Link Between Psoriatic Arthritis and PCOS

What Is the Link Between PCOS and Psoriatic Arthritis (PA)?

Polycystic ovarian syndrome (PCOS) is a common disorder in women and is identified by anovulation (absence of egg release during ovulation). Psoriatic arthritis (PA) is a chronic immune-mediated inflammatory condition characterized by arthritis (inflammation of the joints). Individuals with PA typically also get affected by psoriasis. However, PA without psoriasis is not uncommon.

Women with PCOS and PA have similar comorbidities like metabolic syndrome (caused due to insulin resistance), dyslipidemia (imbalance in lipid metabolism), hyperandrogenism (excess male hormones), obesity, diabetes, and cardiovascular diseases. Because of these similarities and evidential reasoning, it is thought that females with psoriasis and PA in their reproductive period are at a higher risk for PCOS.

The common pathway that links PCOS and PA is unclear, but factors like genetics, inflammation, and their association with other diseases are thought to influence their combined occurrence.

What Is the Role of Genetics in PCOS and PA?

PCOS is an extremely heterogenetic complex condition; gene mutations (alterations) are responsible for steroid hormone biosynthesis or androgen synthesis, or insulin and leptin metabolism can lead to PCOS.

Psoriasis is also a multifactorial disease influenced by several genes. So far, thirteen main chromosomal loci (PSORS1-13) have been identified as related to psoriasis. Also, psoriasis is identified as a polygenetic inherited disease due to gene polymorphism in the immune system and keratinocyte biology.

The genetic link between PCOS and PT is a gene called RARB. This gene encodes a protein called thyroid-steroid hormone receptor - a receptor for retinoic acid, the active form of vitamin A. It is important for cell differentiation and growth. Apart from encoding for the receptor, the RARB gene also promotes the genes - StAR, CYP17A1, and HSD3B2 - involved in androgen production.

Female patients with psoriasis and PT have often been prescribed retinoid acid derivatives as part of the treatment. These derivatives trigger the RARB gene, which concomitantly triggers androgen production. Excess androgen production will lead to hyperandrogenism, one of the key pathogenesis factors for developing PCOS.

PCOS and PT can also be caused due to mutations in the insulin gene (INS) or insulin-receptor gene (INSR). They can also be caused due to genetic alteration in the insulin-mediated pathways. All of these mutations are capable of causing insulin resistance, obesity, metabolic syndrome, and cardiovascular diseases, all of which are the precipitating factors for PCOS and PT.

How is Inflammation Related to PCOS and PA?

PCOS is a proinflammatory condition that induces low-grade inflammation due to ovarian dysfunction and fibrosis. Women with PCOS have elevated levels of IL6 (interleukin 6). IL6 is a soluble mediator with a pleiotropic effect on inflammation, immune response, and hematopoiesis.

The main factor in the development of psoriasis and PA is the cooperation of T cells, keratinocytes, and dendritic cells in the lesion area on the skin. The T cells that are activated in the psoriatic plaques are divided into two groups:

1. Th1 - These are responsible for the production of cytokines (proteins that control the growth and activity of other immune cells).

2. Th2 - These are involved in the production of non-inflammatory cytokines.

The myeloid dendritic cells activate the T cells by releasing IL-23 and IL- 12. The activated T cells produce IL-7, IL-22, interferon (INF)- γ, and tumor necrosis factor (TNF). TNF, IL-23, and IL-17 are the key factors in developing psoriasis and PA.

A proinflammatory cytokine, known as TNF-ɑ, also plays a role in the inflammatory course of PCOS and PA. It is a multifunctional protein that affects lipid metabolism, insulin resistance, and endothelial function, all of which can trigger PCOS and PA.

Are PCOS and PA Related to Any Other Medical Conditions?

PCOS is an endocrine disorder, and PA is an immune-mediated skin condition. The clinical features of each condition are different, but their genetic background and chronic inflammatory process show a link between both conditions. Other conditions resembling these conditions are diabetes, cardiovascular conditions like myocardial infarction and atherosclerosis, and metabolic syndrome.

1. Diabetes - Women withPCOS are more likely to develop a wide spectrum of dysglycemic conditions like glucose intolerance and type 2 diabetes mellitus compared to women with a healthy body mass index. This is attributed to the common pathogenic pathways linking the two entities, such as insulin resistance. Both diabetes and PA share overlapping pathophysiology. The most common pathophysiologic mechanism relating to both is the genetic mechanism. In recent years, it has been evident that both conditions share overlapping genes (PTPN22, ST6GAL1, JAZF1) and susceptibility loci.

2. Cardiovascular Conditions - Women with PCOS are at a higher risk of cardiovascular conditions due to underlying pathophysiologies like lipid/glucose altered metabolism, hypertension, and systemic inflammatory conditions that are accessible by markers such as VES (vascular endothelial system), TNF-ɑ, cytokines, and C-reactive protein.

Patients with PA and psoriasis are at a higher risk of developing cardiovascular conditions due to common inflammatory pathways, secretion of adipokines, insulin resistance, angiogenesis, oxidative stress, microparticles, and hypercoagulability.

3. Metabolic Syndrome - Women with PCOS are more predisposed to metabolic syndrome. This is because the abnormalities (like insulin resistance, obesity, dyslipidemia, and hyperandrogenism) that cause PCOS are also responsible for metabolic syndrome. The pathophysiology linking PA and psoriasis to metabolic syndrome are overlapping inflammatory pathways and genetic predisposition. The genes responsible for shared genetic susceptibility are PSORS2-4, CDKAL1, and ApoE4.

What Is the Treatment for PCOS and PA?

Although both conditions share common etiologies, there is no common treatment. Both conditions get exacerbated with obesity, and reducing weight will have relief to a certain extent, but both of them should be addressed individually to prevent severe complications.

1. Treatment for PCOS involves medication like Clomid (an estrogen receptor modulator), and gonadotropins, both stimulating ovulation. Apart from this, individuals with PCOS can also benefit from Metformin, which lowers insulin and testosterone levels.

2. Treatment for PA and psoriasis include nonsteroidal anti-inflammatory drugs, steroids, biologics (such as Remicade and Humira), and disease-modifying antirheumatic drugs (like Methotrexate and Sulfasalazine).

Conclusion:

PCOS is common in patients with PA and psoriasis, because of which there is a negative impact on the clinical course of the former condition. Genetic, inflammatory, and metabolic disorders contribute to this mechanism. Understanding the exact etiology of PCOS and its association with PA will help devise common treatment options, and better outcomes and studies are underway to understand it.