Systemic Comorbidities in Rosacea

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Systemic Cormobidities
Rosacea is associated with a number of other diseases, referred to as ‘systemic comorbidities’, which one study reports, “Clinicians must be aware of the potential for systemic comorbidities in rosacea patients, which becomes more likely as disease duration and severity increase.” [1] However, one paper cautions, "Rosacea may be a proxy for systemic disease, rather than a mere skin disorder, as it has been linked with metabolic, cardiovascular, autoimmune, and chronic kidney diseases. However, most of the relevant data are from epidemiologic studies without basic experimental details. Thus, further evidence must be sought to support the hypothesis that rosacea is associated with systemic inflammation and systemic diseases." [15] Furthermore, "It may be recommended that clinicians pay careful attention to the clinical follow-up of these patients to avoid missed associated comorbidities." [17] "Clinicians should acknowledge these interrelations and employ comprehensive care with an individual-based approach." [25] These systemic comorbidities are in addition to a number of co-existing conditions with rosacea. 

This is a controversial subject but clinical papers on this subject continue to be published. For example, this paper indicates "evidence on the association between rosacea and several systemic diseases." [32]

"Some of the identified pathways link rosacea with its systemic comorbidities, including atherosclerosis (ICAM1, angiotensinogen, and HMGB1), Alzheimer’s disease (DHCR24 and myeloperoxidase), dementia (PRNP), and Parkinson’s disease (SNCA, HSPA8, and GSK3B), indicating that therapeutic maintenance of rosacea might protect from the development of rosacea-associated cardiovascular and neurological diseases." [34]

The following is a growing list which we are updating as more data is investigated and published that state rosacea is associated with other diseases:

Alcohol Abuse [25]

Allergic Conjunctivitis [25]

Allergic Rhinitis [25]

Allergies (airborne, food, etc.)

Alopecia Areata [25]

Alopecia (Frontal fibrosing) [21]

Alzheimer's Disease

Ankylosing Spondylitis [25]

Anxiety Disorder [3]

Anxiety and Depression

Atherosclerosis [33]

Autoimmune conditions [2] [29]

Autoimmune Thyroiditis [25]

Autosensitization dermatitis

Blepharitis [29]

Body Mass Index (BMI) values higher 

Breast cancer [20]

Cancer [12]

Cardiometabolic Syndrome

Cardiovascular diseases and risk [3] [26]

Celiac Disease [28]

Chalazion [29]

Cholesterol (higher total) [22] [23]

Chronic inflammatory skin diseases (CISD) [18]

Chronic Mucocutaneous Candidiasis (CMC)

Chronic rhinosinusitis (CRS) [4] [25]

CKD

Conjunctivitis [29]

COPD [31]

Crohn Disease [19]

Dementia [24]

Depression/anxiety disorders [3] [24]

Dental foci of infection [13]

Diabetes [3]

Diabetes Mellitus [25]

Dry Eye Disease (DED)

Dry Eye Syndrome [29]

Dyslipidemia [3] [22] [23]

Dysregulation of the innate and adaptive immune responses [16]

Female hormone imbalance [5] [10] [14]

Frontal fibrosing alopecia

Fibromylgia syndrome (FMS)

Gastroesophageal Reflux Disease (GERD) and other GI disorders [1] [14] [25] [28]

Gastrointestinal disease [14]

Glaucoma [29]

Glioma

Glucose (blood glucose higher} [22]

Hair loss

Helicobacter pylori infection [3] [28]

Hepatobiliary Cancer [25]

Hepatobiliary system disorders [1]

Herpes Infection [25]

Higher Systolic Blood Pressure [26]

HLA-DRA Locus [7]

Human Papillomavirus Infection [25]

Hepatobiliary Cancer [25]

Hyperglycemia [27]

Hyperlipidemia [3] [14]

Hypertension [6] [14] [20] [22] [23]

Hyperthyroidism [20] [24] [29]

Inflammatory Bowel Disease (IBD) [19] [28]

Irritable Bowel Syndrome [24] [25] 

Kidney Disease [8]

Low-density lipoprotein (LDL) is higher [22] [23]

Low-grade inflammation

Lung Cancer [25]

Meibomian gland dysfunction

Melasma [20]

Mental Health Disorders [9]

Metabolic diseases [1] [14]

Metabolic Syndrome [23]

MetS

Migraine 

Multiple sclerosis

Obesity [25]

Obstructive Sleep Apnea

Parkinson's disease

Peptic ulcers [20]

Proton Pump Inhibitors

Psychiatric diseases [3]

Respiratory diseases [1] [14] [31]

Raynaud syndrome

Rheumatoid Arthritis [3] [25]

Serum Uric Acid levels higher (Serum UA and CRP values higher)

SIBO [19] [28]

Sleep

Sjögren syndrome [25]

Smoking

Systemic Sclerosis [25]

Teeth and Gum Issues

Thyroiditis [25]

Triglycerides are higher (TG) [22]

Ulcerative Colitis [3] [24]

Urogenital diseases [10] [14] [24]

Venous Thromboembolism

Vitiligo [25]

Virus

More Research Needed
Since the above list keeps growing this complicates the theories on the cause of rosacea increasing the call for further research. For example, 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." [11] Wouldn't this call for more independent research funded by rosaceans since "further evidence must be sought to support the hypothesis that rosacea is associated with systemic inflammation and systemic diseases" ? [15]

Confounding Factors
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." [3] [bold added for emphasis]

image courtesy of WikiMedia Commons

"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

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End Notes

[1] 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

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

[3] 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 R, El Gemayel M.

Anais Brasileiros de Dermatologia
Rosacea associated with increased risk of generalized anxiety disorder: a case-control study of prevalence and risk of anxiety in patients with rosacea
Pinar Incel Uysal, Neslihan Akdogan, Basak Yalcin

One report states, "The pooled analysis found no association between rosacea prevalence and the incidence of CVDs...However, no association was found between rosacea and diabetes mellitus...We found no association between rosacea and high-density lipoprotein cholesterol...or triglycerides..."
Biomed Res Int. 2020;2020:7015249
Association between Rosacea and Cardiovascular Diseases and Related Risk Factors: A Systematic Review and Meta-Analysis.
Li Y, Guo L, Hao D, Li X, Wang Y, Jiang X

J Cosmet Dermatol. 2020 Dec 21;:
Association between rosacea and cardiovascular disease: A systematic review and meta-analysis.
Zhang J, Yan Y, Jiang P, Liu Z, Liu Y, Liu Y, Wang X, Li M, Xu Y

[4] 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

[5] "There is no research regarding hormones and their effect on rosacea," Dr. Bergfeld said. "However, it has been widely observed that rosacea is often aggravated at menopause and sometimes during mid-cycle."
Women May Need Added Therapy, Rosacea Review, NRS

[6] Cardiovascular Diseases and Rosacea

[7] "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

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

[9] 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

[10] J Am Acad Dermatol. 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

[11] Dermatol Ther (Heidelb). 2016 Dec;6(4):649-658. Epub 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,

[12] J Dermatol. 2019 May 23;:
Potential association between rosacea and cancer: A study in a medical center in southern China.
 Long J, Li J, Yuan X, Tang Y, Deng Z, Xu S, Zhang Y, Xie H

"The current literature shows that rosacea is significantly associated with increased odds of nonmelanoma skin cancers, glioma, and breast cancer."

Rosacea and Its Association With Malignancy: Systematic Review

[13] Gen Dent. 2019 Nov-Dec;67(6):52-54
Association of dental foci of infection and rosacea: a case report.
Sopi M, Meqa K

[14] Rosacea Linked to Various Conditions, Including Respiratory, GI Disease, Infectious Disease Advisor

[15] Dermatology 2019;235:255–259 DOI: 10.1159/000496968
Characterization of the Blood Microbiota in Korean Females with Rosacea
Yeojun Yun, Han-Na Kim, Yoosoo Chang, Yunho Lee, Seungho Ryu, Hocheol Shin, Won-Serk Kim, Hyung- Lae Kim, Jae-Hui Nam

[16] J Eur Acad Dermatol Venereol. 2020 Jan 28;:
Rosacea as a striking feature in family members with a STAT1 gain-of-function mutation.
Sáez-de-Ocariz M, Suárez-Gutiérrez M, Migaud M, O Farrill-Romanillos P, Casanova JL, Segura-Mendez NH, Orozco-Covarrubias L, Espinosa-Padilla SE, Puel A, Blancas-Galicia L

[17] Arch Dermatol Res. 2020 Feb 04;:
Evaluation of serum uric acid levels in patients with rosacea.
Karaosmanoglu N, Karaaslan E, Ozdemir Cetinkaya P

See also Immune System Disorder

[18] "Conversely, the mean estimated 10-year survival was higher in pemphigus (P = 0.0451), lichen planus (P = 0.0352), rosacea (P < 0.0001), lower in bullous pemphigoid and dermatomyositis (P < 0.0001), and similar in atopic dermatitis, alopecia areata, and hidradenitis suppurativa compared to psoriasis." [bold added]

Arch Dermatol Res. 2020 Feb 11;:
Multimorbidity and mortality risk in hospitalized adults with chronic inflammatory skin disease in the United States.
Narla S, Silverberg JI

[19] Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea
AG Gravina, A Federico, E Ruocco, A Lo Schiavo, M Masarone, C Tuccillo, F Peccerillo, A Miranda, L Romano, C de Sio, I de Sio,1 M Persico, V Ruocco, G Riegler, C Loguercio, and M Romano

Medicine. 98(41):e16448, OCTOBER 2019
DOI: 10.1097/MD.0000000000016448 ,  
PMID: 31593075
Issn Print: 0025-7974
Association of rosacea with inflammatory bowel disease: A MOOSE-compliant meta-analysis
Fang-Ying Wang;Ching-Chi Chi;

[20] J Dermatol. 2020 Mar 24;:
Epidemiological features of rosacea in Changsha, China: A population-based, cross-sectional study.
Li J, Wang B, Deng Y, Shi W, Jian D, Liu F, Huang Y, Tang Y, Zhao Z, Huang X, Li J, Xie H

[21] "Facial papules were more common in younger patients and both facial papules and rosacea were associated with a greater need for oral treatment."

Actas Dermosifiliogr. 2020 May 14;:
Frontal Fibrosing Alopecia: A Retrospective Study of 75 Patients.
Maldonado Cid P, Leis Dosil VM, Garrido Gutiérrez C, Salinas Moreno S, Thuissard Vasallo IJ, Andreu Vázquez C, Díaz Díaz RM

[22] J Am Acad Dermatol. 2020 Apr 28;:
Association between Rosacea and Cardiometabolic Disease: A Systematic Review and Meta-Analysis.
Chen Q, Shi X, Tang Y, Wang B, Xie HF, Shi W, Li J

[23] Biomed Res Int. 2020;2020:7015249
Association between Rosacea and Cardiovascular Diseases and Related Risk Factors: A Systematic Review and Meta-Analysis.
Li Y, Guo L, Hao D, Li X, Wang Y, Jiang X

J Am Acad Dermatol. 2021 Jan 30;:
Reply to: "Implementing the association between rosacea, hypertension, and dyslipidemia in clinical practice".
Chen Q, Tang Y, Li J

Indian J Dermatol. 2021 May-Jun; 66(3): 302–307.
Skin and Metabolic Syndrome: An Evidence Based Comprehensive Review
Farhat Fatima, Anupam Das, Piyush Kumar, and Debatri Datta

[24] J Clin Aesthet Dermatol. 2020 Jul;13(7):36-40
Rosacea and Associated Comorbidities: A Google Search Trends Analysis.
Marchitto MC, Chien AL

[25] J Clin Med. 2020 Oct 17;9(10):
Systemic Comorbidities in Korean Patients with Rosacea: Results from a Multi-Institutional Case-Control Study.
Woo YR, Kim HS, Lee SH, Ju HJ, Bae JM, Cho SH, Lee JD

[26] Acta Derm Venereol. 2020 Oct 19;:
Cardiovascular Risk and Comorbidities in Patients with Rosacea: A Systematic Review and Meta-analysis.
Tsai TY, Chiang YY, Huang YC

[27] "Patients with rosacea also have a higher incidence of hyperglycemia, which means increased risk of SIBO due to gut hypomotility. Again, the flushing and erythrosis seen in many rosacea patients could be due to the release of angiogenic and vasoactive agents including nitric oxide or TNF-α. The fact is that papulopustular rosacea and erythrotic rosacea could be due to different causes." [bold added]

Rosacea and Small Intestinal Bacterial Overgrowth (SIBO), By Liji Thomas, MD, News Medical

[28] "In addition, a case–control study demonstrated that patients with rosacea had a twofold odds for prevalent CeD compared with age, sex, and calendar time-matched controls (OR 2.03, 95% CI 1.35–3.07), and stratification by gender revealed a significant association of rosacea with CeD in women, but not in men."

Adv Ther. 2021 Jan 28;:
Rosacea, Germs, and Bowels: A Review on Gastrointestinal Comorbidities and Gut-Skin Axis of Rosacea.
Wang FY, Chi CC

Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea
AG Gravina, A Federico, E Ruocco, A Lo Schiavo, M Masarone, C Tuccillo, F Peccerillo, A Miranda, L Romano, C de Sio, I de Sio,1 M Persico, V Ruocco, G Riegler, C Loguercio, and M Romano

[29] Ocular Comorbidities in Rosacea: A Case-Control Study Based on Seven Institutions

[30] Assessment of thyroid disorders in patients with rosacea: a large case-control study

[31[ Relationship between rosacea and chronic obstructive pulmonary disease: Rosacea and comorbidities

[32] Rosacea, not just skin deep: Understanding the systemic disease burden

[33] PubMed RSS Feed - -Evaluation of atherosclerotic risk in rosacea patients through serum fetuin-A and carotid intima media thickness

[34] Flushing New Light on Rosacea

[Guide]

it is quite odd that with over five hundred views of this post that no one has made one reply to this topic. To me this is a fascinating subject that should be investigated more and should be done by rosaceans independent of the pharmaceutical backed research which predominates the clinical papers on rosacea. Why rosaceans don't want to come together as a group and support their own independent research baffles my mind. If we could just get $1000, we could offer one of the RRDi MAC members to investigate a rosacea subject that the RRDi wants investigated and publish the results ourselves as an independent, non profit organization for rosacea. All it would take is for each member to donate ONE US DOLLAR. If you agree, please donate. 

[Guide]

As of this date there are at least 80 systemic comorbidities listed associated with rosacea. Can you find anywhere on the internet a list like this?  That is what the RRDi is about, 'everything rosacea.' We attempt to have on one website a comprehensive database of 'everything rosacea.' Can you find all the information on rosacea at the other non profit organizations for rosacea?  Why not browse the other non profit organizations for rosacea and see if they even come close to all the data we have categorized into logical categories for your investigative research into rosacea?  Do they have the data you are finding on the RRDi website about rosacea even comes close to what you have discovered here on this website?  For example, do they even mention non prescription treatments for rosacea such as over the counter topicals and allowing REVIEWS of these treatments?  Or why not go to your favorite rosacea social media platform like on Reddit, Facebook, Twitter or Instagram and see if you can logically figure out how to search for a subject you are investigating. Difficult task, isn't it? If you appreciate the data found on our website, why not volunteer and support the RRDi?  Could you at least donate one dollar so we can keep this website running?

[Guide]

One report on this subject states, "the risks of some comorbidities in patients with rosacea are somewhat contradictory, depending upon the study design. Moreover, pathomechanisms associated with the comorbidities of patients with rosacea remain poorly elucidated."

Int J Mol Sci. 2020 Nov 10;21(22):
Updates on the Risk of Neuropsychiatric and Gastrointestinal Comorbidities in Rosacea and Its Possible Relationship with the Gut-Brain-Skin Axis.
Woo YR, Han YJ, Kim HS, Cho SH, Lee JD

[Guide]

"As one of the facial inflammatory dermatosis, rosacea has been linked to manifest ocular surface changes, such as blepharitis and conjunctivitis. A multi-institutional case-control study revealed a notable association between rosacea and blepharitis, conjunctivitis, glaucoma, dry eye syndrome, and chalazion in the Korean patient population."

J Clin Med. 2021 Dec; 10(24): 5754.
Special Issue: “Skin Disease and Comorbidities”
Keiichi Yamanaka