Are You Confident of the Diagnosis?
Demodex mites are the most common human ectoparasite. They are normally found in the pilosebaceous glands, and their role in causing human disease is controversial. High numbers of mites as well as the presence of mites free in the dermis has been implicated to cause various clinical manifestations in the sebaceous areas, including pustular folliculitis; erythematous and scaly papules and nodules that resemble rosacea and granulomatous facial dermatitis, blepharitis, abscesses, papulopustular scalp eruptions, and rarely nipple dermatitis, otitis externa and myringitis.
Characteristic findings on physical examination
In a patient who has an erythematous, papulonodular, papulopustular or granulomatous eruption of the face, scalp, neck or chest, demodicidosis should be considered, particularly if there is no history of acne, rosacea or flushing triggers, or if the patient has been unresponsive to acne and rosacea treatment (Figure 1 , Figure 2 ). The differential includes other papulopustular or granulomatous facial eruptions, including acne, papulopustular rosacea, sarcoidosis, lupus vulgaris, lupus miliaris disseminatus facei, and granulomatous perioral dermatitis.
The clinical findings described with demodicidosis are not specific, and physical examination and historical findings should be sought that may help narrow the differential. Patients with acne will usually demonstrate comedones. Patients with sarcoidosis may have skin findings in other areas, may demonstrate typical papules along the nasal rim that are known as lupus pernio, or may have eye, joint, or pulmonary complaints. Lupus miliaris disseminatus facei and forms of perioral dermatitis usually have small (1 to 3mm) monomorphic papules. Ultimately a biopsy may be necessary to distinguish these conditions.
Local or systemic immunosuppression may be factors that predispose to increased numbers of mites and demodicidosis, and a history of topical steroids, calcineurin inhibitors, phototherapy or systemic immunosuppression should be sought. Immunosuppressed patients with demodicidosis often report that the lesions are pruritic.
Expected results of diagnostic studies
Most physicians and reports in the literature define demodicidosis as the presence of typical skin lesions plus either 5 or more mites in a low-power microscopic field of a 10% to 15% potassium hydroxide preparation of skin scrapings, or more than 5 mites/cm2 seen in a skin biopsy or in a standardized skin surface biopsy. A standardized skin surface biopsy is a technique that presses a glass slide covered with cyanoacrylate glue against the skin to remove a portion of the stratum corneum and the tops of the pilosebaceous units, and has been used widely in studies of demodicidosis.
Other reports have added finding mites free in the dermis on histologic examination of typical skin lesions as a defining feature of demodicidosis. Mites in the dermis usually have an associated dense perifollicular infiltrate of neutrophils, lymphocytes, and histiocytes, and may or may not be associated with rupture of the follicle (Figure 3 ).
Demodex mites can not be cultured, and the study of the efficacy of topical therapies has therefore been limited.
Who is at Risk for Developing this Disease?
Although the role of Demodex mites in causing human disease is still controversial, there does seem to be an association between immunosuppression and the pathogenicity of Demodex mites. Multiple cases have been reported of immunosuppressed patients with erythema, papules, and pustules of the sebaceous area that demonstrate large numbers of Demodex mites in or around the pilosebaceous units under microscopic or histologic examination. These patients often have pruritus associated with their lesions. The patients’ lesions and symptoms of itching resolve with treatment directed towards the mites.
Patients who have been reported as having Demodex infections have had immunosuppression from advanced HIV infection, following allogeneic stem cell transplants, and in patients receiving chemotherapy for hematogenous malignancies. There have also been some reports that demodicidosis may occur more frequently in patients with less profound immunosuppression, including end-stage renal disease and diabetes mellitus.
Demodicidosis has also been suggested to be more common in patients receiving psoralen and UVA and narrow-band UVB phototherapy to the face, possibly due to local immunosuppression and sebaceous gland hypertrophy that may be seen with phototherapy.
There have been several case reports of a rosacea-like facial eruption developing following both long- and short-term use of pimecrolimus and tacrolimus to the face. In some of these reports, Demodex mites have been found in large enough number to fit the working definition of demodicidosis. Most of these cases resolved with stopping the tacrolimus or pimecrolimus and instituting tetracycline antibiotics. In these cases it is not entirely clear what role is played by local immunosuppression from the topical calcineurin inhibitor, the underlying inflammatory condition, and the Demodex mites themselves, however, a history of use of topical anti-inflammatory agents should alert the clinician to the possibility of a Demodex infestation.
The role of Demodex mites has been studied extensively in rosacea and does not appear to have a causative role. Some studies have reported high numbers of Demodex mites in patients with rosacea, particularly steroid-induced rosacea, but again it is not clear what is caused by the mite itself, the steroid application and resulting immunosuppression, and the patient’s underlying disease. However, steroid application and its resulting immunosuppression should be taken into consideration when trying to treat a patient with high numbers of Demodex mites.
What is the Cause of the Disease?
Demodex folliculorum and Demodex brevis are species of ectoparasitic mites that normally inhibit the pilosebaceous units of humans and other animals. D folliculorum is found more frequently than D brevis and is usually located in the follicular infundibulum. D brevis is usually found in the Meibomian glands and deep in the sebaceous gland. In healthy hosts, the number of Demodex mites increases with age, with several studies demonstrating that 100% of middle-age adults have at least some mites living in their pilosebaceous units.
Neonates are not colonized with Demodex species but become so after close contact with their caregivers. It has been suggested that children have lower amounts of Demodex colonization compared to adults because children produce less sebum. Studies have demonstrated that the average healthy adult without skin disease has fewer than five D folliculorum mites/cm2 of skin, making them the most common ectoparasite of humans.
Demodex mites have been suggested to cause disease through one or a combination of several mechanisms; large quantities of mites may block the hair follicle or the sebaceous duct, causing clogging of the pilosebaceous unit and rupture of the follicle; or the mites, their waste products, or bacteria carried by the mites may cause an inflammatory or allergic reaction in predisposed hosts or when they are present in large amounts.
Systemic Implications and Complications
In immunosuppressed patients, large numbers of Demodex mites may cause pruritic inflammatory papules, pustules, nodules or abscesses at areas other than those with high numbers of sebaceous glands, including the trunk and extremities.
Successful treatment of demodicidosis has been reported with the following topical therapies: salicylic acid, selenium sulfide, metronidazole, lindane, topical retinoids, crotamiton 10%, benzyl benzoate 10% and sublimed sulfur. Oral therapy with metronidazole at doses of 250mg 3 times daily to 500mg once daily and isotretinoin has been reported.
Optimal Therapeutic Approach for this Disease
Although there have been reports of patients responding to topical therapies alone, oral therapy with metronidazole seems warranted for significant facial demodicidosis. These patients have often gone misdiagnosed for some time because their lesions can appear so much like rosacea or acne, and part of proving the diagnosis of demodicidosis is to see a response to anti-parasitic therapy. Given this, and the fact that immunosuppressed patients are more likely to be symptomatic and require systemic therapy, initial therapy with oral metronidazole is suggested.
If oral metronidazole alone for 3 weeks does not make a significant improvement, or if the patient is not able to tolerate metronidazole, oral ivermectin alone at a dose of 200ug/kg once in conjunction with any of the above mentioned topical therapies may be tried. There is some slight evidence that benzyl benzoate may be superior to other topicals when used alone, but it also has significant irritating properties. Otherwise, there is not enough evidence to suggest one topical over another.
When Demodex mites are found in large numbers or in the dermis in the setting of a patient with red papules, nodules and erythema without another etiology for their symptoms, and particularly if they are found in large numbers in patients with local or systemic immunosuppression, treatment directed at eradicating the mites is a reasonable approach.
Treatment can begin with oral therapy with metronidazole or ivermectin as long as the patient does not have any contraindications to either of these medications. If a patient is treated but relapses, particularly in the setting of long-term immunosuppression, topical therapy can be used indefinitely at intermittent intervals, such as permethrin 5% cream weekly.
If prolonged or repeated treatment directed at decreasing the numbers of mites does not improve the patient’s skin condition, a re-evaluation of the diagnosis is required. A skin biopsy should be performed if it has not yet been done, and the patient’s history, medication, and symptoms should be reviewed.
Unusual Clinical Scenarios to Consider in Patient Management
Systemically immunosuppressed patients may require chronic intermittent topical therapy to keep the number of Demodex mites colonizing their skin at a normal level. Patients who are locally immunosuppressed by topical steroids, topical calcineurin inhibitors, or phototherapy may need the cause of their immunosuppression withdrawn to be treated successfully.
What is the Evidence?
Larios, G, Alevizos, A, Perimeni, D, Rigopolous, D, Katsambas, A. “Rosacea-like demodicidosis”. Lancet Infect Dis. vol. 8. 2008. pp. 804(A single case report of a healthy patient with rosacea-like demodicidosis that was cured with oral metronidazole, 250mg three times per day for two weeks, and subsequently weekly permethrin 5% cream.)
Lee, JY, Hsu, CK. “Granulomatous rosacea-like demodicidosis”. Dermatol On-line Journal. vol. 13. 2007. pp. 9(A single case report of a patient with granulomatous rosacea-like demodicidosis who responded completely to topical and oral metronidazole daily for 3 weeks.)
Allen, KJ, Davis, CL, Billings, SD, Mousdicas, N. “Recalcitrant papulopustular rosacea in an immunocompetent patient responding to combination therapy with oral ivermectin and topical permethrin”. Cutis. vol. 80. 2007. pp. 149-5. (A single case report of a patient with rosacea-like demodicidosis who responded completely to oral ivermectin and topical permethrin 5% cream.)
Baima, B, Sticherling, M. “Demodicidosis revisited”. Acta Derm Venereol. vol. 82. 2002. pp. 3-6. (A single case report of a healthy patient with a rosacea-like demodicidosis who did not respond to tetracycline, that did respond to isotretinoin but relapsed following cessation of therapy, and that was finally treated completely with oral metronidazole 500mg per day for 2 weeks.
Forton, F, Seys, B, Marchal, JL, Song, AM. ” and topical treatment: acaricidal action evaluated by standardized skin surface biopsy”. Br J Dermatol. vol. 138. 1998. pp. 461-6. (Thirty-four patients with skin disease and more than 5 Demodex folliculorum mites per 1cm2 of skin using a standardized skin biopsy were randomized to six different topical treatments; metronidazole 2%, permethrin 1%, sublimed sulphur 10%, lindane 1%, crotamiton 10%, and benzyl benzoate 10%. In this study benzyl benzoate 10%, followed by crotamiton 10% decreased the amount of Demodex seen on the standardized skin surface biopsy. However, significant irritation was also seen in the benzyl benzoate treated patients.
El-Shazly, AM, Hassan, AA, Soliman, M, Morsy, GH, Morsy, TA. “Treatment of human Demodex folliculorum by camphor oil and metronidazole”. J Egypt Soc Parasitol. vol. 34. 2004. pp. 107-16. (Daily metronidazole in the dose of 500mg plus topical use of 1/3 diluted camphor oil in glycerine for 15 days decreased the amount of Demodex mites seen in women who were affected with rosacea-like lesions as well as those without.)
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