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Demodectic Rosacea (Variant)


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Image courtesy of TJ Dunn, Jr.

Introduction

Demodectic rosacea is a variant of rosacea when treatment for demodex mites improves rosacea. There has been in the past some controversy when a discussion about demodectic rosacea is introduced. While very few may still think this a theory, the facts are that there are more clinical reports on demodex mites and rosacea than any other topic, other than prescription drug treatment, i.e. papers on metronidazole, antibiotics. With the introduction of Soolantra by Galderma as an acceptable treatment for demodectic rosacea, more physicians have acknowledged demodectic rosacea to the point that this controversy is no longer viable. [2] In fact, Soolantra is included now as the gold treatment standard for rosacea with the introduction of ivermectin as the active ingredient. Furthermore, ivermectin has been used by rosacea sufferers who have turned to another form of ivermectin treatment, horse paste, since it is readily available without a prescription and is just as effective or better than Soolantra. There will be without a doubt over the counter treatments (non prescription) for rosacea using ivermectin which is so readily available and inexpensive to make coming down the pipeline since the news of using ivermectin for rosacea is spreading. 

Another report says, “Because Demodex mites are ubiquitous, their potential as human pathogens has often been ignored. This contribution focuses on the growing body of evidence linking Demodex mites with various skin disorders. Histologically, spongiosis and lymphoid inflammation are regularly seen in follicles containing Demodex mites. In animals, they are well established as a cause of mange, and a human counterpart-demodectic alopecia-appears to exist. There is also a statistical association between Demodex mite density and rosacea, facial itching, and chronic blepharitis. Papulovesicular rosacealike lesions and spiny blepharitis often respond to agents that reduce Demodex numbers. Although these observations are not sufficient to fulfill Koch’s postulates, Koch’s postulates are also not fulfilled for the association between brown recluse spiders and dermal necrosis or the association between streptococci and guttate psoriasis. The evidence linking Demodex mites to human disease has implications regarding treatment.” [1]

While there may be scant doubters (the number is dwindling to nothing) who still doubt demodex's role in rosacea (such as any who feel demodex is an 'innocent by-stander') [64] there is a growing mount of evidence that demodectic rosacea should be ruled out in a differential diagnosis of rosacea by your physician. If your physician dismisses demodectic rosacea you should refer your physician to this article since keeping up with the latest information is important. There have been a growing number of articles in the media about demodex's role in rosacea. For more info click here. The number of clinical papers by reputable organizations on demodex and rosacea is massive. Click here for a partial list.

It is an established fact that demodectic rosacea occurs since in some cases treatment for demodex improves rosacea. Therefore, it is important to rule out demodectic rosacea in a differential diagnosis if you have a red face. One report said it may be a 'missing link' in the understanding of rosacea. [32] Understanding the history of this controversy and how demodectic rosacea has now become a variant of rosacea is noteworthy. If you are unfamiliar with this history it is worth knowing. 

The History of the Demodex Controversy

The controversy dates back to the 19th century about demodex's role in acne rosacea. For example, Geo E. Fell, MD, wrote in 1886 the following: 
"From these and other statements it is seen that in suggesting the thought that these minute forms of life are etiological factors in even some of the phases of acneform diseases, I shall be but little in accord with the highest authorities. In antagonism to these views, I may say that the results of my observations appear to indicate a close relationship of the parasites with the diseased condition." [63] The 'antagonism to these views' continued for over one hundred years. However, the debate is basically over now. Another source states, "Demodex mites were first reported by Jakup Henle in 1871, and detailed descriptions and demonstrations of the pathogen were made in the following years" [81]

Demodex and its connection with rosacea is without a doubt the most researched and reported topic on rosacea other than clinical reports on metronidazole or other prescription treatments for rosacea. [2] It was not that long ago debated.  A typical example is the view held by Dr. Linda Sy who said in 2000, “I personally believe demodex mites are incidental parasites that prey on compromised skin causing secondary symptoms, not unlike bacteria & fungi. They are not the primary cause of rosacea. Therefore, I suspect that not all rosaceans have demodex as a relevant factor.” She also points out in the same post that “Demodex folliculorum has been mentioned as an aggravating factor to rosaceans for many decades and yet, I have not seen any formal double blind study done on this front. (This supports the wisdom of independent research funding by rosaceans). As you have presented, articles have been published, reporting individuals (a number of whom are immunocompromised) who responded to rx of demodex .” This was reported at David Pascoe's Rosacea Support and gives you an example why some physicians may dismiss demodex's role in rosacea if they are not keeping up with the latest findings. [64] Generally the debate centers on whether demodex plays an active role in rosacea or is passive. The chicken or egg problem of which comes first, the rosacea or demodex. No one really can say for sure. But scant few are dismissing demodex's role in rosacea today. Here are some other examples: 

A paper published by the American Journal of Clinical Dermatology in April 2015 succinctly clarifies the controversy:

 “According to Rothman’s model of causality, Demodex mites are probably a non-necessary and non-sufficient cause of rosacea.”

Ben Gaddie, OD, FAAO, explains in an article,  What's all the craze about demodex?, published in Optometry Times. [78]

The Facts

However, recently the public as well as the medical authorities have now come to realize that demodectic rosacea is a valid concern and should be ruled out in any patient who presents a red face.  "Excess Demodex mites in rosacea skin have been observed for 50 years, but a definite role in rosacea pathogenesis has only been accepted relatively recently, with publication of clear evidence of altered Toll‐like receptor responses to Demodex mites." [80]

Here are some more facts:

Demodectic rosacea is an established fact that should be included in any differential diagnosis of rosacea. As more reports confirm the need to rule out demodectic rosacea, it should be noted that not all cases of rosacea are demodetic, which is very important to understand. But some cases are clearly demodectic, therefore, Demodectic Rosacea is a rosacea variant. The RRDi is the only non profit for rosacea that recognizes Demodectic Rosacea as a variant of rosacea

"While Demodex folliculorum -- a microscopic mite that normally inhabits human skin -- has been found in greater numbers in those with rosacea, it has been long debated whether it may be a cause or simply a result of rosacea. It now appears that its true connection with rosacea's signs and symptoms may be linked to a distinct bacterium associated with the mites, called Bacillus oleronius. In a study funded by the NRS, Dr. Kevin Kavanagh and colleagues at the National University of Ireland-Maynooth found that B. oleronius stimulated an inflammatory response in 79 percent of study patients with subtype 2 (papulopustular) rosacea." [5]

"As early as 1932 Ayres and Anderson called attention to a type of rosacea which they felt was caused in large part by extraordinarily heavy infestation by the mite, Demodex folliculorum, and it was pointed out that the demodex type of rosacea was a further development or complication of an entity that had been described and named by the present author two years previously under the title 'Pityriasis Folliculorum (Demodex) .' Since that time a number of publications have appeared on the subject as well as an exhibit at the thirteenth annual meeting of the American Academy of Dermatology and Syphilology in 1954.......A more recent publication concerning the pathogenic role of Demodex in the production of pityriasis folliculorum (Demodex) and acne rosacea was Ayres and Ayres' summary of 30 years' experience with these two commonly unrecognized entities. Both conditions were referred to as demodicidosis. Inasmuch as the authors' attempts to describe and segregate a particular type of acne rosacea as being caused wholly or in large part by Demodex has led to confusion and to the erroneous statement that the authors have claimed that all cases of rosacea are caused by Demodex, it was felt that a new term should be coined and that rosacea of the Demodex type should henceforth be referred to as 'rosacea-like demodicidosis.' " [6]

The variant, Demodectic Rosacea, that is the name, was due to an email received from Gerg Plewig, M.D. published in this forum. [7] I was trying to understand why demodicosis has never been listed as a variant or subtype of rosacea, attempting to understand if this is a variant of rosacea or not from the professionals in the RRDi MAC and finally got a response explaining how Demodectic Rosacea is the preferred term. This has been a slow process, but I am patient. Dr. Plewig explained that demodicosis is a skin disease all on its own. According to Dr. Plewig, it is only when demodex mites are in increased numbers on pre-existing rosacea that the term demodectic rosacea is used. Demodectic rosacea, the term, has gained use. 

Demodectic rosacea is mentioned by WB Shellby, et. al, in a recent paper published by the Journal of the American Academy of Dermatology. [48] In the Journal of Clinical and Aesthetic Dermatology it is called ‘Demodex Dermatitis.’ [49]

Probably the biggest controversy about demodectic rosacea is whether the mites play the main role in the pathophysiology of rosacea or are as some say simply innocent minor role players aggravating the rosacea.

“In other words, which came first: the mites or the rosacea?” study author Frank Powell, M.D., consultant dermatologist at Mater Misericordiae Hospital in Dublin, Ireland, was quoted as saying. “And now there is evidence that it might be the mites." [8] The old chicken or egg problem. The NRS in July 2012 state in an article, "there may be some evidence that the “chicken” — Demodex mites — and not the “egg” comes first, according to a recent scientific report." [50]

Powell wrote in his noted book on rosacea, "Another theory of pathogenesis relates to the presence of abundant Demodex folliculorum mites in the facial skin of patients with rosacea. These small worm-like organisms are inhabitants of the sebaceous follicles of normal adult facial skin. They were first described in the 1800s, but their role in the homeostasis of facial skin is unknown. They have been reported to transport bacteria on the skin surface, and the population can increase markedly in certain circumstances. They can be easily extracted from the follicles where they are found, often in groups, head downward, feeding on sebaceous material. They have eight short subby legs with claw-like end processes, which they use to move about the facial skin surface from one follicle to another. This apparently occurs at night (it has been shown that the mites react negatively to light.) These organisms seem to live in a harmonious relationship with their hosts and in normal circumstances do not excite an inflammatory reaction in the skin. It is not known if they perform any useful function in human skin, and it is probably impossible to fully eradicate them as the skin seems to become recolonized rapidly following antimite treatment. In patients with rosacea, these mites are greatly increased in number and are found mainly in the centrofacial convexities--the areas typically affected by the inflammatory papules and pustules. Histologic sections of inflammatory lesions show the pathologic changes to be centered on the follicles and mites or the fragments of disrupted mites are often seen in the follicular canals surrounded by inflammatory cells. Sometimes ruptured follicles are seen with particles of demodex mites extruded into the dermis. In these cases foreign body granuloma formation to the follicular aeration and/or the mite is a feature of the histopatholgic changes. Immunosuppressed patients (with HIV infection or on immunosuppressive therapy or patients having renal dialysis) or those who have applied immune-modulating drugs (topical steroids/cacineurin inhibitors) to the face may also have increased numbers of demodex mites on the skin. This suggests a possible role of local immune mechanisms restricting the demodex population in normal facial skin. Some immunosuppressed patients may also develop a pustular eruption similar to rosacea with multiple mites identified not only on skin biopsies, but also visualized by microscopic examination of the scale obtained by gently scraping the skin surface. In some individuals these eruptions were cleared when antimite treatment was used. Finally, it has been shown that these mites have related bacteria, some of which are susceptible to the antibiotics used to treat the papules and pustules of rosacea. These facts could explain the effectiveness of topical and systemic antibiotics in the management of this disorder." [9]

In Chapter 5, on page 75 of Powell's book under the subheading, 'Differential Diagnosis and Investigations,' Powell writes, "These patients have also been shown to have a major increase in the demodex mite count on their facial skin using the cyanoacrylate skin biopsy technique." In discussing Pityriasis folliculorum on pages 81-2 he writes, "The diagnosis of pityriasis folliculorum is facilitated by the use of dermatoscopy, which shows a distinctive picture of the presence of multiple white keratotic material consisting of keratin encrusted demodex mites protruding upwards from the follicular orifices. Scraping the skin surface with the blunt side of a scalpel blade and spreading the scrapings on a glass slide reveals the presence of multiple dead and living D. folliculorum mites. The condition appears to be caused by an overpopulation of mites facilitated by the frequent use of creams and the lack of face washing with soap and water." [9]

He then states on page 82:

"There is no laboratory test or investigation that will confirm the diagnosis of PPR. Specific investigations may be required to rule out similar appearing conditions (many of which will be identified by listening carefully to the patient's medical history and examining the skin lesions). These include skin swabs for bacterial culture, skin scrapings for the presence of demodex mites, scrapings for fungal KOH and fungal culture, skin biopsy for histological examination, (and rarely culture) skin surface biopsy for demodex mite quantification, patch tests, photopatch tests and very rarely systemic workup with appropriate blood tests and radiological examinations." [9]

Another physician says this:

" 'Any patient who presents with a red face — especially a red, dry, scaly face — should have an empirical trial of a topical or systemic medication to treat Demodex,' says Joseph Bikowski, M.D., director, Bikowski Skin Care Center, and clinical assistant professor of dermatology, Ohio State University, Columbus, Ohio." [10]

It has been generally understood that "demodicoses are thought to be rare, occurring mainly for patients with immunosuppression." However, a study released in January 2005 had the objective "to demonstrate the high frequency of demodicoses and the overlapping with papulopustular rosacea (PPR) ." What did the study reveal?

"RESULTS: In all, 4372 diagnoses, in which 115 were demodicoses, were collected among 3213 patients. Demodicosis was the 9th most frequent diagnosis (13th new). Each dermatologist observed an average of 2.4 demodicoses a week (1.2 new). The proportion of demodicoses varied greatly according to the dermatologist. The general status was good in 110 patients; only 3 had known immunodeficiency. The most frequent symptoms were follicular scales (71%) and telangiectasia (63%). The mean Dd was higher in pityriasis folliculorum (m = 61 D/cm 2 ) than in PPR (m = 36 D/cm 2 ; P = .04); 42 patients with PPR had a high Dd, 6 had a low Dd. CONCLUSION: Demodicoses are frequent and occur among patients who are immunocompetent. PPR with normal Dd are rare." [11]

One report in August 2005 says, "Although there are several clinical variants of this disease, a clear classification is missing." The report further says: "We suggest that demodicosis be divided into both primary and secondary types." [12] Another report in 2005 concluded that "MMP-9 may be a further explanatory link between the presence of D. folliculorum and the clinical expression of certain cases of rosacea." [13]

"Although usually considered a non-pathogenic parasite in parasitological textbooks, Demodex folliculorum has been implicated as a causative agent for some dermatological conditions, such as rosacea-like eruptions and some types of blepharitis. Several anecdotal reports have demonstrated unequivocal tissue damage directly related to the presence of the parasite." [14]

A few physicians say that demodicosis is different from demodectic rosacea. For example, this report states, "This observation provides further evidence that demodicosis is a condition distinct from common rosacea." This conclusion was reached after observation of a "24-year-old man presented with papulopustular, rosacea-like centro- facial lesions." [15] However, when demodex quantification density warrants a diagnosis of demodicosis, calling it demodectic rosacea would be just as valid as noted by Dr. Plewig earlier.

In another report about demodex it stated, "In humans, only two species (Demodex folliculorum and D. brevis) have been identified and have been implied to play a role in at least three facial conditions: pityriasis folliculorum, rosacea-like demodicidosis and so-called "demodicidosis gravis." [16]

It has been suggested that demodicosis is a disease that effects primarily people in developing countries and is not prevalent in developed countries. However, it is simple to test for demodex density with a skin biopsy and observation under a microscope for a count which doesn't require an expensive lab test. There has been clinically proven results for treating demodicosis or demodectic rosacea, therefore, rosaceans should insist for tests for demodex to rule out this factor. Demodicosis has been found in developed countries as well and no studies on demographics with demodex density counts have been done in the developed countries. More data is needed. One way this could be done is if one million rosaceans insisted on having a demodex density count with a simple skin biopsy under a microscope. Why physicians don't do this is a question you could ask your physician. However, if one million rosaceans insisted on these tests it would gain the attention of the medical community and the results would be a staggering amount of clinical data on demodex density counts in the rosacea population.

It is very important to understand this fact:

"The features of demodecidosis are often similar to those of rosacea." [17] Demodectic Rosacea is a rosacea mimic and your physician should rule out demodectic rosacea from all the other rosacea mimics.

"Demodex species (mites that normally inhabit human hair follicles) may play a role in the pathogenesis of rosacea. Some studies suggest that Demodex prefers the skin regions that are affected in rosacea, such as the nose and cheeks. Research also supports that an immune response of helper-inducer T-cell infiltrates occurs, surrounding the Demodex antigens in patients with rosacea. Yet, conflicting evidence indicates that Demodex does not induce an inflammatory response in patients with rosacea. Moreover, Demodex is found in large numbers of healthy individuals without rosacea. More studies need to be performed to determine whether Demodex truly is pathogenic." [18]

"The pathophysiology of rosacea remains unknown. A leading theory suggests a vascular basis; however, clinical observations and histopathologic studies suggest that inflammation of the pilosebaceous follicle may be central to the pathogenesis of rosacea. Demodex folliculorum is a frequently seen commensal in the follicles of facial skin. According to evidence from biopsies of the skin surface, individuals with rosacea have a higher density of this parasite. This increased mite density may play a role in the pathophysiology of rosacea by triggering inflammatory or specific immune reactions, mechanically blocking the follicles, or acting as a vector for bacteria. Ongoing research has shown that bacteria from patients with rosacea may behave differently at the higher skin temperature that may be present in patients with rosacea. Another group has isolated bacteria from the Demodex mites; these bacteria may play a pathogenic role in papulopustular rosacea by facilitating follicular-based inflammatory changes." [19]

"Antigenic proteins related to a bacterium (B. oleronius), isolated from a D. folliculorum mite, have the potential to stimulate an inflammatory response in patients with papulopustular rosacea." [20]

"This indicates that the Bacillus bacteria found in the Demodex mite produce an antigen that could be responsible for the tissue inflammation associated with papulopustular rosacea," Dr. Kavanagh said. The researchers located the bacteria in Demodex folliculorum, which are normal inhabitants of human skin. Because these microorganisms often occur in much greater numbers in patients with rosacea, researchers have long theorized that they may play a part in the development of the disorder." [21]

"Demodex folliculorum and Demodex brevis are acari that can be found in hair follicles and sebaceous glands of the skin, especially on face of humans. In this study, Demodex sp was investigated in regard to allergic diseases, age and gender. A total of 197 patients (117 with rosacea, 29 with akne vulgaris, and 51 with allergic diseases) were examined using the standardized skin surface biopsy (SSSB) and 97 out of 197 (49.23%) cases were found to be positive by the Inonu University Medical Faculty Department of Parasitology. There was no significant difference between mite positivity and negativity between the genders, while a higher rate of Demodex sp. was found in patients with rosacea and a lower rate in patients under 20 years old (p0,005). As a result, patients over 20 years old, especially those with rosacea, must be investigated for Demodex sp." [22]

"Could the effects of antibiotics in rosacea be caused by their actions on intracellular bacteria of Demodex, rather than to a postulated anti-inflammatory mechanism? We believe so, and will demonstrate this in a first-of-its-kind poster." [23]

This is my favorite paper on demodectic rosacea which shows the mites all pointing in one direction:

"A random sample of 16 female patients suffering from papulopustular rosacea (PPR) as well as (16) normal female healthy subjects as control group were adopted in this study to assess of Demodex folliculorum pathogenesis. It was done through determination of mite density using a standard skin surface biopsy 10.5 cm2 from different designated 6 areas on the face, and scanning electron microscopic study (SEM) as well as total IgE estimation. A trial of treatment using Crotamiton 10% cream with special program was also attempted. All subjects ranged between 35-55 years old. All patients with rosacea and 15 of the control group i.e. 75.93% were found to harbour mites. The mean mite counts by site distribution were 28.6 & 6.9 on the cheeks, followed by 14.5 & 3.0 on the forehead and lastly 6.8 & 0.8 on the chin in PPR and control groups respectively. The total mean mite count in patients was 49.9 initially and 7.9 after treatment. In the control group it was 10.7 & 10.6 respectively. The mean total IgE was 169.4 & 168.4 and 96.3 & 98.4 in PPR and control groups respectively Light and scanning electron microscopy revealed that all mites were pointing in one direction. Some of them were containing bacteria inside their gut and on their skin. After treatment 3 cases (18.75%) were completely cured, 10 cases (62.5%) gave moderate response while 3 cases (18.75) have no response. In conclusion, this study supports the pathogenic role of D. folliculorum in rosacea." [24]

"Undoubtedly, infestation with D. folliculorum particularly in large number causes rosacea." [25]

"Our results suggest that Demodex mites may play a role in the inflammatory reaction in acne rosacea." [26]

Several papers suggest that increased mites occur after treatment with steroids. Here is an example of just one paper:

"Demodex folliculorum were also more frequently detected in patients who had previously been treated with topical corticosteroids (even in 91.9%), what was often followed by epitheloid granulomas." [27]

According to The Irish Times, Irish Scientists blame bacteria as the cause of rosacea according to a different study. This study is the result of researcher Dr Kevin Kavanagh, a senior lecturer in biology at NUI Maynooth. According to The Irish Times, “Working with the Mater hospital, the researchers previously identified a Bacillus bacterium inside Demodex mites. The bacteria release two proteins that trigger an inflammation in patients with facial rosacea.” [28] Another bacteria may be involved, Bartonella quintana. [60]

"Mites modulated TLR signalling events on both mRNA and protein levels in SZ95 sebocytes. An initial trend towards down modulation of genes in this pathway was observed. A subsequent switch to positive gene up-regulation was recorded after 48 hours of co-culture. Demodex secreted bioactive molecules that affected TLR2 receptor expression by sebocytes. High numbers of Demodex induced pro-inflammatory cytokine secretion whereas lower numbers did not. Demodex mites have the capacity to modulate the TLR signalling pathway of an immortalised human sebocyte line. Mites have the capacity to secrete bioactive molecules that affect the immune reactivity of sebocytes. Increasing mite numbers influenced IL8 secretion by these cells." [76]

"Rosacea was found to be a statistically significant risk factor for Demodex infestation in eyelashes, irrespective of age and sex, with a higher prevalence in papulopustular variety." [77]

There is an increased demodex density count shown in patients hospitalized for worsening heart failure. [82]

Bacteria Associated with Demodex

For years, one type of bacteria is associated with demodex mites and rosacea, Bacillus oleronius, and according to an NRS press release [29] which quotes Dr. Kavanagh as saying, “This indicates that the Bacillus bacteria found in the Demodex mite produce an antigen that could be responsible for the tissue inflammation associated with papulopustular rosacea.”

A study released in September 2007 by Dr. Frank Powell, et.al, also concluded, “Antigenic proteins related to a bacterium (B. oleronius), isolated from a D. folliculorum mite, have the potential to stimulate an inflammatory response in patients with papulopustular rosacea.” [30] Another study released in January 2010 also said, “The strong correlation provides a better understanding of comorbidity between Demodex mites and their symbiotic B oleronius in facial rosacea and blepharitis.” [31] "Although, bacterium Bacillus oleronius, found inside the mite and probably act there like a symbiont, is able to produce proteins causing skin inflammation," [71]

A report by David Pascoe mentions another bacteria is associated with demodex, Bartonella quintana. [58] David also has an interesting article about demodex worth reading. [68]

A third bacteria has been associated with demodex, Bacillus pumilus. [70] 

Now the list is growing further and you can read the complete list of bacteria associated with rosacea by reading this post

Diagnosis

Powell in his book [35] discusses demodex several times. For instance:

Powell explains rosaceiform dermatitis (RD) in which ‘D. folliculorum mites are found in abundance in some individuals affected with this disorder.’ Sometimes RD can be “seen in persons who have applied potent topical steroid creams to their faces over prolonged periods and is referred to as ’steroid induced rosacea-like dermatitis.’ ” These patients ‘have also been shown to have a major increase in the demodex mite count on heir facial skin using the cyanoacrylate skin biopsy technique.’

“Pityriasis folliculorum is an often over-looked clinical entity” and cases are ‘mostly female.’ He explains that there is ‘usually a history of rarely using soap or water to cleanse the facial skin but instead using cleansing creams.’ These individuals often apply moisturizers and complain of a burning or itchy sensation. He states that the diagnosis of PF is ‘facilitated by use of dermatoscopy, which shows a distinctive picture of the presence of multiple white keratotic material consisting of keratin encrusted demodex mites protruding upwards from the follicular orifices.’ This condition ’seems to be caused by an over population of mites facilitated by the frequent use of creams and the lack of face washing with soap and water.’

A very important note for clinicians is found on the last paragraph of page 82 in his book:

“There is no laboratory test or investigation that will confirm the diagnosis of PPR. Specific investigations may be required to rule out similar appearing conditions (many of which will be identified by listening carefully to the patient’s medical history and examining the skin lesions). These include skin swabs for bacterial culture, skin scrapings for the presence of demodex mites, scrapings for fungal KOH and fungal culture, skin biopsy for histologic examination, (and rarely culture) skin surface biopsy for demodex mite quantification, patch tests, photopatch tests, and very rarely systemic workup wih appropriate blood tests and radiological examinations.”

How many dermatologists do you know do such a detailed history and examination? When you were diagnosed with rosacea, did your physician come close to what is mentioned in the above paragraph?

"The presence of D. folliculorum in skin biopsies is associated with the diagnosis of rosacea. The infestation density was increased among the patients with rosacea." [54]

"Rosacea proves to be a significant risk factor for Demodex infestation in the eyelashes. This is independent of age and sex and has a higher prevalence in the papulopustular variety. It is acceptable to search for Demodex infestation in patients diagnosed with rosacea." [73]

Is Demodectic Rosacea Communicable?

There is strong evidence that demodectic rosacea may be contagious. Read this post

Increased Demodex Density 

"Individuals with rosacea exhibit a markedly increased density of demodex on their skin compared to controls in studies with skin surface biopsy specimen" [61]

Quantification and Methods for Demodex Density Counts

What are the numbers revealing? In normal humans demodex density is reported to be "1 or 2 per square centimetre of skin". In rosacea sufferers with demodectic rosacea "the number rises to 10 to 20." [67]

 

http://rosacea-support.org/images/Counting-Demodex-Mites-with-Laser-Micros_98F5/confocal-laser-scanning-microscope_thumb.jpg

A paper published by the British Journal of Dermatology reports, "With the help of CLSM it is possible to non-invasively detect, image and quantify Demodex mites in facial skin of patients with rosacea." [45]

The Confocal Laser Scanning Microscope [CLSM] hopefully will be in every dermatologist's office so that we can get some data on how may sufferers have demodectic rosacea. [46]

Another paper discusses the Confocal LS Microscope and stated, "there are limitations to the use of this method to accurately detect absolute numbers of mites in human skin." [53]

An article in 2014 says, "Reflectance confocal microscopy is a fast, direct and noninvasive method for Demodex-associated diseases and it is superior to SSSB for Demodex mite detection." [55]

"To collect mites for further research, the cellophane tape method (CTP), squeezing method, or skin scrapings can be used. CTP seems to be more effective with a positive rate at 91%, whereas squeezing gives a 34% positive diagnosis  Standardized Skin Surface Biopsy (SSSB) is the most commonly used method for comparing densities of mites between patients with dermatoses and healthy controls." [71]

"Standardized skin surface biopsy (SSSB) and direct microscopic examination (DME) are commonly used to determine Demodex mites density (Dd)." [72]

"High numbers of Demodex induced pro-inflammatory cytokine secretion whereas lower numbers did not. Demodex mites have the capacity to modulate the TLR signalling pathway of an immortalised human sebocyte line. Mites have the capacity to secrete bioactive molecules that affect the immune reactivity of sebocytes. Increasing mite numbers influenced IL8 secretion by these cells." [74]

According to one report,  if you use a skin scraping with a light microscope, no, which says, "The severity of the condition does not depend on the quantitative load of the mites in the scrape." However when using a 'Confocal laser scanning in vivo microscopy', yes, which this same report concludes, "Confocal laser scanning in vivo microscopy is an effective diagnostic method to detect Demodex mites that does not require preliminary preparation for analysis and allows detecting Demodex mites at the level of the spiky epidermis layer, which is not accessible for scarification, to identify the species belonging to the size of Demodex mites (from 100 up to 200 μm - Demodex brevis, 200 to 400 μm – Demodex folliculorum)." [79]

Demodex Density Count - What are the Numbers?

Other Ways to Detect Mites

Scattered Light Intensity (SLI)

More information on demodex density quantification

Scroll to the subheading, Tools to Detect or Quantify Demodex Density Counts, in this post.

Dermoscopy

dermoscopy.png

The advantage of dermoscopy can be shown in a report by Friedman et al which states,"Our case is an example of how dermoscopy could have helped in demodicidosis recognition, since the patient was incorrectly treated with topical steroids possibly with the diagnosis of seborrheic dermatitis. However, when we evaluated the patient, dermoscopy did not reveal what would be expected for seborrheic dermatitis (dotted vessels in a patchy distribution and fine yellowish scales), but revealed, instead, features associated with demodicidosis (“Demodex tails” and “Demodex follicular openings”). [65]

"In 54 patients, the dermoscopy examination yielded a specific picture consisting of Demodex "tails" and Demodex follicular openings. In patients with an inflammatory variant of demodicidosis, reticular horizontal dilated blood vessels were also visualized. Microscopically, skin scrapings demonstrated Demodex in 52 patients. Overall, the dermoscopy findings showed excellent agreement with the microscopy findings (kappa value 0.86, 95% CI 0.72–0.99, P < 0.001)." Dermoscopy of demodicidosis shows the so-called "Demodex tails", which are visualised as creamy/whitish gelatinous threads protruding out of follicular openings (black arrow), and “Demodex follicular openings”, which appear as round and coarse follicular openings containing light brown/greyish plugs surrounded by an erythematous halo (black arrowhead) (f).  See Fig 4, Item f  [66]

A patent for a test for demodex has been proposed. [59]

An interesting comment by Wistar is worth considering:

"The two tests for demodex:

One school of thought is to do the density count. The other school of thought is to perform an empirical test by applying a cream like permethrin or crotamiton daily for 2-3 weeks and see if anything unusual happens.

The first way, counting mite densities, is not too helpful. A person may have many mites or only a few, but the density test provides no indication if you have a problem with the demodex. It merely counts mites in a random column of extracted skin. A nice number is produced for a graph for some researcher's paper. Worse yet, a doctor may even deny treatment to you if the number does not pass some arbitrary threshold.

The second way, the empirical test, is more helpful. If something unusual and significant happens when applying the cream, like a sudden improvement or worsening, then the problem is likely to be linked to the death of demodex. If nothing happens, then demodex is not a problem and can be excluded.

I believe papulopustular rosacea (PPR) is the same thing as what Brady Barrows describes as demodectic rosacea. I believe it is an allergy to demodex or to a bacteria associated with demodex. Some people are allergic, others are not. Unlike other common allergies, this allergen is stuck in your skin as you cannot just choose to avoid demodex. It becomes necessary to kill all the mites to bring relief or to suppress the symptoms with a perpetual course of antibiotics. The symptoms of PPR, the red skin, dry skin, blepharitis, and the relentless onslaught of mosquito bite-like papules that sting/tickle are classic allergy symptoms. Once all the mites are dead and are out of your skin, these symptoms will stop and the skin will return to normal.

If the empirical test is positive, I recommend trying ivermectin or benzyl benzoate. Permethrin and crotamiton alone are not effective enough to completely clear the skin of demodex." [47]

Ben reports how he tested for demodex in this post (go to post #7 by mOrph January 9, 2012 at 4:28 AM).

If you read Samilynn's report (Post #12 December 23, 2012) mentioned above under Anecdotal Reports, she says, "You can see them with a 12X mirror of your face and by putting them on a black background with a $12 hand held mini microscope (60-100X) I purchased from Radio shack."

Treatment

Soolantra

Horse Paste

Sulfur-sodium combination, Crotamiton, and Permethrin

One important item worth mentioning is that IPL kills mites. "Some esthetic improvement may be secondary to clearing of Demodex organisms and reduction of associated lymphocytic infiltrate." [36]

Begin article:

"He then performed a KOH (potassium hydroxide) preparation of the scales and found Demodex mites, at which point he empirically treated the patient with topical Eurax (crotamiton, Ranbaxy). Within two weeks, the patient was clear and has stayed clear for the last two years.

"Since then, I have treated more than 100 patients," Dr. Bikowski says, "and I've reported about 60 of those cases recently in an article. The patients I have clinically diagnosed with Demodex dermatitis were given a therapeutic trial of crotamiton, and within two to four weeks, were clear and stayed clear," he says.

Dr. Bikowski is convinced that there is a large subset of patients who appear to have classic rosacea, are red and scaly, and may or may not have papules and pustules or seborrheic dermatitis, but who in reality have an increased reaction to the Demodex mite."

"At times," he says, "rosacea and seborrheic dermatitis and Demodex dermatitis may all be together; or rosacea and seborrheic dermatitis may be together; or seborrheic dermatitis and Demodex dermatitis may be together. They can overlap, and two or three can exist in one person.

end article [37]

"Dr. Neil Sadick of Cornell University in New York, conducted an investigation of 24 patients with a mean age of 47 years and Fitzpatrick skin types I-IV. He treated them with an IPL device (Quantum SR, ESC-Lumenis), which emits a noncoherent, multiwavelength of light of 500 nm to 1,100 nm. Patients were treated monthly, up to five times, using an average fluence of 25 to 45 J/cm2. At a recent conference he reported that IPL appears to kill mites around hair follicles and sebaceous glands, which could make it useful in treating rosacea." [75]

"A total of 15 females suffering from erythematotelangiectatic rosacea and 12 females free from other dermatological lesions were selected. Demodex folliculorum infestation density in both patients and control were evaluated by non-invasive skin surface biopsies. Five facial sites were selected. The daily topical application of 1/3 diluted camphor oil with glycerol and 500 mg metronidazole orally were given for fifteen days. The results were very successful with no clinical side effects." [38]

"Demodex folliculorum (Follicular or Demodicid mite) is a zoonotic obligatory parasite with clinical manifestations range from normal infestation to complicated ones. Treatment of human facial demodicidosis with freshly prepared camphor oil with or without glycerol dilutions gave complete cure with concentrations of 100%, 75%. and 50%. Incomplete cure but marked drop in infestation density was achieved with diluted camphor oil at concentrations of 25-20%. Camphor oil application proved to be safe with no side effects." [39]

Some prescription drugs used to treat demodectic rosacea are "topical Elimite (permethrin, Allergan), topical Eurax (crotamiton, Ranbaxy) or systemic ivermectin." [40] Ivermectin (Stromectol) is also prescribed orally and topically. [41]

Oil of Oregano has been reported as treatment as well. [42]

Tea Tree Oil is another treatment. [43] One of the authors of this report serves on the RRDi MAC, Scheffer C. G. Tseng, M.D., Ph.D. A word of caution, be sure to dilute it with something. Tea Tree Oil is harsh on rosacea skin. Also, be forewarned if you are a teenager, one report says, "repeated topical use of products containing lavender oil and/or tea tree oil may cause prepubertal gynecomastia ." [44]

50% Sweet almond oil and 50% of the TTO (others report diluting TTO with Macadamia Oil, Rose Hip Oil - the main point is to dilute since pure TTO is usually too harsh on rosacea sensitive skin)

Chia seeds are reported to be able to kill demodex. [57]

tea tree oil mixed with coconut oil

ZOSSO

Topical Ivermectin (Soolantra)

"In conclusion, our results showed that Terpinen-4-ol is the most active ingredient in TTO in exerting Demodex mite-killing effects." [62]

Organophosphate kills larva or eggs of said demodex brevis mites, demodex folliculorum mites or both. [66]

"After clinical manifestations, the mites may be temporarily eradicated with topical insecticides, especially crotamiton cream, permethrin cream, and also with topical or systemic metronidazole. In severe cases, such as those with HIV infection, oral ivermectin may be recommended." [69]

Baby Shampoo and Tea Tree Oil Regimen

Salvia hispanica

ElaineA Borax Bath for Demodectic Rosacea

Topical topical benzyl benzoate (BB) (+crotamiton) treatment for rosacea. 

Remission

Reports of remission from demodectic rosacea are rare. Demodex tend to return after eradicating them months later. [52]

Anecdotal Reports

David Bourke's Web site on his Experience in Treating Demodex Also David has a day by day progress report. David says he has demodicosis (not demodectic rosacea).

Gabranth's Diary on Using the ZZ cream.

Cazini's Report

Ghost's anecdotal report using Ivermectin, etc., (log in and click on Ghost's About Me tab)

Samiylnn's Report (Post #12 December 23, 2012)

Roan's Rifaximin/Ivermectin experience

Conclusion

Soolantra (ivermectin) has proven to be a valid treatment for demodectic rosacea, which validates demodectic rosacea as a rosacea variant, not to mention the horse paste craze that has been discussed in all the rosacea online social groups. There are a number of over the counter, non prescription treatments for rosacea. Without a doubt there will be more treatments available in the future. 

End Notes

[1] Demodex mites: Facts and controversies.
Elston DM.
Department of Dermatology, Geisinger Medical Center, 100 N Academy Ave, Danville, Danville, PA 17822-5206, USA.
Clin Dermatol. 2010 September – October;28(5):502-504.

[2] For a partial list of research articles on demodectic rosacea click here

[3] Beating Rosacea Vascular, Ocular Acne Forms, page 110
Geoffrey Nase, Ph.D.
Nase Publications 2001

[4] "I have always pushed the line that demodex mites have thus far only been proven to be innocent bystanders in rosacea symptoms."
Ocular Demodex, Tea Tree Oil as a treatment, David Pascoe, March 28, 2007, Rosacea Support
Another source of the above statement (April 14, 2007).

David Pascoe has on other occasions has indicated how he feels that the demodex mite is an 'innocent bystander' in rosacea. For example in an article he wrote on February 2, 2006, the following (screen shot) is a statement published on his Rosacea Support Group website:

innocentbystander.png

[5] Rosacea Review, Fall 2010, NRS-Funded Studies Advance Knowledge of Rosacea's Causes

[6] Rosacea Like Demodicidosis, SAMUEL AYRES, JR., M.D., Los Angeles California Medicine, June 1963

[7] Dr. Gerd Plewig is the first reference heard to demodectic rosacea in a response to a question about Demodicosis not being considered a variant or subtype of rosacea in his email dated March 2, 2007 (scroll down to find) Dr. Plewig's email 

[8] Something to Blush About, Medical Breakthoughs, Ivanhoe Newswire, December 11, 2007

[9] Rosacea Diagnosis and Management, pages 69, 70 by Frank C. Powell, Informa Healthcare, 2008

[10] Empirical treatment is key to identifying rosacea, other dermatoses, Modern Medician, John Jesitus, November 1, 2007

[11] Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice.
Forton F, Germaux MA, Brasseur T, De Liever A, Laporte M, Mathys C, Sass U, Stene JJ, Thibaut S, Tytgat M, Seys B.
J Am Acad Dermatol. 2005 Jan;52(1):74-87.

[12] A clinico-pathological approach to the classification of human demodicosis.
Akilov OE, Butov YS, Mumcuoglu KY.
J Dtsch Dermatol Ges. 2005 Aug;3(8):607-14.

[13] Could matrix metalloproteinase-9 be a link between Demodex folliculorum and rosacea?
RR Bonamigo, L Bakos1, M Edelweiss, A Cartell
Journal of the European Academy of Dermatology & Venereology, Volume 19 Issue 5 Page 646 – September 2005

[14] Is demodex really non-pathogenic?
Pena GP, Andrade Filho JS
Rev Inst Med Trop Sao Paulo. 2000 May-Jun;42(3):171-3.

[15] Facial demodicosis.
Zomorodian K, Geramishoar M, Saadat F, Tarazoie B, Norouzi M, Rezaie S.
Eur J Dermatol. 2004 Mar-Apr;14(2):121-2.

[16] Demodicidosis revisited.
Baima B, Sticherling M.
Acta Derm Venereol. 2002;82(1):3-6

[17] Demodecidosis in a patient infected by HIV: successful treatment with ivermectin
Clyti E, Sayavong K, Chanthavisouk K.
Ann Dermatol Venereol. 2005 May;132(5):459-61

[18] Rosacea, eMedicine from WebMD
Author: Agnieszka Kupiec Banasikowska, MD, Consulting Staff, Georgetown Dermatology, PLLC
Coauthor(s): Saurabh Singh, MD, Staff Physician, Department of Dermatology, Georgetown University/Washington Hospital Center

[19] Rosacea and the pilosebaceous follicle.
Powell FC.
Cutis. 2004 Sep;74(3 Suppl):9-12, 32-4.

[20] Mite-related bacterial antigens stimulate inflammatory cells in rosacea.
Lacey N, Delaney S, Kavanagh K, Powell FC.
Br J Dermatol. 2007 Sep;157(3):474-81. Epub 2007 Jun 26

[21] New Study Shows Role for Bacteria in Development of Rosacea Symptoms
National Rosacea Society, May 3, 2004

[22] Frequency of the appearance of Demodex sp. in various patient and age groups
Aycan OM, Otlu GH, Karaman U, Daldal N, Atambay M.
Turkiye Parazitol Derg. 2007;31(2):115-8.

[23] Electronmicroscopic investigation into the possible etiology of rosacea and the implication for treatment
Journal of the American Academy of Dermatology
February 2007 (Vol. 56, Issue 2 (Supplement 2), Page AB44)
Richard Burroughs, MD, National Capital Consortium (Walter Reed Army Medical Center), Washington, DC, United States; Kurt Maggio, MD, Walter Reed Army Medical Center, Washington, DC, United States

[24] A study on Demodex folliculorum in rosacea.
Abd-El-Al AM, Bayoumy AM, Abou Salem EA.
J Egypt Soc Parasitol. 1997 Apr;27(1):183-95.

[25] The pathogenesis of Demodex folliculorum (hair follicular mites) in females with and without rosacea.
el-Shazly AM, Ghaneum BM, Morsy TA, Aaty HE.
J Egypt Soc Parasitol. 2001 Dec;31(3):867-75.

[26] Demodex mites in acne rosacea.
Roihu T, Kariniemi AL.
J Cutan Pathol. 1998 Nov;25(10):550-2.

[27] The possible role of skin surface lipid in rosacea with epitheloid granulomas.
Basta-Juzbasić A, Marinović T, Dobrić I, Bolanca-Bumber S, Sencar J.
Acta Med Croatica. 1992;46(2):119-23.

[28] Study finds cause of rosacea
Claire O’Connell
The Irish Times – Tuesday, July 14, 2009

[29] New Study Shows Role for Bacteria in Development of Rosacea Symptoms
NRS Press Release, May 3, 2004, Suzanne Corr / Barbara Palombo

[30] Mite-related bacterial antigens stimulate inflammatory cells in rosacea.
Lacey N, Delaney S, Kavanagh K, Powell FC.
Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland
Br J Dermatol. 2007 Sep;157(3):474-81

[31] Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Proteins in Patients with Facial Rosacea,
Li J, O’Reilly N, Sheha H, Katz R, Raju VK, Kavanagh K, Tseng SC.
Ophthalmology. 2010 Jan 14,

[32] Abstract

Papulopustular rosacea (PPR) is a common facial skin disease, characterized by erythema, telangiectasia, papules and pustules. Its physiopathology is still being discussed, but recently several molecular features of its inflammatory process have been identified: an overproduction of Toll-Like receptors 2, of a serine protease, and of abnormal forms of cathelicidin. The two factors which stimulate the Toll-like receptors to induce cathelicidin expression are skin infection and cutaneous barrier disruption: these two conditions are, at least theoretically, fulfilled by Demodex, which is present in high density in PPR and creates epithelial breaches by eating cells. So, the major pathogenic mechanisms of Demodex and its role in PPR are reviewed here in the context of these recent discoveries. In this review, the inflammatory process of PPR appears to be a consequence of the proliferation of Demodex, and strongly supports the hypothesis that: (1) in the first stage a specific (innate or acquired) immune defect against Demodex allows the proliferation of the mite; (2) in the second stage, probably when some mites penetrate into the dermis, the immune system is suddenly stimulated and gives rise to an exaggerated immune response against the Demodex, resulting in the papules and the pustules of the rosacea. In this context, it would be very interesting to study the immune molecular features of this first stage, named "pityriasis folliculorum", where the Demodex proliferate profusely with no, or a low immune reaction from the host: this entity appears to be a missing link in the understanding of rosacea.

Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link.
Forton FM.
J Eur Acad Dermatol Venereol. 2011 Oct 24. doi:

10.1111/j.1468-3083.2011.04310.x.
© 2011 The Author. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.
PMID: 22017468 [PubMed - as supplied by publisher]

[33] Demodex Infestation: the Missing Link ?
October 27th, 2011, by David Pascoe

[34] "In my mind, demodex mites remain as an innocent bystander." 
Demodex Mites, Ivermectin (Stromectol) and its use in Dermatology
February 2nd, 2006, by David Pascoe

[35] Rosacea: Diagnosis and Management
Frank Powell, MD, Informa Healthcare, 2008

[36] Intense Pulsed Light Eradicates Demodex Mites
Timothy F. Kirn
Sacramento Bureau, SHARON WORCESTER, Tallahassee bureau, contributed this story • Yahoo source

Lasers Surg Med. 2002;30(2):82-5.
Effects of intense pulsed light on sun-damaged human skin, routine, and ultrastructural analysis.
Prieto VG1, Sadick NS, Lloreta J, Nicholson J, Shea CR.

[37] Rejecting common wisdom: Red, scaly faces not always rosacea or seborrheic dermatitis
Dermatology Times, Modern Medicine, Jane Schwanke, June 1, 2009

[38] Treatment of human Demodex folliculorum by camphor oil and metronidazole.
El-Shazly AM, Hassan AA, Soliman M, Morsy GH, Morsy TA.
J Egypt Soc Parasitol. 2004 Apr;34(1):107-16.

[39] Eucalyptus globulus (camphor oil) in the treatment of human demodicidosis.
Morsy TA, Morsy GH, Sanad EM.
J Egypt Soc Parasitol. 2002 Dec;32(3):797-803

[40] Read the report in footnote [10] above

[41] Ivermectin: pharmacology and application in dermatology
International Journal of Dermatology, Volume 44 Page 981 – December 2005. Pharmacology and therapeutics
Assen L. Dourmishev, Lyubomir A. Dourmishev, and Robert A. Schwartz

[42] Natural remedies aid rosacea management, doctor says Dietary changes, supplements can lead to clearer skin
Lisette Hilton, Dermatology Times, Modern Medicine, December 1, 2004

[43] In vitro and in vivo killing of ocular Demodex by tea tree oil.
Gao YY, Di Pascuale MA, Li W, Baradaran-Rafii A, Elizondo A, Kuo CL, Raju VK, Tseng SC
Br J Ophthalmol. 2005 Nov;89(11):1468-73.

[44] Lavender and Tea Tree Oils May Cause Breast Growth in Boys
NIH News, Wednesday, January 31, 2007

[45] Non-invasive in vivo detection and quantification of Demodex mites by confocal laser scanning microscopy.
Sattler EC, Maier T, Hoffmann VS, Hegyi J, Ruzicka T, Berking C.
Br J Dermatol. 2012 Jun 20. doi: 10.1111/j.1365-2133.2012.11096.x.

[46] Counting Demodex Mites with a Confocal Laser Microscope
David Pascoe
Rosacea Support Group

[47] Wistar's comment on demodex testing
post #4 April 10, 2011 at 10:01 PM

[48] Unilateral demodectic rosacea.
Shelley WB, Shelley ED, Burmeister V.
J Am Acad Dermatol. 1989 May;20(5 Pt 2):915-7.

[49] Demodex Dermatitis A Retrospective Analysis of Clinical Diagnosis and Successful Treatment with Topical Crotamiton
Joseph B. Bikowski, MD, FAAD and James Q. Del Rosso, DO, FAOCD
Journal List >J Clin Aesthet Dermatol >v.2(1); Jan 2009 >PMC2958185

[50] The Chicken, not the Egg?
National Rosacea Society, Thursday, July 5, 2012

Rosacea or Demodex, Which Came First?
by Brady Barrows

[51] More Demodex Dreaming: Mites are the Chicken?
by David Pascoe, July 24th, 2012
Note: On September 18, 2012 David Pascoe wrote an article:
All You Ever Wanted to Know About Demodex Mites

[52] A typical report illustrates what happened to Susanne who treated herself with ivermectin:

"I had what seemed like a total remission back in March and stopped all treatments except dandruff shampoo which I tried because someone told me they had an itchy scalp that dandruff shampoo seemed to relieve. I intended to do maintenance treatments when I became symptom-free, but I neglected to do this. Now, my symptoms are back, though not as strong as they were when I first began treatment. I plan to start using the ivomec again EOD." meridiantoo 16th July 2012 10:02 AM Post #401

[53] Br J Dermatol. 2013 Feb 16. doi: 10.1111/bjd.12280. [Epub ahead of print]

Demodex quantification methods: Limitations of Confocal Laser Scanning Microscopy (CLSM).
Lacey N, Forton FM, Powell FC.

[54] Indian J Dermatol. 2013 Mar;58(2):157. doi: 10.4103/0019-5154.108069.
Evaluation of Demodex folliculorum as a Risk Factor for the Diagnosis of Rosacea In Skin Biopsies.
Mexico's General Hospital (1975-2010).
Ríos-Yuil JM, Mercadillo-Perez P.

[55] Skin Res Technol. 2014 Feb 13.
Reflectance confocal microscopy vs. standardized skin surface biopsy for measuring the density of Demodex mites.
Turgut Erdemir A, Gurel MS, Koku Aksu AE, Bilgin Karahalli F, Incel P, Kutlu Haytoğlu NS, Falay T.

[56] Dermatology 2011;222:128–130
Demodex Mites – Commensals, Parasites or Mutualistic Organisms?
Noreen Lacey Síona Ní Raghallaigh Frank C. Powell

[57] Chia Seed Oil (Salvia hispanica) Also Kills Demodex Mites, David Pascoe, Rosacea Support Group

[58] Another Demodex Bacteria Isolated: Bartonella quintana, David Pascoe, Rosacea Support Group

[59] Method for the diagnosis of rosacea 
WO 2014023803 A1
Applicant: Galderma Research & Development, Universite D'aix-Marseille, Centre National De La Recherche Scientifique

[60] Bartonella quintana detection in Demodex from erythematotelangiectatic rosacea patients
Nathalia Murillo, Oleg Mediannikov, Jérome Aubert, Didier Raoult

[61] Int J Mol Sci. 2016 Sep; 17(9): 1562.
Published online 2016 Sep 15. doi:  10.3390/ijms17091562, PMCID: PMC5037831
Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition
Yu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, Chris Jackson, Academic Editor

[62] Transl Vis Sci Technol. 2013 Nov; 2(7): 2. Published online 2013 Nov 13. doi:  10.1167/tvst.2.7.2, PMCID: PMC3860352
Terpinen-4-ol is the Most Active Ingredient of Tea Tree Oil to Kill Demodex Mites
Sean Tighe, Ying-Ying Gao, and Scheffer C. G. Tseng

More on Terpinen-4-ol

[63] Demodex Folliculorum in Diseased Conditions of the Human Face
Geo. E. Fell
Proceedings of the American Society of Microscopists
Vol. 8, Ninth Annual Meeting (1886), pp. 120-127
Published by: Wiley on behalf of American Microscopical Society
DOI: 10.2307/3220467
Stable URL: http://www.jst

[64] Examples of the demodectic rosacea controversy:

Geoffrey Nase, Ph.D,
Geoffrey Nase, Ph.D., wrote in his book (2001) on rosacea, “Rosacea experts all agree that this mite plays no real role in the development of progression of rosacea (except for the odd pustule).” [3]

David Pascoe
David stated on February 2, 2006, "The status of demodex folliculorum and its role in rosacea is still an open area of study. It has been difficult to prove that there is or isn’t a link between the mite and rosacea. In my mind, demodex mites remain as an innocent bystander." [34]

David, on March 28, 2007, said, “I have always pushed the line that demodex mites have thus far only been proven to be innocent bystanders in rosacea symptoms.” [4]

However, in 2011 David Pascoe has toned his previous remarks some, considering the massive amount of papers written on this subject, and has reluctantly said the following:

"We do need more research. Demodex have been the subject of an enormous amount of rosacea research, so it pains me to say this!" [33] 

In 2016 David now states, "“the role of Demodex mites needs to be better understood”. I agree 100%."  
Demodex Mites are hard to study, by David Pascoe, Rosacea Support Blog, January 5, 2016

Guy Webster, MD
"Although elevated demodex counts are seen in rosacea, Dr. Webster does not see this as a significant factor."
What Works, Rosacea treatments evaluated, By John Jesitus, Dermatology Times

[65] Dermatol Pract Concept. 2017 Jan; 7(1): 35–38.
Published online 2017 Jan 31. doi:  10.5826/dpc.0701a06
PMCID: PMC5315038
Usefulness of dermoscopy in the diagnosis and monitoring treatment of demodicidosis
Paula Friedman, Emilia Cohen Sabban, and Horacio Cabo

[66] Int J Dermatol. 2010 Sep;49(9):1018-23.
Dermoscopy as a diagnostic tool in demodicidosis.
Segal R1, Mimouni D, Feuerman H, Pagovitz O, David M.

[67] Demodex Density Count - What are the Numbers?

[68] All You Ever Wanted to Know About Demodex Mites

[69] Indian J Dermatol. 2014 Jan-Feb; 59(1): 60–66.
doi:  10.4103/0019-5154.123498
PMCID: PMC3884930
Human Demodex Mite: The Versatile Mite of Dermatological Importance
Parvaiz Anwar Rather and Iffat Hassan

[70] Indian J Dermatol Venereol Leprol. 2017 Jul 26;:
Demodex folliculorum associated Bacillus pumilus in lesional areas in rosacea.
Tatu AL, Ionescu MA, Cristea VC

[71]  Iran J Parasitol. 2017 Jan-Mar; 12(1): 12–21.
PMCID: PMC5522688
Human Permanent Ectoparasites; Recent Advances on Biology and Clinical Significance of Demodex Mites: Narrative Review Article
Dorota LITWIN,  WenChieh CHEN, Ewa DZIKA, and Joanna KORYCIŃSKA

[72] Ann Dermatol. 2017 Apr; 29(2): 137–142.
Published online 2017 Mar 24. doi:  10.5021/ad.2017.29.2.137
PMCID: PMC5383737
Demodex Mite Density Determinations by Standardized Skin Surface Biopsy and Direct Microscopic Examination and Their Relations with Clinical Types and Distribution Patterns
Chul Hyun Yun, Jeong Hwan Yun, Jin Ok Baek, Joo Young Roh, and Jong Rok Lee

[73] Indian J Ophthalmol. 2018 Jan; 66(1): 36–38. doi:  10.4103/ijo.IJO_514_17
PMCID: PMC5778578
Demodex and rosacea: Is there a relationship?
Diana Gonzalez-Hinojosa, Alejandro Jaime-Villalonga, Gustavo Aguilar-Montes, and Lorena Lammoglia-Ordiales

[74] Demodex mites modulate sebocyte immune reaction: Possible role in the pathogenesis of rosacea.
Br J Dermatol. 2018 Mar 12;:
Lacey N, Russell-Hallinan A, Zouboulis CC, Powell FC

[75] Dispelling the Mystery of Demodex
Issue Number: Volume 15 - Issue 1 - January 2007
By Neal Bhatia, M.D., and James Q. Del Rosso, D.O., F.A.O.C.D., Using Intense Pulsed Light

[76] Br J Dermatol. 2018 Mar 12;:
Demodex mites modulate sebocyte immune reaction: Possible role in the pathogenesis of rosacea.
Lacey N, Russell-Hallinan A, Zouboulis CC, Powell FC

[77] Indian J Ophthalmol. 2018 Jan;66(1):36-38. doi: 10.4103/ijo.IJO_514_17.
Demodex and rosacea: Is there a relationship?
Gonzalez-Hinojosa D, Jaime-Villalonga A, Aguilar-Montes G, Lammoglia-Ordiales L.

[78] What's all the craze about demodex-Gadie-2016.pdf

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