Manual of Dermatologic Therapeutics
7th Edition

Jeffrey M. Sobell
David E. Geist
I. Definition and Pathophysiology
Psoriasis is a chronic proliferative epidermal disease that affects 2 to 8 million people in the United States and 1% to 3% of the world’s population. Its typical age of onset is in the third decade, although it may develop at any time from birth onward. A family history of psoriasis is found in 30% of patients; a multifactorial mode of inheritance is most likely. If one parent is affected, the incidence in the offspring is 8.1%; if both parents are affected, then 41% of the offspring may have the disease. The concordance rate in monozygotic twins is 65%; it is 30% for dizygotic twins. The histocompatibility antigen HLA-Cw6 is most strongly associated with psoriasis (relative risk is 24), and the coexistence of HLA-B17 or -B27 portends more severe skin disease or associated psoriatic arthritis. However, there does appear to be considerable genetic heterogeneity.
The pathogenesis of psoriasis involves T-cell–mediated inflammation. The clinical signs of psoriasis, epidermal hyperplasia, and vascular changes result from chronic T-cell–mediated inflammation within the psoriatic plaque. Still, the cause of psoriasis is unknown, and there is no cure. Understanding the development and maintenance of the psoriatic plaque requires an understanding of the cytokines and intercellular signaling molecules present in this disease. T-cell activation is likely triggered through typical pathways of adaptive immunity. Antigen-presenting cells (APCs) are activated in the skin, although the antigen is not known, and migrate to the lymph node. In the lymph node, APCs in turn activate T cells and program these T cells to home back to the skin. In psoriasis, APCs elaborate interleukin 12 (IL-12) and interferon-γ (IFN-γ), cytokines which direct T-cell differentiation into type 1 cells, specifically CD4+ helper T cells, which predominate in the dermis, and CD8+ cytotoxic T cells, which predominate in the epidermis. Once resident in the skin, activated type 1 T cells along with activated APCs and keratinocytes produce inflammatory cytokines including IL-2, IL-12, tumor necrosis factor-α (TNF-α), and IFN-γ which help sustain the T-cell response. In addition, APCs are abundant in psoriasis plaques. They may form a lymph node–like environment in the skin, which leads to continuous T-cell activation and maintenance of the psoriatic plaque (1).
In this activated T-cell milieu, psoriatic keratinocytes behave pathologically. In the presence of TNF-α and IFN-γ produced by T cells, they express increased levels of major histocompatibility complex (MHC)-II, intercellular adhesion molecule (ICAM)-1, and CD40. In addition, levels of keratin 6 and 16 (found in hyperproliferative skin) are upregulated, whereas keratin 1 and 10 (involved in terminal differentiation) are downregulated. Psoriatic keratinocytes travel from the basal cell layer to the surface in 3 to 4 days, much more rapidly than the normal 26 to 28 days. This is due to a higher proportion of basal layer keratinocytes that enter the active cell cycle. Decreased keratinocyte transit time does not allow for normal maturation and keratinization. This is reflected clinically by scaling, a thickened epidermis with increased mitotic activity, and by the presence of immature nucleated cells in the stratum corneum.
Effective and sustained T-cell activation in psoriasis requires multiple levels of intercellular signaling between T cells and both APCs and keratinocytes. The primary activation signal is delivered through the T-cell receptor (TCR)/antigen-MHC molecule interaction. Another primary signal necessary for T-cell activation is the interaction of LFA-1 on the T cell with ICAM-1 on the APC or keratinocyte. Costimulatory signals are also necessary to initiate and maintain T-cell activation and include CD28/B7 (CD80 and CD86) interactions, CD2/LFA3 interactions, and CD40Ligand/CD40 interactions. Proliferation and differentiation of T cells is driven by the cytokines IL-2 and IL-12 (and

IL-23). These essential molecular interactions, along with the cytokine TNF-α, provide the targets for several recently U.S. Food and Drug Administration (FDA)-approved psoriasis therapies.
Recently, a role for the transcription activator molecule Stat3 has been proposed. Stat3 participates in keratinocyte proliferation, survival and migration, and in wound healing. In mice, activated Stat3 in the presence of activated T cells can produce a psoriatic plaque de novo, which resolves when Stat3 is blocked. It is hypothesized that sensitivity of the Stat3 pathway may predispose to psoriasis (2). As such, Stat3 may be a potential future therapeutic target in psoriasis.
The course of psoriasis is prolonged but unpredictable. In most patients, the disease remains as discrete localized plaques. However, extensive or even generalized involvement may develop, and in some its severity is incompatible with a productive, happy life. Spontaneous clearing is quite rare, but unexplained exacerbation or improvement is common. Stress and anxiety frequently precede flare-ups of the disease; alcohol and smoking may also contribute to worsening of psoriasis. Psoriasis, psoriatic arthritis, and Reiter’s syndrome have all been associated with human immunodeficiency virus (HIV) infection, often in a period very close to the development of acquired immunodeficiency syndrome (AIDS). Exacerbated or difficult-to-control psoriasis in an at-risk individual warrants inquiry regarding the HIV status.
II. Subjective Data
  • Most lesions are asymptomatic.
  • Pruritus may be noted in 20% of patients.
  • Those with generalized disease may demonstrate all the signs and symptoms of an exfoliative dermatitis (loss of thermoregulation with findings of warm skin, a feeling of chilliness and shivering, increased protein catabolism, and cardiovascular stress).
  • Oligoarticular or polyarticular pain, tenderness, and morning stiffness, especially in the small joints of the hands and feet, are the early manifestations of psoriatic arthritis. Intense pain in larger joints and the cervical and/or lumbosacral spine may also be present.
  • Alcoholism may aggravate psoriasis. A small subset of patients with psoriasis will have worsening of their clinical condition with sun exposure.
III. Objective Data (See color insert)
  • The psoriatic lesion is an erythematous, sharply circumscribed plaque covered by loosely adherent, silvery scales. Acute lesions tend to be small and guttate (drop shaped). There is strong evidence that acute guttate psoriasis is induced by superantigen stimulation of T cells.
  • Inapparent scaling can be made noticeable by scratching the surface of a psoriatic lesion.
  • Any body area may be involved, but lesions tend to occur most often on the elbows and knees, scalp, genitalia, and intergluteal cleft.
  • Lesions of active psoriasis often appear in areas of epidermal injury (Koebner reaction). Scratch marks, surgical wounds, or a sunburn may heal with psoriatic lesions in their place.
  • Fifty percent of patients with psoriasis will have some degree of nail involvement. The nails may show punctate pitting or profuse collections of subungual keratotic material, clinically reflecting psoriatic involvement of the nail matrix or nail bed, respectively. A yellow-brown subungual discoloration (oil spot) is characteristic. Patients with distal interphalangeal joint involvement or arthritis mutilans usually have adjacent nail involvement.
  • Exfoliative psoriasis is clinically indistinguishable from other exfoliative dermatoses. It may occur spontaneously, follow a systemic illness or drug reaction, or occur as a reaction to some drugs or to steroid withdrawal.
  • Ten percent of patients with psoriasis may have either migratory stomatitis or glossitis.
  • Pustular psoriasis occurs in several forms: acute (von Zumbusch), subacute annular, and chronic acral. Sterile pustules are present, covering thin psoriatic plaques—the process may be generalized. The average age of onset is 50 years; flare-ups may be precipitated by infection or recent use of systemic corticosteroids. These patients

    require hospitalization, most necessitating systemic therapy. Impetigo herpetiformis is a rare form of pustular psoriasis during pregnancy.
  • In acute psoriatic arthritis, one or several joints are erythematous and swollen—the distal phalanx classically has a “sausage” appearance. Long-standing or rapidly progressive disease may lead to severe bone destruction. Almost 50% to 55% of patients with psoriatic arthritis have asymmetric oligoarticular arthritis, 25% have symmetric arthritis, and another 25% have spondyloarthritis with or without peripheral arthritis; 5% of patients show a destructive polyarthritis. Most patients with asymmetric arthritis have a mild or moderately progressive course, but approximately 50% with symmetric arthritis suffer from a progressive, slowly destructive arthritis.
IV. Assessment
  • The medical history may reveal a cause for the onset or exacerbation of psoriatic lesions. For example, acute psoriasis or a flare-up in chronic lesions may follow streptococcal pharyngitis by 7 to 10 days. T cells specific for group A streptococcal antigens can be consistently isolated from guttate psoriatic lesions. Psoriasis may be precipitated or exacerbated in patients ingesting lithium carbonate. β-Blockers, nonsteroidal antiinflammatory agents, antimalarials, gemfibrozil, chlorthalidone, and progesterone have also been implicated in aggravating psoriasis.
  • Other causes of exfoliative dermatitis (exfoliative erythroderma) include generalized eczematous dermatitis (e.g., atopic, contact, allergic), drug reactions, lymphoma, leukemia, and several rather uncommon skin diseases; 8% to 10% of cases are idiopathic.
  • Biopsy of lesions will reveal a psoriasiform epidermal thickening, but the histologic picture is often not diagnostic.
  • Hyperuricemia is proportional to the amount of cutaneous involvement and is related to the increased nucleic acid degradation associated with accelerated epidermopoiesis. It rarely causes symptoms or requires therapy.
  • Patients with psoriatic arthritis will typically have an elevated erythrocyte sedimentation rate (ESR) and, by definition, will have negative tests for rheumatoid factor. X-ray films of the hands may show characteristic subcortical cystic changes with relative sparing of the articular cartilage.
V. Therapy
  • It is important to emphasize that psoriasis is a treatable disease. Optimism and encouragement are justified and make it easier for the patient to conscientiously apply sometimes awkward and messy treatments. Pharmacologic data concerning the mode of action of most of these medications are limited.
  • Treatment for mild to moderate cutaneous involvement (For scalp and nail care, see sec. V. D and E.
    • Topical therapies
      • Potent topical corticosteroids applied b.i.d. to localized lesions are quite useful, especially in reducing scaling and thickness. Overnight or 24-hour occlusive therapy with these medications will initiate involution in most lesions. Hydrocolloid dermatologic patches (Actiderm, DuoDerm Extra Thin) can be applied over steroids on localized psoriatic plaques for 2 to 7 days. The patches may be worn while bathing. Corticosteroids exert their beneficial effects in this setting as inhibitors of mitoses and lymphokines and through depletion of Langerhans cells.
        Patients should apply corticosteroids to lesions without occlusion during the day, apply medication to plaques in the evening, immediately after bath or shower, and occlude with plastic wrap for 4 hours or overnight. As lesions subside, decrease the use of occlusion and increase the use of a bland emollient (e.g., Eucerin, Aquaphor, and Vaseline). After lesions have flattened, apply corticosteroids in bursts (e.g., several days on, several days off).
        If superpotent agents are used, they should be applied to limited areas only, and after achieving the desired result, they should be switched to an intermittent or staggered regimen. As little as 2 g/day of topical clobetasol propionate can suppress the hypothalamic pituitary axis (HPA).

        Injection of intralesional corticosteroids beneath isolated chronic plaques will cause involution within 7 to 10 days (triamcinolone acetonide, diluted to 2.5 to 5.0 mg/mL), which lasts 2 to 4 months.
      • Topical vitamin D analogs, both calcitriol and calcipotriol (calcipotriene [Dovonex]), have shown clinical effectiveness comparable with that of topical steroids or anthralin. Vitamin D analogs bind to Vitamin D3 receptors on keratinocytes and regulate keratinocyte proliferation and differentiation and also inhibit T-cell activation.
        Calcipotriene (Dovonex) ointment, cream, or solution is applied b.i.d.; dosages should not exceed 100 g/week as the risk of kidney stones and hypercalcemia increases. Calcipotriene (Dovonex) may irritate facial skin (diluting Calcipotriene [Dovonex] with petrolatum may decrease this irritation). Intertriginous and genital psoriasis can be effectively treated with surprisingly minimal irritation. Any dermatitis is most likely secondary to irritancy and not allergic contact dermatitis.
        A 2-week regimen of calcipotriene and halobetasol ointments daily was superior to monotherapy with halobetasol two times per day. Calcipotriol scalp solution is effective for mild to moderate scalp psoriasis but is inferior to midpotency steroids; a combination rotational therapy between the two products is recommended.
        Calcipotriene (Dovonex) enhances the effectiveness of ultraviolet B (UVB) but also increases photosensitivity in UVB-treated patients. Ultraviolet light, 6% salicylic acid, 12% lactic acid, hydrocortisone valerate 0.2% ointment, and tazarotene (Tazorac) gel degrade calcipotriene (Dovonex). Halobetasol ointment and 5% tar gel are compatible with Calcipotriene (Dovonex). A British study found calcipotriene (Dovonex) to be safe and effective in a pediatric population over the age of 3, although it is not approved by the FDA.
        Several new vitamin D analogs are currently involved in clinical trials.
      • Topical tazarotene gel and cream tazarotene (Tazorac 0.05% and 0.1%) are topical retinoids that modulate abnormal epidermal differentiation and proliferation; there is an upregulation of K10 terminal differentiation. Systemic absorption is minimal, but this is categorized as a category X drug, and special warnings should be provided to women of childbearing potential. Like most retinoids, this topical drug can be inherently irritating. Methods that are helpful in minimizing this irritation are as follows: (i) Apply tazarotene (Tazorac) to affected skin only at bedtime, protect normal skin with Vaseline, (ii) apply a mid-to-high–potency topical steroid in the morning, and (iii) start with a low dose (0.05%) and increase as tolerated. The 0.1% gel is slightly more effective but also more irritating than the 0.05% gel. Tazarotene is not inactivated by ultraviolet light although it will lower the erythema threshold. Tazarotene combined with UVB phototherapy is more effective than phototherapy alone.
      • Coal tar therapy may be combined or alternated with topical corticosteroids. Tars such as T/Derm, which are nearly colorless, or 1 to 5% crude coal tar ointment, which is very messy but may be more effective, are applied overnight. Tars inhibit deoxyribonucleic acid (DNA) synthesis and have an atrophogenic effect on skin, as well as sensitize the skin to long-wave ultraviolet light (UVA). Although they do not offer any advantage over lubricants such as petrolatum when used with an aggressive UVB treatment protocol, tars may provide a beneficial “light-sparing” effect when used with less aggressive UVB regimens. Tars may aggravate acne and cause folliculitis.
        As directed in the instructions for corticosteroids, but on alternate nights, the patient should apply a tar formulation overnight and be exposed to ultraviolet light (UVL) the following morning or apply a corticosteroid cream with or without occlusion during the day, tar overnight, and UVL exposure in the morning.
      • Other topical agents
        • Salicylic acid 2% to 10% formulations help remove scales and crusts and may be used along with corticosteroid or anthralin therapy. Formulations

          commonly used include 3% to 10% salicylic acid cream or 3% to 6% sulfur and salicylic acid ointment.
        • Anthralin (dithranol) is effective for treatment of discrete lesions consisting primarily of thick plaques (see Chap. 40, Keratolytic, Cytotoxic, and Destructive Agents, sec. II). This drug is derived from chrysarobin (active ingredient of Goa powder from the bark of South American Araroba Tree). This drug inhibits keratinocyte proliferation and granulocyte function and exerts an immunosuppressive effect. Anthralin’s disadvantages are that it may be a primary irritant, it stains clothing and skin, and it can be difficult to apply.
          Anthralin paste or cream can be used on an outpatient or inpatient basis and will clear up the lesions on most patients within 2 to 3 weeks. In short-contact therapy, start with 0.1% anthralin applied for 20 to 30 minutes and then washed off. Check for irritation at 48 hours. According to tolerance, the potency can be increased (to 0.3%, 0.5%, or 1.0%) and the contact time shortened or, for resistant plaques, increased. Use daily for clearing and then once or twice weekly for maintenance therapy.
          Micanol is a temperature-sensitive formulation of anthralin that releases the anthralin product only when in contact with skin temperature. There is minimal or no staining of skin or fabrics.
        • Topical tacrolimus or pimecrolimus does not appear effective in typical plaque psoriasis but may be helpful in intertriginous and facial psoriasis where there is better absorption.
    • Repeated exposure to sunlight or middle-wavelength, sunburn-spectrum, ultraviolet light (UVB) from artificial sources to the point of mild erythema will induce flattening or clearing of many lesions. A standardized three times weekly UVB protocol will induce complete clearing in an average of 23 treatments. While various treatment centers continue to refine its optimal parameters, UVB phototherapy remains perhaps the most rapid and effective means of inducing remission in mild to severe disease. UVB inhibits epidermal mitosis and presumably acts by this mechanism.
      A new form of phototherapy is available that utilizes a narrowband wavelength of 311 nm, the wavelength determined to be the most effective in psoriasis. This limited spectrum of UVB may be less carcinogenic than traditional UVB. Widespread use of narrowband UVB treatments is limited by the expense of the units (traditional UVB units cannot be easily converted to accommodate these new bulbs).
      An excimer laser with intense 308-nm UVB radiation can clear a plaque of psoriasis with as little as one treatment, although usually four to eight treatments are required. Remissions of 3 to 4 months are possible. This laser is capable of rapidly delivering multiples of the minimal erythema dose (MED) to lesions without the use of anesthesia, making it an attractive treatment option for localized and limited cutaneous areas. Pulsed dye laser treatment improves limited psoriatic plaques with some chance for pigmentary changes and scarring; the target is the enlarged and dilated blood vessels (3).
  • Treatment for more severe or widespread involvement. The management of severe or extensive psoriasis is a problem that can be best handled by a dermatologist.
    • Phototherapy
      • Aggressive UVB phototherapy is the most rapid and effective single-agent regimen for clearing psoriasis. It may be used by specific protocols three times a week, five times a week, or daily. The latter will clear most patients in 18 treatments. All protocols involve application of lubricants to psoriatic plaques before phototherapy. The 311-nm narrowband phototherapy can be used in place of broadband sources. An initial MED must be performed with narrowband UVB. Long-term studies of safety and efficacy for the 311-nm wavelength are in progress.
      • Tar and UVL therapy (Goeckerman regimen), which was once the standard of care, is little used today. It is best an inpatient or day-care facility treatment,

        because tars are messy to apply and potent or fluorescent lights are needed. Tars and middle-wavelength UV light (UVB) act as separate antipsoriatic agents.
      • Photochemotherapy will bring about marked improvement when used for widespread, severe psoriasis. A photoactive drug (a psoralen) is administered orally, followed 2 hours later by exposure to long-wave UVL (UVA). Psoralens form photoadducts with DNA in the presence of UVA and in this way probably reduce the increased epidermal turnover characteristic of psoriasis. Long-term side effects include increased risk of squamous cell carcinoma (SCC) (especially involving the male genitalia), malignant melanoma, atypical pigmentation, and accelerated skin aging. A long latency period (15 years or longer) and a large number of treatments (>250 J/cm2 or >100 exposures) are required to induce the melanoma and nonmelanoma skin cancers.
        Psoralen plus ultraviolet A (PUVA) is one of the most efficacious treatments for psoriasis. Repeated PUVA exposure causes disappearance of lesions in almost all patients after 10 to 20 treatments over 4 to 8 weeks. Psoriasis often recurs weeks to months after PUVA ceases, and twice-monthly treatment is necessary to keep most patients free of their disease. Scalp, body folds, and other areas not exposed to UVA respond poorly to the therapy. Topical PUVA is helpful in palmar and plantar psoriasis. Outdoor use of PUVA using natural sunlight is also possible, although hazardous (4).
      • Combined therapies appear to be most effective in clearing recalcitrant widespread and severe psoriasis. These include PUVA-UVB, retinoid-PUVA, retinoid-UVB, methotrexate-PUVA, and methotrexate-UVB (5). The latter, for example, combines thrice-weekly UVB treatments with once-weekly methotrexate administration for 8 weeks. This regimen cleared all 26 cases of disabling psoriasis in one half the number of UVB treatments (6) required without methotrexate and utilized relatively low amounts of each agent, thereby reducing cumulative methotrexate and UVL toxicity.
        Six of seven studies failed to demonstrate an advantage to the addition of topical corticosteroids to UVB phototherapy. In contrast to PUVA, topical steroids appear to show a more rapid rate of clearing and a smaller total UVA dose when used in combination.
    • Oral systemic agents
      • Acitretin (Soriatane), a synthetic derivative of vitamin A, is a major metabolite of etretinate with a similar efficacy and side effect profile. Acitretin is less lipophilic than etretinate, with a significant difference in half-life (60 hours vs. 120 days). This agent is helpful in pustular, guttate, and erythrodermic psoriasis; its efficacy is less dramatic in chronic plaque psoriasis unless it is combined with some form of phototherapy, methotrexate, or cyclosporine. Care should be taken to decrease the dose of UVA and UVB by 50% when combined with acitretin.
        Side effects are dose dependent and include elevation of triglycerides, hepatitis, hair loss, thinning of the nails, cheilitis, xerosis, and stickiness of the skin. Gemfibrozil (300 mg b.i.d.) corrects elevated lipid levels on this therapy.
        The usual starting dose of acitretin is 10 to 20 mg/day with maximum dose of 50 mg/day. Etretinate has been identified in plasma samples of some patients treated with acitretin and is converted by ingestion of alcohol. This drug is not recommended for women of childbearing potential; if it is used, pregnancy should be avoided for 3 years after the last dose.
      • Antimetabolite therapy with agents that inhibit DNA synthesis (methotrexate, hydroxyurea) is reserved for those patients unresponsive to other approaches.
        Methotrexate is given orally or by IM administration. Doses begin at 7.5 mg weekly with incremental increases of 2.5 mg/week as tolerated. Typical maximum doses reach 12.5 to 15 mg/week. Side effects include nausea, bone marrow suppression, and liver toxicity. The addition of folic acid 1 to 5 mg/day helps reduce nausea and counteract the macrocytic

        anemia. Complete blood count (CBC) and liver function tests should be carefully followed and a liver biopsy obtained after every 1.5 g of cumulative exposure.
        Hydroxyurea dosing starts at 500 mg/day with weekly monitoring of CBC and platelets. This drug has a very narrow window between toxicity and efficacy; as many as 50% of patients will develop neutropenia at doses of 2 g/day.
      • Cyclosporine A (CSA) administration (3 to 6 mg/kg) causes dramatic clearing of widespread psoriasis. A new microemulsion formula of cyclosporine (Neoral) is better absorbed and the suggested range of dosing is 2.5 to 4 mg/kg. This drug selectively inhibits T-helper cell production of IL-2 while allowing increase of suppressor T-cell populations. Cyclosporine has no direct effect on keratinocytes and is not a mitotic inhibitor. Cyclosporine inhibits cytokine release, which results in a decreased recruitment of APCs into the epidermis and decreases immunoreactivity of lesions.
        Potential long-term side effects preclude cyclosporine’s use in all but very severe and recalcitrant psoriasis. Cyclosporine can be combined with low-dose methotrexate. Cyclosporine’s main side effects, even at low doses, are hypertension and nephrotoxicity. Age, baseline blood pressure, and baseline creatinine levels are predictors of higher risks of side effects. Glomerular filtration rate (GFR) is a more sensitive test than creatinine for evaluating renal function, and a baseline is recommended in any high-risk patient. Long-term treatment with CSA may induce interstitial fibrosis and glomerular sclerosis, with more pronounced changes directly associated with duration of therapy. Discontinuation after 2 years at most is recommended (7). It should be administered only by dermatologists experienced in its use.
      • Treatment schedules are advocated that rotate therapies to try and minimize the adverse effects of each. One recommended schedule is as follows: UVB < PUVA, methotrexate, acitretin, and cyclosporine (8).
      • Other oral agents
        • Mycophenolate mofetil (CellCept), an inhibitor of synthesis of the nucleotide guanosine, is administered at a dose of 500 mg four times a day to a maximum of 4 g/day. The main side effects include an increased incidence of herpes zoster, neutropenia, gastrointestinal symptoms, and opportunistic infections. In the transplant literature, 1% to 2% of patients will develop a lymphoproliferative malignancy at the doses recommended for psoriasis. This is a teratogen and should be avoided in women of childbearing age.
        • Fumaric acid esters have been available for a decade and have a high level of efficacy in psoriasis; the mechanism is unknown but researchers theorize that psoriasis is a disorder of defective citric acid metabolism. Side effects include flushing, gastrointestinal side effects, eosinophilia, and reports of acute renal failure.
        • Oral calcitriol is effective but can increase serum and urinary calcium and result in alteration of creatinine clearance.
    • Biologic therapies
      • Alefacept (Amevive) is a fully human lymphocyte function–associated antigen 3/immunoglobulin 1 (LFA-3/IgG1) fusion protein. It binds to CD2 on T cells, inhibiting T-cell activation and producing selective T-cell apoptosis. Alefacept is FDA approved as a 12-week course of 15 mg weekly intramuscular injections. Long remissions can be seen in responders. Peripheral CD4 counts should be followed and doses withheld if counts drop below 250 cells/μL. Therapy should be discontinued if the CD4 count remains below 250 cells/μL for >4 weeks. A second course lengthens the period of remission without additional toxicities (9).
      • Efalizumab (Raptiva) is a humanized monoclonal antibody that binds to the CD11a subunit of LFA-1. It blocks the interaction of LFA-1 with ICAM-1, thereby interfering with T-cell activation and trafficking. Efalizumab is FDA

        approved at 1.0 mg/kg/week by subcutaneous injection. Common side effects include mild headache, fever, chills, nausea, or myalgia within the first 48 hours of injection in the first 2 to 3 weeks of therapy. Immune-mediated thrombocytopenia is rare. Worsening of psoriasis may occur after discontinuation of therapy or in unresponsive patients during therapy. Transitioning patients to alternative therapies may minimize this risk (10).
      • Etanercept (Enbrel) is a soluble TNF receptor fusion protein. It is FDA approved for moderate to severe psoriasis at a dose of 50 mg twice weekly by subcutaneous injection for the initial 12 weeks, followed by a step-down to 50 mg weekly for maintenance. The most common side effect is injection site reactions. Rare cases of serious infection, demyelinating disease, and congestive heart failure have been reported by postmarketing surveillance (11).
      • Infliximab (Remicade), a chimeric anti-TNF monoclonal antibody, and adalimumab (Humira), a fully humanized anti-TNF monoclonal antibody, are both promising therapies under investigation for psoriasis.
  • Scalp care
    • Mild involvement may be treated by the patient with a tar shampoo (10% liquor carbonis detergens in tincture of green soap, Pentrax, Polytar, Sebutone, T-gel, Zetar) and steroid lotion or solution b.i.d. (betamethasone, halcinonide, Diprolene, Temovate). Steroid-containing shampoos are also available (Capex, Clobex).
    • More severe involvement should be treated as follows:
      • If scaling is thick, it is necessary to first remove the scales and then apply something to inhibit their reformation. Apply a keratolytic gel to a hydrated scalp and then cover it with an occlusive plastic shower cap for several hours or overnight. This will effectively loosen the scales, after which a steroid lotion or solution (Derma-Smoothe/FS, Lidex, Synalar, Valisone) should be applied under a shower cap for the rest of the night or without occlusion during the day. A betamethasone valerate mousse (Luxiq) and a clobetasol propionate mousse (Olux) were recently approved by the FDA for the treatment of scalp psoriasis. The foam distributes easily on the scalp as it liquefies at body temperature and leaves minimal residue on the hair. In warm weather, the can should be stored in the refrigerator to restore the foam to a proper consistency.
      • Alternatively, chronic thick plaques may be treated by the patient as follows:
        • Apply anthralin (Dritho-Scalp), or phenol/saline lotion (P&S liquid), or, in severe cases, 20% oil of cade, 10% sulfur, 5% salicylic acid (20-10-5 ointment) in hydrophilic ointment on the scalp, leaving it overnight.
        • Use tar shampoo (e.g., T/Gel) in the morning.
        • Reapply the preparation as for overnight during the day until scaling is decreased. At that point, substitute a steroid lotion or solution.
      • Intralesional corticosteroid injections will clear isolated plaques.
  • Nail care. There is no consistently effective therapy for psoriatic involvement of the nails. The nails will often improve coincidentally with remission of cutaneous lesions and will almost always improve after systemic antimetabolite or immunomodulator therapy.
    • Removal of subungual debris and application of corticosteroids under occlusion may offer some benefit.
    • Injection of small amounts of triamcinolone (0.1 mL of 3 mg/mL) into the nail bed at 2- to 3-week intervals will result in cure or improvement in approximately 75% of treated nails, but it is painful and time consuming. There will be approximately 50% recurrence rate when treatment is stopped.
      Another regimen is 0.1 mL of 10 mg/mL at 3-month intervals utilizing a ring block to minimize pain. Onycholysis and pitting of the nails respond least well. Postprocedure paresthesias, hematomas, and pain of the distal tip can occur. Steroid benefit could be maintained for 9 months (12).
    • P.172

    • Urea 40% ointment may be useful in removing hypertrophic or dystrophic psoriatic nails. Subsequent topical therapy to the denuded nail bed and proximal nail fold may result in regrowth of “normal” nails in half of those treated.
    • A 1% 5-fluorouracil solution (Fluoroplex) applied twice daily to nail margins has been reported to decrease the severity of involvement by 75% in two thirds of patients within 3 to 6 months.
    • Subungual hyperkeratosis of a solitary nail should be further evaluated for the possibility of a wart or SCC.
    • More than 25% of patients with psoriatic nails will have an associated dermatophyte infection; oral antifungal therapy may help improve the overall condition of the nails although patients should be advised that they have two problems affecting the appearance of the nails.
    • Calcipotriol ointment and/or tazarotene (Tazorac) gel applied b.i.d. to nail beds may have some modest benefits on subungual hyperkeratosis (6).
  • Psoriatic arthritis may respond to a variety of pharmacologic agents. In general, when the disease is mild to moderate, it should be treated with either aspirin or a nonsteroidal antiinflammatory drug; if unresponsive or more severe, with hydroxychloroquine, sulfasalazine, methotrexate, etanercept (Enbrel), or infliximab; and if relentless, with gold or other immunosuppressive agents. Splinting and local heat should also be used.
    • Aspirin must be taken to near toxicity to be effective.
    • Nonsteroidal antiinflammatory agents are very effective in early psoriatic arthritis, and there is some opinion that they may be more useful than aspirin. Indomethacin is given in doses of 75 to 100 mg/day. It is essential that these drugs be administered in amounts sufficient to exert their antiinflammatory effects. Ibuprofen (Motrin) dosage should be 2,400 mg/day, or naproxen (Naprosyn), 500 to 750 mg/day. All these medications are gastrointestinal irritants and are contraindicated in patients with ulcer disease. They also affect platelets in a manner similar to aspirin and, if given to patients already on anticoagulants, may result in bleeding and clotting problems. There is no clear evidence that any one of the nonsalicylate nonsteroidal antiinflammatory agents is more effective than any other in controlling the inflammation of psoriatic arthritis.
    • Hydroxychloroquine (Plaquenil) has been shown to induce a beneficial response in 75% of 100 patients with psoriatic arthritis. The use of this antimalarial drug was not accompanied by an exacerbation in psoriasis, contrary to previous beliefs (13).
    • Sulfasalazine (3.0 g daily). Side effects include drug rash and nausea; severe side effects are minimal, making this a safe alternative to more toxic oral therapies. This can be administered with methotrexate.
    • Gold or folic acid antagonists, particularly methotrexate, are very useful in intractable cases unresponsive to the more conventional therapies. 6-Mercaptopurine may be more effective against the arthritis component but is less useful for the cutaneous lesions. Gold or immunosuppressive drugs may put psoriatic arthritis into remission.
    • TNF blockers (Enbrel and Remicade) are approved for the treatment of psoriatic arthritis. Both agents improve the signs and symptoms of arthritis and prevent the progression of joint destruction. Humira is under investigation and will likely be beneficial as well.
    • Spondylitis associated with psoriatic arthritis is treated with the same medications as spondylitis of other causes. The nonsteroidal antiinflammatory drugs described earlier are the initial agents of choice, and the disease usually responds well. Alternatively, the TNF blockers are effective.
  • Acute psoriasis should be treated gently with just emollients or topical steroids. Avoid tars, salicylic acid, and aggressive UVL therapy, because they may be irritating and lead to a more widespread eruption and chronic course.
  • HIV-associated psoriasis can be extensive and difficult to treat. Therapy with acitretin as monotherapy or in combination with UVB is recommended. Methotrexate therapy is controversial because of its immunosuppressive effects (14).

1. Krueger JG. The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol 2002;46:1–23.
2. Sano S, Chan KS, Carbajal S, et al. Stat 3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005;11:43–49.
3. Ros A-M, Garden JM, Bakus AD, et al. Psoriasis response to the pulsed dye laser. Lasers Surg Med 1996;19:331–335.
4. Parrish JA, White AD, Kingsbury T, et al. Photochemotherapy of psoriasis using methoxsalen and sunlight: a controlled study. Arch Dermatol 1977;113:1529–1532.
5. Paul BS, Momtaz K, Stern RS, et al. Combined methotrexate-ultraviolet B therapy in the treatment of psoriasis. J Am Acad Dermatol 1982;7:758–762.
6. Tosti A, Piraccini BM, Cameli N, et al. Calcipotriol ointment in nail psoriasis: a controlled double-blind comparison with betamethasone dipropionate and salicylic acid. Br J Dermatol 1998;139:655–659.
7. Zachariae H, Kragballe K, Hansen HE, et al. Renal biopsy findings in long-term cyclosporin treatment of psoriasis. Br J Dermatol 1997;136:531–535.
8. Spuls PI, Bossuyt PM, van Everdingen JJ, et al. The development of practice guidelines for the treatment of severe plaque form psoriasis. Arch Dermatol 1998;134:1591–1596.
9. Lebwohl M, Christophers E, Langley R, et al. An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol 2003;139:719–727.
10. Menter A, Gordon K, Carey W, et al. Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis. Arch Dermatol 2005;141:31–38.
11. Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003;349:2014–1022.
12. De Berker DAR, Lawrence CM. A simplified protocol of steroid injection for psoriatic nail dystrophy. Br J Dermatol 1998;138:90–95.
13. Schur PH, Kammer GM, Soter NA. Clinical, immunologic and genetic study of 100 patients with psoriatic arthritis. Arthritis Rheum 1979;22:656.
14. Buccheri L, Katchen BR, Karter AJ, et al. Acitretin therapy is effective for psoriasis associated with human immunodeficiency virus infection. Arch Dermatol 1997;133:711–715.