Dermatologische Externa im Kindesalter

 

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Zusammenfassung

Die kindliche Haut bietet verglichen mit Erwachsenen weniger morphologische als vor allem funktionelle Besonderheiten, die für die topische Applikation von Wirksubstanzen von praktischer Bedeutung sind. Um die Zusammenhänge bewerten zu können, sind Grundkenntnisse von der physikochemischen Organisation des Stratum corneums als Grenzkompartiment zwischen Präparation und vitaler Epidermis von essenzieller Bedeutung. Zudem bedarf es eines Grundverständnisses von galenischen Abläufen und Interaktionen, um Behandlungssituationen hinsichtlich einer individuellen Nutzen-Risiko-Bewertung beurteilen zu können. Insgesamt wird deutlich, dass praktisch relevante Risiken insbesondere bei pathologisch veränderter Haut mit Defekten der physikalischen Barriere- und Reservoir-funktion, bei Wärmeeinwirkung und unter Okklusion beachtet werden müssen. Diese liegen vor allem in einer erhöhten systemischen Bioverfügbarkeit mit toxikologischer Relevanz und in irritativen Effekten insbesondere durch Emulgatorwirkungen. Besonders bedeutsam ist im klinischen Alltag der Umgang mit arzneilichen Präparationen, die nicht für die Anwendung im Kindesalter zugelassen sind (Off-label-use). Hierbei gelten besondere juristische Rahmenbedingungen, die eine besondere Sorgfalt in der Therapiewahl voraussetzen.

Summary

The skin of children has compared to adults some particular characteristics which relate more functionality than morphology that need to be considered when applying active substances. Basic knowledge about the physicochemical set-up of the Stratum corneum as a boundary layer between the vital epidermis and a preparation is needed in order to understand the interactions. Also, some insight into galenic features and procedures will be necessary for an individual risk-benefit assessment of treatment. Attention should be paid to relevant risks associated with heat exposure, occlusion or pathologically altered skin involving malfunction or failure of the physical barrier or reservoir function. The most significant risks here are an increased systemic bioavailability with toxicological relevance as well as irritant effects caused by emulsifying agents. A critical point in daily clinical practice is the use of medicinal preparations that have not been approved for treatment in children (off label use). Specific legal framework conditions require extra care and diligence in choosing a therapy.

¹ meinem akademischen Lehrer, Herrn Prof. Dr. med. habil. Wolfgang Christian Marsch, zum 64. Geburtstag gewidmet

• Literatur

• 1 Elias PM. Stratum corneum architecture, metabolic activity and interactivity with subjacent cell layers. Exp Dermatol 1996; 5: 191-201.
  CrossrefPubMedGoogle Scholar
• 2 Elias PM. Stratum corneum defensive functions: an integrated view. J Invest Dermatol 2005; 125: 183-200.
  CrossrefPubMedGoogle Scholar
• 3 Elias PM. Structure and function of the stratum corneum extracellular matrix. J Invest Dermatol 2012; 132: 2131-2133.
  CrossrefPubMedGoogle Scholar
• 4 Choi EH, Man MQ, Xu P. et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol 2007; 127: 2847-2856.
  CrossrefPubMedGoogle Scholar
• 5 Farwanah H, Wohlrab J, Neubert RH. et al. Profiling of human stratum corneum ceramides by means of normal phase LC/APCI-MS. Anal Bioanal Chem 2005; 383: 632-637.
  CrossrefPubMedGoogle Scholar
• 6 Kessner D, Ruettinger A, Kiselev MA. et al. Properties of ceramides and their impact on the stratum corneum structure. Part 2: stratum corneum lipid model systems. Skin Pharmacol Physiol 2008; 21: 58-74.
  CrossrefPubMedGoogle Scholar
• 7 Norlen L, Plasencia I, Bagatolli L. Stratum corneum lipid organization as observed by atomic force, confocal and two-photon excitation fluorescence microscopy. Int J Cosmet Sci 2008; 30: 391-411.
  CrossrefPubMedGoogle Scholar
• 8 Robinson M, Visscher M, Laruffa A. et al. Natural moisturizing factors (NMF) in the stratum corneum (SC). II. Regeneration of NMF over time after soaking. J Cosmet Sci 2010; 61: 23-29.
  Google Scholar
• 9 Robinson M, Visscher M, Laruffa A. et al. Natural moisturizing factors (NMF) in the stratum corneum (SC). I. Effects of lipid extraction and soaking. J Cosmet Sci 2010; 61: 13-22.
  Google Scholar
• 10 Kezic S, Kammeyer A, Calkoen F. et al. Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: evaluation of minimally invasive methods. Br J Dermatol 2009; 161: 1098-1104.
  CrossrefPubMedGoogle Scholar
• 11 Shwayder T, Akland T. Neonatal skin barrier: structure, function, and disorders. Dermatol Ther 2005; 18: 87-103.
  CrossrefPubMedGoogle Scholar
• 12 Fluhr JW, Behne MJ, Brown BE. et al. Stratum corneum acidification in neonatal skin: secretory phospholipase A2 and the sodium/hydrogen antiporter-1 acidify neonatal rat stratum corneum. J Invest Dermatol 2004; 122: 320-329.
  CrossrefPubMedGoogle Scholar
• 13 Behne MJ, Barry NP, Hanson KM. et al. Neonatal development of the stratum corneum pH gradient: localization and mechanisms leading to emergence of optimal barrier function. J Invest Dermatol 2003; 120: 998-1006.
  CrossrefPubMedGoogle Scholar
• 14 Visscher MO, Utturkar R, Pickens WL. et al. Neonatal skin maturation - vernix caseosa and free amino acids. Pediatr Dermatol 2011; 28: 122-132.
  CrossrefPubMedGoogle Scholar
• 15 Gupta P, Faridi MM, Batra M. Physiological skin manifestations in twins: association with maternal and neonatal factors. Pediatr Dermatol 2011; 28: 387-392.
  CrossrefPubMedGoogle Scholar
• 16 Visscher MO, Taylor T, Narendran V. Neonatal intensive care practices and the influence on skin condition. J Eur Acad Dermatol Venereol 2013; 27: 486-493.
  CrossrefPubMedGoogle Scholar
• 17 Hoeger PH, Enzmann CC. Skin physiology of the neonate and young infant: a prospective study of functional skin parameters during early infancy. Pediatr Dermatol 2002; 19: 256-262.
  CrossrefPubMedGoogle Scholar
• 18 Yamamoto A, Serizawa S, Ito M. et al. Effect of aging on sebaceous gland activity and on the fatty acid composition of wax esters. J Invest Dermatol 1987; 89: 507-512.
  CrossrefPubMedGoogle Scholar
• 19 Stewart ME. Sebaceous gland lipids. Semin Dermatol 1992; 11: 100-105.
  PubMedGoogle Scholar
• 20 Ness MJ, Davis DM, Carey WA. Neonatal skin care: a concise review. Int J Dermatol 2013; 52: 14-22.
  CrossrefPubMedGoogle Scholar
• 21 Bibel DJ, Miller SJ, Brown BE. et al. Antimicrobial activity of stratum corneum lipids from normal and essential fatty acid-deficient mice. J Invest Dermatol 1989; 92: 632-638.
  CrossrefPubMedGoogle Scholar
• 22 Bharathi M, Sundaram V, Kumar P. Skin barrier therapy and neonatal mortality in preterm infants. Pediatrics 2009; 123: e355 author reply e55-56
  PubMedGoogle Scholar
• 23 Garcia Bartels N, Scheufele R, Prosch F. et al. Effect of standardized skin care regimens on neonatal skin barrier function in different body areas. Pediatr Dermatol 2010; 27: 1-8.
  CrossrefPubMedGoogle Scholar
• 24 Gangarosa LP, Park NH, Hill JM. Iontophoretic assistance of 5-lodo-2’-deoxyuridine penetration into neonatal mouse skin and effects on DNA synthesis. Proc Soc Exp Biol Med 1977; 154: 439-443.
  CrossrefPubMedGoogle Scholar
• 25 Elias PM, Wakefield JS. Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis. Clin Rev Allergy Immunol 2011; 41: 282-295.
  CrossrefPubMedGoogle Scholar
• 26 Frobel AK, Läer S. Besonderheiten der Pharmakotherapie bei Kindern. Pharmazeutische Wissenschaft 2006; 24: 168-175.
  Google Scholar
• 27 Derendorf H, Lesko LJ, Chaikin P. et al. Pharmacokinetic/pharmacodynamic modeling in drug research and development. J Clin Pharmacol 2000; 40: 1399-1418.
  PubMedGoogle Scholar
• 28 Weißenborn M, Schmitz E, Kissel M. et al. Gewicht, Alter, Genom. Individuelle Einflussfaktoren auf die Pharmakokinetik. Deutsche Apotheker Zeitung 2013; 152: 62-65.
  Google Scholar
• 29 Derendorf H, Meibohm B. Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: concepts and perspectives. Pharm Res 1999; 16: 176-185.
  CrossrefPubMedGoogle Scholar
• 30 Wohlrab J, Klapperstuck T, Reinhardt HW. et al. Interaction of epicutaneously applied lipids with stratum corneum depends on the presence of either emulsifiers or hydrogenated phosphatidylcholine. Skin Pharmacol Physiol 2010; 23: 298-305.
  CrossrefPubMedGoogle Scholar
• 31 Kongress-Report Therapie und Pflege der Haut im Kindesalter. Der Deutsche Dermatologe. 2009: 2-3.
  Google Scholar
• 32 Werfel S, Boeck K, Abeck D. et al. Besonderheiten der topischen Behandlung im Kindesalter. Hautarzt 1998; 49: 170-175.
  CrossrefPubMedGoogle Scholar
• 33 Grether-Beck S, Felsner I, Brenden H. et al. Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression. J Invest Dermatol 2012; 132: 1561-172.
  CrossrefPubMedGoogle Scholar
• 34 Hafeez F, Maibach H. Occlusion Effect on in vivo Percutaneous Penetration of Chemicals in Man and Monkey: Partition Coefficient Effects. Skin Pharmacol Physiol 2013; 26: 85-91.
  CrossrefPubMedGoogle Scholar
• 35 Gelardi A, Morini F, Dusatti F. et al. Induction by xenobiotics of phase I and phase II enzyme activities in the human keratinocyte cell line NCTC 2544. Toxicol In Vitro 2001; 15: 701-711.
  CrossrefPubMedGoogle Scholar
• 36 Bebia Z, Buch SC, Wilson JW. et al. Bioequivalence revisited: influence of age and sex on CYP enzymes. Clin Pharmacol Ther 2004; 76: 618-627.
  CrossrefPubMedGoogle Scholar
• 37 Wohlrab J. Dermatotherapie in der Schwangerschaft. Hautarzt 2010; 61: 1046-1051.
  CrossrefPubMedGoogle Scholar
• 38 Schaefer C. Off-label-use von Medikamenten in der Schwangerschaft. Frauenarzt 2007; 48: 20-25.
  Google Scholar
• 39 Schaefer C, Spielmann H, Vetter K. Arzneimittelverordnung in Schwangerschaft und Stillzeit. München, Jena: Urban Fischer; 2006
  Google Scholar
• 40 Wohlrab W. Penetration kinetics and effectiveness of urea in human skin following removal of the stratum corneum. Dermatol Monatsschr 1984; 170: 743-749.
  PubMedGoogle Scholar
• 41 Pharmazeutisches Laboratorium des Neuen Rezeptur-Formulariums.. Standardisierte Rezepturen Eschborn: Govi-Verlag; 2012
  Google Scholar