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In the United States, the incidence of psoriasis is 1% to 3%; it can affect persons of any age, although onset is usually during young adulthood.1,2 The disease may erupt on any area of the body, including the nails (see Figure 1 in the Photo Essay on page 810), but it most commonly appears on the elbows and sacrum (see Figure 2 on page 810). It is sometimes associated with a seronegative arthritis. The principal variants of psoriasis are listed in Table 1.

Psoriasis is a lifelong condition characterized by chronic remissions and recurrences. The goals of therapy are to improve the patient's appearance and quality of life and to induce remission. In this article, I review the principal topical and systemic treatments of psoriasis (Table 2).DIAGNOSIS

The first step in management is to verify the diagnosis. Psoriasis typically appears as well-defined reddish lesions with silvery scaling papules and plaques. Conditions that may mimic psoriasis include nummular dermatitis, parapsoriasis, subacute lupus erythematosus, pityriasis rubrapilaris, tinea corporis, squamous cell carcinoma, lichen simplex chronicus, and secondary syphilis.

Although in most cases the diagnosis may be made clinically, diagnostic tests are sometimes appropriate. For example, the lesions of guttate psoriasis (see Figure 3,page 811) are smaller than those of plaque psoriasis and may resemble the lesions of secondary syphilis or pityriasis rosea; however, results of an antistreptolysin-O titer (ASOT) are usually positive for psoriasis. Tests that may help establish a diagnosis of psoriasis and ex- clude other conditions include biopsy, fungal culture, antinuclear antibody and rapid plasma reagin tests, and ASOT.TREATMENT

Topical agents. A variety of therapies are effective for psoria- sis.1-20 The mainstays of topical treatment are corticosteroids, which are available in many vehicles and potencies (Tables 3 and 4).Ointments are preferred because they adhere better than creams and are therefore more potent.5

Corticosteroids are most predictably effective for limited disease and are useful for reducing inflammation. Rotational therapy with topical calcipotriene and corticosteroids is particularly effective and generally safe for long-term treatment. Another advantage of rotational therapy is that tachyphylaxis is avoided. Corticosteroids are less consistently effective for widespread disease and in this setting are best used in conjunction with systemic therapies.

Corticosteroids. The strength of these agents ranges from class 7 (very low potency, such as over-the-counter 1% hydrocortisone) to class 1 (ultra-high potency, such as clobetasol propionate). A class 1 corticosteroid is 1000 to 1500 times stronger than a class 7 corticosteroid.8,20

Initial treatment of mild to moderate plaque psoriasis (see Figure 4, page 812) consists of twice-daily applications of a high-potency corticosteroid (eg, clobetasol propionate, halobetasol propionate, betamethasone dipropionate in an optimized base, or diflorasone diacetate in an augmented base) plus calcipotriene ointment (a derivative of vitamin D). Combination therapy is generally more effective than single-agent treatment. Lesions often resolve in about a month with this regimen, but quickly return once treatment is discontinued.

If combination therapy is successful, patients can switch to a maintenance regimen that consists of calcipotriene twice a day on weekdays and a high-potency corticosteroid twice a day on the weekends. This treatment can be continued indefinitely.

If the corticosteroid-calcipotriene combination does not produce substantial improvement in 2 months, tazarotene cream (a topical retinoid) can be added. With this triple combination, the patient uses a mix of corticosteroid and tazarotene at night and the corticosteroid and calcipotriene during the day.

Topical treatments are preferred for psoriasis that covers less than 5% of the patient and for areas that the patient can reach. If the patient's progress is satisfactory,I substitute a lower-potency corticosteroid or instruct the patient to use the corticosteroid only on weekends.

Topical corticosteroids may produce atrophy and striae and, rarely, cause adrenal suppression. The most common side effect of calcipotriene or tazarotene therapy is an irritant contact dermatitis at the site of application.

High-potency corticosteroids are not recommended for facial psoriasis. Instead, hydrocortisone valerate 0.2% cream, twice a day for 2 weeks, may be tried; a topical immunomodulator, such as tacrolimus or pimecrolimus, may be added if needed. In the groin or axilla (as in so-called inverse psoriasis), I prefer to use tacrolimus or pimecrolimus alone because they do not cause striae or atrophy.

For thick, scaly plaques on the scalp, fluocinolone acetonide 0.1% topical oil may be rubbed in and covered with a shower cap at night. This is washed out with a tar shampoo in the morning, followed by an application of clobetasol propionate foam once a day.5

Noncorticosteroidal agents. These are sometimes used in addition to corticosteroids. Salicylic acid can break up thick, scaly, rough, or fissured plaques. It is not advisable to scrape off scale because of the Köbner phenomenon,whereby psoriasis arises at sites of trauma. Petroleum jelly that contains 2% to 10% salicylic acid may be used with topical corticosteroidsto improve penetration. Salicylic acid tends to neutralize calcipotriene, so these agents should not be used together.5

Coal tar and anthralin (dithranol) are effective antipsoriatic agents; they are inexpensive, relatively free of side effects, and safe for use on large areas of the body. However, these agents have an offensive smell, are irritating, and stain clothing. They are probably best reserved for motivated patients in whom other topical agents have been ineffective.1-7

Systemic treatment. If the eruption covers more than 5% to 10% of the body, consider systemic treatment. Modalities include phototherapy, oral retinoids, cyclosporine, methotrexate, and biologic agents. Use these treatments with caution because they may have side effects or interact with other agents; for example, methotrexate must not be given with trimethoprim-sulfamethoxazole. Alternatively, refer patients to a dermatologist who is experienced in the use of these agents.

Phototherapy. Narrowband UV-B (NB UVB) is effective, has a good safety profile, does not require adjunctive oral medication, and is unlikely to induce skin cancer. The ultraviolet frequency of NB UVB encompasses the sunburn spectrum wavelength of 311 ± 2 nanometers (nm)and offers a significant therapeutic advantage over broadband UV-B (BB UVB, 300 to 320 nm). Disease resolution of more than 80% is achieved after 6 weeks of treatment with NB UVB, compared with 24% to 73% with BB UVB.21

Both NB UVB and oral psoralen and UV-A (PUVA) treatments are highly effective. NB UVB treatments 3 times a week are about as effective as PUVA treatments twice a week.21NB UVB and PUVA can induce remission of psoriasis, whereas BB UVB is less likely to do so. NB UVB is significantly more intense than BB UVB; the initial dose of UV-B is determined by minimum erythema dose testing and close clinical observation during dosage increases.21

PUVA can induce remissions that last for months.22-24 It combines psoralen with UV-A in the range of 320 to 400 nm. Psoralen is given in a dose of 0.6 mg/kg 2 hours before UV-A exposure. PUVA induces clearing in most patients. The therapeutic schedule typically consists of 2 outpatient treatments per week for 10 weeks. This is followed by maintenance treatments that can be as infrequent as once every 2 to 4 weeks, with eventual discontinuation. Short-term side effects include nausea, sunburn, and pruritus in 10% to 20% of patients. There is a small increased risk of squamous cell carcinoma with long-term treatment.

Oral retinoids. When phototherapy alone does not produce optimal results, acitretin--the active metabolite of etretinate, an oral retinoid--may be added. This agent is approved for the treatment of moderate to severe psoriasis.25Acitretin combined with BB UVB, NB UVB, or PUVA is more effective than acitretin alone. The typical dosage of acitretin is 25 mg/d. The patient's lipid level and liver function must be monitored monthly.

Acitretin is contraindicated in women of childbearing age because it causes birth defects; women are advised not to become pregnant for 3 years after using it. Other adverse events associated with acitretin are mucocutaneous effects, such as cheilitis, conjunctivitis, hair loss, nail-plate abnormalities, and dry skin. Periungual pyogenic granulomas may develop, but these usually resolve with dose reduction. Systemic side effects include osteoporosis, calcification of ligaments, and skeletal hyperostosis.

The combination of a topical agent, such as tazarotene, with UV-B or PUVA is also effective.22

Methotrexate. This folic acid antagonist inhibits dihydrofolate reductase, an enzyme necessary for nucleotide and amino acid synthesis. It is a potent alternative for patients with moderate to severe psoriasis that is unresponsive to topical treatment or phototherapy. It is particularly effective for psoriatic arthritis, psoriatic erythroderma, and pustular psoriasis (see Figure 5, page 812 ).26-28 After a test dose of 5 mg, methotrexate is started at 2.5 mg every 12 hours for 36 hours. The dosage is increased by 2.5 mg a week to a maximum dosage of 15 to 30 mg (given every 12 hours 3 times a week).

Methotrexate, which is renally excreted, is immunosuppressive, hepatotoxic, and teratogenic. Patients who use methotrexate must have normal hematologic status and renal and liver function before therapy is initiated. This agent must be avoided in alcoholics and pregnant women. Liver function and blood count must be monitored during methotrexate therapy. The total dosage of the medication is tracked, and a liver biopsy is done after 1 to 1.5 g. Folic acid, 1 to 5 mg/d, is recommended to reduce the risk of hematologic side effects. Methotrexate is not used with phototherapy because of the increased risk of skin cancer.

The most serious short-term side effect of methotrexate is bone marrow toxicity, which can result in particular from concomitant use of trimethoprim-sulfamethoxazole or medications--such as NSAIDs--that synergistically reduce renal clearance of methotrexate. Other side effects include mucosal ulceration or stomatitis, nausea, macrocytic anemia, and pulmonary toxicity.26-28

Cyclosporine (Neoral or Gengraf). This agent suppresses proliferation of activated T cells and inhibits the synthesis of proliferative cytokines.28-30 It is indicated for the treatment of recalcitrant plaque psoriasis in patients who have failed to respond to other systemic therapies or for whom other therapies are contraindicated or intolerable. The usual dosage is 3 to 5 mg/kg/d. It is as effective as higher doses of methotrexate. It may be a good choice in patients who need quick results (eg, for an upcoming wedding). Discontinuation involves tapering the drug by 1 mg every week or every other week.

Short- and long-term side effects of cyclosporine limit its use. Short-term effects include headaches, paresthesias, hypertrichosis, GI disturbances, gingival hyperplasia, hypertension, hyperlipidemia, nephrotoxicity, and electrolyte disturbances. Long-term use may increase the risk of nephrotoxicity and cancer.29-30 Of 122 patients treated with cyclosporine for an average of 22 months in one study, 28% discontinued use because of renal failure and 19% because of hypertension.29 The risk of toxicity increases with age, duration of therapy, preexisting hypertension, and elevated serum creatinine levels.

Biologic therapies. These therapies are expensive ($10,000 to $20,000 a year) but appear to have fewer side effects than methotrexate or cyclosporine. They are more convenient than phototherapy because they can be injected at home or, for a period of weeks, in the office.31 Biologics may increase the risk of infection; because they are relatively new, their safety profile is not as well documented as that of other systemic agents. Agents in this class include etanercept,32,33 infliximab,34,35 efalizumab,36-39 alefacept,40,41 and adalimumab.42

I generally reserve biologics for patients who cannot come into the office for phototherapy at least twice a week or for whom other systemic treatments have failed. A review of treatment with biologics is given in Tables 5 and 6.

Etanercept, a tumor necrosis factor (TNF)-a blocker, is the most frequently used biologic agent; it effectively treats psoriatic arthritis as well as psoriasis. The usual starting regimen is 50 mg twice a week by subcutaneous injection for 2 to 3 months, then 25 mg twice a week until the lesions have resolved, at which point treatment is discontinued.

Infliximab, another anti-TNF agent, is given intravenously. It is the most effective single agent for the treatment of psoriasis, but it increases the risk of infection and lymphoma more than the other biologics and is reserved for refractory cases.

Efalizumab is fast-acting and, unlike infliximab, adalimumab, and etanercept, has not been linked to rare adverse events of heart failure, neurologic problems, reactivation of tuberculosis, or lymphoma. However, it can cause rebound psoriasis when discontinued.

Alefacept is a recombinant, fully human fusion protein that selectively targets the memory T cells implicated in the pathogenesis of psoriasis. It is given by intramuscular injection weekly for 12 weeks and can induce remissions that last 6 months or more.

Adalimumab is a fully human TNF-a monoclonal antibody that has been approved for the treatment of rheumatoid arthritis as monotherapy or in combination with methotrexate. It is administered by subcutaneous injection in a 40-mg dose every other week. It is in phase 3 studies for the treatment of psoriasis.

Because all of the biologics are new, referral to a dermatologist or rheumatologist familiar with their use and side effects is indicated.


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