Psoriasis is no longer confined to the dermatological domain.
It is now clinically classified as a chronic, immune-mediated inflammatory disease (IMID), with systemic implications far beyond the skin.
A recent review in Nature Reviews Immunology (2024) emphasized that the IL-23/Th17 axis—long implicated in cutaneous flare-ups—also drives persistent, low-grade inflammation affecting cardiovascular, hepatic, and joint tissues.
Dr. Nehal Mehta, a leading cardiometabolic dermatologist at the NIH, asserts, "We must treat psoriasis as a multi-system inflammatory condition with dermatological, rheumatological, and cardiovascular expressions. Skin clearance alone is no longer an adequate clinical endpoint."
Molecular Pathways Fueling Persistent Inflammation
At the cellular level, chronic inflammation in psoriasis is maintained through dysregulated innate-adaptive immune interactions. Dendritic cells, upon activation by Toll-like receptors (TLRs), initiate overproduction of interleukin-23 (IL-23). This cytokine is critical for the survival and expansion of Th17 lymphocytes, which secrete effector molecules like IL-17A, IL-22, and TNF-α.
These pro-inflammatory mediators disrupt the epidermal barrier, recruit neutrophils to the dermis, and promote endothelial dysfunction. The inflammatory cascade does not resolve spontaneously; rather, it self-perpetuates, leading to chronic immune activation that persists even in clinical remission.
Systemic Impact: From Cutaneous Lesions to Cardiometabolic Risk
Uncontrolled psoriatic inflammation has been associated with a threefold increased risk of major adverse cardiovascular events (MACE), particularly among patients with high-surface area involvement.
A longitudinal cohort study published in The Lancet Rheumatology (2024) confirmed that patients with untreated moderate-to-severe psoriasis exhibited elevated arterial stiffness, increased carotid intima-media thickness, and coronary artery calcification—independent of conventional risk factors.
These vascular changes are now attributed to immune-cell driven endothelial injury, mediated predominantly by IL-17 and TNF-α. The inflammatory profile of psoriasis parallels that of atherosclerosis, leading researchers to label it a "vascular inflammatory phenotype" within the broader IMID category.
Advancements in Targeted Therapeutics: Cytokine Inhibition
The last five years have witnessed the evolution of highly selective biologic therapies that have revolutionized inflammation control. First-generation biologics like etanercept and adalimumab targeted TNF-α globally. In contrast, second- and third-generation agents—such as guselkumab (IL-23 inhibitor), ixekizumab (IL-17A inhibitor), and bimekizumab (dual IL-17A/F inhibitor)—offer precise molecular blockade with improved tissue specificity.
Recent phase IIIb data from the BE RADIANT study (2024) demonstrated that bimekizumab achieved PASI 100 in 67% of patients by week 16, while also reducing CRP and IL-6 levels to near-physiologic levels. These findings reinforce the view that molecular remission—rather than merely visible plaque resolution—should be the gold standard in psoriasis care.
Precision Immunology: Inflammation Profiling in Clinical Practice
The field is now shifting toward personalized immunomodulation, wherein therapy is guided by each patient's unique inflammatory signature. Peripheral blood RNA sequencing and skin biopsy transcriptomics are being integrated into clinical trials to stratify patients by IL-17-high or TNF-dominant endotypes. This approach helps clinicians choose the most effective biologic pathway from the outset.
Dr. April Armstrong, Professor of Dermatology at USC, notes: "Stratifying patients based on cytokine gene expression allows us to reduce biologic trial-and-error and treat inflammation at its most vulnerable node."
The Silent Threat: Subclinical Inflammation During Skin Remission
Despite visible plaque clearance, subclinical inflammation may persist in vascular, hepatic, or synovial tissues. This residual activity, invisible to the eye, may explain ongoing cardiovascular risk in patients presumed to be in remission. High-sensitivity assays detecting serum amyloid A (SAA), IL-1β, and soluble ICAM-1 are now being considered for routine follow-up, particularly in patients with comorbid metabolic syndrome or early PsA.
Advanced imaging tools like FDG-PET/CT and ultrasensitive vascular ultrasound can also localize persistent inflammation in coronary or carotid vessels—offering an objective basis for continued therapy in asymptomatic patients.
Interdisciplinary Management: Dermatology, Cardiology, Rheumatology
Modern psoriasis care demands collaboration. The growing recognition of systemic inflammatory damage has prompted the rise of multidisciplinary psoriasis clinics, which integrate dermatology with rheumatology, hepatology, and preventive cardiology. In these settings, patients undergo coordinated evaluation for psoriatic arthritis, hepatic steatosis, lipid abnormalities, and insulin resistance—all linked to underlying chronic inflammation.
The overarching goal in managing psoriasis is no longer merely cosmetic. Long-term treatment strategies now prioritize inflammatory suppression at the molecular level to prevent irreversible end-organ damage. This requires continuous monitoring of immune activity—not just symptom reports—and may involve lifetime immunomodulatory therapy in high-risk patients.
As novel biologics and immune biomarkers emerge, the paradigm is shifting from disease management to disease interception, wherein inflammation is neutralized before systemic manifestations take root.
