraping of rashes using lactic acid). The dermatoscopy method is aimed at identifying scabies mites in the skin, and the methods of extracting the pathogen are aimed at establishing the presence of a pathogen in the rash (females, larvae, nymphs, eggs, and empty egg membranes). In this case, the invasive potential of the foci is assessed only by the number of itch tunnels in all patients in the focus. It is almost impossible to resolve the issue of realization an indirect pathway of infection in radiating foci. The use of the scotch-test method in patients with scabies and his bedding with positive results indicates the possibility of indirect infection. Work in irradiating foci of scabies made it possible to determine the diagnostic significance of all listed methods (Table 4).

Table 4. Diagnostic value of methods for laboratory diagnosis of scabies in irradiating foci (rare dermatosis variants)

Note. ++ — high efficacy of the method, + — effective method, (–) — non-effective method.

The method of epidermis scraping is highly effective in all clinical forms of scabies if the specialist knows how to identify scabies and knows their clinical variants. The dermatoscopy method is effective for all clinical forms of disease to determine the stages of development of an itch mite (females, larvae, eggs, empty egg membranes) if specialist is able to use a dermatoscope. The method of scotch tests from the patient's skin and bedding is highly effective for NS, scabious erythroderma and scabies with multiple eruptions of SLS. It can be used for scabies complicated by pyoderma, with its localization on hands, wrists and feet. If patients, especially the elderly, have repeatedly received treatment with scabicides in violation of treatment regimens, the dermatoscopy is indispensable method for examining head skin areas. The data obtained indicate the scotch-tape method can be included in the clinical guidelines for doctors.

The study made it possible to describe the rare variants of scabies. It identifies the reasons for the development of family disease foci around such patients. Study results established a topic of scabies that is unusual for adult patients to adjust the treatment tactics and to evaluate the role of indirect invasion path by identifying the pathogen directly on the skin and on bedding.

Discussion

Patients with diseases of various organs and systems are often infected with scabies. Almost all radiating foci registered in this study formed around elderly and senile patients with rare manifestations of scabies and severe comorbidity of different pathologies. Diagnostic mistakes made repeatedly by doctors of various specialties. Insufficient knowledge of diagnostic laboratory methods to detect mites and prescription of drugs decreasing the itching lead to the emergence of rare but severe forms of scabies with high contagiousness. The hospitalization needs of such patients leads to introduction of infection into multidisciplinary medical institutions, psychiatric hospitals, nursing homes, etc. It was found that in Russia the diagnostic mistakes made by doctors were found in 40% of patients [50]. They are recorded in every 3—4 outpatient and 5—6 inpatient cases [51]. In the foreign literature, just in 2003 the 6146 articles were published in 4000 journals with an analysis of mistakes in the diagnosis and treatment of various origins diseases [52]. With regard to scabies, there was a case when diagnosis mistakes in disease that proceeding with concomitant pathology during several months of outpatient treatment and 3 months of inpatient treatment were made by several specialists (dermatologist, rheumatologist, therapists, neuropathologist, otorhinolaryngologist) [53]. The author reasonably notes that the causes of mistakes were superficial collection of anamnesis, inadequate examination of the skin, poor documentation, violation of the thinking logic, overestimation of the laboratory research role, insufficient knowledge of the clinical features of the most common dermatological diseases. Unfortunately, when analyzing the features of scabies it is often indicated in a number of publications that disease has become «atypical»» in the absence of scabies, «paired elements» are significant diagnostic criterion for scabies, scabies in adults cannot exist on the feet. The cause of diagnosis mistakes in scabies is the lack of knowledge in life cycle of scabies causative agent. Information about «atypical» scabies without scabies tunnels with disease duration more than 2 weeks is absurd. Reproduction of the pathogen population occurs only in the itch tunnels. If there are no tunnels then there are no females laying eggs, and therefore, there are no larvae making lateral tunnels from the maternal tunnel with the appearance of non-inflammatory vesicles near the tunnel. There would also not be larvae that leave the tunnel through the holes and penetrate the hair follicles in the place where follicular papules would arise. A careful examination of the hands in patients allows diagnosing the disease in 98% of cases. The so-called paired elements are not a diagnostic symptom of scabies. Microscopic examination of scrapings of papular, papulo-vesicular «paired rashes» located close to each other, as well as the epidermis between them in different skin areas did not reveal the contents of scabies tunnels (female, eggs, egg membranes, feces) in more than 2000 patients with scabies. There is no information in the foreign literature about any «paired elements» in scabies and their connection with scabies tunnels. If disease lasts more than 2 months and process widespread, the scabies tunnels on the feet can be found almost always. They should be found on the feet arches, in the ankle area, the Achilles tendon, on the lateral surfaces of the fingers, and even in the interdigital folds. If a patient with scabies is exposed to fuels and lubricants (gasoline, diesel fuel, etc.) with acaricidal properties, mites’ females migrate from hands to feet even with a short history of disease. SLS, as a variant of scabies on the abdomen skin, buttocks, male genitals, in the axillary region is a diagnostically significant symptom.

In accordance with the Order of the Ministry of Health of the Russian Federation of 24.04.2003 No. 162 «On the approval of the sectoral standard «Protocol for the patients ’care. Scabies», the diagnosis of the disease must be confirmed by laboratory tests (extraction of the mite with a needle, epidermis scraping using 40% lactic acid) and by dermatoscopy. The scraping method is quite effective when the doctor or laboratory assistant is able to detect the itch rout. In order to realize it, the specialist needs to know the topic of scabies and the classification of their clinical variants [41]. Many authors have showed the effectiveness of the dermatoscopy method [54—57]. Our studies show that the frequency of detecting mites in itch tunnels by this method reaches 97%. Less often, they are detected during examination of follicular papules on the trunk (21%) and vesicles on the hands (32%) [54]. These data are consistent with the results of previous studies of papules and vesicles contents obtained by scraping. Microscopic examination of preparations in lactic acid revealed mites only in one third of cases [58]. The rest of the morphological elements probably arose because of the body's allergic reaction to the mite and its metabolic products. However, the dermatoscopy cannot evaluate the effectiveness of scabies treatment with various anti-scabies drugs. It is possible to confirm the ineffectiveness of the drug only after removing the alive female from the rout. Comparative analysis of the scraping methods effectiveness, dermatoscopy and scotch-tape tests indicates that each of them has its own place for usage [45, 54] that is reflected in this study. It is impossible to agree with the data indicating the high efficiency of the scotch test method in typical scabies [59]. Papules and vesicles where authors propose sticking tape for 12 hours represent the clinical manifestations of the metamorphic part of the life cycle (larva — protonymph — teleonymph — young female / male). The entire process of larva development into a sexually mature individual happens in the skin and takes 12-14 days. In addition, after a few minutes, a water-fat layer of sweat and sebum forms under the adhesive tape glued to the skin that sharply reduces the adhesiveness of the tape.

Thus, the improvement of clinical and laboratory diagnostics is aimed at the timely detection of scabies and is an important mechanism for preventing diagnostic mistakes, the formation of rare and including severe forms of the disease in family foci and their subsequent deployment in organized groups.

Conclusion

1. Criteria for the epidemiological significance of family foci in scabies are the contingent of patients, the size of the foci, morbidity, the number of patients among contact persons, the causes and irradiation, clinical forms of dermatosis, the tine duration of existence, the introduction of scabies from the family into organized groups, the invasive potential, assessed by various methods (determination of the parasitic index, dermatoscopy skin areas that are typical and atypical for itch tunnel localization, pathogen identification on the skin and outside by the method of scotch-tape tests).

2. In families, scabies foci can arise around patients with rare variants of the disease because of pathomorphosis. The reasons for its occurrence are systematized in literature data and based on personal authors’ experience in the examination and treatment of patients with NP (8), scabious erythroderma (5), scabies with SLS imitating other dermatoses (4), complicated by secondary pyoderma in the places of typical localization of the tunnels (6), in case of itch tunnels localization on the head (6).

3. The lesions that arise around patients with rare scabies variants have characteristic features. They form around elderly and senile patients (56-93 years), often in the presence of «bedridden» patients with constant care (58.7%), radiating foci (86.1%) of small size (2-5 members) prevail with adult family members of 2-3 generations (88%); patients among contact persons 89.7%, all of them have typical scabies. The possibility of bringing scabies from family foci to non-dermatological hospitals was noted in 27.6% of cases.

4. Patients with rare scabies variants are characterized by comorbidity (3 or more diseases in 92%), the use of systemic corticosteroids, immunosuppressants, antihistamines, psychotropic drugs that weaken or eliminate itching (55.2%). Mistakes in scabies diagnosis were consistently made by 3–8 doctors of various specialties (3.2 ± 0.9 on average) that led to the long-term existence of parasitosis (from 3 months to 5 years).

5. Evaluation of the invasive potential in primary sources in family foci indicates the patients’ contagiousness with NS, scabious erythroderma, scabies with SLS imitating other dermatoses and complicated secondary pyoderma at the sites of typical localization of tunnels. The detection of mites on bedding indicates the implementation of an indirect route of infection in the foci.

6. The reason for the ineffectiveness of scabicide treatment in most cases (80%) was the violation of treatment regimens (partial treatment of the skin). Episodes of «exacerbation» of scabies in 20% of radiating foci in these cases are associated with the pathomorphosis of scabies. The migration of mites to skin areas that are atypical for adults (neck, face, and scalp) was accompanied by the formation of itch tunnels there and the preservation of a viable population of the pathogen. The treatment of these skin areas in the adult population is not provided for by the existing instructions of manufacturers and is not provided for by the Federal Clinical Recommendations (2016).

7. Assessment of the diagnostic significance of various laboratory methods for scabies indicates the high efficiency of epidermal scrapings and dermatoscopy. Their use made it possible to confirm the diagnosis in all rare variants of the course of the disease. The method of scotch tests from the skin and bedding is relevant only for scabies with a high PI (NS, scabious erythroderma, multiple rashes of SLS).

Authors’ contributions:

The concept and design of the study: T.V. Sokolova, Yu.V. Lopatina

Selection of literature: T.V. Sokolova, Yu.V. Lopatina, A.P. Malyarchuk, K.M. Novolotskaya

Examination of scabies foci in families: A.P. Malyarchuk, Yu.V. Lopatina, K.M. Novolotskaya

Preparing illustrations: A.P. Malyarchuk, T.V. Sokolova

Material analysis and drafting the manuscript: T.V. Sokolova, Yu.V. Lopatina

Revising the manuscript, making a list of references: T.V. Sokolova, Yu.V. Lopatina, A.P. Malyarchuk

The authors declare no conflicts of interest.