There clearly is no treatment of choice in the management
of psoriasis. Many new modalities have
been described recently, such as vitamin D, fish oil, and cyclosporine. At this point, these therapies should be considered investigational. Medical officers are advised to consider first the more traditional, time-honored modalities available.
No treatment is without side effects. The risks for adverse side effects can often be reduced by combination therapy, such as retinoids combined with psoralen and UV-A (PUVA). The advantage of combination therapy is that the cumulative dose of each agent is diminished. Thus, while the beneficial effects may be additive, the adverse effects are
usually decreased. Furthermore, when approaching the treatment of psoriasis, one must realize that the aim of treatment should not be to obtain complete clearing. That is often an unrealistic approach in the management of psoriasis. Complete clearing is often unattainable without experiencing significant toxicity. Realistic expectations by the physician as well as the patient are perhaps the most important aspects of therapy.
Topical Corticosteroids
Topical corticosteroids are frequently employed
in the management of psoriasis and can be quite beneficial. Due to a potent antiinflammatory effect and inhibition of deoxyribonucleic acid (DNA) synthesis (with a subsequent antiproliferative effect), topical steroids are a logical and effective modality in this disease. Intralesional steroids may be considered considered
for isolated or resistant plaques. The limiting factor for topical corticosteroids is epidermal and dermal atrophy, which can result in marked thinning of the skin and striae formation. More importantly, sustained use of potent topical steroids can lead to suppression of the hypothalamic-pituitary-adrenal axis. Pulse dosing may permit extended maintenance with potent topical steroids while limiting adverse effects. Another drawback to consider regarding steroid therapy is the development of tachyphylaxis. For these reasons, one is encouraged to consider alternative topical agents for the treatment of psoriasis.
Anthralin
Anthralin is a synthetic anthrone derivative that reduces mitotic activity and suppresses free radicals. It is widely used in Europe as an integral
component of the Ingram regimen, which consists of a daily coal tar bath followed by suberythemogenic UV-B exposure, then the application of dithranol paste of gradually increasing concentration. Although this method is quite effective and
safe, it is cumbersome. For this reason, short-contact anthralin treatment plans have been devised, frequently with the addition of coal tar to diminish the irritancy of anthralin, which can limit its use. Due to its lack of systemic toxicity, carefully supervised anthralin therapy combined with thorough patient explanation and education is an ideal modality for the treatment of chronic plaque-type psoriasis.
Coal Tar
Coal tar has been widely employed in the treatment of psoriasis for more than a century. It is a complex mixture of over 10,000 substances, which
may possess antimitotic activity. The tar is reapplied after bathing. Coal tar is an extremely safe agent. The most frequent side effect is a tar-induced folliculitis. There
have been reports of skin cancers associated with coal tar application; however, this is an uncommon event, and such case reports usually involve patients who have been exposed to multiple other skin cancer–inducing agents.
Systemic Methotrexate
Methotrexate, given in weekly oral doses of 5 to
25 mg, is an extremely valuable agent for treating severe psoriasis and psoriatic arthritis that are not adequately controlled by more conventional therapies. It is a folate antagonist that exerts its antiproliferative effect on psoriatic epidermal cells
by directly inhibiting DNA synthesis. Methotrexate is absolutely contraindicated in
pregnant or lactating females. Relative contraindications are many, including liver or renal abnormalities, excessive alcohol consumption, and anemia, leukopenia, and thrombocytopenia. Guidelines for appropriate use of methotrexate in psoriasis are
published periodically by the Psoriasis Task Force of the American Academy of Dermatology.Medical officers should be thoroughly knowledgeable with these guidelines before considering methotrexate for the treatment of psoriasis. The greatest limitation of methotrexate is its hepatotoxicity. For this reason, newer folate antagonists with perhaps fewer effects on the liver are being investigated.
Systemic Retinoids
The retinoids are synthetic derivatives of vitamin
A and vitamin A acid. The effects of vitamin A and vitamin A analogs on the growth and terminal differentiation of epidermal cells and the vitamin's beneficial effect on disorders of keratinization have long been known. Retinoids have been shown to affect growth of epidermal cells by altering keratin synthesis and formation of the cell envelope.
Etretinate (0.5–1.0 mg/kg/d) is the retinoid approved for use in the treatment of psoriasis. It should be considered for initial treatment in the management of pustular psoriasis or erythrodermic psoriasis. It is also beneficial for the patient with
extensive plaques and severe involvement recalcitrant to more conventional modalities and has been successful in clearing acrodermatitis continua of Hallopeau. Etretinate has significant risk for adverse effects including teratogenicity, elevation of serum lipids,
liver toxicity, and numerous mucocutaneous side effects. In addition, cases of skeletal hyperostoses have been documented with long-term use. Furthermore, it is known to be stored in adipose tissue for long periods, thus leading to a prolonged halflife
(> 100 d).
In fact, blood levels are detectable for more than 2 years after discontinuation of
therapy. For these reasons, in addition to its potent teratogenicity, etretinate is best avoided in women of child-bearing potential. Alternatives include isotretinoin and, once available, acitretin—the main metabolite of etretinate—which has been shown to
be effective in treating psoriasis and has a much shorter half-life (50 h for acitretin vs 120 d for etretinate). Because the side effects of acitretin are similar to those of etretinate, including potent teratogenicity, effective contraception is essential for
women and long-term use is discouraged. Because risks are greatly increased with long-term use of retinoids, they are probably best used in combination with other modalities such as phototherapy.
Ultraviolet-B Phototherapy
Natural sunlight has long been known to improve
psoriasis. An excellent (and more reliable) substitute is an artificial light source that produces light primarily in the ultraviolet-B (UV-B) range (290–320 nm). This allows for continuous monitoring and metered delivery of UV radiation, thus diminishing the potential for accidental overexposure and burning. Although the mechanism of the therapeutic effect is unknown, UV-B alone or with coal tar is an excellent method for clearing psoriasis
and maintaining remission. Its use should be considered early in the course of management.
Psoralen and Ultraviolet-A Phototherapy
Introduced in 1974 by Parrish and Fitzpatrick, PUVA phototherapy has gained worldwide acceptance in the treatment of psoriasis. Patients ingest a specific dose of methoxsalen (consult chart in
package insert for precise dosage based on weight), followed in approximately 90 minutes by a carefully metered UV-A (320–400 nm) exposure, which is increased with progressive treatments. Initially, Oxsoralen was the drug employed. This has now been replaced by Oxsoralen-Ultra (methoxsalen, manufactured by ICN Pharmaceuticals, Inc., Costa
Mesa, Calif.), a liquid form in a gel capsule that provides more uniform serum drug levels. Patients are treated two to three times per week, and generally respond within 20 to 25 treatments. PUVA can then be continued and gradually tapered to maintain prolonged remission. PUVA exerts its effect through the production of bifunctional DNA adducts and subsequent inhibition of DNA synthesis and epidermal cell replication. It is an excellent modality for managing severe psoriasis on an outpatient basis. However, it
is not without risk. Patients must wear protective eyewear (wraparound UV-A filtering glasses) for 24 hours after ingestion of the drug to prevent cataracts. It has been well documented that PUVA is clearly associated with an increased risk for nonmelanoma skin cancer, particularly squamous cell carcinoma.
Ninety percent clearing is, generally, much easier to attain and maintain at far less
risk, and this is usually quite acceptable to the patient. Clearly, PUVA should not be used unless the patient’s psoriasis is severe. While PUVA-induced squamous cell carcinoma has little potential for metastatic spread, all patients receiving PUVA must be carefully monitored to ensure early detection and prevention of disfigurement. All men should shield the genital region during therapy, as this area has proven to be at particular risk for
developing PUVA-induced tumors. PUVA-associated carcinogenesis may possibly
be avoided by employing PUVA bath treatments using a trioxsalen solution. This technique has been used extensively in Europe and has been shown to be of equal efficacy58 to and probably safer than standard PUVA. This author has found a similar technique using a solution of Oxsoralen, as described by Coleman et al,61 to be extremely effective in the management of pustulosis palmoplantaris. All forms of PUVA may be combined with other
treatments such as retinoids to obtain superior results while diminishing adverse effects.