Ann Dermatol.  2012 Aug;24(3):253-260. 10.5021/ad.2012.24.3.253.

Long Term Treatment Concepts and Proactive Therapy for Atopic Eczema

Affiliations
  • 1Department of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany. wollenberg@lrz.uni-muenchen.de

Abstract

Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized.

Keyword

Atopic eczema; Emollients; Flare prevention; Proactive treatment; Topical calcineurin inhibitors; Topical corticosteroids

MeSH Terms

Adrenal Cortex Hormones
Anti-Inflammatory Agents
Biological Agents
Calcineurin
Dermatitis, Atopic
Emollients
Humans
Inflammation
Off-Label Use
Running
Skin
Skin Diseases
Ultraviolet Rays
Adrenal Cortex Hormones
Anti-Inflammatory Agents
Biological Agents
Calcineurin
Emollients

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Reference

1. Darsow U, Wollenberg A, Simon D, Taïeb A, Werfel T, Oranje A, et al. European Task Force on Atopic Dermatitis/EADV Eczema Task Force. ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol. 2010. 24:317–328.
Article
2. Ring J, Alomar A, Bieber T, Deleuran M, Fink-Wagner A, Gelmetti C, et al. Guidelines for Treatment of Atopic Eczema (Atopic Dermatitis). J Eur Acad Dermatol Venereol. 2011. In press.
3. Ring J, Darsow U. Plewig G, Wolff HH, Burgdorf WH, Landthaler M, editors. Dermatitis. Braun-Falco's Dermatology. 2008. Berlin: Springer.
4. Darsow U, Lübbe J, Taïeb A, Seidenari S, Wollenberg A, Calza AM, et al. European Task Force on Atopic Dermatitis. Position paper on diagnosis and treatment of atopic dermatitis. J Eur Acad Dermatol Venereol. 2005. 19:286–295.
Article
5. Reitamo S, Rustin M, Ruzicka T, Cambazard F, Kalimo K, Friedmann PS, et al. European Tacrolimus Ointment Study Group. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol. 2002. 109:547–555.
Article
6. Reitamo S, Wollenberg A, Schöpf E, Perrot JL, Marks R, Ruzicka T, et al. The European Tacrolimus Ointment Study Group. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. Arch Dermatol. 2000. 136:999–1006.
Article
7. Ogawa H, Yoshiike T. Atopic dermatitis: studies of skin permeability and effectiveness of topical PUVA treatment. Pediatr Dermatol. 1992. 9:383–385.
Article
8. Proksch E, Fölster-Holst R, Jensen JM. Skin barrier function, epidermal proliferation and differentiation in eczema. J Dermatol Sci. 2006. 43:159–169.
Article
9. Werner Y, Lindberg M. Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis. Acta Derm Venereol. 1985. 65:102–105.
10. Wollenberg A, Frank R, Kroth J, Ruzicka T. Proactive therapy of atopic eczema--an evidence-based concept with a behavioral background. J Dtsch Dermatol Ges. 2009. 7:117–121.
Article
11. Weidinger S, O'Sullivan M, Illig T, Baurecht H, Depner M, Rodriguez E, et al. Filaggrin mutations, atopic eczema, hay fever, and asthma in children. J Allergy Clin Immunol. 2008. 121:1203–1209.
Article
12. Macheleidt O, Kaiser HW, Sandhoff K. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol. 2002. 119:166–173.
Article
13. Mihm MC Jr, Soter NA, Dvorak HF, Austen KF. The structure of normal skin and the morphology of atopic eczema. J Invest Dermatol. 1976. 67:305–312.
Article
14. Wollenberg A, Räwer HC, Schauber J. Innate immunity in atopic dermatitis. Clin Rev Allergy Immunol. 2011. 41:272–281.
Article
15. Wollenberg A, Wen S, Bieber T. Phenotyping of epidermal dendritic cells: clinical applications of a flow cytometric micromethod. Cytometry. 1999. 37:147–155.
Article
16. Wollenberg A, Bieber T. Proactive therapy of atopic dermatitis--an emerging concept. Allergy. 2009. 64:276–278.
17. Van Der Meer JB, Glazenburg EJ, Mulder PG, Eggink HF, Coenraads PJ. The Netherlands Adult Atopic Dermatitis Study Group. The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. Br J Dermatol. 1999. 140:1114–1121.
Article
18. Wollenberg A. Proaktive und reaktive Behandlungsansätze der Neurodermitis mit differenten Externa. J Dtsch Dermatol Ges. 2007. 5:Suppl 2. 105.
19. Frankl VE. Der Mensch auf der Suche nach Sinn. 1972. Stuttgart: Ernst Klett Verlag.
20. Hanifin J, Gupta AK, Rajagopalan R. Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol. 2002. 147:528–537.
Article
21. Berth-Jones J, Damstra RJ, Golsch S, Livden JK, Van Hooteghem O, Allegra F, et al. Multinational Study Group. Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study. BMJ. 2003. 326:1367.
Article
22. Glazenburg EJ, Wolkerstorfer A, Gerretsen AL, Mulder PG, Oranje AP. Efficacy and safety of fluticasone propionate 0.005% ointment in the long-term maintenance treatment of children with atopic dermatitis: differences between boys and girls? Pediatr Allergy Immunol. 2009. 20:59–66.
Article
23. Peserico A, Städtler G, Sebastian M, Fernandez RS, 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. 158:801–807.
Article
24. Wollenberg A, Reitamo S, Girolomoni G, Lahfa M, Ruzicka T, Healy E, et al. European Tacrolimus Ointment Study Group. Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy. 2008. 63:742–750.
Article
25. Thaçi D, Reitamo S, Gonzalez Ensenat MA, Moss C, Boccaletti V, Cainelli T, et al. European Tacrolimus Ointment Study Group. Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. Br J Dermatol. 2008. 159:1348–1356.
Article
26. Reitamo S, Allsopp R. Treatment with twice-weekly tacrolimus ointment in patients with moderate to severe atopic dermatitis: results from two randomized, multicentre, comparative studies. J Dermatolog Treat. 2010. 21:34–44.
Article
27. Paller AS, Eichenfield LF, Kirsner RS, Shull T, Jaracz E, Simpson EL. US Tacrolimus Ointment Study Group. Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use. Pediatrics. 2008. 122:e1210–e1218.
Article
28. Breneman D, Fleischer AB Jr, Abramovits W, Zeichner J, Gold MH, Kirsner RS, et al. Tacrolimus Ointment Study Group. Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. J Am Acad Dermatol. 2008. 58:990–999.
Article
29. Wollenberg A, Sidhu MK, Odeyemi I, Dorsch B, Koehne-Volland R, Schaff M, et al. Economic evaluation of maintenance treatment with tacrolimus 0.1% ointment in adults with moderate to severe atopic dermatitis. Br J Dermatol. 2008. 159:1322–1330.
Article
30. Aly R, Maibach HI, Shinefield HR. Microbial flora of atopic dermatitis. Arch Dermatol. 1977. 113:780–782.
Article
31. Wollenberg A, Schnopp C. Evolution of conventional therapy in atopic dermatitis. Immunol Allergy Clin North Am. 2010. 30:351–368.
Article
32. Gauger A, Fischer S, Mempel M, Schaefer T, Foelster-Holst R, Abeck D, et al. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. J Eur Acad Dermatol Venereol. 2006. 20:534–541.
Article
33. Koller DY, Halmerbauer G, Böck A, Engstler G. Action of a silk fabric treated with AEGIS in children with atopic dermatitis: a 3-month trial. Pediatr Allergy Immunol. 2007. 18:335–338.
Article
34. Stinco G, Piccirillo F, Valent F. A randomized double-blind study to investigate the clinical efficacy of adding a non-migrating antimicrobial to a special silk fabric in the treatment of atopic dermatitis. Dermatology. 2008. 217:191–195.
Article
35. Huang JT, Abrams M, Tlougan B, Rademaker A, Paller AS. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics. 2009. 123:e808–e814.
Article
36. Gauger A, Mempel M, Schekatz A, Schäfer T, Ring J, Abeck D. Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Dermatology. 2003. 207:15–21.
Article
37. Dotterud LK, Wilsgaard T, Vorland LH, Falk ES. The effect of UVB radiation on skin microbiota in patients with atopic dermatitis and healthy controls. Int J Circumpolar Health. 2008. 67:254–260.
Article
38. Griffiths CE, Katsambas A, Dijkmans BA, Finlay AY, Ho VC, Johnston A, et al. Update on the use of ciclosporin in immune-mediated dermatoses. Br J Dermatol. 2006. 155:Suppl 2. 1–16.
Article
39. Hijnen DJ, ten Berge O, Timmer-de Mik L, Bruijnzeel-Koomen CA, de Bruin-Weller MS. Efficacy and safety of long-term treatment with cyclosporin A for atopic dermatitis. J Eur Acad Dermatol Venereol. 2007. 21:85–89.
Article
40. Berth-Jones J, Finlay AY, Zaki I, Tan B, Goodyear H, Lewis-Jones S, et al. Cyclosporine in severe childhood atopic dermatitis: a multicenter study. J Am Acad Dermatol. 1996. 34:1016–1021.
Article
41. Norgauer J, Schwarting A, Termeer C, Werfel T, Wollenberg A. Cyclosporin A. Systemische Therapie der Psoriasis und des atopischen Ekzems. Thieme Praxis Report. 2011. 3.
42. Schmitt J, von Kobyletzki L, Svensson A, Apfelbacher C. Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials. Br J Dermatol. 2011. 164:415–428.
Article
43. Bieber T. Atopic dermatitis. Ann Dermatol. 2010. 22:125–137.
Article
44. Liu HN, Wong CK. In vitro immunosuppressive effects of methotrexate and azathioprine on Langerhans cells. Arch Dermatol Res. 1997. 289:94–97.
Article
45. Hon KL, Ching GK, Leung TF, Chow CM, Lee KK, Ng PC. Efficacy and tolerability at 3 and 6 months following use of azathioprine for recalcitrant atopic dermatitis in children and young adults. J Dermatolog Treat. 2009. 20:141–145.
Article
46. Grundmann-Kollmann M, Podda M, Ochsendorf F, Boehncke WH, Kaufmann R, Zollner TM. Mycophenolate mofetil is effective in the treatment of atopic dermatitis. Arch Dermatol. 2001. 137:870–873.
47. Benez A, Fierlbeck G. Successful long-term treatment of severe atopic dermatitis with mycophenolate mofetil. Br J Dermatol. 2001. 144:638–639.
Article
48. Grundmann-Kollmann M, Korting HC, Behrens S, Leiter U, Krähn G, et al. Successful treatment of severe refractory atopic dermatitis with mycophenolate mofetil. Br J Dermatol. 1999. 141:175–176.
Article
49. Bangert CA, Costner MI. Methotrexate in dermatology. Dermatol Ther. 2007. 20:216–228.
Article
50. Schram ME, Roekevisch E, Leeflang MM, Bos JD, Schmitt J, Spuls PI. A randomized trial of methotrexate versus azathioprine for severe atopic eczema. J Allergy Clin Immunol. 2011. 128:353–359.
Article
51. Goujon C, Bérard F, Dahel K, Guillot I, Hennino A, Nosbaum A, et al. Methotrexate for the treatment of adult atopic dermatitis. Eur J Dermatol. 2006. 16:155–158.
52. Weatherhead SC, Wahie S, Reynolds NJ, Meggitt SJ. An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema. Br J Dermatol. 2007. 156:346–351.
Article
53. Buka RL, Resh B, Roberts B, Cunningham BB, Friedlander S. Etanercept is minimally effective in 2 children with atopic dermatitis. J Am Acad Dermatol. 2005. 53:358–359.
Article
54. Jacobi A, Antoni C, Manger B, Schuler G, Hertl M. Infliximab in the treatment of moderate to severe atopic dermatitis. J Am Acad Dermatol. 2005. 52:522–526.
Article
55. Oldhoff JM, Darsow U, Werfel T, Katzer K, Wulf A, Laifaoui J, et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy. 2005. 60:693–696.
Article
56. Forman SB, Garrett AB. Success of omalizumab as monotherapy in adult atopic dermatitis: case report and discussion of the high-affinity immunoglobulin E receptor, FcepsilonRI. Cutis. 2007. 80:38–40.
57. Lane JE, Cheyney JM, Lane TN, Kent DE, Cohen DJ. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol. 2006. 54:68–72.
Article
58. Simon D, Hösli S, Kostylina G, Yawalkar N, Simon HU. Anti-CD20 (rituximab) treatment improves atopic eczema. J Allergy Clin Immunol. 2008. 121:122–128.
Article
59. Werfel T, Breuer K, Ruéff F, Przybilla B, Worm M, Grewe M, et al. Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study. Allergy. 2006. 61:202–205.
Article
60. Kupfer J, Gieler U, Diepgen TL, Fartasch M, Lob-Corzilius T, Ring J, et al. Structured education program improves the coping with atopic dermatitis in children and their parents-a multicenter, randomized controlled trial. J Psychosom Res. 2010. 68:353–358.
Article
61. Grahovac M, Molin S, Prinz JC, Ruzicka T, Wollenberg A. Treatment of atopic eczema with oral alitretinoin. Br J Dermatol. 2010. 162:217–218.
Article
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