Renal and pulmonary pathologies... an association between rosacea and invisible illnesses?

In a Brazilian clinical trial, patients suffering from rosacea exhibited significantly higher epicardial fat thickness and carotid thickness than the control subjects, thereby exposing them to risks of cardiovascular diseases.

structural changes in high-density lipoproteins (HDL) , negatively impacting their ability to remove cholesterol, which can then lead to cardiovascular problems.

Rosacea has been linked to cardiovascular risk biomarkers, such as total cholesterol, low-density lipoproteins, and C-reactive protein. These molecules promote the formation of deposits on the arterial walls, leading to atherosclerosis.

A study has also shown that the serum activity of paraoxonase-1 (PON-1), an antioxidant enzyme associated with high-density lipoproteins, significantly decreases in patients with rosacea. A lower activity of PON-1 has also been demonstrated in dyslipidemic patients (those with high cholesterol levels) and those suffering from hypertension.

Studies on this subject are contentious. This discrepancy could be explained by the fact that the available data comes from studies with a small sample size and insufficient statistical power.

The clinical manifestations of the metabolic syndrome (diabetes mellitus, obesity), such as insulin resistance, may be present in patients with rosacea. Furthermore, the risk of rosacea is high in patients with a high body mass index.

It is hypothesised that the systemic inflammation underlying rosacea induces structural changes in lipoproteins, which negatively impacts the lipid profile and thus increases the risk of metabolic diseases.

The low serum activity of PON-1, which prevents the oxidation of serum lipoproteins, is a common characteristic of rosacea and metabolic diseases, suggesting that oxidative stress contributes to their co-occurrence.

In a meta-analysis involving 5,051,356 patients, the relative risk of rosacea in all inflammatory bowel diseases (IBD), ulcerative colitis, and Crohn's disease, was respectively 1.66, 1.69, and 2.08, which is high.

Rosacea is also correlated with irritable bowel syndrome. However, the underlying mechanisms have not been well elucidated. Rosacea is associated with an innate and adaptive immune activation, and IBD shares innate inflammatory elements with rosacea.

For instance, macrophages and macrophage-derived mediators (ROS, matrix metalloproteinases, IL-1β and TNF-α) pathologically contribute to rosacea and IBD.

Patients suffering from rosacea often experience discomfort, social anxiety, and psychiatric comorbidities. A Chinese study examined the quality of life using the Dermatology Life Quality Index and the psychological situation using the Hospital Anxiety and Depression Scale among 201 rosacea patients and 196 healthy controls. The scores for the Dermatology Life Quality Index, anxiety, and depression were significantly higher in the rosacea group. Furthermore, in a Swedish study, migraine affected 27% of rosacea patients compared to 13% of healthy control subjects. However, the underlying mechanisms remain poorly understood.

Transient receptor potential vanilloid (TRPV) ion channels are cationic channels that mediate neurogenic inflammation. They are activated by heat, alcohol, spicy foods, and more. A study has shown that inflammation in rats induces behaviours similar to anxiety and depression, mediated by the activation of TRPV-1, and that the inhibition of TRPV-1 has an antidepressant effect.

TRPV-1 channels are increased in chronic migraine patients and in the skin of patients suffering from rosacea. Indeed, the activation of TRPV-1 receptors leads to the release of calcitonin gene-related peptide during migraine attacks, which causes vasodilation and pain. The genetic expression of the calcitonin gene-related peptide being higher in patients with rosacea, this suggests that TRPV-1 could play a role in the pathogenesis of rosacea and in the neurological and mental comorbidities associated with it.

A German study involving 70 patients with Parkinson's disease revealed that rosacea was present in 18.6% of the participants. Rosacea-affected skin exhibits increased activation and expression of matrix metalloproteinases (MMP-1, MMP-3, MMP-9), which lead to inflammatory tissue damage and degradation of the extracellular matrix. MMPs have also been implicated in the pathogenesis of Parkinson's disease. Levels of MMP-3 and MMP-9 increase and contribute to the loss of dopaminergic neurons.

Basal cell carcinoma has been found to be significantly associated with rosacea. Previous studies have shown that patients with rosacea tend to have fairly light skin, thus less protected against UV rays, and are likely to be more exposed to ultraviolet light at an early age, which could confer them a high risk of basal cell carcinoma.

Furthermore, it is observed that there is a heightened risk of developing gliomas, brain cancer tumours, in patients suffering from rosacea. This could be linked to common inflammatory pathways dependent on matrix metalloproteinases and the activation of IL-17.

Specifically, MMP-9 plays a significant role in the pathogenesis of rosacea and in the regulation of cellular invasion in malignant gliomas. The increase in IL-17 is also recognised as a characteristic of rosacea and could play a role in immune suppression in glioma.

Rosacea and chronic obstructive pulmonary disease (COPD) have recently been linked in studies, but the mechanisms have not yet been thoroughly investigated. However, it has been suggested that theabnormal activation of immune cells (Th1 lymphocytes, Th17 and human cathelicidin LL-37) and pro-inflammatory cytokines, such as IL-1 and IL-6, involved in the pathogenesis of COPD and rosacea, could be the basis of this hypothesis.

A potential association could be made between rosacea and renal pathologies, such as chronic kidney disease (CKD), and this link has only been investigated very recently. It is primarily based on observations. A Taiwanese study showed that the incidence rate of CKD among patients with rosacea is 16.02 per 1,000 people per year. This link can be explained by the fact that pro-inflammatory cytokines (IL-1β and TNF-α) are involved in the pathogenesis of rosacea, and these inflammatory mediators may play a role in the development of chronic kidney disease.

There also exists a positive correlation between the extent of reduction in skin's antioxidant capacity and the severity of rosacea, indicating that oxidative stress may play a role in the pathophysiology of rosacea. Similarly, clinical studies confirm the significance of oxidative stress in chronic kidney disease, as it can trigger the inflammatory process and accelerate the progression of kidney damage. Although the evidence is not conclusive, mechanisms involving inflammatory pathways and oxidative stress appear to contribute to the association between rosacea and the risk of chronic kidney disease.

Let us remember that understanding of the subject remains quite limited today, and having rosacea does not automatically imply the presence of an underlying disease. Consult your doctor at the slightest doubt.

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