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

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In Study V, eight (12%) patients used regular and two intermittent inhaled corticosteroids at baseline. The dose of the medication remained unchanged during the study. Inhaled corticosteroid was started for one patient by a pulmonologist outside the study after 6 months of tacrolimus treatment, otherwise no changes occurred in asthma medication during the follow-up. The clinical response to tacrolimus was significant in this group as well: BSA decreased from 26.8 ± 16.7 to 8.4 ± 7.7 (p=0.07). Eight patients showed increased BHR at baseline. No significant changes in BHR, sputum eosinophils, respiratory symptoms, or serum IgE were detectable. 54
DISCUSSION The main findings of four of the five studies (I, II, IV, and V) suggest that topical tacrolimus provides several favorable effects in the long-term treatment of AD. The clinical efficacy of topical tacrolimus was very good and sustained throughout the follow-up in all studies, with no marked safety issues, even after several years of intermittent monotherapy. Studies I, II, and V were conducted in the context of multicenter open-label long-term trials, the primary endpoint being the safety of topical tacrolimus in long-term treatment of AD. Although they included no randomized control groups, these studies are the first long-term studies to show significant improvement in staphylococcal colonization, suppression of skin collagen synthesis, and atopic respiratory symptoms, which are typical problems complicating AD and its treatment. Staphylococcus aureus colonization Superinfection with S. aureus is a common and potentially serious complication of AD, and S. aureus is believed to play an etiologic role in AD by release of superantigens. These superantigens are known to induce corticosteroid resistance by stimulating peripheral blood mononuclear cells. A different role for tacrolimus is supported by a study showing that FK506 (tacrolimus) inhibited SEB-induced peripheral blood mononuclear cell proliferation in vitro, whereas dexamethasone did not (Hauk & Leung 2001). The present study discovered a significant and sustained decrease in S. aureus colonization of the AD skin. At present, only one 6-month study with mometasone furoate has shown a decrease in S. aureus colonization in cleared patients (Faergemann et al. 2000). However, in contrast to the present findings, the effect was most marked at 3 weeks of treatment, an effect that weakened thereafter. The present results are similar to those in two short-term studies, one concerning 0.1% tacrolimus ointment in adults (Pournaras et al. 2002) and one 0.03% tacrolimus ointment in children (Park et al. 2005). Tacrolimus has no inhibitory effect on bacteria, including S. aureus. The healing of skin lesions, as demonstrated by the improvement in eczema score and improvement in skin barrier function, probably contributed to the decrease in staphylococcal colonization. The reduction in S. aureus colonization over the long-term suggests that tacrolimus has local immunomodulatory activities in the skin. In agreement with this, clinical long-term studies with tacrolimus ointment to date have shown no evidence of increased risk for bacterial or viral skin infections (Hanifin et al. 2005, Remitz et al. 2007). Reduction in the staphylococcal trigger may benefit patients with AD in the long term. 55
Page 1 and 2:
Topical tacrolimus in atopic dermat
Page 3: To Juha and Veera
Page 6 and 7: Effects of treatment on skin barrie
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 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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