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Managing Comorbidities in Psoriasis: A Comprehensive Approach

By Jennifer Lightowler, MMSc, PA-C

Abstract

Psoriasis, traditionally viewed as a skin disease, is now widely recognized as a systemic inflammatory condition associated with a significant burden of comorbidities that can complicate its management and worsen prognosis. This article provides a detailed overview of the key comorbidities linked to psoriasis, including psoriatic arthritis, cardiovascular disease, obesity, diabetes and metabolic syndrome, fatty liver disease, inflammatory bowel disease, mental health conditions, and other autoimmune diseases. For each comorbidity, we discuss prevalence statistics, underlying pathophysiological mechanisms, and crucial management strategies, emphasizing lifestyle interventions and the impact on dermatological therapy choices. We also explore the emerging evidence suggesting that early and aggressive treatment of psoriasis, particularly with biologic agents, may play a vital role in mitigating the risk and severity of these associated conditions. This review underscores the critical need for a holistic, interdisciplinary approach to optimize outcomes for patients with psoriatic disease.

 

 

Introduction

Psoriasis is a chronic, immune-mediated inflammatory disease primarily manifesting on the skin and joints, affecting approximately 2–4% of the global population. Beyond its cutaneous features, advances in genetics, immunology, and epidemiology have redefined psoriasis as a systemic disease.1-2 Patients with psoriasis are especially susceptible to a range of comorbidities that can profoundly impact overall health and quality of life. These associated conditions are not merely coincidental but are intricately linked by common pathophysiological mechanisms, particularly chronic inflammation, and metabolic dysregulation.1-3 Early identification and comprehensive, multidisciplinary management of these comorbidities are crucial for improving patient prognosis and quality of life. Dermatology clinicians, often the primary medical contact for psoriasis patients, play a pivotal role in this holistic approach.

Psoriatic Arthritis (PsA)

Psoriatic arthritis (PsA) is a chronic inflammatory condition that affects the joints and is a common comorbidity of psoriasis.1,4-9 Approximately one-third of patients with psoriasis will develop PsA. The overall pooled proportion of PsA among adult psoriatic patients is reported at 19.7%, with a lower prevalence in adolescents (3.3%). The risk of developing PsA is correlated with the severity of psoriasis; incidence rates are 1.48 per 100 patient-years in mild psoriasis, 3.00 in moderate, and 5.49 in severe cases. The risk also steadily increases with the duration of cutaneous symptoms following psoriasis onset.2

PsA primarily manifests as joint inflammation. Subclinical signs like active enthesitis and synovitis may be present.2 Patients with PsA experience a greater clinical burden, including higher rates of other comorbidities such as fatigue, diabetes, depression, and obesity, compared to those with psoriasis alone.6,10-11

The association between PsA and psoriasis lies in their shared systemic inflammatory nature. Both conditions are driven by common pathophysiological pathways involving pro-inflammatory cytokines, such as T helper (Th)1 and Th17 cells, and mediators like interferon (IFN)-γ, interleukin (IL)-6, IL-22, and tumor necrosis factor-alpha (TNF-α).2,12-14

PsA Management

A collaborative, multidisciplinary approach is essential for managing PsA.15 As Betsy Kirchner, CNP, a Nurse Practitioner at Cleveland Clinic in Cleveland, OH, explains, “Whether we work in rheumatology or dermatology, our goals when initiating therapy are the same: to decrease pain, improve functioning, and enhance quality of life. But just as importantly, we want to prevent permanent joint damage.”

Early diagnosis of PsA is critical not only to limit irreversible joint damage but also to preserve mental health. Delays of more than six months have been linked to worse patient-reported depression and reduced social functioning.11 Factors such as patients’ lack of awareness of the skin–joint connection and the absence of a specific diagnostic marker often contribute to these delays. For this reason, dermatology clinicians should routinely screen psoriasis patients for joint symptoms and refer to rheumatology when PsA is suspected.8

Treatment strategies should target the underlying inflammatory pathways. Psoriasis and PsA share drivers of systemic inflammation, including TNF-α, IL-17, and IL-23. Biologic therapies that modulate these pathways provide effective control of both skin and joint disease, while also reducing long-term inflammation.9,12-13 Dr. Kirchner emphasizes the importance of timing. “Multiple randomized controlled trials demonstrate that biologic DMARDs—including TNF inhibitors, IL-17 inhibitors, and IL-12/23 inhibitors—are effective in suppressing joint inflammation and [slowing] radiographic progression in PsA.”

Among these, TNF-α inhibitors such as infliximab and adalimumab are considered first-line options, though IL-17 and IL-23 inhibitors are increasingly favored for their dual efficacy in skin and joint disease and potentially improved safety with long-term use.2,9,12

A head-to-head study supports this, says Ben Lockshin, MD, Director, Clinical Trials Center at DermAssociates and EVP of Strategic Initiatives at U.S. Dermatology Partners in Rockville and Silver Spring, MD.

“In a head-to-head study of ixekizumab (Taltz, Eli Lilly & Co.) vs. adalimumab, a significantly greater number of patients on ixekizumab achieved both an American College of Rheumatology [ACR] 50 and a Psoriasis Area and Severity Index [PASI] 100,” referring to a 2022 study examining efficacy and safety of ixekizumab, an IL-17 inhibitor, and adalimumab, a TNF-α inhibitor.16 “Meaning, we can get better skin clearance without sacrificing joint control,” he explains.

Conventional systemic therapies such as methotrexate and cyclosporine remain in use, but their utility is limited by cumulative toxicity and side effects.9 Ultimately, clinicians should individualize treatment choices, balancing efficacy, safety, comorbidities, and cost to optimize outcomes across both skin and joint disease.

Cardiovascular Disease

Psoriasis is intricately related to cardiometabolic disease, and patients with psoriasis face an elevated risk of various cardiovascular diseases (CVDs), including stroke, myocardial infarction (MI), heart failure, atrial fibrillation, and vascular disorders.10,12 The risk of mortality from CVD is higher in psoriatic patients compared to non-psoriatic patients, possibly due to delayed diagnosis and under-recognition of psoriasis as a significant CVD risk factor.1 Psoriasis is recognized as a contributing risk factor, amplifying cardiovascular hazard by 1.5 times.12 Specifically, the risk of CVD is increased by over twofold in patients with psoriasis, independently of other risk factors, particularly in severe forms and in patients under 50 years of age.9

Patients with psoriasis have an increased prevalence of CVD risk factors, including hypertension, diabetes mellitus, dyslipidemia, and obesity.1-6 High-sensitivity C-reactive protein (hsCRP) levels may indicate “residual inflammation” even when skin symptoms are well-controlled by treatment, suggesting a persistent underlying inflammatory component that carries cardiovascular risk.15 Signs of dyslipidemia, such as xanthomas, may also be present.9

“Although we often think that psoriatic arthritis is the most common psoriasis comorbidity, cardiometabolic disease is actually by far the most common comorbidity our patients face,” says Joel M. Gelfand, MD, MSCE, FAAD, the James J. Leyden Professor of Clinical Investigation and Professor of Dermatology and Epidemiology (with tenure) at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, PA. “About 60% of patients seen for psoriasis in routine dermatology practice will have obesity, insulin resistance, dyslipidemia, hypertension, and/or atherosclerotic disease.”

The core reason for this strong association is the systemic inflammatory nature of psoriasis. The “psoriatic march” concept explains this pathogenic link: chronic systemic inflammation in psoriasis can lead to insulin resistance, endothelial dysfunction, and accelerated atherosclerosis.1 Key pro-inflammatory cytokines such as TNF-α, IL-17, and IL-23, which drive psoriasis activity, also contribute to the inflammatory cascade that promotes cardiovascular events.6,10-13 Additionally, visceral adiposity, common in psoriasis patients, produces adipokines and chemokines that stimulate atherosclerosis.15,17

CVD Management

Controlling systemic inflammation with anti-psoriatic drugs can alleviate CVD risk.4-5,9,12 Lifestyle modifications are paramount.6-9,15 A balanced, low-calorie diet is recommended for all psoriasis patients.4,7,8 Regular exercise is crucial, with moderate- to high-intensity physical activity serving as an independent protective factor that can improve disease course, especially in overweight patients.4,6,7,9,15 Smoking cessation is advised, as smoking can increase psoriasis severity and reduce treatment effectiveness.2,6-9,15 Alcohol moderation is important, as frequent use can negatively impact disease severity, increase pro-inflammatory cytokines, and reduce treatment adherence and efficiency.7-9,15

Regular screening for CVD risk factors is important, but inadequate screening and undertreatment have been reported.5 Dermatology clinicians should collaborate with cardiologists to manage these patients comprehensively.18 Biologic therapies, including anti-TNF-α, anti-IL-17, and anti-IL-23 agents, have been associated with a decreased risk of CVD events and improvements in coronary inflammation and plaque characteristics.12 Apremilast has also shown small beneficial cardiometabolic effects.5,9

Obesity

Obesity has emerged as a major driver of psoriasis morbidity. It is a recognized risk factor for developing psoriasis and psoriatic arthritis. The average body mass index (BMI) of psoriasis patients seen by dermatologists in the United States is 30 kg/m2, which meets the criteria for obesity according to the National Institute of Health (NIH).10,19 Epidemiological studies show that high abdominal adiposity doubles the risk of psoriasis, and a BMI over 35 kg/m2 is associated with an even higher risk.1,4

Obesity is also linked to more severe skin involvement. Specifically, increasing body surface area affected by psoriasis is directly related to increasing BMI.10 For every one-unit increase in BMI, the risk of severe psoriasis (defined by PASI ≥ 10, body surface area [BSA] ≥ 10%, and Dermatology Life Quality Index [DLQI] ≥ 10) can increase by 3% to 6%.17

Furthermore, obesity is associated with a reduced response to psoriasis treatments, including biologics, and can lead to a loss of response to biologics over time.6,10,18 A proper response to biologic treatment with fixed doses is less frequently observed in patients with higher body weight, especially those over 100 kg.7

The relationship between obesity and psoriasis is bidirectional. Excess adipose tissue, particularly visceral fat, is metabolically active and aggravates psoriasis by producing various pro-inflammatory adipokines (e.g., leptin, resistin, IL-6, TNF-α) and promoting insulin resistance.4,6,10 Conversely, psoriatic skin inflammation can contribute to obesity through mechanisms like promoting insulin resistance and the adipogenic effect of IL-17, a key cytokine in psoriasis. Chronic inflammation in psoriasis can also lead to visceral fat deposition and, in severe forms, limit mobilization, further increasing the risk of developing obesity.9

Obesity Management

Addressing obesity is crucial in the context of treating patients with psoriatic disease. Weight loss is consistently shown to improve psoriasis severity in both untreated and treated patient populations.6,18 This can also lead to improvements in metabolic syndrome, reducing cardiovascular and cerebrovascular morbidity and mortality, and enhancing response to anti-psoriatic medications.4

Dr. Lockshin emphasizes the importance of initiating these conversations: “Obesity probably is the number one comorbidity that I see associated with psoriasis patients. I think it is my job to at least prime the engine to initiate this conversation.”

Several dietary approaches—including low-calorie, Mediterranean, ketogenic, and intermittent fasting regimens—can improve psoriasis severity, reduce systemic inflammation by modulating pro-inflammatory cytokines, and address common comorbidities like obesity and metabolic syndrome, especially when combined with standard treatment. These diets also offer metabolic and cardiovascular benefits, enhancing overall quality of life.4,7-9,13,17

Recent research also indicates that high intake of ultra-processed foods is associated with active psoriasis, even after accounting for BMI and other comorbidities. This suggests that dietary patterns high in processed foods may contribute to disease activity through pro-inflammatory mechanisms, underscoring the importance of diet quality in addition to weight reduction.20

Regular physical exercise is also recommended as it serves as an independent protective factor, can improve the course of the disease in overweight patients, and is a beneficial adjunct to psoriasis treatment.6,7 For severe obesity, bariatric surgery has demonstrated significant improvement in psoriasis severity, reducing the risk of new-onset psoriasis, progression to severe psoriasis, and development of psoriatic arthritis.17-18

When choosing pharmacological therapies, it’s important to note that TNF-α inhibitors may have lower efficiency in overweight patients and can even lead to weight gain. In contrast, IL-17 inhibitors, IL-23 inhibitors, and small molecules like apremilast are often preferred in overweight patients due to their potential benefits on dyslipidemia, insulin resistance, and weight loss.2,9,10

Diabetes and Metabolic Syndrome

Patients with psoriasis are at increased risk for the development of diabetes and metabolic syndrome. Metabolic syndrome, a cluster of conditions including obesity, insulin resistance, dyslipidemia, and hypertension, affects approximately one-third of individuals with psoriasis and has a high prevalence of around 50% in patients with moderate-to-severe psoriasis.1-2,6,9 The risk of developing metabolic syndrome or its individual components is at least twofold higher in psoriasis patients compared to their counterparts without psoriasis. This risk also increases with older age and the severity of psoriasis. Notably, individuals who develop psoriasis at a younger age have a significantly increased risk of developing type 2 diabetes. Patients with severe psoriasis are also more likely to develop micro- and macrovascular complications related to diabetes.6

Psoriasis and type 2 diabetes share common risk factors and a probable pathophysiological link rooted in chronic inflammation and metabolic dysregulation. Pro-inflammatory cytokines like TNF-α are implicated in the pathogenesis of insulin resistance.4,6,9 The upregulation of the IL-23/Th17 axis has also been linked to cardiometabolic comorbidities in psoriasis.6,9,12 Inflammatory cytokines, such as IL-6 and TNF-α, are associated with insulin resistance and the onset of type 2 diabetes.6,11 Adipocytokines, obesity, and behavioral characteristics like smoking also play key roles in this association.1,4,6-9

Diabetes Management

Lifestyle modifications, including a balanced diet and regular exercise, are the cornerstone of management.6-7,9,18 Pharmacological interventions, such as antidiabetic, lipid-lowering, and antihypertensive medications, may be integrated into the treatment plan. Metformin, a biguanide hypoglycemic drug, is a first-line treatment for type 2 diabetes and has been reported to support good control of psoriasis with long-term use.6,18 Regular screening for diabetes is crucial for early identification and timely intervention.6 Careful consideration of potential drug interactions or exacerbation of metabolic disturbances by certain anti-psoriatic treatments is also necessary.6,9,18 Effective treatment of psoriasis, particularly with biologic agents, appears to reduce the risk of metabolic syndrome.2,4,6,9,12

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide (Ozempic/Wegovy, Novo Nordisk), tirzepatide (Mounjaro/Zepbound, Eli Lilly & Co.) and liraglutide are increasingly recognized for their potential dual benefit in patients with psoriasis and type 2 diabetes. In addition to improving glycemic control and promoting weight loss, GLP1RAs may also reduce systemic inflammation and influence immune cell pathways implicated in psoriasis, such as γδ T cells and iNKT cells.21-23 Clinical studies have shown improvements in psoriasis severity (PASI scores) with GLP-1RA use in patients with type 2 diabetes, suggesting these agents may be a valuable adjunct in managing both metabolic and dermatologic aspects of disease.24 However, their effectiveness in patients without diabetes remains unclear, and further research is warranted.25

Fatty Liver Disease (NAFLD/MASLD)

Psoriasis patients are particularly susceptible to non-alcoholic steatohepatitis (NASH) and exhibit a notably higher prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), compared to the general population.1-2,4,6,10 Patients with psoriasis often develop more severe forms of NAFLD, and conversely, NAFLD patients tend to have more severe psoriasis.6

NAFLD can range from hepatic steatosis (favorable prognosis) to NASH, which carries a risk of progression to fibrosis, cirrhosis, and hepatocellular carcinoma. While abnormal liver enzyme levels may not always be present, ultrasound imaging is recommended to detect NAFLD, even with normal transaminase levels. Severe forms of NAFLD are more commonly associated with exacerbated systemic/hepatic insulin resistance and atherogenic dyslipidemia.6

The primary pathogenic links between psoriasis and NAFLD are chronic inflammation and peripheral insulin resistance.1,6,9 Proinflammatory, procoagulant, and profibrogenic mediators released in NAFLD negatively affect the severity of psoriasis by increasing keratinocyte proliferation and maintaining inflammation.6 IL-17 is also implicated in the pathogenesis of both psoriasis and NAFLD.1,9

Fatty Liver Disease Management

Early identification and continuous monitoring of liver function are essential. Dermatologists should be aware of the high prevalence of NAFLD in severe psoriasis and consider the potential presence of steatohepatitis. Potentially hepatotoxic drugs, such as methotrexate and acitretin, should be administered with extreme caution or avoided if NAFLD is suspected, requiring rigorous monitoring of hepatic transaminase levels.6,9 Cyclosporine, a lipophilic drug, can exacerbate nephrotoxicity in overweight or obese patients due to elevated serum levels.18 Non-invasive tests like Fibrotest and Fibroscan can be used to detect liver fibrosis.6 Biological therapies, particularly TNF-α inhibitors, are often a better solution as they can decrease the risk of hepatic fibrosis and reduce inflammation and dyslipidemia.9 Dietary measures are also important.6,9

Inflammatory Bowel Disease (IBD)

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease, are recognized comorbidities of psoriasis.2,4-5,9,13 Multiple meta-analyses have revealed significant bidirectional associations between psoriasis and IBDs. Specifically, psoriasis patients have an increased risk of Crohn’s disease (relative risk [RR] = 2.53) and UC (RR = 1.71).2,13 Psoriasis patients may report a higher prevalence of gastrointestinal symptoms such as feeling full/bloated, belly pain, diarrhea, and the presence of mucus or blood in stool, along with unintentional weight loss. Sex and PsA are identified as particular risk factors for IBD in psoriasis patients. Psoriasis patients with UC may have a higher BMI and milder skin symptoms, while those with Crohn’s disease might present with mild (early-onset) psoriasis but a more severe Crohn’s disease phenotype.2,13

The association between psoriasis and IBD is thought to stem from shared immune-mediated inflammatory mechanisms, particularly involving the IL-23/Th17 axis and pro-inflammatory cytokines like TNF-α, IL-17, and IL-23.1,26 Genetic overlap, including polymorphisms in IL23R and TNFAIP3, further supports a common pathophysiological foundation.2,13,26 Melissa Davis, PA-C, a Dermatology Physician Assistant at Associates in Dermatology in Louisville, KY, emphasizes the importance of recognizing this overlap in daily practice: “We often see overlap of autoinflammatory conditions such as IBD, psoriasis, and also HS. I frequently see patients with overlap of these diseases, and they are often unaware that there is a connection. The most important thing is to take a thorough history and provide patient education, so we are connecting the dots for them that these conditions are related.”

IBD Management

The presence of IBD significantly influences the management strategy for psoriasis.5,9,12,17 Young patients and those with severe psoriasis may require comprehensive, integrated management.2,5 Biologic agents like infliximab and adalimumab have demonstrated efficacy in treating both psoriasis and IBD (UC and Crohn’s disease), making them suitable choices for patients with both conditions.2,5 IL-23 inhibitors, such as ustekinumab and risankizumab (Skyrizi, AbbVie), have also demonstrated efficacy in both psoriasis and IBD, offering an additional therapeutic option for patients with overlapping conditions.27-28

Davis notes that therapeutic decision-making has become easier with newer options: “Choosing therapies for our patients with concomitant IBD and psoriasis has gotten much easier over time with the approval of risankizumab and guselkumab for IBD. These IL-23 inhibitors are highly efficacious, provide higher levels of skin clearance and joint protection, and have robust safety compared with older options. We typically avoid IL-17 inhibitors in patients with psoriatic disease who also have a history or family history of IBD.”

Mental Health Conditions

Psoriasis is strongly associated with a higher prevalence of mental health disorders, including depression, anxiety, and suicidal ideation and behavior. The risk of suicidal ideation and behavior is notably increased in psoriasis patients compared to the general population.4,9-11,29

Psoriasis patients may experience a range of psychological symptoms including anxiety, depression, obsessive-compulsive disorders, schizophrenia, and even dementia.5,7,10-11 Joint inflammations and skin symptoms can exacerbate anxiety and depression and profoundly affect quality of life. Poor sleep is also a common complaint.2,4-5,11

The “why” behind this link is multifaceted. The visible nature of psoriatic skin lesions often leads to stigmatization, significantly impacting patients’ quality of life and increasing the risk of anxiety and depressive disorders.7,9-11,29 Beyond psychosocial factors, a common underlying pathogenesis involving chronic inflammation, particularly neuroinflammation, is increasingly recognized for both psoriasis and depression.7,10-11,30 The neuro-immuno-endocrine-cutaneous axis plays a role, and inflammatory cytokines like IL-6, IL-17, and TNF-α have been linked to depression.10-11,30 There is also evidence for shared genetic backgrounds and common risk factors such as obesity and nicotinism.4,6,10-12,18

Management of Mental Health Conditions

A holistic approach, which includes psychological and psychotherapeutic support, and potentially psychiatric treatment, is highly recommended.7 It is crucial to observe psoriatic patients for mental health disorders regardless of skin lesion severity, as these conditions can be effectively managed.7,11 Targeted immunomodulators, particularly IL-17 and IL-23 inhibitors, may have direct effects on depressive symptoms.30 While some antidepressants, notably Selective Serotonin Reuptake Inhibitors (SSRIs), may have immunomodulatory effects that could explain their effectiveness in psoriasis and even protective effects on disease onset or course, lithium is explicitly regarded as having a negative impact on psoriasis.11 Increased awareness among both physicians and patients regarding the association between psoriasis and mental health is crucial.2,11

Other Autoimmune Diseases

The systemic inflammatory nature of psoriasis often predisposes patients to other autoimmune conditions:

  • Autoimmune Thyroid Disease: Psoriasis has been associated with an increased risk for various autoimmune thyroid diseases, including Hashimoto’s thyroiditis, hyperthyroidism, and hypothyroidism. Patients with thyroid dysfunction tend to have higher PASI scores and elevated C-reactive protein levels.2
  • Celiac Disease: A bidirectional association between celiac disease and psoriasis has been reported.2,17
  • Vitiligo: There is a bidirectional association between psoriasis and vitiligo, with increased odds for vitiligo in psoriatic patients and vice versa.2,13
  • Bullous Pemphigoid: Psoriasis is independently associated with an increased risk of bullous pemphigoid, a blistering skin condition, particularly in younger patients. Over one-third of bullous pemphigoid cases in psoriatic patients were diagnosed within the first year after incident psoriasis.1-2

Management of Other Autoimmune Diseases

While specific management guidelines for these comorbidities in the context of psoriasis will vary based on the patient and the associated condition, the overarching principle remains early identification, continuous monitoring, and an integrated, interdisciplinary approach. Dermatology clinicians are encouraged to identify comorbidities early to ensure timely treatment and prevention.6 This involves regular screening, collaboration among various medical fields, and close follow-up for associated conditions. Recognizing these associations allows for more comprehensive patient care and appropriate referrals to specialists when necessary. This holistic perspective is crucial for improving patient outcomes and overall quality of life.4,6-7,9

The Role of Early Biologic Intervention in Reducing Comorbidity Risk

Psoriasis is a systemic inflammatory disease, and therapies that effectively control this inflammation are central to managing both the skin disease and its associated comorbidities. Biologic agents, by targeting key inflammatory cytokines such as TNF-α, IL-17, and IL-23, offer enhanced efficacy against psoriasis and show promise in mitigating comorbidity risk.2,5,9,12-13

“The best evidence to date is the reduction of cardiovascular metrics with TNF-α inhibitors and IL-17 inhibitors,” notes Kirk Gautier, PA-C, a Dermatology Provider at US Dermatology Partners in Tyler, TX. “There is some early evidence that IL-23 inhibitors will delay the arthritic component compared to TNF-α inhibitors. These data are exciting as potential preventative measures to deal with comorbidities for our psoriatic patients.”

Evidence suggests that controlling psoriasis inflammation with conventional systemic anti-psoriatic drugs can alleviate CVD risk.4,12 Furthermore, biologic treatment for psoriasis is linked to a greater mitigation in CVD risk.1,5,9,12 Anti-TNF-α, anti-IL-17, and anti-IL-23 biologics are associated with decreased cardiovascular hazards, demonstrating improvements in coronary inflammation and a reduction in non-calcified plaque burden. This risk reduction has been observed across diverse demographics and comorbidities.4,12

Echoing these findings, Dr. Lockshin emphasizes, “Patients with moderate-to-severe psoriasis and psoriatic arthritis have a higher rate of heart attack, stroke, and premature death. Life expectancy is five to six years shorter with untreated disease, and I believe that early intervention can change that course.”

For metabolic syndrome, effective treatment of psoriasis, particularly with biologic agents, appears to reduce the risk.2,4,6,9 Specifically, IL-17 inhibitors, IL-23 inhibitors, and small molecules like apremilast are beneficial in overweight patients by improving dyslipidemia, insulin resistance, and promoting weight loss.5,9,12 TNF-α inhibitors have also been shown to reduce the risk of hepatic fibrosis in patients with NAFLD.9

In the realm of mental health, biologics, especially IL-17 and IL-23 inhibitors, may have direct positive effects on depressive symptoms, improving anxiety, depression, and overall quality of life.11,29-30

Weight reduction through bariatric surgery, a significant intervention, provides crucial support for the idea that targeted BMI reduction can modify disease risk across multiple domains of psoriatic disease, strengthening the evidence for a causal relationship between obesity and psoriatic disease development and progression. This suggests that aggressive management of obesity can lead to reduced risk of new-onset psoriasis, progression to severe psoriasis, and development of psoriatic arthritis.6,10,12,17-18

While some meta-analyses of randomized controlled trials initially showed no difference or even an increased risk of CVDs with biologic treatment, real-world cohort studies suggest a neutral or protective association.12 The strong association between increasing BMI and the development and severity of psoriasis, confirmed by both genetic and clinical analyses, highlights the urgent need for effective obesity management as an integral component of psoriasis treatment.2,4,7,9-10,12,1

Conclusion

Psoriasis is unequivocally a systemic inflammatory disease with a profound impact extending far beyond the skin. The high prevalence and complex interplay of associated comorbidities, including psoriatic arthritis, cardiovascular disease, obesity, diabetes, fatty liver disease, inflammatory bowel disease, and mental health conditions, underscore the critical need for a comprehensive and patient-centric approach to care. These comorbidities not only worsen the disease prognosis and significantly impair quality of life but also increase mortality, particularly due to cardiovascular events.

This reality is echoed by Dr. Gelfand, who states, “We are often the only healthcare professional the patient sees, and frequently their primary clinician may not be aware of the serious nature of psoriatic disease, which results in a reduction of life expectancy.”

As such, dermatology clinicians play a pivotal role in initiating comorbidity screening, educating patients, and coordinating interdisciplinary care.

Given their front-line position, dermatology clinicians are uniquely positioned to identify and manage associated comorbidities early. This includes routine screening, promoting lifestyle changes (such as healthy eating, physical activity, and smoking cessation), and making pharmacologic choices that consider a patient’s broader health profile.

Emerging evidence suggests that early, aggressive treatment of psoriasis—particularly with biologics targeting key inflammatory pathways—can significantly reduce the risk and burden of associated comorbidities. By controlling systemic inflammation, these therapies not only improve skin and joint symptoms but also benefit cardiometabolic health and mental well-being. This growing recognition supports a multidisciplinary approach to care, involving dermatologists, cardiologists, endocrinologists, gastroenterologists, mental health professionals, and nutritionists. Continued long-term studies are essential to deepen our understanding of these complex interconnections and to refine treatment strategies that improve patient outcomes.

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