Today, azelaic acid is particularly praised for the numerous benefits it offers and its ability to target a multitude of skin issues, especially when it comes to minimizing skin imperfections or mattifying the complexion. However, this active ingredient first made its name as a medicinal skin gel that reduces and relieves the visible symptoms of rosacea from mild to moderate. Continue reading if you want to learn more about how azelaic acid can affect this skin condition.
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The benefits of azelaic acid on rosacea.
Summary
- Azelaic Acid for Rosacea: What are the Benefits?
- Rosacea: How to use azelaic acid for optimal results?
- Sources
Published November 5, 2021,
updated on April 12, 2024,
by
Stéphanie, PhD, Doctorate in Life and Health Sciences
—
15 min read
Azelaic Acid for Rosacea: What are the Benefits?
For many individuals, the visible symptoms of rosacea (redness, telangiectasias, papules, inflamed pustules, etc.) impact their willingness to engage socially and their self-esteem. Although there is no cure for rosacea, it is possible to manage its clinical signs with appropriate treatment, thereby improving quality of life. Azelaic acid in the form of a gel or cream is one of the most frequently mentioned topical treatments in the literature.
Available over-the-counter or by prescription, azelaic acid is identified as a first-line topical treatment for rosacea to reduce the appearance of redness and soothe inflammation. Numerous reports have demonstrated its effectiveness against this skin condition and define an optimal role for azelaic acid in rosacea treatment strategies. It could also be a good alternative to other equally effective treatments for certain types of patients, such as during pregnancy.
According to a review, more than twenty randomized controlled trials and comparative studies with other treatments (metronidazole, brimonidine, permethrin, Nd-YAG laser, etc.) focusing on the effects of azelaic acid on rosacea have been conducted to date. The participants in the studies, suffering from moderate to severe rosacea, were aged between 18 and 83 years, of which 75.4% were women and with 89.2% having a light phototype (I and II).
Through various analytical methods, multiple pieces of evidence have shown that azelaic acid (15% or 20%) is more effective than its vehicle (without azelaic acid) in improving the appearance of erythema in subjects. This conclusion is based on several thousand patients who showed improvement after 12 weeks of treatment. For mild to moderate forms of therosacea acne, azelaic acid represents the first established therapeutic option. Indeed, it has also proven to be more effective than the vehicle (without azelaic acid) in reducing the number of inflammatory lesions (papules, pustules) in patients suffering from papulopustular rosacea.
| References | Type of Study | Sampling | Treatment(s) | Frequency of Use and Duration of Treatment | Efficacy Results | Safety (Adverse Effects) |
|---|---|---|---|---|---|---|
| ZAUMSEIL R. & al (1993) | Monocentric comparative study in double-blind, controlled, and split-face design | 33 individuals with papulopustular rosacea (15 men and 18 women) | 20% Azelaic Acid Cream | Twice a day for 9 weeks | Reduction of papules, pustules, and erythema, superior on the side treated with azelaic acid | 24 cases of minor local skin irritation after 3 weeks of application |
| GRAUPE K. & al (1999) | Randomized, double-blind, multicenter study with parallel groups | 114 patients suffering from papulopustular rosacea (55 men and 59 women) | 20% Azelaic Acid Cream | Twice a day for 3 months | Reduction in the total number of inflammatory lesions (73.47% for azelaic acid compared to 50.67% for the placebo) and in the severity of erythema (47.97% for azelaic acid compared to 37.97% for the placebo) | 5 cases of local adverse effects (burning sensation, erythema, irritation, contact dermatitis) |
| MADDIN S. (1999) | A single-center comparative study, double-blind, randomized, and split-face | 40 light phototype patients suffering from symmetrical papulopustular rosacea (11 men and 29 women) | 20% Azelaic Acid Cream versus 0.75% Metronidazole Cream | Twice a day for 15 weeks | Similar reduction in the number of inflammatory lesions and the degree of erythema | A case of tingling upon application |
| GRAUPE K. & al (2003) | Phase III multicenter study, double-blind, randomized, parallel-group, and vehicle-controlled | 329 patients with moderate facial papulopustular eruptions (92.5% of patients with fair skin and 73% women) | 15% Azelaic Acid Gel | Twice a day for 12 weeks | Greater reduction in the number of inflammatory lesions than the placebo (58% versus 40%); higher improvement in erythema compared to the vehicle gel (44% versus 29%) | 10% of local adverse effects (sensations of burning, tingling, and itching) |
| GRAUPE K. & al (2003) | Phase III multicenter study, double-blind, randomized, parallel-group, and vehicle-controlled | 335 patients with moderate facial papulopustular eruptions (92.5% of patients with fair skin and 73% women) | 15% Azelaic Acid Gel | Twice a day for 12 weeks | Greater reduction in the number of inflammatory lesions than the placebo (51% versus 39%); higher improvement in erythema compared to the vehicle gel (46% versus 28%) | 8.4% of local adverse effects (sensations of burning, tingling, and itching) |
| PARISER D. M. & et al. (2003) | A multicenter comparative trial, double-blind, randomized, and controlled | 251 patients suffering from moderate papulopustular rosacea (93.2% of patients with fair skin and 67.7% women) | 15% Azelaic Acid Gel versus 0.75% Metronidazole Cream | Twice a week for 15 weeks | Reduction in the number of inflammatory lesions superior to metronidazole (-72.7% versus -55.8%); improvement in the severity of erythema (56% versus 42%) | 32 cases of side effects (burning sensation, tingling, itching, peeling, skin dryness) |
| ARSONNAUD S. & et al. (2006) | Randomized Controlled Trial | 160 subjects suffering from moderate rosacea | 15% Azelaic Acid Gel versus 1% Metronidazole Gel | Once a day (metronidazole) or twice a day (azelaic acid) | Similar reduction in the number of inflammatory lesions (77% for metronidazole versus 80% for azelaic acid) and erythema (42.7% for metronidazole and 42.3% for azelaic acid) | No adverse event |
| ADISEN E. & others (2008) | Randomized Controlled Trial | 31 adults suffering from mild to moderate rosacea acne (9 men and 22 women) | 15% Azelaic Acid Gel | Twice a day for 4 weeks | Reduction in the number of inflammatory lesions in 58% of subjects; Decrease in facial erythema in 68% of patients | Up to 40% of side effects (tingling and burning sensations) |
| ABDEL GAWAD E. H. & et al. (2009) | Randomized Comparative Study | 24 patients suffering from facial rosacea (23 women and 1 man) | 20% Azelaic Acid Cream versus 0.75% Metronidazole Cream versus 5% Permethrin Cream | Twice a week for 15 weeks | Superior efficacy of azelaic acid cream on inflammatory lesions; less effective on erythema compared to the other two treatments | Instances of side effects (itching, burning sensations, swelling, and flaking) |
| RICH P. A & et al. (2009) | Randomized, multicenter, two-phase controlled study | 172 subjects with moderate to severe papulopustular rosacea | Phase 1: 15% azelaic acid gel + 100 mg oral doxycycline; Phase 2 (maintenance): 15% azelaic acid gel | Phase 1: Twice daily for 12 weeks; Phase 2 (maintenance): Twice daily for an additional 24 weeks | Phase 1: 81.4% of subjects achieved a reduction of at least 75% in the number of inflammatory lesions; Phase 2 (maintenance): remission was maintained in 75% of patients | No adverse event |
| SHAKERY K. & et al. (2015) | Phase III randomized clinical trial, double-blind and vehicle-controlled | 961 subjects suffering from papulopustular rosacea | 15% Azelaic Acid Foam | Twice a day for 12 weeks | Reduction in the number of inflammatory lesions | No adverse event |
| MICALI G. & al (2021) | Multicenter, prospective, and open-label trial | 45 patients suffering from mild to moderate inflammatory rosacea (34 women and 10 men) | Cream with 15% azelaic acid and 1% dihydroavenanthramide D | Twice a day for 8 weeks | Reduction of rosacea symptoms compared to the initial value | 1 case of local skin reaction (severe erythema) |
All clinical studies conducted have shown no effect of topical azelaic acid on the severity of telangiectasias.
What mechanisms does azelaic acid use to help skin prone to rosacea?
Given that inflammation is a central process in the pathogenesis of rosacea, it is possible that the anti-inflammatory activity of azelaic acid could provide a potential mechanistic explanation for its beneficial effect in rosacea observed in clinical trials. Histologically, studies have noted that the improvement of rosacea signs by azelaic acid is accompanied by a reduction in epidermal and dermal inflammatory reactions, and an absence of dilated vessels.
Recently, the role of reactive oxygen species (ROS) in the pathophysiology of rosacea has been recognized, with several biochemical mechanisms involved (deactivation of natural oxidative defenses, oxidative modification of proteins and lipids, alteration of lipid balance, abnormally high levels of cathelicidin, and release of inflammatory mediators).
However, studies in vitro have shown that azelaic acid would exert these effects by inhibiting the metabolic function of neutrophils, which impacts the release of pro-inflammatory ROS in a dose-dependent manner. Furthermore, another study demonstrated its anti-inflammatory effect in vivo on adult female acne by modulating the expression of the TLR-2 receptor, whose activation triggers an inflammatory response via the NF-κB pathway, which then triggers the production of several inflammatory cytokines (IL-1α, IL-8, IL-12), and which is involved in the pathophysiology of rosacea.
Rosacea acne, being a chronic inflammatory disease, its exact mechanism of action is not yet known. However, it is presumed that the beneficial effects of azelaic acid in papulopustular rosacea are related to its anti-inflammatory action.
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Rosacea: How to use azelaic acid for optimal results?
Available in the form of cream, foam, or gel, azelaic acid is to be applied once or twice a day. In 2008, GRAUPE K. and his team observed no difference between the groups receiving a once-daily and twice-daily treatment with a 15% azelaic acid gel in individuals with mild to moderate papulopustular rosacea. Duringapplication, the product should be gently massaged onto perfectly cleansed skin.
Furthermore, it is necessary to consistently use azelaic acid for between 9 and 15 weeks to significantly reduce the symptoms of rosacea. Beyond this period, if no improvement is observed, it is recommended to consult a healthcare professional for an evaluation. For optimal results, individuals are also advised to avoid factors that may exacerbate their rosacea symptoms (spicy foods, alcoholic or hot beverages, excessive UV exposure, emotional stress, etc.).
Unlike other treatments, the topical use of azelaic acid during pregnancy is generally recognized as safe. There is currently no evidence that azelaic acid can harm the fetus. However, if you wish to use azelaic acid, exercise caution and always seek advice from a doctor.
Sources
ZAUMSEIL R. & al. Topical azelaic acid in the treatment of rosacea. Journal of Dermatological Treatment (1993).
GRAUPE K. & al. Double-blind comparison of azelaic acid 20% cream and its vehicle in treatment of papulo-pustular rosacea. Acta Dermato-Venereologica (1999).
MADDIN S. A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Journal of the American Academy of Dermatology (1999).
GRAUPE K. & al. Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies. Journal of the American Academy of Dermatology (2003).
PARISER D. M. & al. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. Archives of Dermatology (2003).
VAN ZUUREN E. J. & al. Interventions for rosacea. Cochrane Review (2003).
EBELL M. Metronidazole vs. azelaic acid for acne rosacea. American Family Physician (2004).
ARSONNAUD S. & al. Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea. Cutis (2006).
GOVER M. D. & al. Azelaic acid (15% gel) in the treatment of acne rosacea. International Journal of Dermatology (2007).
ADISEN E. & al. Photographic evaluation of 15% azelaic acid gel in acne rosacea. Journal Of The Turkish Academy Of Dermatology (2008).
GRAUPE K. & al. Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. Journal of Drugs in Dermatology (2008).
LAYTON A. & al. Azelaic acid 15% gel in the treatment of rosacea Harald. Expert Opinion on Pharmacotherapy (2008).
ABDEL GAWAD E. H. & al. Comparative study of some treatment modalities of rosacea. Journal of the European Academy of Dermatology and Venereology (2009).
JONES D. A. & al. Rosacea, reactive oxygen species, and azelaic acid. Journal of Clinical and Aesthetic Dermatology (2009).
RICH P. A & al. A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy. Journal of Drugs in Dermatology (2009).
A study to evaluate the safety and clinical study of azelaic acid gel 15% in patients with moderate facial rosacea (NCT02120924) – ClinicalTrials.gov (2014).
HEGEL J. K. & al. Azelaic acid: properties and mode of action. Skin Pharmacology and Physiology (2014).
SHAKERY K. & al. Randomized, phase III, double-blind, vehicle-controlled clinical trial to evaluate the safety and efficacy of 12 weeks of twice-daily azelaic acid foam, 15% in papulopustular rosacea. Journal of the American Academy of Dermatology (2015).
Finacea 15% and brimonidine 0.33% gel in the treatment of rosacea – a pilot study (NCT02147691) – ClinicalTrials.gov (2015).
Combination gel and vascular ND in mild to moderate rosacea (NCT01631656) – ClinicalTrials.gov (2017).
BAGATIN E. & al. Modulation of Toll Like Receptor-2 on sebaceous gland by the treatment of adult female acne. Dermato-Endocrinology (2017).
A study to evaluate safety and equivalence of generic azelaic acid foam and Finacea® foam in participants with rosacea (NCT03287791) – ClinicalTrials.gov (2019).
MICALI G. & al. A novel azelaic acid formulation for the topical treatment of inflammatory rosacea: A multicentre, prospective clinical trial. Journal of Cosmetic Dermatology (2021).
MAYBURY C. & al. A systematic review to evaluate the efficacy of azelaic acid in the management of acne, rosacea, melasma and skin aging. Journal of Cosmetic Dermatology (2023).
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