How is papulopustular rosacea treated?

The papulopustular rosacea is distinguished from other forms of rosacea by the presence of papules and pustules. The choice of treatment depends primarily on the severity of symptoms. For mild rosacea, with fewer than ten papules or pustules, the dermatologist generally prescribes a single form of treatment, either topical or oral. However, when lesions are more numerous and acne rosacea takes 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 an evaluation of its efficacy. If found to be effective, it can be continued for 6 to 9 months to stabilise the skin. In the event of an inadequate response, the physician will re-evaluate the strategy: modification of the topical regimen or adjustment of the dosage is then considered to achieve better control of acne-rosacea symptoms.

Topical treatments often form the first-line approach to managing papulopustular rosacea, particularly in mild to moderate cases. They enable direct targeting of cutaneous lesions, reduce inflammation and limit the proliferation of microorganisms involved in the formation of papules and pustules. Localised application has the advantage of limiting systemic side effects while acting directly on the affected area. These treatments are generally prescribed for several weeks, with regular follow-up to adjust frequency and concentration according to the skin’s response.

Metronidazole.

The metronidazole is an antibiotic from 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 reduce erythema. Its effects derive from 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 the symptoms. Thereafter, it may be used as a maintenance treatment 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 in order to minimise any risk of irritation or cutaneous reaction.

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

Azelaic acid.

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

The azelaic acid is generally applied twice a day, morning and evening, to the affected areas. As with metronidazole, it is recommended to protect the skin from sunlight during treatment to prevent any irritation or photosensitisation. Azelaic acid is often prescribed as a second-line treatment, as its efficacy is slightly lower than that of metronidazole, but it is better tolerated and causes fewer side effects, making it an appealing option for sensitive skin.

Several studies have also demonstrated the efficacy of azelaic acid in papulopustular rosacea, including those described below, which were conducted over twelve weeks.

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 activity, thereby limiting symptoms associated with skin inflammation, and also acts against the Demodex, a skin parasite involved in stimulating the inflammatory response in rosacea.

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

The efficacy of ivermectin in alleviating papulopustular rosacea has been evaluated in several investigations. Two recent, parallel studies involving 683 and 688 individuals with papulopustular rosacea examined the daily application for twelve weeks of a 1% ivermectin cream versus a placebo. The results show a significantly greater improvement in the patients treated with ivermectin.

Adapalene.

Adapalene is a antibiotic drug of the retinoid family exhibiting anti-inflammatory activity. It is available as a gel or cream of the same name, formulated at 0.1%, and is prescribed for daily application, preferably in the evening. Adapalene was originally used as anti-acne treatment, but it also exhibits interesting properties in papulopustular rosacea. Its prescription, however, remains limited for this condition due to the side effects it induces (dryness, irritation, burning sensations, erythema...).

To date, relatively few studies have examined the effect of this retinoid on rosacea. However, research by Estürk and his team has demonstrated that adapalene may have some potential in papulopustular rosacea. Over a 55-day period, 27 patients with papulopustular rosacea applied a 0.1% adapalene gel twice daily, obtaining favourable results for papules and pustules. Nevertheless, 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 in rosacea. It exerts an antibacterial action by inhibiting the growth of bacteria involved in the onset and persistence of skin inflammation. At the same time, clindamycin phosphate has anti-inflammatory properties, helping to reduce erythema, papules and pustules associated with rosacea. This molecule 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 assessed in a study conducted by DEWITT and colleagues. 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 daily. 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 decrease of 50% in papules and an almost 75% reduction in pustules in all patients, with no significant difference noted between the two groups.

Benzoyl peroxide.

Benzoyl peroxide is an antioxidant agent. It also acts on hyperkeratinisation and seborrhoeic hypersecretion through its keratolytic and sebostatic activity. Benzoyl peroxide is often prescribed in combination with another antibiotic, typically clindamycin. This combination effectively reduces inflammatory lesions and also lowers the risk of bacterial resistance. The combination of benzoyl peroxide and clindamycin is formulated as a 1 to 5% gel, sold under the name ClindoxylGel in pharmacies.

Few studies have evaluated the efficacy of benzoyl peroxide in papulopustular rosacea, but the following merit mention.

Tretinoin.

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

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

Doxycycline.

Doxycycline is a antibiotic belonging to the tetracycline family, administered orally as tablets or capsules, typically dosed at 50 or 100 mg and marketed under names such as Tolexine. Beyond its antibacterial action, it has significant anti-inflammatory properties, making it a reference treatment for effectively reducing the papules and pustules of papulopustular rosacea. Doxycycline may be prescribed alone or in combination with a topical therapy, 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 cases of known allergy to tetracyclines and must not be used in conjunction with oral retinoid therapies, owing to the increased risk of side effects. As with other anti-inflammatory antibiotics, doxycycline can increase skin sensitivity to sunlight; it is therefore recommended to avoid direct exposure to UV rays and to use appropriate sun protection throughout the course of treatment.

Isotretinoin.

Isotretinoin is a medication belonging to the retinoid family. It is the stereoisomer of tretinoin. It is formulated as capsules containing 5, 10, 20 or 40 mg of isotretinoin, available in pharmacies under the names Curacne, Acnetrait or Roaccutane. Isotretinoin is indicated as a last resort owing to its substantial side effects (teratogenicity, dryness, joint pain, etc.). This medication is prescribed at dosages of 0.5 mg/kg to 1 mg/kg depending on the severity of rosacea and patient tolerance. Isotretinoin is relatively effective for treating the various manifestations of papulopustular rosacea. However, it is contraindicated in pregnant or breastfeeding women, as its use poses a significant risk of foetal malformation. 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).