Psoriasis mechanism of disease: Genetic, environmental, and lifestyle factors
Featuring George Han, MD, PhD |

Chief of Teledermatology 
System Medical Director for Dermatology
Icahn School of Medicine at Mount Sinai
New York, NY

, Andrew Blauvelt, MD, MBA |

Investigator
Oregon Medical Research Center
Portland, OR

| Published September 13, 2023
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In this installment of Discourses in Dermatology, Dr. George Han, Director of Clinical Research at Northwell Health in New York, sits down with Dr. Andrew Blauvelt, Investigator at Oregon Medical Research Center, to discuss the genetic, environmental, and lifestyle factors that influence psoriasis. They also explore the comorbidities associated with psoriasis and how they play into the role of psoriatic disease.

The role of genetics in psoriasis

Dr. Han begins by asking Dr. Blauvelt what role genetics really plays in the development of psoriasis.

Dr. Blauvelt references the first genetic study published on psoriasis, spearheaded by Danish researchers in the Faroe Islands in 1963, which found evidence of a genetic component to psoriasis in the local island population.  

He also comments on a key study examining identical twins that revealed strong evidence in favor of a genetic component to psoriasis.

Dr. Blauvelt notes that while there is a genetic component to psoriasis, it’s not a Mendelian disease. Rather, there are 70 to 80 susceptibility genes that have been identified that either confer a risk for psoriasis or confer some protection.

With those factors considered, he explains to his patients that while there is indeed a significant genetic component, it does not account for the entire picture of psoriasis. He estimates that approximately 40% of patients have a family history of the condition but suggests that even those without a family history may still have a genetic predisposition due to a combination of genes inherited from their parents. 

To summarize, he reiterates that psoriasis is a complex condition with a genetic component with other factors also involved in its development.

Key points

  • A seminal study demonstrating the genetics of psoriasis was conducted by Danish researchers on the Faroe Islands in 1963
  • Twin studies have also revealed strong evidence in favor of a genetic component to psoriasis
  • Psoriasis is not a Mendelian disease, but is influenced by 70 to 80 susceptibility genes
  • While there is a significant genetic component to psoriasis, it does not account for the entire picture

Environmental influences on psoriasis

Dr. Han continues the conversation by asking Dr. Blauvelt about the environmental influences on psoriasis that may encourage psoriasis in susceptible individuals.

Dr. Blauvelt replies by giving more background on the genetics of psoriasis, explaining that there are 2 types of psoriasis as it relates to genetics. The first type is a result of genes that tend to run in families, with HLA-Cw6 being the most common. With this type, there is usually an earlier onset in the late teens or early 20s. 

The second type tends to manifest in the early 40s, and those patients tend not to have a family history of the condition. Rather, this type of psoriasis tends to be more associated with metabolic syndrome, diabetes, or hypertension.

Dr. Blauvelt then begins delving into some of the well-known influences on psoriasis, including stress, infections like strep throat, and certain medications. He specifically mentions lithium and interferon stimulators, remarking that Aldara cream can stimulate psoriasis locally.

He comments that the most common influences on psoriasis he has seen in his career have been strep throat, stress, and cold weather. He advises patients that any kind of stressor on the body, whether emotional or physical stress from temperature, medication, or infection, can trigger the psoriasis immune response.

Key points

  • Influences on psoriasis can include stress, infections, and certain medications
  • Lithium and interferon stimulators can affect psoriasis
  • Cold weather can also trigger the psoriasis immune response

Comorbidities of psoriasis

Dr. Blauvelt comments that the list of comorbidities associated with psoriasis has become quite long and can be overwhelming for healthcare providers who are unsure how to counsel patients on this topic.

He describes his approach to speaking with patients and how he always discusses the 2 most important psoriasis comorbidities, psoriatic arthritis and heart disease, at their first visit. When discussing psoriatic arthritis, he explains that it is the most common comorbidity and will affect treatment choice, and that is an important facet for patients to consider and understand. In his experience, some patients with psoriasis are unaware that they are at risk for arthritis and thus it should be discussed early on.

Dr. Blauvelt also makes sure to discuss heart disease with his patients and emphasize the seriousness of it. He references the literature that is now available on psoriasis as an independent risk factor for heart disease and says it also suggests that the risk of heart disease can be reduced if an impact can be made on the skin.

He mentions large databases that suggest TNF blockers may reduce the risk of cardiovascular events but that we don’t yet have that same kind of data for IL-17s and IL-23s. He also references studies conducted at the NIH that put patients on biologics for one year and measured their atherosclerotic plaques. Those studies demonstrated that IL-17 blockers were the best class of drugs in terms of improving atherosclerosis in patients with psoriasis. While they don’t prevent heart attack and stroke, it’s strong evidence that these therapies are having positive outcomes.

Key points

  • The long list of comorbidities associated with psoriasis can make it overwhelming to counsel patients
  • The 2 most important comorbidities to discuss with patients are psoriatic arthritis and heart disease
  • Psoriatic arthritis should be discussed with patients at their first visit, since it’s the most common comorbidity and can affect treatment choice
  • Literature suggests that psoriasis is an independent risk factor for heart disease and that the risk of heart disease can be reduced if an impact can be made on the skin
  • Large databases suggest TNF blockers may reduce risk of cardiovascular events
  • NIH studies demonstrated that IL-17 blockers were the best class of drugs in improving atherosclerosis in patients with psoriasis

Mental health as a comorbidity of psoriasis

Dr. Han continues the conversation by asking Dr. Blauvelt his thoughts on mental health and psoriasis and how he approaches this discussion with patients.

Dr. Blauvelt references his involvement in one of the first multidisciplinary clinics for psoriasis in the United States that included dermatology, rheumatology, and psychiatry. When he asked patients about their mental health, they often reported they were depressed and anxious due to the condition. He found many were hesitant to be referred to the psychiatry clinic because they felt that if their psoriasis cleared, their mental health would improve, which demonstrates there is a component to the condition that can cause angst and depression.

He remarks that practitioners can assume quality of life is impaired for patients with psoriasis and that patients are likely to score poorly on quality-of-life measures and depression scales. He emphasizes that this should not be ignored and that it’s important to listen to patients and monitor for signs of severe depression and suicidal ideation. 

Dr. Han concludes by agreeing on the importance of listening and caring for the whole patient.

Key points

  • There is a component to psoriasis that can cause angst and depression among patients with the condition
  • Patients with psoriasis will often have impaired quality of life and score poorly on quality-of-life measures and depression scales
  • It’s vital to listen to patients and monitor them for signs of severe depression and suicidal ideation
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