Phototherapy with Narrow-Band UVB in Adult Guttate Psoriasis: Results and Patient Assessment

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1 Original Paper Dermatology 206;232: Received: December 6, 205 Accepted after revision: August 3, 206 Published online: November 25, 206 Phototherapy with Narrow-Band UVB in Adult Guttate Psoriasis: Results and Patient Assessment Montserrat Fernández-Guarino Sonsoles Aboín-González Diana Velázquez Lucia Barchino Natividad Cano Pablo Lázaro Department of Dermatology, Hospital Universitario Sanitas La Zarzuela, Madrid, Spain Key Words Psoriasis Phototherapy Narrow-band UVB Treatment Abstract Background: Acute guttate psoriasis (AGP) is a distinctive clinical entity with good response to treatment with narrowband ultraviolet B (NB-UVB). Objective: To investigate the results of NB-UVB phototherapy in adult patients with adult guttate psoriasis. Material and Methods: We carried out a prospective, open, and observational study. Patients over 8 years with more than 5% of body surface area affected were included. The PASI was assessed prior to and after treatment. The follow-up period was 8 months. After treatment, patients completed a simple questionnaire to assess their overall impression of the treatment. Results: The 67 adult patients with AGP included in this study had an initial PASI of 8.55 (SD 5.03). Patients were treated with a mean of 9.9 sessions (SD 3.5) and mean doses of 4 mj/cm 2 (SD 0.5). Of the 67 patients, 52 achieved PASI90 with 96.5% of PASI reduction, and of these, 46 (88%) maintained PASI90 during the 8 months of follow-up. Patients were very satisfied with the treatment. Discussion: AGP is a defined clinical entity with a variable course. Phototherapy with NB-UVB appears to be a very good option for treatment of AGP because of the good results obtained and patient satisfaction. Introduction 206 S. Karger AG, Basel Guttate psoriasis is a distinctive acute form of psoriasis, which is more frequent in children and young adults. It can be the first manifestation of psoriasis (acute guttate psoriasis, AGP) or an acute flare of a preexisting chronic plaque psoriasis []. The prevalence of psoriasis varies worldwide. The prevalence of psoriasis is 2% in Caucasians, and the prevalence of AGP is 4% of the clinical types of psoriasis [2]. AGP is strongly associated with preceding streptococcal infection which is found in the majority of the patients (clinical symptoms, positive serologies or cultures) [3]. It is accepted that AGP has a better prognosis than other forms of psoriasis; however, the eruption may cure spontaneously or progress into chronic plaque psoriasis or reoccur after some months or years []. The varied clinical picture of this well-defined clinical entity karger@karger.com S. Karger AG, Basel /6/ $39.50/0 Montserrat Fernández Guarino Avenida Ferrol 3, 3-2 ES Madrid (Spain) msn.com

2 Phototherapy with NB-UVB in AGP Patients included Older than 8 years With AGP (acute flare of their disease with plaques <3 cm) Without a history of a previous plaque psoriasis With more than 5% of BSA affected Primary outcome Number of patients achieving PASI90 Data collected Demographic data: age, sex, number of previous flares, age of onset of the psoriasis, history of pharyngitis or vaccination in the month prior to the flare, family history of psoriasis PASI before and after treatment with NB-UVB PASI 8 months after treatment Patient assessment, visual analog scale (0 0) Treatment protocol Phototherapy booth 33 nm UV 7002 (Waldmann, Villingen-Schwenningen, Germany) Three times a week Following patients skin phototype Each dose of irradiation was increased by 0% if there was no erythema Session 30 without PASI90 reached: suspended treatment Statistical analysis Fig.. Flowchart of the Material and Methods. BSA, body surface area. SPSS (IBM, New York, NY, USA) for Windows 2.0 Categorical data: 2 test Continuous data: Student t test p < 0.05 indicates statistical significance has led to a number of studies of possible triggers and its evolution over the years [4 6]. According to guidelines for the treatment of psoriasis, the first line of treatment for psoriasis involving more than 5% of body surface area is ultraviolet phototherapy (preferably narrow-band ultraviolet B, NB-UVB), either alone or in combination with methotrexate or acitretin [7 9]. AGP has been demonstrated to respond to NB- UVB better than other forms of psoriasis [0, ], but there is no consensus for the best treatment of AGP. There is little guidance in the literature as to how this distinctive form of psoriasis should be treated. Recently, a systematic review of intervention in AGP concluded that there is no firm evidence to make any recommendation for the routine treatment of AGP [2]. Most of the studies published about phototherapy in AGP are in children, and only a few of them used the PASI, which is the most studied and validated score to assess the severity of psoriasis, but it has not been assessed in AGP. The PASI was shown in a recent systematic review to be the best outcome measure, and so PASI75 and PASI90 are the most used scores in the recent studies about the treatment of psoriasis [7, 8, 2]. NB-UVB in Adult Guttate Psoriasis Dermatology 206;232:

3 n = 67 (adult patients with AGP) PASI: 8.5 ±5.03; sessions/doses: 9.9 ± 3.5/4 ± 0.5 mj/cm 2 ; PASI reduction: 88.2% CR or PASI90 = 52 (78%) PASI reduction = 96.5% PASI 7.9 ± 4.6; sessions/doses: 9.2 ± 8.5/4 ± 9. mj/cm 2 IR or not PASI90 = 0 (5%) PASI90 = 0% PASI reduction = 42% PASI: 0.4 ± 5.9; sessions/doses: 29.8 ±.8/2.5 ± 5.4 mj/cm 2 Lost to treatment n = 5 (7%) PASI:.4 ± 6.2; sessions/doses: 7.8 ± 4.7/5.6 ± 2.0 mj/cm 2 Color version available online CR or PASI90 after discontinuation = 46 (88%) PASI: 7.9 ± 3.93; sessions/doses: 8.7 ± 7.2/2.6 ± 8.6 mj/cm 2 Fig. 2. Results of the treatment (mean ± SD). Relapse n = 6 (2%) PASI: 8.25 ± 4.3; sessions/doses: 22.8 ± 7.9/20.3 ± 8.9 mj/cm 2 ; relapse: 3.2 months In this article we studied the results of phototherapy with NB-UVB in adult AGP, collected possible triggers, family history and clinical course. Finally, we assessed the patient satisfaction with treatment. Material and Methods For further details, see the supplementary materials (for all online suppl. material, see (Fig. ) [9, 3]. Results A total 67 adult patients with AGP were included in this study with an initial PASI of 8.55 (SD = 503) (see Fig. 2 ). Patients were treated with a mean of 9.9 (SD = 3.5) sessions and a mean dose of 4 mj/cm 2 (SD = 0.5) with a PASI reduction of 88%. A total of 52 out of 67 (78%) achieved complete response (CR) or PASI90, 0 out of 67 (5%) did not reach PASI90 (5%), and 5 out of 67 (7%) were lost to treatment. Among the 52 patients with CR or PASI90, a PASI reduction of 96.5% was obtained. Their initial PASI was 7.9 (SD = 4.6), and they received 9.2 (SD = 8.5) sessions with a cumulative dose of 4 mj/cm 2 (SD = 9.). A total of 46 (88%) of the patients with CR (46/52) maintained PASI90 during an 8-month follow-up period, and 6 of them (2%) lost PASI90 in 3.2 months. A total of 0 patients out of 67 (5%) did not reach PASI90 and obtained a PASI reduction of 42%. Nonresponder patients (incomplete response, IR) presented an initial PASI of 0.4 (SD = 5.9) and received 29.8 (SD =.77) sessions with a cumulative dose of 2.5 mj/cm 2 (SD = 5.4). Table summarizes the characteristics of the 2 groups of patients together with those patients lost to treatment: responders, nonresponders and lost to treatment. Patients who were lost to treatment were all women who had difficulties in coming to the hospital and did not complete the sessions for different reasons. One of them suffered a polymorphic solar eruption during treatment which had to be interrupted. However, most of the patients would repeat the treatment and assessed a global satisfaction of 7.4 out of 0. The differences in the variables measured between responders and nonresponders can be seen in the first 2 columns of Table. A summary of the statistical significance is shown in Table 2. Patients with CR had a mean age of onset of 26.7 years (range 8 58) with a mean of 4.82 years of evolution (range 0 7), and nonresponders had a mean age of 35.2 years at the onset (range 26 37) and a mean of 4.2 years of evolution (range 0 37). The difference in the age of onset and the years of evolution of the AGP previous to treatment was statistically significant (Student t test, p > 0.05, Table 2 ). Patients with CR were 22 males and 30 females (42/64%), 22 (42%) had had only flare and 30 (64%) 2 or more flares, and 24/52 (46%) had a family history of psoriasis. Patients with IR were 4 males and 6 females (40/60%), of them had had only flare (0%), and 2 had a family history of psoriasis (20%). No statistical differences were found between 628 Dermatology 206;232: Fernández-Guarino/Aboín-González/ Velázquez/Barchino/Cano/Lázaro

4 Table. Characteristics and assessment of the patients with respect to response to treatment CR/PASI90 (n = 52) IR/not PASI90 (n = 0) Lost to treatment (n = 5) Total (n = 67) Mean age of onset, years 26.7 (8 58) 34.9 (26 39) Age of treatment, years 33.9 (8 58) 35.2 (26 57) Male/female ratio 22/30 (42/64%) 4/6 (40/60%) 0/5 26/4 Time of evolution since the diagnosis, years 4.82 (0 7) 4.2 (0 37) Number of previous flares 2 >2 or always affected 22 (42%) 7 (4%) 23 (50%) (36%) 8 (%) 35 (53%) Pharyngitis or vaccination 36 (69%) 2 (20%) 3 (60%) 4 (6%) Family history Psoriasis Atopic dermatitis None 24 (46%) 3 (25%) 5 (29%) 8 (80%) 2 (20%) (50.7%) 7 (25.4%) 6 (23.9%) Always guttate psoriasis 52 (00%) 0/0 (00%) 5/5 (00%) 67 (00%) The best of the treatment results 46 fast 2 schedule 2 tanning no contraindications The worst of the treatment travel to hospital 42 nothing 7 erythema 2 multiple sessions results 8 pruritus control duration of response travel to hospital 8 relapse 2 results 3 pruritus control nothing travel to hospital 4 PSE results 57 (85%) move 54 (8%) Would you repeat the treatment? 5/52 (98%) 9/0 (90%) 4/5 (80%) 64 (96%) Global satisfaction score (range 0) PSE, polymorphic sun eruption. these 3 variables (sex, number of flares and family history, p > 0.05, χ 2 test, Table 2 ). A total of 36/52 (69%) patients with CR had a previous clinical history of pharyngitis, in contrast with only 2 out of 0 (20%) patients with IR; this difference was significant ( p < 0.05, χ 2 test). All of the patients with more than flare of AGP (43/67, 64%) had no changes in the form of psoriasis, and the clinical type was always guttate psoriasis. Patient satisfaction with the treatment was high with a mean of 8.75 out of 0 in all patients treated. CR patients had a higher score than IR patients, 9 versus 8.35, but the difference was not significant ( p < 0.05, Student t test). The best of the treatment features for most of the patients was the results (57/67, 85%), and the handicap was going to hospital (54/67, 8%). Nevertheless, most of the patients would repeat the treatment again (96%). This percentage was higher in patients with CR than in patients Table 2. Variables measured associated with response to NB-UVB in adult AGP Variables associated with poor response to NB-UVB (p < 0.05) Older age of onset of the psoriasis (p = 0.02) Longer time of evolution of the psoriasis prior to treatment (p = 0.0) PASI at baseline (p = 0.03) Variables not associated with poor response to NB-UVB (p > 0.05) Age of treatment with phototherapy (p = 0.75) Sex 2 (p = 0.27) Number of previous flares (p = 0.075) 2 Number of sessions needed to clearance (p = 0.0) Family history (p = 0.082) 2 No history of previous pharyngitis (p = 0.0) 2 Student t test. 2 Fisher test. Satisfaction with the treatment (p = 0.29) NB-UVB in Adult Guttate Psoriasis Dermatology 206;232:

5 with IR (98 vs. 90%), but it was also high in patients who were lost to treatment (80%) with no statistical difference ( p > 0.05, χ 2 test). Table 2 summarizes the statistical analysis of the data. The PASI previous to treatment was higher in patients with IR and was significant ( p < 0.05, Student t test). The number of sessions needed for the treatment and doses were lower in patients with CR ( p < 0.05, Student t test). Discussion This is the first study to assess with the PASI score the efficacy of phototherapy with NB-UVB in adult AGP. The effectiveness of the treatment was high, with 78% of the patients achieving PASI90 in a mean of 9.9 sessions with maintained response during 8 months without treatment. The patients treated had small plaques (<3 cm), which usually responded better to treatment with NB-UVB [0]. Other factors which influence the response to treatment are the degree of infiltration and location in the lower limbs [2, 4]. Nevertheless, it is surprising that there are few research studies published on the treatment of AGP [2], and all this evidence is supported by indirect conclusions of studies of psoriasis in general. Previous reports show that the efficacy of NB-UVB in psoriasis decreases when the plaques enlarge [4] and that plaque-type psoriasis requires a significant cumulative higher dose than guttate psoriasis [2]. It is difficult to compare our results with previous studies because they assessed different types of psoriasis together with a logical predominance of the plaque type. A recently published systematic review of 4 randomized controlled trials of phototherapy in psoriasis concluded that NB-UVB achieved PASI75 in 62% of the patients (range 45 79) with a total number of treatments from 4 to 34 sessions [7]. Two more studies investigated the combination of NB-UVB with topical treatments. NB-UVB and tazarotene obtained PASI75 in 0% of the patients [5] and with calcipotriol in 52% (in this study PASI75 is estimated in reference 7) [6]. Only 2 of the studies published in the literature reviewing NB-UVB in psoriasis assessed the size of the plaques [0, 7]. No concomitant treatment and no maintenance treatment were applied because of the good results (88% of CR in 8 months) although a recent study provides some evidence that maintenance with NB-UVB in plaque-type psoriasis may achieve a longer remission [8]. The very good response of adult AGP to NB-UVB in our study exceeds the results obtained with biologics in psoriasis [8] and suggested that NB-UVB should be the first line of treatment of AGP according to guidelines [7 9], but it also raised a number of variables to consider when AGP is evaluated together with plaquetype psoriasis. This was the reason for analyzing other data in our group of patients. Traditionally, patients with AGP have been divided into 2 groups in terms of prognosis, one showing CR and the other progressing into chronic plaque psoriasis without complete involution [20]. The exact percentage of AGP progressing into chronic plaques is not clear and varies in the studies from approximately 5 30% [4] to 68% with a follow-up period up to 0 years [5, 20 23]. In contrast, none of our patients with more than flare of psoriasis (n = 43) presented another clinical type of psoriasis despite being adults with a mean evolution of 6.62 years. AGP occurs more frequently in childhood, and a recent study of 34 patients seen in childhood with guttate psoriasis still had it in adulthood [4]. Maybe there are 2 forms of evolution of an AGP over the years as was proposed in previous works [5], but this does not necessarily involve a change of clinical type. The patients with CR and IR in our study showed some significant differences which could promote 2 different clinical courses, spontaneous healing or chronicity in outbreaks. Patients achieving CR or PASI90 had a mean PASI of 7.9 and needed 9.2 treatments while IR patients had a higher PASI and needed more sessions (0.4, 29.8 sessions, p < 0.05). A direct relationship between PASI and response to NB-UVB in AGP has not been shown in previous reports in the literature reviewed. The age of onset of the AGP and the time of evolution were significantly lower in patients with CR, but not the sex, the age receiving treatment or the number of previous flares. AGP in adults is more frequent with childhood onset but childhood onset does not seem an additional risk factor for higher severity [4, 5]. However, in our study patients with longer courses of AGP exhibited the worst response. In conclusion, good responders to NB-UVB with AGP are young patients with no long flares. In our study a mean of 50.7% of the patients had a firstor second-degree relative affected with psoriasis. This percentage was higher in patients with a bad response to treatment (80%) but it was not significant. In previous reports the family history of psoriasis was found in 33 49% of the patients [ 5, 2, 23, 24] ; AGP with a family history is prone to develop into chronic psoriasis and tends to have a poor prognosis. Curiously, 25% of the patients reported a family history of atopic dermatitis (25% in CR and 20% in IR, p > 0.05). A history of personal and fam- 630 Dermatology 206;232: Fernández-Guarino/Aboín-González/ Velázquez/Barchino/Cano/Lázaro

6 ily atopic dermatitis is presented in all types of psoriasis but it is more frequent in patients with AGP [23]. No history of previous vaccination was reported by any patient. A history of previous pharyngitis as a possible trigger of the flare was significantly ( p > 0.05) more frequent (69%) in patients achieving CR. This could be linked again with a better prognosis of patients with AGP in acute flares. Clinical studies suggest that a clear history of pharyngitis is presented in 9 82% and serological evidence in 54 93% [24 26]. A previous study found that patients with elevated ASLO titers had a better clinical course [5]. The time for considering an upper respiratory infection as a trigger is not clear but it is generally considered to be within a week to a month [25]. We did not routinely perform pharyngeal cultures or determine streptococcal antibodies in patients with AGP because most of them were cured or being treated when attending our outpatient clinic. Only patients with symptoms of pharyngitis were prescribed antibiotics as no benefits of adding antibiotics to the treatment of AGP without previous pharyngitis have been demonstrated [26]. Assessment of patient satisfaction has recently been incorporated in most of the studies about psoriasis treatment. Few previous phototherapy studies in psoriasis patients assess satisfaction or the PASI used. In a recent work, patient satisfaction with phototherapy and biologic treatment was high and comparable [27]. In our study patient global satisfaction was 8.35 out of 0, but it was higher in patients with CR, 9 out of 0. Most of the patients described the necessity to go to the hospital as the main disadvantage of phototherapy and the results as the main advantage of the treatment. Remarkably, 96% of all the patients treated would repeat the treatment again if necessary, even in the case of a bad response. There are no firm recommendations for the treatment of AGP. There are no studies published about PASI improvement or patient satisfaction measures. AGP is a particular entity, and the evidence of the percentage of patients developing chronic plaque psoriasis or patients with no more flares in years is not clear. However, the factors described as good for the course of AGP are also factors of good prognosis for treatment response to NB- UVB. In cases where AGP resolves spontaneously, maybe NB-UVB only accelerates the natural course of the disease and thus the impressive results of the treatment. As it is not possible to distinguish which patients will have one or other course of the disease, NB-UVB should be offered to all of them as a first line of treatment, but in the majority of patients the type of psoriasis remains the same. Patients treated with NB-UVB are very satisfied with the treatment. Acknowledgements We are grateful to Maria Sánchez Ronco for her help with the statistical study and Mery Harper for her editing and language assistance. Statement of Ethics All the patients signed informed consent for the treatment. Disclosure Statement The authors declare no conflicts of interest. There were no funding sources for this work. References Griffiths CE, Christophers E, Barker JN, et al: A classification of psoriasis vulgaris according to phenotype. Br J Dermatol 2007; 56: Takahashi H, Nakamura K, Kaneko F, Nagakawa H, Lizuka H: Analysis of psoriasis patients registered with the Japanese society for psoriasis research from J Dermatol 20; 38: Nahary L, Tamarkin A, Kayam N, et al: An investigation of antistreptococcal antibody responses in gutatte psoriasis. Arch Dermatol Res 2008; 30: De Jager MEA, de Jong EMGJ, Meeuwis KAP, van de Kerkhof PCM, Seyger MMB: No evidence found that childhood onset of psoriasis influences disease severity, future body mass index or type of treatments used. J Eur Acad Dermatol 200; 24: Ko HC, Jwa SW, Song M, Kim MB, Kwon HS: Clinical course of guttate psoriasis: long-term follow-up study. J Dermatol 200; 37: Manolache L, Petrescu-Sceleanu D, Benea V: Life events involvement in psoriasis onset/recurrence. Int J Dermatol 200; 49: Almutawa F, Alnomair N, Wang Y, Hamazavi I, Lim HW: Systematic review of UV-based therapy for psoriasis. Am J Clin Dermatol 203; 4: Chen X, Yang M, Cheng Y, Liu GJ, Zhang M: Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis. Cochrane Database Syst Rev 203; 0: CD Carrascosa JM, López-Estebaranz JL, Carretero G, et al: Documento de consenso de fototerapia en la psoriasis del Grupo Español de Psoriasis: ultravioleta B de banda estrecha (UVBBE), láser y fuentes monocromáticas de excímeros y terapia fotodinámica. Actas Dermosifiliogr 20; 02: NB-UVB in Adult Guttate Psoriasis Dermatology 206;232:

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