Treatment of pustular psoriasis: From the Medical Board of the National Psoriasis Foundation

REVIEWS

Treatment of pustular psoriasis: From the Medical Board of the National Psoriasis Foundation Amanda Robinson, MD,a Abby S. Van Voorhees, MD,b Sylvia Hsu, MD,c Neil J. Korman, MD,d Mark G. Lebwohl, MD,e Bruce F. Bebo, Jr, PhD,f and Robert E. Kalb, MDg Buffalo and New York, New York; Philadelphia, Pennsylvania; Houston, Texas; Cleveland, Ohio; Portland, Oregon; and Worcester, Massachusetts Background: A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for pustular psoriasis. Meetings were held by teleconference. Consensus on treatment of pustular psoriasis was achieved. Pustular psoriasis has been classified into localized and generalized forms. There are a number of treatment modalities, but there is little evidence-based information to guide the management of this type of psoriasis. Objectives: The purpose of this article was to present treatment recommendations to aid in the treatment of patients with pustular psoriasis. Methods: A literature review was conducted to examine treatment options for pustular psoriasis and assess the strength of the literature for each option. Results: Overall the quality of the literature about the treatment of pustular psoriasis is weak. Treatment should be governed by the extent of involvement and severity of disease. Acitretin, cyclosporine, methotrexate, and infliximab are considered to be first-line therapies for those with generalized pustular psoriasis. Adalimumab, etanercept, and psoralen plus ultraviolet A are second-line modalities in this setting. Pustular psoriasis in children, in pregnant women, and in localized forms alter which agents are first-line modalities as concerns such as teratogenicity need to be factored into the decisionmaking for the individual patient. Limitations: There are few high-quality studies examining treatment options for pustular psoriasis. Conclusions: Treatment of patients with pustular psoriasis depends on the severity of presentation and patient’s underlying risk factors. The data are extremely limited for this type of psoriasis and we encourage further exploration. ( J Am Acad Dermatol 2012;67:279-88.) Key words: drug therapy; psoriasis.

From the Division of Dermatology, University of Massachusetts, Worcestera; Department of Dermatology, University of Pennsylvaniab; Department of Dermatology, Baylor College of Medicine, Houstonc; Department of Dermatology and the Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, Cleveland, Ohiod; Department of Dermatology, Mount Sinai School of Medicine, New York Universitye; National Psoriasis Foundation, Portlandf; and Department of Dermatology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo.g Funding sources: None. Disclosure: Dr Van Voorhees has served as a consultant/speaker/ advisor for Amgen, Abbott, Centocor, Genentech, Warner Chilcott, and Leo. She has been an investigator for Amgen and Genentech. She has served on a drug safety monitoring board for Synta. Dr Hsu has been a consultant for Abbott, Amgen, Biogen Idec, Centocor, and Genentech. She has been a clinical investigator for Amgen and Centocor. Dr Korman has been a consultant for Abbott, Astellas, Centocor, and

Genentech; he has also been a speaker for Abbott, Amgen, Astellas, Centocor, and Genentech. Dr Lebwohl has been a consultant for Abbott, Amgen, Astellas, Centocor, Genentech, Galderma, Leo Pharma, and Novartis. Dr Bebo is employed by the National Psoriasis Foundation. The foundation receives unrestricted financial support from Abbott, Centocor, Amgen, Wyeth, Genentech, Astellas, Stiefel, Galderma, Warner Chilcott, and Photomedix. Dr Kalb has been an investigator and consultant for Abbott, Amgen, Centocor, Astellas, Warner Chilcott, and Stiefel. Dr Robinson has no conflicts of interest to declare. Reprints not available from the authors. Correspondence to: Robert E. Kalb, MD, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 295 Essjay Rd, Buffalo, NY 14221. E-mail: [email protected]. Published online May 21, 2012. 0190-9622/$36.00 Ó 2011 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2011.01.032

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Pustular psoriasis is a form of psoriasis characterthe psoriasiform eruptions after antieTNF treatment ized by pustules on normal-appearing or inflamed are not truly psoriasis, but are a lichenoid drug erythematous skin. Historically it has been classified reaction. The withdrawal of topical corticosteroids, into localized and generalized forms. More specific systemic corticosteroids, and cyclosporine have patterns of classification have been proposed, but been shown in case reports to precipitate pustular have not been used routinely in published reports.1 psoriasis.10-13 Generalized pustular psoriasis (GPP) is the develAlthough the exact prevalence is unknown, pusopment of extensive sterile tular psoriasis is believed to pustules with widespread erybe relatively rare.14 This preCAPSULE SUMMARY sumed low incidence, few thema. The von Zumbusch number of reported cases, type often starts abruptly and Treatment of pustular psoriasis should along with an incomplete can be associated with painful be governed by the extent of understanding of the origin skin, fever, and chills. The disinvolvement and severity of disease. of the disease, makes treatease course varies from a beAcitretin, cyclosporine, methotrexate, ment challenging. nign, chronic process to an and infliximab are considered to be firstAnother major challenge is acute life-threatening episode, line therapies for patients with the lack of a standardized and as such optimal treatment generalized pustular psoriasis. method for monitoring disdepends on severity. Adalimumab, etanercept, and psoralen ease response to therapy and Diseases considered within plus ultraviolet A are second-line the lack of quality data regardthe spectrum of GPP include: modalities in this setting. ing therapy. Treatment of pusimpetigo herpetiformis and Unique concerns in specific groups such tular psoriasis has typically childhood GPP. Impetigo heras children or pregnant women with included systemic retinoids, petiformis is pustular psoriapustular psoriasis need to be factored cyclosporine, corticosteroids, sis, von Zumbusch type in a into the decisionmaking for the and methotrexate. More repregnant woman. Childhood individual patient. cently, the biologic agents GPP is the rare presentation of approved for use in plaque the von Zumbusch type in psoriasis have been used to treat patients with pustular children.2,3 Diagnostic criteria for GPP, as suggested by psoriasis. Umezawa et al,4 include: (1) multiple sterile pustules on erythematous skin; (2) systemic symptoms such as fever and malaise; (3) the presence of histopathMETHODS ologically confirmed spongiform pustules; and (4) This article is a review of the established and one or more of the following laboratory test alteracurrent therapies for pustular psoriasis. The tions: leukocytosis with left shift, elevated erythroMEDLINE terms used were ‘‘pustular psoriasis,’’ cyte sedimentation rate, elevated C-reactive protein, ‘‘generalized pustular psoriasis,’’ ‘‘impetigo herpetihigh antistreptolysin O antibody levels, elevation of formis,’’ ‘‘acrodermatitis continua of Hallopeau,’’ IgG or IgA, hypoproteinemia, hypocalcemia, or a ‘‘palmoplantar pustular psoriasis,’’ ‘‘pustular psoriarecurrence of any of the aforementioned clinical and sis in pregnancy,’’ ‘‘juvenile pustular psoriasis,’’ histologic findings. ‘‘pustular psoriasis in childhood,’’ ‘‘pustulosis palLocalized pustular psoriasis, often referred to as maris et plantaris,’’ and ‘‘pustular psoriasis of the palmoplantar pustular psoriasis (PPPP), primarily nail.’’ involves the hands and feet.5 Acrodermatitis conArticles were graded using levels of evidence tinua of Hallopeau is a form of localized pustular developed by Shekelle et al.15 IA evidence includes psoriasis that presents as chronic pustular lesions of meta-analyses of randomized controlled trials. IB the distal fingers, nail folds, and nail beds. evidence includes at least one randomized conAlthough in most cases pustular psoriasis is idiotrolled trial. IIA evidence includes at least one conpathic, a number of potential triggers have been trolled study without randomization. IIB includes identified, primarily drug related. Recently, multiple evidence from at least one type of quasiexperimental case reports describe induction or exacerbation of study. Class III evidence includes nonexperimental psoriasis by antietumor necrosis factor (TNF) agents descriptive studies, such as comparative studies, primarily in patients with psoriasis, rheumatoid correlation studies, or case-control studies. Class IV arthritis, or Crohn’s disease.6-8 These cases were a evidence includes expert committee reports or opinmixture of psoriasis vulgaris and pustular psoriasis, ions, clinical experience of respected authorities, or but PPPP was common. Seneschal et al9 argue that both. d

d

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Abbreviations used: GPP: PPPP: PUVA: TNF: UV:

generalized pustular psoriasis palmoplantar pustular psoriasis psoralen plus ultraviolet A tumor necrosis factor ultraviolet

EVIDENCE AND DISCUSSION The recommendations for the treatment of pustular psoriasis included in this review are primarily based on uncontrolled and open-label reports. There is a lack of evidence-based reports and randomized controlled trials to guide therapeutic recommendations. The only therapeutic guidelines for GPP in the literature, a study by Umezawa et al,4 suggests assessing disease severity using the Ohkawara classification.16 This takes into account skin symptoms, constitutional symptoms, and laboratory abnormalities, grouping patients into mild, moderate, or severe. Many of their treatment recommendations are not generally applicable, such as the use of Chinese herbal therapy. However, no other guidelines have been established to date. Adult GPP Evidence. 1. The recommended first-line therapy for GPP in adults is acitretin, cyclosporine, or methotrexate (Fig 1). Acitretin is the preferred first-line agent based on very limited data (Table I).4,14,17 However, methotrexate and cyclosporine are recommended as good alternatives.18 There is some evidence to indicate that methotrexate is slightly more effective than cyclosporine. Although the data are based on small case reports and series, infliximab is considered by many experts to be first-line therapy especially in patients with extensive disease.19 Because of the faster onset of action with infliximab and cyclosporine, many physicians consider these drugs as first-line treatment in patients with severe, acute disease. 2. The recommended second-line therapy for adult GPP includes adalimumab, etanercept, and combination therapy (Fig 1). Numerous small series and case reports support this recommendation (Table II). Individual case reports discuss the use of topical tacrolimus and topical corticosteroids. Combination therapy, typically using a first-line systemic agent and a biologic agent, has shown efficacy in several case reports. A single case report demonstrated the sequential use of TNFalfa inhibitors to maximize the benefits of each

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agent.20 Psoralen plus ultraviolet (UV) A (PUVA) was demonstrated to be most effective when combined with either an acitretin or cyclosporine. 3. Although systemic steroids are best avoided in the treatment of psoriasis because of the risk of worsening psoriasis, if other choices are not possible, then judicious use of systemic oral corticosteroids may be considered for the treatment of GPP.4 Discussion Both the Japanese guideline for GPP and the retrospective study by Magis et al35 recommend the use of retinoids as first-line therapy in adults with GPP.14 In addition, 89% of the dermatologic departments in France use retinoids as first-line therapy for GPP.36 In a multicenter study in Japan, Ozawa et al14 determined that oral retinoids were effective in 84% of patients with GPP. This was compared to treatment with methotrexate, cyclosporine, and PUVA, which were effective in 76%, 71%, and 46% of patients, respectively. Retinoids are more efficacious compared with other first-line systemic therapies, but also have a higher incidence of dose-dependent adverse effects. One patient with GPP was reported to develop capillary leak syndrome when treated with acitretin.37 Acitretin should not be used in any patient who is pregnant or likely to become pregnant. Mengesha and Bennett17 recommend oral acitretin at a dosage of 0.75 to 1 mg/kg/d. Patients typically respond within 7 to 10 days of oral retinoid therapy. A maintenance dose of 0.125 to 0.25 mg/kg/d should be continued for several months to prevent recurrence. Although isotretinoin is often ineffective in the treatment of psoriasis, it has been anecdotally recommended over oral acitretin for pustular psoriasis because of its dramatically shorter half-life.22,38 Methotrexate is recommended for patients with GPP who are unresponsive to or cannot tolerate retinoids. It typically has a slow onset of action requiring several weeks to reach an effective dose. Umezawa et al4 suggest dosing methotrexate from 5.0 to 15.0 mg/wk depending on disease severity. The weekly dose can be increased at 2.5-mg intervals as tolerated until symptoms respond. Collins and Rogers18 reported success with starting doses of 7.5 mg for patients older than 70 years. These patients need close monitoring for hematologic toxicity. Although there have been recommendations in the older literature to use weekly methotrexate doses up to 50 mg/wk via intramuscular or subcutaneous injections for those with the most severe psoriasis,39 the latest methotrexate guidelines suggest limiting the weekly dosage of methotrexate to no more than 25 mg.40

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Table II. Evidence levels for second-line adult GPP therapies Disease expression

Adult GPP, second line

Treatment modality

Evidence level

References

Adalimumab Etanercept PUVA Topical tacrolimus Combination therapy

III III III III

23 20, 24-26 27-29 30, 31

III

20, 23, 27, 28, 32-34

GPP, Generalized pustular psoriasis; PUVA, psoralen plus ultraviolet A.

Fig 1. GPP treatment algorithm.

Table I. Evidence levels for first-line adult GPP therapies Disease expression

Treatment modality

Evidence level

References

Adult GPP, first line

Cyclosporine Infliximab Methotrexate Retinoids

III III III IIA III IV

4, 14 17-21 4, 14, 18 22 4, 14 17

GPP, Generalized pustular psoriasis.

Cyclosporine is an alternative to retinoids, and has shown efficacy in patients with GPP at doses of 2.5 to 5 mg/kg/d. Umezawa et al4 recommend 3.5 to 5 mg/kg/d for moderate to severe GPP. If patients respond well, the dose can be tapered down by 0.5 mg/kg every 2 weeks. The onset of action for cyclosporine is relatively rapid with improvement reported as early as 2 weeks from the beginning of therapy. There have not been any studies to evaluate a difference in efficacy between methotrexate and cyclosporine, aside from the Japanese study by Ozawa et al,14 which identified methotrexate as slightly more effective than cyclosporine. One study demonstrated that oral corticosteroids have a 60% efficacy rate and 26% incidence of adverse events.4 They are reliably effective for the treatment of serious acute episodes of GPP, but should be avoided if feasible because of the possibility of a withdrawal rebound effect. Although

clinical experience suggests that there may be decreased risk for rebound flares if oral corticosteroids are combined with another systemic agent, which can be continued after the steroid withdrawal, there are no studies to verify this concept. A number of small series document the dramatic and rapid improvement in GPP of infliximab (alone or in combination).19-21,32-34,41-43 Because of the faster onset of action with infliximab and cyclosporine, many physicians consider these drugs as firstline treatment in patients with severe, acute disease. Second-line therapeutic recommendations for GPP in adults include adalimumab, etanercept, topical therapy, and phototherapy. Adalimumab has been suggested in one case report as an effective and well-tolerated monotherapy for severe GPP.23 As more experience accumulates, the antieTNF-alfa agents may be positioned as first line. There are reports of pustular psoriasis worsening on antieTNFalfa biologic therapy. However, the majority of these patients had rheumatoid arthritis or inflammatory bowel disease.44 Topical therapy may be useful as an adjunct to systemic therapy, or as first-line therapy for localized or mild disease. Case reports document the efficacy of topical calcipotriene (calcipotriol) and topical tacrolimus therapy in GPP.30,31 Anecdotal evidence suggests that triamcinolone ointment plus total body wet wraps reduces scaling and discomfort in GPP.17 Whirlpool treatments may also be helpful in removing crust and scale. Based on a small number of case reports, photochemotherapy with PUVA is also considered secondline treatment for adults. PUVA is not recommended for acute inflammatory forms of pustular psoriasis. Once control of the active disease is obtained with other treatment options, patients can be transitioned to a long-term maintenance treatment. Several case reports demonstrate improved efficacy in recalcitrant GPP cases when two or more different classes of therapeutic agents are used in

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Table IV. Evidence levels for second-line childhood GPP therapies Disease expression

Childhood GPP, second line

Treatment modality

Evidence level

References

Adalimumab Infliximab UVB phototherapy

III III III

54 48 55, 56

GPP, Generalized pustular psoriasis; UV, ultraviolet.

based on safety and efficacy results in the treatment of childhood plaque psoriasis. Whether other antieTNF-alfa agents would be a better option is not known.

Fig 2. Childhood GPP treatment algorithm.

Table III. Evidence levels for first-line childhood GPP therapies Disease expression

Childhood GPP, first line

Treatment modality

Evidence level

References

Cyclosporine Etanercept Methotrexate Retinoids

III III III III

3, 46, 47 48 49, 50 51, 52

GPP, Generalized pustular psoriasis.

tandem. These include etanercept and cyclosporine, infliximab and methotrexate, and infliximab followed by etanercept.19,32-34,43,45 Combination therapy allows physicians to maximize benefits and reduce adverse effects associated with various therapies. Childhood GPP Evidence. 1. First-line therapies for childhood GPP includes acitretin, acitretin in combination with oral prednisone, methotrexate, and cyclosporine (Fig 2). A small number of case series and case reports support this recommendation (Table III). Acitretin does not have Food and Drug Administration approval for any indication in children and is relatively contraindicated in females of childbearing potential. In addition there is a slight concern of skeletal toxicity although this has been an issue in children treated with high doses for disorders of keratinization.38,53 Despite the presence of only case report data, some experts would suggest etanercept is first-line therapy

2. Second-line therapy for juvenile GPP includes adalimumab, infliximab, and UVB phototherapy (Fig 2). This is based on a small number of case reports (Table IV). It is possible that as more experience is gained, antieTNF-alfa agents may become first-line agents for juvenile pustular psoriasis. However, at this time there is limited information available in the literature. UVB phototherapy is used after acute disease is controlled with the use of conventional first-line therapy. Discussion Recommendations for first-line therapy for GPP in childhood are similar to those for adults. There is no evidence to suggest any superiority among systemic retinoids, methotrexate, and cyclosporine. Retinoids at doses less than 1 mg/kg/d are considered appropriate for children with severe or recalcitrant GPP. The potential for skeletal toxicity needs to be considered. Acitretin is relatively contraindicated in girls of reproductive age, depending on the patient’s age and the severity of the disease. There is a report of a teenaged girl successfully treated with isotretinoin instead of acitretin in an effort to avoid long-term teratogenic effects.52 Retinoids may be combined with oral prednisone for acute disease.50 Several case studies demonstrate safety and efficacy of cyclosporine in children.3,46,47 Some authors suggest cyclosporine as first-line therapy, as it is associated with fewer long-term adverse effects than retinoids, corticosteroids, or methotrexate.46 Cyclosporine has been successfully used to treat the acute phase of pediatric GPP at doses between 1 and 3 mg/kg/d. Patients are usually treated for 2 to 4 weeks before significant clinical improvement is seen. Low-dose methotrexate (0.2-0.4 mg/kg/wk) is another useful treatment option in children with GPP. Children as young as 2 years of age have been safely treated with methotrexate. Improvement is

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Table V. Evidence levels for first-line therapies for GPP in pregnancy Disease expression

Treatment modality

GPP in pregnancy, Cyclosporine first line Infliximab Oral steroids Topical corticosteroids Topical calcipotriene

Evidence level References

III III III III

57, 58 59 57 4

III

4

GPP, Generalized pustular psoriasis.

Table VI. Evidence levels for second-line therapies for GPP in pregnancy Disease expression

Fig 3. Treatment algorithm for GPP in pregnancy.

typically seen within a few weeks of initiating methotrexate therapy. Although there are very limited data on its use in childhood GPP, some experts believe etanercept has advantages based on the safety information published in the treatment of childhood plaque psoriasis for children 4 to 17 years of age. Etanercept at 0.4 mg/kg twice weekly for 2 months induced slow improvement in a single case of recalcitrant GPP.48 Second-line therapy for GPP in children includes adalimumab, infliximab, and UVB phototherapy. Case reports demonstrate improvement in cases of recalcitrant disease using biologic therapy. Adalimumab given as 40 mg subcutaneously every other week rapidly cleared skin lesions and arthritis.54 Narrowband UVB has been shown in case reports to be an effective adjunctive therapy. Two case reports demonstrate effective use of UVB in combination with systemic retinoids for maintenance of disease.55,56 GPP in pregnancy Evidence. 1. First-line therapy for pregnant women with GPP includes cyclosporine, oral corticosteroids, and topical agents (Fig 3). The data are extremely limited. Although a category C drug, cyclosporine has a significant safety record based on studies in pregnant patients with organ transplantation. Whether category B biologic agents are better options is not known although a recent case report documented the efficacy of infliximab (Table V).60

GPP in pregnancy, second line

Treatment modality

Evidence level

References

Phototherapy PUVA UVB

III III

60 61

GPP, Generalized pustular psoriasis; PUVA, psoralen plus ultraviolet A; UV, ultraviolet.

2. Second-line therapy for GPP in pregnancy is narrowband UVB or oral PUVA treatment based on case reports (Fig 3). These therapies were used after control of disease with other first-line agents (Table VI). Discussion The best therapeutic options in pregnancy are cyclosporine, oral corticosteroids, infliximab, or topical agents. The Japanese guidelines recommend topical corticosteroids as first-line therapy and topical calcipotriene (calcipotriol) or topical PUVA as second-line for mild to moderate disease. Systemic agents should be reserved for severe cases. Oral prednisone at doses of 30 to 40 mg per day has shown limited efficacy, and may be more effective when combined with cyclosporine. Data from patients with transplantation along with several case reports indicate that cyclosporine is not associated with an increased risk of adverse effects during the pregnancy at a dose of 2 to 3 mg/kg.58,62,63 A recent case report documented the efficacy of infliximab.48 With a category B pregnancy status and rapid onset of action, infliximab may offer advantages in acute severe disease. Phototherapy is considered secondline therapy in pregnancy. There are only two case reports. Phototherapy is generally not recommended for acute disease. One case report documents narrowband UVB as an alternative therapy for GPP in pregnancy that is resistant to topical corticosteroid treatment.61 A second case report demonstrated a therapeutic response with oral PUVA.60

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Table VIII. Evidence levels for second-line local therapies for localized pustular psoriasis Disease expression

Localized pustular psoriasis, second-line local therapy

Treatment modality

Evidence level

References

Photodynamic therapy Topical tacrolimus

III

68, 69

III

70

Fig 4. Localized pustular psoriasis treatment algorithm using local therapy.

Table VII. Evidence levels for first-line local therapies for localized pustular psoriasis Disease expression

Treatment modality

Localized pustular PUVA psoriasis, Topical first-line calcipotriene local therapy Topical corticosteroids

Evidence level

References

III III

64 65, 66

III

67

PUVA, Psoralen plus ultraviolet A.

Localized pustular psoriasis/PPPP Evidence. 1. First-line local therapies include topical corticosteroids, calcipotriene (calcipotriol), combination products, and topical or oral PUVA (Fig 4). Randomized prospective trials identified topical steroids under hydrocolloid dressing and topical calcipotriene (calcipotriol) as effective therapies (Table VII). 2. Second-line local treatment includes photodynamic therapy and topical tacrolimus (Fig 4). Photodynamic therapy may not be widely available and the improvement was relatively modest. The recommendation for tacrolimus is based on a single case report when used in combination with calcipotriol (Table VIII).70 3. First-line systemic therapies for PPPP are cyclosporine, retinoids, and PUVA (Fig 5). The only placebo-controlled study was on the use of cyclosporine. Another controlled study compared PUVA to PUVA with etretinate (retinoid-PUVA).

Fig 5. Localized pustular psoriasis treatment algorithm using systemic therapy.

Methotrexate is considered by many experts to be effective but there are no specific data in localized palmoplantar disease (Table IX). 4. Second-line systemic therapies for PPPP are the biologic agents, alefacept, adalimumab, etanercept, and infliximab (Fig 5). Small open-label studies demonstrated efficacy using alefacept and adalimumab whereas etanercept and infliximab were observed to be efficacious in case series (Table X). Although none of the studies were controlled, improvements with alefacept were more modest compared with the other biologic agents. 5. An open-label study suggests that TNF blockers can be combined effectively with methotrexate for PPPP.21 Discussion First-line local therapy for PPPP includes topical corticosteroids, calcipotriene (calcipotriol), combination products, and phototherapy. Topical steroids combined with salicylic acid are equivalent to

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Table IX. Evidence levels for first-line systemic therapies for localized pustular psoriasis Disease expression

Localized pustular psoriasis, first-line systemic therapy

Treatment modality

Evidence level

References

Cyclosporine PUVA Retinoids

IB III III

71 72 65

PUVA, Psoralen plus ultraviolet A.

Table X. Evidence levels for second-line systemic therapies for localized pustular psoriasis Disease expression

Treatment modality

Adalimumab Localized pustular psoriasis, second-line Alefacept Etanercept systemic therapy Infliximab

Evidence level References

III III III III

73, 74 73, 75 76 77

calcipotriene (calcipotriol) alone in treating nail bed psoriasis.78 A randomized trial found that a hydrocolloid occlusive dressing over a medium-strength steroid cream is more effective than a high-potency steroid cream without an occlusive dressing. However, the improvements achieved with steroid cream with or without dressing were not long lasting.67 Piraccini et al65 showed that severe cases or cases with multiple nail involvement are best treated with oral retinoids, whereas topical calcipotriene (calcipotriol) was used to treat single-digit disease and to control relapses after retinoid therapy. Topical calcipotriene (calcipotriol) was effective as monotherapy in only about half of the patients treated. Sotiriadis et al66 demonstrated in a case report that a calcipotriene (calcipotriol) and betamethasone dipropionate two-compound ointment effectively treats acrodermatitis continua of Hallopeau, and suggested that this combination therapy should be used as first line. Topical PUVA is another first-line option.64 Second-line local therapy for PPPP includes photodynamic therapy. A small prospective study demonstrated promising short-term results using a 308-nm monochromatic excimer light delivery system. However, the improvements observed were much less dramatic 6 months out.68 Other therapies used were photodynamic therapy with aminolevulinic acid, and hematoporphyrin-containing ointment. These were all somewhat effective in the short term and well tolerated.69,79,80 First-line systemic therapy for PPPP includes cyclosporine, retinoids, and PUVA.

According to the randomized, double-blind, placebo-controlled study by Erkko et al,71 dosing of cyclosporine for PPPP is typically 1 to 2 mg/kg/d with a mean effective dose of 1.2 to 1.7 mg/kg/d. Oral retinoid treatment for acute disease was beneficial for about half of the patients in a randomized controlled trial. Lawrence et al72 conducted a randomized controlled trial demonstrating that there is a therapeutic advantage to adding etretinate to PUVA therapy with an expected increased amount of retinoid-related side effects. Biologic agents make up the second-line systemic treatment for PPPP. Alefacept, etanercept, and adalimumab have been reported in individual cases and small series to effectively treat pustular psoriasis localized to the hands and feet. A pilot study using alefacept in palmoplantar pustulosis showed that 16 weeks of alefacept 15 mg intramuscularly once weekly led to a modest improvement in 15 of 15 patients.73 A second small prospective study of alefacept at doses of 15 to 30 mg per week showed a modest clinical improvement after 10 weeks of therapy.75 In a study of adalimumab in 7 patients with PPPP, adalimumab cleared clinical disease in 6 of 7 patients.81 Several case reports have demonstrated the efficacy of using infliximab to achieve rapid improvement of symptoms, then switching to another TNF antagonist such as etanercept or adalimumab.74,82 Etanercept was presented in a case report as a successful addition to a treatment regimen of acitretin and topical corticosteroids.83 Conclusion Treatment of patients with pustular psoriasis depends on the severity of presentation and patient’s underlying risk factors. The data are extremely limited in this type of psoriasis and we encourage further exploration into the optimization of these medications in this setting. REFERENCES 1. Bagel J. Be prepared to treat pustular psoriasisean uncommon variant. Pustular psoriasis is a rare form of psoriasis that may require different approaches to treatment. Practical Dermatol 2007:43. 2. Nanda A, Kaur S, Kaur I, Kumar B. Childhood psoriasis: an epidemiologic survey of 112 patients. Pediatr Dermatol 1990; 7:19-21. 3. Alli N, G€ ung€ or E, Karakayali G, Lenk N, Art€ uz F. The use of cyclosporin in a child with generalized pustular psoriasis. Br J Dermatol 1998;139:754-5. 4. Umezawa Y, Ozawa A, Kawasima T, Shimizu H, Terui T, Taqami H, et al. Therapeutic guidelines for the treatment of generalized pustular psoriasis (GPP) based on a proposed classification of disease severity. Arch Dermatol Res 2003;295(Suppl):S43-54.

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