Journal of Dermatological Treatment.

2009; 20:2; 109113

PSORIASIS AND PHOTOTHERAPY

Narrowband ultraviolet-B phototherapy in pityriasis lichenoides chronica

BEl ERsoY-EVAns, Asli AlTAYkAn HAPA, GonCA BoZTEPE, SEdEF S n & Si Ahi FikRET KlEMEn
Department of Dermatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Abstract Background: Current knowledge about the efficacy of narrowband UVB therapy for the treatment of pityriasis lichenoides is limited. Objective: The aim of this study was to investigate the efficacy of narrowband UVB therapy for the treatment of pityriasis lichenoides chronica (PLC). Methods: Data were retrospectively collected following a review of patient phototherapy and medical charts, and telephone interviews were performed for follow-up information. Results: The study included 25patients (14 male, 11 female) with a mean age of 34 13years. Diagnosis was confirmed by histopathological examination in 92% (n = 23) of the patients. The median duration of the disease was 24 months (range: 2192 months). The median number of sessions until response was 25 (8 weeks) (range: 977 sessions), with a median cumulative dose of 15 J/cm (range: 2158 J/cm). Complete response and partial response were achieved in 48% and 44% of the patients, respectively, while 8% of the patients achieved no response. In those patients for whom follow-up data were available (n = 17), 10 (58%) relapsed within a median of 9.5 months (range: 144 months). Conclusions: Our results suggest that narrowband UVB is an effective and well-tolerated treatment option for PLC.

Key words: Narrowband UVB, phototherapy, pityriasis lichenoides

Introduction Pityriasis lichenoides (PL) is a benign acquired disorder that commonly affects children and young adults, although it has been reported in all age groups. Diagnosis, classification, and treatment of PL are challenging. Owing to overlapping clinical and histopathological features, classification is controversial; therefore, it is often considered as a spectrum with two polar ends: pityriasis lichenoides chronica (PLC) and pityriasis lichenoides et varioliformis acuta (PLEVA) (1). PLC is a chronic form that presents with erythematous, scaly macules, and lichenoid papules. PLEVA tends to be more acute and presents with macules, papules, or papulovesicles that may evolve through stages of crusting, necrosis, and varioliform scarring. The lesions tend to localize over

the trunk and extremities, frequently with widespread distribution. Mucosa involvement is usually not seen. Pruritus and arthralgia can accompany PL. It is generally a self-limiting condition with a variable duration ranging between 1.6 months and several years (24). The cause of PL remains unknown; however, recent studies demonstrating T-cell clonality suggest that PL is a benign lymphoproliferative process, probably triggered by an unknown antigenic stimulus (5,6). Although PL is a self-limiting skin condition, treatment is frequently desired due to symptomatic and cosmetic disturbances, especially when the rash is widespread; however, treatment of PL i s not straightforward, as its course is unpredictable and it responds poorly to various treatment m o d a l i ties. At present there is no

Correspondence: Sibel Ersoy-Evans, Department of Dermatology, Faculty of Medicine, Hacettepe University, Shhye, Ankara, Turkey. Fax: 90 312 309 7265. E-mail: [email protected] This study was presented as an oral presentation at the XXI World Congress of Dermatology, October 15, 2007, Argentina. (Recevied 24 Jun 2008; accepted 16 Aug 2008) ISSN 0954-6634 print/ISSN 1471-1753 online 2009 Informa UK Ltd. DOI: 10.1080/09546630802449088

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S. Ersoy-Evans et al. prior to therapy. Test doses administered ranged from 100 to 1200 mJ/cm2 for skin phototype II, and from 200 to 1500 mJ/cm2 for skin phototypes III and IV. The MED was accepted as the lowest dose that yielded perceptible erythema 24 h after exposure. Narrowband UVB phototherapy was initially administered at 70% of the MED and treatment continued with 20% dose increases at each subsequent session. If erythema developed, the dose remained unchanged until the next session. Narrowband UVB was given three times per week and was reduced to twice or once per week when patients had a complete clinical response. Response and recurrence Complete response was defined as > 75% improvement of the rash, partial response as 5075% improvement of the rash, and if there was < 50% improvement of the rash after approximately 50 sessions it was considered as no response. Recurrence was defined as flaring of the eruption (> 10 lesions) after it had improved or cleared completely. Maintenance therapy There was no strict protocol for maintenance treatment. The dose required to achieve response was kept constant during the maintenance treatment period and it was given approximately twice per week for 24 weeks. Then it was decreased to once per week and discontinued after 46 weeks. Statistical analysis Data were analyzed using descriptive statistics and comparisons were made by Students t-test. Median was used instead of mean for continuous variables such as age and duration due to uneven distribution of the patients. Results Demographic and clinical features (Table I) In all, 25patients (14 male, 11 female) with a mean age of 34 13 years (range: 1260 years) were included in the study, of which 17 (68%) had skin phototype III and 8 (32%) had type II. The median duration of the disease before treatment was 24 months (range: 2192 months). Of those patients whose information was available, no triggering factor was noted in 90% (n = 18) and pregnancy was accepted as the trigger in two patients. The disease

established treatment for PL. Herein, we present our experience with narrowband UVB (311 nm) therapy for PLC. Patients and methods This retrospective study included patients treated with narrowband UVB phototherapy in our institution between 1999 and 2006. Our phototherapy unit is staffed by a dermatology resident (on rotation for 1 month) and two staff technicians. The technicians administer the treatment, record the doses, and consult with the dermatology resident, as well as with an attending physician when there is a response and/or side effect. Consequently, the demographic data of the patients, and data concerning the phototherapy sessions, doses, adverse events, and responses are recorded in a special phototherapy chart. In this study, data were retrospectively collected following a review of the patients medical and phototherapy charts. Missing data, as well as follow-up information, were gathered by interviewing the patients by telephone. Diagnoses were made based on clinical findings in all cases, while histopathological examination was performed in 92% (n = 23). Patient age, sex, disease duration, triggering factors, season of onset, distribution, previous treatments, and associated symptoms were recorded. Distribution of lesions Distribution was grouped according to Gelmetti etal. (3). Involvement of the face, trunk, and inguinal region was classified as central, involvement of the extremities was classified as peripheral, while whole body involvement was classified as diffuse. Phototherapy equipment Patients received narrowband UVB treatment either with a Dr K. Hoenle cabin (D-8033; Ringo Dermalight, Martinsried, Germany) equipped with 45 Philips TL100W/01 fluorescent lamps or a Waldman UV 7001K cabin (Waldman Medizintechnik, Villingen-Schwenningen, Germany) with 40 TL-01/100 W fluorescent lamps. The mean radiation intensity was 6 mW/cm2. Radiance in the UVB cabinet was monitored routinely once a month with a UVB detector (Waldmann AG, Schwenningen, Germany). Treatment protocol The minimal erythema dose (MED) was determined in every patient (on a body region without lesions)


Table I. Patient demographics. Sex Mean age Diagnosis Histopathological examination Triggering factor Season of onset 25 patients (14 male, 11 female) 34 13years (range: 1260 years) Based on clinical findings (typical scaly papules) 23 patients (92%) Pregnancy (n = 2) None (n = 18) Four patients in spring Two patients in summer Two patients in fall Pruritus and burning sensation (n = 5) Diffuse in 44% (n = 11) Peripheral in 48% (n = 12) Central in 8% (n = 2) Topical corticosteroids (n = 7) Tetracyclines (n = 3)

Narrowband UVB therapy in pityriasis lichenoides

Table II. Treatment features. Treatment Total cumulative dose Total number of sessions Sessions until response Cumulative dose until response MED Maximum dose Maintenance treatments Median 45 J/cm (range: 7252 J/cm) 45 (range: 15131 sessions)

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25 (range: 977 sessions) (8 weeks) 15 J/cm (range: 2158 J/cm) 550 mJ/cm (range: 3001200 mJ/cm) 1408 mJ/cm2 (range: 2406000 mJ/cm) 21 sessions (range: 554 sessions)

MED = minimal erythema dose.

Symptoms Involvement

Adverse effects and relapse Side effects were observed in 15patients (60%) and included erythema (n = 13), pruritus (n = 3), and folliculitis (n = 1). None of the patients discontinued the treatment due to side effects. The average follow-up period in the present study was 44 months. In those for whom follow-up data was available ( n = 17), relapse was recorded in 58% (n = 10) within a median of 9.5 months (range: 144 months). Discussion Clinical management of PL is difficult due to its uncertain etiology. Topical corticosteroids and antihistamines are helpful in symptomatic cases, but they do not alter the course of the disease. Recently, good responses with topical tacrolimus treatment were reported (7,8). Oral antibiotics, including tetracycline (9) and erythromycin (10,11), are considered first-line treatments for PL, particularly for PLEVA. Systemic treatments, such as systemic corticosteroids (12), methotrexate (13), calciferol (14), chinoline and acridine derivates (15), cyclosporine (16), intravenous gamma globulin and retinoids (17) may be used in severe cases. Recently, oral bromelain (a crude aqueous extract of pineapple) was suggested to be an effective therapeutic option for PLC when used for 3 months (18). Current knowledge about the efficacy of phototherapy for PL is limited and is mostly based on anecdotal reports and small-scale studies. The present study included 25 PLC patients given narrowband UVB therapy. Response was observed, on average, in 25 sessions (8 weeks) and 92% of the patients responded to the treatment. Relapse was observed in 58% of the cases within a median of 9.5 months; only 42% of the patients were relapse-free after a follow-up of an average of 44 months. Recently, Pavlotsky etal. (19) reported their experience with both broadband UVB

Previous treatments

began during spring in four patients, during summer in two patients, and during the fall in two patients. In total, 10 out of 19patients (53%) had one or more previous treatments; either topical corticosteroids (n = 7) or tetracyclines (n = 3). Associated symptoms were observed in only five of 20 (25%) patients, all of whom had pruritus and a burning sensation. Distribution was diffuse in 44% of the cases (n = 11), peripheral in 48% (n = 12), and central in the remainder (n = 2). Treatment features (Table II) The median total cumulative dose was 45 J/cm (range: 7252 J/cm), with a median of 45 sessions (range: 15131 sessions). The median MED was 550 mJ/cm (range: 3001200 mJ/cm). Complete and partial responses were achieved in 48% and 44% of the patients, respectively, while 8% of the patients had no response. The median of total sessions until response was 25 (over the course of 8 weeks) (range: 977 sessions), with a median cumulative dose of 15 J/cm (range: 2158 J/cm). The two patients who had no response were considered as unresponsive after 56 and 57 sessions, respectively. The 22 patients who had maintenance treatment had a median of 21 sessions (range: 554 sessions). The median dose administered for maintenance was 1408.5 mJ/cm2. In all, three patients did not have maintenance therapy: one of them had < 25% improvement of the rash, while the other two discontinued the treatment due to undisclosed personal reasons.

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S. Ersoy-Evans et al. follow-up was not provided. Tay et al. (29) also administered UVB to five children with PL following unsuccessful topical corticosteroids and oral erythromycin treatment. Complete response was achieved in all the patients within a mean of 11.5 weeks. No maintenance was given and two patients with PLEVA relapsed after 7 and 9 months, respectively. UVA1 phototherapy was also reported to be effective in a study with eight PL patients. Complete response was achieved in six patients, while the other two patients showed partial response (30). Narrowband UVB therapy with 311-nm wavelength light was established for the treatment of psoriasis about 20 years ago (31). Since then, narrowband UVB has been shown to be more effective than broadband UVB and equally as effective as PUVA in controlling psoriasis; however, its efficacy in other diseases remains unclear. A recent study by Gambichler et al. (31), which analyzed all the clinical trials of narrowband UVB, showed that narrowband UVB should be considered a first-line therapy in atopic dermatitis and vitiligo. Currently, data about narrowband UVB therapy for PL is mainly based on two studies (19,20). The largest and most recent study included 31 PL patients (of whom eight had PLC) treated with narrowband UVB (20). The other large study included 15 PL patients treated with narrowband UVB (19). To the best of our knowledge, the present study represents another large series especially of PLC patients (n = 25) treated with narrowband UVB. We are aware that the retrospective design of the present study is a limitation; however, we think that our phototherapy charts accurately reflect the data concerning the treatments and treatment outcomes of our patients. Additionally, it is challenging to collect good quality evidence with a randomized controlled trial that includes a large number of patients with a rare disease. In conclusion, narrowband UVB is an efficient and well-tolerated treatment option for PL. Nonetheless, it does not alter the course of the disease greatly. Perhaps a longer maintenance treatment period is required to reduce the rate of relapse. As such, additional data, especially from studies performed to compare other treatments with phototherapy, as well as studies about maintenance therapies for PL, are needed in order to claim that narrowband UVB should be a first-line treatment for PLC.

(n = 14) and narrowband UVB (n = 15) in Israeli PL patients. They stated that complete response was achieved in 92.9% of their patients treated with narrowband UVB. The median time for complete response was 9 weeks (about 27 sessions) with a median total dose of 15 J/cm. In total, 75% of their patients who were treated with narrowband UVB were relapse-free after a mean follow-up of 34 months. Also, Aydogan etal. treated 31 PL (PLC = 8, PLEVA = 23) patients with narrowband UVB and achieved complete response in 87.5% and 65.2% of their PLC and PLEVA patients, respectively (20). Their relapse-free rates were 86% for PLEVA and 71.4% for PLC patients after a follow-up period of 612 months. The discrepancy between the relapse rates in these studies and our study might be due to the smaller (n = 15 and n = 8) sample sizes, shorter follow-up periods, as well as differences in their definition of relapse. In a study of phototherapy in a pediatric population, nine children with PL (PLEVA = 3, PLC = 6) were given narrowband UVB therapy and goodexcellent responses were observed in 66.6% of the patients within an average of 19 sessions (21). Phototherapy consists of broadband UVB, psoralen plus UVA (PUVA), UVA1, and narrowband UVB modalities. The exact mechanism of UVs efficacy in PL is unknown, but the immunomodulating effects of UV light, such as the depletion of Langerhans cells and dermal T cells, and a decrease in natural killer cell activity, have been proposed (22,23). In the past, PUVA, broadband UVB and UVA 1 have also been used for the treatment of PL with good results.The efficacy of PUVA in PL was reported by Boelen et al. (24) who treated four PL patients with PUVA and another patient with a light source emitting UVB and UVA. They achieved complete response in all the patients. In another study, 25 PL patients receiving topical steroid alone (n = 8), tetracycline (n = 14), or PUVA alone (n = 8) were compared and PUVA was superior to the other treatments, in terms of response rate. Moreover, Panse etal. (26) successfully treated three PL patients with a combination of PUVA and acitretin. Similarly, good results in PL treatment were obtained with broadband UVB phototherapy. In a retrospective study involving 17 PL patients (27), it was reported that 14 patients (82.4%) had a good response, nine (53%) of which had complete clearance. In that study, clearance required a mean of 33 sessions, and six of 12 patients who were followed-up for a mean of 22 months had no relapse during that period. Le Vine et al. (28) reported that all of their 11 PL patients showed clearance of the lesions in an average of 29 sessions. No recurrences were observed during the maintenance period, but their data regarding the

Acknowledgement We would like to thank Scott B. Evans for his meticulous editing of the manuscript.

 Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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