Treating Rosacea: Unique Clinical Characteristics Inform Treatment

Rosacea is a common inflammatory skin condition of the central face that produces a significant reddening along with papules and pustules that cause substantial psychological anxiety and embarrassment. The prevalence ranges from 0.1% to 10% of the population, with anywhere from 1 to 10 million people estimated to have some form of rosacea.

The disorder is often treatment resistant and tends to become chronic, despite the availability of multimodal treatments.^1,2 Although no specific genetic influence has been identified, rosacea is most commonly seen in fair-skinned people of northern European or Celtic descent, with a higher reported incidence in women.¹

Clinical Features of Rosacea Subtypes

Rosacea appears to be a global systems disorder that promotes large-scale activation of resident skin cells. The etiology is not fully understood, and is believed to involve multiple mechanisms, including innate and adaptive immune systems stimulation, as well as heightened neuroimmune communications and a hyper-reactivity of blood and lymphatic vessels.^3,4

Erythematotelaniectatic (ETR) is the first of 4 subtypes of rosacea identified in 2002 by the National Rosacea Society, each based on different clinical pathogiologies.⁵ The other variations include papulopustular (PPR), phymatous, and ocular rosacea (OR). Clinical presentations of rosacea vary by sex, as women most often develop the first 2 subtypes, whereas men often have enlargement and reddening of the nose (rhinophyma) and bumpy phymatous formations, which may represent different pathologies.¹

ETR may be the most common form, or possibly an early form of disease that becomes more complicated over time. The most prominent clinical feature of ETR is transient flushing (erythema), usually triggered by stimuli such as spicy foods, alcohol, heat, or ultraviolet exposure, as well as persistent central facial erythema, either alone or accompanied by the appearance of small, dilated blood vessels (telangiectases).^1,3 Other signs include central swelling of the face and stinging or burning sensations, along with possible scaling of the skin.³

PPR often shares the main features of ETR, plus the addition of inflammatory papules or pustules in the central facial areas around the nose, cheeks, chin, and forehead.² A range of other symptoms includes erythematous plaques, scaling, and thickening of the skin as a result of hyperplasia of the sebaceous glands.² The overlap between these 2 conditions indicates a potential progression of disease severity from ETR to PPR. Tan et al⁶ found that 66% of patients with PPR had originally been diagnosed with ETR. According to Mohammed Saleem, MD, from Wake Forest University School of Medicine, Winston-Salem, North Carolina, and coauthor of a recent review of ETR,² “It is not completely clear whether ETR and PPR are separate entities or a continuum; however, there is evidence to suggest they are likely related.”

OR includes symptoms of darkened upper eyelids, formations on lower lids, and foreign body sensation, dryness, itching, photophobia, and tearing in the eyes, along with the appearance of redness and blood vessels on the eyes. An estimated 58% to 72% of cases of OR occur in patients with other forms of rosacea, most often ETR.⁷ Consequences to OR can be serious and threaten vision.

Dr Saleem told Dermatology Advisor, “The clinician should be aware that not all centrofacial erythema and telangiectasis represent ETR, and multiple other skin conditions can present with similar findings. Similarly, not all patients with facial erythema and papules have PPR. A thorough history and physical examination is required to eliminate clinical mimickers and to establish an accurate diagnosis.”

Treatments for ETR and PPR

The multifactorial nature of rosacea both complicates and informs treatment decisions, and despite the availability of numerous topical and laser therapies, rosacea is not curable and remains chronic. Avoidance of triggers is key to management, including ultraviolet light, spicy foods, heat, and alcohol consumption. With the recent approval of new topical agents, beginning with brimonidine in 2013, the first line of therapy for both ETR and PPR is the use of topical treatments:

• Brimonidine tartrate (0.33% gel) is a topical therapy for persistent erythema that provides direct vasoconstriction of small subcutaneous arteries and veins. It has demonstrated good efficacy and is well tolerated, although long-term effects on disease course are not yet known.^3,8
• Ivermectin (1% topical cream) contains a broad-spectrum antiparasitic agent with anti-inflammatory properties that have shown efficacy against demodex skin mites that may be involved in dysregulation of the innate immune system.⁸ It has been shown in clinical trials to reduce inflammatory lesions in PPR and is well tolerated.⁸ Longer-term studies have shown an increase in efficacy.⁸
• Azelaic acid (15% concentrated foam) has also demonstrated efficacy against inflammatory lesions in PPR, although a higher incidence of adverse events was reported when compared with ivermectin.⁸

A 2016 review of therapies by Micali and colleagues³ suggested that because treatment effects are often limited to singular symptoms, it is important to use combination therapies to have a significant effect on skin appearance for the majority of patients with ETR, with or without other symptoms. Their recommendation was to initiate topical treatment with brimonidine gel and to follow up with specific laser and ultraviolet light therapies that target prominent telangiectasia and background erythema.

Current reviews suggest that limited outcomes to individual therapies point to the need for new treatments that target underlying cellular and molecular mechanisms.⁹

References

1. Oge L, Muncie HL, Phillips-Savoy AR. Rosacea: diagnosis and treatment. Am Fam Physician. 2015;92:187-196.
2. Saleem MD, Wilkin JK. Evaluating and optimizing the diagnosis of erythematotelangiectatic rosacea. Derm Clin. 2018;36:127-134.
3. Micali G, Gerber PA, Lacarrubba F, Schafer G. Improving treatment of erythematotelangiectatic rosacea with laser and/or topical therapy through enhanced discrimination of its clinical features. J Clin Aesthet Dermatol. 2016;9:30-39.
4. Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol. 2013;69:S15-S26.
5. Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol. 2002;46:584-587.
6. Tan J, Blume-Peytavi U, Ortonne JP, et al. An observational cross-sectional survey of rosacea: clinical associations and progression between subtypes. Br J Dermatol. 2013;169:555-562.
7. Vieira AC, Höfling-Lima AL, Mannis MJ. Ocular rosacea–a review. Arq Bras Oftalmol. 2012;75:363-369.
8. Gold LM, Draelos D. New and emerging treatments for rosacea. Am J Clin Dermatol. 2015;16:457-461.
9. Vemuri RC, Gundamaraju R, Sekaran SD, Manikam R. Major pathophysiological correlations of rosacea: a complete clinical appraisal. Int J Med Sci. 2015;12:387-396.