Epidemiology

Rosacea affects 16 million Americans and is commonly recognized to be more prevalent in fair-skinned patients of Celtic or Scandinavian origin.⁴ Women are more commonly affected than men, and the onset is typically between the ages of 30 and 50 years.⁴

Etiology

The precise etiology of rosacea is uncertain. Among the various theories of causation are inflammatory, infectious, dietary, and psychological theories. Several studies support an inflammatory mechanism. An elevated concentration of interleukin-1 and greater activity of gelatinase B (MMP-9) were found in the tear fluids of patients with ocular rosacea.⁵ Vascular dilation and incompetence may also contribute to the signs and symptoms of the disease.⁶ Microbial organisms such as Helicobacter pylori and Demodex folliculorum have been identified as possible causative factors of the disease.⁶ Molecular studies suggest that an altered innate immune response may be involved in the pathogenesis of this disorder, inducing high levels of cathelicidin, an antimicrobial peptide with vasoactive and pro-inflammatory actions.⁷

Diagnosis

There is no objective diagnostic test specific to rosacea. The diagnosis is clinical, and the disease is often underdiagnosed since patients may be unaware of their symptoms, and physicians may not recognize the early findings, especially early ocular disease.³

A standard classification proposed by the National Rosacea Society Expert Committee was published in 2002. This classification system describes primary and secondary features of rosacea and defines four subtypes of the disease (erythematotelangiectatic, papulopustular, phymatous, and ocular). Evolution from one subtype to another may or may not occur. The features of rosacea are listed in Table 22.1.⁴

Clinical Findings

Rosacea develops gradually and begins with transient flushing that may be triggered by certain factors that are specific to each individual. The most common triggers are listed in Table 22.2. As disease progresses, transitory erythema and telangiectasia of the skin become apparent. Chronic, untreated disease may present with persistent erythema, telangiectasia, papules, pustules and sebaceous gland hypertrophy localized primarily on the convexities of the central face (cheeks, chin, nose and forehead) (Fig. 22.1).⁴

Ocular Rosacea

Ocular involvement has been reported in up to 58% of patients with rosacea and corneal involvement in 33%.³ As many as 90% of patients with ocular rosacea may have only very subtle skin changes, and in 20% of the cases, the ocular signs may precede skin involvement, making the diagnosis particularly challenging.¹

The ocular rosacea patient may complain of foreign body sensation, ‘bloodshot’ appearance, dryness, photophobia and tearing. Decreased visual acuity may be present in cases with corneal involvement.

The findings in ocular rosacea are often non-specific, the most common being meibomian gland dysfunction and blepharitis (Fig. 22.2). A history of recurrent hordeolum and chalazia is common. Chronic conjunctivitis characterized by interpalpebral conjunctival hyperemia may be present. When corneal involvement is present, it typically begins with peripheral neovascularization, which may coalesce into characteristic triangular subepithelial marginal infiltrates (Fig. 22.3). These ‘spade-shaped’ inflammatory infiltrates can progress to the central cornea and lead to ulceration and perforation.² Other reported ocular findings include dendritic keratopathy, iritis, episcleritis, scleritis and even scleral perforation (Fig. 22.4).^3,8

Treatment

The initial management of rosacea is the identification and avoidance of trigger factors. With manifest early skin disease, the dermatologic manifestations of rosacea may be controlled with topical medications, such as metronidazole cream (0.75% and 1% formulations), azelaic acid gel 15% and sulfacetamide/sulfur.9,10 Other topical treatments include clindamycin, erythromycin, pimecrolimus, tacrolimus and tretinoin.¹⁰ When topical treatment alone is insufficient, systemic therapy should be initiated. Oral tetracyclines (500 mg twice daily) and doxycycline (40–100 mg daily from 8 to 16 weeks) have safely improved both skin and ocular rosacea. In 2006, the FDA approved a daily formulation of 40 mg doxycycline monohydrate (Oracea®, Galderma) for the treatment of rosacea. In unresponsive cases and those when tetracyclines are contraindicated, oral azythromycin (500 mg/day for 2 weeks) is considered an option. Oral isotretinoin (0.3 to 1.0 mg/kg/day) is recommended in more severe intractable cases. Vascular laser therapy and intense pulsed light can be used for treatment of resistant skin telangiectasias and persistent erythema.^9,10

The management of mild ocular rosacea includes warm compresses and lid hygiene. Antibiotic ointments prescribed daily, at bedtime, may decrease eyelid flora and help soften collarettes. Moderate ocular rosacea should be treated with oral tetracycline or doxycycline in addition to local ocular therapy. As in the management of skin rosacea, tetracyclines may be initially administered 500 mg twice daily, or 250 mg four times daily for 3–4 weeks, and then tapered according to monitored clinical response. Doxycycline may be prescribed in a regimen of 40–100 mg once or twice daily for 6–12 weeks.¹⁰ Many patients present with flare-ups once the medication is discontinued and may, therefore, require long-term maintenance therapy at a titrated maintenance dose. Topical azithromycin can be useful as an off-label treatment for posterior blepharitis in ocular rosacea, particularly in patients intolerant to oral antibiotics mentioned earlier.

In cases of severe ocular surface inflammation, episcleritis, iritis and keratitis, topical steroids may prove beneficial but must be monitored for steroid-induced side effects.¹⁰ If corneal thinning or perforation occurs, surgical intervention may be necessary. Placement of cyanoacrylate glue, lamellar patch grafts, and penetrating keratoplasty are management options.

Epidemiology