How is papulopustular rosacea treated?

The papulopustular rosacea is distinguished from other forms of rosacea by the presence of papules and pustules on the skin. Treatment choice mainly depends on symptom severity. For mild rosacea, with fewer than 10 papules or pustules, dermatologists typically prescribe a single treatment modality, either topical or oral. However, when lesions are more numerous and acne rosacea takes on a moderate to severe form, a combination of topical and oral treatments is often recommended.

The initial duration of papulopustular rosacea treatment is generally 6 to 8 weeks, allowing for evaluation of its efficacy. If it proves effective, it may be continued for 6 to 9 months to stabilize the skin. In cases of insufficient response, the physician will reassess the strategy: modifying the topical treatment or adjusting dosages is then considered to achieve better control of acne-rosacea symptoms.

Topical treatments often represent the first-line management for papulopustular rosacea, especially in mild to moderate forms. They allow direct targeting of skin lesions, reduce inflammation, and limit the proliferation of microorganisms involved in papule and pustule formation. Localized application offers the advantage of minimizing systemic side effects while acting directly on the affected area. These treatments are typically prescribed over several weeks, with regular monitoring to adjust the frequency and concentration based on skin response.

Metronidazole.

The metronidazole is an antibiotic in the imidazole family, available as a cream, gel, or emulsion. Marketed under the names Rozacreme, Rozagel or Rozex, it acts directly on skin lesions by reducing the number of papules and pustules, and also helps to partially alleviate erythema. Its effects are due to its anti-inflammatory, antibacterial, and antiparasitic properties, making it a treatment of choice for mild to moderate papulopustular rosacea.

Generally formulated at 0.75% or 1%, metronidazole is applied twice daily for several weeks, the exact duration depending on the severity and chronicity of symptoms. Thereafter, it can be used as maintenance therapy to prevent relapses. It is contraindicated in patients with a known allergy to metronidazole or any of its excipients. During the treatment period, it is recommended to protect the treated area from sun exposure to reduce the risk of irritation or cutaneous reaction.

Several clinical studies have demonstrated the efficacy of metronidazole in treating papulopustular rosacea, including the one presented below, which examined two creams: one containing 0.75% metronidazole and the other 1% metronidazole.

Azelaic acid.

The azelaic acid is an active ingredient available as a cream, marketed under the name Finacea, typically at 15%. It exhibits antibacterial and anti-inflammatory properties, which help reduce rosacea papules and pustules, as well as redness. Additionally, azelaic acid acts on follicular hyperkeratosis by inhibiting keratinocyte proliferation via DNA synthesis modulation, thereby helping to limit the formation of new lesions.

Azelaic acid is generally applied twice daily, morning and evening, to the affected areas. As with metronidazole, it is recommended to shield the skin from sunlight during treatment to prevent any irritation or photosensitization. Azelaic acid is often prescribed as a second-line treatment, because its efficacy is slightly lower than metronidazole’s, but it is better tolerated and causes fewer side effects, making it an attractive option for sensitive skin.

Several studies have also demonstrated the efficacy of azelaic acid against papulopustular rosacea, including those presented below and conducted over a twelve-week period.

Ivermectin.

The ivermectin is an antiparasitic agent which has recently been used to treat the inflammatory lesions of papulopustular rosacea in adults. It exerts anti-inflammatory effects, thereby reducing symptoms associated with skin inflammation, and also acts against the Demodex, a skin parasite involved in triggering the inflammatory response in rosacea.

In pharmacies, ivermectin is available as a 1% cream marketed under the name Soolantra. The treatment is typically applied once a day, preferably in the evening. It can be used alone or in combination with other topical treatments to optimize the therapeutic response. Note that ivermectin is not reimbursed by French health insurance and remains more expensive than traditional topical treatments, which can influence the patient’s and dermatologist’s choice.

The efficacy of ivermectin in alleviating papulopustular rosacea has been investigated through various studies. Two recent parallel trials involving 683 and 688 patients with papulopustular rosacea evaluated the daily application for twelve weeks of a 1% ivermectin cream versus a placebo. The results demonstrated a significantly greater improvement in patients who received ivermectin.

Adapalene.

Adapalene is an antibiotic medication of the retinoid family with anti-inflammatory activity. It is available as a gel or cream under the same name, formulated at 0.1%, and is prescribed for daily application, preferably in the evening. Adapalene was originally developed as an anti-acne treatment, but it also shows promising properties in papulopustular rosacea. However, its use in this condition remains limited due to side effects such as dryness, irritation, burning sensations, and erythema.

To date, relatively few studies have examined the effect of this retinoid on rosacea. Nevertheless, research by Esturk and his team has shown that adapalene may hold some promise in papulopustular rosacea. Over the course of 55 days, 27 patients with papulopustular rosacea applied a 0.1% adapalene gel twice daily, yielding favorable results for papules and pustules. However, no effect was observed on erythema and the visibility of telangiectasias.

Clindamycin phosphate.

The clindamycin is an antibiotic of the lincosamide class, widely used in the management of inflammatory lesions of rosacea acne. It exerts an antibacterial action by inhibiting the growth of bacteria involved in the initiation and maintenance of cutaneous inflammation. At the same time, clindamycin phosphate has anti-inflammatory properties that help reduce erythema, papules, and pustules associated with rosacea acne. This compound is generally well tolerated, even on sensitive skin, making it an attractive option. Clindamycin phosphate can be used as monotherapy or in combination with other topical treatments, such as metronidazole or azelaic acid, to enhance its efficacy.

The effects of clindamycin phosphate were evaluated in a study conducted by DEWITT and his team. To this end, 43 patients with rosacea were recruited. Two groups were formed. Volunteers in the first group applied a clindamycin-based gel twice daily and took 250 mg of tetracycline four times a day. Those in the second group also applied the gel but received placebo capsules. After three months, the scientists observed an overall reduction in erythema, a mean 50% decrease in papules and nearly 75% reduction in pustules across all patients, with no significant difference noted between the two groups.

Benzoyl peroxide.

Benzoyl peroxide is an antioxidant agent. It also addresses hyperkeratinization and seborrheic hypersecretion through its keratolytic and sebostatic activity. Benzoyl peroxide is often prescribed in combination with another antibiotic, most commonly clindamycin. This combination effectively reduces inflammatory lesions. It also reduces the risk of bacterial resistance. The benzoyl peroxide and clindamycin combination is formulated as a 1 to 5% gel, marketed under the name ClindoxylGel in pharmacies.

Few studies have assessed the efficacy of benzoyl peroxide in papulopustular rosacea, but the following are worth mentioning.

Tretinoin.

Tretinoin, like adapalene, belongs to the retinoids family. It regulates the growth and maturation of skin cells. Tretinoin acts on the inflammatory phase, resulting in a reduction of inflammation symptoms such as redness and dilation of blood vessels. Tretinoin also promotes cellular regeneration and improves skin texture. It is notably available as a cream formulated at a 0.05% concentration and marketed under the name Retacnyl.

When inflammatory lesions of papulopustular rosacea are moderate to severe or when topical treatment alone is insufficient, the dermatologist may propose an oral therapy. The goal is to rapidly reduce the number of papules and pustules, limit skin inflammation, and prevent flare-ups. Oral treatments are generally prescribed for a limited duration and are adjusted based on the severity of the rosacea and the individual patient’s characteristics.

Doxycycline.

Doxycycline is an tetracycline-family antibiotic, administered orally as tablets or capsules, typically dosed at 50 or 100 mg and marketed under names such as Tolexine. Beyond its antibacterial activity, it possesses significant anti-inflammatory properties, making it a reference treatment for effectively reducing the papules and pustules of papulopustular rosacea. Doxycycline can be prescribed alone or in combination with a topical treatment, such as metronidazole, for a synergistic effect.

Doxycycline is most often prescribed once a day, preferably in the evening, generally for three months. It is contraindicated in patients with a known tetracycline allergy and should not be used in combination with oral retinoid therapies because of the increased risk of side effects. Like other anti-inflammatory antibiotics, doxycycline can increase skin sensitivity to sunlight; therefore, direct UV exposure should be avoided and appropriate sun protection used throughout the treatment period.

Isotretinoin.

Isotretinoin is a medication of the retinoid family. It is the stereoisomer of tretinoin. It comes in capsules containing 5, 10, 20, or 40 mg of isotretinoin, available in pharmacies under the brand names Curacne, Acnetrait or Roaccutane. Isotretinoin is indicated as a last resort due to its significant side effects (teratogenicity, dryness, joint pain, etc.). This medication is prescribed at doses ranging from 0.5 mg/kg to 1 mg/kg based on rosacea severity and patient tolerance. Isotretinoin is relatively effective in treating the different manifestations of papulopustular rosacea. However, it is contraindicated in pregnant or breastfeeding women because its use carries a high risk of fetal malformations. When prescribed, it requires strict dermatological monitoring and regular assessments.

The study presented below assessed the effects of a low-dose (0.25 mg/kg) isotretinoin treatment over a four-month period.

• DEWITT S. & al. Treatement of rosacea : Topical clindamycine versus oral tetracycline. International Journal of Dermatology (1993).

• BAKER M. D. & al. Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea. Journal of the American Academy of Dermatology (2001).

• 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).

• ESTURK E. & al. Adapalene vs. metronidazole gel for the treatment of rosacea. International Journal of Dermatology (2005).

• JACOVELLA J. & al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: Results of two randomized, double-blind, vehicle-controlled pivotal studies. Journal of Drugs in Dermatology (2014).

• CHOSIDOW O. & al. A randomized-controlled trial of oral low-dose isotretinoin for difficult-to-treat papulopustular rosacea. Journal of Investigative Dermatology (2016).

• FELDMAN S. & al. A review of the current modalities for the treatment of papulopustular rosacea. Dermatologic Clinics (2017).

• GOLD L. S. & al. Efficacy and safety of microencapsulated benzoyl peroxide cream, 5%, in rosacea: Results from two phase III, randomized, vehicle-controlled trials. Journal of Clinical and Aesthetic Dermatology (2023).