Therapy For the Treatment of Psoriasis

Diagnostic Presentation

Distribution: scalp, elbows, knees, gluteal fold

Koebner phenomenon

Nail pitting

Clinical hallmarks

Psoriasis is characterized by the presence of sharply marginated red plaques that are covered by copious amounts of white or silver scale. The scale is made up of fairly large flakes, some of which are large enough to grasp and strip off. Doing so may reveal underlying pinpoint spots of bleeding (Auspitz sign). Newly developed lesions are small (1- to 3-mm) papules but centrifllgal growth with coalescence of adjacent lesions results in the formation of large plaques some of which have a gyrate or serpiginous configuration.

Linear lesions are also often present. This linearity is a reflection of the Koebner phenomenon, wherein lesions preferentially arise at the site of cutaneous trauma. The Koebner phenomenon is highly distinctive, and it is found in only one other commonly encountered disease, lichen planus.

Lesions of psoriasis can occur anywhere on the body, but they are most commonly located on the scalp, elbows, and knees. The extensor surfaces of the arms and legs are also often involved. The presence of sharply marginated red plaques (with or without visible scale) in the gluteal fold and around the umbilicus is a very distinctive sign of psoriasis.

Nail changes are found in many patients. Early changes include nail plate pitting and onycholysis. Later changes include marked nail plate dystrophy and appreciable buildup of subungual, soft yellow keratin. The latter changes are very similar to those that occur in fungal infections of the nail, differentiation depends on KOH examination and fungal culture,

In most instances, the lesions of psoriasis are not pruritic, but those plaques that occur in the scalp and intertriginous folds are sometimes associated with considerable itching. A few patients, presumably those who are genetically atopic, will complain of generalized itching.

Atypical Clinical Presentatians

Very rarely the lesions in psoriatics become extensive enough to involve the entire body surface. In such instances, itching is often severe, and there is evidence of eczematization with weeping and crusting. Distinction from other forms of clinically similar exfoliative erythrodermatitis can be difficult unless certain features such as typical nail changes, seronegative arthritis, and a past history of more typical lesions, are present.

Children and young adults sometimes develop guttate psoriatics. This form of psoriasis is recognized by the sudden outbreak of hundreds of small, red, nonconf]uent papules. Scale fcmnation on these papules is often scanty. Plaque fcmnation is usually minimal, but a cardill search will usually reveal one or more slightly linear lesions as a result of the Koebner phenomenon. The appearance of guttate psoriasis is sometimes triggered by a preceding streptococcal infection. Children with guttate psoriasis sometimes experience long periods of complete remission after the initial episode has subsided.

Pustular psoriasis occurs in two forms that which involves primarily the palms and soles and is acompanied by nonpustular lesions of psoriasis elsewhere (barber type) and that which is completely generalized (Von Zurnbusch type). The latter often evolves into an exfoliative nythrodermatitis and is often accompanied by fever, anemia, Inlkocytosis, and general debilitation.

Course and Prognosis

Psoriasis is a lifelong, chronic disease characterized by exacerbations and remissions. Individual lesions tend to be in a constant state of flux. Plaques are continually growing, resolving, and changing in shape. The overall course of the disease is highly unpredictable. The patient's initial lesions after no clue as to the future course. Months of mild involvement may be followed by a period of severe flaring, halt sometimes the reverse occurs.

Little disability occurs as a result of the skin lesions, but "hout 10% of psoriatics develop arthritic changes. Many of these individuals will experience considerable pain and joint deformity,

Pathogenesis

The cause of psoriasis is unknown, but genetic factors play a role in the development of the disease. About 30% of psoriatic patients have a positive family history. Moreover, psoriatics share a significantly increased incidence of several HLA antigens. Immunologic factors are presumably also important (note the explosive development of psoriasis in some patients with acquired immunodeficiency syndrome (AIDS)), but no consistent explanation of specific immunologic abnormalities has as yet been elucidated.

Psoriatic lesions are characterized histologically by a remarkably expanded thickness of the epidermis (acanthosis) and by the presence of numerous neutrophils in the stratum corneum. The influx of these neutrophils is probably due to the presence of one or more leukotrienes (especially LTB4) with potent chemotactic properties within the stratum corneum.

The acanthosis with accompanying excess keratin production (hyperkeratosis) is most likely due to changes in epidermal cell kinetics. Specifically, the keratinocyte cell eycle is greatly shortened, and there is extraordinarily fast movement of cells from the basal layer to the stratum corneum. Finally, release of certain cytokines by these "activated" epidermal keratinocytes may well account for the multitude of lymphocytes that accumulate in the papillary dermis.

Therapy

Topical Therapy

Sunlight is beneficial to many patients with psoriasis. Some individuals can control their own disease solely with sunbathing. Traditionally, wide-band (280- to 320-nm) ultraviolet light (UYE) therapy has been offered through dermatologists' offices. There now is considerable interest in the use of narrow-band (310- to 313-nm) UVB as a way of decreasing potential oncogenic toxicity. UVA therapy (without psoralens) is less effective than UVB treatment. Nevertheless, some patients do use suntanning booths effectively.

Most patients, however, require additional therapy, such as intermittent use of the mid- and high-potency topically applied steroids. Where necessary, penetration of these topically applied steroids can be enhanced by the use of occlusive dressings, or alternately, individual lesions may be intralesionally injected with triamcinolone acetonide.

Topically applied tar products are also useful, but because of odor and appearance, these modalities are often not acceptable to patients. Historically, most tar therapy has been administered during hospitalization as part of the modified Goeckerman program. In this regimen, crude coal tar ointment is applied each day after UVB has been administered. The tar is reapplied several times during the day, but prior to the next day's UVB treatment, a bath is taken, and the tar products are washed off. This cycle is carried out for about 3 weeks, during which time most patients will have achieved a satisfactory remission. Such remissions can often be maintained for 4 to 8 months. The expense of hospitalization has led to an increased use of day care centers to provide this form of therapy.

Anthralin, a tar-like product, is gaining acceptance for home therapy. Initially, lowconcentrations (about 0.1%) are applied for 15 to 60 minutes; the anthralin is then completely washed off. If in'itation is not a problem, the concentration is gradually increased to 1 %. This "short application" program avoids much of the staining and odor problems associated with tars.

A topically applied analog of vitamin D3 (calcipotriol) is now available for use in some countries. Safety seems to be good, and efficacy is believed to approximate that of topically applied steroids.

Systemic Therapy

When the disease is more generalized PUVA therapy has become the treatment of choice. This Approach is remarkably effective in the treatment of psoriasis, but excellent efficacy is balanced by high cost, the need for continued maintenance treatment,and some toxicity in the form of an increased incidence of melanoma skin cancers and potential eye problems. Approximately 90% of patients can obtain complete clearing when PUVA treatments are given 2 or 3 times a week over a 2-month period. Thereafter, the frequency of treatments can be gradually reduced.

Inay require cytotoxic drugs. Methotrexate, the most widely used agent, is generally given orally in a weekly dose of 15 10 25 mg . Usually, 6 to 10 tablets (2.5 mg each) are taken in a single dose, but split schedule dosages may also be used. Improvement is noted within 4 to 8 weeks; 90% clearing is usually possible within 3 months. Maintenance Iherapy is then continued at the lowest possible dose. Short-term loxicity is not a major problem, but long-term hepatotoxicity is. For this reason, periodic liver biopsies are required. Methotrexate is discontinued when fibrosis is found. Fortunately, psoriatics receiving long-term methotrexate have shown no propensity for the development of nosocomial infection or drug-induced malignancies.

The role for retinoids in the treatment of psoriasis is less clear. Etretinate (Tegison) therapy can certainly be effective, but in my experience its use as monotherapy leads to acceptable clearing in only 40% to 50% of patients. Concern also remains about long-term toxicity, especially as regards hyperlipidemia and calcification in and around the spine. Increasingly, retinoids are being used in concert with PUVA therapy (RePUVA) in an attempt to increase efficacy and decrease toxicity. On the other hand, the short-term use of either etretinate or isotretinoin represents the treatment of choice for most patients with pustular psoriasis.

Cyclosporine administered orally in doses of 3 to 6 mg/kg is remarkably effective in the treatment of psoriasis. Unfortunately, toxicity, particularly renal damage, limits the usefulness of this approach. It is not currently approved by the Food and Drug Administration (FDA) for use in the treatment of psoriasis.

Treatment of the Scalp and Nails

The presence of scalp and nail disease presents special problems in the treatment of psoriasis. Scalp lesions sometimes respond to the use of a tar shampoo alone, but steroid lotions (fluocinonide, clobetasol, etc.) usually must also be applied. Penetration of the steroid solution can be enhanced, if necessary, by using shower cap occlusion at night. The presence of thick scale sometimes prevents adequate topical application. In such instances, softening solutions such as Baker's P & S or T-Derm solution can be applied along with the steroid lotion. Both are left on overnight. The softened scale is then appreciably easier to remove during the morning shampoo.

Local treatment of nail dystrophy is difficult if not impossible. Some authorities recommend the application of high-potency topical steroids with finger cot occlusion. Unfortunately, the onset of cutaneous atrophy often Occurs before normal nails have regrown. Alternately, the nail matrix can be injected with triamcinolone acetonide, but this approach is severely limited by patient discomfort. Methotrexate, retinoid, or PUVA therapy is often accompanied by clearing of the fingernails, but concerns about toxicity limit the applicability of these approaches for patients whose disease involves primarily the nails.

Treatment of Psoriatic Arthritis

The arthritis of psoriasis often improves when skin lesions are successfully treated. To the degree that this does not occur, consideration should be given to the use of methotrexate or retinoids. Symptomatic treatment with nonsteroidal anti-inflammatory agents (NSAIDs) is, of course, also carried out. There is at least theoretical concern, however, that these agents will displace methotrexate from its serum-binding protein and thus increase serum levels and consequent toxicity.