Multiple studies have shown an association between psoriasis and various comorbid conditions, ranging from cardiovascular disease and metabolic syndrome to depression. In an interview with The Dermatologist, Ronald Prussick, MD, the latest research on these comorbidities, evidence on lifestyle and treatment options that could potentially prevent or manage both psoriasis and comorbid conditions, and the importance of screening and aggressively treating psoriatic arthritis.
Dr Prussick is the medical director of the Washington Dermatology Center in Rockville, Maryland, and assistant clinical professor at George Washington University in Washington, DC.
The Dermatologist: Has there been any new development on the association between psoriasis and comorbidities? And, on the impact of lifestyle interventions?
Dr Prussick: In 2018, Noe et al1 published results in the Journal of Investigative Dermatology from the iHOPE study, which used data from the United Kingdom General Practice database to compare body surface area (BSA) and mortality rates, adjusting for age, sex, and comorbidities. They found that patients with a BSA greater than 10% of psoriasis had a 79% increased risk of mortality.1 The bottom line from this study is to lower BSA below 10% for all patients with psoriasis. With regard to reducing mortality, the advantages of lowering BSA even lower than 10% is still unknown.
JAMA Dermatology published a meta-analysis last year that showed an increased risk of cancer mortality among patients with psoriasis. In the meta‑analysis, the authors found that people with severe psoriasis had significantly increased mortality in liver, esophageal, and pancreatic cancers.2
We’ve also learned a lot from the Nurses’ Health Study about the comorbidities of psoriasis and the risks of developing psoriasis. For example, nurses who have the largest body mass index (BMI) were found to have the highest risk of developing psoriasis over time.3 Family history, drinking alcohol (specifically greater than 5 regular beers per week), and smoking were also linked to a higher risk of developing psoriasis.4,5 An interesting aspect of this study was that nurses who performed a vigorous physical activity (such as running) for 105 minutes a week had a 25% to 30% lower risk of eventually developing psoriasis.6 People with a family history of psoriasis can adopt this lifestyle intervention to help reduce their risk of developing psoriasis.
A 2017 study in Europe that examined middle-age psoriasis development found that there was a significant correlation with weight gain, with a 70% increased risk of late-onset psoriasis for individuals who gained weight in middle age.7 Also, smokers have double the risk of late‑onset psoriasis compared with non-smokers.8 These are lifestyle factors that people need to be aware of, including weight gain and smoking, which can increase their risk of developing psoriasis in middle age.
Another meta-analysis, published in British Journal of Dermatology in 2019, found that weight loss in patients with psoriasis, either from diet and/or exercise, significantly reduced their psoriasis compared with controls.9 We know weight loss can improve psoriasis, so patients who are overweight or obese can try to improve their skin disease in this way. Also, there was a randomized controlled trial that showed that weight loss among patients with psoriasis can reduce psoriatic arthritis activity as well.10
In a paper published in Arthritis & Rheumatology in 2018, the researchers looked at the UK General Practice database over a 16‑year period to determine whether changes in BMI among patients with psoriasis would affect the eventual development of psoriatic arthritis. They found that, over a 10‑year period, increases in BMI affected the risk of developing psoriatic arthritis. For example, a patient whose BMI went from 25 kg/m2 to 30 kg/m2 over a 10-year period had a 13% increased chance of developing psoriatic arthritis. The opposite happens too. A patient with BMI of 30 kg/m2 who lost weight and later had a BMI of 25 kg/m2 had a 13% reduced risk of developing psoriatic arthritis. This shows that BMI does affect the risk of eventually developing psoriatic arthritis in patients with psoriasis.11
Lastly, nonalcoholic fatty liver disease (NAFLD) is prevalent in about 30% of the US population, but among patients with psoriasis, it is about 60%, translating to a doubled risk among patients with psoriasis. Studies have shown that diet and exercise can reduce the risk of fatty liver disease, especially progression from benign fat or steatosis to a severe form called nonalcoholic steatohepatitis (NASH). Following a low glycemic diet and lowering insulin levels can reduce the risk of fatty liver disease and progression to NASH. In addition, exercise can significantly reduce liver fat.12
The key message for patients is the need to reduce abdominal obesity. Central fat differs from fat elsewhere as it is metabolically active producing proinflammatory cytokines which can trigger psoriasis and psoriatic arthritis in those who are genetically susceptible.
The Dermatologist: What about the impact of various therapies on comorbidities in psoriasis?
Dr Prussick: We know that tumor necrosis factor (TNF)‑alpha inhibitors and IL‑17 blockers, are useful in treating psoriatic arthritis.
For depression, a study published in the Journal of the American Academy of Dermatology in 2018 that used data from the PSOLAR registry found that patients on biologic therapies had a significantly reduced risk of developing depression over time compared with conventional systemic pills and phototherapy.13
In 2013, the Journal of Gastroenterology published a study that investigated the effects of TNF inhibitors compared with phototherapy on non-alcoholic fatty liver disease (NAFLD) among patients with psoriasis. The researchers found that etanercept (Enbrel) was significantly more effective compared with phototherapy for reducing liver function tests, insulin levels, and insulin resistance over 6 months.14
TNF inhibitors are also useful for treating other autoimmune diseases. If a patient has comorbid Crohn disease, ulcerative colitis, ankylosing spondylitis, autoimmune uveitis, or psoriatic arthritis, we can use a TNF inhibitor to treat both their psoriasis and comorbid condition.
Those are all positive effects. In terms of negative effects, we know NAFLD is worsened by high lipid levels. We want to avoid using cyclosporine and acitretin in patients with NAFLD and those at risk for liver disease. Also, we want to avoid methotrexate in patients with NAFLD because it can have cumulative negative effects on the liver.
IL-17 inhibitors should be avoided in patients with Crohn disease or ulcerative colitis because they can cause disease flares or new onset disease in those genetically predisposed. Patients with psoriasis have a 2-fold increased risk for Crohn disease and a slightly lesser risk for ulcerative colitis so obtaining information on any family history of inflammatory bowel disease is important.15
Apremilast (Otezla) has a warning for depression, and brodalumab (Siliq) also has a warning for depression and suicidal thoughts. Before initiating either of these therapies, patients should be screened for depression and suicidal ideation.
For patients with recurrent infections, it is better to avoid biologics and use an oral small molecule, such as apremilast.
The Dermatologist: Psoriatic arthritis is a very common comorbid condition among patients with psoriasis. What are some of the important diagnostic and treatment considerations for patients with psoriatic arthritis?
Dr Prussick: I think the important thing for dermatologists to know about psoriatic arthritis is that all patients with psoriasis are at risk, not just severe patients. About 30% of patients with psoriasis eventually develop psoriatic arthritis, but rarely, some will develop the psoriatic arthritis first.
A paper published in 2012 in Dermatology that used data from the National Psoriasis Foundation database found that even patients with mild psoriasis had a 28% chance of developing psoriatic arthritis. Among patients with severe disease, the risk was 46%.16 This is an important point for dermatologists to remember. We need to ask everyone, even those with mild psoriasis, about the symptoms and signs of psoriatic arthritis.
I ask every patient: “Do you have any joint stiffness in the morning?” If a patient has morning joint stiffness that lasts more than 30 minutes, this is a sign that they may be developing psoriatic arthritis.
Also, I ask: “Have you ever had a swollen finger or toe? Do you experience back pain or stiffness? Have you had any pain in your elbows and feet, especially in your heel?” A lot of patients with psoriatic arthritis don’t necessarily have swollen joints, but they have tendinitis. It is important to ask about tendon pain, especially heel pain, in addition to joint pain because patients may not realize that this is connected to their skin disease.
The Dermatologist: The 2018 American College of Rheumatology/National Psoriasis Foundation guidelines for psoriatic arthritis recommended TNF therapy as first-line treatment.17 Could you elaborate on why it’s very important to start aggressive treatment as soon as a patient is diagnosed with psoriatic arthritis?
Dr Prussick: Studies have shown that delaying treatment by even 6 months can result in permanent, irreversible joint destruction.18 This is why it is important to ask patients about joint issues at every visit, regardless of their disease severity, to make sure we catch psoriatic arthritis early and start treatment.
The ACR/NPF Guidelines are the first to specify the use of TNF inhibitors as first-line or second-line, therapy (with some exceptions), as opposed to methotrexate, based upon both the efficacy of the therapy and long-term data that showed that this category of drugs can prevent joint destruction over time.
The Dermatologist: What key takeaways would you like to leave with dermatologists?
Dr Prussick: Psoriasis is a systemic inflammatory disease that affects much more than the joints and skin and is associated with considerable morbidity and mortality. Even patients with mild disease have an increased risk for various comorbidities compared with the general population. Of course, the comorbidity risk increases with worsening disease.
Patients need to be aware of these comorbidity risks and need to understand that there could be consequences of not treating their moderate to severe psoriasis in terms of increased risk for cardiovascular events or the development of other comorbid conditions. They also need to understand that being overweight, obese, and smoking will negatively impact their disease. Dermatologists and other health care providers need to counsel patients on the importance of lifestyle changes. We know, for example, that children, adolescents, and early adults have a higher risk for depression, anxiety, and other personality disorders if their psoriasis is not treated aggressively at an early age.
Talking about comorbidities can be frustrating for our patients because they already have a lot to deal with in regard to their skin disease and joint pain. The good news is that they can play a role in reducing their comorbidity risk with lifestyle changes, such as weight loss, exercise, and a high-quality diet (specifically anti‑inflammatory diets). Through lifestyle changes, patients can take control of their skin disease and comorbidity risks to some extent.
In the future, we need to identify which patients are most at risk for the various comorbidities associated with psoriasis, the levels of skin clearance needed to prevent each comorbid condition, and whether therapies that improve the skin are also effective for preventing or treating comorbid conditions.
1. Noe MH, Shin DB, Wan MT, Gelfand JM. Objective measures of psoriasis severity predict mortality: A prospective population-based cohort study. J Invest Dermatol. 2018;138(1):228-230. doi:10.1016/j.jid.2017.07.841
2. Trafford AM, Parisi R, Kontopantelis E, Griffiths CEM, Ashcroft DM. Association of psoriasis with the risk of developing or dying of cancer: A systematic review and meta-analysis. JAMA Dermatol. 2019;155(12):1390-1403. doi:10.1001/jamadermatol.2019.3056
3. Setty AR, Curhan G, Choi HK. Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses' Health Study II. Arch Intern Med. 2007;167(15):1670-1675. doi:10.1001/archinte.167.15.1670
4. Setty AR, Curhan G, Choi HK. Smoking and the risk of psoriasis in women: Nurses' Health Study II. Am J Med. 2007;120(11):953-959. doi:10.1016/j.amjmed.2007.06.020
5. Qureshi AA, Dominguez PL, Choi HK, Han J, Curhan G. Alcohol intake and risk of incident psoriasis in US women: a prospective study. Arch Dermatol. 2010;146(12):1364-1369. doi:10.1001/archdermatol.2010.204
6. Frankel HC, Han J, Li T, Qureshi AA. The association between physical activity and the risk of incident psoriasis. Arch Dermatol. 2012;148(8):918-924. doi:10.1001/archdermatol.2012.943
7. Danielsen K, Wilsgaard T, Olsen AO, Furberg AS. Overweight and weight gain predict psoriasis development in a population-based cohort. Acta Derm Venereol. 2017;97(3):332-339. doi:10.2340/00015555-2530
8. Armstrong AW, Harskamp CT, Dhillon JS, Armstrong EJ. Psoriasis and smoking: A systematic review and meta-analysis. Br J Dermatol. 2014;170(2):304-314. doi:10.1111/bjd.12670
9. Mahil SK, McSweeney SM, Kloczko E, McGowan B, Barker JN, Smith CH. Does weight loss reduce the severity and incidence of psoriasis or psoriatic arthritis? A Critically Appraised Topic. Br J Dermatol. 2019;181(5):946-953. doi:10.1111/bjd.17741
10. Klingberg E, Bilberg A, Björkman S, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21(1):17. Published 2019 Jan 11. doi:10.1186/s13075-019-1810-5
11. Haugeberg G, Michelsen B, Tengesdal S, Hansen IJW, Diamantopoulos A, Kavanaugh A. Ten years of follow-up data in psoriatic arthritis: Results based on standardized monitoring of patients in an ordinary outpatient clinic in southern Norway. Arthritis Res Ther. 2018;20(1):160. Published 2018 Aug 2. doi:10.1186/s13075-018-1659-z
12. Prussick RB, Miele L. Nonalcoholic fatty liver disease in patients with psoriasis: A consequence of systemic inflammatory burden?. Br J Dermatol. 2018;179(1):16-29. doi:10.1111/bjd.16239
13. Strober B, Gooderham M, de Jong EMGJ, et al. Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Am Acad Dermatol. 2018;78(1):70-80. doi:10.1016/j.jaad.2017.08.051
14. Campanati A, Ganzetti G, Di Sario A, et al. The effect of etanercept on hepatic fibrosis risk in patients with non-alcoholic fatty liver disease, metabolic syndrome, and psoriasis. J Gastroenterol. 2013;48(7):839-846. doi:10.1007/s00535-012-0678-9
15. Fu Y, Lee CH, Chi CC. Association of psoriasis with inflammatory bowel disease: A systematic review and meta-analysis. JAMA Dermatol. 2018;154(12):1417-1423. doi:10.1001/jamadermatol.2018.3631
16. Armstrong AW, Schupp C, Bebo B. Psoriasis comorbidities: Results from the National Psoriasis Foundation surveys 2003 to 2011. Dermatology. 2012;225(2):121-126. doi:10.1159/000342180
17. Singh JA, Guyatt G, Ogdie A, et al. 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Care Res. 2019;71(1):2-29. doi:10.1002/acr.23789
18. D'Angiolella LS, Cortesi PA, Lafranconi A, et al. Cost and cost effectiveness of treatments for psoriatic arthritis: A systematic literature review. Pharmacoeconomics. 2018;36(5):567-589. doi:10.1007/s40273-018-0618-5