Rosacea & Gastrointestinal System (Gut Health) Involvement

Introduction

Rosacea is a chronic inflammatory disease that affects about 0.9% to 10% of the American and European population.1 This disease is characterized by facial flushing, telangiectasias, papules, and pustules. Although the pathogenesis of rosacea is not completely understood, possible explanations include abnormal neurovascular activation, uncontrolled production of inflammatory molecules and increased skin dysbiosis.1 Additionally, rosacea patients have increased cathelicidin expression.2 This anti-microbial peptide, expressed by leukocytes and epithelial cells, is involved in increasing chemotaxis, vasodilatation, angiogenesis, and extracellular matrix deposition.

Treatments

Treatment of rosacea consists of topical medications such as topical metronidazole, ivermectin, sodium sulfacetamide, azelaic acid, and topical alpha adrenergic agonists, as well as systemic medications, most commonly tetracycline and ivermectin. Long-term treatment with oral antibiotics is not recommended as increased bacterial resistance may develop.1,2

Association with gut health

Recently, there has been a growing body of evidence to suggest that rosacea may have a more significant association with the gastrointestinal system than previously thought. This is exciting because understanding the gut-skin association in rosacea may help guide treatment strategies. Studies demonstrate that certain bacteria in the gut can alter intestinal permeability and immunity, and that different bacteria may cause alterations in gut function, gut immunity, and gut inflammation.3,4 This article aims to shed light on the current research regarding the gut microbiome, diet, and gastrointestinal comorbidities of rosacea.

The Gut Microbiome

Helicobacter pylori

The gut microbiome is thought to significantly contribute to non-enteric chronic inflammatory disorders, including those of the skin. Previous studies have demonstrated the association of the gut microbiome with atopic dermatitis, psoriasis, and other diseases. In rosacea, studies have attempted to classify the changes in the gut microbiome.5 For example, the most studied bacteria in rosacea patients is Helicobacter pylori (H. pylori). This bacteria is in the stomach of about 50% of the world’s population.5 In a Mongolia-based study of 50 rosacea patients, H. pylori was significantly higher in rosacea patients than healthy controls.6 Another study also illustrated an increased H. pylori positivity in rosacea patients compared to healthy controls.7 It is postulated that H. pylori’s effect on the concentration of nitrous oxide can result in increased vasodilatation, inflammation, and immune stimulation. Additionally, treatment of H. pylori can alleviate the symptoms of rosacea.6 However, there are studies that have not found a significant correlation between H. pylori and rosacea.8–10 Therefore, more research is required to fully understand H. pylori’s association with rosacea.

Other gut flora

Other gut flora are also implicated in rosacea. For example, when comparing the gut flora in Korean females, Acidaminococcus, Megasphaera, and Lactobacillales were in greater concentration in rosacea patients (p < 0.05).11 Conversely, Peptococcaceae, Slackia, Coprobacillus, Citrobacter, Desulfovbrio and Methanobrevibacter were not as prominent in the rosacea patients.11 The alteration of gut flora is proposed to increase intestinal permeability, resulting in the increased “spillage” of inflammatory products into the systemic circulation.5 This is also referred to as “leaky gut syndrome,” which may allow increased accumulation of immunogenic molecules, bacterial toxins and pathogens on the skin.12

Small Intestinal Bacterial Overgrowth (SIBO)

SIBO is an overgrowth of bacteria in the small intestines, often the result of decreased protective function of gastric acid secretion and intestinal motility.13 The most common bacteria include Streptococcus, Escherichia coli, Lactobacillus, and Bacteroides. Endotoxins from these bacteria can result in damage to the intestine, causing a release of inflammatory markers like tumor necrosis factor-alpha.13,14 Clinically, SIBO presents as abdominal discomfort, bloating, flatulence, or watery diarrhea. Chronic damage can result in vitamin deficiencies such as B1, B3, and B12; however, there is an excess of folate and vitamin K as bacteria produce these compounds.

SIBO has been reported to be associated with papulopustular (rather than erythrotelangiectatic) rosacea and treatment of SIBO has illustrated improvement of rosacea. For example, a 2008 prospective study demonstrated increased eradication and improvement of rosacea after treatment of SIBO with rifaximin.15 This study, however, does not provide a mannitol to lactose ratio to quantify the permeability of the gastrointestinal system. Another study also came to a similar conclusion. Sixty patients with rosacea and 40 healthy controls participated in a three-year follow-up study.14 The presence of SIBO was verified with a lactulose hydrogen breath test (LHBT) and glucose breath test (GBT). At first follow-up 30 days after treatment with 400 mg of rifaximin every eight hours for ten days, 58.3% of patients with rosacea in the treatment group were free of rosacea and had normal intestinal flora. Only 5.7% of patients had a positive LHBT/GBT test at the three-year follow-up and 64.5% of patients in the treatment group were free of rosacea. This study also demonstrated an increased prevalence of SIBO in rosacea. Patients with rosacea were more likely to have SIBO compared to controls (odds ratio: 13.6; 95% confidence interval: 2.9-62.9). In light of these findings, it may be reasonable to gather the patient’s gastrointestinal symptoms to determine whether a work-up or empiric treatment for SIBO may be warranted.

Diet and Rosacea

Rosacea is often precipitated by outside factors that include heat, diet, and more. Specifically, these factors may stimulate the transient receptor potential (TRP) cation channels, which result in an increase in the initiation of pro-inflammatory cascades.2 These go on to upregulate pain perception and inflammation, resulting in increased skin blood flow associated with flushing and burning. In a survey conducted by the National Rosacea Society, 78% of rosacea patients altered their diet due to rosacea and of these people, 95% had improvement of their symptoms through diet change. Although the dietary changes are not completely specified, hot beverages, alcohol, spices, and unrelated foods were triggers of rosacea. These foods and beverages included coffee, tea, hot sauce, cayenne pepper, red pepper, citrus, tomatoes, cinnamon, and chocolate; cinnamaldehyde, an ingredient in many of these foods, may be the trigger.2

There are also diets that can improve rosacea. The role of fiber was emphasized in a mice study; a diet lacking in plant fibers degraded the gut mucus barrier by increasing pathogenicity of Citrobacter rodentium.2,16,17 Conversely, fermented foods, which include yogurt, miso, kimchi, and sauerkraut, can bolster the gut microflora with live active microbial communities.2 The mechanism of action in which probiotics improve rosacea is postulated to include hindering pathogenic bacteria, mediating T-cell inflammation, improving skin barrier function, and preventing the formation of reactive oxygen species. Prebiotics, supplements that promote the growth of beneficial bacteria in the gut, may also help in limiting the permeability of the gut and improving rosacea.2 However, probiotics and prebiotics may also have potential to paradoxically worsen SIBO so probiotic based therapies should be discussed with a physician or qualified health care professional.

Omega-3 fatty acids may have positive effects on rosacea. Omega-3 fatty acids contain fatty acid components, which can competitively inhibit pro-inflammatory pathways.2,18 A randomized controlled trial found these fatty acids to improve dry eye symptoms in rosacea patients.19 Understanding the dietary effects in rosacea could significantly help limit the possible triggers involved in rosacea.

Gastrointestinal Comorbidities of Rosacea

Like many skin diseases, rosacea may also have systemic comorbidities that increases the burden of this disease. For example, in a cohort study of 50,000 Danish rosacea patients, celiac disease, Crohn’s disease, ulcerative colitis, SIBO, and irritable bowel syndrome were seen more often in rosacea patients compared to controls.2 Hazard ratios of these associations were all significant except for H. pylori and SIBO.20 However, as mentioned previously, a three-year follow-up study demonstrated SIBO in 46% of patients with rosacea and improvement with rifaximin.14 Although evidence suggests an association between rosacea and gastrointestinal disorders, further research is required to elucidate the pathophysiological connection.

Table 1: Summary Table of Gastrointestinal Involvement in Rosacea

Factor Involved in Rosacea

What?

Potential Recommendation

Gut Microbiota

-        H. pylori’s effect on the concentration of nitrous oxide can result in increased vasodilatation, inflammation, and immune stimulation

-        Alteration of gut flora results in increased intestinal permeability and increased “spillage” of inflammatory products into the systemic circulation

-        Acidaminococcus, Megasphaera, and Lactobacillales were in greater concentration in rosacea patients

-        Peptococcaceae, Slackia, Coprobacillus, Citrobacter, Desulfovbrio and Methanobrevibacter were not as prominent in the rosacea patients

 

-        Conflicting evidence exists, but there may be utility in treating H. pylori

-        Consider a diet that promotes healthy gut bacteria growth and supplements to improve “leaky gut syndrome”

 

Small Intestinal Bacterial Overgrowth

-        Presents with bloating, flatulence, or watery diarrhea. Chronic damage can result in vitamin deficiencies such as B1, B3, and B12

-        Excess of folate and vitamin K as bacteria produce these compounds

-        Decreased protective function of gastric acid secretion and intestinal motility results in an overgrowth of bacteria and, subsequently, endotoxins from these bacteria can result in damage to the intestine

-        Patients with rosacea were 13 times more likely to have SIBO compared to healthy controls

-        If suspecting presence of SIBO, a work-up or empiric treatment of SIBO with rifaximin 400 mg three times daily for 10 days may be appropriate for selecting patients (effects can be long-lasting)

Diet

-        Transient receptor potential cation channel activation results in an increase in the initiation of pro-inflammatory cascades

-        78% of rosacea patients altered their diet due to rosacea and of these people, 95% had improvement of their symptoms through diet change

-        Prebiotics supplements promote the growth of beneficial bacteria in the gut

-        Avoid hot beverages, alcohol, spices, coffee, tea, hot sauce, cayenne pepper, red pepper, citrus, tomatoes, cinnamon, and chocolate (cinnamaldehyde is an ingredient in many of these foods that may be the trigger)

-        Increase intake of fermented foods, which include yogurt, miso, kimchi, and sauerkraut

-        Increase intake of omega-3 fatty acids

-        Increase the intake of fiber

-        Caveat: Probiotics may worsen SIBO

 

Comorbidities

-        Celiac disease, Crohn’s, ulcerative colitis, SIBO, and irritable bowel syndrome were associated with rosacea

-        Studies detailing the attributable risk is needed to quantify the actual risk of comorbidities with rosacea

 

Conclusion

Rosacea’s burden may expand beyond the facial skin. Current research suggests rosacea is related to the gastrointestinal system. Understanding this association may help guide future treatment, recommendations, and research. For example, recommending prebiotics, probiotics, dietary restrictions, and screening for SIBO and other gastrointestinal disorders may be interesting avenues to provide optimal treatment to the patient. Therefore, continued research is required to establish management guidelines to better assist patients with this disease.

Practical Tips

  • Treating pylori may help improve rosacea. However, a definitive link is yet to be elucidated, as there are conflicting data.
  • Probiotics and prebiotics introduce healthy bacteria into the gut to limit intestinal permeability, but should be discussed with a qualified health care practitioner prior to use.
  • SIBO is highly prevalent in patients with papulopustular rosacea. Treatment of SIBO with rifaximin may also improve rosacea.
  • Rosacea may be triggered by certain foods; therefore, it can be beneficial to avoid hot beverages, alcohol, spices, coffee, tea, hot sauce, cayenne pepper, red pepper, citrus, tomatoes, cinnamon, and chocolate.
  • Rosacea is associated with numerous gastrointestinal disorders; thus, it may be worth screening for these comorbidities.
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References

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