- Allison Truong, MD, FAAD
- Comorbidities, Expert Insights, Treatment
The Connection Between Psoriasis and Comorbidities
Psoriasis and its comorbid conditions are linked by altered systemic inflammation.3 Behavioral factors that impact the immune system (e.g., high body mass index, infection, stress, drugs) have been shown to trigger psoriasis in genetically susceptible individuals.3 These same factors, including lifestyle, environmental, and genetic factors, also trigger psoriasis comorbidities. The similarities between psoriasis and its comorbidities are due to its shared molecular mechanisms relating to immune system dysregulation. For example, Patrick et al. applied trans-disease meta-analysis to 11,024 psoriasis and 60,801 coronary artery disease cases and their respective controls. Their study identified one opposing and three shared genetic loci for psoriasis and coronary artery disease (CAD). This discovery demonstrated the causal relationship between the CAD/psoriasis comorbidity. Notably, many of the shared genes between CAD/psoriasis involve systemic inflammation, such as NFKB1, TNF, and IL17.3
Similarly, other studies have also reaffirmed that shared inflammatory pathways drive the association between psoriasis and its comorbidities. Armstrong et al.4 and Armstrong et al.5 highlighted the elevated risk of hypertension and diabetes mellitus in psoriasis patients, respectively, underscoring the systemic nature of this inflammatory disorder. Genetic studies by Hebert et al.6 identified shared genetic susceptibility between psoriasis and inflammatory bowel disease. Additionally, a meta-analysis by Qiao et al.7 found a significant association between psoriasis and metabolic syndrome, reinforcing that chronic inflammation may drive multiple comorbid conditions. Collectively, these findings suggest that managing psoriasis effectively may help mitigate the risk of related systemic diseases.
Systemic Treatments and Their Effects on Comorbidities
The benefits of treating psoriasis extend beyond skin clearance, although the choice of treatment remains controversial. Systemic treatments, such as traditional oral agents (e.g., methotrexate) and biologic therapies, may not only alleviate psoriasis, but also potentially prevent its associated comorbidities. Not only do biologics function to reduce PASI score, they also confer cardiovascular benefits, according to some studies. Evidence suggests that biologics can reduce CAD progression8, restore myocardial dysfunction9, improve endothelial function10, and reduce major cardiovascular events (CVEs; myocardial infarction, stroke or transient ischemic attack, unstable angina)11. For instance, Wu et al. conducted a retrospective cohort study comparing 13,935 psoriasis patients treated with TNF-alpha inhibitors to those receiving methotrexate and found a lower incidence of CVEs among those treated with TNF-alpha inhibitors.11
However, the impact of biologics on cardiovascular outcomes remains uncertain, and further studies are needed to provide real-world evidence, as some authors have failed to find an effect of biologics on the reduction of cardiovascular disease development.12,13 Rungapiromnan et al. performed a prospective cohort study involving 5,468 biologic-naïve patients treated with adalimumab, etanercept, or ustekinumab, and 2,189 patients receiving methotrexate, but found no statistically significant difference in CVE risk between the two groups.12 Similarly, Bissonnette et al., using data from the Psoriasis Longitudinal Assessment Registry (PSOLAR), did not identify a reduction in major adverse cardiovascular events (MACE; myocardial infarction, stroke, or cardiovascular death) among patients with moderate to severe psoriasis receiving biologics compared to those undergoing topical therapy or phototherapy.13 These findings suggest that focusing on reducing skin inflammation might be a more universally beneficial goal than emphasizing a particular therapy until further studies can provide more information on optimal treatment strategies.
Studies on the comorbidity of psoriatic arthritis also demonstrate a similar parallel to cardiovascular disease in the benefits of overall systemic inflammation reduction but limited clarity on a treatment algorithm. Multiple studies have shown how effective systemic treatments with biologics (adalimumab14, secukinumab15, guselkumab16) can improve psoriatic arthritis symptoms and inhibit radiographic progression. However, some studies have reported limited efficacy of biologics in certain patient populations who continue to experience pain and impaired physical function despite being on sustained treatment.17,18,19 As psoriatic arthritis is a complex condition, many patients require combination therapy beyond monotherapy to achieve symptomatic improvement. These findings highlight the need for alternative therapeutic approaches and further research into understanding the variability in treatment responses between certain individuals. Nonetheless, the patients who did not progress radiographically with effective biologic treatment reported a reduction in pain and improvement in physical function, suggesting that effective treatment of skin and joint disease also reduces significant disease morbidity and mortality.16
Effects on Quality of Life, Morbidity and Mortality
Psoriasis and its comorbidities can significantly impact a patient’s quality of life, leading to increased morbidity and mortality. The physical manifestations of the condition (e.g., rash, itching, and pain) combined with psychological factors (e.g., diminished self-esteem, social stigma) can further impair a patient’s quality of life. The physical and psychological elements contribute to additional comorbid conditions of psoriasis, including anxiety, depression, and suicidality.20 A population-based cohort study in the United Kingdom reported an excess of 10,400 diagnoses of depression, 7100 diagnoses of anxiety, and 350 diagnoses of suicidality attributed to psoriasis annually.21 Fortunately, recent evidence has also revealed that biologic therapy, compared to conventional therapy, shows promise in reducing patient’s incidence and risk of developing depression and insomnia.22, 23,24 Thus, psoriasis treatments may improve both the physical and psychological aspects of the disease, ultimately reducing its overall burden.
Although comorbidities may not be obvious to the naked eye, they can significantly impact psoriasis patients, who may experience a range of comorbid conditions within their lifetime. To provide optimal patient care, healthcare providers should address both psoriasis and its comorbidities as early as possible. Systemic therapies, particularly biologics, target systemic inflammation and appear to hold the most promise in helping psoriasis patients treat and prevent comorbidities. Given the complexity of caring for psoriasis patients with comorbid conditions, a multidisciplinary approach is recommended when possible. Future research aimed at identifying which psoriasis patients are at the highest risk for specific morbidities will help healthcare professionals allocate resources more effectively, enabling targeted preventive counseling and the delivery of precise, individualized care.
References
- National Psoriasis Foundation. Related conditions of psoriasis. Updated December 22, 2023. Accessed July 23, 2024. https://www.psoriasis.org/related-conditions/
- Oliveira M, Rocha Bde O, Duarte GV. Psoriasis: classical and emerging comorbidities. An Bras Dermatol. 2015;90(1):9-20.
- Patrick MT, Li Q, Wasikowski R, et al. Shared genetic risk factors and causal association between psoriasis and coronary artery disease. Nat Commun. 2022;13(1):6565. Published 2022 Nov 2. doi:10.1038/s41467-022-34323-4
- Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and hypertension: a systematic review and meta-analysis of observational studies. J Hypertens. 2013 Mar;31(3):433-42; discussion 442-3. doi: 10.1097/HJH.0b013e32835bcce1.
- Armstrong AW, Harskamp CT, Armstrong EJ. Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis. JAMA Dermatol. 2013 Jan;149(1):84-91. doi: 10.1001/2013.jamadermatol.406. PMID: 23407990.
- Hébert HL, Ali FR, Bowes J, Griffiths CE, Barton A, Warren RB. Genetic susceptibility to psoriasis and psoriatic arthritis: implications for therapy. Br J Dermatol. 2012 Mar;166(3):474-82. doi: 10.1111/j.1365-2133.2011.10712.x.
- Qiao J, Jia QN, Jin HZ. Association between metabolic syndrome and psoriasis: a meta-analysis of observational studies with non-psoriasis control groups. Arch Med Sci. 2020 Jan 31;17(6):1558-1565. doi: 10.5114/aoms.2020.92434.
- Hjuler KF, Bøttcher M, Vestergaard C, Bøtker HE, Iversen L, Kragballe K. Association between changes in coronary artery disease progression and treatment with biologic agents for severe psoriasis [published correction appears in JAMA Dermatol. 2016 Oct 1;152(10):1173-1174. doi: 10.1001/jamadermatol.2016.3933]. JAMA Dermatol. 2016;152(10):1114-1121. doi:10.1001/jamadermatol.2016.1984.
- Ahlehoff O, Hansen PR, Gislason GH, et al. Myocardial function and effects of biologic therapy in patients with severe psoriasis: a prospective echocardiographic study. J Eur Acad Dermatol Venereol. 2016;30(5):819-823. doi:10.1111/jdv.13152.
- von Stebut E, Reich K, Thaçi D, et al. Impact of secukinumab on endothelial dysfunction and other cardiovascular disease parameters in psoriasis patients over 52 Weeks. J Invest Dermatol. 2019;139(5):1054-1062. doi:10.1016/j.jid.2018.10.042.
- Wu JJ, Guérin A, Sundaram M, Dea K, Cloutier M, Mulani P. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81-90. doi:10.1016/j.jaad.2016.07.042.
- Rungapiromnan W, Mason KJ, Lunt M, et al. Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study. J Eur Acad Dermatol Venereol. 2020;34(4):769-778. doi:10.1111/jdv.16018.
- Bissonnette R, Kerdel F, Naldi L, et al. Evaluation of risk of major adverse cardiovascular events with biologic therapy in patients with psoriasis. J Drugs Dermatol. 2017;16(10):1002-1013.
- Mease PJ, Ory P, Sharp JT, et al. Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT). Ann Rheum Dis. 2009;68(5):702-709. doi:10.1136/ard.2008.092767.
- Mease P, van der Heijde D, Landewé R, et al. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis. 2018;77(6):890-897. doi:10.1136/annrheumdis-2017-212687.
- Gottlieb AB, McInnes IB, Rahman P, et al. Low rates of radiographic progression associated with clinical efficacy following up to 2 years of treatment with guselkumab: results from a phase 3, randomised, double-blind, placebo-controlled study of biologic-naïve patients with active psoriatic arthritis. RMD Open. 2023;9(1):e002789. doi:10.1136/rmdopen-2022-002789.
- Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH, Sharp JT, Ory PA, Perdok RJ, Weinberg MA; Adalimumab effectiveness in psoriatic arthritis trial study group. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005 Oct;52(10):3279-89. doi: 10.1002/art.21306.
- Zhang KL, Hou SY, Wu D. Efficacy and safety of secukinumab in patients with psoriatic arthritis: A meta-analysis of different dosing regimens. Clinics (Sao Paulo). 2021 Oct 1;76:e2820. doi: 10.6061/clinics/2021/e2820
- Deodhar A, Helliwell PS, Boehncke WH, Kollmeier AP, Hsia EC, Subramanian RA, Xu XL, Sheng S, Agarwal P, Zhou B, Zhuang Y, Ritchlin CT; DISCOVER-1 Study Group. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020 Apr 4;395(10230):1115-1125. doi: 10.1016/S0140-6736(20)30265-8. Epub 2020 Mar 13. Erratum in: Lancet. 2020 Apr 4;395(10230):1114. doi: 10.1016/S0140-6736(20)30680-2.
- Van Voorhees AS, Fried R. Depression and quality of life in psoriasis. Postgrad Med. 2009;121(4):154-161. doi:10.3810/pgm.2009.07.2040.
- Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010;146(8):891-895. doi:10.1001/archdermatol.2010.186.
- Strober B, Soliman AM, Truong B, Patel MB, Barqawi YK, Gisondi P. Association Between Biologic Exposure and the Risk of Depression in Patients with Psoriasis: A Retrospective Analysis of Large US Administrative Claims Data. Am J Clin Dermatol. Published online June 27, 2024. doi:10.1007/s40257-024-00877-w.
- 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.
- Wu CY, Chang YT, Juan CK, et al. Depression and insomnia in patients with psoriasis and psoriatic arthritis taking tumor necrosis factor antagonists. Medicine (Baltimore). 2016;95(22):e3816. doi:10.1097/MD.0000000000003816.
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