Efficacy of topical azathioprine and betamethasone versus betamethasone-only emollient cream in 2-18 years old patients with moderate-to-severe atopic dermatitis: A randomized controlled trial

Iraji, Fariba; Farhadi, Sadaf; Faghihi, Gita; Mokhtari, Fatemeh; Basiri, Akram; Jafari-Koshki, Tohid; Nilforoushzadeh, Mohammad Ali

Efficacy of topical azathioprine and betamethasone versus betamethasone-only emollient cream in 2-18 years old patients with moderate-to-severe atopic dermatitis: A randomized controlled trial

Authors

¹ Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

² Department of Dermatology, Isfahan University of Medical Sciences, Isfahan, Iran

³ Department of Biostatistics and Epidemiology, School of Health, Sabzevar University of Medical Sciences, Sabzevar, Iran

⁴ Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Atopic dermatitis is a chronic skin disease with increasing prevalence worldwide and a considerable burden especially among children. To circumvent the problems related to oral azathioprine (AZT) we aimed to evaluate its topical variant and assess its efficacy in patients aged 2-18.
Materials and Methods: In a single-blind trial, we randomized the patients into two groups, one treated with topical emollient containing AZT and betamethasone (BM), and the other treated solely with topical emollient of BM. The treatments were administered twice a day for 8 weeks in both groups. The efficacy, recurrence, and the presence of side effects were evaluated using SPSS 20.
Results: The amount of reduction in severity scoring for atopic dermatitis (SCORAD) score was significantly greater in the group treated with the topical AZT (P = 0.024). Incidentally, there were no difference between two treatments in difference in proportions of recurrence and adverse effects as well as SCORAD reduction in subgroups of sex and age (all P > 0.05).
Conclusions: Our results showed the superiority of topical AZT over BM with a low recurrence and adverse effects. No expectation of severe side effects, like those of oral AZT, is the major advantage of topical AZT. The sample size was an issue in uncovering the value of AZT in the subgroups. Conducting prolonged studies of quality-of-life and comparing the topical AZT potency relative to the common alternatives are recommended areas of future work.

Keywords

References

1.	Boguniewicz M, Leung DY. Atopic dermatitis: A disease of altered skin barrier and immune dysregulation. Immunol Rev 2011;242:233-46.
2.	Boguniewicz M, Eichenfield LF, Hultsch T. Current management of atopic dermatitis and interruption of the atopic march. J Allergy Clin Immunol 2003;112:S140-50.
3.	Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol 2003;112:S118-27.
4.	Barnetson RS, Rogers M. Childhood atopic eczema. BMJ 2002;324:1376-9.
5.	Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J 1995;8:483-91.
6.	Ben-Gashir MA, Seed PT, Hay RJ. Predictors of atopic dermatitis severity over time. J Am Acad Dermatol 2004;50:349-56.
7.	Diepgen TL. Atopic dermatitis: the role of environmental and social factors, the European experience. J Am Acad Dermatol 2001;45:S44-8.
8.	Dharmage SC, Lowe AJ, Matheson MC, Burgess JA, Allen KJ, Abramson MJ. Atopic dermatitis and the atopic march revisited. Allergy 2014;69:17-27.
9.	Asher MI, Montefort S, Björkstén B, Lai CK, Strachan DP, Weiland SK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368:733-43.
10.	Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol 2001;33:289-94.
11.	Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: A double-blind, randomised controlled trial. Lancet 2006;367:839-46.
12.	Buckley DA, Baldwin P, Rogers S. The use of azathioprine in severe adult atopic eczema. J Eur Acad Dermatol Venereol 1998;11:137-40.
13.	Murphy LA, Atherton D. A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Br J Dermatol 2002;147:308-15.
14.	Kuanprasert N, Herbert O, Barnetson RS. Clinical improvement and significant reduction of total serum IgE in patients suffering from severe atopic dermatitis treated with oral azathioprine. Australas J Dermatol 2002;43:125-7.
15.	Lipozenèiæ J, Wolf R. Atopic dermatitis: an update and review of the literature. Dermatol Clin 2007;25:605-12.
16.	Epstein JB, Gorsky M, Epstein MS, Nantel S. Topical azathioprine in the treatment of immune-mediated chronic oral inflammatory conditions: a series of cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:56-61.
17.	Tashtoush BM, Al-Safi SA, Al-Fanek KJ. Azathioprine transport through rat skin and its immunosuppressive effect. Pharmazie 2004;59:143-6.
18.	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;128:353-9.
19.	Hughes R, Collins P, Rogers S. Further experience of using azathioprine in the treatment of severe atopic dermatitis. Clin Exp Dermatol 2008;33:710-1.
20.	Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology 1993;186:23-31. [PUBMED]
21.	O'Connell EJ. The burden of atopy and asthma in children. Allergy 2004;59 Suppl 78:7-11.
22.	Su JC, Kemp AS, Varigos GA, Nolan TM. Atopic eczema: its impact on the family and financial cost. Arch Dis Child 1997;76:159-62.
23.	Kemp AS. Cost of illness of atopic dermatitis in children: a societal perspective. Pharmacoeconomics 2003;21:105-13.
24.	Kapp A, Papp K, Bingham A, Fölster-Holst R, Ortonne JP, Potter PC, et al. Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug. J Allergy Clin Immunol 2002;110:277-84.
25.	Van Der Meer JB, Glazenburg EJ, Mulder PG, Eggink HF, Coenraads PJ. The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. The Netherlands Adult Atopic Dermatitis Study Group. Br J Dermatol 1999;140:1114-21.
26.	Danby SG, Chittock J, Brown K, Albenali LH, Cork MJ. The effect of tacrolimus compared with betamethasone valerate on the skin barrier in volunteers with quiescent atopic dermatitis. Br J Dermatol 2014;170:914-21.
27.	Jensen JM, Pfeiffer S, Witt M, Bräutigam M, Neumann C, Weichenthal 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.
28.	Jensen JM, Scherer A, Wanke C, Bräutigam M, Bongiovanni S, Letzkus M, et al. Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis. Allergy 2012;67:413-23.
29.	Ricci G, Dondi A, Patrizi A, Masi M. Systemic therapy of atopic dermatitis in children. Drugs 2009;69:297-306.
30.	BuBmann C, Bieber T, Novak N. Systemic therapeutic options for severe atopic dermatitis. J Dtsch Dermatol Ges 2009;7:205-19.
31.	Gelbard CM, Hebert AA. New and emerging trends in the treatment of atopic dermatitis. Patient Prefer Adherence 2008;2:387-92.

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