Pharmacy Times offers relevant, clinical information for pharmacists that they can use in their daily practice. These include OTC and Rx product news, disease conditions, patient education guides, drug diversion and abuse, and more.
Issue link: http://pharmacytimes.epubxp.com/i/614520
December 2015 PharmacyTimes.org 111 involved in antimicrobial defense. 4,5,7 Activation of receptors (TLR-2) on skin cells stimulates defense mechanisms, and an antimicrobial peptide (AMP) called cathelicidin LL-37 is released as a first-line defense. An altered form of LL-37 is thought to amplify the local inflammatory response, increase vascu- larity, produce vasodilation, and activate adaptive immunity. LL-37 is activated by kallikrein-5 (KLK5), which is a serine protease that, in turn, is activated by a matrix metalloproteinase. Patients with rosacea have 10-fold higher levels of cathelicidin than patients with normal facial skin. Triggers that activate the cathelici- din pathway include heat and ultraviolet (UV) exposure. UV exposure triggers vitamin D production, which increas- es cathelicidin production in the skin. Because it is an area highly exposed to UV radiation, the face is the primary site affected by rosacea. Another trigger for activation of LL-37 is thought to be Demodex folliculorum, a mite found in the pilosebaceous follicles of the skin. It has been proposed that the chitin released from the mites may trigger activation of TLR-2 in skin cells, thereby increasing activity of KLK5. This results in an increase in LL-37 fragments, which leads to redness, inflammation, and the presence of visible blood vessels that are called telangiectasis in the patient with rosacea. 5 Other mediators thought to be involved in the pathophysiology of rosa- cea include histamine, prostaglandins, reactive oxygen species (ROS), vascular endothelial growth factor (VEGF), and Bacillus oleronius. Histamine and pros- taglandins are inflammatory mediators that produce vasodilation, which results in symptoms of flushing, erythema, and edema. ROS and degradative proteases such as KLK5 may be released by neu- trophils and can damage the connective tissue support of blood vessels. Exposure to UV radiation has been associated with production of VEGF that has been linked to production of telangiectasia (visible blood vessels). B oleronius, associated with the D folliculorum mites, can stimu- late an inflammatory response in papulo- pustular rosacea. 2 Incidence and Prevalence The prevalence of rosacea has been esti- mated to be between 1% to 20% of the US population. 8 Variability of this estimate is likely due to a high degree of undiagnosed or misdiagnosed disease. 1 Prevalence is reported to be rising in the United States, but this may reflect aging of the baby-boomer generation. Rosacea is more prevalent in women, with the exception of subtype 3, which occurs primarily in men. Fair-skinned Caucasians who have blond hair and blue eyes are more frequently affected, par- ticularly those of Celtic or Scandinavian heritage. Rosacea may be more likely to develop in patients who have frequent episodes of blushing or flushing around the face and neck regions early in life. Rosacea also may occur at any age, but it is primarily diagnosed between 30 and 50 years of age. Patients with rosacea are likely to have a relative with rosacea or severe acne. This suggests a genetic component to the disease, although no causative gene has been identified. 1,5,8 Clinical Presentation Rosacea is characterized by transient or persistent erythema of the central face, including the cheeks, nose, chin, and middle forehead. It may include the presence of inflammatory papules or pustules, telangiectasia, or hyperplasia of the connective tissue. Flushing, or transient erythema, may be accompanied by a feeling of warmth. Other findings seen less commonly include erythema- tous plaques, scaling, edema, thickening of skin due to hyperplasia of sebaceous glands (called phymatous changes), and ocular symptoms. 1 Social Impact Rosacea can have a marked psychoso- cial effect on patients. The most com- monly reported concern is temporary facial flushing, which is followed by persistent redness and the presence of bumps and pimples. 9 Misconceptions about patients with rosacea are common. Some may wrongly conclude that lack of proper personal hygiene is the cause of symptoms or that heavy alcohol con- sumption causes the redness and bulbous appearance of the nose. In a 2013 survey of 800 patients with rosacea, 61% to 85% reported a negative social impact, depending on the type and severity of their disease. Half of the patients sur- veyed cited a concern that consuming certain foods or drinks would trigger a rosacea flare-up, so they felt it was necessary to refuse items they would otherwise enjoy. Other common con- cerns included being the object of stares, comments, or jokes (43%); refusing social engagements due to flares (39%); not participating in physical activities (37%); and avoiding new experiences (28%). Sixty-three percent of patients reported improvement in their social lives following treatment. 10 Other studies have reported high rates of depression, embarrassment, social phobia, and stress in patients with rosacea. 11 Decreased quality of life is commonly noted and is most often associated with the presence of erythema. Diagnosis Rosacea is diagnosed based on patient history and physical examination; labo- ratory testing is not used. One of the following primary features of the cen- tral face is required for diagnosis 12,13 : flushing, nontransient erythema, telan- giectasia, or papules/pustules. Each of the primary signs should be graded on a 0 to 3 scale (Table 1 13 ). 12,13 Flushing should be graded based on frequency, duration, extent, and intensity. The pres- ence of sweating should also be noted. Nontransient erythema, also called back- ground or persistent erythema, should be graded by the degree of redness present. Telangiectasia should be graded based on the number and nature of the blood vessels present. Papules and pustules, giving the appearance of raised spots and pimple-like bumps, should be graded on the number of lesions present and the presence of plaques or red patches on the skin. Secondary features, such as a stinging or burning sensation, dry skin, edema, plaques, involvement of the eye, or the phymatous changes characteristic of sub- TABLE 1: SEVERITY GRADING SCALE FOR PRIMARY SYMPTOMS OF ROSACEA 13 Grading Scale Absent 0 Mild 1 Moderate 2 Severe 3