Rosacea is among the most common conditions treated by dermatologists. In a non-selected population of 809 office employees in Sweden (454 women and 355 men), 81 people were diagnosed as having rosacea, with a prevalence of 10% (women 14%, men 5%).1 And according to the National Rosacea Society, 14 million American men and women have this condition.
As you’re already aware, standard FDA-approved therapies for rosacea include topical preparations: metronidazole, clindamycin, azelaic acid, sulfur, sodium sulfacetamide and oral medications: tetracycline, doxycycline and minocycline. As all dermatologists know, these therapies sometimes do not work, so an awareness of off-label uses of other medication groups and approaches is useful to avoid treatment failure, patient frustration and dermatologist exasperation.
I will focus on four groups and approaches: retinoids, anti-parasitic agents, Helicobacter pylori treatment and second-generation macrolides.
1. Retinoids
Retinoids are useful tools in the treatment of most dermatologic diseases. Rosacea is no exception. Topical retinoids promise a low-risk tool for treatment of rosacea. Ertl found that topical tretinoin was as effective as oral isotretinoin in the treatment of rosacea.2 However, I find rosacea patients have difficulty in tolerating topical tretinoin even when given in the 0.04% micro gel formulation. Therefore, Altinyazar’s report that in a head-to-head trial of adapalene versus topical metronidazole there was a significant reduction in the total number of inflammatory lesions found in the adapalene group compared with the metronidazole group seems to promise a potent alternative tool in the treatment of rosacea. Altinyazar noted there was no significant difference in the scores of erythema and telangiectasia in the adapalene group while there was a significant reduction in erythema seen in the metronidazole group.3 This finding suggests that combination regimens of adapalene and topical metronidazole could treat all faces of rosacea.
The most difficult cases of rosacea can respond to isotretinoin.4 I find that oral isotretinoin is the most effective agent to treat rosacea but while it is curative in acne vulgaris, it is merely remittive in rosacea. Isotretinoin can bring the rosacea flare-up under control.
I give isotretinoin for limited courses at a dose of 0.5 to 1 mg/kg and have seen it break up confluent erythema on patient’s faces. However, rosacea tends to return and thus some have suggested that low continual dosing of isotretinoin (10 mg q.d.) offers a boon for treatment-resistant rosacea.5,6
Isotretinoin has been used in children for rosacea fulminans, but I do not advocate this due to effects on skeletal maturation.7
It is likely that the isotretinoin registry will decrease the use isotretinoin for acne and other diseases, such as rosacea. This is unfortunate as isotretinoin is such a useful therapy for rosacea.
2. Anti-parasitic Agents
Permethrin 5% cream, ivermectin, crotamiton lotion and lindane all have isolated case reports suggesting that they can have a role in the treatment of rosacea.
Permethrin 5% cream is a safe alternative for the topical treatment of papulopustular rosacea. Permethrin 5% cream is superior to metronidazole 0.75% gel and placebo in decreasing Demodex folliculorum, and is as effective as metronidazole 0.75% gel in treating erythema and papules.8,9
This was shown in a study of 60 patients with 20 patients in each the permethrin, metronidazole and placebo groups; however, permethrin has no effect on telangiectasia, rhinophyma and pustules.10
I have used this treatment with some success. In combination with other therapies it is low risk and well tolerated. It can be dosed daily, every other day or weekly.
For those who are more aggressive in their treatment decisions ivermectin, which is approved to treat river blindness (onchocerciasis) and a strongyloidiasis and which is used to treat scabies, might have a role in the treatment of rosacea.
Forstinger reported that a 32-year-old man presented with a 4-year history chronic rosacea-like dermatitis of the facial skin and the eyelids that was unresponsive to multiple previous treatments; oral treatment with 200 µ/kg ivermectin with subsequent weekly topical permethrin showed impressive treatment efficacy.11
Ivermectin has few side effects and no drug interactions. Isolated reports saying it raised the death rate in the elderly have proved false. It can be given 200 µ/kg once a week for a typical dose of 12 mg.
I have not used this treatment but would use it if a patient has failed all other treatments and did not want to take isotretinoin.
A unilateral rosacea-like chronic dermatitis of the right side of the face was shown to harbor innumerable Demodex folliculorum and D. brevis. Treatment with oral metronidazole suppressed the dermatitis but did not significantly reduce the Demodex population.
Treatment with topical crotamiton eliminated the Demodex and was curative. These observations support the view the D. folliculorum and D. brevis may be pathogenic when they are present in extremely large numbers.12
Lindane 1% cream per week overnight with oral erythromycin therapy for 2 successive weeks cleared an eruption consisting of excoriated papules and pustules on the face in which Demodex folliculorum seemed to be the cause whereas topical treatment with metronidazole applied twice a day did not.13
I would not use lindane because permethrin is a safer, more effective agent.
3. Eradicating H. pylori
The cutaneous pathology induced by H. pylori is far from being clear, but it is speculated that the systemic effects may involve increased mucosal permeability to alimentary antigens, immunomodulation, an autoimmune mechanism or the impairment of vascular integrity.14
Reports have conflicted on whether treatment of H. pylori effectively treats rosacea. Reports from the Turkey suggest it is useful but other reports from the United States, Europe and Asia have not borne this out. Nevertheless, treatment for H. pylori has few side effects so considering its use for patients who have failed multiple other treatments is worth consideration.
In a study done in the United States comparing treatment of H. pylori to no treatment in rosacea patients, Bamford15 noted that rosacea abated in most participants in this study, whether they were in the treatment or the control cohort, and there was no statistical difference when the results of active treatment were compared with those of placebo.
Bamford concluded treating H. pylori infection has no short-term beneficial effect on the symptoms of rosacea to support the suggested causal association between H. pylori infection and rosacea.
Herr supported the conclusions of Bamford, although Herr noted temporary improvement in papulopustules exclusively during the treatment (within 2 weeks), which he thought could be independent of H. pylori eradication.16
In a study done in Turkey, Utas came to the opposite conclusion and found H. pylori treatment effective at abating rosacea.17
Eradication of H. pylori can be achieved using a triple therapy regimen lasting 1 to 2 weeks, this treatment includes omeprazole and a combination of two other oral antibiotics (a choice from clarithromycin, metronidazole or amoxicillin).
4. Second-Generation Macrolides
Second-generation macrolides azith-romycin and clarithromycin offer many advantages over erythromycin and reports suggest they can be used to treat rosacea. However, they also have the disadvantage of being more expensive than tetracycline antibiotics, which are the standard oral treatment of rosacea.
Azithromycin is pregnancy category B and has few drug interactions and can be dosed 250 mg three times a week to treat rosacea.
Bakar reported that in an open-label trial of 14 patients, at the end of 12 weeks, there was a 75% decrease in total scores (P<0.001) and an 89% decrease in inflammatory lesion scores compared with basal values with improvement continuing during the 4 weeks after treatment. Adverse effects were minimal and well tolerated in most patients.18
Fernandez-Obregon (2004) had similar conclusions to Bakar.19 I have used azithromycin 250 mg q.o.d. or q.d. for rosacea with good effect. However, I do not think it is better than minocycline, and many insurance companies will only pay for six pills in one prescription. At about $10 a pill, this is a pricey daily medication.
It is safe in pregnancy and so can be used in patients who are trying to get pregnant and want oral treatment for their rosacea.
Clarithromycin is pregnancy category C, and in its extended-release form can be given once a day or every other day for rosacea.
Torresani found that clarithromycin was superior to doxycycline for rosacea and has been vocal that it is a useful agent in the treatment of rosacea.20,21
I have not used it, but there is no reason to think it would not be an effective agent and might be used by a clinician who is very comfortable in administering this therapy.
The Choices Are Not Limited
Consider the four treatment groups that I have outlined when standard treatments fail.
Of course, other non-standard treatments options also exist. Laser and pulsed light therapies as well as photodynamic therapy are now being used to treat rosacea.
The bottom line is that dermatologists have many treatment tools, and if one does not work, then consider another — either alone or in combination with standard and traditional therapies.
THE MANY FACES OF ROSACEA
CME Critical Reviews of Clinical Data:
Fall Clinical Dermatology 2007
Acne Case Reports
2007 ADVANCES IN COSMETIC &
MEDICAL DERMATOLOGY
“MAUI DERM” CONFERENCE
July 2007 CME Supplement
2007 Winter Dermatology Conference Hawaii®
2006 4th Annual Fall Conference Supplemental Proceedings