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Systemic Cormorbidities 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]

The following is a growing list which we are updating as more data is investigated:

Alopecia (Frontal fibrosing) [21]

Autoimmune conditions [2]

Autosensitization dermatitis

Allergies (airborne, food, etc.)

Anxiety Disorder [3]

Alzheimer's Disease

Body Mass Index (BMI) values higher 

Breast cancer [20]

Cancer [12]

Cardiometabolic Syndrome

Cardiovascular diseases [3]

Cholesterol (higher total) [22] [23]

Chronic inflammatory skin diseases (CISD) [18]

Chronic rhinosinusitis (CRS) [4]

CKD

Crohn Disease [19]

Dementia [24]

Depression/anxiety disorders [3] [24]

Dental foci of infection [13]

Diabetes [3]

Dyslipidemia [3] [22] [23]

Dysregulation of the innate and adaptive immune responses [16]

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

Frontal fibrosing alopecia

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

Gastrointestinal disease [14]

Glioma

Glucose (blood glucose higher} [22]

Hair loss

Helicobacter pylori infection [3]

Hepatobiliary system disorders [1]

HLA-DRA Locus [7]

Hyperlipidemia [3] [14]

Hypertension [6] [14] [20] [22] [23]

Hyperthyroidism [20] [24]

Inflammatory Bowel Disease (IBD) [19]

Irritable Bowel Syndrome [24]

Kidney Disease [8]

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

Low-grade inflammation

Melasma [20]

Mental Health Disorders [9]

Metabolic diseases [1] [14]

Metabolic Syndrome [23]

MetS

Migraine 

Multiple sclerosis

Obesity 

Obstructive Sleep Apnea

Parkinson's disease

Peptic ulcers [20]

Proton Pump Inhibitors

Psychiatric diseases [3]

Respiratory diseases [1] [14]

Rheumatoid Arthritis [3]

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

SIBO [19]

Sleep

Triglycerides are higher (TG) [22]

Ulcerative Colitis [3] [24]

Urogenital diseases [10] [14] [24]

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 font added for emphasis]

152px-Simple_Confounding_Case_svg.png.38
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

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

[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

[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] 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

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

 

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  • Root Admin

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 would like to start this project, please donate

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