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Rosacea Theories Revisited


Brady Barrows
  • If you were around in August 2007, there were headlines such as, Scientists unmask the cause of rosacea, [1] and UCSD Researchers Discover Cause of Rosacea [2] not to mention all the other headlines which created quite a stir in all the online rosacea groups and brought a lot of hope for rosacea sufferers. These articles seemed to conclude that rosacea’s mystery is resolved and within time a treatment would be found to eradicate rosacea. These startling headlines were the result of a paper published by researchers at UCSD associated with Richard L Gallo, et.al, in a study published by Nature Medicine [3]. This paper concluded:

Innate Immune System Disorder

“These findings confirm the role of cathelicidin in skin inflammatory responses and suggest an explanation for the pathogenesis of rosacea by demonstrating that an exacerbated innate immune response can reproduce elements of this disease.” 

If you will notice in the above statement that the findings suggest an explanation for the pathogenesis of rosacea. Gallo, et.al, never said they found the cause of rosacea. The newspapers came to the conclusion that now all the mystery of rosacea is over and we have the cause nailed down. All we have to do is wait for the treatment. This is not exactly the truth. While the research of Gallo, et.al, at UCSD is remarkable and insightful, the jury is still out on what causes rosacea. And while the jury is still out, there is more news worth mentioning that may be related to cathelicidin, peptides or antigenic proteins.

However, the cathelicidin theory on the cause of rosacea is rooted in the immune system disorder theory, which is probably the most popular one as of this date. More on cathelicidin

Demodectic Rosacea

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.” [4]

At least one type of bacteria is associated with demodex mites and rosacea. This bacteria is Bacillus oleronius according to an NRS press release [5] 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.” [6] 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.” [7] Now, another bacteria, Bartonella quintana, may be implicated with the mites according to a report by David Pascoe. [17] The consensus has grown that demodectic rosacea is a variant of rosacea. [20] 

IBS

Another theory on the cause of rosacea is that irritable bowel syndrome is related to rosacea. “Rosacea may be a symptom of an unhealthy gastrointestinal system and healing the entire gastrointestinal system may be the basis for eliminating rosacea. Many people with rosacea also have been diagnosed with Irritable Bowel Syndrome (IBS), Crohn’s Disease or some for of Colitis.” [12] This theory falls under Other Theories >  IBS and Rosacea.

Bacteria Theory

The IBS theory also is related to bacteria in the gut and that using antibiotics clears rosacea. An article in the St. Louis Dispatch [13] says that one doctor has been prescribing Xifaxan, an antibiotic for gastric problems and reports clearing of rosacea. Previous to this report a study done in Italy published that eradicating the bacteria in the gut had improved rosacea. [14] This theory falls under Rosacea Theories > Bacteria Theory

SIBO

Another theory that has come up is that SIBO is related to rosacea. The previously mentioned rosacea online guru had this to say about SIBO and rosacea:

“This sort of abstract just make me shake my head. If you read quickly you will think that this abstract suggests that Small Intestinal Bacterial Overgrowth (SIBO) causes rosacea. What this abstract is saying that is that rosacea sufferers seem to have a higher incidence of SIBO than non rosacea sufferers.” [15] “The link between SIBO and the papules and pustules of rosacea is still a mystery.” [16] For more information on rosacea and SIBO click here. This theory falls under Other Theories > SIBO and Rosacea.

H pylori

Speaking of bacteria, particularly gram negative bacteria, there is a continuing controversy as to whether H pylori is a factor in rosacea ( read an article on this subject). This theory falls under Various Environmental Stimuli  Microorganisms  > Helicobacter Pylori.

Associated Diseases

Rosacea is associated with a number of other diseases, such as Migraine, CRS (see below), Multiple sclerosisAlzheimer's Disease, Dementiacardiovascular diseases, Parkinson's disease, cancer, diabetes, GliomaHLA-DRA Locus (see below), inflammatory bowel disease, depression/anxiety disorders, and the list seems to be growing. This complicates the theories on the cause of rosacea increasing the call for further research. However, in one study it was stated, "In this large study of patients with rosacea, atopic dermatitis, and psoriasis, we did not detect an increased 1-year risk of cardiovascular disease after adjusting for confounders." [18]

"The HLA-DRA locus is associated with rosacea as well as with other inflammation-associated disorders, such as inflammatory bowel diseases including ulcerative colitis, Crohn’s disease, and celiac disease....Moreover, Spoendlin et al. found that an increased risk of rosacea was observed particularly during the period of increased gastrointestinal tract inflammation. Thus, the overlap in the genetic relevance of HLA-DRA between rosacea and inflammatory bowel diseases might imply a potential link between these disorders...Patients with rosacea have a higher risk of cardiovascular comorbidities including hypertension, dyslipidemia, and coronary artery disease than that seen in controls. Rosacea severity was also found to be dependent on the presence of cardiovascular comorbidities....In addition, the association between cardiovascular diseases and rosacea might also be explained by enhanced expression of the cathelicidin, which has been observed both in the course of atherosclerosis and rosacea. The GWAS by Chang et al. [20] also revealed that patients with rosacea shared a genetic locus with type 1 diabetes mellitus; this association was further confirmed by a population-based study as well....Patients with rosacea have a significantly increased risk of neurologic disorders such as migraine, depression, complex regional pain syndrome, and glioma...Recently, an increased interest has been shown in the potential associations between neurodegenerative diseases and rosacea....For example,...Parkinson’s disease...dementia, especially Alzheimer disease..." [19]

There may be a relationship between rosacea and chronic rhinosinusitis (CRS) as the following quote concludes: 

"Patients with rosacea and CRS manifested severe erythematotelangiectatic rosacea. There was enough evidence to suggest an association between rosacea and CRS. Clinical and radiological assessments of the paranasal sinuses are recommended." [21]

Conclusion

The jury is still out on what causes rosacea. The headlines may one day report another ’cause’ of rosacea or highlight the ones discussed above. Whatever happens, keep an open mind, since we still don’t know what causes rosacea. We may be surprised one day to actually read a headline that truthfully explains the cause of rosacea or clearly distinguishes rosacea from the plethora of mimics. 

For more information on the cause of rosacea and other theories on this subject click here.

End Notes

[1] Scientists unmask the cause of rosacea
August 06, 2007|Alison Williams, Los Angeles Times Staff Writer

Scientists determine cause of rosacea, UPI

[2] UCSD Researchers Discover Cause of Rosacea
UCSD News Center

[3] Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea
Kenshi Yamasaki1, Anna Di Nardo1, Antonella Bardan1, Masamoto Murakami2, Takaaki Ohtake3, Alvin Coda1, Robert A Dorschner1, Chrystelle Bonnart4,5, Pascal Descargues4,5, Alain Hovnanian4,5,6, Vera B Morhenn1 & Richard L Gallo1
Nature Medicine 13, 975 – 980 (2007)
Published online: 5 August 2007 | doi:10.1038/nm1616

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

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

[6] 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

[7] 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,

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

[9] Mar 29, 2007 R-S post by David Pascoe

[10] The Role of Demodex Mites in the Pathogenesis of Rosacea and Blepharitis and Their Control
Kosta Y. Mumcuoglu, Ph.D., Oleg E. Akilov, M.D., Ph.D.
Journal of the Rosacea Research & Development Institure, Vol.1, No.1

[11] For a partial list of Demodex in rosacea and acne click here.

[12] Dr. David Dahlman, a Chiropractic Physician with a degree in Nutrition

[13] New way to treat skin disorder
By Cynthia Billhartz Gregorian, St. Louis Post Dispatch, 04/29/2010

[14] Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication.
Parodi A, Paolino S, Greco A, Drago F, Mansi C, Rebora A, Parodi A, Savarino V.
Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa, Italy.
Clin Gastroenterol Hepatol. 2008 Jul;6(7):759-64

[15] SIBO eradication clears rosacea: are you serious ?
May 7th, 2008, by David Pascoe

[16] Gut Bacteria and Xifaxan get some press coverage
April 30th, 2010, by David Pascoe

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

[18] Dermatol Ther (Heidelb). 2016 Sep 22. 
Cardiovascular Disease Outcomes Associated with Three Major Inflammatory Dermatologic Diseases: A Propensity-Matched Case Control Study.
Marshall VD, Moustafa F, Hawkins SD, Balkrishnan R, Feldman SR

[19] 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

Study Finds Association Between Rosacea & Migraine
NRS Posted: 01/03/2017

[20] In the past, a couple of noted rosacea online gurus have dismissed the role of demodex in rosacea. One such rosacea guru said, “Rosacea experts all agree that this mite plays no real role in the development of progression of rosacea (except for the odd pustule).” [8] The other rosacea guru says, “I have always pushed the line that demodex mites have thus far only been proven to be innocent bystanders in rosacea symptoms.” [9] However, the NRS continues to sponsor research into demodex and the RRDi released a paper by Dr. Kosta Y. Mumcuoglu and Dr. Oleg E. Akilov on demodex’s role in rosacea. [10] In fact, there is probably not many other types of research with as many papers on the subject of demodex except for a scarce few. The number of these articles on demodex list keeps growing. [11] Currently the demodex mite theory has gained popularitiy in the minds of the public and the medical authorities. This theory falls under Various Environmental Stimuli > Microorganisms > Demodex Mites.  

[21] Med Princ Pract 2014;23:511-516 (DOI:10.1159/000364905)
Rosacea and Chronic Rhinosinusitis: A Case-Controlled Study
Al-Balbeesi A.O. 
Department of Dermatology (82), King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

Edited by Brady Barrows



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