In recent years, research in immune-mediated diseases has yielded valuable insights on the overlapping relationships between the underlying pathogenesis of certain immune-mediated diseases. The immune pathways that are involved in diseases such as psoriasis (PsO) and psoriatic arthritis (PsA) are responsible for mediating inflammatory responses, causing a manifestation of symptoms.1,2
By investigating ways to therapeutically target these pathways, researchers have been able to better understand how to counter-regulate pathogenic immune responses and relieve symptoms by creating treatments that can address the underlying causes of disease. The objective is to help more patients achieve remission by applying these insights on the immune pathway across multiple disease areas and working beyond traditional medical subspecialty divisions.
The symptoms of PsO or PsA can have a substantial impact on patients’ life. People living with PsO experience skin plaques that are often itchy and painful, while those living with PsA can experience painful and swollen joints, axial disease, and debilitating fatigue, along with skin symptoms.3,4 Both PsO and PsA have also been shown to affect patients’ health-related quality of life, as they are associated with metabolic syndrome and increased risks for cardiovascular disease and diabetes.5 The visible symptoms of these diseases correlate with psychologic health as well, with many patients experiencing depression, suicide and alcoholism.6
The Integral Role of Interleukins in PsO and PsA
Alhough PsO and PsA are often treated as different diseases, the immune responses that mediate these diseases include the same dysregulated immune pathways.7 Research has shown that interleukin (IL)-23, a cytokine with 2 subunits (p40 and p19), activates a specific group of T helper cells known as Th17 cells that mediate inflammatory responses in both PsO and PsA.8-12 The dominant role of IL-23 and Th17 cells in PsO and PsA confirmed earlier research from studies of IL-12, which is a related cytokine that shares the same p40 subunit in common with IL-23.8
The discovery of the important role of IL-23 in PsO and PsA has led to the development of a new class of biologics that target modulators of the IL-23 pathway. Earlier therapies targeted inhibition of IL-17, one of the major cytokines produced by Th17 cells that mediates psoriatic inflammation in PsO and PsA.13
Understanding Immune Pathways to Diagnose and Treat PsO and PsA
Currently, approximately 30% of people diagnosed with PsO will develop PsA at some point in their lifetime.14 Dermatologists treating patients with the skin symptoms of PsO should be aware of this possibility and on the lookout for the joint symptoms of PsA, which might suggest the need for a patient to consult a rheumatologist for further treatment. A clinical pearl is to have a high degree of suspicion when patients present with PsO with fingernail and/or toenail involvement, as these patients have a higher risk of developing PsA, with approximately 80% of patients with PsO going on to develop PsA.15 Rheumatologists, too, can bring up PsO skin symptoms with their patients with PsA seeking treatment and collaborate with dermatologists to ensure that their needs are being met.
Although research has not yet indicated that any current treatment can prevent disease progression of PsO to PsA, some therapies that have been proven effective in treating PsO have also been proven effective in treating PsA.16 This is not surprising due to the similarities in the activation of underlying inflammatory responses in both conditions.
It is helpful for health care providers to understand the overlapping immune pathways between diseases to better understand how to optimally provide patient care and develop treatment plans accordingly. Differentiation in PsA data and the efficacy of treatments across varied symptoms can be a deciding factor while developing therapeutic plans for patients with PsO as well. Practicing dermatologists and rheumatologists attest to the importance of being aware of these connections and communicating regularly about the comanagement of their patients.
Researchers also continue to investigate the links between immune-mediated diseases and their effective treatment. A recent study found that patients with lower age at PsO onset or severe PsO were more likely to have a longer time to transition from PsO to PsA.17 Understanding the likelihood of disease progression for different populations enables health care providers to fulfil patients’ needs and helps researchers further scientific advancements.
In a similar manner to which the role of IL-23 was discovered with insights from other effective treatments, further promise lies in investigating these immune-mediated pathways across disease areas. Patients with PsO and PsA also have a higher risk for comorbid diagnoses of inflammatory bowel disease (IBD), indicating inflammatory pathway connections that warrant further research.18
Understanding pathway connections and working across multiple disease areas allows for potential innovations that further our knowledge and our vision of helping more patients achieve their treatment aims. Understanding the connections between immune-mediated diseases, and collaborating across therapeutic areas to do so, can help us move toward achieving these important goals for patients.
Lloyd S. Miller, MD, PhD, is the vice president, immunodermatology disease area leader at Janssen Research and Development, LLC. Dr Miller previously served as the vice chair for research in dermatology at the Department of Dermatology at Johns Hopkins.
- Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018;391(10136):2273-2284. doi:10.1016/S0140-6736(18)30830-4
- Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370(9583):263-271. doi:10.1016/S0140-6736(07)61128-3
- National Psoriasis Foundation. About psoriasis. Updated November 19. 2021. Accessed January 2022. https://www.psoriasis.org/about-psoriasis
- Belasco J and Wei N. Psoriatic arthritis: what is happening at the joint? Rheumatol Ther. 2019;6:305-315. doi:10.1007/s40744-019-0159-1
- National Psoriasis Foundation. Life with psoriasis. Updated November 2, 2020. Accessed March 2021. https://www.psoriasis.org/life-with-psoriasis/
- Reinberg, S. Psoriasis, mental illness often appear together. WebMD. Published online May 9. 2019. Accessed January 2022. https://www.webmd.com/skin-problems-and-treatments/psoriasis/news/20190509/psoriasis-mental-illness-often-appear-together
- Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;23;20(6):1475. doi:10.3390/ijms20061475
- Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13(5):715-725. doi:10.1016/s1074-7613(00)00070-4
- Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744-748. doi:10.1038/nature01355
- Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201:233-240. doi:10.1084/jem.20041257
- Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123-1132. doi:10.1038/ni1254
- Park H, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133-1141. doi:10.1038/ni1261
- Yang K, Oak ASW, Elewski BE. Use of IL-23 inhibitors for the treatment of plaque psoriasis and psoriatic arthritis: a comprehensive review. Am J Clin Dermatol. 2021;22(2):173-192. doi:10.1007/s40257-020-00578-0
- Haberman R, Adhikari S, Ramirez, D, et al. Assessing risk of PsA progression: results from a combined psoriasis-PsA center cohort. Presented at: 2019 American College of Rheumatology/Association of Rheumatology Professionals (ACR/ARP) Annual Meeting. Abstract 2449.
- Sobolewski P, Walecka I, Dopytalska K. Nail involvement in psoriatic arthritis. Reumatologia. 2017;55(3):131-135. doi:10.5114/reum.2017.68912
- Forchhammer S, Ghoreschi K. Update on the treatment of psoriasis and psoriatic arthritis. Psoriasis (Auckl). 2015;5:117-124. doi:10.2147/PTT.S69476
- Karmacharya P, Wright K, Achenbach SJ, et al. Time to transition from psoriasis to psoriatic arthritis: a population-based study. Semin Arthritis Rheum. Published online December 31, 2021. doi:10.1016/semarthrit.2021.12.013
- Canter, J. Digestive problems when you have psoriasis. WebMD. Published online April 14, 2021. Accessed February 2022. https://www.webmd.com/skin-problems-and-treatments/psoriasis/psoriasis-digestive-disorders