Ivermectin is best known for its antiparasitic action. It has been used in veterinary and human medicine to eliminate worm, mite, and lice infections. So you might be wondering--how exactly does this drug work against an inflammatory skin condition like rosacea?
When we talk about rosacea pathogenesis, the first thing that comes to mind is inflammation. The redness, itchiness, and dryness of the skin are caused by a strong and dysregulated immune response. Many researchers have set their sights on finding out what triggers this reaction--and there is evidence to suggest that tiny creepy crawlies contribute to this reaction.
The role of mites in rosacea
The idea of having tiny parasites on your face may sound alarming, but they are part of the normal flora and fauna of the skin. Demodex folliculorum and Demodex brevis are the most common mites found in human skin. Since they feed on components of skin oil and skin cells, you can expect to find them hiding out in hair follicles and their closely-associated sebaceous glands. Normally, these do not cause any reactions.
There is evidence to suggest that an overgrowth of these mites are associated with skin conditions--particularly rosacea. Studies have established that rosacea patients have a higher density of the mite Demodex spp. compared to people without the condition (Bonnar et al., 1993), and to those with other skin conditions like eczema and lupus (Roihu et al., 1998), acne and seborrheic dermatitis (Karabay and Çerman, 2020).
Exactly how mites figure in the pathogenesis of rosacea is not clear, but it is likely that mites are both the trigger and the result of rosacea flare-ups (Jarmuda et al., 2012; Forton et al., 2020). Changes in the skin associated with rosacea breakouts provide the perfect environment for the mites to multiply. The resulting heavy infestations could then provoke inflammatory or allergic reactions, precipitating a rosacea flare-up. It also hypothesized that the mites could be transporting rosacea-associated bacteria from the affected skin to unaffected skin, exacerbating the condition (Forton et al., 2020). With another rosacea episode on the way, the mite-friendly skin environment persists, leading to continued proliferation of the parasites--and the cyle continues.
How ivermectin targets rosacea
Ivermectin is a drug developed from the byproduct of the bacteria Streptomyces avermitilis. It works by binding to the receptors in the glutamate-gated chloride channels present in worms and mites. By opening these channels, chloride ions flood into the motor neurons, paralyzing the parasite. Without the ability to move, the organism cannot feed or reproduce, eventually dying off.
In addition to its anti-parasitic activity, ivermectin also appears to have anti-inflammatory properties that could explain its efficiency at minimizing rosacea outbreaks. A study by Schaller et al. (2017) found that ivermectin not only significantly reduced mite density, but also downregulated pro-inflammatory molecules as early as 6 weeks into treatment.
How ivermectin is used in the management of rosacea
Among the different drug formulations of ivermectin, 1% ivermectin cream is the one most often prescribed to rosacea patients. Typically, it is administered topically once a day for at most four months at a time.
When used properly, ivermectin does a great job at minimizing rosacea symptoms based on systematic reviews (Sahni et al., 2018; Ebbelaar et al., 2018), and multiple studies:
A study of 34 case reports by Eckert and Gundin (2016) found that administration of 1% ivermectin once daily for 2 months led to noticeable results for patients with moderate to severe papulopustular rosacea. In as early as 2 weeks, improvement could already be seen.
In a study conducted by Stein et al. (2014) involving nearly 1000 patients with moderate to severe papulopustular rosacea, ivermectin achieved a greater decrease in inflammatory lesion count and higher subject satisfaction rates than controls during the 12-week treatment period.
The once-daily application of ivermectin makes it a more cost-effective and convenient therapeutic agent compared to the first-line medications for rosacea, metronidazole and azelaic acid, that both require twice daily application (Taieb et al., 2016).
The above study by Stein et al., (2014) was extended in order by another 40 weeks to determine the long-term effects of ivermectin and compare its efficacy to azelaic acid, another pillar in the management of rosacea. With ivermectin, there were less adverse effects reported and a higher percentage of patients that achieved “clear” to “almost clear” scores.
Once-daily application of ivermectin resulted in a greater reduction of inflammatory lesions, higher scores for facial clearing, higher levels of patient satisfaction than twice-daily application of metronidazole cream (Taieb et al., 2015). In addition, it took a longer time (113-165 days) for ivermectin users to relapse following cessation of treatment compared to metronidazole users (85-113 days).
Conclusion
Based on existing clinical research and anecdotal evidence from use in the field, ivermectin produces marked improvement of papulopustular rosacea within 8-12 weeks of administration. It has an excellent safety profile, with no systemic side effects and very low incidence of mild, transient localized irritation to the skin. With more research, it could be well on its way to being considered a first-line therapy for papulopustular rosacea.
This content is for general information only and is not a substitute for medical advice.
References:
Abokwidir, M., & Fleischer, A. B. (2015). An emerging treatment: Topical ivermectin for papulopustular rosacea. The Journal of dermatological treatment, 26(4), 379–380. https://doi.org/10.3109/09546634.2014.991672
Aktaş Karabay, E., & Aksu Çerman, A. (2020). Demodex folliculorum infestations in common facial dermatoses: acne vulgaris, rosacea, seborrheic dermatitis. Anais brasileiros de dermatologia, 95(2), 187–193. https://doi.org/10.1016/j.abd.2019.08.023
Bonnar, E., Eustace, P., & Powell, F. C. (1993). The Demodex mite population in rosacea. Journal of the American Academy of Dermatology, 28(3), 443–448. https://doi.org/10.1016/0190-9622(93)70065-2
Ebbelaar, C.C.F., Venema, A.W. & Van Dijk, M.R. Topical Ivermectin in the Treatment of Papulopustular Rosacea: A Systematic Review of Evidence and Clinical Guideline Recommendations. Dermatol Ther (Heidelb) 8, 379–387 (2018). https://doi.org/10.1007/s13555-018-0249-y
Forton, Fabienne & Forton, F & Ther, Dermatol. (2020). The Pathogenic Role of Demodex Mites in Rosacea: A Potential Therapeutic Target Already in Erythematotelangiectatic Rosacea?. Dermatology and Therapy. 10. 10.1007/s13555-020-00458-9.
Jarmuda, Stanislaw & O'Reilly, Niamh & Zaba, Ryszard & Jakubowicz, Oliwia & Szkaradkiewicz, Andrzej & Kavanagh, Kevin. (2012). Potential role of Demodex mites and bacteria in the induction of rosacea. Journal of medical microbiology. 61. 1504-10. 10.1099/jmm.0.048090-0.
Mendieta Eckert, M., & Landa Gundin, N. (2016). Treatment of rosacea with topical ivermectin cream: a series of 34 cases. Dermatology online journal, 22(8), 13030/qt9ks1c48n.
Roihu, T., & Kariniemi, A. L. (1998). Demodex mites in acne rosacea. Journal of cutaneous pathology, 25(10), 550–552. https://doi.org/10.1111/j.1600-0560.1998.tb01739.x
Dev R. Sahni, Steven R. Feldman & Sarah L. Taylor (2018) Ivermectin 1% (CD5024) for the treatment of rosacea, Expert Opinion on Pharmacotherapy, 19:5, 511-516, DOI: 10.1080/14656566.2018.1447562
Schaller, M., Gonser, L., Belge, K., Braunsdorf, C., Nordin, R., Scheu, A., & Borelli, C. (2017). Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea. Journal of the European Academy of Dermatology and Venereology : JEADV, 31(11), 1907–1911. https://doi.org/10.1111/jdv.14437
Stein L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014;13:316–323.
Taieb A, Ortonne JP, Ruzicka T, et al. Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial. Br J Dermatol. 2015;172(4):1103–10.
Taieb, A., Stein Gold, L., Feldman, S. R., Dansk, V., & Bertranou, E. (2016). Cost-Effectiveness of Ivermectin 1% Cream in Adults with Papulopustular Rosacea in the United States. Journal of managed care & specialty pharmacy, 22(6), 654–665. https://doi.org/10.18553/jmcp.2016.15210
