We categorize all the rosacea theories in our forum. This article is updated as we receive new data on theories relating to the cause of rosacea.
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.
"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." . 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." 
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.” 
At least one type of bacteria is associated with demodex mites and rosacea. This bacteria is Bacillus oleronius according to an NRS press release  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.”  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.”  Now, another bacteria, Bartonella quintana, may be implicated with the mites according to a report by David Pascoe.  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. 
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.”  This theory falls under Other Theories > IBS and Rosacea.
The IBS theory also is related to bacteria in the gut and that using antibiotics clears rosacea. An article in the St. Louis Dispatch  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.  This theory falls under Rosacea Theories > Bacteria Theory.
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.”  “The link between SIBO and the papules and pustules of rosacea is still a mystery.”  For more information on rosacea and SIBO click here. This theory falls under Other Theories > SIBO and Rosacea.
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.
Rosacea is associated with a number of other diseases, such as Migraine, CRS (see below), Multiple sclerosis, Alzheimer's Disease, Dementia, cardiovascular diseases, Parkinson's disease, cancer, diabetes, Glioma, HLA-DRA Locus (see below), inflammatory bowel disease, depression/anxiety disorders, CKD, Obesity , MetS, low-grade inflammation, hair loss, and the 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." 
"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.  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..." 
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." 
However, we should remember that all the above papers stating an association of rosacea with other diseases may actually be premature since one 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." 
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. 
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 as the previous paragraph mentions.
For more information.
The jury is still out on what causes rosacea. "The pathophysiology of rosacea is still poorly understood."
"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." 
"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." 
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.
 Scientists unmask the cause of rosacea
August 06, 2007 by Alison Williams, Staff Writer, Los Angeles Times
 UCSD Researchers Discover Cause of Rosacea
UCSD News Center
 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
 Study finds cause of rosacea
The Irish Times – Tuesday, July 14, 2009
 New Study Shows Role for Bacteria in Development of Rosacea Symptoms
NRS Press Release, May 3, 2004, Suzanne Corr / Barbara Palombo
 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
 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,
 page 110 quote
Beating Rosacea Vascular, Ocular & Acne Forms
Geoffrey Nase, Ph.D.
Nase Publications 2001
 "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).
 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
 For a partial list of Demodex in rosacea and acne click here.
 New way to treat skin disorder
By Cynthia Billhartz Gregorian, St. Louis Post Dispatch, 04/29/2010
 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
 SIBO eradication clears rosacea: are you serious ?
May 7th, 2008, by David Pascoe
 Gut Bacteria and Xifaxan get some press coverage,
April 30th, 2010, by David Pascoe
 Another Demodex Bacteria Isolated: Bartonella quintana,
David Pascoe, Rosacea Support Group
 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
 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
 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).”  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.”  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.  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.  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.
 Med Princ Pract 2014;23:511-516 (DOI:10.1159/000364905)
Rosacea and Chronic Rhinosinusitis: A Case-Controlled Study
Department of Dermatology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
 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.
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
 Int J Med Sci. 2015; 12(5): 387–396.
Published online 2015 May 5. doi: 10.7150/ijms.10608
Major Pathophysiological Correlations of Rosacea: A Complete Clinical Appraisal
Ravi Chandra Vemuri, Rohit Gundamaraju, Shamala Devi Sekaran, and Rishya Manikam
 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
 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
 J Am Acad Dermatol. 2017 Oct 26;:
Comorbidities in rosacea: A systematic review and update.
Haber R, El Gemayel M
 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.
 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.
Edited by Admin