Systemic photoprotection in solar urticaria with α-melanocyte-stimulating hormone analogue [Nle4-D-Phe7]-α-MSH.
BACKGROUND
Solar urticaria is a rare photosensitivity disorder demonstrating a range of action spectra, which can inflict a very large impact on life quality despite available treatments. Melanin broadly reduces skin penetration by ultraviolet-visible wavelengths, thus increased melanization may protect in solar urticaria.


OBJECTIVE
To examine quantitatively for impact of the potent α-melanocyte stimulating hormone analogue afamelanotide ([Nle(4)-D-Phe(7)]-α-MSH, Scenesse(®); Clinuvel Pharmaceuticals Ltd, Melbourne, Vic., Australia) on the solar urticaria response and skin melanization.


METHODS
Five patients with solar urticaria received a single dose of 16 mg subcutaneous afamelanotide implant in winter time. Melanin density was assessed spectrophotometrically from day 0 to day 60. Detailed monochromated light testing to geometric dose series (increment ) of wavelengths 300-600 nm was performed at 0, 30 and 60 days, with assessment of weal and flare area and minimum urticarial dose (MUD). Data were analysed by repeated-measures anova.


RESULTS
Mean melanin density increased by day 7, peaked at day 15 and remained elevated at day 60 (P=0·03, 0·01, 0·02 vs. baseline, respectively). Baseline phototesting revealed action spectra of 320-400 (n=1), 320-500 (n=2), 300-600 (n=1) and 370-500 nm (n=1), and on afamelanotide mean rises in MUD of 1-12 and 1-3 dose increments were seen at the individual wavelengths tested, at 30 and 60 days, respectively. A significant fall in weal area occurred across responding wavelengths from 300 to 600 nm at 60 days postimplant (P=0·049 vs. baseline), accompanied by greater than twofold overall increase in MUD (P=0·058 vs. baseline).


CONCLUSIONS
Melanization following afamelanotide is accompanied by reduction in solar urticaria response across a broad spectrum of wavelengths. Further study is warranted to assess clinical benefit under ambient conditions in summer.
Dermatological Sciences, Inflammation Sciences Research Group, School of Translational Medicine, University of Manchester, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Manchester M6 8HD, UK.
A K
AK
Haylett
Z
Z
Nie
M
M
Brownrigg
R
R
Taylor
L E
LE
Rhodes
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005260:Female; D006728:Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008543:Melanins / Q000378:metabolism; D008875:Middle Aged; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012880:Skin Pigmentation / Q000187:drug effects* / Q000528:radiation effects; D013473:Sunscreening Agents / Q000008:administration & dosage*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014581:Urticaria / Q000188:drug therapy* / Q000378:metabolism; D055815:Young Adult; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D004343:Drug Implants; D006728:Hormones; D008543:Melanins; D013473:Sunscreening Agents; D000521:alpha-MSH; C534526:afamelanotide