Adiposity and Psoriasis Severity: Treating the Fat Helps Treat the Plaque

Key Takeaways:

• Genetic (mendelian randomization) data from more than 390,000 people indicate that higher body mass index causally raises the odds of psoriasis, by about 9 percent for each 1 kg/m² increase, while genetic risk for psoriasis does not raise body mass index.
• In a randomized trial of 303 overweight or obese adults whose moderate-to-severe psoriasis had not cleared on systemic treatment, a 20-week diet-and-exercise program cut the Psoriasis Area and Severity Index by a median of 48 percent, compared with 25.5 percent after counselling alone.
• Across 54 cohorts including 19,372 patients with immune-mediated diseases treated with anti-TNF drugs, people with obesity had 60 percent higher odds of treatment failure, and each 1 kg/m² rise in body mass index added about 6.5 percent to those odds.

Fat tissue, particularly the visceral fat packed around the abdominal organs, is easy to think of as inert storage, extra weight carried around like ballast. Biologically it is nothing of the kind. Adipose tissue is an active endocrine and immune organ that secretes its own signaling molecules, the adipokines, among them leptin, chemerin, visfatin, and adiponectin. As fat mass grows and fat cells become stressed, the balance tips toward the inflammatory members of that family and away from protective adiponectin, and the tissue fills with immune cells of its own. That matters for the relationship between weight loss and psoriasis, because psoriasis runs on many of the same inflammatory currents. The traffic runs in both directions: cytokines that drive psoriatic plaques, including TNF-alpha and IL-17, also disturb glucose and fat metabolism and promote insulin resistance, while adipokines released from enlarged fat depots feed the inflammation back toward the skin. For years it was fair to ask which came first, because the association could run in either direction. Genetics has largely settled the direction. A mendelian randomization study of nearly 400,000 people, which uses inherited body-weight variants as a natural experiment, found that higher body mass index causally increases the odds of psoriasis, by about 9 percent per unit, while genetic risk for psoriasis had essentially no effect on body mass index.

If fat helps drive the disease, losing some of it should help, and randomized trials have tested exactly that. In a Danish trial, 60 adults with psoriasis and a body mass index of 27 to 40 were assigned to a low-energy diet of 800 to 1,000 calories a day for eight weeks followed by a gradual return to normal food, or to their usual healthy eating. At 16 weeks the diet group had lost about 15 kilograms more than controls. Their psoriasis severity scores fell further, although that difference narrowly missed statistical significance, and their dermatology quality-of-life scores improved significantly. A larger Italian trial is more directly relevant to most people. It enrolled 303 overweight or obese adults whose moderate-to-severe psoriasis had not cleared after at least four weeks of systemic treatment and randomized them to a 20-week structured diet with increased physical activity or to simple counselling about the value of weight loss. With medication continuing in both groups, severity scores fell by a median of 48 percent with the diet-and-exercise program versus 25.5 percent with counselling, and half of the program group achieved at least a 50 percent improvement, compared with about a third of controls.

How much does weight loss help psoriasis?

The most striking detail of that Italian trial is how little weight loss it took. Only about 30 percent of the program group reached the modest goal of losing 5 percent of their body weight, yet the group as a whole nearly doubled its improvement. That suggests the benefit comes partly from changing what the body is doing, eating better and moving more, and not only from the number on the scale. Weight also appears to affect how well medication works. A meta-analysis of 54 cohorts and more than 19,000 patients with rheumatic and skin inflammatory diseases found that people with obesity had 60 percent higher odds of failing anti-TNF therapy, with the risk rising steadily as body mass index climbed. That analysis covered one drug class and observational data, and fewer than one in ten eligible trials even reported results by weight, so it should not be read as a verdict on every newer biologic. None of this is a reason to blame anyone for their skin, and lifestyle change is an addition to effective treatment, not a replacement for it. It is a reason to see a kitchen full of autumn vegetables, legumes, and whole grains, a daily walk, and resistance training twice a week as part of the psoriasis plan itself, with every medication given the best possible chance to work.

References:

1. Budu-Aggrey, A., Brumpton, B., Tyrrell, J., Watkins, S., Modalsli, E. H., Celis-Morales, C., et al. (2019). Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study. PLoS Medicine, 16(1), e1002739.
2. Chiricozzi, A., Raimondo, A., Lembo, S., Fausti, F., Dini, V., Costanzo, A., et al. (2016). Crosstalk between skin inflammation and adipose tissue-derived products: Pathogenic evidence linking psoriasis to increased adiposity. Expert Review of Clinical Immunology, 12(12), 1299-1308.
3. Jensen, P., Zachariae, C., Christensen, R., Geiker, N. R., Schaadt, B. K., Stender, S., et al. (2013). Effect of weight loss on the severity of psoriasis: A randomized clinical study. JAMA Dermatology, 149(7), 795-801.
4. Naldi, L., Conti, A., Cazzaniga, S., Patrizi, A., Pazzaglia, M., Lanzoni, A., et al. (2014). Diet and physical exercise in psoriasis: A randomized controlled trial. British Journal of Dermatology, 170(3), 634-642.
5. Singh, S., Facciorusso, A., Singh, A. G., Vande Casteele, N., Zarrinpar, A., Prokop, L. J., et al. (2018). Obesity and response to anti-tumor necrosis factor-α agents in patients with select immune-mediated inflammatory diseases: A systematic review and meta-analysis. PLoS One, 13(5), e0195123.