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Rosacea: Surprisingly effective new treatment of papulopustular rosacea (PPR)

Skin Conditions, General | May 31, 2016 | Author: The Super Pharmacist

Skin conditions, skin, acne, rosacea, age related, PPR

Rosacea: Surprisingly effective new treatment of papulopustular rosacea (PPR)

Rosacea is a common but poorly understood long term skin condition that mainly affects the face. Papulopustular rosacea (PPR) is the classical sign and symptom of rosacea and manifests as flushing and extreme redness of the skin. Rosacea can occur intermittently with different degrees of severity, and it is most prevalent in middle-aged women.

Around 1 in every 600 people will develop rosacea at some point in their lifetime, although prevalence may be greater as rosacea is often mistaken as acne vulgaris, seborrheic dermatitis and perioral dermatitis.

Signs and Symptoms

What causes rosacea?As well as the extreme redness and flushing, people with rosacea will often also experience: 

  • burning or stinging sensations
  • spots that resemble acne - referred to clinically as erythematous papules and pinpoint pustules
  • small blood vessels in the skin becoming visible -known clinically as telangiectasias

What causes Rosacea?

What causes rosacea in the first place is not fully understood. Several triggers have been identified as making the condition worse, including exposure to sunlight, stress, strenuous exercise, hot or cold weather, hot drinks, alcohol, caffeine, and certain foods such as spicy dishes. These triggers tend to make the condition flare after exposure and are common for people with rosacea.

Treating Rosacea

What causes rosacea?The goals of medicine treatment are to reduce severity and prevent further complications associated with rosacea.

The treatment that is chosen is often determined by both the severity and type of rosacea present, and although there are numerous treatments available none have been found to cure rosacea completely.

Many of the symptoms of PPR can be controlled with treatment to a degree, although changes to physical appearance as a consequence of prolonged medication can have a significant psychological and social impact on  people's quality of life.

Treatments Available

  • The most commonly used first-line agent in the treatment of rosacea is topical metronidazole, an anti-bacterial agent.
  • Topical azelaic acid, sulfacetamide products, and topical acne medications are also commonly used. 
  • Topical and oral antibiotics have been evidenced to be very effective, and for oral rosacea they are usually considered as a first-line therapy.
  • Retinoids have also been suggested by authorities as a first line treatment option (1)
  • More recently topical ivermectin has emerged as a popular first line therapy.

A Cochrane review of treatments for rosacea has summarised that there is:

High-quality evidence to support the effectiveness of topical azelaic acid, topical ivermectin, brimonidine, doxycycline and isotretinoin for the treatment of rosacea.

Moderate-quality evidence is available for topical metronidazole and oral tetracycline.

Low-quality evidence for low-dose minocycline, laser and intense pulsed light therapy and cyclosporin ophthalmic emulsion for ocular rosacea (6).

There are a wide range of pharmacotherapies used off-label to treat rosacea but there is no formal evidence base for their use: expert opinion and individual prescribing preference often account for the use of medication that have the effect of reducing flushing such as beta-blockers, clonidine, naloxone, ondansetron, and selective serotonin reuptake inhibitors (6).

Oral contraception: There is limited evidence to suggest that oral contraceptive therapies have also been helpful in patients who provide historical information of worsening rosacea with their hormonal cycle (7).

Here we discuss the newly emerged, and apparent effective treatment option of topical ivermectin.

Ivermectin

Rosacea: Surprisingly effective new treatment of papulopustular rosacea (PPR)Ivermectin 1% is a topical cream used to kill parasites. It does this by binding selectively to glutamate-gated chloride ion channels in nerve and muscle cells, causing parasite death by enhancing cell membrane permeability (2). In addition to killing the Dermodex mites, ivermectin also displays antimicrobial, antibacterial, and anti-inflammatory properties.

The Evidence

A study undertaken in 2015, published in the British Journal of Dermatology, concluded that ivermectin 1% cream was safe and effective for the treatment of inflammatory lesions from PPR.

The findings were based on 2 well designed studies comparing ivermectin 1% cream versus a placebo applied once daily for 12 weeks (3).

Several case reports have described successful rosacea treatment with topical acaricidal agents such as invermectin. One such case includes a 12-year-old girl presenting with PPR displaying a complete resolution of symptoms following a single dose of oral ivermectin (4).

Ivermectin in combination with metronidazole

A number of advanced randomised clinical trials to study the effects of topical ivermectin 1% cream on rosacea have also been completed, with these trials comparing the safety and efficacy of 1% ivermectin with 0.75% metronidazole cream and 15% azelaic acid gel.

The largest and most comprehensive study of topical invermectin and topical metrodinazole was initially set up as a cost-benefit analysis in response to the prohibitive costs of some topical medicines that were new to the market. The study was conceived in order to understand the cost of adding ivermectin as a treatment option that would bring additional clinical benefit for adults with papulopustular rosacea in the United States, and initially found that topical invermectin once per day was more expensive but resulted in a better clinical benefit than metronidazole 0.75%. However, as a result of its clinical benefit it also required less application, and was thus subsequently deemed to be of a lower total cost that metrodinazole.

An additional study also showed Ivermectin 1% cream to be superior to metronidazole 0·75% cream, and also documented much higher levels of patient satisfaction due to a reduction in negative side effects (5).

Topical ivermectin is approved for treatment of the inflammatory lesions of rosacea.

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References

1 Two AM, Wu W, Gallo RL, Hata TR (2015) Rosacea: Part II. Topical and systemic therapies in the treatment of rosacea J Am Acad Dermatol 72(5):761-70

2 Estrada-Mondragon A, Lynch JW (2015) Functional characterization of ivermectin binding sites in α1β2γ2L GABA(A) receptors J Front Mol Neuro 25:8;55

3 Taieb A, Ortonne JP, Ruzicka T et al (2015) Superiority of ivermectin 1% cream over metronidazole 0·75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial Br J Dermatol 172(4):1103-10

4 Brown M, Hernandez-Martin A, Clement A, Colmenero I, Torrelo A (2014) Severe demodexfolliculorum-associated oculocutaneous rosacea in a girl successfully treated with ivermectin JAMA Dermatol 150(1):61-3

5 Taeib A, Gold LS, Feldman SR (2016) Cost-effectiveness of Ivermectin 1% cream in adults with papulopastular rosacea in United States J Manag Care Spec Pharm 22(6):01-13

6 van Zuuren EJ, Fedorowicz Z, Carter B, et al (2015) Interventions for rosacea Cochrane Database Syst Rev 28;4:CD003262. doi: 10.1002/14651858.CD003262.pub5

7 Kircik LH, Del Rosso JQ, Layton AM, Schauber J (2016) Over 25 years of clinical experience with ivermectin: an overview of safety for an increasing number of indications7 J Drugs Dermatol 1:15(3):325-32

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