Acta Derm Venereol 2002; 82: 3–6

MINI REVIEW

Demodicidosis Revisited

B. BAIMA and M. STICHERLING Department of Dermatology, University of Leipzig, Leipzig, Germany

Demodex mites are common commensals of the piloseba- low (4). Dermatologists have not been able to reach ceous unit in mammals. In humans, only two species agreement concerning the pathogenetic potential of the (Demodex folliculorum and D. brevis) have been identiŽ ed mites. The question whether they are mere commensals and have been implied to play a role in at least three coincidentally found in diseased skin or a real cause of facial conditions: pityriasis folliculorum, rosacea-like rosacea remains controversial. demodicidosis and so-called ‘‘demodicidosis gravis’’. However, there is no consensus to what degree the mites are causative of the skin pathology and how they might CLINICAL FORMS OF DEMODEX contribute to the disease. This review presents a demodic- INFESTATION IN MAN idosis case, discusses the clinical features of Demodex Ayres (5, 6) originally described two clinical forms of infestation in man and reviews its pathogenetic implica- Demodex infestation in humans: pityriasis folliculorum tions and the therapeutic options. Key words: Demodex and rosacea-like demodicidosis. Since that time, mites; pityriasis folliculorum; rosacea-like demodicidosis. Demodex mites have been reported in connection with (Accepted December 13, 2001.) clinical entities such as pustular folliculitis (7), papulo- pustular scalp eruptions (8), perioral dermatitis (9) and Acta Derm Venereol 2002; 82: 3–6. hyperpigmented patches of the face (10). Bozena Baima, Department of Dermatology, University Pityriasis folliculorum primarily aVects women and of Leipzig, Stephanstr 11, DE-04103 Leipzig, Germany. presents with diVuse but faint facial erythema, itching E-mail: [email protected] and burning sensations as well as Ž ne follicular plugs and scales which give the face a ‘‘nutmeg-grater’’, ‘‘sand- paper-like’’ or ‘‘frosted’’ appearance. A history of infre- Follicle mites live in the hair follicles or sebaceous glands quent washing and application of heavy creams and in mammals. The species of major importance to make-up helps to conŽ rm the diagnosis (5). domesticated animals belong to the genus Demodex. Histologically, a diVuse and perivascular lymphocytic They are common parasites of cats (Demodex cati), dogs inŽ ltrate is present in the dermis, without the formation (D. canis), horses (D. equi), cattle (D. bovis), swine and of granulomas (11). sheep (D. ovis). In healthy animals, follicle mites do not Rosacea-like demodicidosis with erythema, scaling cause skin deterioration, but in weak or diseased animals and papulopustules (6) clinically mimics the picture of demodectic mange can develop. Heavily infested dogs, common rosacea. However, the scaling in Demodex for instance, initially manifest scaling and wrinkling of infestation is follicular and the lesions are superŽ cial the skin, along with a change of colour from normal to and tend to be small papulovesicles and vesicopustules. red or bruised-looking (‘‘red mange’’). Furthermore, In contrast, common rosacea presents with papulopus- pustules and in ammatory nodules develop, which usu- tules, and the scaling, if present, is rather  aky (10). ally re ects the development of secondary bacterial Additionally, sudden onset, rapid progress and no his- infection (esp. Staphylococcus) of the follicles. In both tory of  ushing, persistent erythema or photosensitivity, conditions, itching appears and can be severe (1). Some sebostatic skin type, burning and itching sensations, the animals seem to be genetically predisposed to demodic- absence of signiŽ cant teleangiectases as well as (more idosis by a speciŽ c T-cell abnormality, and generalized infrequently) asymmetrical distribution, involvement of mange has been associated with depressed T-cell the eyelids (demodectic blepharitis) (12), previous ster- response to a variety of mitogens (2). oid usage and poor general health (e.g. diabetes mellitus) In humans, only two species: Demodex folliculorum help in establishing the diagnosis of demodicidosis. A (DF ) and Demodex brevis (DB) have been identiŽ ed deŽ nite diagnosis can be made by examining scale scraps (3). They inhabit the pilosebaceous unit and utilize after macerating with 40% KOH under low power sebum as nourishment. DF mites are found in the magniŽ cation (13), by standardized skin surface biopsy infundibular portion of hair follicles, while DB burrow (SSSB) (14) or by a punch biopsy. SSSB with the deeper into the sebaceous glands and ducts. The preval- application of cyanoacrylate glue is preferred because it ence approximates 100% in middle-aged and older is a non-invasive sampling method that allows the adults; in healthy skin, however, mite density is normally superŽ cial part of the horny layer and of the follicle

© 2002 Taylor & Francis. ISSN 0001-555 5 Acta Derm Venereol 82 4 B. Baima and M. Sticherling content – the site where the DF mites reside – to be interesting hypothesis that a delayed hypersensitivity collected. The technique also enables the DF population reaction (type IV immune response) to an unknown to be monitored during treatment. The Ž nding of an antigen of follicular or mite origin, could occur in occasional Demodex mite is of no signiŽ cance, but Ž ve Demodex infestation. Roihu & Kariniemi (22) studied or more of them in a single low-power Ž eld (13) or the prevalence of Demodex mites in facial biopsies from more than 5/cm2 in SSSB (14) has deŽ nite pathogenic patients with rosacea, eczema and discoid lupus eryth- implications. Histological examination reveals mono- ematosus (DLE). In the rosacea group, the mites were nuclear, mainly perifollicular in ammatory inŽ ltrate, found more frequently (51%) than in the rest of the which occasionally can assume a granulomatous pattern. study population (eczema 28%, DLE 31%). Vollmer Georgala et al. (15) showed that the inŽ ltrate consists (23) examined 24 large sections of skin with histologic mainly of CD4 positive T lymphocytes, CD8 positive folliculitis and demonstrated DF in 42% follicles with T cells representing less than 5%. This study also showed in ammation, but in just 10% without in ammation. that around the infested follicles CD1a positive macro- Furthermore, 83% of follicles with Demodex showed phages (Langerhans’ cells) could be found. in ammation. The probability that this result could % The third form of demodicidosis in humans, reported occur by random chance alone is less than 0.1 (23). Although it does not prove that DF causes clinical or by De Dulanto & Camacho-Martinez (16), is called histologic folliculitis, it must be concluded that DF and ‘demodicidosis gravis’ and presents a clinical picture follicular in ammation are preferentially associated. similar to severe granulomatous rosacea with dermal Since Ayres’s (5, 6) and Spickett’s (34) studies on granulomas containing mite remnants phagocytized by demodicidosis, it is known that the pathogenicity of foreign-body giant cells and showing central necrosis Demodex mites is a quantitative matter. Bonnar et al. (caseation). Which form the demodicidosis will take in (17), using surface skin samples (SSSB), showed that a particular individual depends on the degree of the average mite count of patients with rosacea was Demodex infestation, the duration of the disease and signiŽ cantly higher than the count of healthy individuals. the patient’s age and general health.

THERAPEUTIC OPTIONS THE PREVALENCE OF DEMODEX IN MAN Since the Ž rst descriptions of demodicidosis, clinicians Demodex is believed to be sparse in children and in have reported the therapeutic eYcacy of salicylic acid adolescents (4). The newborn presumably become (10), selenium sulphide (24), metronidazole (21, 25), infested soon after birth by direct contact, but because crotamitone (14, 26), lindane (10, 11), sublimed sulphur of low sebum production in childhood Demodex density (10), oral ivermectine together with topical permethrin remains low (17). Kligman & Plewig (4) stated that (27) and oral or topical retinoids (11). However, it is they had never observed mites in acne comedones or in diYcult to study any possible long-term eVects of drugs papulopustules. Why mites do not colonize acne patients on mite viability because of the inability to culture in spite of the abundance of sebum remains a puzzle. It Demodex. It might be that in mild demodicidosis cases is possible that the changes in sebum composition topicals that promote desquamation (e.g. salicylic acid and retinoids) alone could be eVective because they reported in adolescent acne suVerers (18) make it prevent follicular plugging and accelerate shedding of impossible for the mites to  ourish. The few reports of the epidermis, thus enabling elimination of the mites demodicidosis in children connected it with leukaemia and their waste products. Regular cleansing with mild (19) or HIV infection (20). Recently, however, Patrizi soap and water and avoidance of potentially occlusive et al. (21) reported 8 immunocompetent children (aged agents is also important. In Demodex blepharocon- 10 months to 5 years) with pityriasis folliculorum and junctivitis, yellow mercury ointment 1% or topical rosacea-like demodicidosis. The reason for this unusual metronidazole gel 2% (28) have been recommended. infestation was not found, but in all cases the lesions In the case presented (Figs. 1–3), our patient was cleared after 3–4 weeks of local therapy with 1% treated with oral metronidazole, which is also eVective metronidazole. in common rosacea. This could point at a relationship Several pathogenic mechanisms have been postulated: between the two clinical entities. However, the mechan- (i) blockage of follicles and sebaceous ducts by the mites ism of the therapeutic response brought about by and by reactive hyperkeratinization and epithelial hyper- metronidazole is not known. It cannot be attributed to plasia, (ii) a vector role for bacteria, (iii) a foreign body its antiparasitic activity against Demodex because in granulomatous reaction to the mite chitinous skeleton, vitro the mite can survive in such a high concentration and (iv) stimulation of the host’s humoral and cell- of metronidazole that cannot be achieved in vivo (29). mediated immune reactions by the mites and their waste However, this does not exclude the possibility of a products (17). Georgala et al. (15) put forward an metronidazole metabolite as an active anti-mite agent.

Acta Derm Venereol 82 Demodicidosis revisited 5

Fig. 1. A 44-year-old woman presented in our outpatient department with a 4-year history of itching and skin lesions in the central region of the face. Previous medication included oral tetracycline, which was ineVective, and oral isotretinoin, which led to a remarkable improve- Fig. 3. A punch biopsy from the patient’s left cheek revealed sparse ment but had to be discontinued because of gastrointestinal complica- lymphohistiocytic perivascular inŽ ltration in the upper dermis. Within tions. On physical examination, the patient presented papulopustules the follicular infundibula and sebaceous glands, multiple Demodex and Ž ne keratotic follicular papules against a vivid background mites can be seen. Direct immuno uorescence examination was erythema localized on the nose, cheeks, chin and forehead. Comedones negative. and teleangiectases were missing. The patient did not report  ushing episodes or any kind of photosensitivity. Past medical history included severe acne in adolescence. The patient was put on a 0.5 g/day dose that metronidazole has an inhibitory eVect on H O and of oral metronidazole for 2 weeks (see Fig. 2). 2 2 OH· generation by neutrophils in a dose-dependent manner (32). The alteration of neutrophil function and metronidazole’s antioxidant eVect could explain why metronidazole is eVective against papulopustular ros- acea where in ammatory neutrophils are involved (33). However, Palotta et al. (26) reported that in rosacea- like demodicidosis a therapy attempt with oral metronid- azole was unsuccessful, while topical crotamitone cleared the lesions. Similarly, Shelley et al. (33) observed that oral metronidazole suppressed the disease but did not reduce the Demodex population. Treatment with topical crotamiton, however, eliminated DF and was curative. Forton et al. (14) recently investigated the eYcacy of 6 diVerent topical treatment modalities in 34 patients with high DF density in SSSB (> 5 mites/cm2). This random- ized study did not show any acaricidal activity of metronidazole 2%, sublimed sulphur 10%, permethrin 1% or lindane 1%, but conŽ rmed the eYcacy of crotami- tone 10% (when used once daily) and benzyl benzoate 10% (used twice daily).

Fig. 2. After 2 weeks of metronidazole therapy: an almost complete CONCLUSION remission with only some residual erythema, patches of post- in ammatorial hyperpigmentaion and a few excoriations on the chin. Common rosacea is essentially a cutaneous vascular To prevent a recurrence the patient received an additional 14-day disorder with a varied degree of sun damage (solar therapy with metronidazole orally (0.5 g/day). elastosis) of the upper dermis and a history of reactive, photosensitive skin. Demodex mites are not causative Metronidazole is degraded in vivo into at least 5 metabol- of rosacea, but they may aggravate the disease. ites with potent biological activity (e.g. its 2-hydroxy- Furthermore, when the mites get the opportunity to methyl derivative is one-third to 10 times more active multiply above a certain limit, which is dependent on as an antibacterial agent than metronidazole itself ) (30). the immunological status of the patient, they are the It has also been suggested that metronidazole can have aetiologic factor of rosacea-like demodicidosis. The dis- an anti-in ammatory in uence on T lymphocytes and ease shows a remarkable similarity to common rosacea, adhesion molecules (29). Further, it has been shown yet can be distinguished from the latter on clinical and

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