Managing Severe Psoriasis


Psoriasis is a common inflammatory and proliferative skin disorder with marked tender plaques topped with a silvery scale. Psoriasis is common, with a prevalence of 1.5-3% in most ethnicities; it is a chronic, persistent condition of variable severity with a relapsing-remitting course. The exact cause of psoriasis is unknown, but it may be a T-cell mediated autoimmune disease.

Assessing severity involves measuring the physical extent of the disease and level of disability – both practical and psychological suffered. Discordance often exists between the patient’s clinical symptoms and level of distress. Psoriasis patients report decreased quality of life similar to cancer and other chronic diseases.

No psoriasis cure exists; treatments include phototherapy; photosensitive drugs plus phototherapy; and systemic treatments – including biologics. Tailoring treatment depends on individual symptoms and level of disability, and aims to improve quality of life.

Phototherapy – ultraviolet B or photochemotherapy using ultraviolet A – alters the immune response. The main adverse effect of ultraviolet B irradiation is redness of the skin; reports remain unproven of an increased incidence of skin cancers. PUVA – a photosensitising agent (psoralens) plus ultraviolet A irradiation- induces complete or partial control of symptoms in 70% or more patients. Two methoxy-psoralen compounds are given – 8-MOP and 5-MOP – either taken orally or by bathing the plaques. 8-MOP is used more often; it the patient suffers nausea it is substituted by 5-MOP.

PUVA is not given long-term because of an associated increased risk of skin cancer; only ten courses of treatment are recommended. Protective glasses are worn for a day after taking psoralen treatment to prevent eye damage.

Low-dose methotrexate is a cheap and effective treatment for sever psoriasis. Nausea is the most common adverse event, but this can be prevented by also giving folic acid. Liver and bone marrow damage can occur, so careful monitoring of the patient’s blood profile is required. If the patient is taking certain antibiotics or has kidney damage while on methotrexate, then bone marrow damage can be acute. Women taking methotrexate should not conceive because of the risk of foetal damage.

Ciclosporin is a fast and effective treatment, but it can cause hypertension and kidney damage.Ciclosporin suppresses the immune response and may increase risk of cancer. Women on ciclosporin should undergo regular cervical smears. Limiting UV exposure is recommended; as are regular dental checks for gingival hyperplasia.

Low doses of acitretin – a second-generation retinoid – is a esafe, effective treatment for psoriasis and well tolerated. Damage to the skin and mucous membranes is common, including conjunctivitis, hair loss and inflammation of the lips. Retinoids affect liver enzymes and blood lipids; toxic reactions are rare. Pregnant women should not take retinoids and women advised not to conceive until two years after stopping treatment.

Retinoids and PUVA act in concert, and are given together to reduce the dose of ultraviolet A irradiation required.

Hydroxyurea inhibits DNA synthesis in proliferating cells and is reported to be effective in treating psoriasis. It is very slow to act and given as a trial for at least 8 weeks.

Immunosuppression occurs as bone marrow cells are suppressed and immune cells in the blood are depleted. Anaemia is uncommon. Blood cell counts are monitored and if levels fall too low the treatment changed. Advise women to wait until six weeks after stopping treatment to conceive.

Half of patients taking fumaric acid esters achieve a 75% improvement in psoriasis in four months. Over 60% of treated patients experience gastrointestinal problems, including abdominal pain, nausea and diarrhoea. Flushing occurs in one-third and can last from minutes to hours. Monitoring blood cell counts, renal function and liver chemistry is recommended.

Two classes of biologic agent are currently in use for treating psoriasis – those that alter cytokine production – TNFα inhibitors – and those that target T cells – efalizumab.

TNFα plays a key pro-inflammatory role in psoriasis. Membrane bound receptors – p55 and p75 – mediate TNFα activity. When released into the circulation,they bind excess TNFα and limit the inflammatory response.

Etanercept – a fusion protein of human immunoglobulin and two soluble p75 receptors – binds circulating TNFα. Given etanercept, 49% of patients achieve a 75% improvement in twelve weeks. Injection site reactions, occur in one third of patients, are usually mild, occur early in treatment and resolve with repeated injections.

Infliximab – a monoclonal antibody (a chimera of human constant and mouse variable regions) – forms stable complexes with soluble and membrane-bound TNFα.Infliximab is rapid-acting and highly effective; 87% of patients get a 75% improvement at 10 weeks. The presence of murine sequences can provoke antibodies causing infusion reactions and reduced efficacy.

Adalimumab – a fully humanised monoclonal antibody – binds  to both soluble and membrane-bound TNFα. On adalimumab, 80% of patients achieve a 75% improvement in 12 weeks.

All three anti-TNFs increased risk of infection (especially TB), exacerbate heart failure, and worsen multiple sclerosis and hepatitis. Antinuclear antibodies and a lupus-like syndrome can develop.

Efalizumab – a recombinant human monoclonal to lymphocyte function associated antigen-1 –  blocks T cell activation, trafficking and adhesion. Efalizumab is less effective than anti-TNFs. Headaches, flu-like symptoms, skin rashes and thrombocytopenia can occur. Disease can flare when treatment is withdrawn. Efalizumab does not increase the risk of infection or malignancy.

Treating severe psoriasis effectively involves choosing the best treatment for individual patients,. In the future, improved understanding of the processes involved in psoriasis may result in new medicines.

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