 Management—Generalized Plaque Psoriasis
General Principles When quantifying disease severity, it is important to consider both the extent of body surface involvement as well as impact on a patient's quality of life. Even mild disease can warrant systemic therapy if it is causing significant disruption in daily life and/or employment. Treatment should aim to clear psoriatic plaques and improve quality of life. Choice of systemic treatment should be individualized and take into account the patient's medical history, current medications, as well as extent of psoriasis and comorbidities such as psoriatic arthritis.
Topical Therapy For extensive psoriasis, topical therapy alone becomes less effective, more expensive, time consuming, and labor intensive, but is often continued alongside phototherapy or systemic therapy.
Phototherapy The observation that most cases of psoriasis improve with sunlight has led to the development of various methods to deliver UV light artificially. UV treatment is used for extensive and widespread moderate to severe plaque psoriasis that is not responding to topical treatment and is often combined with topical treatments. Phototherapy works by reducing epidermal hyperproliferation, reducing angiogenesis, and acting as an immunosuppressor. The two forms of UV light that are used clinically are UVB and UVA.
Narrowband UVB Narrowband UVB is now more widely used. It uses a fluorescent bulb with a narrow emission spectrum that peaks at 311 nm (UVB spectrum, 290 to 320 nm). The selective and relatively longer wavelength is more effective, clears psoriasis faster, produces longer remissions than broadband UVB, and has less risk of burning than broadband UVB. There is no evidence of increased risk of skin cancer from UVB treatment for psoriasis. Narrowband UVB is an alternative to treatment with oral psoralen plus topical UVA (PUVA; see section on UVA treatment below) and is safer over the long term.
Excimer Laser UVB This laser device delivers high-dose light at 308 nm via a hand piece with a spot size that is less than 2 cm2 and is best used for localized plaques. A single excimer treatment can induce a moderately long remission.
UVA UVA irradiation uses light with wavelengths of 320 to 400 nm. PUVA is the administration of UVA with psoralen, a photosensitizing agent. The combination results in enhanced phototoxicity and is more effective than either component alone. The most commonly used psoralen is 8-MOP (methoxsalen) which can be administered orally or topically. PUVA interferes with DNA synthesis, decreases cellular proliferation, and induces apoptosis of cutaneous lymphocytes, leading to localized immunosuppression. Studies have indicated a link between PUVA therapy and the development of squamous cell and basal cell carcinomas and possibly malignant melanoma. Adverse effects of PUVA therapy include nausea (from oral psoralens), pruritus, and a burning sensation.
Advantages Regular UVB phototherapy has been shown to induce disease remission in more than 80% of patients. Unlike biologics and oral immunosuppressants, phototherapy lacks serious systemic risks such as nephrotoxicity, hepatotoxicity, tuberculosis, and malignancy. Both PUVA and UVB can be combined with oral retinoid derivatives (RePUVA or ReUVB) to decrease the cumulative dose of UV radiation to the skin as well as the dosage of retinoid. Home UVB units are available that allow for treatments in patient's own home. The excimer laser is selectively directed toward lesional skin sparing the surrounding normal skin from unnecessary radiation exposure.
Disadvantages Time commitment required for treatments is 2 to 3 visits per week. May be expensive (if not covered by patient's insurance). Lack of accessibility of phototherapy equipment. An increased sensitivity to sunlight or sunburn may result, and there is a theoretical risk of cataracts if the eyes are left unprotected. An average of 30 treatments is often required to reach maximum improvement of psoriatic lesions.
Systemic Therapy Methotrexate, cyclosporine, oral retinoids, and biologic therapies all have helped induce and maintain remission in severe, widespread plaque psoriasis. Methotrexate, as well as several of the biologics (see below), is effective in treating both skin disease and joint disease. Biologics are often introduced while the other systemic agents are gradually tapered.
Methotrexate This antimetabolite inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in tissues with high rates of turnover, such as those found in psoriatic plaques. Methotrexate should be considered as an option for the treatment of extensive chronic plaque psoriasis, erythrodermic psoriasis, or generalized pustular psoriasis. Dosage: Methotrexate is often prescribed in a low-dose weekly regimen. The initial adult dose is 2.5 to 7.5 mg/week PO (can also be given IM) as a single dose or administered in three doses over a 24-hour period, then titrated to a dose between 12.5 and 25 mg/week, depending on the clinical response. Folic acid 1 mg daily should be taken on nontreatment days.
Advantages It may be administered orally, intramuscularly, or subcutaneously. It is effective for psoriatic arthritis. Inexpensive.
Disadvantages The main limitation of methotrexate is hepatotoxicity. Therefore, complete blood counts and regular liver and renal function blood tests should be monitored. Liver enzymes cannot be relied on to monitor liver health, because bridging necrosis can occur in the presence of normal liver enzymes. Liver biopsy is recommended after a total of 1.5 g of methotrexate has been taken. Many drug interactions are possible. Long-term, continuous use may lead to myelosuppression and carcinogenicity. Side effects include nausea, abdominal pain, headache, and fatigue and more serious problems such as hepatoxicity and leukopenia.
Acitretin is in the retinoid family of drugs related to vitamin A. The mechanism of action in treating psoriasis is unknown, but it has antiproliferative, anti-inflammatory, and antikeratinizing effects. In addition, it inhibits neutrophil chemotaxis. Dosage:
Advantages Acitretin should be considered as an option for the treatment of palmoplantar, erythrodermic, or generalized pustular psoriasis. Useful in combination with UVA (RePUVA) and UVB (ReUVB).
Disadvantages Acitretin is a teratogen and is absolutely contraindicated in pregnancy, in women who are likely to become pregnant, intend to become pregnant within 3 years following cessation of treatment, or in those women who cannot use reliable contraception while undergoing treatment (and for at least 3 years after discontinuation). Side effects are numerous: Cheilitis is seen in virtually all patients taking retinoids. May cause lipid elevation, muscle weakness, myalgias, hair loss, nail changes, skin fragility, premature epiphyseal closure or calcification, and ossification of ligaments and tendons.
Cyclosporine (Neoral, Sandimmune) Cyclosporine suppresses humoral immunity and, to a greater extent, cell-mediated immune reactions, such as delayed hypersensitivity. The drug acts by inhibiting production of interleukin 2, the cytokine responsible for inducing T-cell proliferation. Dosage: Initially, 2 to 5 mg/kg/day PO in divided doses. After control is achieved, maintenance therapy is continued at lower doses.
Advantages Remission is quite rapid for severe, uncontrollable psoriasis. Cyclosporine is mostly useful for short-term treatment of significant exacerbations.
Disadvantages Lesions tend to recur within days to weeks after treatment is stopped, and “rebounds” with worse symptoms than before treatment are often seen with abrupt cessation. Many drug interactions are possible. Evaluation of renal and liver functions should be performed often by measuring blood urea nitrogen, serum creatinine, serum bilirubin, and liver enzyme levels. Frequent monitoring of blood pressure is also necessary. Risk of myelosuppression, infection, and lymphoma may be increased. Side effects include nephrotoxicity and hypertension. Hirsutism and gingival hypertrophy have also been reported.
Apremilast is a phosphodiesterase-4 inhibitor and is the latest oral medication approved for the treatment of moderate to severe plaque psoriasis or active psoriatic arthritis in patients >18 years old. Dosage: Start at 10 mg and increase by 10 mg daily to 30 mg twice daily. Lower dosage for those with renal impairment. Common side effects are: Other considerations and possible contraindications: pregnancy and breastfeeding, depression and suicidal ideation, and kidney problems.
The use of a rotational approach with the various systemic agents can minimize the toxic effects of long-term treatment with any one of them. For example, the use of agents such as UVB, PUVA, methotrexate, acitretin, or cyclosporine, which are reserved for more severe, extensive psoriasis, can also be rotated; for example, one treatment may be used from 12 to 24 months and then another modality may be used. On clearing of the condition, treatment is stopped until the psoriasis recurs, at which point another agent is used.
The Biologics Biologics are designed to target a specific cell surface receptor, cytokine or other molecule thought to be important in the pathogenesis of a particular disease. In recent years, there has been a surge in the development of targeted biologic therapeutic agents for psoriasis and psoriatic arthritis. Currently, the biologic strategies to treat psoriasis are TNF- blockade, and antagonism of IL-12/23 and IL-17.
Etanercept is a fusion protein containing the human TNF receptor bound to the Fc portion of human immunoglobulin G (IgG) antibody. It acts by binding and inhibiting TNF from binding to any cell surface receptors. Etanercept is administered as a subcutaneous (SC) injection and recommended dosing is 50 mg twice weekly for 3 months, then 50 mg weekly.
Advantages Can be given at home. Prevents bony erosions in patients with psoriatic arthritis. Leads to tuberculosis activation less commonly than infliximab and adalimumab (see below). Effective for generalized plaque psoriasis, recalcitrant palmoplantar psoriasis, and generalized pustular psoriasis as well as psoriatic arthritis.
Disadvantages May result in injection site reactions. Some patients will require twice-weekly dosing indefinitely to maintain satisfactory control. Side effects (common to all TNF- inhibitors): increased risk of serious infections including TB and hepatitis B reactivation, exacerbation or new-onset congestive heart failure or multiple sclerosis, rarely drug-induced lupus, lymphoma has also been reported.
Adalimumab (Humira) Adalimumab is a recombinant fully humanized IgG1 monoclonal antibody that binds to TNF- and can lyse cells that express TNF- on their surface. Indicated for psoriasis and psoriatic arthritis. Adalimumab is administered as a SC injection and dosed as an 80-mg injection on day 1 followed by 40 mg SC on day 8, then 40 mg SC every other week.
Disadvantages May result in injection site reactions. Rare reports of lupus-like symptoms and multiple sclerosis. Increased risk of infections including TB and hepatitis B reactivation. Heart failure (new or worsening).
Infliximab (Remicade) Infliximab is a chimeric monoclonal antibody that targets TNF- and inhibits its activity. Infliximab is indicated for the treatment of psoriatic arthritis and plaque-type psoriasis. It is administered via IV infusion at specialized infusion centers. For psoriasis, dose is weight based and typically a dose of 5 mg/kg is given at 0, 2, and 6 weeks and then every 8 weeks thereafter.
Disadvantages Administered intravenously at an infusion center. Requires monitoring of platelet counts and liver function studies. Common infusion reactions: pruritus, hives, nausea, and headache. Contraindications: congestive heart failure class III or IV. Same side effects listed under etanercept.
Ustekinumab is a human monoclonal antibody that binds to IL-12 and IL-23 and neutralizes their activity. Ustekinumab is administered by SC injection in a physician's office at weeks 0, 4, and then every 12 weeks. Dosing for ustekinumab is weight based: >220 lb (100 kg) receive 90 mg, <220 lb receive 45 mg on week 0, a second injection 4 weeks later, and then one injection every 12 weeks.
Secukinumab (Cosentyx) Secukinumab is a fully human anti-interleukin-17A monoclonal antibody. Indicated for moderate-to-severe plaque psoriasis in patients who are candidates for systemic therapy. Administered by SC injection; 300 mg at weeks 0, 1, 2, 3, and 4; then, 300 mg monthly beginning at week 8. For some patients, a dose of 150 mg may be acceptable.
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Differential Diagnosis