Considering Comorbidities of Psoriasis as a Basis for Therapeutic Selections

When we think of psoriasis, we often visualize the external manifestations of disease that we can see, such as erythema (redness), induration (thickness), and desquamation (scaling); however, psoriasis is more than cosmetic disfigurement or skin disease. It is a chronic, relapsing, immune deregulatory inflammatory skin and joint disease that has been shown to significantly impact patient quality of life comparable to, if not more than, most other systemic diseases. The large body of literature examining patients with psoriatic disease concludes that comorbid conditions like psoriatic arthritis, irritable bowel, psychological and psychiatric disorders, metabolic syndrome, cardiovascular disease, and lymphomas, are common.[1] As the list of comorbidities continues to expand, Brad P. Glick, DO, MPH, FAAD, who delivered the first educational session of SDPA Annual Summer Conference 2021, asks attendees an obvious question: Why is it so important to know and understand these established and emerging comorbid conditions associated with psoriatic disease? His answer was straightforward.

“These background comorbidities are crucial in terms of their assessment as it relates to your therapeutic selection,” he said.

SPECIAL COVERAGE: SDPA Annual Summer Conference 2021, Chicago, July 22-25, 2021

Dr. Glick explained that psoriasis is a systemic disease caused by a complex interplay of genes, environment, and immune system. The genetic components are particularly important because genetic receptors for psoriasis discovered over the years specifically relate to some of the cytokines that are targets for therapeutic interventions. Many of these patients have a complicated health profile and are often on several medications—all of which need to be considered by the dermatology care provider. The goal is to select psoriasis treatments that maximize benefit and minimize risk.

Established Comorbidities of Psoriasis

Psoriatic Arthritis. When evaluating cutaneous psoriasis location and severity, clinicians should conduct screening for known comorbid conditions, especially psoriatic arthritis. Psoriatic arthritis is a common and established comorbidity which affects between 6% and 42% of patients with psoriasis. The following facts about psoriatic arthritis further illustrate the need to screen:

• Psoriatic arthritis incidence increases with disease severity and duration
• Earlier onset of psoriatic arthritis in patients with psoriasis is associated with worse prognosis
• Psoriasis precedes arthritis in 75% of cases

“I can’t emphasize enough the importance of background psoriatic arthritis [in patients with psoriasis],” Glick said. “And it is my recommendation to screen for this comorbidity at each visit.”

Dr. Glick’s recommendation aligns with the latest guidelines from the American Academy of Dermatology and National Psoriasis Foundation on care for the management and treatment of psoriasis with awareness and attention to comorbidities.[2] These guidelines state that screening patients with psoriasis for psoriatic arthritis is essential and should be considered at each visit. Clinicians are encouraged to fully evaluate patients with signs/symptoms of psoriatic arthritis using screening tools, such as the Psoriasis Epidemiology Screening Tool (PEST). One such resource Dr. Glick showed is a one-page PDF handout from the National Psoriasis Foundation (available at https://www.psoriasis.org/psoriatic-arthritis-screening-tool-for-providers/) that includes a five-question quiz and body location diagram.

In patients with psoriasis and psoriatic arthritis, clinicians might consider agents that halt progression or radiologic damage. Care for this patient population often also includes consults with rheumatology specialists.

Obesity/Metabolic Syndrome. Dr. Glick presented the evidence linking psoriasis to another inflammatory conditions—metabolic syndrome. Metabolic syndrome occurs when three of the following five criteria are met: abdominal obesity, insulin resistance, hypertriglyceridemia, decreased HDL cholesterol. Obesity doubles an individual’s risk of developing psoriasis. Also, body mass index correlates to disease severity. Dr. Glick stated that, according to research, therapies with weight-based dosing might have better outcomes in this patient population. Weight-based treatments to consider in patients with obesity/metabolic syndrome and psoriasis include ustekinumab, infliximab, adalimumab, secukinumab, and apremilast.[3]

Cardiovascular Disease. Numerous studies have confirmed an association between psoriasis and cardiovascular disease. Dr. Glick pointed to eight meta-analyses covering seven to 33 studies involving more than 500,000 patients with psoriasis and more than 29 million control patients. These data conclude that an estimated 11,500 extra major adverse cardiovascular events are attributable to psoriasis in the United States per year.[4] Further, research finds that patients with severe psoriatic disease have higher rates of atherosclerotic outcomes.[5] When selecting therapeutic interventions for patients with psoriasis and cardiovascular disease, care providers should consider treatments that reduce cardiovascular risks like methotrexate and tumor necrosis factor (TNF)-alpha inhibitors.

Quality of Life & Psychological Burden. Another take-home message from Dr. Glick’s presentation was that psoriatic disease carries a significant impact on patients’ quality of life. Patients with psoriasis report that their disease has a negative impact on nearly all areas of life. For instance, many patients report that psoriasis contributes to decreased self-confidence and increased feelings of depression. Psoriasis patients also report that they feel the need to hide their disease and avoid activities like sports. Psoriasis is even a consideration in career choice. Perhaps the most eye-opening statement on the impact this disease has on mental health is that nearly half of psoriasis patients would prefer to have another serious medical condition (e.g., hypertension, asthma) in place of psoriasis. Recommendations on mental health in patients with psoriasis from the AAD/NPF guidelines are to 1) inform patients about psoriasis/anxiety and depression and 2) screen patients for signs symptoms and refer patients to mental health provider. The good news is that studies demonstrate a concurrent improvement in psychiatric symptoms when patients experience treatment and disease control. When selecting a treatment plan for this patient population, recent evidence shows that TNF-alpha inhibitors have a significant improvement in depression and anxiety scores.

After a comprehensive review of established comorbidities of psoriasis, Dr. Glick asked attendees a final question: Does treatment of psoriasis affect comorbidities? He presented the answer with robust evidence for each comorbid condition. Although some research was presented on IL-17’s proatherogenic and atheroprotective effects, TNF-alpha inhibitors appeared to steal the show in almost every category.

• TNF inhibitors prevent structural damage in psoriatic arthritis
• TNF inhibitors are associated with significant reduction in myocardial infarction risk compared to treatment with topicals
• Reduction in cardiovascular events may be greater with TNF inhibitors than with methotrexate when TNF inhibitors are used for treating psoriatic skin disease
• Longer duration of TNF inhibition leads to greater cardiovascular risk reduction
• Studies on TNF inhibitors etanercept and adalimumab found significant improvement in depression and anxiety

In summary, effective treatment of psoriasis has been shown to benefit various known and emerging comorbidities. Biologic agents offer targeted efficacy with favorable safety profiles and may potentially impact the overall health of patients with psoriatic disease. In addition to building their own knowledge by keeping up with the latest and greatest in psoriasis, healthcare providers should be prepared to talk to patients about comorbidities, listening to each circumstance. Even an extra five minutes can make a big difference in a patient’s experience and may potentially impact the overall health of patients with psoriatic disease.

References

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[1] Oliveira MF et al. Psoriasis: classical and emerging comorbidities. Ann Bras Dermatol. 2015;90(1):9-20.

[2] Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019; 80(4):1073-1113 DOI: 10.1016/j.jaad.2018.11.058

[3] Hamminga EA, van der Lely AJ, Neumann HA, Thio HB. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses. 2006;67(4):768-773. DOI:10.1016/j.mehy.2005.11.050

[4] Armstrong EJ, Harskamp CT, Armstrong AW. Psoriasis and major adverse cardiovascular events: a systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013;2(2):e000062. Published 2013 Apr 4. doi:10.1161/JAHA.113.000062

[5] Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol. 2013;149(10):1173-1179. doi:10.1001/jamadermatol.2013.5015

Byline: Angela Saba, Managing Editor, Journal of Dermatology for Physician Assistants

Pictured: Brad P. Glick, DO, MPH, FAAD, Director of the Dermatology Residency, Larkin Hospital, Palm Springs, Florida; Clinical Assistant Professor of Dermatology, Herbert Wertheim College of Medicine Miami, Florida; Director and Principal Investigator, GSI Clinical Research, Margate, Florida; and President, Florida Society for Dermatology and Dermatologic Surgery.

This post is based on the following presentation during SDPA Summer 2021:
Psoriasis Update 2021: A Focus on Comorbidities.