Review

HAIR FOLLICLE MITES (ACARI: DEMODICIDAE) OF MAN WILLIAM B. NUTTING, PH.D.

"Demodex folliculorum," the rubric under which the hair follicle mites of man was recorded for 130 years, has recently been re-evaluated' to distinguish two separate species: a larger, Demodex folliculorum (Simon), located primarily in the hair follicle, and a smaller species, D. brevis Akbulatova, in the main residing in the sebaceous glands. Both species are, as adults, spindle-shaped, minute ( > 350 /-m), sexually dimorphic, obligate parasites which are often obtained in the same skin sample (scrape specimen, biopsy or autopsy). They are, furthermore, ubiquitous,- recorded from all major races of Homo sapiens.'^ To date, no confirmed measures of prevention, control or eradication have been developed.'

From the Department ot Zoology, University ot Massachusetts, Amherst, Massachusetts

which included some measurements with illustrations, and that both long and short forms were present in his sample of Acarus folliculorum. A careful generic re-evaluation was made by Owen in 1843"' (/Acarus to Demodex), which held up with only minor changes through 1961 and again 1972. The work of Raehlmann," 1899, called attention to the possibility that demodicids were involved in blepharitis. A most scholarly review of 145 papers, including a great deal of original work, was provided by Gmeiner in 1908." The same year, Borrel'^ published the first of a series of papers which located the mites in tissue sections and suggested that they could transmit other disease-producing organisms, such as those which cause leprosy and cancer. Lawrence" (1916) was one of the first to present a report on a case of demodicosis of the face accompanied by gross signs of disease.

In this review I will, after a brief historical note, cover the following topics: incidence, species characteristics, locus of parasites, clinical accounts, histopathology, host-parasite interactions, prevention and control and critical problems. Information on other species of demodicid mites will be interjected in support of observations on those of man or in instances wherein they offer analogues that could lead to future research.

Hirst'" (1919) provided a classic and perspectived monograph of the genus Demodex which lists, in appropriate format, the major taxonomic references for "Demodex folliculorum." However, it has no bibliography "due to the high cost of print . . . over 230 references available" (p. 39).'" Except for this last imperfection, this is currently the key work on demodicids. The meticulous studies by Fuss (1933 on) clearly show that the mites are

Historical Note "Demodex folliculorum" was discovered, independently, by Henle and by Berger in 1841. The following year, Simon provided the first description. Address for reprints: William B. Nutting, Ph.D., Department of Zoology, University of Massachusetts, Amherst, MA 01002.

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ubiquitous: she also attempted a correlation with mite and host skin condition, tried to explain the mite life cycle, and discussed measures of treatment. In 1934, the excellent paper of Beerman and Stokes^i was published. This included a careful review of the literature since Cmeiner's work, some clear assessment of the role of "D. folliculorum" in pathogenesis, and original studies of skin conditions, especially rosacea, associated with these mites. Soon after this, a number of surveys and case reports of demodicosis in man appeared in the medical literature (Table 1 and Grosshans et al.i2). Spickett's paper^^ in 1961 contains some very interesting behavioral studies and the only careful attempt to assess the approximate length of time spent in each (then known) stage of the mite life cycle. He also published a report the same year on the possibility that " D . folliculorum" transmits Mycoba'cterium leprae.^* My review of host-parasite relations of demodicids appeared in 1965,* and a reassessment published in 1968'^ of host species specificity indicated that these mites are host species specific. Although several authors suggest subspecific status for many demodicids, Akbulatova"^ showed that, in fact, certain stages (ova, larvae, nymphs, adults) are quite different. She proposed that the two forms be called D. folliculorum brevis and D. folliculorum longus. Norn'^ also suggests subspecific status. In 1972, our laboratory published evidence, discussed later, that two distinct species, ecologically isolated in the skin complex, live on man.^* The larger species was retained as D. folliculorum (Simon) and the smaller was elevated from subspecific status to D. brevis Akbulatova. Both were indicated provisionally as minor pathogens, merely by harvesting

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of cells of the follicular epithelium (the former) or of the sebaceous gland (the latter). Recently, Grosshans et al.'^ have indicated some pathogenesis linked with these two species and included a fine medical review. Table 1 provides an annotated, chronological list of papers of major concern to the medical profession including those noted previously. Accounts are still being published in which not only many of these scholarly discoveries are repeated, but this is done with less rigor and with the introduction of poorer quality observations and multiple errors. In even very recent reports it is neither fully confirmed nor denied that there are two distinct demodicid species on man. For example, Grosshans et al. provides a weak description which could apply to several species of the genus, even though citing our paper in the text. Case reports without assessment of mite species differences are no longer appropriate—even when such distinctions are made, they should now be accompanied by details of histopathology (see later discussion). We presently have over 250 entries, not including texts, in our bibliography on D. folliculorum (sensu latu) with approximately 1300 for the genus as a whole.'** Such information unfortunately is often bypassed in reports: an analysis of recent papers indicates an over-reliance on general texts or those limited to the author's own specialized field of interest. The accelerating rate of publication places a burden not only on reviewers and researchers, but also tends to discourage new workers from entering this interesting field of research. Incidence The papers of Gmeiner^ and of Beerman and Stokes" record a succession of studies which show that "D. follicu-

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HAIR FOLLICLE MITES

Table 1.



m

Nutting

Landmark Papers on Hair Follicle Mites of Man with Brief Annotations*

Major contribution

Authority

Date

Discovery of demodicids of man

Henle"'' Berger^"

1841 1841

Independent recoveries, Berger from cerumen

Scientific description (Acarus tolticulorum)

Simon""

1842

Notes long and short form, data on recovery; first illustrations

1843

Accurate resolution, Acarus became Demodex

Genus renamed Demodex

Details -

Lesions and mites

Raehlmann"

1899

Mites associated with blepharitis

Disease transmission potential

Borrels

1908

Suggests as transfer agents for other disease organisms

Ubiquity of mites, biology, treatment

Gmeiner'

1908

Scholarly review and original work on incidence, treatment, etc.

Relationships of mites, bacteria

Gmeiner^"

1909

Suggests mites may open skin to bacterial infection

Cross signs of disease

Lawrence''

1916

Skin eruptions associated with "D.

folliculorum" Monograph on Demodex

Hirst"

1919

Cancer, mites

Chambers & Somerset""!

1925

Incidence, skin conditions

Fuss=

1933

Review—mites, disease

Beerman & Stokes^^ 1934

Scholarly review and original studies, esp. re rosacea

Behavior, biology

Spickettis

Stereotactic behavior span in life cycle

'

1961

Scholarly survey, all facets of the genus known to 1919 Explores breast cancer and mite invasion 100S incidence, skin condition and therapy

Two subspecific mites of man

Akbulatovai"

1966

Notes differences and incidences; clinical conditions described; seasonal abundance

Host-parasite relations (review)

Nutting'

1965

Review, list of mite-disease reports

Two species extant on man

Desch & Nuttingi

1972

Description, all stages, photos both mite species

Pathogenesis review

Grosshans etal.i=

1974

Derangements associated with each species, fine medical review

Incidence in aborigines

Nutting & Green=°

1974

Incidence, both species, from small sample of Australian aborigines

Anatomy, morphology D. tollicuiorum (Simon)

Desch & Nutting

in ms.

Details to EM level of mite anatomical systems



Other worthwhile papers are available from the reference lists in above.

lorum" has been recovered from infants to aged adults. Simon did not find mites in two newborns. Gmeiner examined

adult cadavers and located demodicids in 97% of these. Fuss,2 in a very careful study of the living, found a 100% in-

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cidence (Table 6). She re-examined subjects until mites were discovered. Epilation of eyelashes is a favorite recovery measure for demodicids of the eyelids.'^ Using this technique, and by plucking an average of 9.4 lashes from each of 100 cadavers, N o r n " recovered 48% positive for demodicids. Mites have now been recovered from all racial groups of man,' although published reports, with few exceptions, fail to differentiate D. brevis from D. folliculorum. The fact that Australian aborigines possess both species, which occur identically in Caucasians,^^ probably shows that these mites are conservative in evolution and that both species will also be discovered eventually in even the most isolated groups of people. Considering these isolated geographic groups of man, our laboratory has accumulated records of both species from pureblood Eskimos (Devon Island), Maoris (New Zealand) and Nigerians (tropical Africa). Akbulatova'*^ suggests a seasonal (spring) increase in clinical signs of demodicosis in the USSR (differing from the wet-dry or dry conditions of the equator). A similar seasonal increase in lesions has been reported by Bennison^i for horses (D. equi) and by Poliakov22 for cattle (D. bovis). Akbulatova"" noted a differential recovery of long and short demodicids in man; however, this was at a time when the life cycle had not been detailed. She found that of 69 patients examined, 25 had the long form, 16 the short and 28 both. Records for incidence for each species are available in a small sample of Australian aborigines.20 In 25, D. folliculorum was found in 6 (24%) and D. brevis in 6 (24%): 3 males with only the former, 3 (2 male, 1 female) with both species, and 3 males with only the latter. Only a single female was parasitized— and with both species.

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A further complication, although without clearly documented taxonomic proof, has been introduced by the suggestion that D. canis is transmissable to man.^^ Cases reputed as such which we have seen have so far proven to be negative for D. canis, but positive for either D. brevis or D. folliculorum. Characteristics for discrimination of these last from D. canis are presented in Table 3 and a more complete description is currently in preparation. Interspecific transfer is unlikely.2'* Furthermore, clinical signs and symptoms due to Sarcoptes spp. are very often found in man during his close association with the dog.25 Incidence studies also raise the problem of mite transference between host individuals and between pilosebaceous components. Evidence from studies on D. canis show that mites are not present in the fetus^*" but do appear on the muzzle as early as 272 days of age.2' Several reports, as Garven (1946),28 have located mites in the human nipple. These reports suggest that both demodicid species of man are passed between mother and young during the nursing process. No data exist on adult-adult transfer, and only speculation on pilosebaceous transfer. Costen" speculates that they move at night and Norn'^ did find adult and nymphal mites moving across the skin in the daytime. In terms of incidence, one can conclude that wherever mankind is found, hair follicle mites will be found and that the transfer mechanism is 100% effective! (One of my students noted it was undoubtedly the first invertebrate metazoan to visit the moon!) This worldwide distribution should make it feasible to assess the impact of genetic, nutritional or environmental factors on the hosts and mites, but difficult to assign a causal relationship to skin lesions, because the mites are prob-

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ably present in all conditions, diseases or excoriations which affect the skin.

Table 2. Comparative Measurements — Means and Standard Deviations ot Each Stage and Sex ot Demodex folliculorum and D. brevis*

Species Characteristics

Stage, Sex

Up to this point, the discussion has included little evidence that two synhospitalic species (two obligate species of the same genus resident on one host species) reside on man. Statistically acceptable measurements, drawings of critical taxonomic features, and photographs of the stages in the life cycles of both D. folliculorum and D. brevis have been presented elsewhere.' The following brief characterization of these two is provided so that they may be readily separated, taxonomically, as whole-mounts under "high-dry" (X 400) magnification (Figs. 112; Table 2), in sections of skin, and from their most similar counterparts, D. canis and D. phylloides, resident in the dog and the pig, respectively (Table 3).29 First let us separate D. folliculorum from D. brevis (Figs. 1-12).

Ova

Whole

Mounts*

(All measurements in micrometers— Table 2) 1- Eggs larger (100) arrow-head shaped in D. folliculorum: smaller (60) oval, D. brevis (Figs. 11, 12). 2. Larvae, protonymphs, and nymphs longer in the former ( < 235 vs > 120; < 325 vs > 165; < 340 vs 195—figures approximate, but reduced in upper register, increased in lower (Figs. 5-10). 3. Adults in D. folliculorum larger than D. brevis (males 279.7 ± 52.0 vs 165.8 ± 18.5: females 294.0 d= 58.1 vs 208.3 ± 26.5) with some overlap in females for the 2 species (Figs. 1-4, Table 3). Large male D. folliculorum overlaps small female D. Scrapings or expressed material may easily be permanently mounted in Hoyer's medium.

length width

D. folliculorum 104.7 ± 6.3 41.8 ±: 1.8

D. brevis 60.1 ± 34.4 ±

3.4 2.2

Larvae length width

282.7 ± 45.1 33.5 ± 2.6t

105.4 ± 11.5 33.8 ±: 4.0t

Protonymphs length width

364.9 ± 36.4 36.3 ± 4.4t

147.6 ± 14.1 34.4 ± 3.5t

Nymphs length width

392.0 ± 46.8 41.7 ± 6.3t

165.0 ± 26.3 41.2 ± 5.4t

Adult males length width

279.7 ±: 52.0+ 45.0 ± 2.0t

165.8 ± 18.5 46.0 ± 4.2t

Adult females length width

294.0 ± 58.n 51.9 ± 3.0t

208.3 ± 26.5* 50.2 ± 3.4t

* Selected from Reference 1. All measurements in micrometers. t Width dimensions of overlap. t Length overlaps.

brevis. Male genital opening large (5) midway between posterior dorsal dots (podosomal tubercles) in D. folliculorum, whereas opening small ( > 3) in D. brevis and anterior to midpoint between tubercles. Vulva in former behind closed ventral plate (epimera IV) sutures: in D. brevis epimera IV open. Opisthosomal ("abdomen") terminae more acute, both sexes, in D. brevis. Opisthosomal organ (function unknown) present only in females of D. folliculorum (Fig. 17). In Section Use characters as in No. 3 when possible; dimensions must usually be reconstructed from serial sections. Use locus

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Fig. 1-12—Photomicrographs of Demodex folliculorum and D. brevis arranged for comparison of stages in the life cycle. Sequence starting with D. folliculorum (1), D. brevis (2) etc., for males, females, nymphs, protonymphs, larvae, and ova {X185). (All photos except 11 reprinted from Reference by permission.)

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"absolute" only for D. brevis when deeply situated in sebaceous glands. Single cross-sections are rarely separable. Critical identification in sections should ideally be made with oil immersion. In the absence of a calibrated microscope with ocular micrometer, adequate comparsions can be made by placing human blood beside the whole mount specimen (rbc = approx. 7.5 /xm). In sectioned material the two species are much niore difficult to separate. Longi-sections should be searched out and structures noted above measured by reconstruction from serial sections (6 such at 8-10 /tm often needed). In sections thicker than 8 ju.m, red blood cells in adjacent vessels fTiay be used for comparison. Width Tieasurements of body elements all show considerable overlap in dimension for all stages but ova. In several hundred skin sections studied in our laboratory, we usually find one, and never more than 3, D. brevis in a single sebaceous gland, whereas D. folliculorum is apparently more colonial, with 6 to 8 mites often together in one hair follicle (Figs. 14, 16). Identification of species in the skin of dogs and pigs as opposed to that of man 's. We believe, no problem for differentiation because demodicids are apparently host species specific's In view of the marked degree of overlap in meristic data, and the fact that many demodicids nave not been described, unlabeled cross-sections, unless supported by whole-mount specimens, are better abandoned. For whole mounts, see Table 3. Although the two demodicid life cycles of man were not differentiated, Spickett'^ made time-based population counts on these mites in vitro. Using the formula t^

^^

(number in one stage -^-

time equals number in another stage -^ time), he concluded that the life cycle was approximately 141/2 days—ova, 21/2



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Table 3. Key to Demodicids ot Man, Dog and Pig* 1. a. Eggs spindle-shaped, legs of immatures very small stumps, genital shield (around opening in males) larger than 7 and oval, vulva 5 or less. 2 b. Eggs arrowhead shaped or oval, legs immatures prominent, genital shield males) smaller (5 or less), vulva 6.5 more.

of (in or 3

2. a. Eggs over 95 long, immatures with acuminate or hooked posteriors, adult posteriors also acuminate and male podosomal leg-bearing area) width over 45: female over 50. D. phylloides from Sus scrofa b. Eggs under 85 long, immatures with rounded posteriors, adults posteriors also rounded and male and female podosomal widths under 40. D. canis from Canis familiaris 3. a. Eggs larger ( < 100) arrowhead shaped, immatures very long ( < 210), adults larger except for a few females—in this case opisthosomal organ present. D. toiiiculorum. b. Eggs small (> 65) oval, immatures small (under 200), and adults small except females but no opisthosomal organ. D. brevis * Using characteristics discernable under X400 magnification. All measurements in micrometers.

days; larvae, 1^/2 days; nymphs, 51/2 days; adults, 5 days. Despite the errors and assumptions in this work, it is still the best estimate. As members of the genus Demodex, both species affecting man share certain characteristics and yet show differences, especially in habitat, which are important to a consideration of pathogenesis. Locus of Mites "D. folliculorum" has been reported from scraped and squeeze-scraped material from many (topographic distribution) areas of the body such as nasolabial folds, chin, forehead, scalp, ear canal (cerumen), mammary nipple, back, buttocks, chest, mons veneris, penis, etc.-^o Both species have been found in our laboratory in sections of skin of the eye-

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lid, nasolabial folds, scalp, forehead and tissue of the ear canal. Also, D. folliculorum is present in the follicles of the eyelashes and large scalp hairs. A demodicid has been found in the Meibomian glands.^' Beerman and Stokes" suggest that the most fertile area from which to retrieve demodicids is the nasolabial folds. This has been borne out in our current studies of topographic distribution and by the careful studies of Riechers and Kopf The precise locus of each of the two species in the pilosebaceous complex was not noted until 1972.' This report shows that D. folliculorum seems restricted to hair follicles, whereas D. brevis is localized in the sebaceous glands. In this last, although 90% of 135 individual mites were so located, the remainder were in the follicle above the glands or sebaceous duct. We assume the 12 individuals were en route to or departing from the sebaceous glands. Both mite species apparently are stereotactic,'' and undoubtedly enter the pilosebaceous apparatus through the follicular orifices or gland ducts. Demodex folliculorum is found, in all stages, anterior down and with legs toward the follicular epithelium (Fig. 16). In all sections we have examined to date, D. folliculorum is superficially positioned in the hair follicle above the level of the sebaceous duct, although Figure 2 (p. 16) in Norn'^ indicates that they may be very deep, even to the hair bulb, in the eyelid. Sections of D. brevis in the hair follicle show that, in this site, they are likewise so oriented. On the other hand, in the sebaceous gland proper, D. brevis has no set pattern of orientation (Fig. 14), although they parallel the long axis of the sebaceous duct during gland entry.

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In no cases have we found mites penetrating the dermis or the blood vessels as in our studies of Demodex antech/n/.f'-* Spickett'-' examined internal tissue sections and concluded that "D. folliculorum" was not an endoparasite— D. can;s is known from many internal organs.3-' We would anticipate from the account by Marples-^"* on the distribution of sebaceous glands as opposed to hair follicles that D. brevis would be most common in the nasolabial fold area (as discussed), whereas the largest populations of D. folliculorum should be found in the scalp area. These areas would then be most fertile for assessing pathogenesis for each, as well as descrying differences in associations with other disease entities. Demodicids of man are also reported from sputum," earwax^'' and bedding (specimen sent our laboratory for identification). Although they survived several days under refrigeration at about 80% RH, specimens of both species in our laboratory will live only 11/2 hours at 20° C and RH about 40%. In terms of transmission of other disease organisms, one would anticipate that D. brevis, which chronically resides deeply embedded in the less keratinized, large and vacuolated sebaceous gland cells, would be a more likely transfer agent than D. folliculorum. Clinical Accounts The features of mite distribution, incidence, locus and minute size plus the difficulties of providing controlled experiments all make clinical evaluation of the causal relationship between these mites and disease in man extremely difficult. Gmeiner^ pointed out that in a wide range of skin diseases, demodectic mites were no more numerous in the lesions than elsewhere in the same host.

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He later (1909)-'^ discussed the likelihood that these mites open the tissue to invasion of other organisms whose activities may, in turn, influence the mite population. Sato et al.^*^ indicate that other skin conditions may also increase the mite populations! In terms of transmission of disease organisms, English et al.^' has reported bacteria adherent to the demodicid exoskeleton. Despite these caveats, a causal role for "Demodex folliculorum" has been postulated for an amazing list of diseases. These include acne, blepharitis, pityriasis rosacea, and so on.^- " This, obviously, does not mean that there is no causal or symbiotic effect for any of these clinical conditions; rather that, as pointed out by Beerman and Stokes," each of these need further study and solid evidence before conclusions can be drawn. One cannot answer each of the causal claims, however, as Lawrence^ and others'"' suggest, in the absence of solid proof they must be held suspect. One of the few instances in which gross pathologic conditions seem assuredly caused by demodicids in man is reported by Miskjian.-" In a personal reply to my questions, this author states that these microvesicular papules (conical, approximately 1 mm broad, and 1 mm high with whitish tip) were found in 3 instances on the alopecic foreheads of men over 50 years of age. Mites (probably D. folliculorum) were numerous on examination of expressed material and bacteria appeared absent. Unfortunately, biopsies were not permitted. Post and Juhlin''2 have provided a most interesting review, analysis and account of their observations of demodectic blepharitis. They noted that of the two major types of this disease, suppurative and ulcerative, demodicids seemed responsible for an ulcerative condition.



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They characterized demodectic blepharitis as showing the following signs: 1. Scanty, loose eyelashes with irregular growth. 2. Mucoid discharge with matting of lashes. 3. Amorphous debris at the eyelid base. . 4. Erythema of the lids. The account of English^' would seem to concur with this analysis. In neither case, however, were bacteria ruled out as either accessary or primary causative agents. Sections of skin, such as Fig. 16, do show a marked and somewhat papillary keratinization of the hair follicle and surrounding epidermis—much as indicated by Ayres'^ for gross signs of demodicosis and by Norn''' for blepharitis. Even larger mite populations are occasionally found in our series with distension of the epithelium, only moderate keratinization, and, as mentioned by Marks and Harcourt-Webster,•"> no indication of any effect on the surrounding dermis. Symptoms of demodicosis occasionally have been noted in the literature. Ayres'** reports that a feeling of dryness, burning and intense itchiness accompanies clinical signs of demodicosis ("pityriasis folliculorum" or rosacea-like demodicidosis). Garven^s thought that demodicids produced an irritation and itching of the nipple. However, many of our subjects under study maintain large populations of both D. folliculorum and D. brevis with no observable signs or reported symptoms of disease. Our list of clinical signs and symptoms causally related to either D. folliculorum or D. brevis (Table 4) is "anemic," not for want of "proven" published reports, but rather because we find most reports scientifically unconvincing (see Beerman and Stokes").

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Demodex spp.

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Clinical Manifestations Associated with Demodicids*

Cross signs/symptoms

Authority

Notes

In man—many other reports claim causal relationships (see text) D. folliculorum

Micro-vesicular papules

Miskjian'M951

Thought free oi bacteria

D. brevis

Dry, scaley, sandpapery, erythematous and itching

Sato et al.-'''1965 (as Ayres 1930 on)

Photos show clearly D. brevis

Other mammalst—review and discussion in press—some values changed for present report. D. antechini D. caprae

Micro to 3 cm naked tumors Minute to 5 cm naked papules

D. bovis

Minute to 3 cm nodules

D. sp.

Subdermal 1-3 mm masses

D. can/5

Small (1-3 mm) papules, pustules,nodules, erythema, hair loss

Nutting & Wooleyc- 1965 No bacteria evident Nutting=» 1950

Plated contents sterile except for mites Nemeseri & Szeky":' 1961 Marked granuloma with and without(?) bacteria Nulting in ms 1909

No tissue reaction Bacteria involved in most instances

* Representative cases in mammals other than man. t See Table 5 for scientific names of hosts.

We should all be alert, however, to the marked clinical signs of demodicosis in other mammals (Table 4). These could provide valuable leads to assessment of clinical cases in man. Note that in some of the mammalian cases no pathogenesis is found; examination at the histological level has been necessary in all to be sure that demodicids were causing the signs of disease (Table 5).

Histopathology It is apparent that only by careful attention to sections or "spreads"-^2 of biopsy or autopsy material can causal or symbiotic connections for clinical signs and symptoms of demodicosis in man be explained. In all of the specimens we have examined using such techniques, we find relatively normal pilosebaceous components next to abnormal and/or infested components. A comparative study, as this suggests, led Marks and HarcourtWebster^o to conclude that "D. follicu-

lorum" produced no extrafollicular derangements; this would rule out an immune response! The difficulties in the assessment of reports for demodicid pathogenesis are compounded by the failure to provide (1) histologic information, (2) comparison of normal with deranged, and (3) details of other organisms or conditions found in the area of concern. Also, differentiation between the two mite species must be made in detailing pathogenesis. This has been done in only two reports.'- '2 Evidence indicates some histologic changes related to the activities of D. brevis and D. folliculorum. The first indication is the often-reported granulomatous condition:"* in our case (Fig. 15), serial sections show that the mite Is D. brevis. Note the giant cells and polymorphonuclear leukocytes. Whether or not the granulomatous condition is caused by Demodex brevis is not known; however, giant cells do cue into, invest and phagocytose the mites, as noted by

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Fig. 13 Lett, photomicrograph of Demodex tollicuiorum (nymph) in situ. Note undercutting of follicular epithelium near mouthparts (arrow) (X 750). Fig. 14—Right, photomicrograph of D. brevis in sebaceous gland. Destruction of gland cells near mouthparts (arrow) (X 750).

Grosshans et al.'^ A foreign body reaction has been experimentally evoked by demodicids in other mammals.•'' Sections also often reveal that both D. folliculorum and D. brevis (immatures and adults) undercut and/or destroy cells (Figs. 13 ,14). This seems to be the major method of feeding in other demodectic mites.'"' Demodex folliculorum does distend, and in large numbers is often associated with hyperkeratinization (Fig. 16, and Ref. 17). Finally, pigmentation, as reported by Dubreuilh''' and by Blackmar,''^ has been found causally associated with

demodicids in several other mammals."* It seems likely that this condition, for D. folliculorum, is present in man. Table 5 lists some of the known instances of demodectic pathogenesis in both man and other animals. Again, the records for man are probably not sufficiently inclusive, but lack of species discrimination in reports published before 1972 jeopardize other inclusions. As with clinical records, the representative cases of histopathology from other mammals should provide suggestions for further studies on demodicid histopathogenesis in man.

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Fig. 15—Left, photomicrograph of section through granuloma showing cross section of D. brevis with giant cells (X 750). Section obtained from the Dermatopathology Laboratory, Stanford Medical School, of Dr. Alvin Cox. Fig. 16—Right, photomicrograph of section through entry to hair follicle. Note D. toiiiculorum (arrows) distension of follicle, heavy multiple keratin layering, and segment of hair—x (X 375).

Serial sections of biopsies or autopsies should not only be made, but checked histochemically for bacteria,'" examined for dermatophytes, searched for trauma and scanned for evidences of abnormal host physiology before demodicid pathogenesis is proposed. Host-Parasite Interactions This topic is crucial to studies of human demodicosis. Embracing the ecology and the biology of man, as well as the ecologic conditions provided by man

for the overall life of the parasite, it is also the most complex (Fig. 18). Host condition in demodicosis will be considered in an effort to reduce this complexity. Then we will consider demodicid potential for pathogenesis, before linking interactions. Host Condition and Demodicosis The most interesting report is that of Fuss:2 in Table 6 part of her data are presented in rearranged form. It shows that mite populations were high in 30 of 33 individuals with seborrhea (90.9%),

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Table 5.

Nutting

Pathogenesis Causally Associated with Demodicids at the Histological Level of Examination*

Demodex spp. (Host) In Man D. tollicuiorum

D. brevis

Histological details

Authority

Epithelial cell destruction keratinization, pigmentation

Desch & Nutting^ 1972 Norn" 1971 Dubreuilh-'' 1901

Gland cell destruction

Desch & Nutting^ 1972

Early records do not distinguish between species. Other Mammals D. aurati (Mesocricetus auratus) D. antechini (Antechinus stuartii)

D. caprae (Capra hircus) D. bovis (Bos taurus) D. sp. (Onychomys leucogaster) D. sp. (Odocoileus virginianus)

Hair loss, epithelial undercutting, pigmentation, epithelial distension Hypertrophy, hyperplasia of epithelium, epidermal giant cells, granuloma, penetration of blood vessels Hyperplasia of epithelium, vascular system Cell destruction, hyperplasia, dermal penetration(?) Epithelial undercutting (below keratin in anterior digestive tract) No response or perivascular infiltration (mites in lipid blebs in fascia)

Nutting & Rauch"' 1963 Nutting & Beerman"' 1965

Lebel & Nutting-"-' 1969 Nemeseri & Szeky"^ 1961 Nutting et al.-"'' 1973 Nutting in ms.

* Representative cases noted in mammals other than man.

whereas in normal and dry skin categories only 56.6 and 52.4% of the subjects showed high populations. Whether or not the mites were mainly D. brevis (sebaceous gland inhabitants), using sebum as a spur to increase, or increasing by their activities the flow of sebum is unknown. Her figures also indicate a modest difference between sexes, 73.6 as opposed to 66.7%—male:female for heavy infestations, and an 80% high mite recovery for the 51 to 80 age bracket as contrasted with 63.2 to 65.0% for the 31 to 50 and 14 to 30 age groups. In the survey paper separating the two demodicids in aborigines,2o no correlation was found for skin condition and

either species. Older males were more heavily parasitized than were young males, or females of any age. However, the sample was much too small for statistical treatment. Predisposing conditions, as recorded so often in canine demodicosis, eg., distemper, skin temperature,'" are rarely considered for man. Several accounts of "D. folliculorum," as the Breckenridge report,-^" note no correlation with host sex and yet the sebaceous glands, site of D. brevis, are notoriously responsive to hormones. The suggestion of Ayres'''* that the use of facial creams or absence of use of soaps produces increase of the mites is

INTERNATIONAL JOURNAL OF DERMATOLOGY

92

D. folliculorum

GENITALIA

Vol. 15

March 1976 _D. brevis

epimeron IVFemale Venlral

10pm j

Male Dorsal

vulva

tubercles O

o -penis

tubercles

o -penis

OPISTHOSOMA Dorsal Female (organ lateral)

rounded

pointed

opisthosomal organ 40annuli

Fig. 17—Diagnostic features of Demodex tollicuiorum and D. brevis. In part redrawn from Reference 1. Table 6. Rearrangement and Analysis ot the Data of Fuss n933j for Her Recovery of 'D. folliculorum'* 'D. folliculorum'

'D. folliculorum' (Numbers)

Male

High

5

1

12 17 34

17

40.5

73.6t

Low

Female

High

16

10

6

18

10

8

16

13

3

50

33

17

59.5

66.7

34.0

Lovi/

Host condition Dry

Normal Seborrheic Totals Percentage (Totals) Percentage condition Percentage age

Dry

4 5 0 9

7 25

52.4;

14-30 yrs 65.0;

26.5 Normal 56.6; 31-50 yrs 63

* Categories of high and low arbitrarily set by Fuss, t Values show correlations.

Seborrheic 90.9t 51-80 yrs 80.0t

No. 2

Nutting

HAIR FOLLICLE MITES

offset by the study of Beerman and Stokes." Nearly equal numbers of washed and unwashed were shown as positive. Much of this information would imply a correlation between sebum production and mite increase; in fact, many authors such as Spickett have stated that demodicids rely solely on sebum for nourishment. However, this is unlikely* because the nitrogen content of sebum is low, although mites could use some sebum during egg maturation. Discovery of the species of demodicid in the anterior d i gestive tract of the grasshopper mouse-''^ shows that these mites can survive and reproduce without sebaceous gland products. In any event, and as noted earlier, we believe that demodicids harvest host cell contents (Fig. 18 D). Sato et al.-^8 detail a sequence of examinations following hydrocortisone therapy which indicates a marked increase in D. brevis—photomicrographs assuredly show this species. The effect of hydrocorticosteroids on host condition vis a vis the mites is hard to assess: we have as yet no firm evidence (but see Scott et al.-''" for D. canis) for an immune response to demodicids in man. Skin therapy or vitamin deficiencies such as biotin that effect keratinization, especially in the hair follicle, should have some effect on the mites (Fig. 18C). Experiments with biotin deficiency reduced, but did not extirpate, hair follicle mites in Golden hamsters.'' This experiment also showed that under this particular avitaminosis, the mite population was reduced rather than increased. Vitamin therapy regimens have often been suggested for cases of demodicosis in dogs.^" The host mechanism for a foreign body response leading to granuloma and mite phagocytosis has already been noted; how the giant cell degrades and disposes

93 PARASITE CHEMICAL

PHYSICAL — \

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A.

\ Foreign

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(adapiaiions) \

''

p

, prolonymptr^^ DEMODix ipp, y

Xovum/''

Puncture cells

, j ;

Y V Dermi>.Fo.ero in.oMon

y

Reproductive

/

m.=,ion / \

/ lRcpr,Ju==) \

Salivary

/

, /

\

pressure

, /

Tissuc decoy

Chitin

/

Guonine'

I C; ;T: ; T BACTERIAL*.^ ^ / \B - ^I^O ; IT ;— ^ /S \ X MECHANICAL DERANCEMENT

/

i

\

iLU W m ^ i Cell contents

/ / ^ r*^

Gland products A " ' ' *

— O " ®

.ii.ironmtnl\Foieign body r i & Co re

/ s Gianf cell phoqocytoii*

therapy

A G^

Hair follicle mites (Acari: Demodicidae) of man.

Review HAIR FOLLICLE MITES (ACARI: DEMODICIDAE) OF MAN WILLIAM B. NUTTING, PH.D. "Demodex folliculorum," the rubric under which the hair follicle mi...
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