Demodex infestation

From EyeWiki


Demodex mites are considered a normal occupant of hair follicles and exist in a commensal relationship with humans. At times, though, these mites can become more parasitic, resulting in a variety of ocular diseases. Due to non-specific clinical manifestations, Demodex infestation can be an often overlooked etiology for multiple ocular conditions such as keratitis or blepharitis.

Disease Entity

Demodex infestation of the eyelids

Disease

Demodex mites are considered a normal occupant of hair follicles and exist in a commensal relationship with humans. At times, though, these mites can become more parasitic, resulting in a variety of ocular diseases. Due to non-specific clinical manifestations, Demodex infestation can be an often overlooked etiology for multiple ocular conditions such as keratitis or blepharitis.

Demodex infestation is a commonly overlooked cause of ocular inflammation. Though true pathogenicity in humans is controversial, Demodex has been linked to many ocular conditions including blepharitis, conjunctivitis, chalazia, recurrent trichiasis, rosacea, and keratitis.[1] [2] [3] [4]

Etiology

  • Demodex mites are considered part of the normal skin fauna.
  • Demodex mites have been thought to be first acquired from mother-to-infant through breast feeding due to their presence on the nipple. [1]
  • These mites typically exhibit a relationship of commensalism with humans (Demodex benefit, humans unaffected); however, in certain disease states, the relationship with Demodex becomes more parasitic.[5]
  • They reside within the pilosebaceous units and are therefore most prevalent on the face.[1]

Risk Factors

Risk factors include increasing age and individuals who care for the elderly.[1]

As previously stated, Demodex is acquired shortly after birth and their numbers increase during puberty as sebaceous glands proliferate. The prevalence continues to increase with age, with 13% of 3-15 year olds infested, 69% of 31-50 year olds, 84% by age 60, and 100% after 70 years of age.[1]

General Pathology

There are two main types of Demodex: D. folliculorum and D. brevis. D. folliculorum measures 0.3-0.4 mm long and is found in clusters around lash follicles while D. brevis measures 0.2-0.3 mm long and is found solely in the sebaceous units and Meibomian glands.[6] Thus, D. folliculorum has been associated more closely with anterior blepharitis and D. brevis more closely with posterior blepharitis and Meibomian gland dysfunction.

Pathophysiology

Demodex mites are readily transferred via skin-to-skin contact.[6] Demodex can cause problems through the following mechanisms:

  1. The mites consume the lining of follicles in order to lay their eggs. This results in the distention of the follicle and mal-direction of the lashes.[7][8]
  2. Mechanical blockade of the sebaceous ducts by the mites results in irritation of the eyelid margin.[9]
  3. The chitin-formed exoskeleton of the mites can induce both a general inflammatory response as well as a foreign body-like granulomatous reaction that has been implicated in the formation of chalazia.[10]

Primary prevention

Good lid hygiene with soaks and scrubs can be helpful. Infestations with Demodex are more common in patients who are immunocompromised. In patients with HIV, eruptions generally occur when CD4 count drops below 150/mm3.[11]

Diagnosis

As Demodex mites are implicated in a variety of diseases, patients may present with a variety of signs and symptoms. Clinical suspicion for Demodex as the causal etiology must therefore be high. Since these mites can be seen in normal skin, the clinical presentation must coordinate with any physical exam findings or pathologic diagnoses.

History

Patients with symptomatic Demodex infestation can present with several corneal and external diseases resulting in symptoms including itching, burning, foreign body sensation, blurry vision, and pain. As these symptoms are common in many disorders, additional evidence in conjunction with strong clinical suspicion is necessary to establish the diagnosis. Demodex infestation may be suspected as the cause if a patient reports recurrence of these symptoms that are refractory to conventional treatments.[6]

Clinical photo of cylindrical dandruff from Demodex:  Lash sampling and microscopic examination reveal cylindrical dandruff harboring mites (photo from Cheng, Sheha, & Tseng 2015)[6]

Physical examination

There is often poor correlation between symptoms and objective signs indicating Demodex infestation.[8] Slit-lamp exam can be used to detect cylindrical dandruff at the root of the lashes, a pathognomonic sign for Demodex [see figure].[6][9] Otherwise, exam findings are typical for the diseases listed above and are therefore non-specific for Demodex.

Signs

  • Cylindrical cuff at the root of eyelashes
  • Blepharitis
  • Lid margin erythema

Symptoms

  • Itching
  • Burning
  • Foreign body sensation
  • Crusting/mattery lashes
  • Tearing
  • Blurry vision
  • Discomfort/irritation
Histologic picture of Demodex:  typical cross-section of Demodex seen within hair follicles (H&E, 20x). Photo courtesy of Martin,Reddy,Burkat.

Clinical diagnosis

Microscopic and Pathologic Diagnosis

Sampling of lashes can allow for detection of mites microscopically. This can be done by epilating lashes, placing them on a glass slide, adding fluorescein on top, covering with a cover slip, and examining them under the microscope for the presence of mites.[12]

In biopsy samples containing skin, multiple sectioned Demodex mites can be seen filling the space occupied by the follicle. There are typically chronic inflammatory cells surrounding the follicles. [see figure]


Differential diagnosis

The differential diagnosis of Demodex infestation depends on the particular manifestation. Given that Demodex is associated with a variety of pathologies, the differential can include infectious/inflammatory causes of conjunctivitis, keratitis, keratoconjunctivitis, blepharitis, dry eye syndrome, chalazia, and trichiasis. It is also important to distinguish Demodex from phthiriasis palpebrum (infestation with pubic lice) when examining dandruff of the lashes.[13]

Management

As previously stated, detection of Demodex without clinical symptoms does not warrant treatment. The treatment of clinically significant Demodex infestation generally involves the use of tea tree oil and its derivatives.

Medical therapy

Eradication of Demodex infestation is accomplished using daily lid scrubs with tea tree oil (TTO). 50% TTO was initially used as the therapeutic dosing and was shown to reduce symptoms and inflammation of the cornea, conjunctiva, and lid margin.[14] This dosing, however, caused irritation in some patients. Thus, the active ingredient of TTO, terpinen-4-ol (T4O), was isolated. T4O was more potent at equivalent doses of TTO, thus allowing for effective treatment at lower concentrations.[15]

The discovery of T4O allowed for the development of Cliradex®. This product is a facial wipe containing T4O that patients use daily to treat the various manifestations of Demodex infestation. Treatment regimen is recommended to last at least 6 weeks in order to cover the patient through two life cycles of Demodex.[6]

Additionally, an in-office treatment has been developed called Cliradex® Complete. This involves an initial treatment by applying a stronger concentration of T4O to the lid margin followed by thorough cleaning of the root of the lashes and removal of debris. The patient then follows this initial therapy with Cliradex® wipes at home[6]

Additional therapies that have been used for Demodex-associated skin disease include topical sulfur products, permethrin, and ivermectin. Facial eruptions have also been treated with oral metronidazole and with dilute topical camphor oil.[1]


References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 Elston CA and Elston DM. Demodex mites. Clinics in Dermatology. 2014;32: 739-743.
  2. Schear MJ, Milman T, Steiner T, et al. The Association of Demodex with Chalazia: A Histopathologic Study of the Eyelid. Ophthal Plast Reconstr Surg. 2016;32(4): 275-278.
  3. Holmes AD. Potential role of microorganisms in the pathogenesis of rosacea. Journal of the American Academy of Dermatology. 2013;69(6): 1025-1032.
  4. Zhao YE, Wu LP, Hu L, Xu JR. Association of blepharitis with Demodex: a meta-analysis. Ophthalmic Epidemiol. 2012;19(2): 95-102.
  5. Chen W and Plewig G. Are Demodex Mites Principal, Consipiratory, Accomplice, Witness or Bystander in the Cause of Rosacea?. Am J Clin Dermatol. 2015;16: 67-72.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Cheng A, Sheha H, and Tseng S. Recent advances on ocular Demodex infestation. Curr Opin Ophthalmol. 2015;26: 295-300.
  7. Liu J, Sheha H, and Tseng S. Pathogenic role of Demodex mites in blepharitis. Curr Opin Allergy Clin Immunol. 2010;10(5): 505-510.
  8. 8.0 8.1 Nicholls S, Oakley C, Tan A, Vote B. Demodex species in human ocular disease: new clinicopathological aspects. Int Ophthalmol. 2016 May 9 [Epub ahead of print].
  9. 9.0 9.1 Gao Y, Di Pascuale M, Li W, et al. High prevalence of Demodex in eyelashes with cylindrical dandruff. Invest Ophthalmol Vis Sci. 2005;46(9): 3089-3094.
  10. Liang L, Ding X, Tseng S. High prevalence of Demodex brevis infestation in chalazia. Am J Ophthalmol. 2014;157(2): 342-348.
  11. Yamaoka T, Murota H, Tani M, Katayama I. Severe rosacea with prominent Demodex folliculorum in a patient with HIV. J Dermatol. 2014;41(2): 195-196.
  12. Kheirkhah A, Blanco G, Casas V, Tseng S. Fluorescein dye improves microscopic evaluation and counting of Demodex in blepharitis with cylindrical dandruff. Cornea. 2007;26(6): 697-700.
  13. Turqut B, Kurt J, Catak O, Demir T. Phthriasis palpebrarum mimicking lid eczema and blepharitis. J Ophthalmol. 2009;2009: 803951.
  14. Gao Y, Di Pascuale M, Elizondo A, Tseng S. Clinical treatment of ocular demodecosis by lid scrub with tea tree oil. Cornea. 2007;26: 136-143.
  15. Tighe S, Gao Y, Tseng S. Terpinen-4-ol is the Most Active Ingredient of Tea Tree Oil to Kill Demodex Mites. Transl Vis Sci Technol. 2013;2(7): 2.