Interventions for chronic palmoplantar pustulosis Edited (no change to conclusions)

Abstract

Chronic palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition characterised by crops of sterile pustules (yellow pus spots) on the palms and soles which erupt repeatedly over months or years. The affected areas tend to become red and scaly; cracks may form and these are often painful. Many different treatments have been used for palmoplantar pustulosis but none is generally accepted as being reliably effective.

To assess the effects of treatments for palmoplantar pustulosis, both in reducing disease severity and in maintaining remission once achieved.

We searched the Cochrane Skin Group Specialised Register (January 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to February 2003). We also cross‐checked with the Salford Database of Psoriasis Trials and reference lists of articles. We also contacted authors included trials, members of the Cochrane Skin Group and dermatologists interested in psoriasis.

Any randomised controlled trial in which patients with chronic palmoplantar pustulosis were randomised to receive one or more interventions.

At least two reviewers independently assessed trial eligibility and quality. Study authors were contacted for additional information. Adverse effects information was collected from the trials.

Twenty‐three trials involving 724 people were included. There is evidence supporting the use of systemic retinoids (improvement rate difference 44%, 95 CI 28 to 59%), oral PUVA (improvement rate difference 44%, 95 CI 26 to 62%). However, a combination of PUVA and retinoids is better than the individual treatments. The use of topical steroid under hydrocolloid occlusion is beneficial. It would also appear that low dose ciclosporin, tetracycline antibiotics and Grenz Ray Therapy may be useful in treating PPP. Colchicine has a lot of side effects and it is unclear if it is effective and neither was topical PUVA (rate difference of 0.00, 95% CI ‐0.04 to +0.04). There is no evidence to suggest that short‐term treatment with hydroxycarbamide (hydroxyurea) is effective.

Many different interventions were reported to produce "improvement" in PPP. There is, however, no standardised method for assessing response to treatment, and reductions in pustule counts or other empirical semi‐quantitative scoring systems may be of little relevance to the patient. This review has shown that the ideal treatment for PPP remains elusive and that the standards of study design and reporting need to be improved to inform patients and those treating them of the relative merits of the many treatments available to them.

Author(s)

Robert Chalmers, Sally Hollis, Jo Leonardi‐Bee, Christopher EM Griffiths, Alexander Marsland Bsc MRCP

Abstract

Treatments for chronic palmoplantar pustulosis (a skin disease where repeated crops of painful yellow pus spots form on the palms and soles) 

Chronic palmoplantar pustulosis is a skin disease where repeated crops of painful yellow pus spots form on the palms and soles, often over many years. Many different treatments have been used including topical creams and ointments, drugs by mouth and ultraviolet radiation. The review of trials found that several treatments improve the symptoms of chronic palmoplantar pustulosis, although no treatment was shown to suppress the condition completely. Oral retinoid therapy (acitretin) appears to be helpful at relieving symptoms, particularly if combined with PUVA. Ciclosporin and tetracycline antibiotics can also provide some relief. Topical treatments were generally less helpful. As yet there is no ideal treatment for chronic palmoplantar pustulosis, though oral retinoids, particularly when combined with psoralens and ultraviolet radiation (PUVA), may help

Author(s)

Robert Chalmers, Sally Hollis, Jo Leonardi‐Bee, Christopher EM Griffiths, Alexander Marsland Bsc MRCP

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

With the exception of corticosteroids under occlusion, there is little evidence for efficacy of topical therapy in PPP. The efficacy of topical corticosteroids is increased by occlusion with hydrocolloid gel dressings: such therapy may be expected to affect clearance within 12 days in about two thirds of people with PPP. This remission may, however, be short‐lived. There is some evidence to suggest that additional short‐term PUVA does not prevent relapse. We found no eligible studies examining other topical therapies such as tar, anthralin, calcipotriol or tazarotene. Grenz Ray therapy has been shown to produce moderate improvement in about two‐thirds of patients with PPP. There are no studies examining the use of this as an adjunct to other interventions. There is little evidence from RCTs to support the use of topical PUVA.

Systemic photochemotherapy and systemic retinoids are both of value for PPP. Systemic PUVA can induce clearance in up to two fifths of people with PPP though larger studies are needed to confirm this figure. Systemic retinoids (etretinate and acitretin) at a dose of 0.5 mg/kg bw/day produce objective improvement in about two thirds of people with PPP. A good or excellent response is seen in about two fifths. Many patients who do improve will not, however, achieve satisfactory control of disease either because of an insufficient response or because of intolerance of retinoid side effects. Continuation of retinoid therapy after induction of remission reduces the incidence of relapse. Limited data suggest that liarozole might be similarly efficacious in producing objective improvement in PPP. Comparison between retinoids and PUVA suggests that retinoids are more likely to induce clearance but there is little difference in the proportions of people who will show improvement. A combination of systemic retinoids and PUVA produces clearance in about two‐thirds of people with PPP, and compares favourably with PUVA or retinoid therapy alone.

There is evidence that ciclosporin and tetracycline antibiotics may be of some benefit for PPP. Ciclosporin at low dose (1 to 2.5 mg/kg bw/day) produces moderate objective improvement in about two‐thirds of patients over one month. The evidence which suggests that about one‐fourth of patients may be expected to maintain the improvement gained for one year needs confirmation by further studies. The response rates reported in uncontrolled studies and case series using higher doses of ciclosporin suggest that the doses used in published studies may be suboptimal; further studies using higher doses are required to establish whether this is so. Tetracycline antibiotics produce objective improvement in about half of patients with PPP. Clearance is rarely seen.

There is a paucity of evidence supporting the use of colchicine in PPP. There is no evidence to suggest that short term treatment with hydroxycarbamide is effective in PPP. There are no randomised controlled trials to date that support the use of methotrexate, although one uncontrolled prospective study claimed benefit in only a third of treated patients, mainly those people with evidence of psoriasis at other sites (Thomsen 1971).

Implications for research 

The clinical outcomes of trials for PPP are not standardised and this makes it difficult to compare studies. Although many investigators use changes in pustule counts or clinical scores of erythema and scaling, these on their own are insufficient. It should always be possible to dichotomise the results into categories such as improved/not improved or clear/not clear. Of equal importance are the assessments of patients receiving the treatment both in terms of efficacy and acceptability.

We suggest that future trials should report specifically:

  • numbers of patients randomised into each treatment arm as well as the numbers completing each arm according to protocol
  • numbers of randomised patients who achieve clearance
  • numbers of randomised patients who show objective improvement
  • numbers of randomised patients who report significant benefit
  • numbers of randomised patients who regard the intervention as acceptable or "worth‐while"

We also suggest that:

  • the presence or absence of evidence of psoriasis at other body sites should be recorded
  • trial design should incorporate separate stratification for this
  • data should be presented in such a way that differential response rates of hand and feet can be identified

Further studies of systemic PUVA against placebo may help to determine more precisely the proportion of people who may be expected to clear with PUVA and to clarify the differences in response rates to systemic PUVA reported by Murray 1980 and Rosen 1987 on the one hand and Lassus 1988 on the other. There is much uncertainty as to the efficacy of topical PUVA in PPP and, ideally, a treatment arm using topical PUVA should be included in order to determine whether this modality has any place in its management. A study of ciclosporin at a dose of 3.0 to 5.0 mg/kg bw/day would help to establish the value of this drug for PPP.

A comparison of liarozole with acitretin would help to establish whether the former can achieve response rates to compare with acitretin and, if so, whether it offers benefits in terms of reduced side effects.

A comparison of methotrexate with acitretin would establish whether there is a place for the former in the management of PPP.

In view of the encouraging reports regarding the use of oral pimecrolimus in the treatment of psoriasis, and of its apparent improved side‐effect profile over ciclosporin, a study of this drug as a treatment for PPP would seem appropriate. Although there have been anecdotal reports that the new biological agents which have been introduced for psoriasis may be beneficial in PPP, RCTs should be performed to evaluate their efficacy.

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