Psoriasis: Evolving treatment for a complex disease
ABSTRACTThe cutaneous manifestations of psoriasis can vary in morphology and severity, and therapy should be tailored accordingly. Biologic agents are important new options for treating patients with the most severe forms of the disease. All physicians should be aware that severe psoriasis may increase cardiovascular morbidity and the risk of death, and preventive strategies for patients with severe disease should be considered.
KEY POINTS
- Studies in the past 10 years have uncovered a link between psoriasis, metabolic syndrome, and cardiovascular disease. Interestingly, the risk grows less with age; patients at greatest risk are young men with severe psoriasis.
- The most common presentation of psoriasis is plaque psoriasis. However, there are several other clinical variations of psoriasis, each of which has a distinct response to treatment and may be associated with significant systemic symptoms.
- Tumor necrosis factor inhibitors should be considered first-line in the treatment of psoriatic arthritis.
- Phototherapy and systemic medications including methotrexate, acitretin (Soriatane), cyclosporine (Gengraf, Neoral, Sandimmune), and biologic agents are the most effective treatments for moderate-to-severe psoriasis.
PSORIASIS IS DIAGNOSED CLINICALLY
In most cases, the diagnosis of psoriasis is made clinically and is straightforward. However, in more difficult cases, biopsy may be needed. In particular:
- The plaques of psoriasis may be confused with squamous cell carcinoma in situ, dermatophyte infection, or cutaneous T-cell lymphoma, especially if they are treatment-resistant.
- Guttate psoriasis may be difficult to distinguish from pityriasis rosea.
- Erythrodermic psoriasis must be distinguished from other causes of erythroderma, including Sézary syndrome, pityriasis rubra pilaris, and drug reactions.
- Intertrigo, candidiasis, extramammary Paget disease, squamous cell carcinoma, and contact dermatitis all may mimic inverse psoriasis.
- Palmoplantar pustulosis may be difficult to differentiate from dyshidrotic eczema.
- Generalized pustular psoriasis should be distinguished from a pustular drug eruption (acute generalized exanthematous pustular drug eruption or acute generalized exanthematous pustulosis), impetigo, candidiasis, or an autoimmune blistering disorder such as pemphigus.
TREATMENT OF LIMITED DISEASE
,Topical corticosteroids
A topical corticosteroid, either by itself or combined with a steroid-sparing agent, is the first-line therapy for patients with limited disease. The potency required for treatment should be based on the extent of disease and on the location, the choice of vehicle, and the patient’s preference and age.
Several double-blind studies have assessed the efficacy of various topical corticosteroids in treating psoriasis. In general, super-potent (class I) and potent (class II) topical corticosteroids are more efficacious than mild or moderate corticosteroids.38 Class I and class II steroids include agents such as clobetasol propionate 0.05% (Temovate), betamethasone dipropionate 0.05% (Diprolene), fluocinonide 0.05% (Lidex), and desoximetasone 0.25% (Topicort).
Use of class I steroids should be limited to an initial treatment course of twice-daily application for 2 to 4 weeks in an effort to avoid some of the local toxicities such as skin atrophy, telangiectasia, and striae. Decreasing class I topical steroid use to 1 to 2 times per week with the gradual introduction of a steroid-sparing agent following the initial 2 to 4 weeks of treatment is advised.
Steroid-sparing agents
Steroid-sparing agents include vitamin D analogues, retinoids, and tacrolimus ointment (Protopic).
Vitamin D analogues and retinoids are thought to decrease keratinocyte proliferation and enhance keratinocyte differentiation.39 The vitamin D analogues are also considered first-line topical agents and include calcipotriol (Dovonex), calcipotriene (Dovonex), and calcitriol (Vectical). To prevent hypercalcemia, use of more than 100 g of vitamin D analogues per week should be avoided.39
Treatment of inverse psoriasis and scalp psoriasis may be challenging
The areas affected in inverse psoriasis, such as the genitalia and axillae, are more prone to side effects when potent topical steroids are used because of increased absorption and occlusion in these areas. Agents that minimize irritation and toxicity in sensitive areas, such as topical tacrolimus, less-potent topical steroids, or calcitriol, can be used.39
For scalp psoriasis, alternative vehicles such as shampoos, gels, solutions, oils, sprays, and foams have improved patient compliance and efficacy of treatment.40
PHOTOTHERAPY FOR SEVERE DISEASE
Narrow-band ultraviolet B
Narrow-band ultraviolet B, ie, light confined to wavelengths of 311 to 313 nm, is a first-line treatment for moderate to severe psoriasis, either as monotherapy or in combination with other treatments. It is an especially attractive option in patients who are on medications or who have comorbidities that may preclude treatment with other systemic agents.
The mechanism of action may be via immunosuppressive effects on Langerhans cells, alteration of cytokines and adhesion molecules that lead to an increase in Th2 cells, and induction of apoptosis of T lymphocytes. Additionally, ultraviolet light affects the proliferation and differentiation of keratinocytes.41
Dosing is based on skin type, and treatment usually involves two or three visits per week for a total of 15 to 20 treatments, with additional therapy for maintenance. Adding acitretin (Soriatane), with close monitoring of aspartate aminotransferase and alanine aminotransferase levels and the patient’s lipid panel, can be considered in treatment-resistant cases.42
Psoralen combined with ultraviolet A
Psoralen combined with ultraviolet A is another option. It can be considered if narrow-band ultraviolet B treatment fails. It is also useful for dark-skinned patients and those with thicker plaques because ultraviolet A penetrates deeper than ultraviolet B. Oral or topical treatment with psoralen is followed by ultraviolet A treatment.
The duration of remission is much longer with psoralen plus ultraviolet A than with narrow-band ultraviolet B. However, this treatment caries a significant risk of cutaneous squamous cell carcinoma and melanoma, especially in light-skinned people and those who receive high doses of ultraviolet A (200 or more treatments) or cyclosporine.40,41,43–46 Long-term effects include photoaging, lentigines, and telangiectasias. As a consequence of these well-established side effects, this treatment is used less frequently.
Cautions with phototherapy
Careful screening and caution should be used in patients who have:
- Fair skin that tends to burn easily
- A history of arsenic intake or treatment with ionizing radiation
- A history of use of photosensitizing medications (fluoroquinolone antibiotics, doxycycline, hydrochlorothiazide)
- A history of melanoma or atypical nevi
- Multiple risk factors for melanoma
- A history of nonmelanoma skin cancer
- Immunosuppression due to organ transplantation.
