Narrowband ultraviolet B phototherapy for pityriasis lichenoides: A real‐life experience

Pityriasis lichenoides (PL) is a papulosquamous disease affecting both children and adults, for which narrowband‐UVB (NB‐UVB) phototherapy is regarded as a commonly used treatment option. The aim of this study was to investigate the efficacy of NB‐UVB phototherapy in the management of PL and to compare response rates in pediatric and adult age groups.

and plaques with a centrally adherent scale that periodically relapse and undergo remission over several years. 2,3Many treatment options including topical or systemic corticosteroids, oral antibiotics, systemic immunosuppressants, and phototherapy were suggested for the treatment of PL. 4,5 Although the etiopathogenesis of PL has not been fully elucidated, predominantly T lymphocyte infiltrate in the epidermis and dermis on histopathological examination suggests that PL may occur as an inflammatory response secondary to a cutaneous T cell dyscrasia.7][8] NB-UVB phototherapy is considered as an effective and tolerable treatment option which has been used with variable success rates in PL. [3][4][5] In this study, patients with PLEVA who failed to respond topical and/or systemic treatments were evaluated together with patients with PLC.We aimed to evaluate efficacy and safety of the NB-UVB in the management of PL comparing response rate in PLEVA and PLC as well as in subgroups of pediatric and adults.

| MATERIAL S AND ME THODS
Twenty PL patients (12 PLC and 8 PLEVA) treated with NB-UVB phototherapy between 2008 and 2018 were retrospectively reviewed in this study.The phototherapy data were evaluated from the followup forms of the phototherapy unit.The diagnosis of PL was based on clinical findings and confirmed with histopathological examination in all patients before initiation of NB-UVB phototherapy.Detailed whole-body dermatologic examination, evaluation of the patient for premalignant skin lesions, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma performed before phototherapy.
Involvement of the face, trunk, and inguinal region was considered as central, involvement of the extremities as peripheral and whole-body involvement as diffuse involvement. 9Disease subtype, affected body involvement, previous treatments and clinical response rates were evaluated in both pediatric and adult patients.
Sociodemographic and clinical features of the patients with PL, duration of disease, previous treatments received for PL, skin type according to Fitzpatrick's classification, and response to phototherapy were recorded.

| Phototherapy protocol
All patients included in this study were treated by application of NB-UVB with the Daavlin Spectra 305/350 model UV device.NB-UVB treatment was started with 70% of the minimal erythema dose (MED).The subsequent dosage of NB-UVB increased by 10%-20% of the previous dose at each session, according to the clinical response of the patient.Treatment was continued with 10% increases in the case of minimal erythema presence during the application with NB-UVB.The dose was not increased in the case of continuous moderate erythema.The treatment was interrupted until symptoms regressed in the cases of severe erythema, edema and bullae development.After symptoms regressed, treatment was continued with 50% of the last dose, and dose increases were determined as 10%.NB-UVB therapy was started three times per week and was reduced to twice or once per week when patients had a clinical response at monthly visits.Maintenance therapy was applied to every patient who achieved clearance of at least 50% in order to prevent exacerbation of the disease.In maintenance therapy, although there is no strict protocol, the last phototherapy dose received by the patient was kept constant throughout the treatment.During the maintenance period, NB-UVB was given approximately once a week for 2-4 weeks and then phototherapy discontinued.

| Evaluation of the treatment response
Patients with more than 90% clearance of the initial body surface area (BSA) were considered as complete response (CR) and those with between 50% and 90% were considered as partial response (PR). 10The number of sessions and the cumulative dose required to achieve CR and PR were recorded in both PLEVA and PLC patients.Side effects during NB-UVB phototherapy were recorded.
The patients were followed up for relapse of the disease throughout 6-9 months period.The study protocol was approved by Eskişehir Osmangazi University Ethics Committee (approval number: 24, date: 04.02.2020).

| Statistical analysis
Continuous data are given as mean ± standard deviation.Categorical data are given as a percentage (%).Shapiro Wilk test was used to investigate the suitability of the data for normal distribution.In the comparison of normally distributed groups, independent sample t-test analysis was used for cases with two groups.Fisher's exact chi-square analyses were used in the analysis of the created cross program was performed in the analysis.The p value <.05 was considered statistically significant.

| Demographics, clinical and treatment features of PL
Twenty patients (13 adults, 7 children) with PL were included in this study.According to the disease subtype, 12 (60%) patients were diagnosed as PLC and 8 (40%) patients were diagnosed as PLEVA.Fifty percent of the patients with PLEVA and 41.6% of the patients with PLC were male.Mean age of the patients with PL was 30.3 ± 18.6.
Mean duration of disease was 20 weeks for the patients with PLEVA and 26 weeks for the patients with PLC.Five (62.5%) of the patients with PLEVA and 9 (75%) patients with PLC had received treatment before NB-UVB phototherapy.No significant differences between PLEVA and PLC groups were found regarding sex, age, duration of disease, previous treatments, and skin types (Table 1).
The clinical and treatment features of patients with PL were evaluated in two groups as children and adults groups.Mean age of the children was 12.14 (range: 10-15) and mean age of adults was 40.07 (range: 22-71).57.1% of the PLC patients were children, and 61.5% of the patients were adults.Diffuse involvement was detected in 57.1% of children and 61.5% of adult patients.Before phototherapy, topical steroids were administered in 3 (42.9%) of the pediatric patients, topical and systemic steroids in 1 (14.3%)patient, and oral azithromycin in 1 (14.3%)patient.In adults, 5 (38.5%) of the patients received topical steroids, 1 (7.7%) patient topical and systemic steroids, 2 (15.4%) patients azithromycin, and 1 (7.7%) patient doxycycline.During the phototherapy and the follow-up period, patients used only emollients for topical skin care.No statistically significant differences between children and adult patients were found in disease subtype, involvement, and previous treatments before phototherapy.CR was obtained in all pediatric patients with a mean cumulative dose of 88.86 J/cm 2 after a mean number of 43.29 exposures, while CR was achieved in 7 (53.8%) of the adult patients with a mean cumulative dose of 38.85 J/cm 2 after a mean number of 37.38 exposures.Additionally, the mean cumulative dose required to achieve the CR was statistically higher in pediatric patients than in adult patients with PL (p < .05)(Table 2).

| Phototherapeutic data according to the disease subtype
NB-UVB treatment led to CR in 6 (75%) of 8 PLEVA patients with a mean cumulative dose of 40.1 J/cm 2 after a mean number of 30 exposures.The PR had achieved in 2 (25%) PLEVA patients with a mean cumulative dose of 26 J/cm 2 after a mean number of 54 exposures.Eight (66.7%) of 12 PLC patients had reached to CR with a mean cumulative dose of 95.0 J/cm 2 after a mean number of 51.2 exposures.The PR had achieved in 4 (33.3%)PLC patients with a cumulative dose of 18.5 J/cm 2 after a mean number of 22.7 exposures.
The mean number of exposures for patients with PLC to achieve a CR was found to be statistically higher than patients with PLEVA (p < .05)(Table 3).However, no significant relationship was found between PLEVA and PLC patients regarding the mean cumulative dose required to achieve CR.

| Adverse effects and relapse
Adverse effects were observed in about 5 (35.7%) of the PL patients undergoing NB-UVB phototherapy.Erythema with burning sensation was developed as the most common side effect during phototherapy in 2 (33.3%) of the patients with PLEVA and 3 (37.5%) of the patients with PLC who had achieved CR.All patients who developed erythema responded to topical application of emollients without discontinuation of phototherapy (Table 3).After the phototherapy, patients were followed up in our clinic for 6-9 months at intervals of 1-2 months and no relapse was observed.

| DISCUSS ION
Despite the continued expansion of knowledge into various treatment options in dermatology, phototherapy still has a role as a wellestablished and cost-effective treatment option.Phototherapy has long been utilized alone or in combination with topical and/or systemic treatments of a wide range of chronic dermatological conditions including psoriasis, atopic dermatitis, vitiligo, prurigo, lichen planus, photodermatoses and mycosis fungoides, as well as many other dermatoses.[13] Phototherapy emerges as an effective and safe treatment option with a good long-term response which is relevant due to the fact that PL is more frequently seen in the child-young population who TA B L E 1 Demographic and clinical features of the patients according to the disease subtype.
requires long-term treatment.Ultraviolet therapy, consisting of psoralen plus UVA (PUVA), broad-band UVB (BB-UVB), and NB-UVB, has been shown to be effective in PL. 8,14 As a phototherapeutic treatment option for PL, NB-UVB induces apoptotic cell death and immunosuppression in inflammatory skin diseases that are characterized by epithelial and dermal infiltrates rich with T lymphocytes. 15 is also demonstrated that UVB prevents the antigen-presenting capacity of Langerhans cells and modulates interleukin-1 (IL-1), IL-6, IL-8, IL-10, IL-12, and tumor necrosis factorα (TNFα) production by human keratinocytes.The favorable immunotherapeutic effect of NB-UVB in PL might be explained by these anti-inflammatory and immunologic alterations. 16Several studies documented the efficacy of NB-UVB 3,8,10,17,18 therefore it has been recommended as first-line treatment option for generalized PL. 4 In a study by Ersoy-Evans et al., in which they documented the clinical features of 124 children with PL, it was reported that 77% of the patients had a chronic recurrent course in a median duration of 18.5 months (range: 3-132 months). 19 median duration of 30 months, while almost 80% of adult patients went into remission by this time.In this study, they suggested that PL in children demonstrates more likely a chronic course as compared to adult patients with widespread body involvement by these lesions and are less responsive to conventional treatment options. 140][21][22] Additionally, topical steroids were the most frequently used treatment before phototherapy in our pediatric patients with PL.
It is postulated that lymphoproliferative reaction induced by antigenic stimulus, such as bacterial and viral infectious agents play an important role in the pathogenesis of PL.Children are more susceptible to such infectious agents than adults, therefore it is expected that PL might follow different clinical courses in pediatric and adult age groups, and their treatment responses might be dissimilar. 14,23,24though there are fewer studies in the pediatric population as compared to adult PL patients, NB-UVB phototherapy appears to be an effective treatment modality in pediatric PL patients. 8,21,25In a systematic evidence-based review which evaluated the use of different phototherapy modalities (PUVA, NB-UVB, BB-UVB) for treating PL in pediatric patients, NB-UVB phototherapy showed the lowest recurrence rate. 8It was postulated that 311-nm wavelengths used in NB-UVB phototherapy have an excellent penetration capability into the dermis and the epidermis, so inducing more complete apoptosis of T lymphocytes. 26garding the response rates during phototherapy, NB-UVB treatment led to CR in 14 (70%) of 20 PL patients with a mean cumulative dose of 71.5 J/cm 2 after a mean number of 42.1 sessions.The PR had achieved in 6 (30%) of 20 PL patients with a mean cumulative dose of 22.2 J/cm 2 after a mean number of 33.1 sessions.In our study, the total cumulative dose and the number of sessions were found to be higher than the studies conducted in dermatoses such as psoriasis and atopic dermatitis reported in the literature. 11,27,28 the best of our knowledge, there is no study in the literature comparing the efficacy of NB-UVB in pediatric and adult patients with PL.Wahie et al. used BB-UVB for eight children and reported that seven (88%) of these children cleared completely or almost cleared of the lesions after phototherapy.In this study, 8 of the 14 adult patients received BB-UVB, while the remaining 6 patients received NB-UVB.Overall, 10 (71%) of the adult patients achieved complete clearance which was lower than children.Additionally, they concluded that UVB phototherapy was more effective than antibiotics in children. 14In our study, CR was obtained in all pediatric patients with a higher cumulative dose compared to adult patients and this was statistically significant.
Brazelli et al. reported five children with PL who failed to respond to topical steroids and/or oral erythromycin.In their study, all five patients showed CR following phototherapy after an average of 21 exposures (range 13-40) and the mean cumulative dose was 21 J/ cm 2 (range 15-32 J/cm 2 ). 21A study by Ersoy-Evans et al. all five pediatric patients with PL treated with NB-UVB achieved greater than 75% improvement after an average of 22 treatments. 29Pasic et al.
used NB-UVB for nine children with PL and they reported that three (33.3%) of the patients showed excellent response with a mean cumulative dose of 6.50 J/cm 2 and a mean number of 19 sessions. 25 our study, all pediatric patients showed CR, and both the mean number of exposures (43.29) and cumulative dose (88.86 J/cm 2 ) required to achieve CR were found to be higher than in other studies. 21,25,29Additionally, the cumulative UVB dose given to achieve the CR in children was found to be statistically significantly higher than in adults.This might be due to the more chronic course of PL in children than in adult patients.
Since PL has two clinically different spectrums including acute (PLEVA) and chronic (PLC) forms, 1,4  than our study and found in 48% of the 25 PLC patients. 3These differences in response rates may be due to varied severity of disease or individual response to phototherapy.Additionally, a lower CR rate was obtained in our PLC patients compared to PLEVA, and the mean number of sessions given to achieve a CR was found statistically higher in PLC patients than PLEVA.This can be explained by the fact that our patients with PLC have a longer disease duration (PLC: 26 weeks vs. PLEVA: 20 weeks) and the more chronic course than patients with PLEVA.
Previous studies showed 42%-73% relapse-free rates after NB-UVB, with mean follow-up duration of 9.5-34 months. 3,10This variation in relapse rates might be related to the heterogenous mean follow-up period of these studies.Our patients were followed up for a short period of time (6-9 months) compared to other studies in literature 3,5,10 and no relapse was observed after phototherapy.
Contrary to other studies in the literature, 10,18,22,25 in our study maintenance treatment was given approximately once a week for 2-4 weeks after finishing the main course of phototherapy in order to prevent exacerbation of the disease.Therefore, the reason why our patients did not relapse in the 6-9 months follow-up period might be the effect of the maintenance treatment.
The most commonly reported side effects of NB-UVB phototherapy are erythema, xerosis, and reactivation of herpes virus. 25 our study, short-term side effects such as erythema with burning sensation were observed in 5 (35.7%) of the PL patients.There was no statistically significant difference regarding the incidence of side effects between pediatric and adult patients and PLEVA and PLC subgroups.
Limitations of this study are being a retrospective design and the short follow-up period of patients after NB-UVB phototherapy compared to the literature.
In conclusion, our results suggest that NB-UVB is an effective and well-tolerated treatment option for PL, especially in diffuse types.In our study, although CR was obtained with higher cumulative UVB in all pediatric patients than in adults, there was no increase in the incidence of adverse effects in the short term.In order to achieve a CR, patients with PLC may require more sessions than patients with PLEVA.Further studies with long-term data in larger patient populations are warranted for the evaluation of clinical response of PL to phototherapy.

CO N FLI C T O F I NTE R E S T S TATE M E NT
None declared.
Wahie et al. compared the clinical and treatment features of children and adult patients with PL, and reported that 80% of children had active disease after a Abbreviations: PLC, pityriasis lichenoides chronica; PLEVA, pityriasis lichenoides et varioliformis acuta.*Independent sample t test; **Fisher exact chi-square test.*Independent sample t test; **Fisher exact chi-square test.