The immune system is made up of a complex network of cells, tissues and organs that work in a coordinated way to defend the body against foreign invaders – germs or substances capable of causing us problems; But when it hits the wrong target, it can trigger a variety of disorders. This is the case of psoriasis, a chronic inflammatory disease of the skin, of autoimmune origin, which causes scaly lesions.
As Rubén Francés, an immunologist at the General University Hospital of Alicante, explains, it can affect internal organs. “Therefore, its relationship with other comorbidities – a term that describes two or more disorders or diseases that occur in the same person – is very important.” In particular, according to this specialist, with ailments mainly related to metabolism: among others, the metabolic syndrome – a group of disorders that occur at the same time and increase the risk of suffering from heart disease, type 2 diabetes and stroke -, chronic obstructive pulmonary disease (COPD), depression and even cancer. In addition, they tend to share characteristics with diseases that also have an immunological basis and develop chronic inflammation: the so-called IMID – immune-mediated inflammatory diseases.
The lesions – or plaques – of psoriasis are produced by the stimulation and overproduction of keratinocytes, the cells most present in the epidermis – they represent around 80% and 90% -. This excess production is driven by increased activity of a type of immune cell, T lymphocytes, due to environmental and genetic triggers – from trauma to emotional stress or certain medications.
“The basis of everything is the inflammation it generates,” explains Dr. Francés. Depending on the environment and whether the individual is genetically predisposed, the failure of the immune system response may be more or less feasible ”.
How is this abnormal response generated?
Interleukins are immune system molecules that play a key role in the activation and survival of T lymphocytes, including Helper 17 or Th17, with an orchestrating role in the inflammatory response. This is activated, in particular, through interleukin-23 (IL-23), which stimulates the survival and expansion of Th17. In fact, IL-23 binds to T cells to produce specialized Th17 cells, and then that proliferation leads to the expression of interleukin-17A and other cytokines – proteins that mediate cell activation and communication. , which leads to the production of a proliferation of keratinocytes and the formation, therefore, of plaques in the skin.
Fortunately, as Dr. Francés explains, the knowledge of how this disease works is increasing, which allows the development of treatments with more selective profiles and, therefore, more effective: they act faster and their effects last longer. Likewise, they are safer, “and the immunosuppression – reduction or cancellation of the body’s immune response through medical treatment – that they generate is increasingly specific,” says the specialist.
Biological treatments
Psoriasis was the first of the dermatological diseases to benefit from biological treatments. “It happened fifteen years ago”, recalls Lluís Puig, director of the Dermatology Service of the Hospital de la Santa Creu i Sant Pau (Barelona). Focused on stimulating, replenishing or modulating defenses, this type of therapy receives that name because it is based on living cells. For the most part, their main actor is immunoglobulins –antibodies– that block molecules that, in this specific case, intervene in the inflammatory pathways of psoriasis. Immunoglobulins act only on tumor necrosis factor alpha – cytocin that stimulates the acute phase of the inflammatory reaction – rather than suppressing the entire immune system, and they did not have the drawbacks of the then available systemic treatments, although they were associated with some risk infection and reactivation of latent infections, such as tuberculosis.
A problem with some of these biological agents is the loss of efficacy in a significant percentage of patients who develop antibodies to the drug. Years later, a breakthrough occurred: the introduction of a biological agent directed against interleukin 23, the main regulator of Th17 lymphocyte activation. Although it also inhibits the pro-inflammatory cytokine IL-12, the safety profile of this drug is excellent, it can be administered every 12 weeks, and it produces antibodies in very few patients.
The next development was the introduction of drugs directed against IL-17, the main activator of keratinocytes and determinant of the inflammatory response in psoriasis. These monoclonal antibodies – proteins produced in the laboratory that, like guided missiles, bind to target substances in the body – are characterized by the rapidity of their onset of action, and for the first time allowed to achieve a 90% improvement in more than two thirds of the patients, and a complete whitening of the skin in 40% of the cases from twelve weeks, which is maintained in the majority when continuing the treatment.
The regulator of IL-17 production is precisely IL-23, so by acting specifically on the latter it achieves a more persistent effect; The biological agents of this new family are administered every eight or twelve weeks, and are capable of inducing remission of the disease – that is, it takes many months to reactivate even if treatment is suspended – in a large number of patients. On the other hand, “these are very effective molecules that work in most patients, regardless of their characteristics – weight, failure of previous treatments, etc. – with an excellent safety profile,” says Dr. Puig. Most of the sufferers achieve a complete whitening of the skin.
What tool is used to measure the severity of psoriasis?
According to Dr. Lluís Puig, the psoriasis area severity index (PASI) is the most frequent to measure the progression of the disease: both the affected areas and the redness, thickness and peeling of the plates.
A PASI 75 refers to a 75% reduction in psoriasis. Until recently, this was considered the standard for determining the effectiveness of a treatment. However, with the latest advances in this field, as confirmed by Dr. Puig, the PASI 90 and PASI 100 are becoming the new references. ” As of today, we have PASI 100 in 50% -60% of the cases .”
However, according to the immunologist Rubén Francés, recent advances in the mechanism of development, progression and maintenance of the disease are assuming that the most uncontrolled and active immune pathways “can be treated and identified effectively.” The treatments, he points out, have different strategies to try to control the inflammatory response, but all are based on the identification of specific processes that occur within the development of the disease.
By Carmen M. López
