Rosacea Epidemiology and Genetics

  • Gerd Plewig
  • Bodo Melnik
  • WenChieh Chen


Rosacea is a chronic inflammatory skin condition that affects approximately 16 million US Americans. Considering the prevalence of rosacea in a US community setting, 6% of individuals had rosacea. Older, white individuals with fairer skin types (Fitzpatrick skin types I–III) were more likely to have rosacea. The largest epidemiological study of rosacea, a British trial including 60,042 rosacea cases, reported an incidence rate of 1.65 per 1000 person-years. A German registry study with a cohort of 90,880 office employees exhibited a prevalence of 2.3%, while a Swedish study with 809 office employees revealed prevalence rates of 14% in women and 5% in men. An Estonian study with 348 employees, who were over 30 years old, exhibited a prevalence of 22%. According to a recent study, rosacea prevalence was 12.3% in Germany and 5.0% in Russia. In Tunisia, where photo skin types IV and V predominate, a hospital prevalence rate of 0.2% was reported. Whereas rosacea is diagnosed more frequently in Caucasians, the disease appears in Black, Asian, and Hispanic populations. Patients with colored skin rarely receive the diagnosis of rosacea, even when they have symptoms suggesting it. Ocular involvement is not uncommon and has been reported in the range of 3–58% of rosacea patients. Although rare, childhood rosacea should be recognized. Rosacea in childhood is more frequently associated with ocular involvement, which may represent the only manifestation of the disease in this age group.



  1. Abram K, Silm H, Oona M. Prevalence of rosacea in an Estonian working population using a standard classification. Acta Derm Venereol. 2010a;90:269–73.PubMedGoogle Scholar
  2. Al-Dabagh A, Davis SA, McMichael AJ, Feldman SR. Rosacea in skin of color: not a rare diagnosis. Dermatol Online J. 2014;20:10.Google Scholar
  3. Alexis AF. Rosacea in patients with skin of color: uncommon but not rare. Cutis. 2010;86:60–2.PubMedGoogle Scholar
  4. Augustin M, Herberger K, Hintzen S, et al. Prevalence of skin lesions and need for treatment in a cohort of 90880 workers. Br J Dermatol. 2011;165:865–73.PubMedGoogle Scholar
  5. Bae YI, Yun SJ, Lee JB, et al. Clinical evaluation of 168 Korean patients with rosacea: the sun exposure correlates with the erythematotelangiectatic subtype. Ann Dermatol. 2009;21:243–9.PubMedPubMedCentralGoogle Scholar
  6. Chamaillard M, Mortemousque B, Boralevi F, et al. Cutaneous and ocular signs of childhood rosacea. Arch Dermatol. 2008;144:167–71.Google Scholar
  7. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Clustering of autoimmune diseases in patients with rosacea. J Am Acad Dermatol. 2016;74:667–72.PubMedGoogle Scholar
  8. Gether L, Overgaard LK, Egeberg A, Thyssen JP. Incidence and prevalence of rosacea: a systematic review and meta-analysis. Br J Dermatol. 2018;179:282-9.Google Scholar
  9. Hong E, Fischer G. Childhood ocular rosacea: considerations for diagnosis and treatment. Australas J Dermatol. 2009;50:272–5.PubMedGoogle Scholar
  10. Khaled A, Hammami H, Zeglaoui F, et al. Rosacea: 244 Tunisian cases. Tunis Med. 2010;88:597–601.PubMedGoogle Scholar
  11. Kroshinsky D, Glick SA. Pediatric rosacea. Dermatol Ther. 2006;19:196–201.PubMedGoogle Scholar
  12. Kyriakis KP, Palamaras I, Terzoudi S, et al. Epidemiologic aspects of rosacea. J Am Acad Dermatol. 2005;53:918–9.PubMedGoogle Scholar
  13. McAleer MA, Fitzpatrick P, Powell FC. Papulopustular rosacea: prevalence and relationship to photodamage. J Am Acad Dermatol. 2010;63:33–9.PubMedGoogle Scholar
  14. Moustafa F, Hopkinson D, Huang KE, Feldman S. Prevalence of rosacea in community settings. J Cutan Med Surg. 2015;19:149–52.PubMedGoogle Scholar
  15. Spoendlin J, Voegel JJ, Jick SS, Meier CR. A study on the epidemiology of rosacea in the U.K. Br J Dermatol. 2012;167:598–605.PubMedGoogle Scholar
  16. Tan J, Berg M. Rosacea: current state of epidemiology. J Am Acad Dermatol. 2013;69(6 Suppl 1):S27–35.PubMedGoogle Scholar
  17. Tan J, Schöfer H, Araviiskaia E, et al. Prevalence of rosacea in the general population of Germany and Russia - the RISE study. J Eur Acad Dermatol Venereol. 2016;30:428–34.PubMedPubMedCentralGoogle Scholar

Predisposing Genetic Factors

  1. Agliardi C, Guerini FR, Saresella M, et al. Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15-positive individuals. Brain Behav Immun. 2011;25:1460–7.PubMedGoogle Scholar
  2. Aponte JL, Chiano MN, Yerges-Armstrong LM, et al. Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes. Hum Mol Genet. 2018; [Epub ahead of print].Google Scholar
  3. Awosika O, Oussedik E. Genetic predisposition to rosacea. Dermatol Clin. 2018;36:87–92.PubMedGoogle Scholar
  4. Chang AL, Raber I, Xu J, et al. Assessment of the genetic basis of rosacea by genome-wide association study. J Invest Dermatol. 2015;135:1548–55.PubMedPubMedCentralGoogle Scholar
  5. Delmotte P, Sieck GC. Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca(2+) regulation in airway smooth muscle (ASM). Can J Physiol Pharmacol. 2015;93:97–110.PubMedGoogle Scholar
  6. Glasmacher E, Agrawal S, Chang AB, et al. A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science. 2012;338:975–80.PubMedPubMedCentralGoogle Scholar
  7. Hebbring SJ. The challenges, advantages and future of phenome-wide association studies. Immunology. 2014;141:157–65.PubMedPubMedCentralGoogle Scholar
  8. Hebbring SJ, Schrodi SJ, Ye Z, et al. A PheWAS approach in studying HLA-DRB1*1501. Genes Immun. 2013;14:187–91.PubMedPubMedCentralGoogle Scholar
  9. Huber M, Lohoff M. IRF4 at the crossroads of effector T-cell fate decision. Eur J Immunol. 2014;44:1886–95.PubMedGoogle Scholar
  10. Jacobs LC, Hamer MA, Gunn DA, et al. A genome-wide association study identifies the skin color genes IRF4, MC1R, ASIP, and BNC2 influencing facial pigmented spots. J Invest Dermatol. 2015;135:1735–42.PubMedGoogle Scholar
  11. Karpouzis A, Avgeridis P, Tripsianis G, et al. Assessment of tachykinin receptor 3′ gene polymorphism rs3733631 in rosacea. Int Sch Res Notices. 2015;2015:469402.PubMedPubMedCentralGoogle Scholar
  12. Keestra-Gounder AM, Byndloss MX, Seyffert N, et al. NOD1 and NOD2 signalling links ER stress with inflammation. Nature. 2016;532:394–7.PubMedPubMedCentralGoogle Scholar
  13. Kim SH, Yang IY, Kim J, et al. Antimicrobial peptide LL-37 promotes antigen-specific immune responses in mice by enhancing Th17-skewed mucosal and systemic immunities. Eur J Immunol. 2015;45:1402–13.PubMedPubMedCentralGoogle Scholar
  14. Law MH, Medland SE, Zhu G, et al. Genome-wide association shows that pigmentation genes play a role in skin aging. J Invest Dermatol. 2017;137:1887–94.PubMedGoogle Scholar
  15. Maggi CA. The mammalian tachykinin receptors. Gen Pharmacol. 1995;26:911–44.PubMedGoogle Scholar
  16. Mahnke J, Schumacher V, Ahrens S, et al. Interferon regulatory factor 4 controls TH1 cell effector function and metabolism. Sci Rep. 2016;6:35521.PubMedPubMedCentralGoogle Scholar
  17. Maingat F, Halloran B, Acharjee S, et al. Inflammation and epithelial cell injury in AIDS enteropathy: involvement of endoplasmic reticulum stress. FASEB J. 2011;25:2211–20.PubMedPubMedCentralGoogle Scholar
  18. Mandal D, Fu P, Levine AD. REDOX regulation of IL-13 signaling in intestinal epithelial cells: usage of alternate pathways mediates distinct gene expression patterns. Cell Signal. 2010;22:1485–94.PubMedPubMedCentralGoogle Scholar
  19. Nalbant A, Eskier D. Genes associated with T helper 17 cell differentiation and function. Front Biosci (Elite Ed). 2016;8:427–35.Google Scholar
  20. Okada S, Mori K, Kai H. Endoplasmic reticulum stress increases the expression and function of toll-like receptor-2 in epithelial cells. Biochem Biophys Res Commun. 2010;402:235–40.PubMedGoogle Scholar
  21. Palleschi GM, Torchia D. Rosacea in a monozygotic twin. Australas J Dermatol. 2007;48:132–3.PubMedGoogle Scholar
  22. Park K, Ikushiro H, Seo HS, et al. ER stress stimulates production of the key antimicrobial peptide, cathelicidin, by forming a previously unidentified intracellular S1P signaling complex. Proc Natl Acad Sci U S A. 2016;113:E1334–42.PubMedPubMedCentralGoogle Scholar
  23. Popkin DL. Genetic vs environmental factors that correlate with rosacea: a cohort-based survey of twins. JAMA Dermatol. 2015;151:1213–9.PubMedGoogle Scholar
  24. Schrumpf JA, van Sterkenburg MA, Verhoosel RM, et al. Interleukin 13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide 18/LL-37 in bronchial epithelial cells. Infect Immun. 2012;80:4485–94.PubMedPubMedCentralGoogle Scholar
  25. Staudt V, Bothur E, Klein M, et al. Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells. Immunity. 2010;33:192–202.PubMedGoogle Scholar
  26. van Steensel MA, Badeloe S, Winnepenninckx V, et al. Granulomatous rosacea and Crohn’s disease in a patient homozygous for the Crohn-associated NOD2/CARD15 polymorphism R702W. Exp Dermatol. 2008;17:1057–8.PubMedGoogle Scholar
  27. Takci Z, Bilgili SG, Karadag AS, et al. Decreased serum paraoxonase and arylesterase activities in patients with rosacea. J Eur Acad Dermatol Venereol. 2015;29:367–70.PubMedGoogle Scholar
  28. Wang X, Yang X, Li Y, et al. Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma. EBioMedicine. 2017;15:137–49.PubMedGoogle Scholar
  29. Yamasaki K, Di Nardo A, Bardan A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13:975–80.PubMedPubMedCentralGoogle Scholar
  30. Yamasaki K, Kanada K, Macleod DT, et al. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J Invest Dermatol. 2011;131:688–97.PubMedPubMedCentralGoogle Scholar
  31. Yazici AC, Tamer L, Ikizoglu G, et al. GSTM1 and GSTT1 null genotypes as possible heritable factors of rosacea. Photodermatol Photoimmunol Photomed. 2006;22:208–10.PubMedPubMedCentralGoogle Scholar

Rosacea-Associated Comorbidities

  1. Abram K, Silm H, Maaroos HI, Oona M. Risk factors associated with rosacea. J Eur Acad Dermatol Venereol. 2010b;24:565–71.PubMedGoogle Scholar
  2. Akin Belli A, Ozbas Gok S, Akbaba G, et al. The relationship between rosacea and insulin resistance and metabolic syndrome. Eur J Dermatol. 2016;26:260–4.PubMedGoogle Scholar
  3. Almeida R, Ricaño-Ponce I, Kumar V, et al. Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant. Hum Mol Genet. 2014;23:2481–9.PubMedGoogle Scholar
  4. Bagcchi S. Link between rosacea and glioma in nationwide cohort. Lancet Oncol. 2016;17:e94.PubMedGoogle Scholar
  5. Battson ML, Lee DM, Gentile CL. Endoplasmic reticulum stress and the development of endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2017;312:H355–67.PubMedGoogle Scholar
  6. Cai Y, Arikkath J, Yang L, Guo ML, et al. Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders. Autophagy. 2016;12:225–44.PubMedPubMedCentralGoogle Scholar
  7. Cao SS. Epithelial ER stress in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2016;22:984–93.PubMedGoogle Scholar
  8. Cao SS, Luo KL, Shi L. Endoplasmic reticulum stress interacts with inflammation in human diseases. J Cell Physiol. 2016;231:288–94.PubMedPubMedCentralGoogle Scholar
  9. Caruso R, Núñez G. Innate immunity: ER stress recruits NOD1 and NOD2 for delivery of inflammation. Curr Biol. 2016;26:R508–11.PubMedGoogle Scholar
  10. Cheretis C, Dietrich F, Chatzistamou I, et al. Expression of ERp29, an endoplasmic reticulum secretion factor in basal-cell carcinoma. Am J Dermatopathol. 2006;28:410–2.PubMedGoogle Scholar
  11. Cimellaro A, Perticone M, Fiorentino TV, et al. Role of endoplasmic reticulum stress in endothelial dysfunction. Nutr Metab Cardiovasc Dis. 2016;26:863–71.PubMedGoogle Scholar
  12. Ciornei CD, Tapper H, Bjartell A, et al. Human antimicrobial peptide LL-37 is present in atherosclerotic plaques and induces death of vascular smooth muscle cells: a laboratory study. BMC Cardiovasc Disord. 2006;6:49.PubMedPubMedCentralGoogle Scholar
  13. Cunnea P, Mháille AN, McQuaid S, et al. Expression profiles of endoplasmic reticulum stress-related molecules in demyelinating lesions and multiple sclerosis. Mult Scler. 2011;17:808–18.PubMedGoogle Scholar
  14. Duman N, Ersoy Evans S, Atakan N. Rosacea and cardiovascular risk factors: a case control study. J Eur Acad Dermatol Venereol. 2014;28:1165–9.PubMedGoogle Scholar
  15. Egeberg A, Fowler JF Jr, Gislason GH, Thyssen JP. Nationwide assessment of cause-specific mortality in patients with rosacea: a cohort study in Denmark. Am J Clin Dermatol. 2016b;17:673–9.PubMedGoogle Scholar
  16. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Assessment of the risk of cardiovascular disease in patients with rosacea. J Am Acad Dermatol. 2016c;75:336–9.PubMedGoogle Scholar
  17. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Patients with rosacea have increased risk of dementia. Ann Neurol. 2016d;79:921–8.PubMedGoogle Scholar
  18. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Exploring the association between rosacea and Parkinson disease: a Danish nationwide cohort study. JAMA Neurol. 2016e;73:529–34.PubMedGoogle Scholar
  19. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Clustering of autoimmune diseases in patients with rosacea. J Am Acad Dermatol. 2016f;74:667–72.PubMedGoogle Scholar
  20. Egeberg A, Ashina M, Gaist D, et al. Prevalence and risk of migraine in patients with rosacea: a population-based cohort study. J Am Acad Dermatol. 2017a;76:454–8.PubMedGoogle Scholar
  21. Egeberg A, Weinstock LB, Thyssen EP, et al. Rosacea and gastrointestinal disorders: a population-based cohort study. Br J Dermatol. 2017b;176:100–6.PubMedGoogle Scholar
  22. Gutiérrez A, Holler E, Zapater P, et al. Antimicrobial peptide response to blood translocation of bacterial DNA in Crohn’s disease is affected by NOD2/CARD15 genotype. Inflamm Bowel Dis. 2011;17:1641–50.PubMedGoogle Scholar
  23. Haber R, El Gemayel M. Comorbidities in rosacea: a systematic review and update. J Am Acad Dermatol. 2018;78:786–92.PubMedGoogle Scholar
  24. Holmes AD, Spoendlin J, Chien AL, et al. Evidence-based update on rosacea comorbidities and their common physiologic pathways. J Am Acad Dermatol. 2018;78:156–66.PubMedGoogle Scholar
  25. Hua TC, Chung PI, Chen YJ, et al. Cardiovascular comorbidities in patients with rosacea: a nationwide case-control study from Taiwan. J Am Acad Dermatol. 2015;73:249–54.PubMedGoogle Scholar
  26. Huang HC, Tang D, Lu SY, Jiang ZF. Endoplasmic reticulum stress as a novel neuronal mediator in Alzheimer’s disease. Neurol Res. 2015;37:366–74.PubMedGoogle Scholar
  27. Kim M, Choi KH, Hwang SW, et al. Inflammatory bowel disease is associated with an increased risk of inflammatory skin diseases: a population-based cross-sectional study. J Am Acad Dermatol. 2017;76:40–8.PubMedGoogle Scholar
  28. Li WQ, Zhang M, Danby FW, et al. Personal history of rosacea and risk of incident cancer among women in the US. Br J Cancer. 2015;113:520–3.PubMedPubMedCentralGoogle Scholar
  29. López-Isac E, Martín JE, Assassi S, et al. Brief report: IRF4 newly identified as a common susceptibility locus for systemic sclerosis and rheumatoid arthritis in a cross-disease meta-analysis of genome-wide association studies. Arthritis Rheumatol. 2016;68:2338–44.PubMedPubMedCentralGoogle Scholar
  30. Luo K, Cao SS. Endoplasmic reticulum stress in intestinal epithelial cell function and inflammatory bowel disease. Gastroenterol Res Pract. 2015;2015:328791.PubMedPubMedCentralGoogle Scholar
  31. Marré ML, James EA, Piganelli JD. β cell ER stress and the implications for immunogenicity in type 1 diabetes. Front Cell Dev Biol. 2015;3:67.PubMedPubMedCentralGoogle Scholar
  32. McMahon JM, McQuaid S, Reynolds R, FitzGerald UF. Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis. Mult Scler. 2012;18:1437–47.PubMedGoogle Scholar
  33. Meier CR. Rosacea, inflammatory bowel disease and the value of big data and of epidemiological studies. Br J Dermatol. 2017;176:9–10.PubMedGoogle Scholar
  34. Melnik BC. Endoplasmic reticulum stress: key promoter of rosacea pathogenesis. Exp Dermatol. 2014;23:868–73.PubMedPubMedCentralGoogle Scholar
  35. Melnik BC. Rosacea: the blessing of the Celts - an approach to pathogenesis through translational research. Acta Derm Venereol. 2016;96:147–56.PubMedPubMedCentralGoogle Scholar
  36. Mercado G, Castillo V, Soto P, Sidhu A. ER stress and Parkinson’s disease: pathological inputs that converge into the secretory pathway. Brain Res. 2016;1648:626–32.PubMedGoogle Scholar
  37. Navid F, Colbert RA. Causes and consequences of endoplasmic reticulum stress in rheumatic disease. Nat Rev Rheumatol. 2017;13:25–40.PubMedGoogle Scholar
  38. Park YJ, Yoo SA, Kim WU. Role of endoplasmic reticulum stress in rheumatoid arthritis pathogenesis. J Korean Med Sci. 2014;29:2–11.PubMedGoogle Scholar
  39. Peñaranda Fajardo NM, Meijer C, Kruyt FA. The endoplasmic reticulum stress/unfolded protein response in gliomagenesis, tumor progression and as a therapeutic target in glioblastoma. Biochem Pharmacol. 2016;118:1–8.PubMedGoogle Scholar
  40. Rainer BM, Kang S, Chien AL. Rosacea: epidemiology, pathogenesis, and treatment. Dermatoendocrinology. 2017;9:e1361574.Google Scholar
  41. Roussel BD, Kruppa AJ, Miranda E, et al. Endoplasmic reticulum dysfunction in neurological disease. Lancet Neurol. 2013;12:105–18.PubMedGoogle Scholar
  42. Sha Y, Markovic-Plese S. Activated IL-1RI signaling pathway induces Th17 cell differentiation via interferon regulatory factor 4 signaling in patients with relapsing-remitting multiple sclerosis. Front Immunol. 2016;7:543.PubMedPubMedCentralGoogle Scholar
  43. Spoendlin J, Voegel JJ, Jick SS, Meier CR. Migraine, triptans, and the risk of developing rosacea: a population-based study within the United Kingdom. J Am Acad Dermatol. 2013;69:399–406.Google Scholar
  44. Spoendlin J, Karatas G, Furlano RI, et al. Rosacea in patients with ulcerative colitis and Crohn’s disease: a population-based case-control study. Inflamm Bowel Dis. 2016;22:680–7.PubMedGoogle Scholar
  45. Stone S, Lin W. The unfolded protein response in multiple sclerosis. Front Neurosci. 2015;9:264.PubMedPubMedCentralGoogle Scholar
  46. Sun L, Wang W, Xiao W, Yang H. The roles of cathelicidin LL-37 in inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:1986–91.PubMedGoogle Scholar
  47. Vera N, Patel NU, Seminario-Vidal L. Rosacea comorbidities. Dermatol Clin. 2018;36:115–22.PubMedGoogle Scholar
  48. Wingo TS. Parkinson disease risk in patients with rosacea. JAMA Neurol. 2016;73:501–2.PubMedGoogle Scholar
  49. Wood H. Parkinson disease: new evidence for a pathogenic link between rosacea and Parkinson disease. Nat Rev Neurol. 2016;12:250–1.PubMedGoogle Scholar
  50. Wu CY, Chang YT, Juan CK, et al. Risk of inflammatory bowel disease in patients with rosacea: results from a nationwide cohort study in Taiwan. J Am Acad Dermatol. 2017;76:911–7.PubMedGoogle Scholar
  51. Zavorins A, Voicehovska J, Kisis J, Lejnieks A. Overlaps in the pathogenesis of rosacea and atherosclerosis. Proc Natl Acad Sci B. 2018;72:152–9.Google Scholar
  52. Zhong J, Rao X, Xu JF, et al. The role of endoplasmic reticulum stress in autoimmune-mediated beta-cell destruction in type 1 diabetes. Exp Diabetes Res. 2012;2012:238980.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Gerd Plewig
    • 1
  • Bodo Melnik
    • 2
  • WenChieh Chen
    • 3
  1. 1.Department of Dermatology and AllergyLudwig-Maximilian-University MunichMunichGermany
  2. 2.Department of Dermatology, Environmental Medicine and Health TheoryUniversity of OsnabrückOsnabrückGermany
  3. 3.Department of Dermatology and AllergyTechnical University of MunichMunichGermany

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