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  1. 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). 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. 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. Here are some of the 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] 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] 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] Other Ways to Detect Mites Scattered Light Intensity (SLI) More information on demodex density quantification. Dermoscopy 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 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 SupportAnother source of the above statement (April 14, 2007). [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: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu 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: PMC5522688Human Permanent Ectoparasites; Recent Advances on Biology and Clinical Significance of Demodex Mites: Narrative Review ArticleDorota 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.2017.29.2.137PMCID: PMC5383737Demodex Mite Density Determinations by Standardized Skin Surface Biopsy and Direct Microscopic Examination and Their Relations with Clinical Types and Distribution PatternsChul 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 DemodexIssue Number: Volume 15 - Issue 1 - January 2007By 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 [79] Dermatol Reports. 2019 Jan 23; 11(1): 7675.Clinical picture, diagnosis and treatment of rosacea, complicated by Demodex mitesAlexey Kubanov, Yuliya Gallyamova, and Anzhela Kravchenko
  2. Candida albicans (a fungus or yeast) and rosacea have been linked in a few research papers. One report said that a “patient was treated with intermittent pulses of itraconazole for the candidasis and doxycycline initially before being substituted with isotretinoin 6 months later for the rosacea.” and the outcome was that “the patient’s candidiasis responded well and has been in remission for 3 months while his rosacea continues to improve.”[1] Antibiotic resistance and bacterial overgrowth are other complications of long term antibiotic treatment for rosacea. Walter Last dubs this 'antibiotic syndrome.' [2] "The use of invasive devices and broad spectrum antibiotics has increased the rate of candidal superinfections." [3] More info on bacterial overgrowth and antibiotic resistance. One report said, "These findings suggest that S. salivarius K12 may inhibit the invasion process of C. albicans into the mucous surfaces or its adhesion to denture acrylic resins by mechanisms not associated with the antimicrobial bacteriocin activity. S. salivarius K12 may be useful as a probiotic as a protective tool for oral care especially with regards to candidiasis." [4] Candida Albicans And Rosacea Chronic Mucocutaneous Candidiasis (CMC) in Demodectic Rosacea "CMC was diagnosed in our patient despite poor clinical features. Sequencing of the genome revealed STAT1GOF mutation. This mutation affects production of IL-17, an important cytokine in mucocutaneous defense against Candida. The association with mycobacterial adenitis is rare and continues to be poorly understood. The presence of atypical rosacea in this setting is suggestive of this entity. Antifungal therapy and prevention of complications are necessary to reduce the morbidity and mortality associated with this condition." [5] [bold added] End Notes [1] Autosomal Dominant Familial Chronic Mucocutaneous Candidiasis Associated with Acne Rosacea HL Ee, HH Tan, SK Ng; Ann Acad Med Singapore 2005; 34:571-4 • Full Article [2] CANDIDA and the ANTIBIOTIC SYNDROME By Walter Last [3] Candida sepsis following transcervical chorionic villi sampling. A Paz, R Gonen, and I Potasman Infectious Diseases, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Hafa, Israel [4] Effect of Streptococcus salivarius K12 on the in vitro growth of Candida albicans and its protective effect on oral candidiasis model. Ishijima SA, Hayama K, Burton JP, Reid G, Okada M, Matsushita Y, Abe S. Appl Environ Microbiol. 2012 Jan 20. [5] Ann Dermatol Venereol. 2019 Oct 30;: Chronic mucocutaneous candidiasis with STAT1 gain-of-function mutation associated with herpes virus and mycobacterial infections. Baghad B, Benhsaien I, El Fatoiki FZ, Migaud M, Puel A, Chiheb S, Bousfiha AA, Ailal F
  3. An article in the June 1, 2004 Dermatolgy Times by Rebecca Bryant quotes Michael Detmar, M.D., as saying, "Bacteria are likely involved because what works to some extent as a treatment are antibiotics. Also there appears to be a relationship to photo damage." Rosacea: turning all stones for source of pathology, Jun 1, 2004, Rebecca Bryant, Modern Medicine "A bacterial cause for the disease has been hypothesized, but no consistent findings of one bacteria have been demonstrated." Acne Rosacea, Marian S. Macsai, Mark J. Mannis, and Arthur C. Huntley, Chapter 41, DISEASE ENTITY, 1996 by Lippincott-Raven Publishers At least five different types of bacteria have been implicated, suggested or investigated with rosacea: Helicobacter Pylori Chlamydophila pneumoniae Propionibacterium Bacillus oleronius [1] Staphylococcus epidermidis [2] Staphylococcus aureus [3] Also see Microorganisms End Notes [1] 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 Positive correlation between serum immuno-reactivity to Demodex-associated Bacillus proteins and Erythematotelangiectic Rosacea. O'Reilly N, Menezes N, Kavanagh K. Br J Dermatol. 2012 Jun 18. doi: 10.1111/j.1365-2133.2012.11114.x. Demodex-associated Bacillus proteins induce an aberrant wound healing response in a corneal epithelial cell line (hTCEpi). O'Reilly N, Gallagher C, Katikireddy K, Clynes M, O'Sullivan F, Kavanagh K. Invest Ophthalmol Vis Sci. 2012 Apr 24. The potential role of Demodex folliculorum mites and bacteria in the induction of rosacea. Stanislaw Jarmuda, Niamh O'Reilly, Ryszard Zaba, Oliwia Jakubowicz, Andrzej Szkaradkiewicz and Kevin Kavanagh. Journal of Medical Microbiology, 2012 DOI: 10.1099/jmm.0.048090-0 Article at PubMed Media reports have highlighted demodectic rosacea. More info [2] Staphylococcus epidermidis: A possible role in the pustules of rosacea. J Am Acad Dermatol. 2010 Oct 11; Authors: Whitfeld M, Gunasingam N, Leow LJ, Shirato K, Preda V J Am Acad Dermatol. 2010 Oct 11. [3] "No study in rosacea met our inclusion criteria....No studies could be included that assessed S. aureus colonization in patients with rosacea. Also in current review literature S. aureus is not implicated in the pathophysiology of rosacea ...As S. aureus is common at all depths of the skin...For patients with acne a relation between colonization and the disease was less evident and for rosacea no information about colonization could be obtained from the literature." A systematic review and meta-analysis on Staphylococcus aureus carriage in psoriasis, acne and rosacea J. E. E. Totté,corresponding author W. T. van der Feltz, L. G. M. Bode, A. van Belkum, E. J. van Zuuren, and S. G. M. A. Pasmans Eur J Clin Microbiol Infect Dis. 2016; 35: 1069–1077. Published online 2016 May 5. doi: 10.1007/s10096-016-2647-3
  4. The current, as of this date, most popular theory on rosacea was postulated by Dr. Richard Gallo at UCSD, who began postulating the 'innate immune system dysfunction' theory which is a complicated theory. It has become one of the most discussed and hopefully closer to the truth about what is at the heart of rosacea's cause, first postulated in an article in the June 1, 2004 Dermatolgy Times by Michelle Stephenson, who quotes Richard L. Gallo, M.D., Ph.D., saying rosacea may be an 'abnormality in the innate immune system...caused by too much cathelicidin." Dr Gallo says, "if we believe that the disease is caused by too much cathelicidin, we could develop a strategy to block the effects of the cathelicidins by making molecules that mimic that protein but don't have the same effects." Source. This may eventually happen; see Anti-Sting Therapy for Rosacea? "Antimicrobial peptides are central effector molecules in skin immunology. The functions of antimicrobial peptides in skin diseases include the ability to act as cytokines or growth factors, driving disorders such as psoriasis and rosacea, as well as their action as natural antibiotics to control bacteria that influence diseases such as atopic dermatitis and acne." Dermatol Clin. 2017 Jan;35(1):39-50 The Critical and Multifunctional Roles of Antimicrobial Peptides in Dermatology. Takahashi T, Gallo RL "Abnormalities of innate immunity can increase the skin’s susceptibility to the external environment, which might represent an influential factor in initiating or aggravating rosacea. Additionally, studies have also recently been conducted to identify possible abnormalities in adaptive immunity in rosacea, which might contribute to further inflammatory responses in rosacea." Int J Mol Sci. 2016 Sep; 17(9): 1562.Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, "Recent molecular studies suggest that an altered innate immune response is involved in the pathogenesis of the vascular and inflammatory disease seen in patients with rosacea." Postgraduate Medicine, DOI: 10.3810/pgm.2009.09.2066 Updates on the Pathophysiology and Management of Acne Rosacea, Mohamed L. Elsaie, MD, MBA and Sonal Choudhary, MD, "Rosacea is increasingly being viewed as an immune-based disorder." Cutis. 2004 Jan;73(1 Suppl):5-8 Rosacea as an inflammatory disorder: a unifying theory?, Millikan LE "It is suggested that altered immune function plays a significant role in the pathogenesis of the disease." Involvement of immune mechanisms in the pathogenesis of rosacea. Br J Dermatol. 1982 Aug;107(2):203-8. Manna V, Marks R, Holt P. "Besides confirming the data in the literature on the positivity of the basal zone, anticollagen antibodies were found, and eluted antinuclear antibodies were detected against nuclei of cells in the epidermis and dermis, namely, scattered dermal, endothelial and eccrine duct cells." Br J Dermatol. 1980 Nov;103(5):543-51. Immunopathological studies on rosacea. Nunzi E, Rebora A, Hamerlinck F, Cormane RH. "Elevated ANA titers are commonly found in rosacea patients..." Postep Derm Alergol 2013; XXX, 1: 1-5 Antinuclear antibodies in rosacea patients Anna Woźniacka, Małgorzata Salamon, Daniel McCauliffe, Anna Sysa-Jędrzejowska "Expression of TLR2, TLR4 and iNOS was higher in rosacea samples than in normal skin controls. This research demonstrates early and late stage components of innate immunity in specimens of rosacea ratifying the existence of an altered innate immunity in its pathogenesis." Inate immunity in rosacea. Langerhans cells, plasmacytoid dentritic cells, Toll-like receptors and inducible oxide nitric synthase (iNOS) expression in skin specimens: case-control study. Arch Dermatol Res. 2018 Jan 12;: Moura AKA, Guedes F, Rivitti-Machado MC, Sotto MN More info on Cathlecidin An interesting thread on this subject for your information. Theories Revisited
  5. "The pathophysiology of rosacea appears to be inflammatory, and most of the interventions modulate the inflammatory process in some way." The pharmacologic therapy of rosacea: a paradigm shift in progress., Bikowski JB., Cutis. 2005 Mar;75(3 Suppl):27-32; discussion 33-6. "Although the fundamental pathogenesis of rosacea remains unknown, inflammation is a central process in this disorder." Reactive oxygen species and rosacea., Jones D., Cutis. 2004 Sep;74(3 Suppl):17-20, 32-4. "...Many pharmacologic agents that effectively treat the symptoms of rosacea show anti-inflammatory and/or immunomodulating effects, providing further evidence that rosacea is an inflammatory disorder..." Rosacea as an inflammatory disorder: a unifying theory?, Millikan LE., Cutis. 2004 Jan;73(1 Suppl):5-8. "The stigmata of rosacea may be manifestations of an inflammatory process: neutrophilic dermatosis." The Proposed Inflammatory Pathophysiology of Rosacea: Rosacea as an Inflammatory Disorder, Larry Millikan, MD, Medscape "Based on the theory that rosacea shares the same inflammatory features of acne a recent study showed that, ..." P. Acnes Possible Factor in Rosacea, BenzaClin a significant Tx in lesion reduction, Beth Kapes, Dermatology Times Oracea, a popular prescription for rosacea, is used not for its antibiotic effect but instead for its an anti-inflammatory effect. One study in Finland looked at levels of C-reactive protein (CRP), commonly used in clinical studies as a strong marker for inflammation. The researchers found that individuals with slightly elevated blood levels of CRP were 1.7 times more likely to have rosacea than normal individuals. The study concluded, "low grade inflammation is present in several skin diseases," including rosacea. Acta Derm Venereol. 2017 Sep 13. doi: 10.2340/00015555-2795. The Association Between Low Grade Systemic Inflammation and Skin Diseases: A Cross-sectional Survey in the Northern Finland Birth Cohort 1966.Sinikumpu SP, Huilaja L, Auvinen J, Jokelainen J, Puukka K, Ruokonen A, Timonen M, Tasanen K. "Researchers from the University of Illinois at Chicago have identified a protein that is crucial for activating inflammation....Researchers led by Asrar Malik, Schweppe Family Distinguished Professor and head of pharmacology in the UIC College of Medicine, have now identified the channel, called TWIK2, and have studied its function in macrophages, a type of immune cell involved in fending off infections as well as clearing debris during inflammation. "Now that we have identified this crucial channel, it opens up the possibility of developing targeted new anti-inflammatory drugs to modify its function and help and reduce inflammation," said Malik. While some drugs currently exist that target potassium channels, drugs specific to the TWIK2 channel still need to be developed." [1] End Notes Key protein involved in triggering inflammation, University of Illinois at Chicago, Science Daily
  6. One of the more popular theories on the cause of rosacea is the genetic theory. "A primary genetic cause for rosacea is suggested as single genes often control such mediators: enzymes, neuroendocrine transmitters, and cytokines are found in pathways to rosacea signs and symptoms. Currently, neither a specific cause nor a laboratory indicator of rosacea has been suggested." [1] The number one reason why the genetic theory persists is that rosacea does indeed tend to run in families. As Dr. Bernstein says about the cause, "it's probably some kind of combination of genetic and environmental factors" and "No specific rosacea-causing genes have been identified, but the condition tends to run in families — and almost always among those with fair skin." The genetic theory usually comes up when discussing the cause in just about every discussion. However, recent thought on this subject is that while rosacea may be genetic the evidence seems to point to the environmental factors. For instance, notice what this article concluded regarding this subject: "The epidemiological data have always indicated that Western diseases are determined overwhelmingly by diet and other non-genetic factors. Similarly, clinical data have frequently shown that many diseases can be reversed or accelerated by diet and other lifestyle choices. The crucial importance of the new genomic findings is therefore to show that genetic research does not after all contradict these environmental explanations of disease. Rather, it now very strongly supports them." [2] "Data regarding the inheritance of rosacea are scarce. Patients with rosacea have a markedly increased tendency to exhibit a positive family history than do control groups. Furthermore, owing to its higher prevalence among Northern Europeans, a genetic predisposition toward developing rosacea has been hypothesized; however, the specific genes related to this association have not yet been identified." [3] "This cohort study also indicated that approximately half of the factors affecting the pathophysiology of rosacea were genetic, whereas the remainders were environmental, such as smoking, alcohol consumption, skin cancer history, and age." [3[ "Collectively, the gene variants identified in this study support the concept of a genetic component for rosacea, and provide candidate targets for future studies to better understand and treat rosacea." [4] "Nevertheless, the potential genetic basis of this common, disfiguring yet incurable condition is not known. Evidence for a genetic component to rosacea has been hypothesized, with a retrospective study showing that rosacea patients have a greater than fourfold increased odds of having a family member with rosacea (Abram et al., 2010; Steinhoff et al., 2013), but the genes leading to this association are not known. This current study explores genes that associate with rosacea in a large population of individuals of European descent by genome-wide association study." [4] An interesting Medscape video lecture by Dr. Gallo, New Insights Into the Science of Treating Rosacea, which relates to this theory since the innate immune system and cathelicidin (LL-37) is discussed. "Data regarding the inheritance of rosacea are scarce. Patients with rosacea have a markedly increased tendency to exhibit a positive family history than do control groups. Furthermore, owing to its higher prevalence among Northern Europeans, a genetic predisposition toward developing rosacea has been hypothesized; however, the specific genes related to this association have not yet been identified." [5] "Our current hypothesis is that a genetic predisposition, together with trigger factors, leads to the clinical occurrence of transient flushing, which may be because of overstimulation of the sensory and/or autonomic nervous system in the skin and induction of innate immune responses. The concrete relationship between the skin nervous system and the innate immune system is still unclear." [6] While the genetic theory makes us feel like we can't do anything about it the environmental evidence suggests we can do something about it. This theory will no doubt continue to be studied and researched. End Notes [1] Rosacea: current thoughts on origin., Bamford JT., Semin Cutan Med Surg. 2001 Sep;20(3):199-206. [2] The Causes Of Common Diseases Are Not Genetic Concludes A New Analysis, Medical News Today, 07 Dec 2010 [3] Int J Mol Sci. 2016 Sep; 17(9): 1562.Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, [4] J Invest Dermatol. 2015 Jun; 135(6): 1548–1555. Published online 2015 Mar 12. Prepublished online 2015 Feb 19. doi: 10.1038/jid.2015.53, PMCID: PMC4434179 Assessment of the Genetic Basis of Rosacea by Genome-Wide Association Study Anne Lynn S Chang, Inbar Raber, Jin Xu, Rui Li, Robert Spitale, Julia Chen, Amy K Kiefer, Chao Tian, Nicholas K Eriksson, David A Hinds, and Joyce Y Tung [5] 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 [6] J Investig Dermatol Symp Proc. Author manuscript; available in PMC 2013 Jul 8. Published in final edited form as: J Investig Dermatol Symp Proc. 2011 Dec; 15(1): 2–11. doi: 10.1038/jidsymp.2011.7 PMCID: PMC3704130 NIHMSID: NIHMS479650 Clinical, Cellular, and Molecular Aspects in the Pathophysiology of Rosacea Martin Steinhoff, Jörg Buddenkotte, Jerome Aubert, Mathias Sulk, Pawel Novak, Verena D. Schwab, Christian Mess, Ferda Cevikbas, Michel Rivier, Isabelle Carlavan, Sophie Déret, Carine Rosignoli, Dieter Metze, Thomas A. Luger, and Johannes J. Voegel
  7. About eleven years ago the most popular theory on the cause of rosacea was the vascular theory. Since then, other theories seem to have taken over this one. J Bradley Randleman, MD, and C Diane Song, MD in an article, Ocular Rosacea, stated that "...rosacea may be thought of as a disease spectrum with 2 primary etiologic components, vascular and inflammatory. The earliest manifestations of the disease are cutaneous vascular dilatory changes with subsequent increased blood flow in the form of telangiectasias and erythema...." Probably one of the reasons that the vascular theory was so popular ten years ago was when Geoffrey Nase, Ph.D., popularized the theory in his book Beating Rosacea, and stated in his book, "rosacea is primarily a facial vascular disorder in which the affected blood vessels are functionally and structurally abnormal." In 2004, a leading rosacea expert, Dr. Frank Powell, stated in an article in Cutis, "A leading theory suggests a vascular basis...". According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, "Some researchers believe that rosacea is a disorder where blood vessels dilate too easily, resulting in flushing and redness." In Postgraduate Medicine, February, 1999, Dr. Millikan wrote, "The cause of rosacea is unknown, but it is commonly thought to be of vascular origin because of a clinical association with flushing, development of telangiectasia and tissue swelling, and ultimately, tissue proliferation and rhinophyma (enlargement of the nose)." "Flushing and burning sensations in the skin are considered to represent a main clinical feature in rosacea and are regarded as being primarily caused by neurovascular dysregulation. In patients with rosacea, dilatations of the precapillary arterioles lead to flushing and erythema and dilatations of the postcapillary venules result in edema caused by protein leakage and the recruitment of leukocytes." [1] This source refers to this as "Neurovascular Dysregulation." Now other theories are more popular such as the genetic, inflammatory, immune system dysfunction and others. For a complete list click here. End Notes [1] Int J Mol Sci. 2016 Sep; 17(9): 1562.Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, Chris Jackson, Academic Editor
  8. Matthew, Oliver Lawer has posted a question about what you posted above here. If you could reply to this post that would be a kindness.
  9. Due to responsibilities Cathy Rupert, Treasurer for the RRDi and board member for over the past six years has resigned. We will miss her generous giving and volunteer spirit she has manifested over the past years. Cathy was instrumental in getting about a hundred copies of the journal into the hands of the MAC members and important individuals. Thanks Cathy for all your work.
  10. The RRDi is now on Twitter and Facebook. This forum is the state of the art. We have over 600 members now in the RRDi. However, due to the expense of publishing the Journal of the RRDi our funds are now depleted. We could use some volunteers to recruit more members, get more donations and write articles for the next edition of the journal. If you want to do something, make a suggestion or give us an idea of how we can get rosaceans to come together in our community, please post.
  11. This is to announce that volunteer members can receive a free Google apps and Gmail account associated with the RRDi domain. For more info click here.
  12. Email from: From: Robert Brodell, MD Subject: Re: Please take five minutes to comment Date: July 21, 2010 10:52:08 AM HST To: Barrows Brady The best way to categorize acne rosacea would be into subgroups that are treated in the same manner......I like erythrotelangiectatic rosacea as a subset where infection is not a key issue and antibiotics might be less important than evolving vasoconstricting drugs, laser therapy and coverups. Papulopusular acne and many of the variants mentioned in the previous comment are related to demodex, bacterial infection, and pityrosporon yeast.....to the extent that most respond to antibiotics, I have always favored bacteria as a key part of the pathogenesis in most patients, though the antiinflammatory effects of antibiotics may explain their benefits as well. The subset that is associated with seborrheic dermatitis is best treated like rosacea, plus ketoconazole cream bid to cover the pityrosporon that induces seb derm. There will always be some controversy here, but this is the approach I would take if I were a thought leader! Robert Brodell, MD
  13. From: Latkany, MD Robert Subject: RE: RRDi MAC Members Please Comment on Topic Date: July 6, 2010 10:33:48 AM HST To: Brady Barrows In general I would agree. However, if dividing the type of rosacea into subtypes helps explain different etiologies then it is necessary and will be helpful to guide physicians into different treatment directions. But until we better understand why people get rosacea this is all insignificant. Robert Latkany, MD __________________________________________________________________________________
  14. This post has been promoted to an article The RRDi has now endorsed the new phenotype classification of rosacea.
  15. We have received only one review of the Journal of the RRDi so far which has been a rather negative one from David Pascoe. We could use some positive ones but if you feel David is warranted in his criticism of our new journal please post your thoughts here as well. I have written my thoughts on David's review on my personal web site and also thought it would be fair to post it here as well. But please give us your reviews of our new journal in this thread. My thoughts on David's negative review can be read at this article: Is Rosacea a ‘Complicated Diagnosis Path’ and Mysterious Disorder? I would hope that members of the RRDi would read the Journal of the RRDi for themselves and decide what they think of the journal and then post a review here in this thread. Thanks
  16. Jeffry B. Stock, Ph.D., has volunteered to serve on the RRDI MAC. Dr. Stock is on some cutting edge research for a treatment for rosacea at Signum Bioscience.
  17. Lance Christiansen is no longer serving on the RRDi Board of Directors. We appreciate Lance's volunteering to serve the RRDi.
  18. Admin

    Some My Idea

    Welcome Nick to the RRDi. I googled it and haven't heard of using "0.375% lidocaine applied to specific sites modifies the state of the nervous system in the place where you applied and thus acts on the entire body." I had to have google translate the page. Have you actually tried this?
  19. This is to announce that Begül Ya&#287;c&#305;-Küpeli, M.D. has volunteered to serve on the RRDi MAC. Dr. Begül Ya&#287;c&#305;-Küpeli, M.D. suffers from rosacea and is a Pediatric Oncologist. The RRDi is grateful for her volunteering.
  20. IP.Content 2.3 includes a new feature designed to help you build your forums and website out the way you want to: control over your primary navigational menu. The primary navigation menu is the the "tab" bar across the top of the page that includes links to each major section of your site. IP.Board builds this automatically based on the applications you have installed, but when you use IP.Content, you will likely find yourself creating new pages that you wish you could quickly link to in that same bar. It is possible to edit your skin templates manually to accomplish this, but this presents a few problems: Your template edits may need to be reverted when upgrading in the future in order to inherit updates in the skin in future releases. You will have to determine the logic necessary to show the tab as "lit up" when someone is viewing that page (and to ensure other tabs do not appear to be lit up). It is inconvenient repeating this process each time a new page is created. This is no longer a problem with IP.Content 2.3. You can now visit the "Navigation Menu" page available under the Settings module in the IP.Content ACP area and build tabs through an easy to use interface. You can control what order your tabs display in, and even put them before or in between default application tabs. You can control almost every aspect of the tab from the title, the textual tooltip, any additional non-default attributes (for instance, including a javascript click handler that will log the click in an analytics program) and more. You can even create submenus that will display on click or on hover, including many links underneath one tab. You can also modify many aspects of your default application tabs as well, going beyond what IP.Board offers by default. For instance, using this tool you can add additional attributes to your application tabs, change the title, and modify the textual tooltip shown when a user hovers over the tab. The best part about this new feature - IP.Content automatically figures out which tab to light up without any extra work on your part! We hope this new feature in IP.Content 2.3 helps you better control your site the way you want it to be.
  21. When you edit content in IP.Content, whether it be blocks, templates or pages, there are many built in tags that you will need to or want to utilize in order to generate the content appropriately. Blocks have variables containing data that may be of use to your users. Page templates have variables that perform important functions, such as inserting the page title or marking where the page content should be displayed. It is nearly impossible to simply remember every variable that can be utilized in your pages and templates. IP.Content features a template tag help panel that you can use to alleviate this problem. The panel can be minimized if you don't need it (and your preference is remembered so you won't have to minimize it each time you load a new template to edit). The panel is tabbed, providing you with various tag options based on the specific content you are editing. Database templates will show you the database tags you will need to use, while blocks will show you the variables being passed into the block template. You are able navigate some of the tabs when necessary in order to better determine the appropriate variables for the specific area you are editing. A small icon is shown next to each tag, and clicking this icon will insert it into your templates automatically wherever the cursor is blinking. You need not manually copy and paste the tag - simply click to insert! Some tags will have additional information or perhaps a relevant example of the data it represents. These tags will have an arrow indicator next to them to let you know that you can click on the arrow to view further details about that specific tag. This panel is always available and dynamically adjusts to the type of content you are editing. It is but one small feature available in IP.Content designed to help you build your site the way you want, as efficiently as possible.
  22. IP.Board 3.1 introduces a new feature that is available for any application to make use of: sharing links. IP.Content makes use of this feature in the custom databases (and articles) modules to allow you to more easily expose your content to a wider audience. Along with supporting sharing of your content with third party services such as Facebook and Twitter, you can now also send an article via email, print the article, and download the article easily by clicking the appropriate icon under the article body. The additional printing and downloading features allow the content to be shared, online as well as offline. Within the articles module specifically, the article image that you upload when posting the article (optionally) will automatically be flagged for use with Facebook when someone uses Facebook to share the link. This ensures that the correct image is the one Facebook displays to other users. Similarly, we pull out an appropriate extract of textual content for Facebook to use as well. If the user is logged in to Twitter or Facebook, sharing the content becomes even easier, not requiring you to even leave the site. We hope that by providing tools to make it easier to share content on your site, your content will be exposed to a wider audience, bringing you more traffic and making your content more easily and readily available to the world.
  23. With IP.Content articles and custom databases you can mirror a topic to the forums when a new article or database record is submitted. In doing so, IP.Content can also utilize that automatically-generated topic as the comment "storage" for the article or record. When a comment is submitted to the article, the comment is actually stored as a reply to the topic. Similarly, replies made directly to the topic in the forum also show up as comments for the record. This functionality can be enabled at a per-database and per-category level. You can specify separate forums for each category in your article section, for instance, or you can turn off forum commenting for a specific category, while enabling it for all others. A few additional configuration options, such as allowing you to automatically remove the topic when the record is removed, and specifying a prefix and/or suffix for the topic title so that your users can more easily identify that such topics were stemmed from the articles section help round out the feature, giving you better control over how these automatically posted topics are handled. The forum cross-posting capabilities allow the administrator to better tie in articles with the forums, giving you better opportunities to expose your content to a wider audience. Additionally, forum management of comments provides for easier maintenance and stronger managerial options of the comments, utilizing IP.Board's powerful, proven feature set.
  24. The media module in the IP.Content ACP section allows you to quickly and easily manage multimedia files you may need to use with IP.Content. While you can certainly upload your files through FTP, or link to offsite files, you may find it easier to upload the files using the media section of the ACP, and then copy the links for use within pages, templates, and blocks. Media files uploaded through the IP.Content Media Manager are also easily inserted using the Template Tag helper window available when editing pages, blocks and templates with just a single click. From within the media module, you can create folders, upload files, move files and folders, rename files and folders, and delete files and folders. When viewing a listing of files you will see a preview (if the file can be previewed), and selecting a file will present some other pertinent details. You can also right click on the file and use your browser's "Copy Link" option to quickly get the link to the file. This tool can be a timesaver when you simply need to upload an image quickly for use within a page, block or template. The media folder is defined in the media_path.php file in your forum root directory, giving you the freedom to move and organize your paths as needed.
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