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To cite this article: Zeinab A. Ibrahim, Shereen F. Gheida, Naglaa I. Sarhan, Nashwa N. Elfar
& Samah A. Eldelee (2019): Evaluation of the Effect of Combined Intralesional Injection of
Prostaglandin F2α with Narrow Band UVB Phototherapy in Treatment of Resistant Cases of Vitiligo,
Journal of Dermatological Treatment, DOI: 10.1080/09546634.2019.1658860
Vitiligo
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Samah A. Eldelee1 Department of Dermatology & Venereology1, Department of
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Histology2, Faculty of Medicine, Tanta University, Tanta, Egypt
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Zeinab Abdelsamd Ibrahim: MD, Professor of Dermatology and Venereology, Faculty of
Nashwa Naeem Elfar: MD, Assistant professor of Dermatology and Venereology, Faculty of
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Tanta University.
Tel: 0403418800
Mob: 01006023298
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E-mail: nashwaelfar3@gmail.com
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Text count: 3173 words
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Tables count: 3
Figures count: 9
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Abstract
on the outcome of narrow band ultraviolet rays B (NBUVB) for patients with
stable vitiligo.
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Patients and methods: The study included 27 stable vitiligo patients with
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overall symmetrical lesions. For each patient one patch was treated with
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NBUVB alone (control side) while another symmetrical patch was treated with
in the combination group compared with NBUVB group. Side effects were
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minimal.
follow up is needed.
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(1)
without complete satisfactory therapeutic outcome . The narrow band
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ultraviolet B (NB-UVB) phototherapy is considered to be a very important
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modality in vitiligo treatment since its first use in 1997. It was proved to be of
(7)
higher efficacy, better tolerated, and superior to the other lines of treatment .
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Nevertheless, it is an office-based treatment that may require more than 1 year
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for its completion. Although successful in many cases, some patients may find
this long duration of therapy inconvenient due to social and financial reasons
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(8)
.
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(9)
reversible peri-ocular hyperpigmentation observed in glaucoma patients .
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PGF2α however exerts its effect indirectly through induction of COX-2 and
PGE2 and has been reported to be a promising therapeutic option for vitiligo
This study aimed to evaluate the safety & efficacy of intralesional injection of
vitiligo.
Patients and Methods:
December 2017 to September 2018 after obtaining the approval of the research
symmetrical [site, size and duration] stable lesions [absence of new areas of
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absence of koebner phenomena during the same period]. Patients who were
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known to have a good or rapid response to conventional modalities
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[Phototherapy, medical or topical treatment] were excluded from the study.
Pregnant or lactating females were also excluded from this study. For each
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patient, one vitiligo patch was treated with NB-UVB alone to be considered as
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control, while another more or less symmetrical patch was treated with NB-
week. Patients were photographed at the first visit, in the middle and at the end
NB-UVB therapy
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All patients received NB-UVB sessions twice per week until complete
installed in a Waldmann UV-100 unit. The dose of UVB was 0.33 J/cm2 (we
started with 0.21 J/cm2 and increased gradually by 20% every session till the
For treated areas, after local anesthesia, the vitilignous lesions were
cleaned and sterilized with 70% alcohol. The injection was done using insulin
point of injection. The procedure was repeated once weekly for each patient
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until improvement occurred or for maximum 3 months (12 sessions).
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Evaluation of the treatment
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The patients were examined in the first visit and were reviewed weekly
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for the progress of therapy and the presence of any side effects. Evaluation of
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pigmentation was done by three independent dermatologists. The
Safety assessment
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manifestations.
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2 millimeter punch biopsy specimens were taken from the lesional sites
before treatment, and another biopsy was taken from the same site after the
end of treatment sessions from each side of 6 patients. The biopsy specimens
treatment sessions.
Follow-up assessment
The patients were followed-up monthly for 3 months after the end of
the lesions.
Statistical analysis
The data were collected, tabulated and statistically analyzed using SPSS
software statistical computer package version 12. For quantitative data, the
mean and standard deviation were calculated. The difference between two
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means was statistically analyzed using the Student’s t-test. P-value less than
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0.05 was considered statistically significant.
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Results
symmetrical vitiligo, regarding the gender of the patients, there were 11 males
(40.7%) and 16 females (59.3%), the age of the patients ranged from 11 to 55
years with a mean of 29.93 ± 15.32 and median 30. Six patients (22.2%) had
family history of the disease. Regarding the skin type of the patients, 8 patients
(29.6%) were skin type III and 19 patients (70.4%) were of skin type IV.
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While regarding the duration of vitiligo; it ranged from 1 to 9 years with a
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mean of (2.67 ± 1.66) with median 2 years.
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Clinical assessment
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Electron microscopic monomorphic findings and image analysis (Photos 6-
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9):
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Regarding the number of melanosomes per keratinocyte: before treatment with
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combined NB-UVB/PGF2α ranged from 4.2 - 15.0 with a mean of 9.08 ± 3.81
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and a median of 8.60, while after treatment the number of melanosomes per
keratinocyte ranged from 12.5 - 24.7 with a mean of 16.45 ± 5.12 and a
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them (p = 0.028).
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25.96 and a median of 14.0, while after treatment with combined NB-
to 189.0 with a mean of 76.50 ± 57.39 and a median of 59.50, and there was
melanocyte number in five non overlapping fields in each slide among each
vitiligo patient, the number of melanocytes in each patient ranged from 0 to 1
with a mean of 0.67 ± 0.52, while after treatment with combined intralesional
ranged from 1 - 3 with a mean of 2 ± 0.89 and a median of 2 and there was
(p=0.039),(Table3).
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Discussion
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In this study after 3 months of the treatment sessions repigmentation was
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observed in 96.2% of patients treated with combination PG F2α/NBUVB with
to NB-UVB alone.
(13)
These findings were similar to that of Parsad et al. 2002 and Kapoor et
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al. 2009 (14) , but they used PGE2 gel for 6 months.
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(13,14)
The previous studies were performed on PGE2 to induce repigmentation
in vitiligo, while PGF2α is a newer agent that is introduced and it was reported
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F2α.
(16)
However our results were superior to Stanimirovic et al. 2016 ,who used
was observed in 36% and 32% of lesions with and without microneedling,
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was 0.5mm which remains epidermal, while in our study, repigmentation was
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observed in 96.2% of cases probably because the intradermal injection of
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Lotti, et al. 2018(17), achieved superior results to ours by using a Fraxel
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Erbium laser, the successive topical application of PG F2α, and by the
(Fraxel Erbium and UVA -1 laser) and the longer duration of treatment as the
treatment has been repeated every 21 days, for nine month, while in ours it
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One of the remarkable finding in our study was that, the reported side
minor if not at all, and all patients tolerated the procedure well. Pain during
(14) (11)
Consistent with these findings Kapoor et al 2009 , Anbar et al 2015 ,
(15) (17)
Korobko et al 2016 and Lotti et al. 2018 . They recorded no or minimal
side‐ effects for the treatment with PG F2α, either topical or after dermaroller.
The commonest side effects were transient burning sensation, transient
UVB showed excellent to good response in the trunk and face, while
extremities and acral parts showed moderate response, but there were no
Parallel to our observation, Anbar et al. (18), Yones et al., (19) and Kanwar et
al (20) who found that vitiligo of the face achieved the best results.
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Kapoor et al. 2009(14), also confirmed that head and neck lesions showed the
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best response, when he assessed using topical PG E2 , while in the contrary
different localization.
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(21)
Halder and Chappell in 2009 proposed that facial skin has greater
mechanisms for PGF2α -induced repigmentation. All the PGF2α was reported
melanogenesis (24).
The PGE2 also has other biologic activities. It increases the formation of
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release of PGs in situ allowing the applied exogenous PGF2α to exert an
(24)
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additive effect on pigmentation . The second possibility is the synergistic
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alpha-melanocyte-stimulating hormone, adrenocorticotropic hormone, stem
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(25)
cell factor, and nerve growth factor28 with topically applied PGF2α .
treatment of vitiligo, to our knowledge this is the first study to date to use
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in treatment of vitiligo.
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observation in our study was detected by Ding et al.(29) and and Fawzy et al.(30)
‘‘melanocytorrhagy’’.
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indicating an impairment in the adhesion of melanocytes also involved in the
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retraction of dendrites.
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exhibited few small electron-dense melanosomes and some electron-lucent
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vacuoles also it showed dilated rough endoplasmic reticulum (RER) which is
Fawzy et al.(30) added the finding that two types of degenerative changes
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dense (dark) degeneration and were both reduced after treatment. Regarding
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as well as melanocytes.
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result, and this prove that PGF2α increased the efficacy of NB-UVB and
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repigmentation of lesions in stable vitiligo. This combination seems to be safe
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and effective in different body sites, cheap, shortens the duration of NB-UVB
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therapy and does not require costly devices and well equipped rooms. Further
studies are required with larger number of cases, longer treatment periods, and
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follow up to determine the long term efficacy and safety of intradermal
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2.Le Poole IC, van den Wijngaard RM, Westerhof W, et al. Tenascin is
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Dermatol. 1997; 137: 171–8.
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3.Ongenae K, Van Geel N, Naeyaert JM. Evidence for an autoimmune
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pathogenesis of vitiligo. Pigment cell Res. 2003; 16: 90–100.
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4.Dell’anna ML, Picardo M. A review and a new hypothesis for non-
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immunological pathogenetic mechanisms in vitiligo. Pigment cell Res. 2006;
19: 406–11.
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and turnover in patients with vitiligo. Mol Genet Metab. 2005; 86: 27–33.
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10.Anbar TS, El-Ammawi TS, Barakat M, et al. Skin pigmentation after NB-
54: 587–93.
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12.Bansal S, Sahoo B, Garg V. Psoralen-narrowband UVB phototherapy for
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Photodermatol Photoimmunol Photomed. 2013; 29: 311–7.
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13.Parsad D, Pandhi R, Dogra S, et al. Topical prostaglandin analog (PGE2)
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in vitiligo--a preliminary study. Int J Dermatol. 2002; 41: 942–5.
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861–3.
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8: 1–5.
latanoprost and successive irradiation with UVA - 1 Laser. Maced J Med Sci.
2018; 6: 49–51.
163.
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19.Yones SS, Palmer RA, Garibaldinos TM. , et al. Randomized double-blind
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trial of treatment of vitiligo: efficacy of psoralen-UV-A therapy vs
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Narrowband-UV-B therapy. Arch Dermatol. 2007; 143: 578–84.
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20.Kanwar AJ, Dogra S, Parsad D. Topical tacrolimus for treatment of
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childhood vitiligo in Asians. Clin Exp Dermatol. 2004; 29: 589–92.
21.Halder RM., Chappell JL. Vitiligo update. Semin Cutan Med Surg. 2009;
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28: 86–92.
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26.Tobin DJ, Swanson NN, Pittelkow MR, , et al. Melanocytes are not absent
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alterations of mitochondria in perilesional vitiligo skin. J Dermatol Sci. 2009;
54: 157–67.
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28.Prignano F, Ricceri F, Bianchi B, et al. Dendritic cells: ultrastructural and
30.Fawzy MM, El Maadawi ZM, Hegazy RA, et al. Vitiligo - The story from
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395–404.
34.Anbar TS, El-Sawy AE, Attia SK, et al. Effect of PUVA therapy on
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Legends of figures:
Photo 1: A-Male patient before treatment with prostaglandin F2α / NB-UVB sessions. B- At
Photo 2: A- Female patient before treatment with prostaglandin F2α / NB-UVB sessions. B-
Photo 3: A-Male patient before treatment with prostaglandin F2α / NB-UVB sessions. B- At
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Photo 4: A- Female patient before treatment with prostaglandin F2α / NB-UVB sessions. B-
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At the end of treatment showing poor improvement.
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Photo 5: A- Male patient before treatment with prostaglandin NB-UVB sessions. B- At the
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end of treatment showing poor improvement.
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Photo 6: A-Electron micrograph of ultrathin section of skin biopsy from vitiligo patient before
treatment with PGF2α/NB-UVB showed melanocyte (M) that contains few melanosomes
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(arrow) with multiple large cytoplasmic vacuoles (V) and dilated rough ER (RER). B- After
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treatment showed melanocyte with relatively many melanosomes, dilated RER and
Photo 7: A- Electron micrograph of ultrathin section of skin biopsy from vitiligo patient
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before treatment with PGF2α/NB-UVB showing many keratinocytes (K) with few or without
melanosomes. The nearby white bounded melanocyte (M) is swollen, distorted and devoid of
melanin with cytoplasmic rarefaction. The melanocytic nucleus shows dark chromatin
(x5850).
Photo 8: Electron micrograph of ultrathin section of skin biopsy from vitiligo patient before
treatment with PGF2α/NB-UVB showing keratinocytes (K) with central nucleus and
prominent nucleolus and few cytoplasmic melanosomes and complexes. The white bounded
melanocyte shows few melanin, cytoplasmic vacuoles and retracted dendrites. B- After
treatment showing keratinocytes with relatively many electron dense melanosomes (x5850).
Photo 9: Electron micrograph of ultrathin section of skin biopsy from vitiligo patient before
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The white bounded melanocyte displays depletion from melanosomes (M), indented nucleus
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and retracted dendrites. B- After treatment showing keratinocytes with few melanosomes and
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indented nucleus (x5850).
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Tables:
Table (1): Comparison between prostaglandin F2α/NB-UVB site and NB-UVB site according
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Poor 9 33.3 22 81.5
Moderate 2 7.4 0 0.0 MH <0.001*
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Good 9 33.3 0 0.0
Excellent 6 22.2 0 0.0
Percentage of
improvement us
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Min. – Max. 0.0 – 96.67 0.0 – 30.0
Z=
Mean ± SD. 47.22 ± 32.26 15.19 ± 10.42 <0.001*
3.701*
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Before
Average number of After prostaglandin
prostaglandin F2α/ Z p
melanosomes F2α/ NB-UVB
NB-UVB
Per keratinocyte
Min. – Max. 4.20 – 15.0 12.50 – 24.70
2.201* 0.028*
Mean ± SD. 9.08 ± 3.81 16.45 ± 5.12
Median 8.60 13.80
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Per melanocyte
Min. – Max. 3.0 – 74.0 35.0 – 189.0
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Mean ± SD. 22.0 ± 25.96 76.50 ± 57.39 2.201* 0.028*
Median
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59.50
Before After
Number of
prostaglandin prostaglandin Z p
melanocyte
F2α/ NB-UVB F2α/ NB-UVB
Min. –Max. 0.0 – 1.0 1.0 – 3.0
Mean ± SD. 0.67 ± 0.52 2.0 ± 0.89 2.060* 0.039*
Median 1.0 2.0
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*: Statistically significant at p ≤ 0.05
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