Emerging data suggest that environmental exposure to barium, a heavy metal found in drinking water and industrial waste, may contribute to the development of psoriasis by disrupting potassium channel signaling.

Psoriasis is a chronic autoimmune condition primarily mediated by T-cell activation and characterized by keratinocyte hyperproliferation. It affects an estimated 2% to 4% of the global population, with prevalence reaching as high as 11% in some Western European countries. While genetic and lifestyle factors are established contributors, recent evidence has turned attention toward environmental pollutants as potential triggers.

Two epidemiologic studies have highlighted barium as a leading environmental correlate of psoriasis. In the first, researchers conducted a machine learning–based analysis of over 1 billion billable medical visits across 20,000 U.S. ZIP codes and found that barium and nitrogen dioxide were the pollutants most strongly associated with psoriasis diagnoses. A second study, using National Health and Nutrition Examination Survey (NHANES) data and multivariable logistic regression, demonstrated that individuals in the highest quartile of urinary barium levels had an odds ratio (OR) of 1.794 (95% CI, 1.189–2.743) for having a psoriasis diagnosis compared with those in the lowest quartile. The association was strongest in individuals under 60 years of age. Cesium, another heavy metal known to inhibit potassium channels, was also consistently associated with psoriasis across models.

Barium is used in industrial applications such as drilling muds, glass, plastics, cosmetics, and paints. It can enter the body through drinking water, air, and food. In its soluble forms (e.g., barium chloride), barium dissociates into Ba²⁺, which can inhibit potassium (K⁺) channels by mimicking K⁺ and binding with high affinity to the selectivity filter within these channels, thereby blocking K⁺ efflux.

Two potassium channels—Kv1.3 and KCa3.1—are particularly relevant to psoriasis and immune function. Kv1.3 is a voltage-gated K⁺ channel abundantly expressed in T cells and implicated in chronic autoimmune activity. KCa3.1 is a calcium-activated K⁺ channel expressed in T cells, epithelial tissue, and endothelial cells; overexpression in mouse skin models led to hyperplasia and hyperkeratosis, which were reversed with KCa3.1 blockade. Psoriatic lesions contain elevated levels of Kv1.3-expressing T cells.

Researchers hypothesize two possible mechanisms by which barium may alter potassium signaling and contribute to psoriasis:

• Indirect modulation: Barium blocks other potassium channels, leading to compensatory upregulation or overuse of Kv1.3 and KCa3.1 channels.

• Direct inhibition: Chronic exposure to barium may inhibit Kv1.3 and KCa3.1 directly—though this has not yet been demonstrated in immune or epithelial cells—resulting in a compensatory increase in their expression and activity.

Both pathways are hypothesized to result in excessive K⁺ efflux through these channels, potentially triggering inflammasome activation (NLRP3 and NLRP1), which promotes the release of IL-1β and IL-18—pro-inflammatory cytokines known to be elevated in psoriatic skin.

The review also draws parallels to drug-induced psoriasis. Several medications known to trigger psoriasis—including lithium, β-blockers, chloroquine, insulin, bupropion, and terbinafine—interfere with potassium channel function. TNF-α inhibitors may also indirectly affect Kv1.3 expression.

Therapeutic targeting of these channels is under investigation. Kv1.3 blockers, such as curcumin and dalazatide, have shown promise in reducing inflammation and Psoriasis Area and Severity Index (PASI) scores in preclinical and early clinical studies. KCa3.1 blockers, though not yet tested in psoriasis, have demonstrated safety in trials for other inflammatory conditions.

While the epidemiologic data support an association, causality cannot be established due to the cross-sectional nature of the studies. Longitudinal and mechanistic research is needed to confirm whether barium exposure plays a direct role in psoriasis pathogenesis and to explore whether limiting exposure could reduce disease risk.

The authors of the reviewed article declared no conflicts of interest and reported that no generative artificial intelligence was used in creating their manuscript. Funding was provided by the NIH’s Intramural Research Program.

Source: Frontiers in Medicine