Psoriasis is a chronic inflammatory disorder that affects approximately 3.2% of the US population.1 Although psoriasis was long considered to affect only the skin and joints, its underlying cause involves helper T-cell type 1 (TH1) immune dysregulation that can affect other organ systems.2 Individuals with psoriasis are at increased risk for cardiovascular disease, hypertension, and diabetes.3,4 Because a person’s psoriasis symptoms can be visible to others, patients with this disease may have a greater incidence of anxiety and depression.5

Assessment

Approximately 80% to 90% of patients with psoriasis have plaque psoriasis,5 which is characterized by the appearance of sharply demarcated plaques with an adherent scale. Nails may manifest pitting, onycholysis, and oil-drop discoloration. Psoriatic arthritis, which affects 25% to 30% of patients,6 is a related spondyloarthropathy that usually presents as an asymmetrical oligoarthritis that over time can result in joint destruction. Associated findings include enthesitis and dactylitis.5  Guttate, inverse, pustular, and erythrodermic psoriasis subtypes occur in less than 10% of patients with psoriasis.7

The severity of psoriasis is defined in part by the total body surface area (BSA) involved, with involvement of less than 3% of BSA considered mild, 3% to 10% of BSA considered moderate, and greater than 10% BSA considered severe disease.8 However, psoriasis can be defined as severe irrespective of BSA when it causes serious emotional distress; is located on the hands, feet, scalp, face, or genital area; or causes intractable pruritus.8

The Psoriasis Area Severity Index (PASI) is a research tool used in clinical trials to quantify the extent and severity of psoriasis, which takes into account the extent BSA as well as redness, scaling, and plaque thickness (0, no disease; 72, maximum disease). The PASI is also used to monitor response to treatment. When reviewing the literature, it is important to consider the PASI when evaluating the effectiveness of a medication.

Management

Many patients with mild to moderate psoriasis are adequately controlled with topical agents and/or phototherapy. Topical agents are available in a variety of strengths and formulations allowing for titration based on disease severity and location.9 Phototherapy is an effective treatment modality for psoriasis and UV light sources can treat a large body surface area but require multiple treatment sessions and specialized equipment.10 Topical agents used alone or combined with phototherapy may not adequately control symptoms of moderate to severe plaque psoriasis. In these cases, the use of systemic oral medication or biologics is recommended.

Oral Medications

Acitretin, cyclosporine, and methotrexate are oral systemic medications used to treat moderate to severe psoriasis. The efficacy of these agents is variable and all require some degree of laboratory monitoring.11 Acitretin is teratogenic and can raise serum triglyceride levels. Cyclosporine, especially if continued long-term, can impair renal function. Methotrexate also is teratogenic and may induce leukopenia, pulmonary fibrosis, elevation of liver enzymes, and, on rare occasions, cirrhosis.11

Apremilast, a phosphodiesterase 4 inhibitor, is the most recently approved oral agent for the management of psoriasis and psoriatic arthritis. Laboratory monitoring of patients taking apremilast is not required, but gastrointestinal side effects such as nausea and diarrhea are encountered frequently.12

Biologics

Tumor necrosis factor-alpha (TNF-α) and interleukin (IL) inhibitors are biologic agents that selectively inhibit cytokines involved in the pathogenesis of psoriasis (Table).11,13 Biologics have revolutionized the management of psoriasis and several are approved for this indication. The majority of these agents are administered subcutaneously, and dosing schedules range from weekly to quarterly depending on the agent. Tuberculosis testing is required before treatment, and all of the agents carry warnings of an increased risk for infection.13 

Suboptimal Response to Treatment

Approximately 52% of patients with psoriasis are not satisfied with their current treatment regimen.14 The reasons for this are multiple and include nonadherence to therapy, inadequate dosing of medications, and development of antibodies to systemic therapy. There are no formal therapeutic guidelines addressing treatment resistance, so each case should be approached using the best available data coupled with shared decision-making parameters. For example, simplifying a treatment regimen may greatly enhance compliance and switching from one class of biologic to another may offer improved efficacy when adequate control is not achieved.

Tumor necrosis factor-alpha agents were the initial biologics approved to treat psoriasis and soon became a first-line option for patients. Although these agents are more effective than traditional oral therapies, approximately 30% to 50% of patients have suboptimal responses.15

A recent meta-analysis of patients with moderate to severe plaque psoriasis found that IL-17 and IL-23 inhibitors have superior efficacy compared with oral agents. In the study, IL-17 and IL-23 inhibitors were associated with the highest PASI response rates for both short- and long-term therapy.16  

Pharmacogenetics and pharmacogenomics testing for biomarkers have the potential to predict treatment outcomes of these therapies and individualize care for patients.15 These biomarkers could improve patient quality of life and reduce health care costs and potential side effects.17

Shared Decision-Making

Shared decision-making is of paramount importance in the management of psoriasis. More than 70% of patients with psoriasis have at least 1 comorbidity.18 Psoriasis is associated with metabolic syndrome, diabetes, premature cardiovascular disease, psychiatric disorders, and inflammatory bowel disease. Patients with psoriasis are more likely to smoke and have a higher incidence of obesity than the general population; therefore, lifestyle counseling should address factors that negatively affect health and well-being. Referral to additional specialists for specific workup and comprehensive management often is required. A significant percentage of patients with psoriasis have concomitant arthritis, and progressive disease may warrant co-management with a rheumatologist.

An ever-increasing number of therapeutic options for psoriasis are available, each requiring a thorough discussion of potential benefits and risks that addresses questions about psoriasis care, such as: Can a patient be managed with topicals alone? This becomes quite difficult when a significant volume of body surface area is involved. Can a patient travel to an office for phototherapy 3 times weekly? Is the patient needle-phobic, preferring instead oral therapy? Does the patient have an underlying disease that may limit the choice of therapy? Is the patient of childbearing age (precluding options such as acitretin and methotrexate)?

Finally, shared decision-making must address access to care. Does the patient have insurance coverage or qualify for assistance to offset the cost of therapy? For those who are insured, is a tiered approach to therapy dictated by the patient’s insurance company? If so, shared decision-making involves not only the patient and medical provider but also a third party as well.

Zachary Sabaday, PA-C, is a physician assistant at DermDox Dermatology Centers in Sugarloaf, Pennsylvania. Stephen Schleicher, MD, is director of DermDox Dermatology Centers in Pennsylvania, associate professor of medicine at Geisinger Commonwealth Medical College, and clinical instructor of dermatology at Arcadia University and Kings College.

References

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2. Mahajan R, Handa S. Pathophysiology of psoriasis. Indian J Dermatol Venereol Leprol. 2013;79 Suppl 7:S1-S9. doi:10.4103/0378-6323.115505

3. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741. doi:10.1001/jama.296.14.1735

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8. Menter A, Stober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. .J Am Acad Dermatol. 2019;80(4):1029-1072. doi. 10.1016/j.jaad.2018.11.057

9. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60(4):643-659. doi:10.1016/j.jaad.2008.12.032

10. Elmets CA, Lim HW, Stoff B, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy. J Am Acad Dermatol. 2019;81(3):775-804. doi:10.1016/j.jaad.2019.04.042

11. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61(3):451-485. doi:10.1016/j.jaad.2009.03.027

12. Crowley J, Thaçi D, Joly P, et al. Long-term safety and tolerability of apremilast in patients with psoriasis: pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2). J Am Acad Dermatol. 2017;77(2):310-317.e1. doi:10.1016/j.jaad.2017.01.052

13. Jeon C, Sekhon S, Yan D, Afifi L, Nakamura M, Bhutani T. Monoclonal antibodies inhibiting IL-12, -23, and -17 for the treatment of psoriasis. Hum Vaccin Immunother. 2017;13(10):2247-2259. doi:10.1080/21645515.2017.1356498

14. Heath MS, Kolli SS, Dowling JR, Cline A, Feldman SR. Pharmacotherapeutic strategies for stand treatment-resistant psoriasis. Expert Opin Pharmacother. 2018;20(4):443-454. doi:10.1080/14656566.2018.1559819

15. Ovejero-Benito M, Muñoz-Aceituno E, Reolid A, Saiz-Rodriguez M, Abad-Santos F, Dauben E. Pharmacogenetics and pharmacogenomics in moderate-to-severe psoriasis. Am J Clin Dermatol. 2018;19(2):209-222. doi: 10.1007/s40257-017-0322-9

16. Armstrong AW, Puig L, Joshi A, et al. Comparison of biologics and oral treatments for plaque psoriasis: a meta-analysis. JAMA Dermatol. 2020;156(3):258-269. doi:10.1001/jamadermatol.2019.4029

17. Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475. doi:10.3390/ijms20061475

18. Machado-Pinto J, dos Santos Diniz M, Bavoso NC. Psoriasis: new comorbidities. An Bras Dermatol. 2016;91(1):8-14. doi:10.1590/abd1806-4841.20164169