Continuing medical educationRosacea: Part I. Introduction, categorization, histology, pathogenesis, and risk factors
Section snippets
Rosacea classification
Key points Rosacea is typically categorized into 4 main subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular Each subtype is distinguished by the presence of certain primary and secondary characteristics
In 2002, the National Rosacea Society Expert Committee developed a classification system for rosacea to help standardize its diagnosis amongst clinicians and researchers.1 The committee divided rosacea's diagnostic criteria into primary and secondary characteristics, with the presence
Histology
Key point Skin biopsy findings in rosacea are usually nonspecific and are therefore rarely indicated in the diagnosis of this condition
It is not necessary to obtain a skin biopsy specimen in order to reach a diagnosis of rosacea. Many of the histopathologic findings in the different rosacea subtypes are nonspecific, and therefore obtaining a biopsy specimen should be reserved for cases in which the diagnosis is uncertain or when other diagnoses must be ruled out. In ETR, typical histologic findings
Pathophysiology
The exact pathogenesis of rosacea remains unclear. Although the higher incidence of rosacea in individuals of Celtic and Northern European descent suggests that there may be a genetic component to the disorder, genomic association studies have failed to identify a causative gene. Instead, rosacea patients have an increased expression of a variety of genes with roles in both the innate and adaptive immune systems. These results are consistent with findings in the laboratory, where significant
Dysregulation of the innate immune system
Key points Rosacea patients have an increased baseline expression of cathelicidin and kallikrein 5, the predominant serine protease responsible for cleaving cathelicidin into its active form Increased levels of Toll-like receptor 2, which activates kallikrein 5, are seen in patients with rosacea Matrix metalloproteinases that activate kallikrein 5 are also increased in patients with rosacea
Under normal physiologic conditions, triggering the innate immune system leads to controlled increases in cytokines and
Microorganisms
Key points Demodex folliculorum and Staphylococcus epidermidis may contribute to rosacea's pathophysiology by stimulating Toll-like receptor 2 Helicobacter pylori's contribution to rosacea symptoms are unclear, but are suggested by the high prevalence of H pylori seropositivity in the rosacea population, including a high prevalence of virulent strains of this bacterium Bacillus oleronius exposure may contribute to rosacea's pathophysiology by causing production of matrix metalloproteinase-9, tumor necrosis
Ultraviolet light radiation
Key point Ultraviolet light radiation increases reactive oxygen species in the skin, which can signal through Toll-like receptor 2 to propagate the kallikrein 5–cathelicidin inflammatory cascade
UV radiation is a known trigger of flushing and can worsen the symptoms of rosacea. The presence of solar elastosis on skin biopsy specimens obtained from patients with rosacea and the high prevalence of rosacea among individuals with fair skin also suggest a role for UV radiation in the pathogenesis of rosacea;
Neurogenic dysregulation
Key points Four vanilloid receptors and one ankyrin receptor within the transient receptor potential family of cation channels have been shown to be active in rosacea Although signaling pathways of these receptors are not completely understood, these receptors can be activated by stimuli, such as heat and inflammation In turn, they may contribute to rosacea symptoms, such as flushing and burning
The fact that many of rosacea's triggers, including temperature changes and spicy food, activate sensory nerves
Abnormal barrier function
Key points The skin of patients with rosacea has increased transepidermal water loss and decreased epidermal hydration These changes may be related to increased serine protease levels in rosacea and can be reversed with treatment
As a result of the pathophysiologic changes in rosacea, the skin of these patients has been shown to have a decreased barrier function. Compared to control subjects, subjects with both ETR and PPR have increased transepidermal water loss and heightened reactivity to the lactic acid
Risk factors
To date, no specific risk factors have been associated with rosacea. Given that vascular dysregulation has been recognized in the pathophysiology of rosacea, several studies have investigated a potential relationship between rosacea and other conditions in which vascular dysregulation is known to occur. For example, a recent case control study of subjects who suffer from migraines found that women >50 years of age who had migraines had a slightly increased risk of developing rosacea.77
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Funding sources: None.
Dr Two has served as an unpaid consultant for Bayer Pharmaceuticals, Dr Gallo has served as an investigator for Bayer Pharmaceuticals and Galderma, and Dr Hata has served as an investigator for Bayer Pharmaceuticals. Dr Wu has no conflicts of interest to declare.
Date of release: May 2015
Expiration date: May 2018