Cross-sectional evaluation of acute adverse reactions during ultraviolet A1 phototherapy

Dear Editor, Phototherapy with ultraviolet A1 (UVA1) can induce durable remissions in sclerosing disorders such as morphoea.1 Optimal UVA1 dosing remains an area of research.2,3,4 Acute adverse reactions to UVA1 include erythema, pruritus and polymorphic light eruption (PMLE).5 The acute adverse reaction rate during UVA1 phototherapy has been reported to be as high as 15%, half of which was attributable to erythema.6 However, other articles report minimal acute UVA1 toxicity.7 Our objectives were to report on the chronology of acute adverse reactions and to identify associated factors. A chart review of patients who received UVA1 phototherapy at the Vancouver General Hospital Phototherapy Center was conducted for the period between June 2009 and April 2015 (University of British Columbia Ethics Review Board, Protocol H13‐01989). Demographic, clinical and UVA1 treatment data were captured. Adverse reactions (erythema, pruritus, PMLE, other rashes) were extracted from the charts. For the purpose of this study, each treatment exposure of UVA1 phototherapy was defined as a single medium (40–90 J cm−2) or high‐dose (100–130 J cm−2) exposure, and each treatment course was defined as 20–40 consecutive exposures. Our facility uses a metal halide full‐body unit to deliver UVA1 phototherapy [ML24000™ (Daavlin, Bryan, OH, U.S.A.)]. Treatments were given at constant doses throughout courses, scheduled 5 days per week and could be repeated after 6 months, up to three times. Prior to the first UVA1 course, minimal erythema dose (MED) testing to UVA1 was performed on the majority of patients. Nearly all patients were treated with medium‐dose UVA1 for the entire first course; if they had a partial response, a high‐dose course was considered. When adverse reactions occurred, therapeutic adjustments were left at the discretion of the supervising physician. To analyse if adverse events were more frequent in either half of the treatment in each course, the Wilcoxon test was performed. For binary end points, logistic regression analyses were performed and for count end points, Poisson regressions were carried out. The regression analyses were performed for treatment courses using the random‐effects model with Stata version 9 (StatCorp., College Station, TX, U.S.A.). Seventy‐two UVA1 phototherapy courses were administered, corresponding to 1581 exposures. The mean age was 45 years, the majority of patients were white (n = 49) and they were treated for morphoea (n = 47). Most patients had a MED to UVA1 of ≥ 130 J cm−2 (n = 55). Fifty‐seven medium‐dose and 15 high‐dose courses were administered. Rates of adverse reactions to UVA1 phototherapy are summarized in Table 1. Of note, there were no severe adverse reactions such as blistering or herpes simplex reactivation. At least one episode of erythema occurred in 29% of courses. Because PMLE persisted over many exposures during a course, it was the adverse reaction reported over the most exposures (4%). Significantly more adverse reactions occurred in the first half of courses (Wilcoxon test, P = 0·020 for first courses; P = 0·016 for second courses). Age, sex, ethnicity, phototype, diagnosis, MED to UVA1, course iteration (first, second or third) and number of exposures given were not statistically significant variables in the regression models. High‐dose UVA1 was significantly associated with any adverse reactions [odds ratio (OR) 20·33, 95% confidence interval (CI) 2·66–155·61], any erythema (OR 17·81, 95% CI 2·91–108·84) and number of episodes of erythema (OR 3·78, 95% CI 1·84–7·77). Adverse reactions occurring during ultraviolet A1 phototherapy Data are n (%). PMLE, polymorphic light eruption. Adverse reactions occurring during ultraviolet A1 phototherapy Data are n (%). PMLE, polymorphic light eruption. Adverse event rates are higher in our study than those previously reported in the literature.6 Our facility administers UVA1 phototherapy five times per week on consecutive days at a stable dose. The rationale for this treatment regimen is to maximize the delivery of UVA1 before a photoprotective tanning response occurs.8 Accumulation of radiation on consecutive days may increase the likelihood of development of erythema. In this study, 44% of UVA1 phototherapy courses had at least one acute adverse reaction, but overall the majority of individual treatment exposures were uneventful. We suspected adverse reactions during UVA1 phototherapy to cluster during the first half of treatment, and statistically this was confirmed in our study population. We also wondered if lower MEDs to UVA1 (< 130 J cm−2) could be linked with the development of acute adverse reactions and analyses did not reveal an association, but only nine patients had MEDs to UVA1 < 130 J cm−2. We continue to recommend routine MEDs to UVA1 prior to starting UVA1 phototherapy. Our study is limited by its small sample size, cross‐sectional nature and tertiary care centre setting. Another limitation of this study is its focus on acute toxicity rather than chronic toxicity or therapeutic effect. Clinical benefit of UVA1 phototherapy was observed in 82%, and we believe this has the potential to outweigh the adverse effects experienced by patients. In this study, most acute adverse events occurred during the first half of UVA1 phototherapy courses and high‐dose UVA1 was associated with more acute toxicity than medium‐dose UVA1. As the optimal UVA1 dosing regimens are further delineated, understanding the chronology and factors associated with increased acute toxicity can help guide clinical decision‐making. We would like to thank Dr Michael Schulzer and Mr Edwin Mak for their contribution to the statistical analysis. Funding sources: none. Conflicts of interest: none declared.

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