Psoriasis

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Psoriasis

Mark G. Lebwohl and Peter C.M. van de Kerkhof

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Plaque psoriasis is a common disorder in which environmental factors contribute to the development of sharply demarcated erythematous scaling plaques in genetically predisposed individuals. As there is an overlap in treatments, guttate psoriasis, inverse psoriasis, and impetigo herpetiformis will be discussed under ‘Management strategy’ below. Erythrodermic psoriasis and pustular psoriasis will be discussed at the end of the chapter. Palmoplantar pustulosis is addressed in its own chapter. Patients should be questioned and examined for psoriatic arthritis, and, because of recent evidence linking psoriasis to cardiovascular disease, risk factors should be addressed. Involvement of rheumatologists or cardiologists may be necessary.

Management strategy

The treatment of psoriasis must take many factors into account, including the extent of involvement, areas of involvement, the patient’s lifestyle, and other health problems and medications. For example, patients who live far from phototherapy centers may not have the option to be treated with psoralen and UVA (PUVA), but a home phototherapy unit can be ordered for patients who can be taught to administer their own UVB therapy. In sunny climates, sun exposure can be added to the therapeutic regimen. If patients are taking medications such as lithium that are known to exacerbate psoriasis, alternatives should be sought. In patients who have had multiple skin cancers, PUVA and cyclosporine should be avoided as they increase the tendency to develop skin cancers; acitretin, which suppresses the development of skin cancers, should be considered for these individuals.

The body surface area affected in patients with psoriasis is important in the selection of therapies. In individuals with less than 5% body surface area involvement, topical therapy is usually started unless the patient has previously failed topical therapy or the psoriasis is debilitating because of the site of involvement. In patients with mild localized plaques, mild, mid-potency or potent topical corticosteroids can be prescribed, or other topical agents such as calcipotriol (calcipotriene), calcitriol or tazarotene can be tried. Anthralin preparations have fallen into disfavor because they are messy, but they still offer an effective alternative to corticosteroids. In Europe anthralin preparations are used in some day-care centers. Often patients have been using a topical medication that is inadequate as monotherapy, and in such cases combination therapy is warranted. The combination of a superpotent corticosteroid and calcipotriol or tazarotene is often effective when monotherapy with either of the agents does not work, and new formulations that combine betamethasone dipropionate with calcipotriol are available.

Some areas may be limited in extent, but require alternative treatments. For example, involvement of the palms and soles can be debilitating, and these areas are notoriously difficult to treat. Pustular psoriasis of the palms and soles, for example, only occasionally responds to topical therapy. Although the palms and soles involve only a small percentage of the body surface area, treatment with oral medications or injected medications or phototherapy may be warranted. The combination of acitretin 25 mg daily with ‘bath-PUVA’ – applied by soaking the hands in a water-filled basin to which methoxsalen has been added, followed by UVA irradiation – has been used successfully. The excimer laser can also be effective for palm and sole psoriasis, as can oral methotrexate, acitretin and cyclosporine. Double-blind placebo-controlled trials have demonstrated the efficacy of adalimumab for palm and sole psoriasis, and it is likely that other biologic therapies are effective, though they are not as effective for palms and soles as they are for psoriasis on other parts of the body. Involvement of the scalp is common and requires gels, solutions, sprays or foams that are not as messy as ointments and creams. Shampoos containing tars, salicylic acid, or corticosteroids are useful adjunctive therapies for the scalp. A new home device that delivers narrowband UVB to the scalp through fiber-optic filaments has recently been introduced.

The face and intertriginous sites are highly responsive to topical medications, but are particularly sensitive to the side effects of many topical agents. Topical corticosteroids cause cutaneous atrophy, telangiectasia, and striae. Therefore, only milder, safer corticosteroids should be used on the face and intertriginous sites, and alternating with non-corticosteroids may be optimal if psoriasis recurs. The topical immunomodulators tacrolimus 0.1% ointment and pimecrolimus 1% cream are effective and safe for facial and intertriginous psoriasis, but not as effective on thick plaques on the rest of the body. Calcipotriol (50 µg/g) can be irritating on facial or intertriginous psoriasis, but alternative vitamin D analogs such as calcitriol and tacalcitol are less irritating and therefore particularly suited for facial or flexural psoriasis. Tazarotene may be too irritating to use on genital skin, but it can be used on the face. The irritation of tazarotene can also be minimized by using it in a regimen with topical corticosteroids.

With 5–10% body surface involvement, topical therapy is usually prescribed, but may require the addition of phototherapy or oral medications. In those with more than 10% body surface involvement, topical therapy may be impractical for all lesions but may provide a useful adjunct to phototherapy or systemic therapy.

Phototherapy with UVB has been in use in the treatment of psoriasis for a century and has a proven record of safety and efficacy. It is particularly useful in patients who have responded well to sun exposure. Patients who have failed UVB or have not done well with sun exposure often respond to narrowband UVB. PUVA is one of the most effective treatments for psoriasis and offers long remissions for many patients. Because of its increased risk of cutaneous malignancy, PUVA is usually reserved for those who do not achieve adequate remissions with UVB.

In patients who have not achieved satisfactory results with these treatments, low-dose oral retinoids can be added. Acitretin in doses of 10–25 mg daily dramatically improves the response to UVB and to PUVA. By keeping the dose at 25 mg or less, the side effects of acitretin can be minimized. For those who are not candidates for UVB phototherapy or PUVA, oral methotrexate is highly effective in combination with other treatments or as monotherapy. It is associated with hepatic fibrosis in some patients and regular monitoring of liver function tests in addition to blood counts is necessary. Current guidelines in the US call for periodic liver biopsies in selected patients treated with methotrexate. In parts of Europe, the serum level of the amino-terminal propeptide of type III procollagen has been used as a marker for hepatic fibrosis as an alternative to routine use of liver biopsy. Cyclosporine is also dramatically effective as monotherapy for psoriasis, but is associated with nephrotoxicity as well as hypertension and a theoretical risk of malignancy with long-term use. Consequently, current guidelines call for limiting use of cyclosporine to 1 or 2 years. Other oral agents under investigation for psoriasis include apremilast and tofacitinib.

In recent years, the ability to create new drugs that target specific parts of the immune system has led to the development of biologic agents for psoriasis. These drugs are not associated with the nephrotoxicity of cyclosporine or the hepatotoxicity and bone marrow toxicity of methotrexate. The long-term side effects of biologics are not known, however, and their cost is often prohibitive. Psoriasis experts are divided on the point at which biologics should be considered. Some consider them first-line therapy when the disease is too extensive for topical therapy. Because of their expense, biologics are used by others only after phototherapy or other systemic therapies have been tried.

Multiple biologic agents have been approved or have completed large clinical trials for psoriasis or psoriatic arthritis. Agents that block tumor necrosis factor-α (TNF-α), including etanercept, infliximab, adalimumab, golimumab, and certolizumab, are ideal for patients with psoriatic arthritis. TNF-blocking agents have unique side effects, including the reactivation of latent tuberculosis, exacerbation of multiple sclerosis, and the development of antinuclear antibodies. A drug that blocks the p40 component of IL-12 and IL-23 has recently been introduced and is highly effective for psoriasis. Ustekinumab has been studied in 45 mg and 90 mg doses; dose elevation can be beneficial in overweight patients. The drug can be administered as infrequently as every 3 months. Ixekizumab and secukinumab drugs that block IL-17, and brodalumab which blocks the IL-17 receptor are highly effective therapies that are likely to gain approval for psoriasis. Other biologic therapies targeting IL-17 and IL-23 are on the way. Because of the toxicities of psoriasis therapy, several concepts have evolved for controlling the disease while minimizing side effects. Rotational therapy, for example, involves treating psoriasis with a medication such as methotrexate for varying periods, followed by switching to PUVA, retinoids, or cyclosporine for limited periods. The different treatments used in rotation are determined by patient response. Because biologic therapies have not been associated with major organ toxicity, they are often used long term without the need for rotation.

Combination therapy involves the mixing of two or more treatments. Topical therapies are often used in combination with phototherapy and systemic therapy. Phototherapy with UVB or PUVA is often combined with oral retinoids or methotrexate, thereby minimizing the number of treatments and the toxicity of each of the therapies. Phototherapy has also been used with many of the biologic agents for psoriasis, resulting in improved response rates. Low doses of methotrexate and cyclosporine can be used in combination to minimize the nephrotoxicity of cyclosporine and the hepatotoxicity of methotrexate. The latter combination can be effective in patients who have failed monotherapy with either agent. Biologics have been used in combination with methotrexate, cyclosporine, and acitretin. Because acitretin is not immunosuppressive, it is an ideal agent for combination therapy with the new drugs that target the immune system. Many advocate combining biologics with methotrexate, not only to achieve better results, but to reduce the development of antibodies to the biologic agent. Antibody formation can be associated with infusion reactions in patients on infliximab and reduced efficacy of several biologics.

Sequential therapy refers to the concept of treatment in which potent agents are used to clear the disease, and safer but less effective agents are used to maintain remission. For example, cyclosporine can be used to clear psoriasis and patients can then be switched to oral retinoids in combination with UVB for maintenance or to a biologic agent. Similarly, sequential therapy can be applied to topical medications. Calcipotriol or tazarotene can be used in combination with superpotent corticosteroids to clear psoriasis and to reduce irritation induced by calcipotriol or tazarotene monotherapy. The corticosteroid can then be tapered to a regimen where it is used only 2 days per week or eliminated altogether, while the non-corticosteroid agent can be continued.

Inverse psoriasis

Patients with inverse psoriasis develop lesions in the axillae, between the buttocks, on the medial aspects of the thighs, and in the umbilicus. These sites are easily treated with mild topical corticosteroids, but are more susceptible to corticosteroid side effects such as atrophy and formation of striae. Consequently, non-steroidal treatments can be attempted. Calcipotriol (50 µg/g) can be irritating on intertriginous sites but is nevertheless effective. Other vitamin D analogs (calcitriol, tacalcitol) cause less irritation. Tazarotene can be used on the face, but is usually too irritating to use in the axillae or groin. Tars and anthralin are likewise irritating in intertriginous sites. Topical tacrolimus ointment and pimecrolimus cream, albeit not approved for psoriasis, are highly effective for facial and intertriginous psoriasis, but less effective for thick plaques elsewhere on the body. Topical phosphodiesterase inhibitors and Janus kinase inhibitors are likely to be introduced for psoriasis, and these may be effective for facial and intertriginous psoriasis without the atrophogenicity of corticosteroids.

Impetigo herpetiformis

Impetigo herpetiformis is characterized by a generalized pustular eruption with fever and leukocytosis developing during pregnancy. Many consider this to be a variant of pustular psoriasis that occurs during pregnancy. If bed rest, emollients, compresses, and mild topical corticosteroids are ineffective, systemic corticosteroids have been used effectively in the past. More recently, oral cyclosporine has proved effective for impetigo herpetiformis. This drug, which has a pregnancy category C rating, is administered in two divided doses totalling 4–5 mg/kg daily. Concerns about cumulative toxicity, such as nephrotoxicity, are less worrisome in impetigo herpetiformis because the disorder may resolve at the end of pregnancy, limiting the amount of cyclosporine prescribed. Although there is not as much experience in the use of biologic agents for impetigo herpetiformis, the limited data available for these agents suggest that they are relatively safe during pregnancy. Most are rated as pregnancy category B, meaning that there is no evidence of fetal toxicity in animal studies; however, these drugs can affect the fetal immune system and postnatal immune infection has occurred.

Specific investigations

Investigation is not required in the majority of cases. Skin biopsy may be helpful if the diagnosis is in question, but is usually not needed.

As discussed below, a range of investigations is required for screening and monitoring when using systemic therapies.

Routine screening for tuberculosis has been advised for patients treated with biologic therapies. Because methotrexate and cyclosporine are also immunosuppressive, testing for tuberculosis and, if positive, chest radiography has been suggested prior to treatment with these agents. Cyclosporine guidelines call for frequent monitoring of blood pressure and chemistry screening, with particular attention to serum creatinine and magnesium. Methotrexate guidelines call for periodic monitoring of complete blood count (CBC) and platelet counts, and chemistry screening with liver function tests. Assays for hepatic fibrosis such as the serum amino-terminal propeptide of type III procollagen, or liver biopsies, are advised in certain patients. Monitoring for viral hepatitis or HIV infection should be considered in populations at risk for those disorders, and many advocate routine hepatitis screening in any patient prior to biologic therapy, methotrexate or cyclosporine. Serum cholesterol and triglycerides are particularly important in patients treated with oral acitretin.

Cyclosporine and psoriasis: 2008 National Psoriasis Foundation Consensus Conference.

Rosmarin DM, Lebwohl M, Elewski BE, Gottlieb AB; National Psoriasis Foundation. J Am Acad Dermatol 2010; 62: 838–53.

Oral cyclosporine in doses up to 5 mg/kg daily is dramatically effective for psoriasis, but is limited by the development of nephrotoxicity.

This article presents guidelines regarding dosage and monitoring, drug interactions, and complications of cyclosporine.

In patients treated with cyclosporine, blood and platelet counts as well as comprehensive serum chemistries are warranted, including blood urea nitrogen, creatinine, potassium, magnesium, uric acid, liver function tests, and lipids. Two baseline serum creatinine levels and two baseline blood pressure measurements should be obtained prior to starting cyclosporine therapy. Baseline testing for hepatitis B and C is advocated. Tuberculosis testing should be performed at baseline and annually thereafter.

Methotrexate in psoriasis: consensus conference.

Roenigk HH Jr, Auerbach R, Maibach H, Weinstein G, Lebwohl M. J Am Acad Dermatol 1998; 38: 478–85.

Methotrexate remains one of the most effective systemic agents for psoriasis. Following an initial test dose of 2.5–7.5 mg, weekly doses ranging from 15–30 mg can be used to clear psoriasis in most patients. The most worrisome side effects are hepatotoxicity and bone marrow suppression.

These articles review many of the publications on methotrexate and cover laboratory monitoring guidelines, including blood work and liver biopsy, dosage guidelines, drug interactions, and side effects.

Patients treated with methotrexate should have baseline blood and platelet counts as well as liver function tests and creatinine. Many advocate baseline serological studies for hepatitis B and hepatitis C, and new guidelines require baseline and annual testing for tuberculosis. In Europe, assays for the amino-terminal propeptide of type III procollagen are obtained. In patients without risk factors for hepatic fibrosis (such as obesity), liver biopsies may not be required or their frequency markedly reduced. Many dermatologists in the US still obtain periodic liver biopsies to monitor hepatic fibrosis.

First-line therapies

image Anthralin (dithranol) B
image Coal tar A
image Salicylic acid C
image Topical corticosteroids A
image Vitamin D analogs A
image Tazarotene A
image Sun exposure B
image Tacrolimus ointment A
image Pimecrolimus cream A

A randomized, double-blind, vehicle-controlled study of a novel liposomal dithranol formulation in psoriasis.

Saraswat A, Agarwal R, Katare OP, Kaur I, Kumar B. J Dermatol Treat 2007; 18: 40–5.

Twenty patients were enrolled in a bilateral comparison controlled trial of 0.5% dithranol entrapped in phospholipid liposomes on one side of the body compared to the vehicle (10 patients) or a conventional 1.15% dithranol, 1.15% salicylic acid, and 5.3% coal tar preparation (10 patients) applied daily, using a 30-minute short-contact regimen for 6 weeks. Both active preparations resulted in significant improvement in psoriasis, but there was less perilesional erythema and skin staining on the side treated with the liposome preparation than with the conventional cream.

Anthralin preparations have been used successfully for psoriasis for decades, but staining and irritation have limited their acceptance by both patients and physicians. Attempts to formulate non-staining, non-irritating versions of anthralin have had limited success.

Clobetasol propionate shampoo 0.05%: a new option to treat patients with moderate to severe scalp psoriasis.

Jarratt M, Breneman D, Gottlieb AB, Poulin Y, Liu Y, Foley V. J Drugs Dermatol 2004; 3: 367–73.

The efficacy of topical corticosteroids for psoriasis has been demonstrated in numerous double-blind, placebo-controlled trials of large numbers of patients. Topical corticosteroids are available in many vehicles, including foams, emollient foams, sprays, shampoos, solutions, lotions, creams, emollient creams, ointments, tapes, and gels.

Superpotent corticosteroids such as clobetasol can be associated with cutaneous and systemic side effects. Clinically significant adrenal suppression is seldom considered, and tests for adrenal function are virtually never performed. Practicing dermatologists are more concerned with the side effects of atrophy, telangiectasia, striae, and tachyphylaxis. For all the above reasons, superpotent corticosteroid use should be limited to 2 to 4 weeks, and less than 50 g/week. Superpotent corticosteroids should not be occluded and should not be used on the face or intertriginous sites. If at all possible, they should be avoided in children.

An investigator-masked comparison of the efficacy and safety of twice daily applications of calcitriol 3 µg/g ointment vs. calcipotriol 50 µg/g ointment in subjects with mild to moderate chronic plaque-type psoriasis.

Zhu X, Wang B, Zhao G, Gu J, Chen Z, Briantais P, et al. J Eur Acad Dermatol Venereol 2007; 21: 466–72.

In this investigator-blinded study, 250 subjects were treated twice daily for 12 weeks with either calcitriol or calcipotriol ointments. Both agents were comparably effective, but there were more local cutaneous adverse events in patients treated with calcipotriol than those treated with calcitriol.

As local irritation occurs in up to 20% of patients treated with calcipotriol on facial or intertriginous skin, calcitriol may be a better therapeutic option for those sites.

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