From the Guidelines
Psoriasis is a chronic inflammatory skin condition caused by a complex interplay of genetic predisposition and environmental triggers, with the primary pathophysiological mechanism involving an abnormal immune response where T cells, particularly Th1 and Th17 cells, become overactive and release inflammatory cytokines such as TNF-alpha, IL-17, and IL-23, as reported in the guidelines of care for the management of psoriasis and psoriatic arthritis 1.
Etiology of Psoriasis
The etiology of psoriasis is multifactorial, involving both genetic and environmental factors. Genetic factors play a significant role, with over 60 genetic loci identified, particularly PSORS1 on chromosome 6, which contains HLA-Cw6, as mentioned in the guidelines 1. Environmental triggers that can initiate or exacerbate psoriasis include:
- Physical trauma (Koebner phenomenon)
- Infections (especially streptococcal)
- Medications (beta-blockers, lithium, antimalarials)
- Stress
- Smoking
- Alcohol consumption
- Obesity
Pathophysiology of Psoriasis
The pathophysiology of psoriasis involves an abnormal immune response where T cells become overactive, particularly Th1, Th17, and Th22 cells. These activated T cells release inflammatory cytokines such as TNF-alpha, IL-17, and IL-23, which accelerate skin cell production, as discussed in the guidelines 1. This results in keratinocytes multiplying approximately ten times faster than normal, completing their life cycle in just 3-4 days instead of the typical 28-30 days. Consequently, immature skin cells accumulate on the surface, forming the characteristic thick, silvery scales and red, inflamed plaques.
Systemic Inflammation and Comorbidities
The disease involves not only skin manifestations but also systemic inflammation, explaining the association with comorbidities like:
- Psoriatic arthritis
- Cardiovascular disease
- Metabolic syndrome
- Depression As reported in the guidelines, patients with psoriasis have an increased incidence of lymphoma, heart disease, obesity, type 2 diabetes, and the metabolic syndrome, and are at a higher risk for mortality, largely attributable to cardiovascular death 1.
Treatment Implications
Understanding the immunopathogenesis of psoriasis has led to targeted biologic therapies that block specific cytokines in the inflammatory cascade, revolutionizing psoriasis treatment, with biologics such as alefacept, efalizumab, infliximab, adalimumab, golimumab, etanercept, and ustekinumab, as discussed in the guidelines 1.
From the Research
Etiology of Psoriasis
- Psoriasis is a common cutaneous disease with multifactorial etiology, including genetic and non-genetic factors such as drugs, smoking, drinking, diet, infection, and mental stress 2
- The interaction between environmental factors and genetics is considered a main factor in the pathogenesis of psoriasis 2
- Genetic, epigenetic, and environmental influences contribute to the development of psoriasis 3
Pathophysiology of Psoriasis
- Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes 3
- The interplay of immune cells and cytokines, including Th1/Th2 homeostasis, the Th17/Treg balance, and the IL-23/Th17 axis, is critical in the pathogenesis of psoriasis 3
- Th17 is believed to be particularly important in psoriasis due to its pro-inflammatory effects and involvement in an integrated inflammatory loop with dendritic cells and keratinocytes 3
- Innate lymphoid cell (ILC)3 induces psoriasis rashes directly without T-cell/antigen interaction in response to released antimicrobial peptides from activated keratinocytes and inflammatory cytokines 4
Risk Factors for Psoriasis
- Classic risk factors for psoriasis include mechanical stress, infections, dysbiosis of the skin, common drugs, environment and pollution, lifestyle, psychological stress, hormonal and metabolic alterations 5
- Emerging risk factors for psoriasis include biological drugs, immunotherapy for oncologic disease, Covid-19, and vaccines 5
- Accurate patient information and monitoring of risk factors, as well as planned follow-ups, may help prevent and treat the worsening of psoriasis 5
Relationship with Other Skin Conditions
- Psoriasis is related to other autoinflammatory and autoimmune dermatological diseases, including vitiligo, alopecia areata, hidradenitis suppurativa, atopic dermatitis, and bullous dermatoses 6
- These conditions share overlapping immune system dysfunction, making their relationship with psoriasis significant 6
- Understanding the intricate interconnection between psoriasis and these conditions is important for developing novel research directions and providing holistic care 6