Skip to main content
SpringerLink
Log in

Pathophysiology of Rosacea

  • Chapter
  • First Online:
Rosacea

Part of the book series: Updates in Clinical Dermatology ((UCD))

Abstract

The pathophysiology underlying rosacea is an active area of investigation. A variety of mediators and mechanisms that trigger disease onset and progression have been implicated in this phenotypically heterogenous and clinically diverse condition. The frequent occurrence of rosacea in people with Celtic ancestry is consistent with a genetic predisposition in certain skin types. In addition to or in combination with genetic factors, the involvement of and connections between the immune, neuronal, and vascular systems are thought to contribute to the dysfunctional responses that lead to the clinical presentation of rosacea. Trigger factors may induce the release of inflammatory and neurogenic mediators from skin, neuronal, and immune cells. The multitude of responses results in the erythema and lesions of rosacea. An improved understanding of the underlying pathophysiology has the potential to lead to effective management.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 54.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 99.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Gallo RL, et al. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78:148–55.

    Article  PubMed  Google Scholar 

  2. Woo YR, Lim JH, Cho DH, Park HJ. Rosacea: molecular mechanisms and management of a chronic cutaneous inflammatory condition. Int J Mol Sci. 2016;17(9):1562.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol. 2013;69:S15–26.

    Article  CAS  PubMed  Google Scholar 

  4. Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7.

    Google Scholar 

  5. Al-Dabagh A, Davis SA, McMichael AJ, Feldman SR. Rosacea in skin of color: not a rare diagnosis. Dermatol Online J. 2014;20.

    Google Scholar 

  6. Dlova NC, Mosam A. Rosacea in black South Africans with skin phototypes V and VI. Clin Exp Dermatol. 2017;42:670–3.

    Article  CAS  PubMed  Google Scholar 

  7. Bae YI, et al. Clinical evaluation of 168 Korean patients with rosacea: the sun exposure correlates with the erythematotelangiectatic subtype. Ann Dermatol. 2009;21:243–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Aldrich N, et al. Genetic vs environmental factors that correlate with rosacea: a cohort-based survey of twins. JAMA Dermatol. 2015;151:1213–9.

    Article  PubMed  Google Scholar 

  9. Chang ALS, et al. Assessment of the genetic basis of rosacea by genome-wide association study. J Invest Dermatol. 2015;135:1548–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yamasaki K, Gallo RL. Rosacea as a disease of cathelicidins and skin innate immunity. J Investig Dermatol Symp Proc. 2011;15:12–5.

    Article  CAS  PubMed  Google Scholar 

  11. Yazici AC, et al. GSTM1 and GSTT1 null genotypes as possible heritable factors of rosacea. Photodermatol Photoimmunol Photomed. 2006;22:208–10.

    Article  CAS  PubMed  Google Scholar 

  12. Yu Y, et al. LL-37-induced human mast cell activation through G protein-coupled receptor MrgX2. Int Immunopharmacol. 2017;49:6–12.

    Article  CAS  PubMed  Google Scholar 

  13. Schwab VD, et al. Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15:53–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Madva EN, Granstein RD. Nerve-derived transmitters including peptides influence cutaneous immunology. Brain Behav Immun. 2013;34:1–10.

    Article  CAS  PubMed  Google Scholar 

  15. Seeliger S, et al. Pituitary adenylate cyclase activating polypeptide: an important vascular regulator in human skin in vivo. Am J Pathol. 2010;177:2563–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Moran EM, Foley R, Powell FC. Demodex and rosacea revisited. Clin Dermatol. 2017;35:195–200.

    Article  PubMed  Google Scholar 

  17. Yamasaki K, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13:975–80.

    Article  CAS  PubMed  Google Scholar 

  18. Yamasaki K, et al. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J Invest Dermatol. 2011;131:688–97.

    Article  CAS  PubMed  Google Scholar 

  19. Koczulla R, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003;111:1665–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Morizane S, Gallo RL. Antimicrobial peptides in the pathogenesis of psoriasis. J Dermatol. 2012;39:225–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Morizane S, et al. Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. J Invest Dermatol. 2012;132:135–43.

    Article  CAS  PubMed  Google Scholar 

  22. Muto Y, et al. Mast cells are key mediators of cathelicidin-initiated skin inflammation in rosacea. J Invest Dermatol. 2014;134:2728–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Di Nardo A, Vitiello A, Gallo RL. Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol. 2003;170:2274–8.

    Article  PubMed  Google Scholar 

  24. Di Nardo A, Yamasaki K, Dorschner RA, Lai Y, Gallo RL. Mast cell cathelicidin antimicrobial peptide prevents invasive group A Streptococcus infection of the skin. J Immunol. 2008;180:7565–73.

    Article  PubMed  Google Scholar 

  25. Mascarenhas NL, Wang Z, Chang Y-L, Di Nardo A. TRPV4 mediates mast cell activation in cathelicidin-induced rosacea inflammation. J Invest Dermatol. 2017;137:972–5.

    Article  CAS  PubMed  Google Scholar 

  26. Buhl T, et al. Molecular and morphological characterization of inflammatory infiltrate in rosacea reveals activation of Th1/Th17 pathways. J Invest Dermatol. 2015;135:2198–208.

    Article  CAS  PubMed  Google Scholar 

  27. Sakabe J, et al. Calcipotriol increases hCAP18 mRNA expression but inhibits extracellular LL37 peptide production in IL-17/IL-22-stimulated normal human epidermal keratinocytes. Acta Derm Venereol. 2014;94:512–6.

    Article  CAS  PubMed  Google Scholar 

  28. Chen X, et al. Human antimicrobial peptide LL-37 modulates proinflammatory responses induced by cytokine milieus and double-stranded RNA in human keratinocytes. Biochem Biophys Res Commun. 2013;433:532–7.

    Article  CAS  PubMed  Google Scholar 

  29. Brown TT, Choi E-YK, Thomas DG, Hristov AC, Chan MP. Comparative analysis of rosacea and cutaneous lupus erythematosus: histopathologic features, T-cell subsets, and plasmacytoid dendritic cells. J Am Acad Dermatol. 2014;71:100–7.

    Article  CAS  PubMed  Google Scholar 

  30. Kim M, et al. Recombinant erythroid differentiation regulator 1 inhibits both inflammation and angiogenesis in a mouse model of rosacea. Exp Dermatol. 2015;24:680–5.

    Article  CAS  PubMed  Google Scholar 

  31. Ahn CS, Huang WW. Rosacea pathogenesis. Dermatol Clin. 2018;36:81–6.

    Article  CAS  PubMed  Google Scholar 

  32. Niizeki H, Kurimoto I, Streilein JW. A substance p agonist acts as an adjuvant to promote hapten-specific skin immunity. J Invest Dermatol. 1999;112:437–42.

    Article  CAS  PubMed  Google Scholar 

  33. Streilein JW, Alard P, Niizeki H. A new concept of skin-associated lymphoid tissue (SALT): UVB light impaired cutaneous immunity reveals a prominent role for cutaneous nerves. Keio J Med. 1999;48:22–7.

    Article  CAS  PubMed  Google Scholar 

  34. Azimi E, et al. Dual action of neurokinin-1 antagonists on Mas-related GPCRs. JCI Insight. 2016;1:e89362.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ali H. Mas-related G protein coupled receptor-X2: a potential new target for modulating mast cell-mediated allergic and inflammatory diseases. J Immunobiol. 2016;1(4):115.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Sulk M, et al. Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea. J Invest Dermatol. 2012;132:1253–62.

    Article  CAS  PubMed  Google Scholar 

  37. Chen Y, et al. TRPV4 moves toward center-fold in rosacea pathogenesis. J Invest Dermatol. 2017;137:801–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Moore C, et al. UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling. Proc Natl Acad Sci U S A. 2013;110:E3225–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lee WJ, et al. Histopathological analysis of 226 patients with rosacea according to rosacea subtype and severity. Am J Dermatopathol. 2016;38:347–52.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Illustration designed by Dani Guralnick, DGD LLC.

Author information

Authors and Affiliations

  1. Program in Itch, Department of Dermatology, Massachusetts General Hospital, Cutaneous Biology Research Center, Charlestown, MA, USA

    Ethan A. Lerner

  2. Dermira, Inc., A Wholly-owned Subsidiary of Eli Lilly and Company, Menlo Park, CA, USA

    Ferda Cevikbas

Authors
  1. Ethan A. Lerner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ferda Cevikbas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ethan A. Lerner or Ferda Cevikbas .

Editor information

Editors and Affiliations

  1. Louisiana State University, New Orleans, LA, USA

    John Havens Cary

  2. Dermatology Clinic, University of California San Francisco, San Francisco, CA, USA

    Howard I. Maibach

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lerner, E.A., Cevikbas, F. (2020). Pathophysiology of Rosacea. In: Cary, J.H., Maibach, H.I. (eds) Rosacea. Updates in Clinical Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-030-52097-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-52097-7_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-52096-0

  • Online ISBN: 978-3-030-52097-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation