Long-term treatment is associated with squamous cell carcinoma (but not with melanoma). A combination therapy for moderate to severe psoriasis using PUVA plus acitretin resulted in benefit, but acitretin use has been associated with birth defects and liver damage. Systemic agents
Psoriasis resistant to topical treatment and phototherapy may be treated with systemic therapies including medications by mouth or injectable treatments. People undergoing systemic treatment must have regular blood and liver function tests to check for medication toxicities. Pregnancy must be avoided for most of these treatments. The majority of people experience a recurrence of psoriasis after systemic treatment is discontinued. Non-biologic systemic treatments frequently used for psoriasis include methotrexate, ciclosporin, hydroxycarbamide, fumarates such as dimethyl fumarate, and retinoids. Methotrexate and ciclosporin are medications that suppress the immune system; retinoids are synthetic forms of vitamin A. These agents are also regarded as first-line treatments for psoriatic erythroderma. Oral corticosteroids should not be used, for they can severely flare psoriasis upon their discontinuation.Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalized immunosuppressive medical therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis. These medications are generally well-tolerated, and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis. However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.Guidelines regard biologics as third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments.
Medications
Drug-induced psoriasis may occur with beta blockers, lithium, antimalarial medications, nonsteroidal anti-inflammatory drugs, terbinafine, calcium channel blockers, captopril, glyburide, granulocyte colony-stimulating factor, interleukins, interferons, lipid-lowering medications,: 197  and paradoxically TNF inhibitors such as infliximab or adalimumab. Withdrawal of corticosteroids (topical steroid cream) can aggravate psoriasis due to the rebound effect. Pathophysiology
Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin. Abnormal production of skin cells (especially during wound repair) and an overabundance of skin cells result from the sequence of pathological events in psoriasis. The sequence of pathological events in psoriasis is thought to start with an initiation phase in which an event (skin trauma, infection, or drugs) leads to activation of the immune system and then the maintenance phase consisting of chronic progression of the disease. Skin cells are replaced every 3–5 days in psoriasis rather than the usual 28–30 days. These changes are believed to stem from the premature maturation of keratinocytes induced by an inflammatory cascade in the dermis involving dendritic cells, macrophages, and T cells (three subtypes of white blood cells). These immune cells move from the dermis to the epidermis and secrete inflammatory chemical signals (cytokines) such as interleukin-36γ, tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-22. These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate. One hypothesis is that psoriasis involves a defect in regulatory T cells, and in the regulatory cytokine interleukin-10.