Residual inflammation can linger in psoriasis patients despite skin treatment

New research shows that in patients with psoriasis, even though their skin responds well to treatment with biologics, inflammation can linger, leading to broader health implications such as obesity and cardiovascular and fatty liver disease. The findings of the study in the Journal of Investigative Dermatology (JID), published by Elsevier, could lead to more targeted and effective treatments that address the systemic aspects of psoriasis, beyond just the skin.

Systemic chronic inflammation has been implicated in several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease, and autoimmune and neurodegenerative disorders. Psoriasis, with its systemic inflammatory nature, high atherosclerosis burden, and frequent use of biologic drugs, could provide a valuable framework for studying residual inflammation. Prior to the present study, a comprehensive assessment of this concept was lacking.

Lead investigator Álvaro González-Cantero, MD, PhD, Department of Dermatology, Hospital Universitario Ramón y Cajal, and Faculty of Medicine, Universidad Francisco de Vitoria, Madrid, says, "Patients with psoriasis have a reduced life expectancy due to an increased risk of cardiovascular disease. With the goal of better understanding this, we wanted to explore psoriasis as a systemic disease and its broader health implications."

This prospective observational study assessed residual inflammation in 209 psoriasis patients across three international cohorts (Spain, USA, and Sweden) who had achieved a ≤ 2 on the Psoriasis Area Severity Index (PASI) indicating no or mild psoriasis on stable biologic therapy. The key findings revealed that residual inflammation was present in 36.3% of these patients and was significantly linked to higher BMI, metabolic dysfunction-associated steatotic liver disease (MASLD), increased baseline systemic inflammation, and greater adipose tissue.

Dr. González-Cantero explains, "Our present study offers novel insights into psoriasis management by characterizing residual inflammation in patients undergoing biologic therapy across three independent international cohorts. This is particularly important now because it highlights that despite achieving good skin responses with biologics, a significant subset of patients, predominantly those with obesity (especially central obesity), higher baseline systemic and organ inflammation (as shown by PET/CT), increased subcutaneous and visceral adipose tissue, and markers of MASLD, continue to exhibit residual inflammation. This underscores a critical unmet need to address the systemic inflammatory burden beyond skin symptoms in psoriasis, potentially requiring interventions targeting obesity and metabolic dysfunction to improve overall patient outcomes."

Co-first author Alba Lecumberri, MD, Department of Dermatology, Hospital Universitario Ramón y Cajal, Madrid, notes, "The strong association identified between residual inflammation and obesity, particularly central obesity and markers of hepatic inflammation, suggests that these patients may benefit from a more intensive cardiovascular risk assessment and management. This could involve closer monitoring of inflammatory markers like high-sensitivity C-reactive protein, as well as parameters related to liver health, by integrating lifestyle modifications or weight management strategies, potentially leading to earlier detection and intervention for associated comorbidities."

Commenting on the study, noted expert Michael Garshick, MD, MBBS, Department of Medicine, New York University Grossman School of Medicine, adds, "This research emphasizes the elevated cardiovascular risk in patients with psoriasis and that dermatologists (and rheumatologists) should be at the forefront of recognizing the cardiometabolic and cardiovascular concerns in the psoriasis patient population. An elevated high-sensitivity C-reactive protein testing can be used to further refine assessment of which psoriasis may be candidates for both lipid lowering and weight loss treatments."

The investigators point out that further studies are needed to confirm their findings and better understand the long-term implications for patient management.

Co-first author Emilio Berna-Rico, MD, PhD, Department of Dermatology, Hospital Universitario Ramón y Cajal, Madrid, concludes, "We believe this to be a relevant study for dermatology, as it has assigned the term 'residual inflammation' for the first time in psoriasis patients, taking into account the systemic inflammation of the disease. We hope that our results can pave the way for a broader approach in psoriasis research, which will allow us to mitigate the effects of systemic inflammation and improve patient management through the use of the innovative therapies available to us, in addition to educating patients on a healthy and anti-inflammatory lifestyle, in collaboration with other healthcare professionals."

According to Joel M. Gelfand, MD, MSCE, Department of Dermatology, University of Pennsylvania Perelman School of Medicine, and JID Deputy Editor for Clinical Research & Epidemiology, "Despite excellent control of skin disease, a substantial percentage of psoriasis patients demonstrate residual systemic inflammation. These findings emphasize that just treating the skin signs of psoriatic disease is not sufficient, and patients often need additional approaches to lowering systemic inflammation."