Examining 15% Azelaic Acid Foam for the Treatment of Folliculitis: A Pilot Study

J Clin Aesthet Dermatol. 2020;13(4):36–38

by Zoe Diana Draelos, MD

Dr. Draelos is with Dermatology Consulting Services, PLLC in High Point, North Carolina.

FUNDING: Funding was provided by Leo Pharma.

DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article.

ABSTRACT: Background. Folliculitis is a frequently recurrent skin condition characterized by inflammatory papules and pustules on numerous body areas arising from follicular irritation induced by shaving or trauma but might also arise in the presence of bacterial or fungal organisms. Oral and topical antibiotics remain the mainstay of treatment, but the chronicity of the condition requires a safe maintenance therapy.

Objective. The objective of this study was to examine the off-label use of 15% azelaic acid foam in the treatment of folliculitis.

Design. Subjects received 15% azelaic acid foam for twice daily application to all areas of folliculitis for four weeks.

Participants. Twenty-six male or female subjects with dermatologist diagnosed folliculitis participated in this research.

Measurements. Assessments consisted of the dermatologist investigator and subjects evaluating several parameters on a five-point scale (0=none, 1=minimal, 2=mild, 3=moderate, 4=severe) at baseline, Week 2, and Week 4. The dermatologist investigator evaluated lesional erythema, lesional inflammatory papule size, extent of inflammatory papules, lesional pus, lesional pustule size, extent of pustules, and overall folliculitis assessment. The subjects assessed itching associated with folliculitis, pain associated with folliculitis, lesional pus, lesional redness, extent of involvement, and overall folliculitis assessment.

Results. After four weeks of 15% azelaic acid foam treatment, the investigator noted a 67-percent reduction in lesional erythema, 73-percent reduction in lesional inflammatory papule size, 87-percent reduction in extent of pustules, and 78-percent reduction in overall folliculitis. The subjects reported a reduction of 60-percent in folliculitis itching, 67-percent reduction in pain, 73-percent reduction in lesional pus, 51-percent reduction in lesional redness, and 59-percent reduction in extent of folliculitis involvement.

Conclusion. Azelaic acid 15% foam used off-label might be a useful treatment or adjunctive therapy for folliculitis.

KEYWORDS: Azelaic acid foam, folliculitis, ingrown hairs, pustulosis

Folliculitis is a common challenging dermatologic condition characterized by inflammatory papules and pustules on the hair bearing skin of the scalp, neck, chest, back, arms, and/or legs.¹ Inflammation can be induced by physical injury, infection, or chemical irritation. The most common physical injury is shaving either with a nonmechanized razor or a mechanized shaver. When the cause is infectious, Staphylococcus aureus is the most likely pathogen; however, commensal organisms, such as yeast or the the fungi pityrosporum, might also cause infection.^2,3 While folliculitis can be treated on an episodic basis with oral/topical antibiotics, recurrence is common and frequent once the antibiotics are discontinued. Patients with folliculitis might even elect to stay on antibiotics long term for maintenance therapy, which is undesirable.

There is need for a topical folliculitis treatment that can both improve the inflammatory papules and pustules while possessing the ability to function as a safe maintenance therapy. Several topical antibiotics are used off-label for folliculitis treatment, including erythromycin, clindamycin, mupirocin, dapsone, and azelaic acid.⁴ Topical erythromycin is seldom used due to widespread bacterial resistance arising from its extensive use in the treatment of acne.⁵ Clindamycin has replaced erythromycin topically in acne treatment and is used off-label for the treatment of folliculitis as less resistance has developed. Dapsone is also a synthetic antibiotic that could be used off-label for folliculitis.

Azelaic acid is a naturally occurring nontoxic preservative found in grains, such as wheat, barley, and rye, which prevent spoilage by functioning as an antibacterial. It has in-vitro and in-vivo antimicrobial effects against both aerobic and anaerobic microorganisms, such as P. acnes.^6,7 Azelaic acid, also known as nonanedioic acid, is a saturated C9 dicarboxylic acid produced by Malassezia furfur, a normal fungal component of the skin biofilm. At present, azelaic acid foam is approved for the treatment of facial rosacea,⁸ but also has utility in the treatment of acne.⁹ This study sought to evaluate the efficacy of azaleic acid foam in the off-label treatment of folliculitis.¹⁰

Method

This was a single-site, monadic, open-label study to evaluate the efficacy of twice-daily application of 15% azelaic acid foam (Finacea foam; Leo Pharma, Madison, New Jersey) in the treatment of folliculitis of the scalp, neck, chest, back, arms, and/or legs. The study enrolled 26 male or female patients, aged 18 years or older, of all Fitzpatrick Skin Types who were diagnosed by the dermatologist investigator with folliculitis. Subjects washed out of all topical and oral folliculitis treatments for four weeks prior to the study enrollment and all medicated cleansers for two weeks prior to study enrollment. Subjects were eligible for inclusion if they had no known medical conditions that, in the investigator’s opinion, would interfere with study participation, nor any skin diseases other than folliculitis in the area of evaluation. Women of childbearing age were included in the study only if they were willing to use a form of birth control during the study period. Potential participants were excluded from the study if they had demonstrated a previous hypersensitivity reaction to any of the ingredients of the study products, were pregnant, breast feeding, or planning a pregnancy, or had clinically significant unstable medical disorders. Following completion of informed consent and inclusion/exclusion criteria evaluation, suitable subjects with folliculitis received 15% azelaic acid foam for twice-daily application to all affected areas and a nonmedicated cleansing bar (Dove Sensitive Skin Bar Unscented; Unilever, London, United Kingdom) for all bathing during the study. The first study product application occurred at the research center under the supervision of the dermatologist investigator to ensure adequate medication was applied to all affected areas by the subjects. A diary was given to each participant to monitor adherence.

Assessments consisted of the dermatologist investigator and subjects evaluating several parameters on a five-point scale (0=none, 1=minimal, 2=mild, 3=moderate, 4=severe) at baseline, Week 2, and Week 4. The dermatologist investigator evaluated lesional erythema, lesional inflammatory papule size, extent of inflammatory papules, lesional pus, lesional pustule size, extent of pustules, and overall folliculitis assessment. The subjects assessed itching associated with folliculitis, pain associated with folliculitis, lesional pus, lesional redness, extent of involvement, and overall folliculitis assessment. A two-tailed Mann-Whitney t-test was used to analyze the nonparametric investigator and subject ordinal data sets with significance set at p<0.05.

Results

All subjects (N=26) successfully completed the four-week azelaic acid foam evaluation. One subject experienced a slight irritant contact dermatitis on the upper inner thigh after three days of use, but the dermatitis resolved when she reduced the amount of azelaic acid foam applied to the area and she successfully completed the trial. The azelaic acid foam was highly effective in treating the signs and symptoms of folliculitis in all body areas. At Weeks 2 and 4, highly statistically significant (p<0.001) improvement was seen in all investigator evaluated attributes, including lesional erythema, lesional inflammatory papule size, extent of inflammatory papules, lesional pus, lesional pustule size, extent of pustules, and overall folliculitis assessment. At Week 4, this translated into a 67-percent reduction in lesional erythema, 73-percent reduction in lesional inflammatory papule size, 75-percent reduction in extent of inflammatory papules (Figure 1), 87-percent reduction in lesional pus, 87-percent reduction in lesional pustule size, 87-percent reduction in extent of pustules, and 78-percent reduction in overall assessment of folliculitis.

The subject evaluations mirrored the investigator assessments in all body areas at Weeks 2 and 4. After two weeks of twice-daily azelaic acid foam treatment, the subjects assessed statistically significant improvement in itching associated with folliculitis (p=0.004), pain associated with folliculitis (p=0.002), lesional pus (p=0.008), lesional redness (p=0.002), extent of involvement (p=0.001), and overall assessment of folliculitis (p=0.001). At Week 4, this translated into a reduction of 60-percent in itching associated with folliculitis, a 67-percent reduction in pain associated with folliculitis (Figure 2), a 73-percent reduction in lesional pus, a 51-percent reduction in lesional redness, a 59-percent reduction in extent of involvement, and 63-percent reduction in overall assessment of folliculitis. All of these reductions were statistically significant.

Discussion

No on-label topical treatments exist for the common dermatologic problem of folliculitis. Inflammatory papules and pustules are found in hair bearing intertriginous areas or areas where sweat retention is prevalent. Moisture accompanied by warmth from two adjoining skin folds creates the ideal environment for bacterial growth. However, folliculitis can also result from perifollicular irritation, a phenomenon commonly referred to as razor burn, where trauma producing inflammation rather than bacterial presence is causative. Thus, folliculitis can be found in the scalp, at the nape of the neck, in the armpits, between and beneath the breasts, under the pannus, in the pubic hair, and on the upper inner thighs in both males and females of all ages. Dermatologists can treat folliculitis with oral or topical antibiotics, antibacterial soaps, and/or topical corticosteroids. The challenge is to treat both the possible bacterial and inflammatory nature of the disease.

The present study examined azelaic acid, which possesses both antibacterial and anti-inflammatory qualities, in the topical treatment of folliculitis.^11,12 The anti-inflammatory mechanism of action is unknown, but thought to be due to neutrophil function inhibition.¹³ The inflammatory response in keratinocytes might be due to PPAR gamma activation.¹⁴ In addition, azelaic acid is able to enter the milieu of the follicle, the site of pathology in folliculitis.¹⁵

The primary efficacy endpoint in this study was the investigator-assessed improvement in folliculitis following four weeks of twice-daily application of azelaic acid foam. The secondary efficacy endpoint was the subject-assessed improvement in folliculitis following four weeks of twice daily application of azelaic acid foam. Both endpoints were met successfully. Many topical preparations are ointments, creams, or lotions that might leave behind a residue, possibly encouraging additional sweat retention and possessing limited suitability for application to intertriginous areas. The foam formulation with minimal residue was well received by the subjects both functionally and aesthetically.

Limitations. One limitation of this pilot study was the absence of a control group. Subjects selected for entry into this study had folliculitis remaining despite treatment, thus their historical baseline was used as a control. However, based on the initial success achieved in these 26 subjects, additional research that includes a control group is needed to further validate the use of 15% azelaic acid foam in folliculitis.

Conclusion

The results of this study suggest that azelaic acid 15% foam could be used off-label both as treatment and maintenance therapy for patients with folliculitis of all body areas. More research is necessary to confirm the findings of this study.

References

1. Luelmo-Aguilar J, Santandreu MS. Folliculitis. Am J Clin Dermatol. 2004;5:301-310.
2. Stulberg DL, Penrod, MA, Blatny RA. Common bacterial skin infections. Am Fam Physician. 2002;66:119-24.
3. Rubenstien RM, Malerich SA. Malassezia (pityrosporum) folliculitis. J ClinAesthet Dermatol. 2014;7(3):37-41.
4. Sadick NS. Current aspects of bacterial infections of the skin. Dermatol Clin. 1997;15:341-9.
5. Gelmetti C. Local antibiotics in dermatology. Dermatol Ther. 2008;21:187-195.
6. Nazzaro-Porro M. Azelaic acid. J Am Acad Dermatol. 1987;17:1033-1041.
7. Thiboutot D. Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris. J Drugs Dermatol. 2008;7:13-16.
8. Frampton JW, Wagstaff AJ. Azelaic acid 15% gel in the treatment of papulopustular rosacea. Am J Clin Dermatol. 2004;5:57-64
9. Sieber MA, Hegel JKE. Azelaic acid: properties and mode of action. Skin Pharmacol Phyciol.
   2014;27:9-17.
10. Del Rosso JQ. Azelaic acid topical formulations: differentiation of 15% gel and 15% foam. J Clin Aesthet Dermatol. 2017;10:37–40.
11. Holland KT, Bojar RA. Antimicrobial effects of azelaic acid. J Dermatol Treat. 1993;4:S8-S11.
12. Leeming JP, Holland KT, Bojar RA. The in vitro antimicrobial effect of azelaic acid. Br J Dermatol. 1986;115:1365-2133.
13. Akamatsu H, Komura J, Asada Y, Miyachi Y, et al. Inhibitory effect of azelaic acid on neutrophil function: a possible cause for its efficacy in treating pathogenetically unrelated diseases. Arch Dermatol Res. 1991;283:162–166.
14. Mastrofrancesco A, Ottaviani M, Aspite N, et al. Azelaic acid modulate the inflammatory response in normal human keratinocytes through PPARgamma activation. Exp Dermatol. 2010;19:813-20.
15. Bojar RA, Cutcliffe AG, Graupe K, et al. Follicular concentrations of azelaic acid after a single topical application. Br J Dermatol. 1993;129:1365-2133.