THERAPEUTICS BJD British Journal of Dermatology 5-Methoxypsoralen plus ultraviolet (UV) A is superior to medium-dose UVA1 in the treatment of severe atopic dermatitis: a randomized crossover trial S. Tzaneva, H. Kittler,* G. Holzer, D. Reljic, M. Weber, H. Ho ¨nigsmann and A. Tanew Division of Special and Environmental Dermatology and *Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Wa ¨hringer Gu ¨rtel 18–20, 1090 Vienna, Austria  Seibersdorf Labor GmbH, 2444 Seibersdorf, Austria Correspondence Stanislava Tzaneva. E-mail: stanislava.tzaneva@meduniwien.ac.at Accepted for publication 10 September 2009 Key words atopic dermatitis, psoralen plus ultraviolet A, randomized crossover trial, ultraviolet A1 Conflicts of interest None declared. DOI 10.1111/j.1365-2133.2009.09514.x Summary Background Ultraviolet (UV) A1 and psoralen plus UVA (PUVA) are effective treat- ment options for severe atopic dermatitis (AD); however, their relative efficacy has not yet been determined in a head-to-head study. Objectives To compare UVA1 and oral 5-methoxypsoralen (5-MOP) plus UVA with respect to efficacy, tolerability and duration of response in patients with severe generalized AD. Methods Forty patients were included in this randomized observer-blinded cross- over trial. The patients received either 15 exposures to medium-dose UVA1 as the first treatment and, in cases of relapse, another 15 exposures to 5-MOP plus UVA as the second treatment, or vice versa. All patients were followed until 12 months after discontinuation of the last treatment. The SCORAD score was determined by a blinded investigator at baseline, after 10 and 15 treatments each and during the follow-up period. In addition, all adverse events were recorded during the whole study period. Results Twenty-three patients completed the crossover treatment. Both photothera- pies resulted in clinical improvement; however, PUVA reduced the baseline SCORAD score to a significantly greater extent than UVA1 (mean ± SD 54Æ3 ± 25Æ7% vs. 37Æ7 ± 22Æ8%; P =0Æ041). The median length of remission was 4 weeks (interquartile range 4–12) after UVA1 and 12 weeks (interquartile range 4–26) after PUVA therapy (P =0Æ012). Conclusions PUVA provides a better short- and long-term response than medium- dose UVA1 in patients with severe AD. Atopic dermatitis (AD) is an itchy, chronic inflammatory skin disease with an increasing prevalence worldwide, particularly in developed nations. 1,2 The pathophysiology of AD is com- plex and several genetic, immunological and environmental factors are thought to be involved. 3,4 Severe generalized AD often remains a therapeutic challenge both in terms of short- term improvement of the clinical condition and long-term control of the disease activity. Not infrequently, the use of topical treatments alone is not sufficient for managing patients with AD. Phototherapies are established and very potent treatment modalities for severe AD. Nowadays, mainly narrowband (NB) ultraviolet (UV) B, UVA1 and photochemotherapy (the com- bined use of psoralens and UVA, PUVA) are used for moderate to severe AD. It has been shown that medium-dose (single exposure doses of 50–70 J cm )2 ) UVA1 is superior to UVA ⁄ UVB and that UVA1 and NB UVB are equally effective in the management of AD. 5–8 Most studies on UVA1 have demon- strated a rapid improvement of AD upon UVA1 treatment. However, not all patients respond to UVA1 and improvement is often followed by early relapse. 5–11 In older trials PUVA was found to be highly effective in patients with AD; however, there are no recent controlled trials on oral PUVA. 12–17 Fur- thermore, PUVA and UVA1 have never been compared directly in a head-to-head study. We therefore initiated a prospective randomized investigator-blinded crossover trial to evaluate these two phototherapeutic modalities with regard to efficacy, tolerability and length of treatment-induced remission. Ó 2009 The Authors Journal Compilation Ó 2009 British Association of Dermatologists • British Journal of Dermatology 2010 162, pp655–660 655