Dermatology: Practical and Conceptual 132 Research | Dermatol Pract Concept 2018;8(2):13 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Introduction Phototherapy is an effective treatment method for many skin diseases. The most important chronic side effect of photother- apy is carcinogenesis. According to the information available, although the carcinogenetic effects of narrowband ultraviolet B (NBUVB) treatment seems more moderate when compared to other forms of phototherapy, its long-term reliability is not known exactly [1]. Dermoscopy is among the optical techniques with higher efficacy in the earlier diagnosis of skin cancer compared to naked-eye examination [2]. For this reason, total body exami- nations, both clinical and dermoscopic, are being performed in many centers before and during phototherapy. Dermoscopic changes in melanocytic nevi covered with both opaque tape and sunscreen cream during narrowband ultraviolet B therapy Derya Ök Kekeç1, Nida Kaçar2, Işıl Kılınç Karaarslan3 1 Denizli Public Hospital, Denizli, Turkey 2 Department of Dermatology, Pamukkale University, Denizli, Turkey 3 Department of Dermatology, Ege University, Izmir, Turkey Key words: dermoscopy, sunscreen, melanocytic nevus, phototherapy, narrowband ultraviolet B Citation: Ök Kekeç D, Kaçar N, Kilinç Karaarslan I. Dermoscopic changes in melanocytic nevi covered with both opaque tape and sunscreen cream during narrowband ultraviolet B therapy. Dermatol Pract Concept. 2018;8(2):132-139. DOI: https://doi.org/10.5826/ dpc.0802a13 Received: January 25, 2018; Accepted: February 20, 2018; Published: April 30, 2018 Copyright: ©2018 Ök Kekeç et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was financially supported by grant number 2015TPF011 from the Scientific Research Projects Foundation of Pamukkale University. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Nida Kaçar, MD, Pamukkale Universitesi Tip Fakultesi, Dermatoloji Anabilim Dali, Kırmızı Bina, 3. Kat Kinikli, 20070 Pamukkale Denizli, Turkey. Tel. +902582965875. Email: n_gelincik@yahoo.com Background: Ultraviolet (UV) light may cause dermoscopic changes on melanocytic nevi (MN). Objectives: To investigate the effects of sunscreen cream (SSc) application on dermoscopic changes in MN during narrowband UVB (NBUVB) therapy. Methods: Half of the randomly selected MN in each patient were covered with opaque tape and SSc [SSc(+)], and the rest were covered with only opaque tape [SSc(-)] during NBUVB treatment sessions. Results: More SSc(-) MN displayed dermoscopic changes at end of NBUVB therapy compared to the start of therapy (p=0.035). The number of the MN that decreased in size and showed loss of structure was significantly higher in SSc(-) MN (p=0.04 and p=0.026, respectively). Conclusions: Sunscreen in combination with opaque tape may contribute to some dermoscopic changes in melanocytic nevi, including decrease in size and loss of structure. ABSTRACT Research | Dermatol Pract Concept 2018;8(2):13 133 opaque tape—without SSc application SSc(-). SSc was applied approximately 20 minutes before the opaque tape was applied. SPF 50 + SSc containing organic and inorganic filters against UVA-UVB (Solante; Buergli Pharma, Inc., Makati, Philippines) was used. Dermoscopic images of the selected MN were captured with a digital dermoscopy system at the beginning, at the end, and 3-6 months after the end of NBUVB therapy. At all follow-ups, total body mole mapping was performed with a fully automated body mole-mapping programme (Body Studio ATBM; FotoFinder Systems Inc, Columbia, MD, USA). Dermoscopic photographing, total body mole mapping, and arrangement of photographs were performed by one researcher (DÖK). The evaluation of the images was done by another researcher (NK) without know- ing whether the lesion was SSc(+) or SSc(-). The MN that showed unexpected dermoscopic findings, such as decrease in size or loss of structure, were further evaluated by another researcher (IKK). The data were analyzed with the SPSS Statistics 21 packet programme. Sustained variables were given as average ± stan- dard deviation, minimum – maximum assets and categorical variables for numbers and percentages. In order to compare the independent group discrepancies, the Mann-Whitney U test was used. The differences between categoric variables were examined with Chi-square test. For examination of risk factors, the logistic regression test was used. Results Of the 24 patients enrolled, a total of 165 MN were identified. Excluded from the study were 6 patients with 34 MN, who were lost to follow-up and 11 MN of included patients that had poor image quality. In sum, the study included 120 MN belonging to  18  patients (mean age: 44.7±14.2  years; 13 women). The majority of patients were diagnosed with mycosis fun- goides (n:5; 27.8%) and psoriasis (n:5; 27.8%); the remain- ing diagnoses were pruritus, granuloma annulare, pityriasis lichenoides chronica and perforating dermatoses. Fitzpatrick skin type 3 was the most common skin type (n:14; 77.8%). The mean cumulative treatment dose was 32.9±33.3 joule/ cm2 (range 1.53-100.14 joule/cm2). One patient received acitretin treatment in addition to phototherapy. Forty-two MN [18 SSc(+); 24 SSc (-)] were reexamined after a mean of 4.2±1.2 months (range: 3-6 months) after the end of NBUVB therapy. SSc(-) and SSc(+) groups constituted 68 (56.7%) and 52 (43.3%) patients, respectively. The most frequently observed dermoscopic pattern was reticular pattern (n=50; 41%), followed by homogenous- reticular pattern (n=31; 25.8%), homogenous pattern (n=17; 14.2%), globular pattern (n=12; 10.0%), homogenous- globular pattern (n=8; 6.7%), and multicomponent pattern UV light can cause clinical, histopathologic and dermo- scopic changes in melanocytic nevi (MN) [3-5]. The dermo- scopic changes observed in MN after NBUVB or ultraviolet A1 (UVA1) exposure did not occur in MN covered with opaque tape or sunscreen cream (SSc). In the direction of these findings, it was suggested that the dermoscopic changes induced by UVA1 and ultraviolet B (UVB) can be prevented successfully with either opaque tape or highly protective factor SSc; however, no significant histologic and immunohistochemical changes were detected in MN showing dermoscopic changes [6]. Although dermoscopic changes were recorded in a significantly few amount of cov- ered MN during phototherapy sessions, they still occured in a noteworthy part of the covered MN [5,7,9]. The Turkish Dermatology Society Phototherapy Guidelines advise cover- ing big and atypical MN and premalignant lesions before phototherapy [9]. Based on the above findings, we covered half of the selected MN with opaque tape and SSc and the rest with only opaque tape during all phototherapy sessions in order to investigate whether the use of SSc in addition to opaque tape has an additive effect in preventing dermoscopic changes induced by UV exposure. We also evaluated the development of new MN during follow-up. As far as we know, our study is the first study searching dermoscopic changes in covered MN with both opaque tape and SSc and new MN development during phototherapy. Materials and Methods All patients with a variety of dermatologic diseases were refered to our phototherapy unit for NBUVB therapy between January 28, 2015 and July 25, 2016 were evalu- ated in terms of eligibility for the study. The patients who were older than 1 year old and had at least two MN >2 mm size located on body and/or proximal extremity without melanoma suspicion were invited to participate in the study. Exclusion criteria included personal or family his- tory of melanoma or cutaneous malignant epithelial tumor, active infection, atypical mole syndrome, active or previous history of systemic inflammatory or neoplastic disease, immunosuppressive medication, phototherapy history, and artificial UV exposure. MN located on sun-exposed body parts such as the head, neck, and distal extremities were not taken into consideration. Every study participant signed an Informed Consent Form. Phototherapy was given using a Waldman UV 7001K (TL-01) device equipped with F85/100W-01 (TL01) Phil- ips fluorescent tubes. At least two MN sized >2 mm were selected randomly in each patient. Half of the selected MN in each patient were covered with opaque tape after SSc application SSc(+), and the rest were covered only with 134 Research | Dermatol Pract Concept 2018;8(2):13 SSc(+) MN; but not at a significant level (p>0.05) (Table 2). The ratio of SSc(+) MN that showed darkening pigmentation, darkening pigment network, increase in size, and decrease in the number of dot and/or globules were higher than SSc(-) MN (p>0.05) (Table 3). T h e d e r m o s c o p i c ch a n g e s 3 - 6 months after the end of NBUVB ther- apy compared to the beginning and the (n=2; 1.7%). Seventy percent of MN were located on the body, 25.8% on the arms, and 4.2% on the legs. New MN development was not established during the study. Although the ratio of SSc(-) MN displaying der- moscopic changes was higher than SSc(+) MN at the end of NBUVB ther- apy compared to the beginning; the ratio of MN displaying dermoscopic changes was similar in both SSc(-) and SSc(+) groups  3-6  months after the end of NBUVB therapy compared to the beginning and the end of therapy (Table 1). No differences in dermoscopic changes according to anatomic loca- tions were detected between SSc(-) and SSc(+) groups (p>0.05). Dermoscopic changes at the end of NBUVB therapy compared to the of therapy: The ratios of SSc(-) MN that showed decrease in size and loss of structure were higher than SSc(+) MN (p=0.04 and p=0.026, respectively) (Figure 1). Failure to apply SSc over MN increased the ratio of decrease in size 4,681 times compared to MN applied with SSC (Exp(B): 4.681). The ratio of loss of structure was found to be increased 5.932 times in SSc(-) MN compared to SSc(+) MN (Exp(B):5.932). The mean exposed joules were com- parable between the SSc(-) and SSc(+) MN showing decrease in size and loss of structure (p>0.05). More SSc(-) MN showed fading in pigmentation, fading in pigment network, new structure and/ or color development, and increase in the number of dot and/or globules than TABLE 1. MN showing dermoscopic changes at the beginning, at the end, and 3-6 months after end of therapy Beginning vs. end End vs. 3-6 months after the end End vs. 3-6 months after the end SSc(+); n(%) 19 (15.8%) 6 (14.2%) 6 (14.2%) SSc (-); n(%) 38 (31.6%) 6 (14.2%) 3 (7.1%) P value =0.035 >0.05 >0.05 Total n(%) 57 (47.5%) 12 (28.5%)* 9 (21.4%)* *These ratios were calculated within 42 MN that were reexamined after discontinuing therapy. Figure 1. The nevi that showed fading in pigmentation and pigment network (B); fading in pigmentation together with decrease in size (D), and decrease in dots/globules together with increase in streaks and blue-gray color formation (F) at the end of therapy compared to the beginning (A, C and E, respectively). [Copyright: ©2018 Ök Kekeç et al.] end of therapy: These analyses were performed in SSc(-) 24 MN and SSc(+) 18  MN that were reexamined after discontinuing therapy. Dermoscopic changes persisted in 7 MN [4 SSc (+); 3 SSc(-)] and new dermoscopic changes (late onset) emerged in 2 MN [2 SSc (+)] 3-6 months after the end of therapy. When the dermoscopic changes were considered separately, it was observed that most returned to their former state Research | Dermatol Pract Concept 2018;8(2):13 135 Discussion Prevelance of MN changes according to age, genetic and environmental factors, and the number of MN, which are low in childhood can increase in time [10]. The most studied enviromental factor in terms of relevance with MN develop- ment is UV light. An animal model demonstrated that UVB and UVA2 both induce MN development [11,12]. Epidemio- logical and twin studies revealed a relationship between the number of MN and the intermittant intense UV exposure; however, no relationship was established between daily UV exposure and MN number [13,14]. It was shown that as the experienced sunburn number and severity increase, new MN or had a tendency to do so (Table 4, Figure 2). The dermo- scopic changes and histopathologic results of excised MN are summarized in Table 5. Before starting the study, it was calculated with 80% power that 95% confidence could be achieved if 49 MN would be included in each group (at least 98 MN) when power analysis had been performed, assuming the obtainable ratios would be 10% and 30%. When the results of the study were examined, power analysis was performed according to these results [for size decrease SSc(+) 9.6% vs SSC(-) 33.8%, and for structure loss SSC(+) 3.8% vs. SSC(-) 19.1%], and it was determined that the present study had 95% and 86% power, respectively, with 95% confidence. TABLE 2. More frequently observed dermoscopic changes in SSc(-) MN compared to SSc(+) MN at the beginning vs. end of NBUVB therapy** (n=120) SSc(+); n (%) SSc(-); n (%) P Decrease in size 5 (9.6%) 23 (33.8%) =0.04 Symmetric 5 19 >0.05 Asymmetric 0 4 Loss of construction 2 (3.8%) 13 (19.1%) =0.026 Loss of pigment network 2 11 >0.05 Dots/globules 0 1 Branched streaks 0 1 Fading in pigmentation 19 (34.6%) 33 (47.1%) p>0.05 Symmetric-homogeneous 17 30 >0.05 Asymmetric 0 2 Central 2 0 Peripheral 0 1 Fading in pigment network 11 (21.2%) 19 (27.9%) p>0.05 Symmetric-homogeneous 11 19 NA New structure formation 1 (1.9%) 6 (8.8%) p>0.05 Pigment network 0 3 NA Streaks 0 1 Dot-globul 0 1 White scar-like Depigmentation 1 1 Structureless areas 1 0 Ulcer 1 0 Chrysalis structures 1 0 New color formation 1 (%1.9%) 4 (5.9%) p>0.05 Blue 0 1 NA White 1 1 Blue-gray 0 2 Loss of color 0 (0%) 1 (1,5%) NA Black 0 1 NA Increase of dots-globules 1 (1.9%) 1 (1.5%) NA *NA= No Analysis **The above given MN and the dermoscopic parameter numbers do not match, because more than one dermoscopic parameter was observed in one MN. 136 Research | Dermatol Pract Concept 2018;8(2):13 treatment [16,17] and even in 43.2% of covered MN dur- ing psoralen-ultraviolet A (PUVA) and NBUVB treatment [7]. We observed dermoscopic changes in most of the MN (65%) despite being covered with opaque tape in all and with SSc in half of them. Higher ratios that are found in our study may be related to the detailed dermoscopic evaluation parameters. Lin et al recognized size changes in a larger proportion of the MN located on the abdominal region in comparison to the MN located on other body sites but noted no significant relation with skin type [16]. In our study, we did not detect any differences in dermoscopic changes between SSc(+) and SSc(-) MN groups according to anatomical location. Kılınç Karaaslan et al observed increase in size in uncov- ered MN but not in opaque tape-covered MN at the end of development increases [15]. These findings explain that the nevogenic effect of UV is dose dependent and is distinctive in areas where environmental UV is much more intense. We did not observe new MN development in our study. It can be related to other factors, including that almost all our patients were dark phenotype, all were over 18 years old, and we had short-term follow-up. In addition, the ones who had severe sunburn history were excluded from the study, and during treatment the UV dosage were raised gradually. There are genetic factors that have not been identified, yet might have a role. UV light can cause clinical, histopathologic and der- moscopic changes in MN by increasing melanin synthesis or inducing melanocyte proliferation [3-5]. Dermoscopic changes were reported in 27-50% of MN during NBUVB TABLE 3. More frequently observed dermoscopic changes in SSc(+) MN compared to SSc(-) MN at the beginning vs. at the end of NBUVB therapy (n=120) SSc(+); n (%) SSc(-); n (%) P* Increase in size 3 (5.8%) 3 (4.4%) p>0.05 Symmetric 2 3 NA Asymmetric 1 0 Darkening in pigmentation 4 (7.7%) 4 (5.9%) p>0.05 Symmetric –homogenous 4 4 NA Darkening in pigment network 4 (7.7%) 2 (2.9%) p>0.05 Symmetric –homogenous 4 2 NA Decrease in the number of dots/globules 4 (7.7%) 4 (5.9%) p>0.05 *NA= No Analysis TABLE 4. The course of dermoscopic changes 3-6 months after end of therapy* Returned to the original state or tended to do so Persisted or progressed Late onset Increase in size 9.5 [4.6:4.6] 2.3 [2.3:0] 4.6 [2.3:2.3] Decrease in size 21.4 [0:21.4] 4.6 [2.3:2.3] 2.3 [2.3:0] Darkening in pigmentation 9.5 [4.6:4.6] 4.6 [4.6:0] 0 Fading in pigmentation 28.5 [6.9:21.4] 11.9 [4.6:6.9] 4.6 (4.6:0] Darkening in pigment network 9.5 [4.6:4.6] 2.3 [2.3:0] 0 Fading in pigment network 16.6 [4.6:11.9] 9.5 [2.3:6.9] 0 New structure development 6.9 [2.3:4.6] 2.3 [0:2.3] 4.6 [2.3:2.3] Loss of structure 14.2 [2.3:11.9] 2.3 [0:2,3] 2.3 [2.3:0] Increase in the number of dots/globules 0 2.3 [2.3:0] 2.3 [0:2.3] Decrease in the number of dots/globules 6.9 [2.3:4.6] 0 0 New color development 2.3 [0:2.3] 2.3 [2.3:0] 0 Loss of color 2.3 [0:2.3] 0 0 * %total [%SSc(+): %SSc(-)]; these ratios were calculated within 42 MN that were reexamined after discontinuing therapy Research | Dermatol Pract Concept 2018;8(2):13 137 NBUVB, UVA1 and PUVA treatments for three months [17]. None of the above studies mention decrease in size in MN and it was not stated whether size decrease was taken into consideration. Lin et al detected size change in 40% of MN during NBUVB treatment, and similar to our study, they evalu- ated MN size in terms of both decrease and increase. They a mean 9 weeks of NBUVB treatment [8]. Similarly to their observation, Ghani-Nejad et al determined a significant increase in size in uncovered MN, but not in opaque tape- covered MN, after NBUVB treatment for 30-60 sessions [7]. Contrary to these studies, Karaca et al established a statisti- cally significant mean area measurement increase in MN, despite being uncovered, in patient groups who received Figure 2. Darkening in pigmentation and pigment network (B, E) and fading in pigmentation and pigment network (H) at the end of ther- apy compared to the beginning (A, D, G) in three MN. It is seen that dermoscopic changes showing tendency to return back (C), increasing (F) and persisting (I) 3-6 months after the end of therapy. [Copyright: ©2018 Ök Kekeç et al.] TABLE 5. Dermoscopic changes in excised MN Dermoscopic changes MN1 MN2 MN3 MN4 Structureless areas + - - - Ulcer + - - - Chrysalis structures + - - - Streaks formation - - - + White scar-like depigmentation + + - - Decrease in size - + + - Increase in size - - - + Fading in pigmentation - + + + Darkening in pigmentation - - - + Fading in pigment network - - + - Decrease in the number of dots/globules - - - + Loss of pigment network - + - - Histopathologic diagnosis Intradermal nevus Junctional nevus Junctional nevus Dysplastic nevus 138 Research | Dermatol Pract Concept 2018;8(2):13 NBUVB exposure in both study groups. However, dermo- scopic changes remained in some MN. In addition, dermo- scopic changes emerged 3-6 months after the end therapy in some MN that did not show any dermoscopic changes at the end of therapy. Those dermoscopic changes can be due to late- onset or persistent effects of NBUVB but can also be related to the natural evolution of MN, independent from NBUVB, as claimed by Dobrosavljevic et al. Long-term follow up studies may clarify this condition [18]. Conclusion In conclusion, NBUVB treatment causse various dermoscopic changes in MN; some of these changes can be prevented with opaque tape. SSc in combination with opaque tape helps in preventing the development of dermoscopic changes in MN, including size decrease and structure loss. Acknowledgments This study was financially supported by grant num- ber 2015TPF011 from the Scientific Research Projects Foun- dation of Pamukkale University. We thank Hande S enol, Lecturer, for her help and comments in statistical analyses. References 1. Sokolova A, Lee A, D Smith S. The safety and efficacy of narrow band ultraviolet B treatment in dermatology: a review. Am J Clin Dermatol. 2015;16(6):501-531. 2. Seebode C, Lehmann J, Emmert S. Photocarcinogenesis and Skin Cancer Prevention Strategies. Anticancer Res. 2016;36(3):1371- 1378. 3. Hofmann-Wellenhof R, Soyer HP, et al. Ultraviolet radiation of melanocytic nevi: a dermoscopic study. Arch Dermatol. 1998;134(7):845-850. 4. Stanganelli I, Rafanelli S, Bucchi L. Seasonal prevalence of digital epiluminescence microscopy patterns in acquired melanocytic nevi. J Am Acad Dermatol. 1996;34(3):460-464. 5. Hofmann-Wellenhof R, Wolf P, Smolle J, Reimann-Weber A, Soyer HP, Kerl H. Influence of UVB therapy on dermoscopic fea- tures of acquired melanocytic nevi. J Am Acad Dermatol. 1997; 37(4):559-563. 6. Manganoni AM, Rossi MT, Sala R, et al. Dermoscopic, histologi- cal and immunohistochemical evaluation of cancerous features in acquired melanocytic nevi that have been repeatedly exposed to UVA or UVB. 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