Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Die Dermatologie
Erschienen in: Der Hautarzt 11/2016

21.10.2016 | Atopische Dermatitis | CME

Epidermale Barrierestörung bei Dermatosen

verfasst von: Prof. Dr. Dr. E. Proksch, D. Dähnhardt, S. Dähnhardt-Pfeiffer, R. Fölster-Holst

Erschienen in: Die Dermatologie | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Zusammenfassung

Die Permeabilitätsbarriere spielt bei zahlreichen Hauterkrankungen eine Rolle. Besonders gut aufgeklärt ist die Bedeutung der Barriere bei ekzematösen Erkrankungen. Bei einem irritativ-toxischen Kontaktekzem ist die Störung der Permeabilitätsbarriere durch irritativ-toxische Noxen der erste Schritt in der Pathogenese. Nur nach Schädigung der Barriere können Irritanzien und Allergene in die lebende Epidermis eindringen. Beim atopischen Ekzem penetrieren aufgrund der gestörten Barriere Typ-I-Allergene aus der Umwelt in die Haut und verursachen oder verschlimmern das Ekzem. Bei der anderen häufigen chronisch entzündlichen Dermatose, der Psoriasis, ist die Rolle der Permeabilitätsbarriere nur teilweise bekannt. Bei einem Exanthem verursachen Infektionserreger oder Medikamente eine systemische Entzündung, wobei der Inflammation der Haut eine Barrierestörung folgt. Prinzipiell liegt bei allen entzündlichen Erkrankungen eine gestörte Permeabilitätsbarriere der Haut vor.
Literatur
1.
Elias PM, Goerke J, Friend DS (1977) Mammalian epidermal barrier layer lipids: composition and influence on structure. J Invest Dermatol 69:535–546CrossRefPubMed
2.
Menton DN (1976) A liquid film model of tetrakaidekahedral packing to account for the establishment of epidermal cell columns. J Invest Dermatol 66:283–291CrossRefPubMed
3.
Naegel A, Heisig M, Wittum G (2013) Detailed modeling of skin penetration – an overview. Adv Drug Deliv Rev 65:191–207CrossRefPubMed
4.
Elias PM, Cullander C, Mauro T, Rassner U, Kömüves L, Brown BE, Menon GK (1998) The secretory granular cell: the outermost granular cell as a specialized secretory cell. J Investig Dermatol Symp Proc 3:87–100CrossRefPubMed
5.
Holleran WM, Man MQ, Gao WN, Menon GK, Elias PM, Feingold KR (1991) Sphingolipids are required for mammalian epidermal barrier function. Inhibition of sphingolipid synthesis delays barrier recovery after acute perturbation. J Clin Invest 88:1338–1345CrossRefPubMedPubMedCentral
6.
Ishikawa J, Narita H, Kondo N, Hotta M, Takagi Y, Masukawa Y, Kitahara T, Takema Y, Koyano S, Yamazaki S, Hatamochi A (2010) Changes in the ceramide profile of atopic dermatitis patients. J Invest Dermatol 130:2511–2514CrossRefPubMed
7.
Marekov LN, Steinert PM (1998) Ceramides are bound to structural proteins of the human foreskin epidermal cornified cell envelope. J Biol Chem 10(273):17763–17770CrossRef
8.
Kalinin A, Marekov LN, Steinert PM (2001) Assembly of the epidermal cornified cell envelope. J Cell Sci 114:3069–3070PubMed
9.
Steinert PM, Cantieri JS, Teller DC, Lonsdale-Eccles JD, Dale BA (1981) Characterization of a class of cationic proteins that specifically interact with intermediate filaments. Proc Natl Acad Sci U S A 78:4097–4101CrossRefPubMedPubMedCentral
10.
Brandner JM, Kief S, Wladykowski E, Houdek P, Moll I (2006) Tight junction proteins in the skin. Skin Pharmacol Physiol 19:71–77CrossRefPubMed
11.
Yokouchi M, Kubo A, Kawasaki H, Yoshida K, Ishii K, Furuse M, Amagai M (2015) Epidermal tight junction barrier function is altered by skin inflammation, but not by filaggrin-deficient stratum corneum. J Dermatol Sci 77(1):28–36CrossRefPubMed
12.
Elias PM, Fritsch P, Epstein EH (1977) Staphylococcal scalded skin syndrome. Clinical features, pathogenesis, and recent microbiological and biochemical developments. Arch Dermatol 113:207–219CrossRefPubMed
13.
Nakatsuji T, Chen TH, Two AM, Chun KA, Narala S, Geha RS, Hata TR, Gallo RL (2016) Staphylococcus aureus exploits epidermal barrier defects in atopic dermatitis to trigger cytokine expression. J Invest Dermatol 2. doi:10.​1016/​j.​jid.​2016.​05.​127
14.
Proksch E, Elias PM, Feingold KR (1990) Regulation of 3‑hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements. J Clin Invest 85:874–882CrossRefPubMedPubMedCentral
15.
Ekanayake-Mudiyanselage S, Aschauer H, Schmook FP, Jensen JM, Meingassner JG, Proksch E (1998) Expression of epidermal keratins and the cornified envelope protein involucrin is influenced by permeability barrier disruption. J Invest Dermatol 111:517–523CrossRefPubMed
16.
Proksch E, Holleran WM, Menon GK, Elias PM, Feingold KR (1993) Barrier function regulates epidermal lipid and DNA synthesis. Br J Dermatol 128:473–482CrossRefPubMed
17.
Nishijima T, Tokura Y, Imokawa G, Seo N, Furukawa F, Takigawa M (1997) Altered permeability and disordered cutaneous immunoregulatory function in mice with acute barrier disruption. J Invest Dermatol 109:175–182CrossRefPubMed
18.
Proksch E, Brasch J, Sterry W (1996) Integrity of the permeability barrier regulates epidermal Langerhans cell density. Br J Dermatol 134:630–638CrossRefPubMed
19.
Ahrens K, Schunck M, Podda GF, Meingassner J, Stuetz A, Schröder JM, Harder J, Proksch E (2011) Mechanical and metabolic injury to the skin barrier leads to increased expression of murine β‑defensin-1, -3, and -14. J Invest Dermatol 131:443–452CrossRefPubMed
20.
Gläser R, Meyer-Hoffert U, Harder J, Cordes J, Wittersheim M, Kobliakova J, Fölster-Holst R, Proksch E, Schröder JM, Schwarz T (2009) The antimicrobial protein psoriasin (S100A7) is upregulated in atopic dermatitis and after experimental skin barrier disruption. J Invest Dermatol 129:641–649CrossRefPubMed
21.
Jensen JM, Schütze S, Förl M, Krönke M, Proksch E (1999) Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier. J Clin Invest 104:1761–1770CrossRefPubMedPubMedCentral
22.
Wang XP, Schunck M, Kallen KJ, Neumann C, Trautwein C, Rose-John S, Proksch E (2004) The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis. J Invest Dermatol 123:124–131CrossRefPubMed
23.
Denda M, Tsuchiya T, Elias PM, Feingold KR (2000) Stress alters cutaneous permeability barrier homeostasis. Am J Physiol Regul Integr Comp Physiol 278(2):R367–72PubMed
24.
Endo K, Suzuki N, Yoshida O, Sato H, Fujikura Y (2007) The barrier component and the driving force component of transepidermal water loss and their application to skin irritant tests. Skin Res Technol 13:425–435CrossRefPubMed
25.
Jensen JM, Pfeiffer S, Witt M, Bräutigam M, Neumann C, Weichenthal M, Schwarz T, Fölster-Holst R, Proksch E (2009) Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol 124(3 Suppl 2):R19–R28CrossRefPubMed
26.
Dähnhardt-Pfeiffer S, Surber C, Wilhelm KP et al (2012) Noninvasive stratum corneum sampling and electron microscopical examination of skin barrier integrity: pilot study with a topical glycerin formulation for atopic dermatitis. Skin Pharmacol Physiol 25:155–161CrossRefPubMed
27.
Dähnhardt-Pfeiffer S, Dähnhardt D, Buchner M, Walter K, Proksch E, Fölster-Holst R (2013) Comparison of effects of tacrolimus ointment and mometasone furoate cream on the epidermal barrier of patients with atopic dermatitis. J Dtsch Dermatol Ges 2013(4):437–443
28.
Stettler H, Kurka P, Lunau N, Manger C, Böhling A, Bielfeldt S et al (2016) A new topical panthenol-containing emollient: Results from two randomized controlled studies assessing its skin moisturization and barrier restoration potential, and the effect on skin microflora. J Dermatolog Treat 2:1–8
29.
Dähnhardt-Pfeiffer S, Dähnhardt D, Schmetz C, Buchner M, Fölster-Holst R (2014) Corneocyte membrane undulation and intercellular lipid membranes as an indicator for severity in netherton syndrome, ichthyosis vulgaris and atopic dermatitis? Comparison of SC ultrastructures and barrier lipids in a pilot study using electron microscopy and Lipbarvis. J Dtsch Dermatol Ges 12s2(2014):1610–0379
30.
Elias PM, Schmuth M, Uchida Y, Rice RH, Behne M, Crumrine D, Feingold KR, Holleran WM, Pharm D (2002) Basis for the permeability barrier abnormality in lamellar ichthyosis. Exp Dermatol 11:248–256CrossRefPubMed
31.
Stick C, Proksch E (2012) The influence of the climate on the treatment of dry skin with moisturizers. In: Loden M, Maibach H (Hrsg) Treatment of dry skin syndrome: the art and sience of moisturizers. Springer, Heidelberg, S 503–513CrossRef
32.
Proksch E, Brasch J (2012) Abnormal epidermal barrier in the pathogenesis of contact dermatitis. Clin Dermatol 30(3):335–344CrossRefPubMed
33.
Fölster-Holst R, Hausen BM, Brasch J, Christophers E (2001) Contact allergy caused by poison ivy Toxicodendron spp. Hautarzt 52:136–142CrossRefPubMed
34.
Jensen JM, Scherer A, Wanke C, Bräutigam M, Bongiovanni S, Letzkus M, Staedtler F, Kehren J, Zuehlsdorf M, Schwarz T, Weichenthal M, Fölster-Holst R, Proksch E (2012) Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis. Allergy 67:413–423CrossRefPubMed
35.
Proksch E, Jensen JM, Elias PM (2003) Skin lipids and epidermal differentiation in atopic dermatitis. Clin Dermatol 21:134–144CrossRefPubMed
36.
Proksch E, Fölster-Holst R, Bräutigam M, Sepehrmanesh M, Pfeiffer S, Jensen JM (2009) Role of the epidermal barrier in atopic dermatitis. J Dtsch Dermatol Ges 7:899–910PubMed
37.
Melnik B, Hollmann J, Hofmann U, Yuh MS, Plewig G (1990) Lipid composition of outer stratum corneum and nails in atopic and control subjects. Arch Dermatol Res 282(8):549–551CrossRefPubMed
38.
Janssens M, van Smeden J, Gooris GS, Bras W, Portale G, Caspers PJ, Vreeken RJ, Hankemeier T, Kezic S, Wolterbeek R, Lavrijsen AP, Bouwstra JA (2012) Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. J Lipid Res 53:2755–2766CrossRefPubMedPubMedCentral
39.
Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of epidermal barrier in atopic dermatitis. Cell death in the skin. Nat Rev Mol Cell Biol 6:328–340CrossRefPubMed
40.
Palmer CN, Irvine AD, Terron-Kwiatkowski A et al (2006) Common loss-offunction variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38:441–446CrossRefPubMed
41.
Ruether A, Stoll M, Schwarz T, Schreiber S, Fölster-Holst R (2006) Filaggrin loss-offunction variant contributes to atopic dermatitis risk in the population of Northern Germany. Br J Dermatol 155:1093–1094CrossRefPubMed
42.
Weidinger S, Illig T, Baurecht H et al (2006) Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol 118:214–219CrossRefPubMed
43.
Kezic S, Novak N, Jakasa I, Jungersted JM, Simon M, Brandner JM, Middelkamp-Hup MA, Weidinger S (2014) Skin barrier in atopic dermatitis. Front Biosci (Landmark Ed) 19:542–556CrossRef
44.
45.
Chen H, Ho JC, Sandilands A et al (2008) Unique and recurrent mutations in the filaggrin gene in Singaporean Chinese patients with ichthyosis vulgaris. J Invest Dermatol 128:1669–1675CrossRefPubMed
46.
Enomoto H, Hirata K, Otsuka K et al (2008) Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population: a family and case-control study. J Hum Genet 53:615–621CrossRefPubMed
47.
Nomura T, Akiyama M, Sandilands A et al (2009) Prevalent and rare mutations in the gene encoding filaggrin in Japanese patients with ichthyosis vulgaris and atopic dermatitis. J Invest Dermatol 129:1302–1305CrossRefPubMed
48.
Brown SJ, McLean WH (2009) Eczema genetics: current state of knowledge and future goals. J Invest Dermatol 129(3):543–552CrossRefPubMed
49.
Ried, et al, Consortium 73 authors, EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium, Australian Asthma Genetics Consortium(AAGC) (2015) Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet 47:1449–1456CrossRefPubMedPubMedCentral
50.
Fölster-Holst R, Dähnhardt-Pfeiffer S, Dähnhardt D, Proksch E (2012) The role of skin barrier function in atopic dermatitis:an update. Expert Rev Dermatol 7:247–257CrossRef
51.
Carlsten C, Dimich-Ward H, Ferguson A, Watson W, Rousseau R, Dybuncio A, Becker A, Chan-Yeung M (2013) Atopic dermatitis in a high-risk cohort: natural history, associated allergic outcomes, and risk factors. Ann Allergy Asthma Immunol 110:24–28CrossRefPubMed
52.
Wiechers JW (1989) The barrier function of the skin in relation to percutaneous absorption of drugs. Pharm Weekbl Sci 11(6):185–198CrossRefPubMed
53.
Fölster-Holst R, Galecka J, Weißmantel S, Dickschat U, Rippke F, Bohnsack K, Werfel T, Wichmann K, Buchner M, Schwarz T, Vogt A, Lademann J, Meinke MC (2015) Birch pollen influence the severity of atopic eczema – prospective clinical cohortpilot study and ex vivo penetration study. Clin Cosmet Investig Dermatol 8:539–548PubMedPubMedCentral
54.
Siwak E, Skotny A, Zbrojewicz E, Wolańczyk-Mędrala A, Mędrala W, Kustrzeba-Wójcicka I (2014) Allergens of mites. Postepy Hig Med Dosw (Online) 68:369–374CrossRef
55.
Kumar S, Zakrewsky M, Chen M, Menegatti S, Muraski JA, Mitragotri S (2015) Peptides as skin penetration enhancers: mechanisms of action. J Control Release 199:168–178CrossRefPubMed
56.
Werfel T, Heratizadeh A, Niebuhr M, Kapp A, Roesner LM, Karch A, Erpenbeck VJ, Lösche C, Jung T, Krug N, Badorrek P, Hohlfeld JM (2015) Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber. J Allergy Clin Immunol 136:96–103CrossRefPubMed
57.
Magnani ND, Muresan XM, Belmonte G, Cervellati F, Sticozzi C, Pecorelli A, Miracco C, Marchini T, Evelson P, Valacchi G (2016) Skin damage mechanisms related to airborne particulate matter exposure. Toxicol Sci 149:227–236CrossRefPubMed
58.
Ring J, von Zumbusch A (2000) Neurodermitis: Ursachen und Therapien. Beck, München, S S28–29
59.
Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 10;347(15:1151–1160CrossRef
60.
Harder J, Dressel S, Wittersheim M, Cordes J, Meyer-Hoffert U, Mrowietz U, Fölster-Holst R, Proksch E, Schröder JM, Schwarz T, Gläser R (2010) Enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury. J Invest Dermatol 130:1355–1364CrossRefPubMed
61.
Jensen JM, Ahrens K, Meingassner J, Scherer A, Bräutigam M, Stütz A, Schwarz T, Fölster-Holst R, Harder J, Gläser R, Proksch E (2011) Differential suppression of epidermal antimicrobial protein expression in atopic dermatitis and in EFAD mice by pimecrolimus compared to corticosteroids. Exp Dermatol 20:783–788CrossRefPubMed
62.
Vogt KA, Lohse CM, El-Azhary RA, Gibson LE, Lehman JS (2015) Kaposi varicelliform eruption in patients with Darier disease: a 20-year retrospective study. J Am Acad Dermatol 72(3):481–484CrossRefPubMed
63.
Werfel T, Heratizadeh A, Aberer W, Ahrens F, Augustin M, Biedermann T, Diepgen T, Fölster-Holst R, Gieler U, Kahle J, Kapp A, Nast A, Nemat K, Ott H, Przybilla B, Roecken M, Schlaeger M, Schmid-Grendelmeier P, Schmitt J, Schwennesen T, Staab D, Worm M (2016) S2k guideline on diagnosis and treatment of atopic dermatitis – short version. J Dtsch Dermatol Ges 14(1):92–105PubMed
64.
Fölster-Holst R, Schwarz T (2011) Atopisches Ekzem – Grundlagen und Updates. UNI-MED, Bremen
65.
Hon KL, Leung AK, Barankin B (2013) Barrier repair therapy in atopic dermatitis: an overview. Am J Clin Dermatol 14(5):389–399CrossRefPubMed
66.
Schmuth M, Blunder S, Dubrac S, Gruber R, Moosbrugger-Martinz V (2015) Epidermal barrier in hereditary ichthyoses, atopic dermatitis, and psoriasis. J Dtsch Dermatol Ges 13:1119–1123PubMed
67.
Grice K, Sattar H, Baker H, Sharratt M (1975) The relationship of transepidermal water loss to skin temperature in psoriasis and eczema. J Invest Dermatol 64:313–315CrossRefPubMed
68.
Hagemann I, Proksch E (1996) Topical treatment by urea reduces epidermal hyperproliferation and induces differentiation in psoriasis. Acta Derm Venereol 76:353–356PubMed
69.
Bergboer JG, Dulak MG, van Vlijmen-Willems IM, Jonca N, van Wijk E, Hendriks WJ, Zeeuwen PL, Schalkwijk J (2014) Analysis of protein-protein interaction between late cornified envelope proteins and corneodesmosin. Exp Dermatol 23:769–771CrossRefPubMed
70.
Waisman M (1981) Historical note: Koebner on the isomorphic phenomenon. Arch Dermatol 117:415CrossRefPubMed
71.
72.
Suga H, Sugaya M, Miyagaki T, Ohmatsu H, Kawaguchi M, Takahashi N, Fujita H, Asano Y, Tada Y, Kadono T, Sato S (2014) Skin barrier dysfunction and low antimicrobial peptide expression in cutaneous T‑cell lymphoma. Clin Cancer Res 15:4339–4348CrossRef
73.
Engelke M, Jensen JM, Ekanayake-Mudiyanselage S, Proksch E (1997) Effects of xerosis and ageing on epidermal proliferation and differentiation. Br J Dermatol 137:219–225CrossRefPubMed
74.
75.
Harber LC, Hermann F, Mandol L, Sulzberger MB (1957) Lipid studies on the human skin surface by means of the monomolecular layer method. I. Findings obtained in the same and in different skin areas in identical and in different healthy subjects. J Invest Dermatol 29:55–65CrossRefPubMed
76.
Dirschka T, Tronnier H, Fölster-Holst R (2004) Epithelial barrier function and atopic diathesis in rosacea and perioral dermatitis. Br J Dermatol 150(6):1136–1141CrossRefPubMed
77.
Proksch E, Lachapelle JM (2005) The management of dry skin with topical emollients – recent perspectives. J Dtsch Dermatol Ges 3:768–774CrossRefPubMed
78.
Proksch E (2008) The role of emollients in the management of diseases with chronic dry skin. Skin Pharmacol Physiol 21:75–80CrossRefPubMed
79.
Draelos ZD (2013) Modern moisturizer myths, misconceptions, and truths. Cutis 91:308–314PubMed
80.
Lynde CW, Andriessen A (2014) A cohort study on a ceramide-containing cleanser and moisturizer used for atopic dermatitis. Cutis 93:207–213PubMed
81.
Miller DW, Koch SB, Yentzer BA, Clark AR, O’Neill JR, Fountain J, Weber TM, Fleischer AB Jr (2011) An over-the-counter moisturizer is as clinically effective as, and more cost-effective than, prescription barrier creams in the treatment of children with mild-to-moderate atopic dermatitis: a randomized, controlled trial. J Drugs Dermatol 10:531–537PubMed
82.
Mueller J, Oliveira JS, Barker R, Trapp M, Schroeter A, Brezesinski G, Neubert RH (2016) The effect of urea and taurine as hydrophilic penetration enhancers on stratum corneum lipid models. Biochim Biophys Acta 1858(9):2006–2018CrossRefPubMed
Metadaten
Titel
Epidermale Barrierestörung bei Dermatosen
verfasst von
Prof. Dr. Dr. E. Proksch
D. Dähnhardt
S. Dähnhardt-Pfeiffer
R. Fölster-Holst
Publikationsdatum
21.10.2016
Verlag
Springer Medizin
Erschienen in
Die Dermatologie / Ausgabe 11/2016
Print ISSN: 2731-7005
Elektronische ISSN: 2731-7013
DOI
https://doi.org/10.1007/s00105-016-3883-2

Weitere Artikel der Ausgabe 11/2016

Der Hautarzt 11/2016 Zur Ausgabe

Leitthema

Was gibt es Neues zum Basalzellkarzinom?

Dermatoskopie – Fall des Monats

Dermatoskopie ohne Dermatoskop

Kasuistiken

Schwere Akne bei Autoinflammationskrankheiten

Einführung zum Thema

Epitheliale Hauttumoren

Kasuistik

Disseminiertes nekrobiotisches Xanthogranulom

Leitthema

Kutanes Plattenepithelkarzinom

Weitere Lesetipps

Was eine strahlend schöne Haut ausmacht

Neue therapeutische Wege bei fortgeschrittenem Leberzellkarzinom

Empfehlungen der Fachgesellschaft zu okulären Nebenwirkungen von Dupilumab

ANZEIGE

Spektrum Dermatologie: Jetzt auch auf medbee – die App für Mediziner*innen

ANZEIGE

Neue Konzepte beim Handekzem

ANZEIGE

Dexpanthenol verstärkt die positiven Effekte der LASH-Methode

Bildnachweise