Published on 16/03/2015 by admin
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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
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.
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.
Guttate psoriasis is characterized by widespread erythematous, scaling papules. The management of guttate psoriasis is very similar to that of extensive plaque psoriasis. Because streptococcal infection often precedes guttate psoriasis, underlying infection should be sought and treated. Lesions are usually too widespread for topical therapy, so most patients are started on phototherapy with UVB. If that is ineffective, oral retinoids can be added or patients can be switched to narrowband UVB or PUVA. This form of psoriasis frequently responds to phototherapy, so it is only occasionally necessary to resort to the more aggressive second-line or third-line therapies listed below.
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 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.
Skin biopsy (if the clinical diagnosis of psoriasis is uncertain)
Laboratory investigations
– Serum electrolytes and calcium for patients with pustular psoriasis
– Anti-streptolysin O or bacterial cultures for patients with guttate psoriasis
– Appropriate drug-related monitoring for patients on systemic therapies
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.
From the Medical Board of the National Psoriasis Foundation: monitoring and vaccinations in patients treated with biologics for psoriasis.
Lebwohl M, Bagel J, Gelfand JM, Gladman D, Gordon KB, Hsu S, et al. J Am Acad Dermatol 2008; 58: 94–105.
Apart from history, physical examination, routine chemistry screening, CBC and platelet counts, testing for tuberculosis is advised for patients treated with all of the biologics. Liver function tests should be monitored more frequently in patients treated with infliximab; testing for hepatitis B and C is now advocated prior to starting biologic therapy.
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 and psoriasis: 2009. National Psoriasis Foundation Consensus Conference.
Kalb R, Strober B, Weinstein G, Lebwohl M. J Am Acad Dermatol 2009; 60: 824–37.
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.
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.
Efficacy of topical 5% liquor carbonis detergens vs. its emollient base in the treatment of psoriasis.
Kanzler MH, Gorsulowsky DC. Br J Dermatol 1993; 129: 310–14.
Liquor carbonis detergens 5% resulted in more improvement in psoriasis than its vehicle emollient base in a bilateral-paired comparison study.
Tars are available in gels, creams, emollient creams, and ointments, and are also available in emulsions that are added to the bath. There is a general belief that more cosmetically elegant preparations are better tolerated by patients but less effective. Crude coal tar is quite effective, but quite messy.
The role of salicylic acid in the treatment of psoriasis.
Lebwohl M. Int J Dermatol 1999; 38: 16–24.
Salicylic acid is a keratolytic agent that removes scale and allows other topical medications to penetrate. There is a marked increase in penetration of topical corticosteroids when combined with 2–10% salicylic acid. Combinations of salicylic acid and tar or anthralin have also been used successfully, but salicylic acid inactivates calcipotriol. Moreover, salicylic acid blocks UVB and should therefore not be applied prior to phototherapy.
Evaluation of the efficacy and safety of clobetasol propionate spray in the treatment of plaque-type psoriasis.
Jarratt MT, Clark SD, Savin RC, Swinyer LJ, Safley CF, Brodell RT, et al. Cutis 2006; 78: 348–54.
The efficacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions.
Gottlieb AB, Ford RO, Spellman MC. J Cutan Med Surg 2003; 7: 185–92.
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.
Once daily treatment of psoriasis with tacalcitol compared with twice daily treatment with calcipotriol. A double-blind trial.
Veien NK, Bjerke JR, Rossmann-Ringdahl I, Jakobsen HB. Br J Dermatol 1997; 137: 581–6.
Tacalcitol ointment applied once daily proved to be slightly less effective than calcipotriol ointment twice daily in this 8-week, double-blind study conducted in 287 patients.
A 52-week randomized safety study of a calcipotriol/betamethasone dipropionate two-compound product (Dovobet/Daivobet/Taclonex) in the treatment of psoriasis vulgaris.
Kragballe K, Austad J, Barnes L, Bibby A, de la Brassinne M, Cambazard F, et al. Br J Dermatol 2006; 154: 1155–60.
Six hundred and thirty-four patients were treated once daily for 4 weeks with a combination ointment containing calcipotriol and betamethasone dipropionate. After 4 weeks they were randomized to receive either the combination product or the combination product alternating with calcipotriol ointment at 4-week intervals, or calcipotriol ointment alone as needed for 48 weeks in this double-blind trial. The combination product was consistently more effective than calcipotriol, and patients treated throughout with combination product had the fewest side effects. Cutaneous atrophy occurred in four (1.9%) of those randomized to receive the combination ointment for 52 weeks.
Calcipotriol is a relatively unstable molecule which is inactivated upon mixing with many other topical agents, so the availability of a stable combination ointment of calcipotriol with a corticosteroid is desirable. Long-term therapy with any product containing a topical corticosteroid should be done with caution to avoid cutaneous atrophy, and especially the development of striae. To minimize local cutaneous side effects, avoid strong corticosteroids on the face and intertriginous sites. Use intermittent dosing such as weekend therapy for maintenance of therapeutic effect.
Tazarotene cream in the treatment of psoriasis: two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks.
Weinstein GD, Koo JY, Krueger GG, Lebwohl M, Love NJ, Menter MA, et al. Tazarotene Cream Clinical Study Group. J Am Acad Dermatol 2003; 48: 760–7.
Tazarotene creams 0.1% and 0.05% were compared to vehicle once daily for 12 weeks in this double-blind study. Tazarotene 0.1% was more effective but also more irritating than the 0.05% cream, and both were superior in efficacy to vehicle.
Tazarotene creams are slightly less effective but also less irritating than tazarotene 0.1% and 0.05% gels.
Tacrolimus ointment is effective for facial and intertriginous psoriasis.
Lebwohl M, Freeman AK, Chapman MS, Feldman SR, Hartle JE, Henning A. Tacrolimus Ointment Study Group. J Am Acad Dermatol 2004; 51: 723–30.
One hundred and sixty-seven patients were treated in this double-blind, placebo-controlled trial of tacrolimus 0.1% ointment applied twice daily for 8 weeks for facial and intertriginous psoriasis. At the end of 8 weeks 65.2% of tacrolimus ointment-treated patients and 31.5% of vehicle-treated patients were clear or almost clear.
Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study.
Gribetz C, Ling M, Lebwohl M, Pariser D, Draelos Z, Gottlieb AB, et al. J Am Acad Dermatol 2004; 51: 731–8.
In this double-blind study 57 patients were treated with 1% pimecrolimus cream or placebo. At the end of week 8, 71% of pimecrolimus-treated patients were clear or almost clear, compared to 41% of vehicle-treated patients.
Topical calcineurin inhibitors are valuable alternatives for psoriasis in facial and intertriginous sites which are particularly susceptible to corticosteroid side effects and easily irritated by calcipotriol or tazarotene.
The percentage of patients achieving PASI 75 after 1 month and remission time after climatotherapy at the Dead Sea.
Harari M, Novack L, Barth J, David M, Friger M, Moses SW. Int J Dermatol 2007; 46: 1087–91.
Sixty-four patients were treated with climatotherapy at the Dead Sea, which included bathing in Dead Sea water and gradually increasing sun exposure. All patients achieved PASI 50 and 75.9% achieved PASI 75. The median time to recurrence of a lesion of psoriasis was 23.1 weeks and the median duration of effect, defined as the time to 50% relapse in the PASI improvement, was 33.6 weeks.
The Dead Sea is the lowest point on earth and has the highest concentration of minerals of any body of water on the earth. The mineral haze in the atmosphere through which sunlight passes results in a unique spectrum of sunlight that accounts for the exceptional therapeutic responses. Two to four weeks of Dead Sea sun exposure and bathing are required to achieve significant benefit.
Components of the Goeckerman regimen.
Le Vine MJ, White HA, Parrish JA. J Invest Dermatol 1979; 73: 170–3.
The efficacy of UVB phototherapy is improved by the addition of a topical tar preparation or lubricating base; 5% crude coal tar is no more effective than lubricating base when combined with a phototherapy regimen.
The original Goeckerman regimen involved inpatient application of crude coal tar, which was removed prior to daily UVB phototherapy. Most current phototherapy regimens involve outpatient treatment three times per week with topical application of mineral oil or petrolatum.
Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B.
Coven TR, Burack LH, Gilleaudeau R, Keogh M, Ozawa M, Krueger JG. Arch Dermatol 1997; 133: 1514–22.
Twenty-two patients were treated in a bilateral comparison study with narrowband UVB on one side and broadband UVB on the other. The side treated with narrowband UVB cleared more quickly and more completely than the side treated with broadband UVB.
Randomized double-blind trial of the treatment of chronic plaque psoriasis: efficacy of psoralen-UV-A therapy vs. narrowband UV-B therapy.
Yones SS, Palmer RA, Garibaldinos TT, Hawk JL. Arch Dermatol 2006; 142: 836–42.
In this double-blind study 93 patients were treated twice weekly with either narrowband UVB or PUVA until clearance or up to a maximum of 30 sessions. In patients with skin types I–IV, PUVA was significantly more effective than UVB, with 84% of PUVA-treated patients clearing compared to 65% of narrowband UVB-treated patients. PUVA cleared patients after a median of 17 treatments, compared to 28.5 treatments for narrowband UVB. Six months after the last treatment 68% of patients treated with PUVA remained clear, compared to 35% of patients treated with narrowband UVB.
Although PUVA is more effective than narrowband UVB, it is more difficult to administer and has an increased risk of phototoxicity and carcinogenicity. Baseline and annual eye examinations have been suggested for patients treated with oral PUVA, but initial concerns about the development of cataracts in these patients have not been borne out over time. Baseline serologies for lupus were once recommended prior to starting patients on PUVA, but are now only obtained in patients who have other signs or symptoms of the disease.
PUVA therapy for psoriasis: comparison of oral and bath-water delivery of 8-methoxypsoralen.
Lowe NJ, Weingarten D, Bourget T, Moy LS. J Am Acad Dermatol 1986; 14: 754–60.
Bath-water delivery of methoxsalen (bath-PUVA) 3.7 mg/L (approximately 60 mg dissolved in a tub of water) is as effective as oral PUVA, but requires less UVA and is not associated with systemic side effects such as nausea. Phototoxicity may be increased.
Side effects of burning, sun sensitivity, and, especially, photocarcinogenicity are of concern. Topically applied methoxsalen has also been shown to be effective for psoriasis, but is associated with more phototoxicity.
Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION).
Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG, Ortonne JP, et al. Br J Dermatol 2008; 158: 558–66.
Adalimumab 40 mg every other week following an 80 mg loading dose was compared to methotrexate 7.5 mg orally, increased according to clinical response up to 25 mg/week or placebo for 16 weeks. Of adalimumab-treated patients, 79.6% achieved PASI 75, compared to 35.5% of those patients treated with methotrexate and 18.9% of those treated with placebo. Methotrexate patients suffered the most adverse events leading to study discontinuation, mostly related to hepatic complications.
This was the first placebo-controlled trial of methotrexate for psoriasis. The trial design has been criticized for starting methotrexate at a low dose. Nevertheless, the clear efficacy of adalimumab and the side effects of methotrexate were demonstrated by this study.
A double-blind, placebo-controlled trial of acitretin for the treatment of psoriasis.
Olsen EA, Weed WW, Meyer CJ, Cobo LM. J Am Acad Dermatol 1989; 21: 681–6.
In a double-blind study 15 patients were treated with a daily acitretin dose of 25 mg or 50 mg or placebo for 8 weeks. All were then treated in an open-label study with either 25 mg or 75 mg of acitretin daily. Improvement in psoriasis was only moderate.
Acitretin plus UVB therapy for psoriasis. Comparisons with placebo plus UVB and acitretin alone.
Lowe NJ, Prystowsky JH, Bourget T, Edelstein J, Nychay S, Armstrong R. J Am Acad Dermatol 1991; 24: 591–4.
Photochemotherapy for severe psoriasis without or in combination with acitretin: a randomized, double-blind comparison study.
Tanew A, Guggenbichler A, Hönigsmann H, Geiger JM, Fritsch P. J Am Acad Dermatol 1991; 25: 682–4.
This was a double-blind study of 60 patients treated with either PUVA alone or PUVA in combination with acitretin. Ninety-six percent of patients treated with acitretin and PUVA achieved marked or complete clearing, compared to 80% of patients treated with PUVA alone. The cumulative UVA dose used for the acitretin + PUVA group was 42% lower than for the patients treated with PUVA alone.
Acitretin monotherapy has limited benefit for psoriasis, partly because of its limited efficacy and partly because higher dosing results in more mucocutaneous side effects, such as hair loss and cheilitis. In combination with other treatments such as UVB or PUVA, even low doses of acitretin result in dramatically enhanced efficacy. It is also useful in combination or monotherapy for palm and sole psoriasis.
Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis.
Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, et al. N Engl J Med 2003; 349: 658–65.
Eighty-eight patients were randomized to treatment with either methotrexate starting at 15 mg and adjusted according to clinical response or cyclosporine starting at 3 mg/kg and adjusted according to clinical response. Psoriasis improved in both groups, with a slightly greater response in the cyclosporine group. Twelve of 44 patients in the methotrexate group had to discontinue treatment because of liver function test abnormalities.
Etanercept treatment for children and adolescents with plaque psoriasis.
Paller AS, Siegfried EC, Langley RG, Gottlieb AB, Pariser D, Landells I, et al. Etanercept Pediatric Psoriasis Study Group. N Engl J Med 2008; 358: 241–51.
Two hundred and eleven patients age 4–17 years participated in this double-blind trial of weekly injections of placebo or 0.8 mg/kg of etanercept. Fifty-seven percent of etanercept-treated children achieved PASI 75, compared to 11% of those treated with placebo.
In adults etanercept can be administered in doses of 50 mg twice weekly. In the US, after 3 months the dosage is lowered to 50 mg administered subcutaneously once weekly, but in other countries the twice-weekly dosing can continue. As in adults, the pediatric dose of 0.8 mg/kg is effective in children with psoriasis and psoriatic arthritis.
Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial.
Menter A, Tyring SK, Gordon K, Kimball AB, Leonardi CL, Langley RG, et al. J Am Acad Dermatol 2008; 58: 106–15.
In this 1212-patient double-blind, placebo-controlled trial of adalimumab 40 mg every other week for 15 weeks, 71% of adalimumab-treated patients achieved PASI 75, compared to 7% of placebo-treated patients.
Even higher response rates were achieved in patients treated with adalimumab 40 mg subcutaneously every week. A loading dose of 80 mg of adalimumab results in much faster clinical responses.
A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis.
Menter A, Feldman SR, Weinstein GD, Papp K, Evans R, Guzzo C, et al. J Am Acad Dermatol 2007; 56: 31.e1–15.
In this double-blind study 835 patients with moderate-to-severe psoriasis were treated with either infliximab 3 mg/kg or 5 mg/kg or placebo at weeks 0, 2, and 6. PASI 75 was achieved by 75.5% of patients in the 5 mg/kg group, compared to 70.3% in the 3 mg/kg group. At week 14, infliximab-treated patients were re-randomized to continuous or intermittent maintenance regimens. Greater improvements in psoriasis occurred with continuous rather than intermittent treatment, and with the 5 mg/kg dose.
Continuous infliximab therapy may suppress the development of human antichimeric antibodies, which have been associated with more infusion reactions and reduced responsiveness to the drug.
Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2).
Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Lancet 2008; 371: 1675–84.
In this double-blind study 1230 patients were treated with ustekinumab 45 mg or 90 mg or placebo. The drug was administered subcutaneously at weeks 0 and 4, and every 12 weeks thereafter. Of those treated with 45 mg, 66.7% achieved PASI 75 compared to 75.7% of those treated with 90 mg and 3.7% of those treated with placebo. At week 28 partial responders (i.e., those who achieved PASI 50 but not PASI 75) were re-randomized to increase dosing to every 8 weeks, or to continue every 12 weeks. Of those who increased to 90 mg of ustekinumab every 8 weeks, 68.8% achieved PASI 75 by week 52, compared to only 33.3% of those who continued dosing every 12 weeks.
Anti-IL-12/IL-23 therapies are highly effective for psoriasis, but long-term side effects are not yet known. In the pivotal ustekinumab trials, there were two myocardial infarctions, two strokes and one cardiac arrhythmia among the more than 1500 subjects treated with the drug, but none in the placebo group. The cardiovascular events occurred in patients with multiple risk factors and other studies did not show the increase in cardiovascular events. Five-year safety data are promising with regard to infection, malignancy, and cardiovascular disease.
Combination treatments for psoriasis: a systematic review and meta-analysis.
Bailey EE, Ference EH, Alikhan A, Hession MT, Armstrong AW. Arch Dermatol 2012; 148: 511–22.
The side effects of psoriasis treatments can be minimized and efficacy enhanced by combining low doses of different therapies. Rotational therapy refers to a method in which patients cleared with one psoriasis therapy are subsequently treated with different therapies to minimize the cumulative toxicity of any given treatment. Thus, the hepatotoxicity of cumulative doses of methotrexate, the nephrotoxicity of cyclosporine, and the carcinogenicity of PUVA can be minimized.
The most commonly used combinations involve retinoids and UVB, and retinoids and PUVA. UVB and PUVA have been used in combination with one another as well as with methotrexate. Retinoids are among the safest systemic agents for psoriasis and have been combined with methotrexate and cyclosporine, though liver function tests should be watched carefully when methotrexate and acitretin are used together. The combination of methotrexate and cyclosporine is a dramatically effective therapy, as is the combination of cyclosporine and hydroxyurea. Methotrexate has also been used with hydroxyurea, but blood counts must be watched very carefully.
Although this conference predated the introduction of biologic therapies for psoriasis, all of the currently approved biologics have been administered with methotrexate, acitretin, cyclosporine, and phototherapy. Because methotrexate and cyclosporine are immunosuppressive, they should be used cautiously with biologics and for as short a period of combination as possible. An exception may be the combination of methotrexate with inflixmab, as concomitant methotrexate has been shown to reduce the development of antichimeric antibodies.
Clinical efficacy of a 308 nm excimer laser for treatment of psoriasis vulgaris.
He YL, Zhang XY, Dong J, Xu JZ, Wang J. Photodermatol Photoimmunol Photomed 2007; 23: 238–41.
In this open-label study 40 patients were treated twice weekly for up to 15 treatments. PASI scores improved by approximately 90%.
The excimer laser is a useful therapy for localized plaques of psoriasis. Its main side effect is local cutaneous burning.
Targeted UVB phototherapy for psoriasis: a preliminary study.
Lapidoth M, Adatto M, David M. Clin Exp Dermatol 2007; 32: 642–5.
This high-intensity targeted UVB lamp (290–320 nm; Be Clear™ resulted in significant improvement in localized plaques without treating normal surrounding skin.
Efficacy of the pulsed dye laser in the treatment of localized recalcitrant plaque psoriasis: a comparative study.
Erceg A, Bovenschen HJ, van de Kerkhof PC, Seyger MM. Br J Dermatol 2006; 155: 110–14.
Pulsed dye laser was compared to the combination calcipotriol/betamethasone dipropionate ointment in an open-label, bilateral comparison study. Twelve weeks after treatment there was 62% improvement in psoriasis severity scores on the PDL-treated side, compared to 19% reduction on the combination calcipotriol/betamethasone dipropionate side.
Weekly pulse dosing schedule of fluorouracil: a new topical therapy for psoriasis.
Pearlman DL, Youngberg B, Engelhard C. J Am Acad Dermatol 1986; 15: 1247–52.
Fourteen patients were treated with topical 5-fluorouracil with occlusion two to three days per week for a mean of 15.7 weeks. Eleven patients achieved 90% clearing of treated lesions, compared to 6% for placebo.
Because of concern about absorption, topical 5-fluorouracil should only be used on isolated plaques. Irritation is the main side effect.
Weekly psoriasis therapy using intralesional fluorouracil.
Pearlman DL, Youngberg B, Engelhard C. J Am Acad Dermatol 1987; 17: 78–82.
Eleven patients were treated with intralesional injection of 1 mL of fluorouracil (50 mg/mL). Injections were repeated at one to two-week intervals, with each patient receiving an average of two injections. Nine of 11 patients improved, with maximal clearing occurring four weeks after the first injection. There were no systemic side effects, but local irritation and hyperpigmentation occurred.
Clinical assessment of patients with recalcitrant psoriasis in a randomized, observer-blind, vehicle-controlled trial using indigo naturalis.
Lin YK, Chang CJ, Chang YC, Wong WR, Chang SC, Pang JH. Arch Dermatol 2008; 144: 1457–64.
Indigo naturalis proved to be an effective topical therapy for psoriasis with clearance or near clearance in 31 of 42 subjects (74%). Staining of skin and clothing is a drawback.
Sulfasalazine improves psoriasis. A double-blind analysis.
Gupta AK, Ellis CN, Siegel MT, Duell EA, Griffiths CE, Hamilton TA, et al. Arch Dermatol 1990; 126: 487–93.
Fifty patients participated in this double-blind, placebo-controlled trial. Marked improvement was reported in 41% of the sulfasalazine-treated patients, and moderate improvement in another 41%. Over one-quarter of the sulfasalazine-treated patients discontinued the study because of side effects of rash or nausea.
Mycophenolate mofetil (CellCept) for psoriasis: a two- center, prospective, open-label clinical trial.
Zhou Y, Rosenthal D, Dutz J, Ho V. J Cutan Med Surg 2003; 7: 193–7.
Twenty-three patients were treated in an open-label study of mycophenolate mofetil 2–3 g daily for 12 weeks. At the end of 12 weeks PASI scores improved by 47%. Only 22% of patients did not have a significant response. Five patients developed nausea and one developed transient leukopenia.
Mycophenolate mofetil is highly effective in a subset of psoriasis patients. Gastrointestinal side effects can be limited by administering the drug in four divided daily doses instead of the twice-daily dosing recommended in the package insert. An enteric-coated form is also helpful in reducing nausea.
Hydroxyurea in the management of therapy resistant psoriasis.
Layton AM, Sheehan-Dare RA, Goodfield MJ, Cotterill JA. Br J Dermatol 1989; 121: 647–53.
Eighty-five patients with psoriasis were treated with long-term hydroxyurea in doses of 0.5–1.5 g daily. Remissions occurred in 61%. Reversible bone marrow suppression occurred in 35% of patients. Four patients developed cutaneous side effects.
6-Thioguanine treatment of psoriasis: experience in 81 patients.
Zackheim HS, Glogau RG, Fisher DA, Maibach HI. J Am Acad Dermatol 1994; 30: 452–8.
This was a retrospective study of 81 patients treated with 6-thioguanine for psoriasis. Improvement was maintained in nearly 50% of patients for a median of 33 months. Treatment with 6-thioguanine had to be discontinued most commonly because of reversible bone marrow suppression.
Pulse dosing of thioguanine in recalcitrant psoriasis.
Silvis NG, Levine N. Arch Dermatol 1999; 135: 433–7.
Bone marrow suppression can be avoided by treating patients with oral thioguanine two to three times per week with maintenance doses ranging from 120 twice weekly to 160 three times weekly. In this open study a marked improvement was noted in 10 of 14 patients.
Azathioprine in psoriasis.
Greaves MW, Dawber R. Br Med J 1970; 2: 237–8.
Azathioprine can be effective monotherapy for psoriasis, but its use is limited by bone marrow toxicity.
As with 6-thioguanine and hydroxyurea, the therapeutically effective dose of azathioprine is close to doses that are toxic to the bone marrow. With all three of these drugs, frequent blood counts are essential.
Systemic tacrolimus (FK 506) is effective for the treatment of psoriasis in a double-blind, placebo-controlled study.
European FK, 506 Multicentre Psoriasis Study Group. Arch Dermatol 1996; 132: 419–23.
Fifty patients with psoriasis were treated for 9 weeks in this double-blind, placebo-controlled study. Starting doses were 0.05 mg/kg daily and could be increased up to 0.15 mg/kg daily. Tacrolimus-treated patients had significantly greater improvements in PASI scores than those receiving placebo. Diarrhea, paresthesias, and insomnia were the most commonly reported side effects.
Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study: German Multicentre Study.
Mrowietz U, Christophers E, Altmeyer P. Br J Dermatol 1998; 138: 456–60.
Of 101 patients who started this prospective study, 70 completed 4 months of treatment. There was an 80% reduction in PASI scores. Side effects consisted of lymphocytopenia, gastrointestinal complaints, and flushing.
Although not noted in this study, nephrotoxicity has been a recognized side effect of fumaric acid therapy.
Use of rifampin with penicillin and erythromycin in the treatment of psoriasis. Preliminary report.
Rosenberg EW, Noah PW, Zanolli MD, Skinner RB Jr, Bond MJ, Crutcher N. J Am Acad Dermatol 1986; 14: 761–4.
All nine patients with streptococcal-associated psoriasis responded to a 5-day course of rifampin (rifampicin) combined with 10 to 14 days of oral penicillin or erythromycin.
The use of oral antibiotics has been championed by Rosenberg and colleagues. Although supported by sound theories and numerous anecdotes, the use of antibiotics for psoriasis has not been supported by controlled clinical trials. Other infections have been linked to psoriasis flares and other agents that have been used include oral nystatin and oral fluconazole; even tonsillectomy has been advocated.
Therapeutic trials with oral colchicine in psoriasis.
Wahba A, Cohen H. Acta Derm Venereol 1980; 60: 515–20.
Twenty-two patients were treated in an open trial of colchicine 0.02 mg/kg daily for 2 to 4 months. Of the nine patients with thin papules and plaques, eight noted marked improvement or clearing, but there was little improvement in patients with thick plaques.
Propylthiouracil in psoriasis: results of an open trial.
Elias AN, Goodman MM, Liem WH, Barr RJ. J Am Acad Dermatol 1993; 29: 78–81.
Propylthiouracil at a dose of 100 mg was administered orally every 8 hours for 8 weeks to 10 patients with psoriasis. Seven had marked improvement in their psoriasis and the others showed moderate improvement. Thyroid function tests were unaffected, except for a mild increase in serum thyroid-stimulating hormone after 6 weeks of therapy in a single patient.
Cryotherapy for psoriasis.
Nouri K, Chartier TK, Eaglstein WH, Taylor JR. Arch Dermatol 1997; 133: 1608–9.
Target plaques of psoriasis were treated with cryotherapy, resulting in improvement. Local reactions including pain and vesiculation were the only side effects other than discoloration.
As with lasers, cryotherapy is only practical for isolated, localized plaques. Despite the Koebner phenomenon, psoriasis does not commonly occur in frozen plaques, but scarring or discoloration can occur.
Psoriasis of the scalp treated with Grenz rays or topical corticosteroid combined with Grenz rays. A comparative randomized trial.
Lindelof B, Johannesson A. Br J Dermatol 1988; 119: 241–4.
Forty patients were treated with either Grenz rays or Grenz rays plus topical corticosteroids for scalp psoriasis. Grenz rays were administered at a dosage of 4 Gy at weekly intervals for six treatments; 84% of the Grenz ray-treated patients and 72% of the Grenz ray plus corticosteroid group healed. The addition of topical corticosteroids offered little benefit.
The association between X-ray therapy and squamous cell carcinomas, particularly in patients subsequently treated with PUVA, has led to less use of this valuable modality.
Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial.
Kaltwasser JP, Nash P, Gladman D, Rosen CF, Behrens F, Jones P, et al. Treatment of Psoriatic Arthritis Study Group. Arthritis Rheum 2004; 50: 1939–50.
One hundred and ninety patients with psoriasis and psoriatic arthritis were treated in this double-blind, placebo-controlled trial.
Leflunomide proved to be effective for psoriatic arthritis but only modestly effective for psoriasis.
Golimumab, a human TNF-alpha antibody, administered every 4 weeks as a subcutaneous injection in psoriatic arthritis. Clinical efficacy, radiographic, and safety findings through 1 year of the randomized, placebo-controlled, GO-REVEAL® study.
Kavanaugh A, van der Heijde D, McInnes I, Krueger GG, Gladman D, Gómez-Reino J, et al. Arthritis Rheum 2012; 64: 2504.
Golimumab 50 mg or 100 mg administered subcutaneously every 4 weeks resulted in significant improvement in symptoms of psoriatic arthritis. Prevention of X-ray progression of disease was documented.
Although golimumab is approved for psoriatic arthritis, this TNF antagonist also benefits skin lesions of psoriasis.
Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab’ certolizumab pegol. Results of a phase II randomised, placebo-controlled trial with a re-treatment extension.
Reich K, Ortonne JP, Gottlieb AB, Terpstra IJ, Coteur G, Tasset C, Mease P. Br J Dermatol 2012; 167: 180–90.
Following a loading dose of certolizumab pegol 400 mg, subjects were treated with subcutaneous injections of either 200 mg, 400 mg or placebo every other week; 75%, 83%, and 7% of subjects achieved PASI 75, respectively.
Although certolizumab is approved for Crohn disease and for rheumatoid arthritis in the US, this TNF antagonist is highly effective for psoriasis.
Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis.
Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, et al. N Engl J Med 2012; 366: 1190–9.
Subjects were treated with subcutaneous injections of 10, 25, 75, or 150 mg of ixekizumab or placebo at 0, 2, 4, 8, 12, and 16 weeks in this dose ranging study. With the exception of the lowest dose (10 mg) and placebo groups, PASI 75 was achieved in more than 75% of subjects.
Erythrodermic psoriasis is characterized by marked erythema and scaling affecting the entire cutaneous surface. All the protective functions of the skin are lost, including protection against infection, temperature control, and prevention of fluid loss. Loss of nutrients through the skin leads to anemia and electrolyte imbalance. The most common precipitating cause of erythrodermic psoriasis is the withdrawal of systemic corticosteroids; this should be avoided in patients with psoriasis. Excessive use of topical superpotent corticosteroids, phototherapy burns, and infections have also been implicated as causes of erythrodermic psoriasis.
Patients may require hospitalization with bed rest, emollients, and application of mild topical corticosteroids. Because sepsis and shock are complications of erythrodermic psoriasis, monitoring of temperature, blood pressure, urine output, and weight may be important, depending on the severity of the condition. In males and in females not of childbearing potential, oral retinoids are among the safest treatments for erythrodermic psoriasis, but are not as reliably effective as infliximab, cyclosporine, or methotrexate. Acitretin can be started in doses of 25 mg daily and can be increased to 50 mg or higher. Cyclosporine in doses of 4–5 mg/kg daily results in rapid improvement. Oral methotrexate starting at 15 mg/week and gradually increasing up to 30 mg/week is effective within a few weeks. Once erythema has cleared with topical or systemic agents, patients can occasionally be switched to phototherapy or PUVA or to other long-term therapies, including the biologics. Infliximab is rapidly effective for erythrodermic psoriasis, and is emerging as an important treatment option. Because antichimeric antibodies are more likely to develop against this agent if treatments are not maintained, long-term therapy with infliximab infusions must be considered if this treatment is chosen. Other biologics are likely to emerge as potential therapies for erythrodermic psoriasis; etanercept has been used with some success, but it is slower acting than infliximab.
When the above agents either do not work or cannot be used, many of the third-line therapies listed for psoriasis are effective. For example, there are anecdotal reports of 6-thioguanine, mycophenolate mofetil, azathioprine, and hydroxyurea working for erythrodermic psoriasis. Combination therapy such as the combination of methotrexate and cyclosporine in low doses, or the combination of methotrexate and infliximab, can also be effective. There are also anecdotal reports of carbamazepine clearing erythrodermic psoriasis.
Use of short-course class 1 topical glucocorticoid under occlusion for the rapid control of erythrodermic psoriasis.
Arbiser JL, Grossman K, Kaye E, Arndt KA. Arch Dermatol 1994; 130: 704–6.
Erythrodermic psoriasis will respond rapidly to oral corticosteroids or to superpotent corticosteroids with occlusion, but withdrawal of these agents often results in a more severe flare. Consequently, these treatments are avoided in patients with erythrodermic psoriasis.
Management of erythrodermic psoriasis with low-dose cyclosporine.
Studio Italiano Muticentrico nella Psoriasi (SIMPSO). Dermatology 1993; 187: 30–7.
Thirty-three patients with erythrodermic psoriasis were treated with cyclosporine, starting with up to 5 mg/kg daily; 67% achieved complete remission in a median of 2 to 4 months, and another 27% noted substantial improvement.
Life-threatening pustular and erythrodermic psoriasis responding to infliximab.
Lewis TG, Tuchinda C, Lim HW, Wong HK. J Drugs Dermatol 2006; 5: 546–8.
The authors report a rapid response of life-threatening erythrodermic psoriasis to intravenous infliximab.
There have been a number of anecdotal reports citing infliximab’s successful treatment of erythrodermic psoriasis.
Treatment of erythrodermic psoriasis with etanercept.
Esposito M, Mazzotta A, de Felice C, Papoutsaki M, Chimenti S. Br J Dermatol 2006; 155: 156–9.
Ten patients were treated with open-label etanercept 25 mg subcutaneously twice weekly. By week 12, 50% had achieved at least 75% improvement in psoriasis severity scores, and that number increased by week 24.
Erythrodermic psoriasis can be a life-threatening condition requiring more rapid-acting agents than etanercept. The latter biologic can be useful in more chronic and stable forms of the disease.
Treatment of pustulous and erythrodermic psoriasis with PUVA therapy and methotrexate.
Lekovic B, Dostanic I, Konstantinovic K, Kneitner I. Hautarzt 1982; 33: 284–5. (In German.)
The combination of PUVA and methotrexate successfully treated five patients with erythrodermic psoriasis and two with pustular psoriasis. According to the authors, annual methotrexate doses could be reduced by 50% by adding PUVA to the regimen.
It is difficult to distinguish a PUVA burn from erythrodermic psoriasis. Nevertheless, some patients with erythrodermic psoriasis are successfully controlled with PUVA. Monotherapy with methotrexate is used more typically.
The treatment of psoriasis with etretinate and acitretin: a follow up of actual use.
Magis NL, Blummel JJ, Kerkhof PC, Gerritsen RM. Eur J Dermatol 2000; 10: 517–21.
In a retrospective review of 94 patients treated with retinoids, there were no serious side effects after 10 years of follow-up. The efficacy of retinoids for pustular and erythrodermic psoriasis was stressed.
Accidental success with carbamazepine for psoriatic erythroderma.
Smith KJ, Skelton HG. N Engl J Med 1996; 335: 1999–2000.
A patient with HIV infection and erythrodermic psoriasis was inadvertently treated with carbamazepine instead of etretinate. The patient’s erythroderma cleared.
Carbamazepine in doses of 200–400 mg daily has been reported to clear erythrodermic psoriasis in some but not all patients. Further controlled clinical studies are warranted.
Management of pustular psoriasis begins with the removal of precipitating causes. Lithium, antimalarials, diltiazem, propranolol, and irritating topical therapy with tar have all been implicated, but the most common cause is the withdrawal of systemic corticosteroids. As in erythrodermic psoriasis, all the protective functions of skin are compromised and patients are susceptible to infection, fluid loss, electrolyte imbalance, loss of nutrients through the skin, and loss of temperature control. Supportive care and treatment of infection are mandatory. Oral acitretin results in rapid improvement. In women of childbearing potential isotretinoin may be preferred because the period of teratogenicity of this drug is shorter than that of acitretin. Cyclosporine, infliximab, adalimumab, and methotrexate are also highly effective for this life-threatening condition. TNF blockers have been used to treat pustular psoriasis, but caution should be exercised as there have been rare cases of pustular psoriasis caused by their use. Hydroxyurea, 6-thioguanine, mycophenolate mofetil, azathioprine, dapsone, and colchicine have also been used in isolated patients.
Systemic corticosteroids and folic acid antagonists in the treatment of generalized pustular psoriasis. Evaluation and prognosis based on the study of 104 cases.
Ryan TJ, Baker H. Br J Dermatol 1969; 81: 134–45.
Despite the short-term benefit of systemic corticosteroids for pustular psoriasis, once the dose is reduced rebound flares occur. In this study a significant proportion of patients treated with systemic corticosteroids died.
Methotrexate remains a highly effective modality for the treatment of pustular psoriasis. Doses beginning at 15 mg/week (following an initial test dose) are used.
Isotretinoin vs etretinate therapy in generalized pustular and chronic psoriasis.
Moy RL, Kingston TP, Lowe NJ. Arch Dermatol 1985; 121: 1297–301.
Although isotretinoin was less effective than etretinate for plaque psoriasis, 10 of 11 patients with pustular psoriasis responded.
Many consider acitretin or isotretinoin to be the treatment of choice for patients with pustular psoriasis. Apart from the shorter period of teratogenicity of isotretinoin, it also causes less hair loss than acitretin.
Generalized pustular psoriasis (von Zumbusch) responding to cyclosporin A.
Meinardi MM, Westerhof W, Bos JD. Br J Dermatol 1987; 116: 269–70.
This is one of numerous case reports documenting the dramatic response of pustular psoriasis to cyclosporine.
Cyclosporine in doses of 4–5 mg/kg daily is usually effective in the treatment of pustular psoriasis.
Infliximab in recalcitrant generalized pustular arthropatic psoriasis.
Vieira Serrão V, Martins A, Lopes MJ. Eur J Dermatol 2008; 18: 71–3.
This is a case report of a patient with psoriatic arthritis and acute generalized pustular psoriasis refractory to acitretin, methotrexate, and corticosteroids which responded rapidly to treatment with infliximab, with complete clearing of lesions by week 12, along with improvement in psoriatic arthritis.
Pustular psoriasis induced by infliximab.
Thurber M, Feasel A, Stroehlein J, Hymes SR. J Drugs Dermatol 2004; 3: 439–40.
Despite several reports describing the efficacy of infliximab in pustular psoriasis, there are a small number of reports of pustular psoriasis developing in patients treated with infliximab for other indications.
Several reports of psoriasis, and specifically pustular psoriasis, developing after treatment with TNF-α blockers have emerged. Nevertheless, these agents can be highly useful for the treatment of pustular psoriasis.
Long-term efficacy of adalimumab in generalized pustular psoriasis.
Zangrilli A, Papoutsaki M, Talamonti M, Chimenti S. J Dermatol Treat 2008; 19: 185–7.
Adalimumab 40 mg subcutaneously once weekly resulted in rapid remission of chronic pustular psoriasis. The remission persisted throughout 72 weeks of treatment.
Etanercept at different dosages in the treatment of generalized pustular psoriasis: a case series.
Esposito M, Mazzotta A, Casciello C, Chimenti S. Dermatology 2008; 216: 355–60.
Six patients with generalized pustular psoriasis who failed to respond to conventional treatments were treated with etanercept 25–50 mg twice weekly for 48 weeks, with good efficacy.
Because etanercept can be slower acting than other systemic or biologic agents, and because generalized pustular psoriasis can be life-threatening, a more rapidly acting agent should be considered for severe disease.
Generalised pustular psoriasis: response to topical calcipotriol.
Berth-Jones J, Bourke J, Bailey K, Graham-Brown RA, Hutchinson PE. Br Med J 1992; 305: 868–9.
Three cases of pustular psoriasis responded to topical application of calcipotriol and the treatment was well tolerated.
It is important to monitor serum calcium when using calcipotriol in this way. Although irritation was not a problem in the reported cases, some care is required in case this develops.
Colchicine in generalized pustular psoriasis: clinical response and antibody-dependent cytotoxicity by monocytes and neutrophils.
Zachariae H, Kragballe K, Herlin T. Arch Dermatol Res 1982; 274: 327–33.
Three of four patients with pustular psoriasis cleared within 2 weeks of starting oral colchicine.
Colchicine 0.6 mg twice daily can be effective for pustular psoriasis. The dose can be increased by one pill daily, but side effects of diarrhea frequently intervene.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Anthralin (dithranol)
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Salicylic acid
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Tazarotene
Sun exposure
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UVB
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PUVA
Acitretin
Adalimumab
Etanercept
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Methotrexate
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Indigo naturalis
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Sulfasalazine
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Hydroxyurea
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Antibiotics
Colchicine
Propylthiouracil
Laser (excimer, pulsed dye)
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Secukinumab A
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Emollients
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Retinoids
Cyclosporine
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Combination therapy
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Azathioprine
Carbamazepine
Topical corticosteroids
Retinoids
Cyclosporine
Infliximab
Adalimumab
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Etanercept
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Hydroxyurea
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