According to Dr. Graeme M. Lipper, MD

Rosacea is a chronic inflammatory skin disease that centers on the pilosebaceous units and presents with at least one of the following features:

• Centrofacial erythema with telangiectatic mats and flushing;
• Inflammatory lesions (papules, pustules, cysts);
• Phymatous changes (skin hypertrophy and fibrosis), usually affecting the nose; and/or
• Ocular inflammation (conjunctivitis, blepharitis, chalazion).

The cardinal symptoms of rosacea are stinging, burning, and itching. The National Rosacea Society Expert Committee delineates four subtypes of rosacea—erythematotelangiectatic, papulopustular, phymatous, and ocular—although these patterns overlap in clinical practice^[1,2] (Figure). Although rosacea classically presents during adulthood, there are rarer pediatric and granulomatous presentations.

 

Figure. The four rosacea subtypes. Top left: . Erythematotelangiectatic rosacea. Top right: Papulopustular rosacea. Bottom left: Phymatous rosacea. Bottom right: Ocular rosacea.

Rosacea affects all ethnicities, but light-skinned people of European descent are the most prone, with one Swedish study showing a prevalence of 10% (women 14%, men 5%; 81% erythematotelangiectatic type, 19% papulopustular type). The global prevalence of rosacea is 5.41% in women and 3.9% in men, and the condition primarily affects adults between 45 and 60 years of age.

Here are five things to know about rosacea.

 

1. It’s Not Just a Skin Disease

Rosacea is associated with hyperreactivity of the innate immune system, which protects epithelial barriers against infection, and chemical or physical (eg, ultraviolet radiation, extreme heat or cold) injury. This primitive, nonspecific inflammatory network is triggered by a range of environmental, dietary, hormonal, and lifestyle factors.^[5] In this broader context, rosacea may just be the superficial tip of an inflammatory iceberg.

Rosacea has a strong hereditary component, with recent genome-wide association studies showing a clustering of the genetic risk loci for rosacea, type 1 diabetes, celiac disease, rheumatoid arthritis, and multiples sclerosis.^[6,7]Women with rosacea are more likely to have these autoimmune disorders, with increased odds ratios (ORs) of 2.59 for type 1 diabetes, 2.03 for celiac disease, 1.65 for multiple sclerosis, and 2.14 for rheumatoid arthritis; intriguingly, this same study showed a striking gender difference, with rosacea in men only increasing the prevalence of rheumatoid arthritis (OR, 2.05).

 

Epidemiologic studies have linked rosacea to comorbid conditions affecting almost every organ system^{[4,8,9,10,11,12]}:

• Immune (dietary and airborne allergies);
• Gastrointestinal (ulcerative colitis, Crohn disease, Helicobacter pyloriinfection, gastroesophageal reflux disease, celiac disease);
• Cardiovascular (hypertension, coronary artery disease, dyslipidemia);
• Endocrine (types 1 and 2 diabetes mellitus);
• Musculoskeletal (rheumatoid arthritis);
• Neurologic (migraine, dementia, Parkinson disease); and
• Psychiatric (depression, anxiety, alcoholism).

Furthermore, many of these associations strengthen with rosacea severity.^[13]

Should every patient with rosacea be screened for each of these illnesses? That would hardly be feasible, given the high prevalence of rosacea. But clinicians should consider targeted screening questions for individuals with rosacea who have additional risk factors for these comorbid conditions.

 

2. Antibiotics Work, but Not for the Reason You Might Think

Low-dose doxycycline (40 mg once daily) is the only US Food and Drug Administration (FDA)-approved oral treatment for rosacea, although off-label systemic therapies include other antibiotics (minocycline, azithromycin), oral ivermectin, and isotretinoin.

Historically, tetracyclines for rosacea were assumed to target proinflammatory bacteria, such as Propionibacterium acnes and Staphylococcus epidermidis. Similar assumptions were made for topical antimicrobials (metronidazole, azelaic acid, sodium sulfacetamide) and the antiparasitic drug ivermectin, which was thought to work by suppressing overgrowth of the cutaneous mite Demodex folliculorum.

But is rosacea really an infectious process? A growing body of evidence points to a different etiology: hyperactivity of the cutaneous innate immune system.

Simply put, innate immunity is a primitive, nonspecific immune system that protects epithelial barriers, such as the skin and gut, from microbial, chemical, and physical injury. Critical components of this pathway include the Toll-like receptor and nucleotide-binding domain and leucine-rich repeat-containing families; when activated, these increase expression of proinflammatory cytokines, proteases, and antimicrobial peptides (eg, cathelicidin) in the skin.

In rosacea, inflamed skin expresses increased levels of cathelicidin and proteases. In a 12-week study, doxycycline (40 mg/day) reduced inflammatory lesions and improved global assessment scores compared with placebo. Clinical improvement correlated with a drop in cathelicidin and protease activity, supporting the idea that doxycycline improves rosacea via anti-inflammatory rather than antimicrobial mechanisms. Similar anti-inflammatory effects have been demonstrated for topical metronidazole, azelaic acid, and ivermectin

 

3. There Is No One-Size-Fits-All Treatment

As mentioned above, rosacea has several variants, each of which can manifest in the same patient in overlapping fashion or at different times. Rarer pediatric granulomatous and pyodermic (rosacea fulminans) variants also exist.

All patients with rosacea should be educated about gentle skin care and avoidance of triggers, such as intense sun exposure, strongly acidic or basic cleansers, facial cosmetics with fragrance, and dietary triggers (eg, alcohol, spicy foods). Daily sunscreen use and avoidance of such mechanical irritants as facial scrubs should also be encouraged.

Different rosacea components respond best to different treatments. In this context, each patient with rosacea needs his or her own individualized plan.

Papulopustular rosacea. This subtype responds well to topical metronidazole (0.75%, 1%), azelaic acid, and ivermectin. Off-label treatments, such as topical sulfacetamide or dapsone, may be beneficial too, either alone or as part of a combination regimen.^{[14,15,20,21,22]} Vehicle choice is important too, because patients with oily skin may prefer a gel or foam, whereas those with dry skin tend to do best with creams or lotions.

Low-dose doxycycline (40 mg/day) is the only FDA-approved treatment for papulopustular rosacea; however, data support the off-label use of minocycline and azithromycin. Some refractory cases of papulopustular rosacea respond well to low-dose oral isotretinoin (off-label), but patients tend to have relapse after drug cessation.

Erythematotelangiectatic rosacea. In contrast, this subtype rosacea responds poorly to topical or oral antibiotics. These patients benefit most from trigger avoidance, gentle skin care, photoprotection, and judicious use of topical vasoconstrictors. To date, two topical alpha-adrenergic receptor agonists are FDA-approved to treat the persistent facial erythema of rosacea: brimonidine tartrate 0.5% gel and oxymetazoline hydrochloride 1% cream. Patients using these topical vasoconstrictors enjoy a transient fading of erythema, but rebound flaring may be problematic for some.

Phymatous rosacea. This subtype is the most challenging to treat, and typically requires a combination of topical antimicrobials; low-dose doxycycline; and mechanical, laser, and/or radiofrequency debridement of hypertrophic tissue for optimal management.

 

4. Red Skin, Red Eyes

Rosacea is associated with ocular involvement in up to 50% of cases, with up to 10 million cases of ocular rosacea in the United States alone. Ocular rosacea may be asymptomatic at first, but usually progresses with pruritus and burning. The most common signs of ocular rosacea are blepharitis, meibomian gland dysfunction (eg, chalazion formation), and conjunctival redness.^[28] If left untreated, ocular rosacea can lead to disfigurement and permanent morbidity.

Patients with signs or symptoms of ocular rosacea should be referred to an ophthalmologist for optimal management; this may require a combination of low-dose doxycycline, topical azithromycin, and/or cyclosporine. Ocular rosacea is easier to manage when symptoms are mild, so early detection and intervention are critical. Of note, significant ocular rosacea may be present even with minimal cutaneous disease.

5. Persistent Erythema? Don’t Forget Lasers and Light

Chronic inflammation in rosacea leads to elevated expression of vascular endothelial growth factor and other angiogenic factors; this results in the characteristic telangiectatic mats of rosacea, which are concentrated centrofacially, in contrast to the lateral and diffuse telangiectasia of chronic photodamage.

Topical alpha-adrenergic receptor agonists can reduce background erythema, but have little effect on fixed telangiectatic mats. To treat these effectively, laser and intense pulsed-light devices are needed. Comparable good results can be obtained with a wide range of vascular (hemoglobin-targeting) lasers and intensed pulsed light, with protocols designed for both purpuragenic (bruising) and nonpurpuragenic settings.^[32,33] Laser and pulsed-light treatments may also reduce background erythema and flushing.^[34] To prevent blistering and postinflammatory hyper- or hypopigmentation, patients should avoid tanning before starting laser therapy.