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Rosacea Theories Revisited

  • 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 was 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 in Nature Medicine [3]. That was then and this is now. Below are the RRDi thoughts on the more popular rosacea theories on the cause of rosacea. 

Note: This article is updated as we receive new data on theories relating to the cause of rosacea. We categorize all the rosacea theories in our forum.

Innate Immune System Disorder

Cytokines and Rosacea is the direction that rosacea research is heading. 

“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.” [3]

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 media 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. 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.

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

"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." [22]. So the nervous system is also being considered important to the innate immune system disorder.  

"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." [28]

"TLR3-stimulated epidermal keratinocytes and rosacea epidermis enhance the expression of glucocorticoid-synthetic enzymes, which would promote cortisol activation in the epidermis. The innate immunity modulates glucocorticoid-synthetic enzymes expression via the TLR3 pathway in epidermal keratinocytes." [35]

Inflammatory Theory

The Inflammatory Theory is one of the leading therories on the cause of rosacea and continues as such, because rosacea is considered an inflammatory skin condition

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. [27]

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 while other bacteria are also implicated. 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]  A number of other bacteria has now been added to list connected to demodex. The consensus has grown that demodectic rosacea is a variant of rosacea. [20] 

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, which is probably one of the oldest theories on the cause of rosacea.

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 (Systemic comorbidities)
Rosacea is associated with a number of other diseases, referred to as 'systemic comorbidities' and this list keeps 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]

Therefore, papers stating an association of rosacea with other diseases should all be taken with a grain of salt due to 'confounders' since another paper states, "Limitations included the accuracy of the published data, potential patient selection, and possible confounding factors. The true nature of the drawn correlations is uncertain, and causality cannot be established." [26]

"In statistics, a confounder (also confounding variable, confounding factor or lurking variable) is a variable that influences both the dependent variable and independent variable causing a spurious association." Wikipedia

Trigeminal sensory malfunction theory
In 2017 another proposed theory on the cause of rosacea is the Trigeminal sensory malfunction theory which we await further discussion and development to see if this becomes popular or not. This theory involves inflammation which a previous subheading on the inflammatory theory shows is still a significant theory. 

Bradykinin Theory
For more information

Low Gastric Acid Theory
There is evidence you should consider that low gastric acid is a factor in rosacea. 

Virus and Rosacea
Virus and rosacea has never been ruled out as a cause of rosacea. Since there are some anti-viral medications that have shown to be effective in improving rosacea you may want to read this post on this subject

Independent Rosacea Research
Could a group of rosacea sufferers in a non profit organization like the RRDi collectively get together and sponsor their own research on rosacea? For example, if 10K members each donated a dollar, could it be possible that this money could be used to sponsor their own independent rosacea research on a subject rosaceans want investigated?  What do you think? If you want to do something about this read this post


The jury is still out on what causes rosacea. "The pathophysiology of rosacea is still poorly understood."[22]

"Demodex folliculorum, the small intestinal bacterial overgrowth (SIBO) and Helicobacter pylori are the most investigated, studied but also debated regarding their contribution in the pathogenesis of rosacea." [24]

"Vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested and microorganisms either alone or in combination are responsible for rosacea....In conclusion, we can say that there are multiple factors responsible for the disease." [23]

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.

Reply to this Topic
There is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post?  And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register?  We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post.  

End Notes

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

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 Yamasaki, Anna Di Nardo, Antonella Bardan, Masamoto Murakami, Takaaki Ohtake, Alvin Coda, Robert A Dorschner, Chrystelle Bonnart, Pascal Descargues, Alain Hovnanian, Vera B Morhenn & Richard L Gallo
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] "I have always pushed the line that demodex mites have thus far only been proven to be innocent bystanders in rosacea symptoms."
Ocular Demodex, Tea Tree Oil as a treatment, David Pascoe, March 28, 2007, Rosacea Support
Another source of the above statement (April 14, 2007).

[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 papers linking Demodex with 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

In another study it was noted, "In the multivariate logistic regression analysis, epicardial fat thickness was independently related to presence of rosacea (P<0.001, OR=13.31)." 
Thickness of carotid intima and epicardial fat in rosacea: a cross-sectional study.
An Bras Dermatol. 2017 Nov-Dec;92(6):820-825
Belli AA, Altun I, Altun I

[19] "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..."
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. However, it should be noted that not all rosacea cases are demodectic. Hence, Demodectic Rosacea is a rosacea variant

[21] 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."

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, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

[22] 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
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

Rosacea Research in Perspective of Idiopathic Diseases

[23] Int J Med Sci. 2015; 12(5): 387–396.
Published online 2015 May 5. doi:  10.7150/ijms.10608
PMCID: PMC4441063
Major Pathophysiological Correlations of Rosacea: A Complete Clinical Appraisal
Ravi Chandra Vemuri, Rohit Gundamaraju, Shamala Devi Sekaran, and Rishya Manikam

[24] Clinical, Cosmetic and Investigational Dermatology, Dove Press
Volume 10, Aug 10, 2017
Rosacea and Helicobacter pylori: links and risks
Lazaridou E, Korfitis C, Kemanetzi C, Sotiriou E, Apalla Z, Vakirlis E, Fotiadou C, Lallas A, Ioannides D

[25] J Am Acad Dermatol. 2017; doi:10.1016/j.jaad.2017.08.032.
Obesity and risk for incident rosacea in US women
Suyun Li, PhD, Eunyoung Cho, ScD, Aaron M. Drucker, MD, ScM, Abrar A. Qureshi, MD, MPH, Wen-Qing Li, PhD

Obesity parameters may predict incident rosacea risk in women, Healio Dermatology

Excess Weight May Raise Rosacea Risk, By Maureen Salamon, HealthDay Reporter, WebMD

[26] J Am Acad Dermatol. 2017 Oct 26;:
Comorbidities in rosacea: A systematic review and update.
Haber R, El Gemayel M

For an example of the odd results in a study, one clinical paper concluded, "In summary, based on a large, well-established cohort, we provide evidence in US women that past smoking is associated with an increased risk of rosacea, while current smoking is associated with a decreased risk of rosacea."

[27] 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.

[28] Arch Dermatol Res. 2018 Mar;310(2):139-146. doi: 10.1007/s00403-018-1806-z. Epub 2018 Jan 12.
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.
Moura AKA, Guedes F, Rivitti-Machado MC, Sotto MN.

[29] J Am Acad Dermatol. 2015 Oct;73(4):604-8. doi: 10.1016/j.jaad.2015.07.009. Epub 2015 Aug 6.
Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study.
Rainer BM, Fischer AH, Luz Felipe da Silva D, Kang S, Chien AL.

[30] Dermatol Clin. 2018 Apr;36(2):115-122. doi: 10.1016/j.det.2017.11.006. Epub 2017 Nov 29.
Rosacea Comorbidities.
Vera N1, Patel NU2, Seminario-Vidal L3.

[31] J Am Acad Dermatol. 2018 Apr;78(4):786-792.e8. doi: 10.1016/j.jaad.2017.09.016. Epub 2017 Oct 26.
Comorbidities in rosacea: A systematic review and update.
Haber R1, El Gemayel M2.

The American Journal of Cardiology
Volume 121, Issue 8, Supplement, 15 April 2018, Page e106

OP-264 - Investigation of Cardiovascular Risk Factors in Rosacea Patients
Muhammed Karadeniz

J Dermatol. 2018 Nov 22;:
Risk of psychiatric disorders in rosacea: A nationwide, population-based, cohort study in Taiwan.
Hung CT, Chiang CP, Chung CH, Tsao CH, Chien WC, Wang WM

[32] Study Finds Possible Link Between Kidney Disease and Rosacea, NRS

[33] Int J Dermatol. 2018 Dec 21;:
Systemic comorbidities associated with rosacea: a multicentric retrospective observational study.

Aksoy B, Ekiz Ö, Unal E, Ozaydin Yavuz G, Gonul M, Kulcu Cakmak S, Polat M, Bilgic Ö, Baykal Selcuk L, Unal I, Karadag AS, Kilic A, Balta I, Kutlu Ö, Uzuncakmak TK, Gunduz K

[34] Clin Exp Dermatol. 2019 Jan 31;:
The mental health burden in acne vulgaris and rosacea: an analysis of the US National Inpatient Sample.

Singam V, Rastogi S, Patel KR, Lee HH, Silverberg JI

[35] J Dermatol Sci. 2020 Aug 29;:
TLR3 augments glucocorticoid-synthetic enzymes expression in epidermal keratinocytes; Implications of glucocorticoid metabolism in rosacea epidermis.
Shimada-Omori R, Yamasaki K, Koike S, Yamauchi T, Aiba S

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