Topical treatment of atopic dermatitis in children: current challenges and answers

Cover Page


Cite item

Full Text

Abstract

Atopic dermatitis (AD) is the most prevalent skin disease in the early childhood and is a considerable problem both for patients and members of their families and for the society on the whole. In most cases, AD requires a long-term therapy such as the use of anti-inflammatory drugs. Selective inhibitors of the synthesis and release of proinflammatory cytokines - topical calcineurin inhibitors (Tcis) - are now used to solve this problem, with pimecrolimus being one of them. Pimecrolimus has been thoroughly examined for the past decade in different clinical studies involving a total of over 4,000 infants (below 2 years of age). These studies demonstrated the efficacy and safety of pimecrolimus for AD in children provided it is used in a long-term therapy on an intermittent basis. Unlike topical corticosteroids, the long-term use of pimecrolimus is not associated with any risk of development of systemic immunosuppression, skin atrophy, skin barrier dysfunction or systemic absorption so it is safe even if applied to the most sensitive skin areas. In view of this, the authors make a conclusion that pimecrolimus used in the form of a cream is a safe and efficient drug for the treatment of infants aged over three months suffering from atopic dermatitis.

About the authors

L. S. Namazova-Baranova

ФГАУ «Научный центр здоровья детей» Министерства здравоохранения Российской Федерации

Author for correspondence.
Email: lsnamazova@yandex.ru
Россия

N. N. Murashkin

ФГАУ «Научный центр здоровья детей» Министерства здравоохранения Российской Федерации; ФГБОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России

Email: noemail@neicon.ru
Россия

A. I. Materikin

ФГАУ «Научный центр здоровья детей» Министерства здравоохранения Российской Федерации

Email: noemail@neicon.ru
Россия

E. T. Ambarchyan

ФГАУ «Научный центр здоровья детей» Министерства здравоохранения Российской Федерации

Email: noemail@neicon.ru
Россия

R. V. Epishev

ФГАУ «Научный центр здоровья детей» Министерства здравоохранения Российской Федерации

Email: noemail@neicon.ru
Россия

References

  1. Watson W., Kapur S. Atopicdermatitis. Allergy Asthma Clin Immunol 2011; 7 (Suppl): S4.
  2. Bieber T. Atopic dermatitis. N Engl J Med 2008; 358: 1483-94.
  3. Illi S., von Mutius E., Lau S. et al. The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. J Allergy Clin Immunol 2004; 113: 925-31.
  4. Zheng T., Yu J., Oh M.H., Zhu Z. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res 2011; 3: 67-73.
  5. Kapoor R., Menon C., Hoffstad O., Bilker W., Leclerc P., Margolis D.J. The prevalence of atopic triad in children with physician-con.rmed atopic dermatitis. J Am Acad Dermatol 2008; 58: 68-73.
  6. Mancini A.J., Kaulback K., Chamlin S.L. The socioeconomic impact of atopic dermatitis in the United States: a systematic review. Pediatr Dermatol 2008; 25: 1-6.
  7. Elias P.M., Hatano Y., Williams M.L. Basis for the barrier abnormality in atopic dermatitis: outsideinside-outside pathogenic mechanisms. J Allergy Clin Immunol 2008; 121: 1337-43.
  8. Lee H.J., Lee S.H. Epidermal permeability barrier defects and barrier repair therapy in atopic dermatitis. Allergy Asthma Immunol Res 2014; 6: 276-87.
  9. Tang T.S., Bieber T., Williams H.C. Are the concepts of induction of remission and treatment of subclinical in.ammation in atopic dermatitis clinically useful? J Allergy Clin Immunol 2014; 133: 1615-25.
  10. Hani.n J., Gupta A.K., Rajagopalan R. Intermittent dosing of.uticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol 2002; 147: 528-37.
  11. Peserico A., Städtler G., Sebastian M., Fernandez R.S., Vick K., Bieber T. Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double-blind, controlled study. Br J Dermatol 2008; 158: 801-7.
  12. Namazova-Baranova L.S., Vishneva E.A., Torshhoeva R.M., Dzagoeva Z.N., Alekseeva A.A., Levina Yu.G., Efendieva K.E., Voznesenskaya N.I., Aslamyazyan L.K. Nesteroidnyie topicheskie preparatyi v terapii atopicheskogo dermatita u detey. Pediatricheskaya farmakologiya. 2012; 9(1): 66-71. doi: 10.15690/pf.v9i1.166 [Намазова-Баранова Л.С., Вишнева Е.А., Торшхоева P.M., Дзагоева З.Н., Алексеева А.А., Левина Ю.Г., Эфендиева К.Е., Вознесенская Н.И., Асламязян Л.К. Нестероидные топические препараты в терапии атопического дерматита у детей. Педиатрическая фармакология. 2012;9(1):66-71. doi: 10.15690/pf.v9i1.166 ]
  13. Glazenburg E.J., Wolkerstorfer A., Gerretsen A.L., Mulder P.G., Oranje A.P. Ef.cacy and safety of uticasone propionate 0.005% ointment in the longterm maintenance treatment of children with atopic dermatitis: differences between boys and girls? Pediatr Allergy Immunol 2009; 20: 59-66.
  14. Namazova-Baranova L.S., Kulichenko T.V., Borovik T.A. , Makarova S.G. , Novik G.A. , Petrovskiy F.I. , Vishnyova E.A. , Alekseeva A.A. Atopicheskiy dermatit (rukovodstvo dlya vrachey pod red. L.S. Namazovoy-Baranovoy). Moskva: PediatTb, 2014; 72 s. (Bolezni detskogo vozrasta ot A do Ya / Soyuz pediatrov Rossii; vyip. 6). [Намазова-Баранова Л.С., Куличенко Т.В., Боровик Т.А., Макарова С.Г., Новик Г.А., Петровский Ф.И., Вишнёва Е.А., Алексеева А.А. Атопический дерматит (руководство для врачей под ред. Намазовой-Барановой Л.С.). Москва: Педиатрь, 2014; 72 с. (Болезни детского возраста от А до Я / Союз педиатров России; вып. 6).]
  15. Ring J., Alomar A., Bieber T. et al. Guidelines for treatment of atopic eczema (atopic dermatitis) part I. J Eur Acad Dermatol Venereol 2012; 26: 1045-60.
  16. Hengge U.R., Ruzicka T., Schwartz R.A., Cork M.J. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol 2006; 54: 1-15.
  17. Murashkin N.N. Osobennosti klinicheskogo polimorfizma atopicheskogo dermatita u detey. Strategiya individualnogo podhoda k terapii. Consilium Medicum Pediatriya 2014; № 1: S. 23-27. [Мурашкин Н.Н. Особенности клинического полиморфизма атопического дерматита у детей. Стратегия индивидуального подхода к терапии. Consilium Medicum Педиатрия 2014; № 1: С. 23-27.]
  18. Aschoff R., Schmitt J., Knuschke P., Koch E., Brautigam M., Meurer M. Evaluation of the atrophogenic potential of hydrocortisone 1% cream and pimecrolimus 1% cream in uninvolved forehead skin of patients with atopic dermatitis using optical coherence tomography. Exp Dermatol 2011; 20: 832-6.
  19. Jensen J.M., Pfeiffer S., Witt M. et al. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol 2009; 124: R19-28.
  20. Jensen J.M., Scherer A., Wanke C. et al. Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis. Allergy 2012; 67: 413-23.
  21. Aubert-Wastiaux H., Moret L., Le Rhun A. et al. Topical corticosteroid phobia in atopic dermatitis: a study of its nature, origins and frequency. Br J Dermatol 2011; 165: 808-14.
  22. Krejci-Manwaring J., Tusa M.G., Carroll C. et al. Stealth monitoring of adherence to topical medication: adherence is very poor in children with atopic dermatitis. J Am Acad Dermatol 2007; 56: 211-6.
  23. Murashkin N.N. Narusheniya dermalnogo barera kak faktor hronizatsii dermatozov v detskom vozraste, podhodyi k terapii: teoreticheskie i prakticheskie innovatsii. Lechaschiy vrach. 2014; № 6: S. 19-23. [Мурашкин Н.Н. Нарушения дермального барьера как фактор хронизации дерматозов в детском возрасте, подходы к терапии: теоретические и практические инновации. Лечащий врач. 2014; № 6: С. 19-23.]
  24. Grassberger M., Steinhoff M., Schneider D., Luger T.A. Pimecrolimus - an anti-in.ammatory drug targeting the skin. Exp Dermatol 2004; 13: 721-30.
  25. Siegfried E.C., Jaworski J.C., Hebert A.A. Topical calcineurin inhibitors and lymphoma risk: evidence update with implications for daily practice. Am J Clin Dermatol 2013; 14: 163-78.
  26. Mandelin J.M., Rubins A., Remitz A. et al. Long-term ef.cacy and tolerability of tacrolimus 0.03% ointment in infants:* a two-year openlabel study. Int J Dermatol 2012; 51: 104-10.
  27. Reitamo S., Mandelin J., Rubins A. et al. The pharmacokinetics of tacrolimus after.rst and repeated dosing with 0.03% ointment in infants with atopic dermatitis. Int J Dermatol 2009; 48: 348-55.
  28. Kapp A., Papp K., Bingham A. et al. Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid antiin. ammatory drug. J Allergy Clin Immunol 2002; 110: 277-84.
  29. Papp K.A., Werfel T., Folster-Holst R. et al. Long-term control of atopic dermatitis with pimecrolimus cream 1% in infants and young children: a two-year study. JAm Acad Dermatol 2005; 52: 240-6.
  30. Paller A.S., Eicheneld L.F., Kirsner R.S., Shull T., Jaracz E., Simpson E.L. Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use. Pediatrics 2008; 122: e1210-8.
  31. Thaci D., Reitamo S., Gonzalez Ensenat M.A. et al. Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. Br J Dermatol 2008; 159: 1348-56.
  32. Ruer-Mulard M., Aberer W., Gunstone A. et al. Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis. Pediatr Dermatol 2009; 26: 551-8.
  33. Sigurgeirsson B., Boznanski A., Todd G. et al. Safety and ef.cacy of pimecrolimus in atopic dermatitis: a 5-year randomized trial. Pediatrics 2015; 135: 597-606.
  34. Ho V.C., Gupta A., Kaufmann R. et al. Safety and ef.cacy of nonsteroid pimecrolimus cream1%in the treatmentof atopic dermatitis in infants. J Pediatr 2003; 142: 155-62.
  35. Kaufmann R., Folster-Holst R., Hoger P. et al. Onset of action of pimecrolimus cream 1% in the treatment of atopic eczema in infants. J Allergy Clin Immunol 2004; 114: 1183-8.
  36. Lübbe J., Friedlander S.F., Cribier B. et al. Safety, ef.cacy, and dosage of 1% pimecrolimus cream for the treatment of atopic dermatitis in daily practice. Am J Clin Dermatol 2006; 7: 121-31.
  37. Ring J., Abraham A., de Cuyper C. et al. Control of atopic eczema with pimecrolimus cream 1% under daily practice conditions: results of a > 2000 patient study. J Eur Acad Dermatol Venereol 2008; 22: 195-203.
  38. McKenna S.P., Whalley D., de Prost Y. et al. Treatment of paediatric atopic dermatitis with pimecrolimus (Elidel, SDZ ASM 981): impact on quality of life and health-related quality of life. J Eur Acad Dermatol Venereol 2006; 20: 248-54.
  39. Whalley D., Huels J., McKenna S.P., Van Assche D. The bene.t of pimecrolimus (Elidel, SDZ ASM 981) on parents’ quality of life in the treatment of pediatric atopic dermatitis. Pediatrics 2002; 110: 1133-6.
  40. Staab D., Kaufmann R., Bräutigam M., Wahn U. Treatment of infants with atopic eczema with pimecrolimus cream 1% improves parents’ quality of life: a multicenter, randomized trial. Pediatr Allergy Immunol 2005; 16: 527-33.
  41. Lewis-Jones S. Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema. Int J Clin Pract 2006; 60: 984-92.
  42. Chamlin S.L., Chren M.M. Quality-of-life outcomes and measurement in childhood atopic dermatitis. Immunol Allergy Clin North Am 2010; 30: 281-8.
  43. Hani.n J.M., Boguniewicz M., Eichen.eld L. et al. A long-term study of safety and allergic comorbidity development in a randomized trial of pimecrolimus cream in infants with atopic dermatitis. J Invest Dermatol 2010: 130: Abstract 328.
  44. Langley R.G., Luger T.A., Cork M.J., Schneider D., Paul C. An update on the safety and tolerability of pimecrolimus cream 1%: evidence from clinical trials and post-marketing surveillance. Dermatology 2007; 215(Suppl 1): 27-44.
  45. McCollum A.D., Paik A., Eichen.eld L.F. The safety and ef.cacy of tacrolimus ointment in pediatric patients with atopic dermatitis. Pediatr Dermatol 2010; 27: 425-36.
  46. Paul C., Cork M., Rossi A.B., Papp K.A., Barbier N., de Prost Y. Safety and tolerability of 1% pimecrolimus cream among infants: experience with 1133 patients treated for up to 2 years. Pediatrics 2006; 117: e118-28.
  47. Eichen.eld L.F., Thaci D., de Prost Y., Puig L., Paul C. Clinical management of atopic eczema with pimecrolimus cream 1% (Elidel) in paediatric patients. Dermatology 2007; 215(Suppl 1): 3-17.
  48. Elidel (pimecrolimus cream 1%). US prescribing information. Novartis. 2010.
  49. Lakhanpaul M., Davies T., Allen B.R., Schneider D. Low systemic exposure in infants with atopic dermatitis in a 1-year pharmacokinetic study with pimecrolimus cream 1%*. Exp Dermatol 2006; 15: 138-41.
  50. Allen B.R., Lakhanpaul M., Morris A. et al. Systemic exposure, tolerability,andef.cacy of pimecrolimus cream 1% in atopic dermatitis patients. Arch Dis Child 2003; 88: 969-73.
  51. Harper J., Green A., Scott G. et al. First experience of topical SDZ ASM 981 in children with atopic dermatitis. Br J Dermatol 2001; 144: 781-7.
  52. Staab D., Pariser D., Gottlieb A.B. et al. Low systemicabsorptionand good tolerability of pimecrolimus, administered as 1% cream (Elidel) in infants with atopic dermatitis-a multicenter, 3-week, open-label study. Pediatr Dermatol 2005; 22: 465-71.
  53. Eichen.eld L.F., Ho V., Matsunaga J., Leclerc P., Paul C., Hani.n J.M. Blood concentrations, tolerability and ef.cacy of pimecrolimus cream 1% in Japanese infants and children with atopic dermatitis. J Dermatol 2007; 34: 231-6.
  54. Billich A., Aschauer H., Aszodi A., Stuetz A. Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus. Int J Pharm 2004; 269: 29-35.
  55. Turpeinen M., Salo O.P., Leisti S. Effect of percutaneous absorption of hydrocortisone Pediatric Allergy and Immunology 26 (2015) 306-315. 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Luger et al. Pimecrolimus in infants with AD on adrenocortical responsiveness in infants with severe skin disease. Br J Dermatol 1986; 115: 475-84.
  56. Hultsch T., Kapp A., Spergel J. Immunomodulation and safety of topical calcineurininhibitorsforthet-reatmentofatopic dermatitis. Dermatology 2005; 211: 174-87.
  57. Feldmann R.J., Maibach H.I. Regional variation in percutaneous penetration of 14C cortisol in man. J Invest Dermatol 1967; 48: 181-3.
  58. Papp K.A., Breuer K., Meurer M. et al. Longterm treatment of atopic dermatitis with pimecrolimus cream 1% in infants does not interfere with the development of protective antibodies after vaccination. J Am Acad Dermatol 2005; 52: 247-53.
  59. Stamatas G.N., Nikolovski J., Luedtke M.A., Kollias N., Wiegand B.C. Infant skin microstructure assessed in vivo differs from adult skin in organization and at the cellular level. Pediatr Dermatol 2010; 27: 125-31.
  60. Haapasaari K.M., Risteli J., Karvonen J., Oikarinen A. Effect of hydrocortisone, methylprednisolone aceponate and momethasone furoate on collagen synthesis in human skin in vivo. Skin Pharmacol 1997; 10: 261-4.
  61. Oikarinen A., Haapasaari K.M., Sutinen M., Tasanen K. The molecular basis of glucocorticoid-induced skin atrophy: topical glucocorticoid apparently decreases both collagen synthesis and the corresponding collagen mRNA level in human skin in vivo. Br J Dermatol 1998; 139: 1106-10.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2016 Namazova-Baranova L.S., Murashkin N.N., Materikin A.I., Ambarchyan E.T., Epishev R.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 60448 от 30.12.2014.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies