Dear Editor,
Much of what we know about atopic dermatitis (AD) pathogenesis revolves around the fundamental concepts of barrier dysfunction, pruritus/inflammation, and a dysfunctional immune response. Dermatologists often give advice concentrating on moisturizing, bathing, cleansing, and reducing symptoms of itching and dryness for patients with AD. A recent observation in AD research is that oxidative stress plays a central role in the pathogenesis of this chronic relapsing skin disorder. Events that lead to skin barrier defects have also been correlated with the release of reactive oxygen species, which directly damage the skin’s cellular components, such as the cell membrane, organelles, and even DNA (Fig. 1; Ji and Li, 2016).
Fig. 1.
Interplay among oxidative stress, skin barrier defect, and inflammation in atopic dermatitis.
Oxidative stress is recognized as having an impact on hypertension, diabetes, heart disease, and certain cancers, as well as skin disorders. Studies have highlighted oxidative stress and the effects of antioxidant therapy on skin diseases (Fig. 2). For certain skin diseases (e.g., AD), higher levels of oxidative damage markers are seen during exacerbations (Baek and Lee, 2016). Also, at least one of the following defects can be found in patients with AD: Oxidative stress, increased oxidative stress signals during flares, and/or decreased antioxidant levels (Ji and Li, 2016). Patients with AD often have lower systemic antioxidant levels and may have lower dietary intake of nutrients with antioxidant properties, but the relationship between systemic antioxidant status and AD risk warrants further evaluation in large, prospective studies.
Fig. 2.
Oxidative stress has been defined as a state of imbalance wherein reactive oxygen species overwhelm the capacity of the intrinsic antioxidant systems to inhibit cellular damage due to oxidation (Adapted from Baek and Lee, 2016).
Standard moisturizer therapy with emollients has been the therapy of choice for barrier repair. Growing evidence shows that topical antioxidants could provide additional protection against oxidative stress when admixed with moisturizers. Barrier-enhancing moisturizers in combination with antioxidants were observed to have comparable effects as topical corticosteroids on the permeability of the skin barrier (Man et al., 2015).
Recently, a review of the antioxidant furfuryl palmitate and its effect on mild-to-moderate AD and other related skin disorders (i.e., atopic, seborrheic, irritative, allergic contact dermatitis, xerosis, and cutaneous inflammatory pathologies) has been published. Furfuryl palmitate and its derivatives were effective and safe in treating AD, may be used as an adjunct to moisturizers, and may even be considered as a replacement for topical corticosteroids and calcineurin inhibitors (Table 1; Pigatto and Diani, 2018).
Table 1.
A summary of reports on furfuryl palmitate and its derivatives (Pigatto and Diani, 2018).
| Lead author; year | Agent | Study design; number of patients | Results; adverse events | Formulation; duration of treatment; frequency of applications |
|---|---|---|---|---|
| Patrizi et al., 2012 | Sorbityl furfural palmitate vs. placebo | Single-center, double-blinded, randomized, placebo-controlled study; 60 pediatric patients | Significant reduction of itching and severity; no severe adverse events | Cream; 30 days; twice a day |
| Nemelka et al., 2002 | Superoxide dismutase, 18 beta-glycyrrhetinic acid, vitamin E, alpha bisabolol, and furfuryl palmitate | Unilateral trial; 60 pediatric patients | Improvement of inflammatory skin conditions; no relevant adverse events | Cream; 2 weeks; twice a day |
| Bocchietto et al., 2002 | Superoxide dismutase, 18 beta-glycyrrhetinic acid, vitamin E, alpha bisabolol, and furfuryl palmitate | Unilateral trial; 64 adults and 44 pediatric patients | Reduction of erythema and itching; no relevant adverse events | Cream; 2 weeks; twice a day |
| Pigatto et al., 2011 | Furpalmate vs. vehicle | Double-blinded, randomized, placebo-controlled study; 40 adult patients | Reduction of signs and symptoms of atopic dermatitis; no severe adverse events | Cream; 21 days; twice a day |
| Lauriola et al., 2011 | Furpalmate vs. topical corticosteroid | Investigator-blinded, randomized, placebo-controlled study; 40 adult patients | Both groups significantly improved from baseline with no difference between the groups | Cream; 14 days; twice a day |
| Tripodi et al., 2009 | Emollient cream enriched with furfuryl palmitate vs. emollient cream | Randomized controlled trial; 117 pediatric patients | No statistical difference, but treatment product was less tolerated | Cream; 14 days; twice a day |
In conclusion, oxidative stress may be another potential target in AD management. Alternative pharmaceutical antioxidant agents, such as furfuryl palmitate and its derivatives, may provide effective and safe steroid-sparing options for AD in the future. More robust trials are needed to show the definitive effects of these agents on the prevention and treatment of AD exacerbations.
Conflict of Interest
None.
Funding
I would like to thank Relife s.r.l for the unrestricted educational grant provided for this research.
Study Approval
The author(s) confirm that any aspect of the work covered in this manuscript that has involved human patients has been conducted with the ethical approval of all relevant bodies.
Acknowledgments
The author thanks Dr. Dennis Malvin H. Malgapo of MIMS Pte Ltd for his medical writing services.
References
- Baek J., Lee M.G. Oxidative stress and antioxidant strategies in dermatology. Redox Rep. 2016;21(4):164–169. doi: 10.1179/1351000215Y.0000000015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bocchietto E., Pecis L., Lisi P. Furfuril palmitato: Un nuovo antiossidante topico efficace nel trattamento di dermatiti eczematose. G Ital di Dermatologia e Venereol. 2002;137(2):1–13. [Google Scholar]
- Ji H., Li X.K. Hindawi Publishing Corporation; New York, NY: 2016. Oxidative stress in atopic dermatitis. Oxidative medicine and cellular longevity. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lauriola M, Pigatto P, Pedrelli V. A single-center, randomized, perspective, investigator blinded controlled trial to examine efficacy and safety of a furpalmate cream in comparison to topical corticosteroid in atopic dermatitis of hands of 40 adult patients. In: Poster session 20th EADV Congress. Lisbon, Portugal; 2011.
- Man G., Elias P.M., Man M.Q. Therapeutic benefits of enhancing permeability barrier for atopic eczema. Dermatol Sin. 2015;33(2):84–89. [Google Scholar]
- Nemelka O., Bleidel D., Fabrizi G., Camplone G., Occella C., Marzatico F. Experimental survey of a new topical anti-oxidant based on furfuryl palmitate in the treatment of child’s and baby’s dermatitis with eczema: results from a multicenter clinical investigation. Minerva Pediatr. 2002;54(5):465–474. [PubMed] [Google Scholar]
- Patrizi A, Raone B, Raboni R, Neri I. Efficacy and tolerability of a cream containing AR-GG27(R) (sorbityl furfural palmitate) in the treatment of mild/moderate childhood atopic dermatitis associated with pityriasis alba. A double-blind, placebo-controlled clinical trial. G Ital Dermatol Venereol. 2012 Dec; 147 (6 Suppl 1):1–8. [PubMed]
- Pigatto P, Lauriola M, Vaccari G. A single-center, randomized, double-blind, perspective, controlled study of efficacy and safety of a furpalmate-containing cream versus vehicle in the treatment of 40 adult patients with mild to moderate atopic dermatitis. In: Poster session 20th EADV Congress. Lisbon, Portugal; 2011.
- Pigatto P.D., Diani M. Beneficial effects of antioxidant furfuryl palmitate in non-pharmacologic treatments (prescription emollient devices, PEDs) for atopic dermatitis and related skin disorders. Dermatol Ther (Heidelb) 2018;8(3):339–347. doi: 10.1007/s13555-018-0239-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tripodi S., Di Rienzo Businco A, Panetta V., Pingitore G., Volterrani A., Frediani T. Lack of efficacy of topical furfuryl palmitate in pediatric atopic dermatitis: a randomized double-blind study. J Investig Allergol Clin Immunol. 2009;19(3):204–209. [PubMed] [Google Scholar]