D
ERMATOPATHOLOGY
Demodicosis: A clinicopathological study
Chao-Kai Hsu, MD,a,b Mark Ming-Long Hsu, MD,aand Julia Yu-Yun Lee, MDa,cTainan, Taiwan
Background: Demodex mites are common commensal organisms of the pilosebaceous unit in human beings and have been implicated in pityriasis folliculorum, rosacea-like demodicosis, and demodicosis gravis.
Objective:We sought to describe the spectrum of clinicopathological findings and therapeutic responses of demodicosis in Taiwanese patients.
Methods: We conducted a retrospective study to review clinicopathologic findings and therapeutic responses of 34 cases of diagnosed demodicosis.
Results: Fifteen cases with positive results of potassium hydroxide examination, standardized skin surface biopsy specimen, and/or skin biopsy specimen, and resolution of skin lesions after anti-Demodex treatment were included for final analysis. Nineteen cases were excluded because of insufficient positive data to make a definite diagnosis. There were 4 male and 11 female patients (age 1-64 years, mean age 38.7 years). The disease was recurrent or chronic with a duration ranging from 2 months to 5 years (mean 15.7 months). The skin lesions were acne rosacea-like (n = 8), perioral dermatitis-like (n = 5), granulomatous rosacea-like (n = 1), and pityriasis folliculorum (n = 1). Skin biopsy was performed in 7 patients. Overall, the histopathology was characterized by: (1) dense perivascular and perifollicular lymphohistiocytic infiltrates, often with abundant neutrophils and occasionally with multinucleated histiocytes; (2) excessive Demodex mites in follicular infundibula; and (3) infundibular pustules containing mites or mites in perifollicular inflammatory infiltrate. The skin lesions resolved after treatment including systemic metronidazole, topical metronidazole, crotamiton, or gamma benzene hexachloride.
Limitations:Small sample size and a fraction of patients without long-term follow-up are limitations. Conclusion: Demodicosis should be considered in the differential diagnosis of recurrent or recalcitrant rosacea-like, granulomatous rosacea-like, and perioral dermatitis-like eruptions of the face. Potassium hydroxide examination, standardized skin surface biopsy, skin biopsy, or a combination of these are essential to establish the diagnosis. ( J Am Acad Dermatol 2009;60:453-62.)
Key words:Demodexgranuloma; demodicosis; pathology; perioral dermatitis; rosacea-like dermatitis.
‘‘D
emodicosis’’ (or ‘‘demodicidosis’’) is the term applied to cutaneous diseases caused by Demodex mites. Dfolliculo-rum and D brevisare common commensals of the
pilosebaceous units in human beings.1,2 The face, scalp, and upper aspect of the chest are the predilection sites.D folliculorumis usually found in the follicular infundibulum, andD brevis in sebaceous ducts and meibomian glands.Demodexmites are thought to play a pathogenic role when present in excessive num-ber1,3-5or penetrating into the dermis6,7and have been implicated in papulopustular rosacea,3,4pityriasis fol-liculorum,5,8rosacea-like demodicosis,9demodicosis gravis (granulomatous rosacea-like demodicosis),10 and blepharitis.11However, there is no consensus as to what degree these mites are contributing to these skin lesions.
Demodicosis appears to be uncommon among Taiwanese patients. We report a series of 15 cases of From the Departments of Dermatologyaand Pathology,cCollege
of Medicine, University Hospital, and Institute of Clinical Medicine,bNational Cheng Kung University.
Funding sources: None.
Conflicts of interest: None declared.
Reprint requests: Julia Yu-Yun Lee, MD, Departments of Dermatology and Pathology, National Cheng Kung University College of Medicine and Hospital, 138 Sheng-Li Rd, Tainan, Taiwan. E-mail:[email protected].
0190-9622/$36.00
ª2008 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2008.10.058
Case No. Age, y/sex Clinical picture
Diagnosis at
presentation Duration
KOH
examination/SSSB Pathology Treatment Outcome
Follow-up duration
1 53/M Acne rosacea-like Demodicosis 1 y Positive ND MN 250 mg tid 3 wk;
MNG bid 3 wk
CR 2 wk
2 38/F Acne rosacea-like Demodexfolliculitis 6 mo Positive ND MN 250 mg tid 1 wk CR 15 mo
3 27/F Acne rosacea-like Demodexfolliculitis 6 mo Positive ND MN 250 mg tid 3 wk; MNG bid 3 wk CR; two relapses (at 40 and 47 mo) 82 mo
4 18/F Acne rosacea-like Demodicosis 6 mo * ND MN 250 mg tid 3 wk;
MNG bid 3 wk
CR 2 mo
5 1/F Acne rosacea-like Demodicosis vs impetigo
2 mo * ND Crotamiton 10% qd 1 wk CR ND
6 64/M Perioral dermatitis-like
Acne rosacea 1 y Positive ND MN 500 mg bid 1 wk, 500 mg bid 3 wk
CR 3 wk
7 60/F Acne rosacea-like (nose only)
Rosacea 3 y Positive ND Crotamiton 10% qd 1 wk
(minimal effect), switched to MNG bid 1 wk CR ND 8 28/F Pityriasis folliculorum Rosacea with steroid rosacea
2 y Positive ND MNG 1 wk (minimal effect), switched tog-BHC 2 wk
CR 3 mo
9 34/M Acne rosacea-like Demodicosis vs perioral dermatitis 3 mo Positive Demodex folliculitis Doxycycline 250 mg 3 wk, prednisolone 10 mg bid tapered in 3 wk;g-BHC 2 wk CR; one relapse at 2 mo 10 mo 10 44/F Acne rosacea-like (severe) Extensive demodicosis vs fungal infection 2 mo Positive Demodex folliculitis MN 250 mg tid 3 wk, prednisolone 10 mg bid tapered in 3 wk; MNG bid 3 wk CR 6 wk 11 42/F Perioral dermatitis-like Eosinophilic folliculitis vs rosacea 2 y Positive Demodex folliculitis MNG bid 2 wk CR ND
12 24/F Perioral dermatitis-like Demodexfolliculitis 5 y Positive Demodex
folliculitis
MN 500 mg tid 2 wk;
g-BHC 2 wk
CR 3 mo
13 52/M Perioral dermatitis-like (right eyelids only)
Demodicosis 1 y * Demodex folliculitis MN 250 mg tid 1 wk CR ND JA M A CAD D ERMATOL M ARCH 2009 Hsu, and Lee
demodicosis in which the diagnosis was confirmed based on the clinicopathological findings and ther-apeutic responses.
METHODS
In this retrospective study, we searched our department database (July 1990-June 2007) for cases with clinical or pathologic diagnosis or ten-tative diagnosis of demodicosis (or demodicidosis)
or Demodex folliculitis by the Crux Integrated
System, a database system developed in our de-partment. The clinical picture, the initial clinical diagnosis at the time of the first visit, the pathologic slides, and the response to therapy were reviewed. Microscopic examination of mites was done either by potassium hydroxide (KOH) examination of skin scrapings or by cyanoacrylate glue standard-ized skin surface biopsy (SSSB). The result was considered positive when there were more than 5 mites either in one follicle or in one low-power field by scraping or in 1-cm2 area by SSSB.3,4 Pathological findings, including the pattern of in-flammation, presence of infundibular pustules con-taining mites, and density of infundibularDemodex mites and inflammatory cells were analyzed. The density of inflammatory cells or mites was graded using an arbitrary scale of 1 to 41 in increasing density.
RESULTS
In all, 34 cases were retrieved from the database originally. Nineteen of them were excluded because of the lack of clinical photographs or follow-up information, incomplete clinical or pathological evaluation, or poor response to anti-Demodex ther-apy. The remaining 15 cases showed good responses to antiacarid therapy. Based on the clinical presen-tations, positive histopathological and/or KOH ex-amination, and positive response to anti-Demodex therapy, these 15 cases were concluded to be demodicosis. The clinicopathological findings are summarized in Table I. Case 15, a patient with granulomatous rosacea-like demodicosis, has been described previously.12
Of the 15 confirmed patients, 4 were male and 11 were female (age range 1-64 years, mean age 38.7 years). The disease duration at presentation ranged from 2 months to 5 years (mean 15.7 months). Three patients had history of malignancy, buccal cancer, colon cancer, and nasopharyngeal carcinoma, one each, and were not receiving chemotherapy at pre-sentation. Clinically, the lesions consisted of many erythematous papulopustules, dome-shaped pap-ules, or tiny follicular papules on the face and/or
14 47/F Perioral dermatitis-like, steroid rosacea Granulomatous rosacea vs perioral dermatitis 2 y ND Demodex folliculitis MN 250 mg tid 3 wk; tacrolimus 0.03% bid 5 wk, changed to pimecrolimus 1% 11 wk CR 7 mo 15 y 48/F Granulomatous rosacea-like (whole face, neck, and upper aspect of chest) Granulomatous rosacea 6 mo ND Demodex granuloma MN 500 mg tid tapered in 3 wk, prednisolone 5 mg tid tapered in 3 wk; MNG bid 8 wk CR 7 wk BHC ,Ben zene hexachlo ride 1%; bid ,twi ce per day; CR ,complete res olutio n of skin lesions ; F ,femal e; KOH ,po tassium hydroxide; M ,m ale; MN ,metroni dazo le; MN G ,met ronidaz ole gel 0. 75%; ND :not done; qd , onc e a day; SSSB: standar dized skin surface biopsy ; ti d , thre e times per d ay. *KOH examin ation rev ealed pre sence of Demo dex mites with unspecified nu mber. yCas e repor ted separ ately. 12 J AMACADDERMATOL VOLUME60, NUMBER3
neck area with a predilection for the perioral area and cheeks. Based on the morphology and distribu-tions of the lesions, the clinical picture was classified into 4 types as follows. Eight patients had acne rosacea-like rash with erythematous papulopustular lesions involving multiple areas of the face (Figs 1 and 2). Five patients manifested as perioral der-matitis-like rash with papulopustular lesion limited to the perioral areas (4 patients) or eyelids (one patient) (Figs 3 to 5). One patient (case 15) presented with granulomatous rosacea-like eruption consisting of discrete erythematous dome-shaped papules without obvious pustules on the entire face, neck, and upper aspect of chest (Fig 6). One patient (case 8) had pityriasis folliculorum with numerous tiny follicular plugs and scales and a faint background erythema accompanied by itching and burning sen-sations (Fig 7). KOH examination or SSSB was performed in 11 patients; 10 showed positive results (Fig 7). Demodicosis was diagnosed or suggested at presentation in 9 patients; other diagnoses were impetigo, acne rosacea, perioral dermatitis, eosinophilic folliculitis, and granulomatous rosacea (Table I).
Skin biopsy was performed in 7 patients (cases 9 to 15). In cases 9 to 14, the biopsy specimens were taken from papulopustular lesions, and case 15 from a dome-shaped papule. Multiple step sections were examined. The main pathologic findings are sum-marized in Table II. Multiple Demodex mites were found in dilated infundibula (cases 9 to 15); mites were found also within infundibular pustules (cases 11 to 14) (Figs 1, 3, and 5). The dermis showed a moderate to dense perivascular and perifollicular lymphohistiocytic infiltrate with various amounts of neutrophils. The suppurative infiltrate in case 10 was associated with a ruptured hair follicle. Numerous plasma cells were present in two specimens (cases 9 and 12). Multinucleated histiocytes without obvious foreign body giant cells were present in two speci-mens (cases 14 and 15), and were more numerous in case 15 where two Demodex mites were found within the inflammatory infiltrate surrounding an apparent intact infundibulum (Fig 6). Cases 9 to 14 showed features ofDemodexfolliculitis, which dif-fered from theDemodex granuloma in case 15 by lacking an obvious granulomatous component in the inflammatory infiltrate.
Fig 1. Perioral dermatitis-like demodicosis (case 9; D07-0936). A, Many erythematous papulopustules were present on chin and left cheek of 34-year-old man for 3 months. B, Rash resolved after 2 weeks of treatment.C, Histologically, there is dense perifollicular and perivascular lymphohistiocytic infiltrate with abundant neutrophils and plasma cells in dermis.
D, At least 5Demodexmites are packed inside neutrophil-infiltrated infundibulum. (CandD, Hematoxylin-eosin stain; original magnifications:C,320;D,3100.)
The disease was recurrent or chronic persistent in most patients with poor responses to prior treat-ments, but resolved completely after a short course of treatments that included topical metronidazole gel 0.75% (8 patients), topical gamma benzene hexa-chloride cream 1% (3 patients) and crotamiton 10% (two patients), and oral metronidazole (250 mg three times per day) for 1 to 3 weeks (10 patients) (Table I). A short course of low-dose oral prednisolone was given in 3 patients to reduce inflammation.
DISCUSSION
We described the clinical and pathologic findings of 15 cases of demodicosis, the first series in Taiwan. In our series, the mean age was 38.7 years with a female predominance. In the report by Forton et al,13 the mean age was 49 years with male:female ratio of 2:5. Children are rarely affected by demodicosis.1 Our series included a 1-year-old child. Some studies showed that immunocompromised hosts, such as patients with AIDS14,15and leukemia,15,16 are more prone to Demodex infestation. In our study, no patient was immunocompromised.
Ayres and Ayres5 initially described two clinical forms of Demodex infestation in human beings: pityriasis folliculorum and rosacea-like demodicosis. Since then,Demodexhas been implicated in various dermatoses, including papulopustular rosacea,3
demodicosis gravis (granulomatous rosacea-like demodicosis),1,17 pustular folliculitis,18,19 perioral dermatitis,20 Demodex abscesses,21 and blephari-tis.11,22 The clinical manifestations in our series were consistent with acne rosacea-like in 8 patients, perioral dermatitis-like in 5, granulomatous rosacea-like in one, and pityriasis folliculorum in one. Interestingly, pityriasis folliculorum seems to be very uncommon in our experience. It is possible that this variant had been underdiagnosed because of the subtlety of the lesions and our staff’s lack of familiarity with this variant. On the other hand, the climate in Taiwan is relatively hot and humid, and does not require frequent use of facial skin care products with high oil contents.
Three histopathological variants of demodicosis have been described.23Rosacea-like demodicosis is characterized by presence of Demodex mites in infundibula with a primarily perifollicular infiltrate of mononuclear cells that occasionally assumed a granulomatous pattern.1,24In our series, 6 cases with papulopustular lesions and one case with granu-loma-like lesion were examined. They all showed moderate to dense perivascular and perifollicular lymphohistiocytic infiltrates with variable amounts of neutrophils. More importantly, multiple mites were present within infundibular pustules or in-flamed infundibula, findings supporting the patho-genic role of this organism.
Fig 2. Severe acne rosacea-like demodicosis (case 10; D07-0066).A, Numerous papulopus-tules were present over entire face in 44-year-old woman for 2 months.B, Rash resolved after 3 weeks of systemic and topical metronidazole and low-dose prednisolone.
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Demodicosis gravis resembles severe granuloma-tous rosacea clinically, and is characterized patho-logically by dermal granulomas with central caseation necrosis and mite remnants phagocytized by foreign-body giant cells.10In a series of 53 cases of granulomatous rosacea, intact or fragmented
Demodexmites in granulomas were observed in 10
specimens.25 In demodectic mange of the dog, the histopathology shows disruption of the follicle with
Demodexmites lying free within inflammatory
infil-trates.6Clinically the rash in our case 15 mimicked granulomatous rosacea, and it differed from acne rosacea-like or perioral dermatitis-like cases in the current series by lacking obvious pustules. Histopathologically, it showed intact mites within the suppurative and granulomatous inflammatory infiltrate outside an apparent intact follicle. Similar
findings were reported in case of Demodex
granuloma.6
Pityriasis folliculorum is characterized by follicu-lar hyperkeratosis filled withDemodex mites and a perivascular and diffuse dermal lymphocytic infil-trate without granuloma formation.5,8No biopsy was
performed in the only case of pityriasis folliculorum in our series. However, a large number ofDemodex mites were found in a single extracted follicular plug (Fig 7).
Overall, the histopathology in our series was characterized by: (1) dense perivascular and peri-follicular lymphohistiocytic infiltrates, often with abundant neutrophils and occasionally with multi-nucleated histiocytes; (2) excessiveDemodex mites in follicular infundibula; and (3) infundibular pus-tules containing mites or mites in perifollicular inflammatory infiltrate. In cases 9 to 14, no obvious granulomatous component in the perifollicular inflammatory infiltrate was present, and the changes were interpreted asDemodexfolliculitis. In contrast, the presence of obvious granulomatous component in case 15 qualified it as aDemodexgranuloma. The granuloma, however, was not associated with case-ation necrosis. Instead, it showed focal suppurcase-ation around the extruded intact mites. This reaction pattern may represent an early stage of granuloma-tous demodicosis. Based on our observation and those of others,1,26,27 the variation in the clinical Fig 3. Perioral dermatitis-like demodicosis (case 11;
D05-1078).A, Many small erythematous papulopustules were present on chin of 42-year-old woman for 2 years. B, Histologically, there is pustule next to follicular orifice and dense perifollicular and perivascular lymphohistiocytic infiltrate with neutrophils in dermis. Note that infundibu-lum is packed with many mites. (Hematoxylin-eosin stain; original magnification:340.)
Fig 4. Perioral dermatitis-like demodicosis (case 12; D07-0344). A, Multiple erythematous papulopustules were present around mouth of 24-year-old woman for 5 years.B, Histologically, there is dense perifollicular and perivascular lymphohistiocytic infiltrate with large, par-tially destroyed infundibular pustule containing multiple mites. (Hematoxylin-eosin stain; original magnification:
manifestation and histopathology of demodicosis may depend on the degree ofDemodexinfestation, duration of the disease, host’s age and general health, and evolutional stage of individual lesions.
The causal relationship of Demodex mites in various forms of demodicosis remains controversial. Only a small number of people develop skin lesions despite a very common presence of these mites in human skin. The rate ofDemodexmite infestation in healthy skin increases with age in general popula-tion,28up to 100% in elderly people.26,29 However, the density in normal-appearing skin is generally low.30 Aylesworth and Vance26 found Demodex mites in 10% of all skin biopsy specimens and in 12% of all follicles in a study of consecutive skin biopsy specimens, and the prevalence rate increased with age. In a study by Vollmer,27 Demodex mites were found in 42% of 388 follicles with inflammation, but only in 10% of noninflamed follicles. Overall, 83% of the follicles with mites showed inflammation in that series. Granulomatous reaction to
extrafollic-ularDemodexhas also been observed in
granulom-atous rosacea-like skin lesions25,31and in rosacea-like demodicosis.9In the latter, up to 10 or 15 mites were found in the affected follicles.32It has been suggested that an increasing density of mites correlates with an increasing perifollicular inflammation and clinical manifestation.3A density of more than 5 mites/follicle or 5 mites/cm2of SSSB specimen has been considered to be pathogenic.2,3Symptoms may develop when the follicles become heavily infested, or when the mites penetrate into the dermal tissue.5
The density ofDemodexmites can be studied by KOH preparations of follicular plugs, skin scrap-ings, and SSSB specimens.18,30,33In our series, the examination was performed in 11 patients, and only one had a negative result (3 mites/follicle). Forton and Song34 found that when the first SSSB specimen was negative, a subsequent SSSB speci-men from the same site had yielded more than 5 mites/cm2. Therefore, a second SSSB should be performed at the same site to avoid a false-negative result.34
Several pathogenic mechanisms have been pro-posed for demodicosis, including: (1) blockage of hair follicles and sebaceous ducts by the mites or the reactive hyperkeratosis; (2) stimulation of the host’s humoral and cell-mediated immune reactions by the mites and their waste products; (3) a foreign body granulomatous reaction to the mite’s chitin-ous skeleton; and (4) a vector role for bacteria.1,4,35 Recently, Lacey et al36 reported that antigenic proteins related to Bacillus oleronius isolated from
D folliculorum mites are capable of stimulating
an inflammatory response in patients with
papulopustular rosacea. Akilov and Mumcuoglu37 showed that an increasing density of the mites was associated with an increasing trend of apoptosis in lymphocytes. This could result in local immuno-suppression, allowing the mites to survive in the host.
With regard to the terminology of the disease, both ‘‘demodicosis’’ and ‘‘demodicidosis’’ have been used with the latter being more commonly used in the older dermatologic literature. ‘‘Demodicidosis’’ with the suffix ‘‘id’’ is analogous to ‘‘tuberculid’’ or ‘‘bacterid,’’ and implies a state of hypersensitivity or allergic reaction to substances of the pathogen. Therefore, ‘‘demodicidosis’’ does not reflect the current view on the pathogenesis of this dermatosis, and ‘‘demodicosis’’ would be a preferred term.
Various regimens have been used to treat demo-dicosis, including systemic metronidazole and iver-mectin as well as topical metronidazole, salicylic acid, gamma benzene hexachloride, sublimed sulfur, permethrin, crotamiton, and benzyl benzo-ate.1,38,39Among these, metronidazole 2%, sublimed sulfur 10%, permethrin 1%, and lindane 1% did not show any acaricidal activity, whereas the efficacy of Fig 5. Perioral dermatitis-like demodicosis (case 13; D07-0148). A, Multiple erythematous papulopustules were present over right periorbital area of 52-year-old man for 1 year.B, Histologically, more than 5Demodexmites are found in pustule within partially destroyed infundib-ulum. (Hematoxylin-eosin stain; original magnification:
3100.)
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crotamiton 10% once a day was confirmed by SSSB.40Demodex can survive in the presence of as much as 1 mg/mL of metronidazole, a concentration
that cannot be achieved in vivo.41 It has been proposed that metronidazole may act on the mite via one or more of its active metabolites formed in vivo.1In the current series, the skin lesions resolved rapidly after systemic and/or topical metronidazole therapy in most patients, and after topical crotam-iton or gamma benzene hexachloride treatment in a few patients. Of the patients who had follow-up longer than 10 months, two had relapses but responded again to antiacarid treatments. One of our patients (case 14) was treated initially with 0.03% tacrolimus because of the clinical diagnosis of perioral dermatitis and steroid rosacea. Oral metro-nidazole was added when the skin biopsy specimen revealed Demodex folliculitis. The lesions re-sponded to the combination therapy. It should be noted that there are reports of demodicosis induced by tacrolimus/pimecrolimus.42,43
In summary, we described the clinicopathologic findings of 15 cases with confirmed diagnosis of demodicosis based on the clinicopathological cor-relation and positive responses to antiacarid ther-apy. Our patients often had a long history of papulopustular or acne rosacea-like eruptions on the face with poor response to nonantiacarid treat-ments before the correct diagnosis was rendered. Demodicosis should be considered in the differen-tial diagnosis of recurrent or recalcitrant facial eruptions, including rosacea-like, granulomatous rosacea-like, and perioral dermatitis-like dermatitis, steroid rosacea, and eosinophilic folliculitis. KOH Fig 6. Granulomatous rosacea-like demodicosis (case 15; D05-0959).A, Many discrete dull red
papules with no obvious pustules were present on face of 48-year-old woman for 6 months.B, Histopathological examination reveals dense perifollicular lymphohistiocytic infiltrate with multinucleated histiocytes and neutrophils. Note presence of two mites (arrow) within suppurative (asterisk) and granulomatous infiltrate around apparently intact follicle plugged by keratin and inflammatory cells.Inset, Close-up view of mite and granulomatous infiltrate. (Hematoxylin-eosin stain; original magnification:340.)
Fig 7. Pityriasis folliculorum (case 8). A, Numerous tiny follicular plugs with faint erythematous background were present for 2 years on both cheeks of 28-year-old woman.
B, Potassium hydroxide examination revealed 7Demodex
examination, SSSB, skin biopsy, or a combination of these are essential to establish the correct diagnosis.
REFERENCES
1. Baima B, Sticherling M. Demodicidosis revisited. Acta Derm Venereol 2002;82:3-6.
2. Erbagci Z, Ozgoztasi O. The significance ofDemodex folliculo-rumdensity in rosacea. Int J Dermatol 1998;37:421-5. 3. Forton F, Seys B. Density ofDemodex folliculorumin rosacea: a
case-control study using standardized skin-surface biopsy. Br J Dermatol 1993;128:650-9.
4. Bonnar E, Eustace P, Powell FC. TheDemodexmite population in rosacea. J Am Acad Dermatol 1993;28:443-8.
5. Ayres S Jr, Ayres S III. Demodectic eruptions (demodicido-sis) in the human: 30 years’ experience with 2 commonly unrecognized entities; pityriasis folliculorum (Demodex) and acne rosacea (Demodex type). Arch Dermatol 1961;83: 816-27.
6. Ecker RI, Winkelmann RK.Demodexgranuloma. Arch Dermatol 1979;115:343-4.
7. Hoekzema R, Hulsebosch HJ, Bos JD. Demodicidosis or rosa-cea: what did we treat? Br J Dermatol 1995;133:294-9. 8. Dominey A, Tschen J, Rosen T, Batres E, Stern JK. Pityriasis
folliculorum revisited. J Am Acad Dermatol 1989;21:81-4. 9. Ayres S Jr, Mihan R. Rosacea-like demodicidosis involving the
eyelids: a case report. Arch Dermatol 1967;95:63-6.
10. De Dulanto F, Camacho-Martinez F. Demodicidosis gravis. [French]. Ann Dermatol Venereol 1979;106:699-704. 11. Post CF, Juhlin E.Demodex folliculorumand blepharitis. Arch
Dermatol 1963;88:298-302.
12. Lee JY, Hsu CK. Granulomatous rosacea-like demodicidosis. Dermatol Online J 2007;13:9.
13. Forton F, Germaux MA, Brasseur T, De Liever A, Laporte M, Mathys C, et al. Demodicosis and rosacea: epidemiology and
significance in daily dermatologic practice. J Am Acad Dermatol 2005;52:74-87.
14. Dominey A, Rosen T, Tschen J. Papulonodular demodicidosis associated with acquired immunodeficiency syndrome. J Am Acad Dermatol 1989;20:197-201.
15. Ashack RJ, Frost ML, Norins AL. Papular pruritic eruption of
Demodex folliculitis in patients with acquired
immunodefi-ciency syndrome. J Am Acad Dermatol 1989;21:306-7. 16. Sahn EE, Sheridan DM. Demodicidosis in a child with leukemia.
J Am Acad Dermatol 1992;27:799-801.
17. Helm KF, Menz J, Gibson LE, Dicken CH. A clinical and histopathologic study of granulomatous rosacea. J Am Acad Dermatol 1991;25:1038-43.
18. Karincaoglu Y, Bayram N, Aycan O, Esrefoglu M. The clinical importance ofDemodex folliculorumpresenting with nonspe-cific facial signs and symptoms. J Dermatol 2004;31:618-26. 19. Purcell SM, Hayes TJ, Dixon SL. Pustular folliculitis associated
with Demodex folliculorum. J Am Acad Dermatol 1986;15:
1159-62.
20. Dolenc-Voljc M, Pohar M, Lunder T. Density of Demodex
folliculorumin perioral dermatitis. Acta Derm Venereol 2005;
85:211-5.
21. Schaller M, Sander CA, Plewig G.Demodexabscesses: clinical and therapeutic challenges. J Am Acad Dermatol 2003; 49(Suppl):S272-4.
22. Smith S, McCulloch C.Demodex folliculorumpalpebrarum. Can J Ophthalmol 1969;4:3-15.
23. Loffreda MD. Inflammatory diseases of hair follicles, sweat glands, and cartilage. In: Elder DE, Elenitsas R, Johnson BL Jr, Murphy GF, editors. Lever’s histopathology of the skin. Phila-delphia: Lippincott: Williams and Wilkins; 2005. pp. 469-512. 24. Georgala S, Katoulis AC, Kylafis GD, Koumantaki-Mathioudaki E,
Georgala C, Aroni K. Increased density ofDemodex folliculorum and evidence of delayed hypersensitivity reaction in subjects with papulopustular rosacea. J Eur Acad Dermatol Venereol 2001;15:441-4.
Table II.Pathological features of demodicosis in 7 patients
Case
No. Clinical picture
Histologic pattern diagnosis
Density of mites
Changes in
infundibulum Dermal infiltrate
9 Perioral dermatitis-like Folliculitis with early pustule
31 N 31 N 21L/H 21P 21
10 Acne rosacea-like Disrupted infundibulum with nodular suppurative infiltrate
11 Disrupted N 41L/H 21
11 Perioral dermatitis-like Folliculitis with infundibular pustule
41 Pustule containing mites
N 11L/H 21
12 Perioral dermatitis-like Dense diffuse lymphohistiocytic infiltrate with infundibular pustule 21 Disrupted, pustule containing mites N 11L/H 21P 21
13 Perioral dermatitis-like Folliculitis with infundibular pustule
31 Disrupted, pustule containing mites
N 21L/H 21
14 Perioral dermatitis-like Folliculitis with infundibular pustule 31 Pustule containing mites N 21L/H 21MNH 11 15 Granulomatous rosacea-like Suppurative granulomatous infiltrate with extrafollicular mites 21 Intact, with hyperkeratosis, inflammatory cells N 21L/H 31MNH 21
Density of inflammatory cells or mites in infundibula are graded using arbitrary scale of 1 to 41in increasing density. L/H, Lymphocyte/histiocyte;MNH, multinucleated histiocyte;N, neutrophil;P, plasma cell.
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25. Grosshans EM, Kremer M, Maleville J. Demodex folliculorum and the histogenesis of granulomatous rosacea. [German]. Hautarzt 1974;25:166-77.
26. Aylesworth R, Vance JC.Demodex folliculorumandDemodex
brevisin cutaneous biopsies. J Am Acad Dermatol 1982;7:583-9.
27. Vollmer RT.Demodex-associated folliculitis. Am J Dermatopa-thol 1996;18:589-91.
28. Andrews JR. The prevalence of hair follicle mites in Caucasian New Zealanders. N Z Med J 1982;95:451-3.
29. Boge-Rasmussen T, Christensen JD, Gluud B, Kristensen G, Norn
MS.Demodex folliculorumhominis (Simon): incidence in a
normo-material and in patients under systemic treatment with erythro-mycin or glucocorticoid. Acta Derm Venereol 1982;62:454-6. 30. Plewig G, Kligman AM. The role ofDemodex. Berlin:
Springer-Verlag; 2000. p. 507-12.
31. Mehregan AH, Hashimoto K. Pinkus’ guide to dermatohisto-pathology. New York: Appleton and Lange; 1991. pp. 260-2. 32. Ayres S Jr, Mihan R.Demodexgranuloma. Arch Dermatol 1979;
115:1285-6.
33. Ayres S Jr. Rosacea and rosacea-like demodicidosis. Int J Dermatol 1987;26:198-9.
34. Forton F, Song M. Limitations of standardized skin surface biopsy in measurement of the density ofDemodex folliculo-rum: a case report. Br J Dermatol 1998;139:697-700.
35. Rufli T, Buchner SA. T-cell subsets in acne rosacea lesions and the possible role of Demodex folliculorum. Dermatologica 1984;169:1-5.
36. Lacey N, Delaney S, Kavanagh K, Powell FC. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol 2007;157:474-81.
37. Akilov OE, Mumcuoglu KY. Immune response in demodicosis. J Eur Acad Dermatol Venereol 2004;18:440-4.
38. Forstinger C, Kittler H, Binder M. Treatment of rosacea-like demodicidosis with oral ivermectin and topical permethrin cream. J Am Acad Dermatol 1999;41:775-7.
39. Shelley WB, Shelley ED, Burmeister V. Unilateral demodectic rosacea. J Am Acad Dermatol 1989;20:915-7.
40. Forton F, Seys B, Marchal JL, Song AM.Demodex folliculorum and topical treatment: acaricidal action evaluated by stan-dardized skin surface biopsy. Br J Dermatol 1998;138:461-6. 41. Persi A, Rebora A. Metronidazole andDemodex folliculorum.
Acta Derm Venereol 1981;61:182-3.
42. Lubbe J, Stucky L, Saurat JH. Rosaceiform dermatitis with follicularDemodexafter treatment of facial atopic dermatitis with 1% pimecrolimus cream. Dermatology 2003;207:204-5. 43. Antille C, Saurat JH, Lubbe J. Induction of rosaceiform
dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment. Arch Dermatol 2004;140:457-60.