What’s Old Is New: An Emerging Focus on Dermatoporosis

February 2024 | Volume 23 | Issue 2 | 113 | Copyright © February 2024


Published online January 30, 2024

Cleo Whiting BA, Sara Abdel Azim MS, Adam Friedman MD FAAD

Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC
 

discussed above, as well as supplementing with oral vitamin C and a bioflavonoid complex.10,11 A mainstay of treatment is the application of topical retinoids as they upregulate HA and CD44 synthesis in mouse skin and reduce the signs of photoaging in clinical studies.5,12,13 Moreover, the application of topical retinaldehyde plus intermediate-size hyaluronate fragments shows synergistic effects, with clinical improvement of purpura and skin thickness in addition to a significant reduction in p16Ink4a-positive cells in the epidermis and dermis.14-16

Moreover, while vitamin D (VD) is a critical regulator of systemic calcium absorption and storage, it has essential functions in the skin. Notable effects of VD relevant to dermatoporosis include stimulating collagen synthesis, modulating the expression of genes contributing to epidermal development and maintenance, mitigating chronic inflammation associated with aging through anti-inflammatory effects, and providing cytoprotection in the setting of UV irradiation.17 Given this relationship between VD and normal skin homeostasis, the use of VD analogs to treat dermatoporosis may be promising. The use of calcipotriene, a synthetic derivative of vitamin D3 (calcitriol), is well-established for the treatment of psoriasis through its inhibition of keratinocyte proliferation and induction of keratinocyte terminal differentiation.18 Calcipotriene also improves wound healing through its promotion of keratinocyte migration and upregulation of human cathelicidin antimicrobial protein (hCAP18), a regulator of the innate immune response in the setting of tissue injury that promotes re-epithelialization and tissue repair.19,20 Considering these results, focal supplementation of VD in the skin using an active analog such as calcipotriene may serve to reverse the dermatoporotic state, particularly in combination with a topical retinoid (Figure 2). 
 

CONCLUSION

Dermatoporosis is a detrimental condition to the aging population and warrants continued study of its mechanisms and novel treatment options. While topical retinoids are well-known to effectively treat dermatoporosis, a vitamin D3 analog such as calcipotriene may be an additional, useful tool for treating and preventing this prevalent and deleterious skin disease.  
 

Disclosure

CW's work is funded through an independent fellowship grant from Galderma; SAA's work is funded through independent fellowship grants from Lilly and Pfizer. AF has no relevant conflicts to disclose. 
 

REFERENCES

 

1. Kaya G, Saurat JH. Dermatoporosis: a chronic cutaneous insufficiency/fragility syndrome. Clinicopathological features, mechanisms, prevention and potential treatments. Dermatology. 2007;215(4):284-294. doi:10.1159/000107621 
2. Kluger N, Impivaara S. Prevalence of and risk factors for dermatoporosis: a prospective observational study of dermatology outpatients in a Finnish tertiary care hospital. J Eur Acad Dermatol Venereol. 2019;33(2):447-450. doi:10.1111/ jdv.15240 
3. Mengeaud V, Dautezac-Vieu C, Josse G, Vellas B, Schmitt AM. Prevalence of dermatoporosis in elderly French hospital in-patients: a cross-sectional study. Br J Dermatol. 2012;166(2):442-443. doi:10.1111/j.1365-2133.2011.10534.x 
4. Kaya G, Kaya A, Sorg O, Saurat JH. Dermatoporosis, a prevalent skin condition affecting the elderly: current situation and potential treatments. Clin Dermatol. 2019;37(4):346-350. doi:10.1016/j.clindermatol.2019.04.006 
5. Kaya G, Tran C, Sorg O, et al. Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism. PLoS Med. 2006;3(12):e493. doi:10.1371/journal. pmed.0030493 
6. Kaya G, Rodriguez I, Jorcano JL, Vassalli P, Stamenkovic I. Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation. Genes Dev. 1997;11(8):996-1007. doi:10.1101/gad.11.8.996 
7. Calikoglu E, Sorg O, Tran C, et al. UVA and UVB decrease the expression of CD44 and hyaluronate in mouse epidermis, which is counteracted by topical retinoids. Photochem Photobiol. 2006;82(5):1342-1347. doi:10.1562/2006-02-10-RA-801 
8. Barnes L, Saurat JH, Kaya G. Senescent atrophic epidermis retains Lrig1+ stem cells and loses Wnt signaling, a phenotype shared with CD44KO mice. PLoS One. 2017;12(1):e0169452. doi:10.1371/journal.pone.0169452 
9. Darbellay B, Barnes L, Boehncke et al. Reversal of murine epidermal atrophy by topical modulation of calcium signaling. J Invest Dermatol. 2014;134(6):1599-1608. doi:10.1038/jid.2013.524 
10. Humbert P, Fanian F, Lihoreau T, et al. Bateman purpura (dermatoporosis): A localized scurvy treated by topical vitamin C - double-blind randomized placebo-controlled clinical trial. J Eur Acad Dermatol Venereol. 2018;32(2):323-328. doi:10.1111/ jdv.14525 
11. Berlin JM, Eisenberg DP, Berlin MB, et al. A randomized, placebo-controlled, double-blind study to evaluate the efficacy of a citrus bioflavonoid blend in the treatment of senile purpura. J Drugs Dermatol. 2011;10(7):718-722. 
12. Weiss JS, Ellis CN, Headington JT, et al. Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study. JAMA. 259(4):527-532. 
13. Lever L, Kumar P, Marks R. Topical retinoic acid for treatment of solar damage. Br J Dermatol. 1990;122(1):91-98. doi:10.1111/j.1365-2133.1990.tb08244.x 
14. Barnes L, Tran C, Sorg O, et al. Synergistic effect of hyaluronate fragments in retinaldehyde-induced skin hyperplasia which is a Cd44-dependent phenomenon. PLoS One. 2010;5(12):e14372. doi:10.1371/journal.pone.0014372 
15. Nikolic DS, Ziori C, Kostaki M, et al. Hyalurosome gene regulation and dose-dependent restoration of skin atrophy by retinaldehyde and defined-size hyaluronate fragments in dermatoporosis. Dermatology. 2014;229(2):110-115. doi:10.1159/000362594 
16. Kaya A, Saurat JH, Kaya G. Senotherapeutic effect of retinaldehyde and hyaluronate fragments in dermatoporosis. Dermatopathology (Basel). 2023;10(2):168-172. doi:10.3390/dermatopathology10020024 
17. Romano F, Serpico D, Cantelli M, et al. Osteoporosis and dermatoporosis: a review on the role of vitamin D. Front Endocrinol (Lausanne). 2023;14:1231580. doi:10.3389/fendo.2023.1231580 
18. Kragballe K, Beck HI, Sogaard H. Improvement of psoriasis by a topical vitamin D3 analogue (MC 903) in a double-blind study. Br J Dermatol. 1988;119(2):223-230. doi:10.1111/j.1365-2133.1988.tb03204.x 
19. Heilborn JD, Weber G, Gronberg A, et al. Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/ LL-37 during wounding in human skin in vivo. Exp Dermatol. 2010;19(4):332-338. doi:10.1111/j.1600-0625.2009.00997.x 
20. Wang D, Lin L, Lei K, et al. Vitamin D3 analogue facilitates epithelial wound healing through promoting epithelial-mesenchymal transition via the Hippo pathway. J Dermatol Sci. 2020;100(2):120-128. doi:10.1016/j.jdermsci.2020.08.015 

AUTHOR CORRESPONDENCE

Adam Friedman MD FAAD ajfriedman@mfa.gwu.edu
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