Treatments for Chronic Palmoplantar Pustular Psoriasis

A.M. Marsland BSc, MRCP, R.J.G. Chalmers FRCP, and C.E.M. Griffiths MD,FRCP


Dermatology Centre, University of Manchester School of Medicine, Hope Hospital, Manchester, UK

ABSTRACT

Chronic palmoplantar pustular psoriasis (PPP) is a disabling condition characterized by recurrent crops of sterile pustules on a background of erythema, fissuring and scaling. Genetic and environmental factors have been implicated in its etiology. Topical treatments are frequently ineffective although corticosteroids under hydrocolloid occlusion have been demonstrated to be useful. There is evidence supporting the use of systemic retinoids, PUVA and a combination of both. Oral tetracycline antibiotics may be helpful, but rarely clear PPP. Cyclosporine has been shown to be of some benefit at low doses. The choice of systemic treatments for an individual patient is influenced as much by their potential side effects as by differences in efficacy.

Key Words:
evidence, palmoplantar pustular psoriasis, review, therapy

Chronic palmoplantar pustular psoriasis, or pustulosis palmaris et plantaris (PPP), is an idiopathic condition characterized by recurrent sterile pustules on the palms and soles on a background of erythema, scaling and fissuring. Once established, it may last for decades. Significant morbidity can impair dexterity or mobility, and cause pain, pruritus and embarrassment. PPP may affect people of all ages and either sex, although it is more commonly seen in middle-aged women. It may be associated with other forms of psoriasis, although it appears to be a distinct entity in terms of epidemiology and pathophysiology. The onset of PPP has been closely linked with cigarette smoking in a number of studies from different parts of the world. Another environmental factor proposed to be of etiological importance is recurrent streptococcal tonsillitis.¹

The choice of treatment is heavily influenced by its side effect profile. Treatments are often disappointing and may cause side effects. This article summarizes the existing treatments and evidence available to support their use. It should be noted that most trials have been conducted over short time periods for what is essentially a chronic, relapsing-remitting disease that frequently requires longterm therapy. Outcome measures in these trials are poorly defined and few studies report on patients’ subjective views.

Topical Treatments

Emollient Creams and Ointments

Topical treatments alone tend to be ineffective for PPP, although some patients may benefit from using emollient creams or ointments, particularly when the disease is mild. These can safely be used as frequently as the patient wishes.

Topical Corticosteroid Preparations

Superpotent topical corticosteroids may be effective in reducing the severity of PPP in the short term, and hydrocolloid gel occlusion has been shown to increase the numbers of patients who respond even when only a moderately potent steroid is used.^2,3 Reapplication of cream under gel occlusion is applied every third day for a maximum of four weeks. In order to maintain remission, some physicians prescribe a weaker topical steroid for daily use, but evidence supporting this intervention is lacking. The potential side effects of topical steroids are well known to dermatologists: in particular, the skin around the medial longitudinal arch may be prone to atrophy.

Tar and Anthralins

Some dermatologists advocate the use of tar and anthralin preparations for PPP. There are no published randomized controlled trials (RCTs) that demonstrate their efficacy. In addition, treatment can be messy and irritating.

Topical Retinoids

Although systemic retinoid therapy is effective, there is no published evidence to support the use of topical retinoids for PPP. Tazarotene gel, which was recently introduced to treat mild to moderate plaque psoriasis, has not yet been formally evaluated in PPP.

Systemic Treatments

Systemic Retinoids

Oral etretinate, at a dose of 0.6mg/kg/day, produces objective improvement in about 2/3 of PPP patients^4,5 and remission has been maintained in those who responded to initial treatment.⁶ There is evidence to show that acitretin, which has now superseded etretinate, is as effective in the treatment of PPP at the same dose.⁷

Retinoids are highly teratogenic, and female patients must be warned of the risks. Acitretin, the hydrolysis product of etretinate, was developed because of the initial belief that it was eliminated from the body much more rapidly. However, subsequent analysis has shown that it may, under certain circumstances, be esterified in vivo into etretinate. Since terminal elimination of etretinate from body fat stores is very slow, contraceptive measures must be taken during treatment and for at least two years after discontinuing acitretin.

Side effects of acitretin include xerosis, photosensitivity, epistaxis and (reversible) alopecia. Fasting lipid and liver function tests should be checked prior to commencing and at intervals during treatment. There is a small risk of hyperostosis and extraosseous calcification in patients on long-term therapy.

Liarozole is a novel drug that inhibits breakdown of all-trans retinoic acid, causing elevation of all-trans retinoic acid levels in the skin and plasma. Its effects and side effects are similar to synthetic retinoids but it is not believed to have a prolonged action following withdrawal. A small pilot study suggests that it may be effective in the treatment of PPP and may be worthy of further investigation.⁸

PUVA

Oral psoralen followed by irradiation with ultraviolet A (PUVA) has been shown to effect remission in PPP.^5,9 Disadvantages include the need for the patient to attend a dedicated unit on a regular basis, a small incidence of nausea, and the inconvenience of having to protect skin and eyes from sunlight on treatment days.

Topical psoralen paint or gel avoids the systemic side effects of oral psoralens. It may, however, be irritating and poorly tolerated. Unlike systemic PUVA, studies have failed to demonstrate the superiority of topical PUVA over placebo,^10,11 although a study comparing topical with systemic PUVA found no significant difference between them.¹²

PUVA was reported in different trials to be either better⁵ or worse¹² than systemic retinoids at effecting remission. Short-term PUVA, as a maintenance measure following remission brought about by potent topical steroid under occlusion, was not effective in a randomized control trial (RCT), which compared it with no treatment.³ A combination of retinoid and PUVA (re-PUVA) was demonstrated to be superior to PUVA alone in clearing PPP.¹³

Table 1: Treatments for Chronic Palmoplantar Pustular Psoriasis: Induction of remission
*Relative Efficacy: NA Data not available; +/- poor; + moderate; ++ good; +++ excellent
**Evidence Quality: NA not available; + randomized controlled trial (RCT); ++ two or more RCTs

Table 2: Treatments for Chronic Palmoplantar Pustular Psoriasis: Maintenance of remission
*Relative Efficacy: NA Data not available; +/- poor; + moderate; ++ good; +++ excellent
**Evidence Quality: NA not available; + randomized controlled trial (RCT); ++ two or more RCTs

Tetracycline Antibiotics

Patients who were treated with tetracycline antibiotics including clomocycline 170mg, three times daily,¹⁴ and tetracycline 250mg, twice daily demonstrated objective improvement over placebo.¹⁵ Adverse effects include nausea, phototoxicity and hepatitis. Few patients achieved clearance.

Cyclosporine

Erkko and colleagues demonstrated that cyclosporine was effective in improving chronic PPP at a dose of 2.5mg/kg daily in 2/3 of patients.¹⁶ They found that doses as low as 1mg/kg/day may be effective but suggest increasing the dose stepwise up to 4mg/kg/day if a satisfactory response is not obtained within 1-2 months.¹⁷ Patients must be monitored for hypertension and renal dysfunction. Some patients experience side effects, including gastrointestinal symptoms, hypertrichosis and headaches.

Other Treatments

Colchicine has been advocated for chronic PPP¹⁸ but evidence from RCTs suggests that its value is limited.^19,20 Grenz ray therapy was shown to give some limited improvement and, where it is available, it may be valuable as an adjunct to other therapies.²¹ There is limited evidence suggesting that hydroxyurea is ineffective.²² There are no RCTs to date that support the use of methotrexate, and an uncontrolled trial did not show evidence of benefit.²³ The absence of even anecdotal reports of the use of topical vitamin D analogues such as calcipotriol and tacalcitol for PPP suggests that these are likely to be of limited benefit, though they have not as yet been formally evaluated.

Conclusion

A systematic review of published evidence supports the use of treatments for PPP that are listed here. None can reliably induce remission, nor maintain it once it is achieved. When side effects or inconvenience of available treatments are set against the often incomplete therapeutic responses achieved, it is clear that no treatment is yet ideal.

References

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