ROSACEA

By Gary M. White, MD


Rosacea Multiple, inflammatory papules on the forehead, nose and cheeks in an adult.


Rosacea is a papular inflammatory eruption of the face in adults. It is not acne and this author prefers to avoid the term "acne rosacea." Rosacea seems to represent a mild surface infection or overgrowth by normal flora. Fair-skinned adults, particularly those of Celtic origin, are preferentially affected.

Clinical

Erythematous papules and pustules develop on the nose and cheeks. Often there is a background of erythema, telangiectasia and flushing. Soft tissue swelling of the nose (rhinophyma) is rare and may occur without any signs of rosacea. Men are more commonly affected. Ocular rosacea is characterized by conjunctival erythema (red eyes) and ocular dryness (dry eyes). Sties and hyperemia of the lid margin may be seen. The patient should be asked if they have trouble with dry eyes or blood-shot eyes for no apparent reason. Extra-facial rosacea may occur, e.g. in the scalp as a pustular eruption.

A rosacea-like eruption may occur with chronic steroid use, so called steroid-rosacea. Similarly, rosacea-like eruptions have been associated with topical tacrolimus and pimecrolimus [Dermatol Online J. 2015 May 18;21(5)]. A form called granulomatous rosacea occurs.

Rarely, significant facial edema, called Morbihan disease, may occur in a patient with rosacea. Patients with rosacea are more likely to have dyslipidemia, hypertension and coronary artery disease [JAAD 2015;73;249].

Is Erythematotelangiectatic Rosacea any Different from Photoaging?

A report from the National Rosacea Society Expert Committee states "erythematotelangiectatic rosacea is mainly characterized by flushing and persistent central facial erythema. The appearance of telangiectasias is common but not essential for a diagnosis of this subtype." [JAAD 2002;46;584]. The difference between erythematotelangiectatic rosacea, flushing and telangiectatic photoaging is debated [JAMA Derm 2015;151;821 and 825].

Differential Diagnosis

Occasionally, the red malar rash of rosacea may be confused with that of lupus erythematosus. Tip-offs to rosacea include sebaceous hyperplasia and ocular signs and symptoms. If there is any doubt, a small punch biopsy can be done and sent for both H&E and immunofluorescence.

Rosacea and acne are distinct diseases, but occasionally, they are hard to distinguish. Comedones are often present in acne, but not in rosacea. The pimples of acne tend to occur about the mouth, chin and jawline whereas they occur most commonly on the cheeks and nose in rosacea.

Rosacea and seborrheic dermatitis (SD) can sometimes be confused. SD is red and scaly whereas rosacea is red and bumpy. Look for signs of SD on the scalp and for signs of rosacea in the eyes.

Treatment

Oral Tetracyclines

First-line treatment for rosacea is the oral antibiotic, e.g., tetracycline 500 mg or doxycycline 20-100 mg BID initially and then tapered to once every day or every other day. Many advocate "sub-microbial therapy", and indeed,
low-dose doxycycline, (e.g., 20 mg BID), does seem to be effective. Minocycline 50-100 QD-Bid is very effective as well, but since therapy is chronic, the risk of blue teeth and other signs of minocycline pigmentation make it second choice. Although rosacea usually responds within weeks, the patient may have to stay on the oral antibiotic for years to decades. Control, not cure, is the rule. Treating with an oral tetracycline may reduce the incidence of vascular events [JID 2014;134;2267].

Topical Ivermectin

Topical ivermectin 1% cream (Soolantra) once daily is approved in the US for the treatment of rosacea. In two pivotal studies, the number of patients who were clear or almost clear at 12 weeks was 38%-40% for ivermectin vs. 12%-19% placebo. Side effects were actually less in the ivermectin group than the placebo group. A systematic literature review of 57 studies [Springerplus. 2016 Jul 22;5(1):1151] found ivermectin 1 % cream QD more effective than topical metronidazole and azelaic acid topical in the treatment of inflammatory rosacea.

Topical Sodium Sulfacetamide/Sulfur

Topical Sodium Sulfacetamide/Sulfur is a topical antibiotic agent applied 1-3/day that that may be helpful for rosacea, seborrheic dermatitis and acne. It may be particularly advantageous in overlap situations and in those who wish to avoid oral antibiotics.

Topical Praziquantel

Topical praziquantel 3% ointment BID in a placebo-controlled trial showed benefit as a topical agent for rosacea [Int J Dermatol. 2015 Apr;54(4):481-7.]. 41.9% of patients in the PZQ group and 18.2% of those in the placebo group achieved an equivalent score of "clear". Also, topical praziquantel 3% ointment was significantly better than placebo in the treatment of perioral dermatitis [Clin Exp Dermatol 2014;39;448-453]. Praziquantel is an anti parasitic agent used to treat schistosomiasis, flat worms, and other parasites.

Other Topical Agents

Topical metronidazole, azelaic acid or sodium sulfacetamide and sulfur may be given topically as monotherapy for mild disease in conjunction with a tetracycline initially or to maintain a remission. Any of these topical agents should be applied once or twice daily in the areas that the rosacea occurs. It is important to try to prevent the rosacea, not just spot-treat those pimples that have already developed. This is a common mistake made by patients using topical therapy. Topical 5% permethrin BID decreases demodex density and improves the clinical appearance [JEADV 2016;30;2105].

It is always important to determine if ocular rosacea is present. If so, the oral tetracyclines should be the preferred therapy both to remit the condition and for maintenance.

Isotretinoin

For resistant rosacea (which is uncommon), oral isotretinoin may be given. It is usually given at a slightly lower dose than for acne patients as the drying symptoms may be harder for the rosacea patient to handle. One study found that very low-dose isotretinoin (e.g., 10-20 mg once to five times a week, equivalent to 5 mg/day) is an effective treatment for mild to moderate papulopustular rosacea and is well tolerated [Australas J Dermatol. 2016 Jul 20]. Higher doses may aggravate any ocular rosacea.

Rifaximin

Two studies link rosacea and small intestinal bacterial overgrowth (SIBO) and show a benefit of rifaximin (e.g., 400 mg TID for 10 days) in clearing rosacea [Clin Gastro Hep] and [JAAD]. Rifaximin (Rifagut) is a semisynthetic antibiotic based on rifamycin. It has poor oral bioavailability, meaning that very little of the drug is absorbed into the blood stream when it is taken orally. In the second study, among 28 patients who took rifaximin for their SIBO, the rosacea cleared in 46%, moderately improved in 25%, mildly improved in 11% and failed to improve in 18%.

Spironolactone

One study has shown that rosacea develops at a substantially decreased rate during spironolactone exposure [Journal of Investigative Dermatology 2013;133;2480–2483]. As no other class of diuretics affected the risk estimate, a diuretic drug effect is an unlikely cause for the observed effect.

Treatment for Flushing/Redness

Brimonidine

Brimonidine 0.33% topical gel (Mirvaso) is FDA-approved for the facial erythema associated with rosacea in patients 18 and over. It is applied BID and is generally well tolerated. Potential side effects include worsening erythema and/or flushing, pruritus, skin irritation, allergic contact dermatitis, and worsening of rosacea. Rebound erythema has been reported greater than baseline [JAAD Feb and May 2014] and counseling about the potential for worsening erythema, initial use in a test area, and limiting use to special occasions may be warranted. Erythema in skin adjacent to the area of long-term use has been reported [JAMADerm 2015;151;136].

Oxymetazoline HCL 1% cream (Rhofade) is also FDA-approved for facial redness in rosacea. If one dose not work, the other may be tried. In one national speaker's opinion, oxymetazoline might be just slightly less efficacious, but with fewer side effects.

Other Strategies

Avoidance of excessively hot foods or liquids, sun, wind and other triggers.

Sucking on ice chips once the flushing begins may be tried.

Flushing may be treated with propranolol 40 mg BID or clonidine 50 mg BID. The telangiectasias--whether rosacea is present or not--may be removed with the pulsed dye laser.

Botox

Intradermal injection of botulism toxin is an effective and safe method of treating facial erythema of rosacea according to one study of 25 patients [Dermatol Surg 2015 Jan.:S9-S16].

Additional Pictures

Close-up of above, showing that sometimes rosacea can give the patient a "butterfly rash" reminiscent of lupus.
Rosacea of the Cheeks

Unilateral rosacea may occur, but always consider demodicosis.
Unilateral Rosacea

Rosacea of the Chin Rosacea of the Chin

Telangiectasias alone is not rosacea.
Telangiectasias of the Face

Chronic edema from rosacea, so called Morbihan disease.
Morbihan Disease

References

Rebound erythema with brimonidine. First picture is 1 hour after application with improvement of redness. Second photos is 12 hours later with worsening of erythema beyond baseline. Dermatology Online Journal 21(3)

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