Alternative therapies hold promise for rosacea

Papules, pustules, and erythema are the hallmarks of rosacea, the chronic inflammatory skin disorder that generally involves the central face. Rosacea typically affects adults in the third decade and has a predilection for those with fair skin, blue eyes, and Celtic heritage.¹

Dr. Lio, Medical Dermatology Associates of Chicago While the underlying pathophysiologic details remain obscure, recent studies suggest that rosacea is initiated by inappropriate innate immune responses to environmental stimuli which then lead to inflammation, skin barrier dysfunction, and vascular abnormalities.²

What is clear is that patients are often very troubled by rosacea.

Conventional therapies are generally effective, yet few adequately treat the erythema or flushing component.³ Some patients also dislike the notion of being on oral antibiotic therapy, even low-dose sub-antimicrobial preparations. In concert, these perhaps fuel the desire for alternatives, some of which hold promise, as we shall see.

Next: Nicotinamide

Nicotinamide

Nicotinamide is also known as niacinamide. It is a water-soluble vitamin found in meat, fish and wheat. Despite the insistence of some pharmacists, it is not equivalent to niacin and has different pharmacologic effects. Unlike niacin, nicotinamide does not cause a flushing reaction, which is of particular importance in rosacea. Nicotinamide is thought to have both anti-inflammatory and barrier-enhancing effects; these match up nicely with the proposed derangements in rosacea and make it an attractive candidate. However, the actual data is somewhat sparse.

In a somewhat messy open-label prospective cohort study⁴ of oral nicotinamide (notably combined with several other minerals and vitamins) in 198 patients with acne vulgaris or rosacea, a nicotinamide-containing combination was found to be effective for reducing disease severity: nearly 80% reported “moderate” or “much better” improvement after two months. Of interest, in the group who received concurrent oral antibiotics, there was no significant improvement beyond this. The authors suggested its anti-inflammatory properties were responsible, but mixing acne and rosacea and using a combination of nicotinamide, zinc, copper and folic acid makes it much more difficult to discern what actually was at play.

In another trial, randomized and controlled with 50 patients, a niacinamide-containing moisturizer improved the skin barrier and hydration on the face, suggesting that there is some benefit for the skin barrier beyond moisturization alone.⁵

Finally, 34 patients with rosacea were treated with a gel containing a nicotinamide metabolite (MNA) twice daily for four weeks, and found good improvement in 9/34 and moderate improvement in 17/34, with one case of skin irritation resulting in withdrawal from the study.⁶

Despite the relatively sparse data, nicotinamide continues to surface as a potential treatment for rosacea, even in more recent reviews.⁷ Its relative safety and now frequent appearance in many facial moisturizers allows for complementary placement of nicotinamide in almost any rosacea regimen.

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Next: Chrysanthellum indicum

Chrysanthellum indicum

Wild chrysanthemum (Chyrsanthellum indicum) has been shown to possess anti-inflammatory and anticancer activities.⁸ Its extract also appears to protect the skin from UVB-induced skin damage and photoaging by decreasing the intracellular reactive oxygen species and inhibiting p38 MAPK phosphorylation.⁹Chrysanthellum indicum contains a number of flavonoids and has a documented effect on vascular wall permeability, improving the mechanical resistance of capillaries.¹⁰

In a randomized, placebo-controlled trial¹⁰ of 246 patients with moderate rosacea, patients were instructed to apply the C. indicium extract cream twice daily for 12 weeks. Severity of erythema and an overall assessment of the rosacea were found to be significant reduced in the treatment group compared to both baseline scores and placebo, with adverse effects mild and no different from the placebo group.

Unfortunately, that appears to be the limit of clinical trials for this promising intervention, underscoring the need to revisit alternatives with such potential. This is especially true given the paucity of treatments that are useful for erythema.

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Next: Quassia extract

Quassia extract

Quassia amara is a small South American tree thought to have anti-inflammatory and anti-parasitic properties.¹¹Quassia amara contains high levels of active phytochemicals and has been shown to be effective against facial seborrheic dermatitis as compared to topical ketoconazole 2%, a condition that is sometimes found to overlap with rosacea.¹²

In an open-label uncontrolled study of 30 patients with a wide range of rosacea severity from mild to severe, a 4% Quassia amara extract gel was applied for six weeks. Throughout the study, there was continued improvement noted in telangiectasia, papules, pustules and in overall improvement. Of the 30 patients who participated, 27 patients completed the six weeks, with three lost to follow up. At the end of the study, 37% of patients reported excellent improvement or complete remission, 22% reported marked improvement, and 11% had no improvement at all. The authors posit that the effect may be due to the anti-inflammatory properties or perhaps the anti-parasitic effect on Demodex mites that have a somewhat controversial relationship to rosacea.¹²

Conclusion

Rosacea continues to challenge both patients and practitioners. With careful avoidance of known triggers such as caffeine, alcohol, heat and sun, along with standard conventional therapies like topical metronidazole, azelaic acid preparations and oral tetracyclines, many patients can achieve excellent control. For those who cannot, newer therapies such as vasoconstrictor agents, anti-parasitic topical preparations and sub-antimicrobial antibiotics may be of tremendous value.

However, lack of efficacy, intolerability, cost, and even patient preference can sometimes force the need to think outside the box.  For these cases, looking into these alternatives could hold promise for the outliers but also, perhaps, even for the mainstream.

Disclosures: Dr. Lio reports no relevant disclosures.

References:

1.       Gupta AK, Chaudhry MM. Rosacea and its management: an overview. J Eur Acad Dermatol Venereol. 2005 May;19(3):273-85.

2.       Steinhoff M, Schauber J, Leyden J. New insights into rosacea pathophysiology: A review of recent findings. J Am Acad Dermatol 2013; 69:S15-26

3.       Layton A, Thiboutot D. Emerging therapies in rosacea. J Am Acad Dermatol 2013; 69:S57-65

4.       Niren, NM.Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review. Cutis77:11-16, 2006.

5.       Draelos Z, Ertel K, Berve C: Niacinamide-containing facial moisturizer improves the skin barrier and can benefit people with roscea. Cutis 76;135-141, 2005.

6.       Wozniacka A, Wieczorkowska M, Gebick J, et al. Topical application of 1-methylnicotinamide in the treatment of rosacea: a pilot study. Clin Exp Dermatol. 2005. Nov;30(6):632-5.

7.       Rolfe HM. A review of nicotinamide: treatment of skin diseases and potentialside effects. J Cosmet Dermatol. 2014 Dec;13(4):324-8.

8.       Kim C, Kim M, Kim S. Chrysanthemum indicum L. extract induces apoptosis through suppression of constitutive STAT3 activation in human prostate cancer DU145 cells. Phtother Res. 2013 Jan; 27(1): 30-8.

9.       Sun S, Jiang P, Su W, et al. Wild chrysanthemum extract prevents UVB radiation-induced acute cell death and photoaging. Cytotechnology. 2014 Jul 23

10.   Rigopoulos D, Kalogeromitros D, Gregoriou S et al. Randomized placebo-controlled trial of a flavonoid-rich plant extract cream in the treatment of rosacea. J Eur Acad Dermatol Venereol 2005 19(5): 654-8.

11.   Toma W, Gracioso J, Hiruma-Lima CA, et al. Evaluation of the analgesic and antiedematogenic activities of Quassia amara bark extract. Journal of Ethnopharmacology 85 (2003): 19-23.

12.   Diehl, C, Ferrari M. Efficacy of Topical Quassia amara Gel in Facial Seborrheic Dermatitis: A randomized, Double-Blind, Comparative Study. Journal of Drugs in Dermatology 2013; 12 (3):312-315