Topical tacrolimus in atopic dermatitis: Effects of ... - Helda - Helsinki.fi

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Effects of treatment on skin barrier function .............................................................. 33� Skin atrophy and collagen synthesis of the skin ......................................................... 33� Effects of glucocorticosteroids on skin collagen synthesis......................................... 34� Effects of AD treatment on skin infections................................................................. 37� AIMS OF THE STUDY............................................................................................................ 38� SUBJECTS AND METHODS.................................................................................................. 39� Study designs ..................................................................................................................... 39� Subjects .............................................................................................................................. 39� Inclusion criteria ......................................................................................................... 40� Exclusion criteria ........................................................................................................ 40� Methods.............................................................................................................................. 42� Treatment with tacrolimus ointment........................................................................... 42� Assessment of atopic dermatitis ................................................................................. 42� Staphylococcus aureus colonization ........................................................................... 43� Skin collagen synthesis and skin thickness................................................................. 43� Respiratory symptoms and findings ........................................................................... 44� Lung function tests ............................................................................................. 44� Questionnaire...................................................................................................... 44� Induced sputum .................................................................................................. 44� Skin prick tests and serum IgE ........................................................................... 45� Conjunctival cytology................................................................................................. 45� Statistical methods...................................................................................................... 46� RESULTS................................................................................................................................... 47� Clinical efficacy and safety............................................................................................... 47� Staphylococcus aureus colonization ................................................................................ 48� Skin collagen synthesis and skin thickness ..................................................................... 48� Conjunctival cytology ....................................................................................................... 49� Respiratory symptoms and findings................................................................................ 49� Respiratory symptoms ................................................................................................ 50� Bronchial hyper-responsiveness ................................................................................. 50� Induced sputum........................................................................................................... 51� Skin prick tests and serum IgE ................................................................................... 52� Patients on inhaled corticosteroids.................................................................................. 53� DISCUSSION ............................................................................................................................ 55� ACKNOWLEDGEMENTS...................................................................................................... 62� REFERENCES.......................................................................................................................... 64� Appendix: ORIGINAL PUBLICATIONS
LIST OF ORIGINAL PUBLICATIONS The thesis is based on the following original articles, which are cited in the text by their Roman numerals: I. Remitz A, Kyllönen H, Granlund H, Reitamo S: Tacrolimus ointment reduces staphylococcal colonization of atopic dermatitis lesions. J Allergy Clin Immunol 107:196-197, 2001. II. Kyllönen H, Remitz A, Mandelin JM, Elg P, Reitamo S. Effect of one-year intermittent treatment with topical tacrolimus monotherapy on skin collagen synthesis in patients with atopic dermatitis. Br J Dermatol 150:1174-1181, 2004. III. Kyllönen H, Malmberg P, Remitz A, Rytilä P, Metso T, Helenius I, Haahtela T, Reitamo S. Respiratory symptoms, bronchial hyper-responsiveness, and eosinophilic airway inflammation in patients with moderate-to-severe atopic dermatitis. Clin Exp Allergy 36:192-197, 2006. IV. Virtanen H, Kari O, Kari M, Reitamo S. Tacrolimus ointment in the treatment of atopic blepharoconjuntivitis. A retrospective study. Acta Ophth Scand. 84:693-695, 2006. V. Virtanen H, Remitz A, Malmberg P, Rytilä P, Metso T, Haahtela T, Reitamo S. Topical tacrolimus for atopic dermatitis. Does it benefit the airways? A four-year follow-up. J Allergy Clin Immunol 120:1464-1466, 2007. Reprinted with the publishers’ permission. Some previously unpublished data are also presented. 7
Page 1 and 2: Topical tacrolimus in atopic dermat
Page 3: To Juha and Veera
Page 8 and 9: ABBREVIATIONS AD Atopic dermatitis
Page 10 and 11: and bronchial hyper-responsiveness
Page 12 and 13: REVIEW OF THE LITERATURE Atopic der
Page 14 and 15: probably plays a protective role ag
Page 16 and 17: e induced by IL-2 and bacterial sup
Page 18 and 19: and has a lower risk for asthma and
Page 20 and 21: Both asthma and allergic rhinitis i
Page 22 and 23: early childhood, and is accompanied
Page 24 and 25: naturally occurring glucocorticoste
Page 26 and 27: severe atopic dermatitis, hand ecze
Page 28 and 29: and their complex inhibits activati
Page 30 and 31: extent of topical absorption decrea
Page 32 and 33: of one type of treatment can be bet
Page 34 and 35: liver (Burgeson & Nimni 1992). At l
Page 36 and 37: UVA therapy suppresses collagen syn
Page 38 and 39: AIMS OF THE STUDY Atopic dermatitis
Page 40 and 41: Inclusion criteria Patients with mo
Page 42 and 43: Methods Treatment with tacrolimus o
Page 44 and 45: Respiratory symptoms and findings T
Page 46 and 47: Statistical methods In Studies I, I
Page 48 and 49: Staphylococcus aureus colonization
Page 50 and 51: Table 7. Subject characteristics; o
Page 52 and 53: physician-diagnosed asthma (2.09 vs
Page 54 and 55: In Study V, eight (12%) patients us
Page 56 and 57:
Skin collagen synthesis The results
Page 58 and 59:
Results of the present uncontrolled
Page 60 and 61:
al. 1986, Burrows et al. 1989, Kono
Page 62 and 63:
ACKNOWLEDGEMENTS This study was car
Page 64 and 65:
REFERENCES Aberer W, Wolff K. Syste
Page 66 and 67:
Bousquet J; Jeffery PK, Busse WW, J
Page 68 and 69:
Dold S, Wjst M, von Mutius E, Reitm
Page 70 and 71:
Haapasaari K. Rossi O. Risteli J. O
Page 72 and 73:
Krutmann JT, Morita A. Phototherapy
Page 74 and 75:
Nishino K, Fukushima A, Okamoto S,
Page 76 and 77:
Quanjer PH, Tammeling GJ, Cotes JE,
Page 78 and 79:
Schultz-Larsen F, Diepgen T, Svenso
Page 80 and 81:
Tsai WC, Pang JH, Hsu CC, Chu NK, L
Page 82:
ERRATA Page 36: In Table 2 in the c
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