The Role of Demodex in Rosacea

The Role of Demodex in Rosacea

Rosacea is a common condition affecting anywhere from 1% to 20% of the population.[1] It is an inflammatory skin condition affecting the face and predominately characterized by facial redness.[2] Rosacea has multiple subtypes, so patients can experience significant differences in addition to facial redness. Some patients may have facial dryness and scaling, acne-like bumps, stinging and burning of their skin or many other symptoms of rosacea.[2] The 4 subtypes of rosacea include: erythematotelangiectatic, papulopustular, phymatous, and ocular. The cause of rosacea is still unclear, but there are plenty of thoughts as to what causes rosacea. These include abnormal regulation of the immune system, increased blood flow to the vessels in the skin of the face, damage to the blood vessels and second layer of the skin, and extra sensitivity to heat.[3] Another thought is the presence of too many Demodex mites on the face, which triggers an inappropriate immune response by people with rosacea. Erythematotelangiectatic and papulopustular rosacea are the subtypes most commonly associated with Demodex mites, although associations with the other subtypes have been described.

Demodex mites are organisms that live on the skin of older children and adults.[4] These mites live within the oil glands, or sebaceous glands, on the skin. The face has the most oil glands of any part of the skin, so Demodex mites are found in greatest number on the face. There are a variety of mites, but the majority on the face are Demodex folliculorum and the second most common being Demodex brevis. Most people have mites on their face, but with too many mites, irritation and redness can occur. While this does not mean patients with many mites always have rosacea, it seems the majority of patients with rosacea may have large numbers of Demodex mites.

More Demodex Mites Associated with Rosacea

Although Demodex mites are found on the skin of the majority of people, studies have shown that patients with rosacea have greater numbers of mites. In one study, multiple skin biopsies were collected and evaluated for the overabundance of mites. Overabundance was defined as having more than 5 mites in a 1 x 1 cm skin biopsy of the face.[5] Of the 57 patients with papulopusturlar rosacea, 42 were found to have an overabundance of Demodex mites on the skin biopsy. The study showed that rosacea patients rarely have normal numbers of mites on their skin.[5] In another study that looked at 49 rosacea patients, there were 10 times the number of Demodex mites on rosacea patients than the patients without rosacea.[6] 98% of patients in the study without rosacea had less than 5 mites per cm2 on their skin biopsies. This study suggested rosacea could be diagnosed based on the density of the mites on a patient’s face due to the lack of numerous mites on normal skin and abundance on rosacea skin.[6]

Although evaluating skin biopsies may be useful in identifying Demodex mites in rosacea, it requires removing a piece of skin from the face. This is not a procedure most patients  want to undergo. For this reason, a different study looked at the mite count on rosacea patients without skin biopsies.[7] They were able to simply scrape the surface of the cheek to measure Demodex follicularum DNA. This was the first study to use this method to identify mites. The researchers in the study were able to measure the amount of mite DNA to measure what they estimated to be the number of mites on the skin. They estimated that there were 6 times the number of mites on rosacea patients, both papulopustular and erythematotelangiectatic rosacea patients, than on patients without rosacea.[7]

Successful Rosacea Treatments Target Demodex

Researchers discovered that Demodex mites were associated with rosacea when a topical medication known to kill mites worked for rosacea. This mite-killing medication called ivermectin was initially used because it seemed to decrease inflammation, but more evidence has shown that it likely works against the mites as well to improve rosacea. Ivermectin 1% cream applied directly to the face is a safe and very effective treatment currently used for papulopustular rosacea.[8] The topical cream improves rosacea within 3 months and can be used in the long-term, up to 1 year according to one long-term study.[9] Another mite-killing medication called praziquantel was also shown to improve rosacea after 12-16 weeks of topical application compared to a placebo.[10]

There are several documented cases of severe rosacea successfully treated with mite-killing medications. In one severe case of oculocutaneous rosacea in a 12-year-old girl, oral ivermectin was used after the failure of three different medications, namely oral doxycycline (an antibiotic), oral isotretinoin (Accutane), and topical tacrolimus (a non-steroid anti-inflammatory).[11] A skin biopsy showed numerous mites indicating a role for ivermectin. After a single oral dose of ivermectin, the rosacea resolved.[11] In a different case report, a 68-year-old man with papulopustular rosacea underwent skin biopsy after trying multiple therapies, similar to those listed above.[12] The skin biopsy showed significant Demodex mites at which point the patient was given oral ivermectin and topical permethrin, another anti-mite medication, resulting in symptom resolution.[12]

How Demodex May Cause Rosacea

How Demodex mites cause rosacea or rosacea-like symptoms is still a topic of debate. In one study, skin biopsies from rosacea patients were analyzed to measure mites and genes associated with inflammation.[7] They found increased levels of several genes for inflammatory proteins. One specific gene associated with mites is NLRP3. This gene is known to activate a cascade that includes caspase-1 and results in production of a major inflammatory protein known as IL-8. The study found higher levels of IL-8 and molecules that are precursors to NLRP3 and caspase-1 supporting the significant impact that Demodex mites have on rosacea.[7]

Additional studies have looked into the bacteria associated with the Demodex mites. These bacteria, Bacillus species specifically, have been shown to induce an inflammatory reaction that signals for a type of white blood cell called a neutrophil to stimulate the inflammation in the skin.[13,14] Neither of the studies directly implicated the mite-associated bacteria in rosacea development, but each of the studies looked at the specific inflammatory reaction caused by the bacteria. More research needs to be conducted to determine the absolute association between the Demodex mite and rosacea development.

The Bottom Line

Demodex mites are present on the skin of most people, but the more mites, the more likely rosacea is present. The vast majority of people without rosacea have fewer numbers of mites and the majority of rosacea patients have greater numbers of mites. There are, however, people that fall in between. Some patients with large numbers of mites present with similar symptoms to rosacea solely because of the Demodex mites on their face, but do not have true rosacea.[15] In these cases, it may be difficult to determine the cause of the symptoms. Demodex mites do not cause rosacea, but likely precipitate or exacerbate rosacea. If regular rosacea treatments do not work for a patient with rosacea or rosacea-like symptoms, therapy targeting Demodex should be considered. For more information, read “Is Rosacea Caused by Demodex Mite Overgrowth?

* This Website is for general skin beauty, wellness, and health information only. This Website is not to be used as a substitute for medical advice, diagnosis or treatment of any health condition or problem. The information provided on this Website should never be used to disregard, delay, or refuse treatment or advice from a physician or a qualified health provider.

References

1.         Tan J, Berg M. Rosacea: current state of epidemiology. J Am Acad Dermatol.2013;69(6 Suppl 1):S27-35; PMID: 24229634 https://www.ncbi.nlm.nih.gov/pubmed/24229634.

2.         Wilkin J, Dahl M, Detmar M, et al. Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol.2004;50(6):907-912; PMID: 15153893 https://www.ncbi.nlm.nih.gov/pubmed/15153893.

3.         Vemuri RC, Gundamaraju R, Sekaran SD, et al. Major pathophysiological correlations of rosacea: a complete clinical appraisal. Int J Med Sci.2015;12(5):387-396; PMID: 26005373 https://www.ncbi.nlm.nih.gov/pubmed/26005373.

4.         Elston CA, Elston DM. Demodex mites. Clin Dermatol.2014;32(6):739-743; PMID: 25441466 https://www.ncbi.nlm.nih.gov/pubmed/25441466.

5.         Forton F, Germaux MA, Brasseur T, et al. Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice. J Am Acad Dermatol.2005;52(1):74-87; PMID: 15627084 https://www.ncbi.nlm.nih.gov/pubmed/15627084.

6.         Forton F, Seys B. Density of Demodex folliculorum in rosacea: a case-control study using standardized skin-surface biopsy. Br J Dermatol.1993;128(6):650-659; PMID: 8338749 https://www.ncbi.nlm.nih.gov/pubmed/8338749.

7.         Casas C, Paul C, Lahfa M, et al. Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation. Exp Dermatol.2012;21(12):906-910; PMID: 23171449 https://www.ncbi.nlm.nih.gov/pubmed/23171449.

8.         Stein L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol.2014;13(3):316-323; PMID: 24595578 https://www.ncbi.nlm.nih.gov/pubmed/24595578.

9.         Stein Gold L, Kircik L, Fowler J, et al. Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials. J Drugs Dermatol.2014;13(11):1380-1386; PMID: 25607706 https://www.ncbi.nlm.nih.gov/pubmed/25607706.

10.       Bribeche MR, Fedotov VP, Gladichev VV, et al. Clinical and experimental assessment of the effects of a new topical treatment with praziquantel in the management of rosacea. Int J Dermatol.2015;54(4):481-487; PMID: 25040098 https://www.ncbi.nlm.nih.gov/pubmed/25040098.

11.       Brown M, Hernandez-Martin A, Clement A, et al. Severe demodexfolliculorum-associated oculocutaneous rosacea in a girl successfully treated with ivermectin. JAMA Dermatol.2014;150(1):61-63; PMID: 24284904 https://www.ncbi.nlm.nih.gov/pubmed/24284904.

12.       Allen KJ, Davis CL, Billings SD, et al. Recalcitrant papulopustular rosacea in an immunocompetent patient responding to combination therapy with oral ivermectin and topical permethrin. Cutis.2007;80(2):149-151; PMID: 17944176 https://www.ncbi.nlm.nih.gov/pubmed/17944176.

13.       O'Reilly N, Bergin D, Reeves EP, et al. Demodex-associated bacterial proteins induce neutrophil activation. Br J Dermatol.2012;166(4):753-760; PMID: 22098186 https://www.ncbi.nlm.nih.gov/pubmed/22098186.

14.       Lacey N, Delaney S, Kavanagh K, et al. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol.2007;157(3):474-481; PMID: 17596156 https://www.ncbi.nlm.nih.gov/pubmed/17596156.

15.       Forton FM, Germaux MA, Thibaut SC, et al. Demodicosis: descriptive classification and status of Rosacea, in response to prior classification proposed. J Eur Acad Dermatol Venereol.2015;29(4):829-832; PMID: 25600359 https://www.ncbi.nlm.nih.gov/pubmed/25600359.

 
 
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