Table 5.

Summarizing the known environmental triggers of macrophage activation in rosacea.

Trigger	Mechanism of Activation	Effect on Macrophages	Effect on Skin	Examples	Reference
Ultraviolet radiation	Induces production of reactive oxygen species and pro-inflammatory cytokines	Activates macrophages and increases production of pro-inflammatory cytokines	Promotes inflammation, angiogenesis, and oxidative stress	Sun exposure, tanning beds	36, 45, 104
Temperature changes	Activates sensory neurons that release neuropeptides	Induces vasodilation and increases blood flow, which may activate macrophages	Promotes flushing, inflammation, and nerve sensitivity	Hot showers, exercise	36, 45, 105
Emotional stress	Activates the hypothalamic-pituitary-adrenal axis and sympathetic nervous system	Increases production of stress hormones and pro-inflammatory cytokines	Promotes inflammation and nerve sensitivity	Anxiety, anger, embarrassment	106, 107
Alcohol consumption	Increases blood flow and permeability of blood vessels	Activates macrophages and increases production of pro-inflammatory cytokines	Promotes flushing, inflammation, and nerve sensitivity	Wine, beer, liquor	23, 108
Spicy foods	Activates sensory neurons and increases blood flow	May induce vasodilation and activate macrophages	Promotes flushing, inflammation, and nerve sensitivity	Chili peppers, hot sauce	23, 109, 110
Hot beverages and food	Increasing body temperature and capillary dilation	May increase activity due to elevated body temperature	Can cause flushing, heat sensation	Coffee, Tea, Spicy food	111–113
Certain drugs (vasodilators or nicotinic acid)	Increasing blood flow by dilating blood vessels	Nicotinic acid could impact macrophages directly by modulating inflammation	Vasodilators can cause flushing, nicotinic acid can cause flushing and itching	Nicotinic Acid (Niacin), Nitroglycerin	114–116
Irritation (cosmetic or other topical products)	Topical irritation causes an immune response	Can trigger an inflammatory response	May cause redness, swelling, itching	Certain cosmetics, soaps, lotions	117, 118
Exercise	Increase in body temperature and blood flow	Likely increases activity due to elevated body temperature and increased blood flow	Increased blood flow can cause flushing, sweating	Cardio exercises, Strength training	119, 120