Psoriasis: What’s the genetic link?

The pathogenesis of psoriasis is not fully understood, but a large heritable component of the etiology cannot be overlooked, writes Dr Sachith Abraham

Psoriasis is a chronic, inflammatory, autoimmune disorder with a multifactorial origin, being influenced by genetic as well as environmental, hormonal and psychosomatic factors. The increased rate of cell turnover and hyperproliferation of keratinocytes is a characteristic feature of psoriasis.

Patients who have psoriasis are more at risk for arthritis, skin cancer, diabetes, lymphoma, metabolic syndrome, obesity, stroke, and heart attack.

Causes of psoriasis

Familial association as well as higher rates of occurrence in monozygotic vs dizygotic twins have established a genetic link for the occurrence of psoriasis, with the interplay of genetic, environmental stressors and hormonal influences being the cause of occurrence of the disease.

The genetic link in psoriasis

There is a strong genetic link to psoriasis. If one of your parents has psoriasis, you have about a 10% chance of getting it. If both of your parents have psoriasis, you have a 50% chance of developing it.

Almost one-third of people with psoriasis have a relative who also has psoriasis. Researchers have identified over 100 genes that are associated with psoriasis.

These genes are involved in a variety of processes, including the immune system, skin cell growth, and inflammation.

Environmental factors

The disease presents with itchy, red, scaly lesions, with impaired quality of life due to its chronic course and incurable nature. Certain factors like alcohol, smoking, lack of sleep and a sedentary lifestyle have been shown to worsen the disease and patients have been advised to avoid these factors during the course of their treatment. Lifestyle modifications added to the standard treatment have shown significant benefits in aiding in the relief of symptoms.

Intake of alcohol increases an inflammatory mediator TNF-alpha, and since psoriasis is an inflammatory disorder, increased inflammatory mediators would increase the production of the scaly plaques. Similarly, smoking increases the production of free radicals which trigger inflammation and worsen the severity of the disease. Psoriatic patients already have an increased risk of cardiovascular complications and cigarette smoking may further worsen this condition as well. Therefore, alcohol abstinence and smoking cessation are important lifestyle interventions to be implemented.

Treatment options 

Dietary intervention is helpful as an adjunct to first-line therapy, with a diet high in fruits, vegetables, fibre, nuts and legumes, antioxidants, polyunsaturated fatty acids, olive oil, and low saturated fats, red meat, alcohol and dairy reducing the risk of chronic inflammatory disorders and improving the prognosis in psoriasis. Foods that have an anti-inflammatory effect on the body like fish oil or olive oil have proven to be helpful to some extent.

Weight reduction has also been helpful in many cases of psoriasis as obesity has been linked to increased inflammatory mediators stored in the fat tissue and weight reduction leads to increased efficacy of the treatment. It also helps to improve the overall prognosis with regard to the comorbidities associated with cardiovascular disease, metabolic syndrome, etc.

Medical management

Medical management for the disease includes topical corticosteroids in mild cases, with severe forms of the disease requiring treatment with retinoids and vitamin D analogues.

The most commonly used systemic medications include methotrexate, apremilast and cyclosporine, which are immunosuppressant drugs that suppress the immune response of the body, thus controlling the flare-up of the symptoms. They have shown increased safety and efficacy when used in combination with biologics like infliximab, secukinumab, and ixekizumab, which are drugs produced from human blood cells. Newer drugs used are Janus kinase inhibitors like tofacitinib which have shown promising results. 

Phototherapy with narrow band UVB is used in the treatment of moderate to severe disease, and also in cases of failure of response to topical treatment. An excimer laser is used to deliver this ultraviolet radiation. Vitamin D, the sunshine vitamin, is the key factor in the maintenance of the integrity of the musculoskeletal system. Supplementation of vitamin D for the management of psoriasis still remains a controversial discussion, even though numerous studies have reported that patients with psoriasis have lower levels of vitamin D when compared to a healthy individual. Vitamin D also shows potent anti-inflammatory effects which could prove beneficial in aiding psoriatic treatment regimes.

Studies have shown effects comparable to topical steroids as well as decreased side effects due to vitamin D and its analogues, which would make it a powerful tool in the management of psoriasis in the future when added alongside the first-line treatment modalities.

(The author is a consultant dermatologist.)