Palmoplantar pustulosis: Treatment

INTRODUCTION — Palmoplantar pustulosis (PPP) is an uncommon chronic skin disorder characterized by recurrent eruptions of pustules on the palms and soles (picture 1A-F). Scale, erythema, pruritus, burning sensations, and pain are common associated features.

Although PPP involves a limited area, the disorder can have a significant negative effect on quality of life and can interfere with performance of activities of daily living. Patients with PPP on the soles of the feet may experience difficulty walking, and hand involvement may interfere with other activities.

PPP tends to have a prolonged course consisting of periods of exacerbation and partial remission. The treatment of the disease is often challenging, as responses to individual treatments are variable and unpredictable.

The management of PPP will be reviewed here. The clinical manifestations and diagnosis of PPP are reviewed separately. (See "Palmoplantar pustulosis: Epidemiology, clinical features, and diagnosis".)

OVERVIEW — High-quality data on the treatment of palmoplantar pustulosis (PPP) are limited, contributing to uncertainty about the ideal approach to treatment. Although multiple randomized trials have been performed, most are small and of poor methodologic quality [1]. Moreover, the lack of a standardized method for assessing the response to treatment, as well as the wide variability in treatment regimens, complicate comparisons of study findings.

Because of the variable and unpredictable response to treatment, our therapeutic approach consists of first treating with generally well-tolerated therapies that have been reported to be effective for improving PPP in conjunction with benign general measures to minimize symptoms. Our preferred first-line therapies are topical corticosteroids, oral retinoids, and photochemotherapy. Patients who do not respond to these interventions are candidates for other treatments. (See 'First-line therapy' below and 'Second-line therapy' below.)

GENERAL MEASURES — Regardless of the severity of the disease, we encourage all patients to engage in the following behavioral changes in an attempt to minimize symptoms and disease exacerbations:

●Skin moisturization – Moisturization of the skin can help to mediate the discomfort associated with palmoplantar pustulosis (PPP) by helping to minimize formation of cracks and fissures in skin. We encourage patients to apply a bland, unscented, emollient moisturizer on affected areas and surrounding skin several times daily as needed.

●Avoidance of irritants – Clinical experience suggests that skin irritation may contribute to exacerbations of PPP. In particular, we encourage patients to avoid wet work with the hands (eg, washing items with detergents or soaps) or to use gloves when engaging in such activity.

●Smoking cessation – Although data are insufficient for definitive conclusions on the effect of smoking cessation on the course of PPP [1], we encourage all of our patients with PPP to stop smoking based upon knowledge of the strong link between smoking and PPP [2]. The findings of an uncontrolled prospective study of 63 adult smokers with PPP suggest there may be a benefit of smoking cessation; statistically significant improvements in the number of pustules and patient scores for disease severity were noted after three to six months among patients who stopped smoking, but not among the remainder of the patients [3]. A high dropout rate was among the limitations of this study. Additional studies are needed to explore the effect of smoking cessation. (See "Palmoplantar pustulosis: Epidemiology, clinical features, and diagnosis", section on 'Pathogenesis'.)

FIRST-LINE THERAPY — First-line therapeutic options for palmoplantar pustulosis (PPP) include topical corticosteroids, an oral retinoid, and photochemotherapy.

Topical corticosteroids are often our initial choice for limited PPP (focal involvement on the palms or soles) based upon the ease of administration and well-tolerated nature of these agents. However, when patients present with extensive disease (diffuse palmar or plantar involvement) we usually begin oral retinoid treatment or photochemotherapy immediately in conjunction with topical corticosteroid therapy.

Topical corticosteroids — Topical corticosteroid therapy is an accepted first-line therapy for PPP and is the most widely used treatment [4,5]. The major advantage of topical corticosteroid therapy is that it is a skin-directed treatment with a low risk for serious adverse effects that can be administered by the patient. Clinical follow-up to ensure proper use of topical corticosteroids is still required:

●Efficacy – There are few data on the efficacy of topical corticosteroids for PPP. An open-label right-left trial in which 19 patients with bilateral PPP were randomly assigned to apply triamcinolone 0.1% cream (a medium potency topical corticosteroid) under a hydrocolloid dressing to sites of PPP on one side of the body every three days and to apply clobetasol propionate 0.05% cream (a super high-potency topical corticosteroid) twice daily without occlusion to the contralateral side found that both treatments induced improvement in PPP after four weeks [6]. However, significantly greater clinical improvement developed in sites treated with triamcinolone under occlusion than in sites treated with clobetasol without occlusion. Additionally, complete clearance occurred more frequently in the triamcinolone under occlusion areas (63 versus 16 percent of treated areas). Responses to both treatments were transient; symptoms recurred within a few weeks after treatment cessation.

Benefit of topical corticosteroid therapy is also suggested by a retrospective study [4]. Among 49 patients with PPP who were treated with high potency topical corticosteroids (twice daily for up to four weeks followed by less frequent use of lower potency topical corticosteroids), marked, moderate, partial, and no improvement were documented in 27, 29, 20, and 24 percent of patients, respectively.

●Administration – Our preferred regimen for topical corticosteroid therapy is a super high-potency topical corticosteroid applied under occlusion (table 1). We typically instruct patients to apply the topical corticosteroid under a hydrocolloid dressing. The topical corticosteroid and a hydrocolloid dressing are reapplied every three days until clearance of active PPP or for a maximum of four weeks. A response to treatment is usually evident within the first two weeks [6].

If there are no signs of clinical improvement after four weeks or worsening of symptoms occurs, we usually begin oral retinoid treatment or photochemotherapy. If the patient has partial improvement that seems likely to continue to improve with a longer course of topical corticosteroid therapy, we continue topical corticosteroid monotherapy for up to an additional four weeks, but decrease the intensity of treatment as tolerated (eg, treatment in place two days per week). If the response remains insufficient, we transition to other treatments. (See 'Oral retinoids' below and 'Photochemotherapy' below.)

Alternative methods to perform occlusion (eg, plastic wrap) are an option, but may require more frequent dressing changes. When plastic wrap occlusion is used, we instruct patients to apply the plastic wrap over the topical corticosteroid every night for one week, then every other night for two weeks followed by twice-weekly applications under plastic wrap for up to 13 additional weeks. Topical corticosteroids are not applied on the intervening occlusion-free days. We often see partial improvement within the first 10 to 20 days.

Once patients achieve resolution of active disease with topical corticosteroid therapy, we institute maintenance therapy. Our goal is to reduce the intensity of treatment to application of the high potency topical corticosteroid without occlusion two days per week.

Cutaneous atrophy is a potential adverse effect of topical corticosteroid therapy, particularly when high potency topical corticosteroids are used. The potential adverse effects of topical corticosteroid treatment are reviewed in greater detail separately. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Oral retinoids — Systemic treatment with oral retinoids (eg, acitretin, etretinate) can be effective for PPP:

●Efficacy – A 2006 systematic review identified several randomized trials that evaluated oral retinoid therapy for PPP [1]. Pooling of data from four randomized trials that compared etretinate with placebo demonstrated that 72 percent of 67 patients treated with etretinate compared with 28 percent of 60 patients given placebo showed some improvement in PPP (rate ratio 2.54, 95% CI 1.65-3.91). Moreover, 39 versus 17 percent, respectively, achieved good or excellent responses (rate ratio 2.31, 95% CI 1.20-4.46). The doses used for etretinate therapy in these trials varied; the duration of treatment ranged from 8 to 16 weeks.

Although etretinate is no longer available in many locations, including the United States, acitretin, a metabolite of etretinate, appears to be similarly effective for PPP. A randomized trial that compared etretinate with acitretin in 60 adults with PPP found that both treatments were similarly effective for improving clinical manifestations of PPP [7]. Patients in both groups were given 30 mg of the assigned medicine for four weeks followed by upward or downward dose adjustments according to clinical improvement and tolerance of therapy.

Although alitretinoin, a newer oral retinoid, appeared beneficial for PPP in an uncontrolled study [8], a phase 2 randomized trial, in which 33 adults with PPP (with or without psoriasis) were randomly assigned in a 2:1 ratio to alitretinoin (30 mg once daily) or placebo for up to 24 weeks, did not find alitretinoin more effective than placebo [9]. Additional study is necessary to confirm the effects of alitretinoin in PPP.

●Administration – Our preferred treatment regimen for PPP in adults is an initial three-month course of acitretin (50 mg per day). We usually begin with a 25 mg dose of acitretin and increase the dose by 10 mg per week as tolerated. Reductions in dose to reduce side effects are sometimes necessary.

Once satisfactory improvement is achieved, we aim to taper the drug to the lowest dose required to maintain improvement. In two randomized trials, maintenance treatment with etretinate demonstrated greater efficacy for maintaining remissions than placebo [10,11].

Side effects of oral retinoids can be limiting factors for therapy. Potential adverse effects include xerosis, cheilitis, dry mucous membranes, hypertriglyceridemia, hair loss, liver function test abnormalities, bone changes, and visual changes. Oral retinoids are teratogenic, and pregnancy should be avoided for three years following acitretin therapy. Therefore, acitretin has a relative contraindication for use in women of childbearing age.

Photochemotherapy — Psoralen plus ultraviolet A (PUVA) photochemotherapy, which involves the oral or topical administration of a psoralen (methoxsalen) prior to exposure of affected areas to ultraviolet A light, can be effective for PPP. We typically administer oral PUVA rather than topical PUVA because there is greater support for the efficacy of oral PUVA therapy. Also, in our experience, topical PUVA can be irritating to the skin and is poorly tolerated by some patients (see "Psoralen plus ultraviolet A (PUVA) photochemotherapy"):

●Efficacy – The use of oral PUVA for PPP is supported by randomized trials that compared oral PUVA with placebo [12,13]. In a trial of 22 patients with bilateral PPP, a total of 30 treatment sessions of PUVA given four times per week on one randomly selected side of the body resulted in complete clearance of treated areas in 12 patients and great improvement in an additional five patients, whereas none of the untreated sides achieved these levels of improvement [12]. The difference in effect between treated and untreated areas was statistically significant. In most cases, improvement was not seen until 10 to 20 treatments were administered and the mean number of treatments required for clearance of lesions was 26 (range 18 to 30).

The second trial compared oral PUVA (three times per week), etretinate (0.6 mg/kg per day), combination therapy with oral PUVA and etretinate, and placebo and no PUVA over a course of 12 weeks [13]. In this open trial, thirty patients with severe bilateral PPP were randomly assigned to etretinate or placebo therapy, and after two weeks began oral PUVA photochemotherapy on affected areas of one side of the body. The proportion of the 12 areas that received 12 weeks of PUVA monotherapy that cleared or exhibited much improvement was significantly greater than among the 12 affected areas assigned to placebo and no PUVA (75 versus 17 percent). The results among areas treated with etretinate monotherapy did not differ significantly from oral PUVA monotherapy, a finding that contrasts with another 12-week trial that favored etretinate over oral PUVA [14]. Combination therapy with an oral retinoid and PUVA appeared to be the most effective therapy. (See 'Re-PUVA' below.)

Although favorable responses to topical PUVA have been documented [12], randomized trials evaluating topical PUVA have not demonstrated superior efficacy over placebo [15,16]. One trial comparing oral PUVA and topical PUVA did not find a significant difference in efficacy [14]. However, the response rates to oral PUVA reported in this trial were lower than reported in other studies.

●Administration – We usually aim to administer oral PUVA three times per week and continue treatment for at least 12 weeks prior to concluding treatment inefficacy. Potential adverse effects of PUVA include burns, blistering, nausea, pruritus, phototoxicity, hyperpigmentation, premature aging of skin, and skin cancer. Adverse effects of PUVA are discussed in greater detail separately. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

SECOND-LINE THERAPY — Patients who do not respond sufficiently to first-line treatment may benefit from combination therapy with an oral retinoid and psoralen plus ultraviolet A (PUVA) or from immunosuppressive therapy.

Re-PUVA — The term "Re-PUVA" is often used to refer to combination therapy with an oral retinoid and oral or topical psoralen plus ultraviolet A (PUVA) photochemotherapy. The small randomized trials that have investigated the efficacy of this treatment support greater efficacy of Re-PUVA compared with either an oral retinoid or PUVA alone [1,13,15,17]. As an example, an unblinded trial in which 20 patients with bilateral palmoplantar pustulosis (PPP) were randomly assigned to treatment with oral etretinate or no etretinate and given topical PUVA only on the right hand and foot found complete clearance occurred in 6 of 10 sites treated with etretinate and PUVA, 2 of 10 sites treated with etretinate alone, 1 of 10 sites treated with PUVA alone, and none of 10 sites that received neither treatment after 12 weeks [15]. A separate 20-week randomized trial that compared etretinate and oral PUVA with oral PUVA and placebo in 17 patients with PPP and 3 patients with hyperkeratotic palmoplantar psoriasis found that combination therapy was associated with a greater likelihood of response, significantly fewer treatments required for clearance, and a shorter time to response [17]. Oral PUVA was started two weeks after the start of etretinate therapy and was given three times per week.

We usually begin acitretin therapy (25 to 50 mg per day) two to four weeks before the start of PUVA therapy when administering Re-PUVA treatment. Once PUVA treatment is started, we reduce the dose of acitretin to 10 to 20 mg per day. PUVA treatments are given two or three days per week. We are cautious with the initial dose of PUVA in this population because of concern for retinoid-induced thinning of the stratum corneum resulting in an increased propensity to burn. Thus, we reduce our initial PUVA dose by 30 to 50 percent compared with the dose we would use for a patient who is not on oral retinoid therapy. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Oral PUVA'.)

Immunosuppressants — Immunosuppressive therapy with cyclosporine or methotrexate can be beneficial for some patients with PPP. The potential for serious adverse effects should be considered prior to the initiation of these therapies:

●Cyclosporine – A few randomized trials support the use of cyclosporine for PPP. In a trial in which 40 patients with PPP were randomized to treatment with oral cyclosporine (2.5 mg/kg per day) or placebo, 17 of 19 patients who completed the four-week treatment phase had at least a 50 percent reduction in the number of pustules compared with 4 of 15 patients in the placebo group (89 versus 27 percent) [18]. Lower doses of cyclosporine may also be effective. A randomized trial by the same group in which 58 patients were randomly assigned to oral cyclosporine (1 mg/kg per day) or placebo for one month found at least a 50 percent reduction in pustules in 48 percent of 27 patients in the cyclosporine group compared with 19 percent of 31 patients in the placebo group [19].

Uncontrolled studies have also suggested benefit. In a prospective study in which 48 adults with PPP received oral cyclosporine (3 mg/kg per day) for eight weeks, 17 percent achieved complete remission (≥90 percent reduction in the Palmoplantar Psoriasis Area and Severity Index [PPPASI] score), 6 percent had no response, and the remaining patients had partial improvement [20].

In general, we treat adults with a 3 mg/kg dose of cyclosporine and begin to taper the dose after 10 days of sustained clinical improvement (at least 75 percent improvement from baseline). We taper the dose of cyclosporine by 25 to 50 mg per week.

Short-term use of the lowest effective dose of cyclosporine is preferred to minimize adverse effects such as hypertension and renal toxicity. Our typical duration of cyclosporine treatment lasts 12 to 24 weeks. Close monitoring for side effects is required. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Side effects'.)

Our personal experience suggests that higher doses of cyclosporine may be effective for some patients who fail to respond to 3 mg/kg per day; we have successfully used doses of up to 8 mg/kg per day. However, increased risk for side effects is a concern for treatment with higher doses.

●Methotrexate – Although our personal experience suggests that methotrexate can be useful for PPP, data to support this assertion are limited. A retrospective study of 114 patients with PPP or palmoplantar psoriasis found that four of seven patients with PPP who were treated with 15 to 25 mg per week of methotrexate (57 percent) achieved marked improvement in their disease [4]. A separate uncontrolled study in which patients were treated with 25 mg of methotrexate for two months found complete or almost complete resolution of PPP in 8 of 25 patients (32 percent) [21]. Most of the responders also had psoriatic skin lesions at other sites.

We typically treat adults with 7.5 to 22.5 mg of methotrexate per week given intramuscularly or subcutaneously. Methotrexate is not given daily. Oral administration of methotrexate (10 to 25 mg per week) is an additional option, though the risk for drug-related gastrointestinal distress may be higher.

Methods for beginning methotrexate therapy vary. We usually begin at a dose of 15 mg per week subcutaneously for adults. If complete blood count with differential and liver function test results are normal at weeks 2 and 4 of treatment, we continue giving 15 mg per week. We expect to see clinical improvement within 12 to 16 weeks.

If the response to methotrexate is not satisfactory after 12 to 16 weeks, we increase the dose to 17.5 mg per week and re-evaluate the patient after four weeks. If no improvement is seen, we discontinue methotrexate and proceed to an alternative therapy. If improvement is seen but not satisfactory, we increase the dose to 20 mg per week for an additional four weeks and then increase up to a maximum dose of 22.5 mg per week if the response to 20 mg per week is inadequate. We discontinue methotrexate if patients have an inadequate response to 22.5 mg per week.

Following achievement of satisfactory improvement, we aim to taper the dose to 5 to 7.5 mg per week for maintenance therapy.

Monitoring for adverse effects is important during methotrexate therapy, particularly at the start of therapy and following dose increases. Hematologic toxicity is a potentially life-threatening side effect. Gastrointestinal distress and liver or pulmonary toxicity are additional side effects. Liver and renal function tests should be monitored periodically. Folic acid supplementation should be given to patients receiving methotrexate therapy to reduce the risk of some side effects. (See "Major side effects of low-dose methotrexate" and "Major side effects of low-dose methotrexate", section on 'Prevention of side effects with folate'.)

SEVERE RECALCITRANT DISEASE — Despite the observation that biologic anti-tumor necrosis factor (anti-TNF) drugs (infliximab, etanercept, and adalimumab) may induce palmoplantar pustulosis (PPP) [22,23], there is some evidence that these agents can be effective for treating PPP. A 24-week, randomized trial supports the efficacy of etanercept for PPP [24]. TNF-alpha inhibitors also have been reported as effective for the treatment of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, a disorder that may present with PPP [25-30]. (See "Palmoplantar pustulosis: Epidemiology, clinical features, and diagnosis", section on 'SAPHO syndrome'.)

Treatment with other biologic agents has been attempted for severe or recalcitrant PPP occurring with or without associated plaque psoriasis. Data suggesting a role for interleukin (IL) 23 production and the resulting proliferation of T helper type 17 (Th17) cells and Th17 cytokines (eg, IL-17A, IL-17F, IL-22) in the pathogenesis of PPP has contributed to trials of therapies that inhibit this pathway [31-33] (see "Palmoplantar pustulosis: Epidemiology, clinical features, and diagnosis", section on 'Pathogenesis' and "Pathophysiology of plaque psoriasis", section on 'T helper type 17 cells'):

●Ustekinumab – The efficacy of ustekinumab, a biologic inhibitor of IL-12 and IL-23, for PPP is uncertain. A 16-week randomized trial that included 13 patients with PPP and 20 patients with palmoplantar pustular psoriasis failed to find a statistically significant difference in the response of patients to ustekinumab (45 mg given at weeks 0 and 4) versus placebo [34]. However, benefit of ustekinumab for PPP or palmoplantar pustular psoriasis has been reported in an uncontrolled study, case series, and case reports [35-40].

●Guselkumab – Two randomized trials suggest benefit of guselkumab, another biologic agent targeting IL-23 [41,42]. In a phase 3 trial, 159 adults with refractory PPP were randomly assigned to guselkumab 100 mg, guselkumab 200 mg, or placebo given at weeks 0, 4, and 12 and then every 8 weeks thereafter [42]. Patients in the placebo group were rerandomized to guselkumab 100 mg or guselkumab 200 mg after week 16. At week 16, both the 100 mg and 200 mg guselkumab groups exhibited greater improvement in the Palmoplantar Psoriasis Area and Severity Index (PPPASI) total score than the placebo group (least squares mean change of -15.3, -11.7, and -7.6, respectively). In addition, more patients in the guselkumab 100 mg group had at least 50 percent improvement in the PPPASI total score (PPPASI-50) at week 16 than in the placebo group (57 versus 34 percent). Although the proportion of patients achieving this endpoint in the guselkumab 200 mg group (37 percent) was similar to the placebo group, increasing response to guselkumab was detected over time, and PPPASI-50 response rates at week 52 were similar in the 100 mg and 200 mg guselkumab groups (83 and 85 percent, respectively). Sustained efficacy and safety of guselkumab for PPP through week 84 has been demonstrated in patients with PPP [43].

●Secukinumab – Additional study is necessary to clarify the effects of secukinumab, an anti-IL-17A monoclonal antibody. In the 2PRECISE trial (n = 237), patients with moderate to severe palmoplantar pustular psoriasis were randomly assigned to 300 mg of secukinumab, 150 mg of secukinumab, or placebo given at weeks 1, 2, 3, and 4 and then every four weeks. The trial did not achieve the primary endpoint of superiority of the 300 or 150 mg doses of secukinumab over placebo after 16 weeks (27, 18, and 14 percent achieved 75 percent improvement in the PPPASI score, respectively) [44]. Although benefit of a longer course of treatment was proposed based upon a second phase in which patients in the secukinumab groups were allowed to continue treatment and nonresponders in the placebo group were rerandomized to 300 or 150 mg of secukinumab, further study to confirm benefit is warranted. At week 52, 42 percent of patients in the secukinumab 300 mg group and 35 percent of patients in the secukinumab 150 mg group achieved at least 75 percent improvement in the PPPASI score.

The efficacy of other biologic and small molecule therapies used for psoriasis is unclear. Improvement of PPP with tofacitinib, tildrakizumab, or apremilast has been reported in individual patients [45-47]. In a series of four patients treated with brodalumab (including two who failed to respond to secukinumab) for severe, recalcitrant PPP associated with plaque psoriasis and/or psoriatic arthritis, three did not respond to treatment and one had a partial response but discontinued therapy due to oral candidiasis [48].

Anakinra, a biologic IL-1 inhibitor, did not appear effective for PPP in an eight-week, placebo-controlled, randomized trial (n = 64) [49]. However, improvement of severe or recalcitrant palmoplantar pustular psoriasis or acrodermatitis continua of Hallopeau (pustular psoriasis of the digits) during treatment with anakinra has been documented in case reports [50,51]. Canakinumab was not effective for palmoplantar pustular psoriasis in a case report [52].

Examples of additional therapies under investigation for PPP include the IL-36 inhibitors spesolimab and imsidolimab [53-55], RIST4721 (a CXC chemokine receptor type 2 antagonist) [56], and CSL324 (a recombinant anti-granulocyte colony-stimulating factor receptor monoclonal antibody) [57].

OTHER THERAPIES — Other interventions have been reported to be useful for palmoplantar pustulosis (PPP), including other topical and systemic drugs, tonsillectomy, a gluten-free diet in patients with associated gluten intolerance, and light-based or radiation therapy. Data on most of these therapies are limited:

●Other topical drugs – In addition to topical corticosteroids, which represent the mainstay of topical therapy for PPP, topical therapies such as topical retinoids, tar, anthralin, or calcipotriol are sometimes used in the clinical setting, though there are few data to support their efficacy. No randomized trials have evaluated the efficacy of these therapies. We have not had success with these therapies.

●Oral tetracyclines – Oral tetracyclines are a less commonly used treatment for PPP. Two randomized crossover trials in which patients were treated with tetracycline or clomocycline support the efficacy of these drugs over placebo for inducing improvement in PPP [58,59]. We do not use oral tetracyclines for PPP.

●Colchicine – Although colchicine was associated with marked improvement in 15 of 25 patients treated for PPP in a retrospective study [4], findings of randomized trials have been disappointing [60,61]. In addition, rates of adverse effects (diarrhea, headaches, and nausea) in the randomized trials were high.

●Itraconazole – Two small case series document clinical improvement in PPP (especially new pustule formation) during treatment with itraconazole [62,63]. Relapses occurred after cessation of therapy. No randomized trials have evaluated the efficacy of itraconazole therapy.

●Tonsillectomy – Japanese studies linking PPP to tonsillar infections and reports of improvement in PPP following tonsillectomy suggest that some patients may benefit from this procedure [64-66]. Improvement of PPP after tonsillectomy has been reported in several Japanese series [64,67-69].

●Gluten-free diet – Patients with gluten sensitivity and PPP may benefit from gluten-free diet [70]. In a Swedish series, all of nine patients who had elevated anti-gliadin antibodies and/or elevated tissue transglutaminase antibodies and adhered to a gluten-free diet experienced clearance or great improvement in PPP [70]. Improvement was slow, occurring over the course of a few months in patients with moderate PPP and over several years in patients with longstanding severe PPP.

●Other light-based therapies – Exposure to an excimer light source or a narrowband ultraviolet B (UVB) light source has been associated with improvement in PPP in uncontrolled studies [71-73]. Findings of an eight-week, randomized trial (n = 77) that compared three dose regimens for excimer laser therapy for PPP suggest that higher-dose regimens may be of greater benefit than lower-dose regimens but are also associated with greater risk of side effects [74]. An ultraviolet A1 (UVA1) 355 nm laser appeared effective for PPP in an uncontrolled study [75]. Responses to photodynamic therapy have been documented in case reports [76].

●Radiation therapy – Limited data suggest benefit of superficial radiation therapy [77,78]. A six-week trial in which 17 patients with PPP were randomly assigned to treatment of PPP on one side of the body with Grenz ray therapy and a sham treatment on the contralateral side found greater improvement in PPP on the side of the body exposed to Grenz rays [77]. However, the response was moderate, and no patients achieved disease clearance. In two case reports, superficial radiation therapy administered with a megavoltage beams technique was associated with dramatic, rapid improvement of severe, refractory PPP [78].

Other interventions described as beneficial in case reports include oral tofacitinib [79] and high-dose rate brachytherapy [80].

PATIENT FOLLOW-UP — The purpose of patient follow-up is to assess the response to treatment and to evaluate for adverse effects. Therefore, the frequency of follow-up should be individualized based upon the severity of disease and the selected therapeutic regimen. Patients with poorly controlled or severe disease on systemic therapy will require more frequent follow-up than patients with milder disease.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Palmoplantar pustulosis".)

SUMMARY AND RECOMMENDATIONS

●Overview – Palmoplantar pustulosis (PPP) is a skin disorder that presents with recurrent eruptions of pustules on the palms or soles (picture 1A-F). PPP is associated with symptoms of pruritus, burning sensations, or pain in involved areas and can have a significant negative effect on quality of life. (See 'Introduction' above and "Palmoplantar pustulosis: Epidemiology, clinical features, and diagnosis".)

PPP exhibits a chronic course characterized by exacerbations and partial remissions and can be difficult to treat. Treatment consists of interventions to reduce associated symptoms, smoking cessation, and various medical therapies.

●Skin moisturization and avoidance of irritants – In an attempt to reduce associated symptoms of PPP, we advise patients to keep skin moisturized and to avoid irritants that may exacerbate PPP. (See 'General measures' above.)

●Smoking cessation – Although data are insufficient for conclusions on the effect of smoking cessation on the course of PPP, we encourage all patients to stop smoking. There is a strong relationship between smoking and the development of PPP. (See 'General measures' above and "Palmoplantar pustulosis: Epidemiology, clinical features, and diagnosis", section on 'Pathogenesis'.)

●Pharmacologic therapy – Therapeutic options include topical therapy, systemic therapy, and photochemotherapy. No treatment is uniformly effective, and the response to treatment is unpredictable (see 'Overview' above):

•Initial therapy for limited disease – For patients with PPP that is limited to focal areas of involvement, we suggest a super high-potency topical corticosteroid applied under occlusion for the initial treatment of PPP (Grade 2C).

•Initial treatment for diffuse disease – For patients with diffuse eruptions on the palms and/or soles, we suggest initial treatment with oral acitretin or oral psoralen plus ultraviolet A (PUVA) (Grade 2B). Topical corticosteroid therapy may be administered concomitantly. (See 'First-line therapy' above.)

•Failure of initial treatment – Patients who do not respond to treatment with topical corticosteroids, acitretin, or PUVA may benefit from other therapies. Combination therapy with acitretin and PUVA and systemic treatment with cyclosporine or methotrexate are our preferred second-line options for therapy. (See 'Second-line therapy' above.)