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Aktuelles Verständnis der Pathophysiologie der Rosazea

Current insights into the pathophysiology of rosacea

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Zusammenfassung

Rosazea ist eine chronisch entzündliche Hauterkrankung, die vor allem das Gesicht betrifft. Vier klinische Subformen werden beobachtet: die erythematoteleangiektatische, papulopustulöse und phymatöse sowie die okuläre Rosazea. Im Moment ist unklar, ob diese Subtypen unterschiedliche Schweregrade einer Erkrankung darstellen, die ineinander übergehen können, oder ob es sich bei den Unterformen der Rosazea um distinkte Formen eines Krankheitskomplexes handelt. Die Symptome der Rosazea umfassen anfallsartige Schübe eines Gesichtserythems, persistierende Rötung, chronische Entzündung, ein Ödem und eine Fibrose. Unterschiedliche Triggerfaktoren können wiederkehrende Entzündungsschübe auslösen. Obwohl in den letzten Jahren verschiedene Aspekte der Pathophysiologie der Rosazea charakterisiert wurden, ist das genaue Zusammenspiel der verschiedenen fehlregulierten Systeme noch inkomplett verstanden. Bei frühen Manifestationen der Rosazea spielt eine Störung der neurovaskulären Regulation und des angeborenen Immunsystems der Haut eine wesentliche Rolle. Ein gestörtes Chemokin- und Zytokinmikromilieu trägt zum weiteren Krankheitsverlauf bei. Diese Übersichtsarbeit diskutiert aktuelle pathogenetische Erkenntnisse bei Rosazea und mögliche Zielstrukturen für die zukünftige Therapie dieser Erkrankung.

Abstract

Rosacea is a chronic inflammatory skin disease mainly affecting the face. Four major clinical subtypes of rosacea can be identified: erythemato-telangiectatic, papulopustular, phymatous and ocular rosacea. Still, it is currently unclear whether these subtypes develop consecutively or if any subtypes may occur individually as part of a syndrome. Rosacea is characterized by facial flushing, erythema, chronic inflammation, edema and fibrosis. Several trigger factors can worsen the disease or cause recurring episodes of inflammation. Although some aspects in the pathophysiology of rosacea have been characterized in more detail during the past years, the precise interplay of the various dysregulated systems is still poorly understood. In early disease manifestations and milder stages, dysfunction of neurovascular regulation and the innate immune system seem to be driving forces in rosacea pathophysiology. A disturbed chemokine and cytokine network further contributes to disease progression. This current review highlights some of the recent findings in rosacea pathophysiology and points out novel targets for therapeutic intervention.

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Literatur

  1. Abram K, Silm H, Maaroos HI et al (2010) Risk factors associated with rosacea. J Eur Academy Dermatol Venereol 24:565–571

    Article  CAS  Google Scholar 

  2. Aubdool AA, Brain SD (2011) Neurovascular aspects of skin neurogenic inflammation. J Investig Dermatol Symp Proc 15:33–39

    Article  CAS  PubMed  Google Scholar 

  3. Bakar O, Demircay Z, Yuksel M et al (2007) The effect of azithromycin on reactive oxygen species in rosacea. Clin Exp Dermatol 32:197–200

    Article  CAS  PubMed  Google Scholar 

  4. Caterina MJ, Schumacher MA, Tominaga M et al (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    Article  CAS  PubMed  Google Scholar 

  5. Chosidow O, Cribier B (2011) Epidemiology of rosacea: updated data. Ann Dermatol Venereol 138(Suppl 2):S124–S128

    Article  PubMed  Google Scholar 

  6. De Y, Chen Q, Schmidt AP et al (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med 192:1069–1074

    Article  Google Scholar 

  7. Del Rosso JQ, Webster GF, Jackson M et al (2007) Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. J Am Acad Dermatol 56:791–802

    Article  Google Scholar 

  8. Dispenza MC, Wolpert EB, Gilliland KL et al (2012) Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients. J Invest Dermatol 132:2198–2205

    Article  CAS  PubMed  Google Scholar 

  9. Gerber PA, Buhren BA, Steinhoff M et al (2011) Rosacea: the cytokine and chemokine network. J Investig Dermatol Symp Proc 15:40–47

    Article  CAS  PubMed  Google Scholar 

  10. Gomaa AH, Yaar M, Eyada MM et al (2007) Lymphangiogenesis and angiogenesis in non-phymatous rosacea. J Cutan Pathol 34:748–753

    Article  PubMed  Google Scholar 

  11. Guzman-Sanchez DA, Ishiuji Y, Patel T et al (2007) Enhanced skin blood flow and sensitivity to noxious heat stimuli in papulopustular rosacea. J Am Acad Dermatol 57:800–805

    Article  PubMed  Google Scholar 

  12. Hsu CK, Hsu MM, Lee JY (2009) Demodicosis: a clinicopathological study. J Am Acad Dermatol 60:453–462

    Article  PubMed  Google Scholar 

  13. Huggenberger R, Detmar M (2011) The cutaneous vascular system in chronic skin inflammation. J Invest Dermatol 15:24–32

    Article  CAS  Google Scholar 

  14. Jones D (2004) Reactive oxygen species and rosacea. Cutis 74:17–20, 32–14

    PubMed  Google Scholar 

  15. Kanada KN, Nakatsuji T, Gallo RL (2012) Doxycycline indirectly inhibits proteolytic activation of tryptic kallikrein-related peptidases and activation of cathelicidin. J Invest Dermatol 132:1435–1442

    Article  CAS  PubMed  Google Scholar 

  16. Kim JT, Lee SH, Chun YS et al (2011) Tear cytokines and chemokines in patients with Demodex blepharitis. Cytokine 53:94–99

    Article  CAS  PubMed  Google Scholar 

  17. Kis K, Bodai L, Polyanka H et al (2006) Budesonide, but not tacrolimus, affects the immune functions of normal human keratinocytes. Int Immunopharmacol 6:358–368

    Article  CAS  PubMed  Google Scholar 

  18. Koczulla R, Von Degenfeld G, Kupatt C et al (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111:1665–1672

    CAS  PubMed  Google Scholar 

  19. Lacey N, Delaney S, Kavanagh K et al (2007) Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol 157:474–481

    Article  CAS  PubMed  Google Scholar 

  20. Lazaridou E, Giannopoulou C, Fotiadou C et al (2011) The potential role of microorganisms in the development of rosacea. J Dtsch Dermatol Ges 9:21–25

    PubMed  Google Scholar 

  21. Lee Y, Kim H, Kim S et al (2009) Myeloid differentiation factor 88 regulates basal and UV-induced expressions of IL-6 and MMP-1 in human epidermal keratinocytes. J Invest Dermatol 129:460–467

    Article  CAS  PubMed  Google Scholar 

  22. Meller S, Winterberg F, Gilliet M et al (2005) Ultraviolet radiation-induced injury, chemokines, and leukocyte recruitment: an amplification cycle triggering cutaneous lupus erythematosus. Arthritis Rheum 52:1504–1516

    Article  CAS  PubMed  Google Scholar 

  23. Nilius B, Owsianik G, Voets T et al (2007) Transient receptor potential cation channels in disease. Physiol Rev 87:165–217

    Article  CAS  PubMed  Google Scholar 

  24. Park K, Elias PM, Oda Y et al (2011) Regulation of cathelicidin antimicrobial peptide expression by an endoplasmic reticulum (ER) stress signaling, vitamin D receptor-independent pathway. J Biol Chem 286:34121–34130

    Article  CAS  PubMed  Google Scholar 

  25. Peric M, Lehmann B, Vashina G et al (2010) UV-B-triggered induction of vitamin D3 metabolism differentially affects antimicrobial peptide expression in keratinocytes. J Allergy Clin Immunol 125:746–749

    Article  CAS  PubMed  Google Scholar 

  26. Roosterman D, Goerge T, Schneider SW et al (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86:1309–1379

    Article  CAS  PubMed  Google Scholar 

  27. Schauber J, Dorschner RA, Coda AB et al (2007) Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 117:803–811

    Article  CAS  PubMed  Google Scholar 

  28. Schauber J, Gallo RL (2009) Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol 124:R13–R18

    Article  CAS  PubMed  Google Scholar 

  29. Schwab VD, Sulk M, Seeliger S et al (2011) Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc 15:53–62

    Article  CAS  PubMed  Google Scholar 

  30. Shibata M, Katsuyama M, Onodera T et al (2009) Glucocorticoids enhance Toll-like receptor 2 expression in human keratinocytes stimulated with Propionibacterium acnes or proinflammatory cytokines. J Invest Dermatol 129:375–382

    Article  CAS  PubMed  Google Scholar 

  31. Steinhoff M, Bergstresser PR (2011) Pathophysiology of rosacea: introduction. J Investig Dermatol Symp Proc 15:1

    Article  PubMed  Google Scholar 

  32. Steinhoff M, Buddenkotte J, Aubert J et al (2011) Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc 15:2–11

    Article  CAS  PubMed  Google Scholar 

  33. Sulk M, Seeliger S, Aubert J et al (2012) Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea. J Invest Dermatol 132:1253–1262

    Article  CAS  PubMed  Google Scholar 

  34. Wilkin J, Dahl M, Detmar M et al (2002) Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatolol 46:584–587

    Article  Google Scholar 

  35. Yamasaki K, Di Nardo A, Bardan A et al (2007) Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 13:975–980

    Article  CAS  PubMed  Google Scholar 

  36. Yamasaki K, Gallo RL (2009) The molecular pathology of rosacea. J Dermatol Sci 55:77–81

    Article  CAS  PubMed  Google Scholar 

  37. Yamasaki K, Kanada K, Macleod DT et al (2011) TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J Invest Dermatol 131:688–697

    Article  CAS  PubMed  Google Scholar 

  38. Yamasaki K, Schauber J, Coda A et al (2006) Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J 20:2068–2080

    Article  CAS  PubMed  Google Scholar 

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Interessenkonflikt

Der korrespondierende Autor weist für sich und seine Koautoren auf folgende Beziehung hin: Referententätigkeit für Galderma.

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Authors and Affiliations

  1. Klinik und Poliklinik für Dermatologie und Allergologie, Ludwigs Maximilians Universität München, Frauenlobstr. 9–11, 80337, München, Deutschland

    J. Schauber

  2. Hautklinik, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Deutschland

    B. Homey

  3. Dept. of Dermatology, University of California, San Francisco, USA

    M. Steinhoff

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  1. J. Schauber
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  2. B. Homey
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  3. M. Steinhoff
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Correspondence to J. Schauber.

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Schauber, J., Homey, B. & Steinhoff, M. Aktuelles Verständnis der Pathophysiologie der Rosazea. Hautarzt 64, 481–488 (2013). https://doi.org/10.1007/s00105-012-2516-7

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  • DOI: https://doi.org/10.1007/s00105-012-2516-7

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