Psoriasis is a skin disorder that is chronic proliferative and inflammatory in nature. Extensor surfaces, scalp, and lumbosacral area are covered in erythematous plaques with silvery scales. The disease can also impair the eyes and joints. It has no cure. Because of their low quality of life, many psoriasis patients experience depression. In addition to the cutaneous manifestations, it is associated with an increased risk of psoriatic arthritis, depression and cardiovascular disease.

Psoriasis is known to be affecting 3% to 4% of the general population worldwide. While the prevalence of psoriasis in Egypt ranges 0.19-3% Psoriatic arthritis (PsA) most commonly develops in 20-30% of psoriatic patients with preceding psoriasis or develops concomitantly with psoriasis, and it manifests all features of arthritis, including enthesitis.

The pathogenesis of psoriasis is multifactorial, involving a complex interplay between genetic predisposition, immune system dysregulation, and environmental triggers. Central to the disease process is the activation of T-cells, particularly Th1, Th17, and Th22 subsets, which release pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-22 (IL-22)

. These cytokines drive the abnormal growth and differentiation of keratinocytes and induce the inflammatory cascade that results in the characteristic skin lesions. Genetic factors, including polymorphisms in genes related to the immune system, such as HLA-Cw6.Additionally, environmental factors like infections, stress, and trauma (Koebner phenomenon) can exacerbate or trigger the onset of the disease.

The Psoriasis Area and Severity Index (PASI) is a widely used tool for assessing the severity of psoriasis and evaluating treatment efficacy. It combines the extent of skin involvement and the degree of erythema, scaling, and thickness across four body regions: the head, upper limbs, trunk, and lower limbs. Each region is assigned a score for surface area involvement (0-6) and for each symptom (0-4), which are then combined to yield an overall PASI score ranging from 0 to 72. Higher scores indicate more severe disease. Typically, a PASI score below 10 suggests mild psoriasis, while scores between 10 and 20 indicate moderate severity, and scores above 20 reflect severe psoriasis. PASI serves as a critical endpoint to gauge disease burden.

Interleukin-12B (IL12B) encodes the p40 subunit shared by both IL-12 and IL-23, cytokines that are pivotal in the differentiation of naive T-cells into Th1 and Th17 cells, respectively. The IL-12/IL-23 axis is well-established in contributing to the immune pathology seen in psoriasis. Genetic studies have shown that polymorphisms within the IL12B gene are associated with an increased risk of psoriasis.

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in humans. SNP rs3213094, located within the IL12B gene, has been identified as a potentially significant variant that could alter the expression or function of the cytokines involved in immune responses. Previous studies have suggested that SNP rs3213094 within the IL12B gene is associated with psoriasis, although the strength of this association varies across different populations.

Humira (adalimumab) is a monoclonal antibody targeting TNF-α, widely used for treating moderate-to-severe psoriasis and PsA. It works by neutralizing the activity of TNF-α, thereby reducing inflammation, decreasing keratinocyte proliferation, and alleviating joint symptoms. However, individual responses to Humira can vary significantly, with some patients experiencing limited or no therapeutic benefits

Inclusion Criteria:

- Patients having psoriasis diagnosed clinically for at least 6 months and who have a severity grade of severe, defined as a Psoriasis Area and Severity Index (PASI) score greater than 10, and involvement of greater than 10% of the body surface area (BSA) with psoriatic arthritis.

Exclusion Criteria:

• Patients with other autoimmune or inflammatory conditions (e.g., rheumatoid arthritis, lupus).
• Pregnancy and lactation.
• Patients currently undergoing any treatment other than Humira.
• Patients with known genetic disorders affect immune system function.
• Patients were undergoing any treatment other than Humira in the last 6 months.
• Patients with active infections, including tuberculosis or chronic viral infections (e.g., hepatitis B or C, HIV).
• Patients with contraindication to Humira.
• Renal &Vascular diseases