A randomized trial of etretinate (Tigason) in palmoplantar pustulosis. The effect of etretinate compared with different regimens of PUVA in the treatment of persistent palmoplantar pustulosis. A double-blind, placebo-controlled trial of topical PUVA in persistent palmoplantar pustulosis. Efficacy of etretinate (Tigason) in clearing and prevention of relapse of palmoplantar pustulosis. Cyclosporine in the treatment of palmoplantar pustulosis. A randomized, double-blind, placebo-controlled study. Etretinate in pustular psoriasis of palms and soles. Low-dose etretinate in the maintenance of remission of palmoplantar pustular psoriasis. Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled study. A hydrocolloid occlusive dressing plus triamcinolone acetonide cream is superior to clobetasol cream in palmo-plantar pustulosis. Pustulosis palmaris et plantaris. Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial. Pustulosis palmaris et plantaris treated with hydroxyurea. A comparison of PUVA-etretinate and PUVA-placebo for palmoplantar pustular psoriasis. Double-blind placebo-controlled study of long-term low-dose cyclosporin in the treatment of palmoplantar pustulosis. A controlled trial of photochemotherapy for persistent palmoplantar pustulosis. Topical PUVA, etretinate, and combined PUVA and etretinate for palmoplantar pustulosis: comparison of therapeutic efficacy and the influences of tonsillar and dental focal infections. Failure of colchicine for palmo-plantar pustulosis. The effect of grenz ray therapy on pustulosis palmoplantaris. A double-blind bilateral trial. PUVA, etretinate, and PUVA-etretinate therapy for pustulosis palmoplantaris. A placebo-controlled comparative trial. Treatment of pustulosis palmaris et plantaris with colchicine. A double-blind cross-over trial. A double-blind trial of clomocycline in the treatment of persistent palmoplantar pustulosis.
5 patients with palmoplantar pustulosis (PPP) were randomized to 8 weeks of daily treatment with either oral etretinate, 1 mg/kg b.w. or placebo. Good or moderate effect was obtained in 18 or 20 patients on etretinate compared o 6 of 21 patients on placebo (p less than 0.001). Etretinate proved to be significantly superior to placebo with regard to influence on the individual symptoms and signs of pustulosis. All patients on etretinate experienced some side effects from the mucous membranes, but they were generally mild. Treatment was discontinued after 4 weeks in 3 patients for reasons unrelated to treatment, in 4 for lack of effect (all on placebo) and in 2 for side effects (both or etretinate). Etretinate is a good alternative to other systemic treatments of PPP. Eighty-four patients with persistent palmoplantar pustulosis (PPP) of long duration were treated with either etretinate or one of three PUVA regimens. PUVA was given either with oral methoxsalen (thirteen cases), with a 1% methoxsalen cream (thirty-three cases) or with trioxsalen baths (eighteen cases). Twenty patients were treated with etretinate. Patients were assessed every fourth week. A mean score for each group was calculated at each visit based on erythema, desquamation, induration and pustulation. In addition, the number of pustules was calculated at each visit. After 12 weeks four of twenty-eight patients treated with local methoxsalen and fourteen of seventeen patients treated with etretinate had completely cleared. At this stage no patient treated with local trioxsalen or oral methoxsalen showed complete clearance. The effect of topical PUVA was investigated in the treatment of patients with persistent palmoplantar pustulosis (PPP). In this double-blind, placebo-controlled trial of 27 patients with PPP there was an overall improvement of the hands and feet in both the active and placebo-treated areas and little difference between them. A total of 40 patients with palmoplantar pustulosis (PPP) were initially treated with oral etretinate (Tigason) in an open trail with a maximum treatment period of 16 weeks. Remission, with only slight residual changes in some cases, was achieved in 26 patients (65%) who were randomized to either a low dose of Tigason or placebo. In the Tigason group, 7 of 11 patients were still in remission afer 6 months while in the placebo group, remission persisted in 4 of the 10 patients who stayed in the study throughout the whole 6 months' period. Alopecia led to stopping the treatment in 6 patients and desquamation of the healthy skin in 2 patients. Other side-effects were only mild. As a conclusion, Tigason shows a beneficial effect in the majority of patients with PPP and is better than placebo in preventing relapse of the disease but intolerable side-effects restrict its use in many patients. Palmoplantar pustulosis (PPP) is an inflammatory skin disease characterized by pustule formation, erythema, induration, and scaling of the affected skin of the palms and soles. Palmoplantar pustulosis is usually resistant to treatment. In a double-blind study (phase 1) of 4 weeks, 40 patients with PPP were randomized to receive oral cyclosporine, 2.5 mg/kg per day, or placebo. An open-label dose-finding phase 2 with cyclosporine doses of 1.25, 2.5, and 3.75 mg/kg per day was performed in the following 3 months. The patients were then followed for at least 2 months after termination of cyclosporine treatment. Response to treatment was judged by the number of fresh pustules. Patients displaying a reduction of 50% or greater in the number of pustules, compared with baseline, were defined as responders.
                Of the patients who completed phase 1, 17 of 19 patients in the cyclosporine group and four of 15 in the placebo group were classified as responders (P < .001). Cyclosporine, but not placebo, significantly reduced formation of new pustules (P = .001). In the subsequent open phase, a daily cyclosporine dose of 1.25 mg/kg appeared to be an effective treatment of PPP in approximately half of the treated patients. Many patients relapsed after initial success with cyclosporine. However, only one patient studied totally failed to respond to cyclosporine treatment. At the end of phase 3, most of the studied parameters had returned to pretreatment levels. The most common side effect was headache in the 2.5 mg/kg per day dosage group; no significant side effects were observed in the 1.25 mg/kg per day dosage group.
                Low-dose cyclosporine treatment (1.25 to 2.5 mg/kg per day) is effective in PPP. In a double-blind controlled study of patients with pustular psoriasis of palms and soles who were allocated at random to etretinate or placebo, we found that etretinate improved the condition as assessed by pustule count and overall clinical response. Side-effects occurred but were accepted by the patients in the short-term. The clinical usefulness of etretinate in this condition will depend on time to relapse, and whether this can be prevented or postponed by continuous treatment. Toxicity in the long-term will also be important. Twenty patients with palmoplantar pustular psoriasis were treated initially for 4 weeks with 70 mg etretinate daily. This led to clinical improvement and a significant fall in pustule count. The patients were then allocated randomly to 30 mg etretinate daily or placebo for a further 12 weeks. There was a rapid deterioration in the clinical condition and a rise in pustule count in the placebo group. The etretinate-treated group still showed clinical improvement and a significantly lower pustule count after 12 weeks. Clinical side-effects were few and adverse effects on liver function and serum lipids were not found. Palmoplantar pustular psoriasis (PPP) is a chronic, relapsing condition often recalcitrant to therapy. Synthetic retinoids have been found to be efficacious in the treatment of PPP, but their use is limited by side-effects. Liarozole is an imidazole-like compound that inhibits the retinoic acid (RA) 4-hydroxylase-mediated breakdown of all-trans RA, causing elevation of plasma and cutaneous levels of RA. Thus liarozole acts as a retinoid-mimetic drug. Liarozole has already been found to be effective in the treatment of retinoid-responsive conditions such as chronic plaque psoriasis and ichthyoses.
                To assess the efficacy and side-effect profile of liarozole in the treatment of PPP.
                We performed a double-blind, randomized, placebo-controlled trial of oral liarozole 75 mg twice daily for 12 weeks in the treatment of PPP. The trial was conducted at two centres and involved 15 patients.
                Using the PPP Area and Severity Index we found a statistically significant (P = 0.02) improvement in PPP in subjects on liarozole (median 3, range 1.8-14.1) as compared with placebo (median 12.1, range 5-18) by the end of the treatment phase. There was also a statistically significant difference (P = 0.006) in the number of fresh pustules after treatment for the two study groups (liarozole median 2, range 0-18; placebo median 38, range 2-75). The severity of disease (on a scale of 0-8) between the two groups was significantly different at the end of treatment (liarozole median 1, range 1-5; placebo median 3, range 2-6; P = 0.04). No patients withdrew from the trial because of adverse events. The most commonly reported side-effects were pruritus, cheilitis and xerosis but these were rarely severe and resolved rapidly on discontinuation of treatment. Laboratory results, including haematology, liver function tests and serum cholesterol and triglycerides were not significantly different between the liarozole and placebo groups.
                The results of this pilot study suggest that liarozole 75 mg twice daily is an effective and well-tolerated therapy for PPP. In addition, the pharmacokinetics of liarozole may help to circumvent side-effects associated with synthetic retinoids and allow its use in premenopausal women. The purpose of this study was to compare the therapeutic efficacy of a hydrocolloid dressing (Actiderm) over a medium strength corticosteroid (triamcinolone acetonide (TAA) 0.1% cream) with that of a highly potent corticosteroid (clobetasol propionate 0.05% cream) in palmo-plantar pustulosis and localized pustular psoriasis. It was a randomized, open, prospective, right-left comparative trial in 19 patients. The Actiderm dressing and the TAA cream were applied every third day, whereas the clobetasol cream was applied twice daily for 4 weeks. Both treatments resulted in a significant improvement. On completion of treatment, complete clearance was found in 13 patients (63%) with Actiderm plus TAA, but in only 3 patients (21%) with clobetasol (p = 0.001). Four weeks after stopping therapy, the clinical parameters had returned to their pre-treatment level, except for erythema on the Actiderm plus TAA treated lesions (p less than 0.05). No clinically important adverse effects were reported or observed; in particular there was no sign of skin atrophy at the end of study. The results of this study demonstrate that Actiderm applied over a medium strength corticosteroid every third day is highly effective against palmoplantar pustulosis and localized pustular psoriasis. However, it is necessary to develop treatment regimens to maintain the improvement achieved. nan Sixty patients with palmoplantar pustulosis were treated in a double-blind trial with either acitretin (etretin, Ro 10-1670) or with etretinate. The study consisted of 4 weeks of therapy with three 10 mg capsules/day followed by 8 weeks of therapy with a varying number of capsules given daily according to therapeutic response. At the end of the 12-week treatment period, the mean number of pustules (+/- SEM) had decreased from 57.8 (+/- 8.6) to 3.9 (+/- 1.6) in the acitretin group and from 57.1 (+/- 14.1) to 5.7 (+/- 2.7) in the etretinate group. With regard to influence on erythema, infiltration, scaling, and area involved, similar improvements were obtained in both treatment groups. Adverse reactions of the hypervitaminosis A type were observed with almost the same frequency and severity in both treatment groups. The mean number of 10 mg capsules used daily was comparable in the two groups: 2.82 (range 1.23-4.67) for acitretin and 2.77 (range 1.60-4.82) for etretinate. It can be concluded that acitretin and etretinate do not significantly differ with regard to efficacy and overall safety in the treatment of patients with palmoplantar pustulosis. nan Seventeen patients with palmoplantar pustular psoriasis and three with hyperkeratotic psoriasis of palms and soles were treated with either PUVA-etretinate (1 mg/kg) or PUVA-placebo. Patients were randomly allocated to each group and the trial was conducted according to a double-blind protocol, so far as the side-effects of etretinate made this possible. PUVA was given three times a week for a maximum of 18 weeks, after 2 weeks on daily placebo or etretinate alone. All ten patients in the PUVA-etretinate group cleared, but there were four failures in the PUVA-placebo group (P = 0.03). The PUVA-etretinate treated patients required significantly fewer PUVA treatments (13.1 +/- 2.9; mean +/- s.e.) and cleared in a significantly shorter time (30.3 +/- 7.1 days) than the PUVA-placebo group (23.2 +/- 4.2 treatments; 59.2 +/- 11.5 days, P less than 0.05). The cumulative UV-A dose to clear was less in the PUVA-etretinate group (53.9 +/- 18.5 J/cm2) than the PUVA-placebo group (113.1 +/- 33.4 J/cm2). This difference was not significant due to the exceptionally large dose of UV-A used on one patient but the results were significant when it was excluded. The therapeutic advantage of adding etretinate to PUVA is offset by the side-effects of cheilitis, hair loss and peeling skin which occurred in eight of the ten PUVA-etretinate patients, and an increase in fasting triglyceride concentrations and serum alkaline phosphatase activity. We previously showed in a double-blind, placebo-controlled study that cyclosporin at a dose of 2.5 mg/kg per day is an effective treatment for palmoplantar pustulosis (PPP). In the present randomized, double-blind, placebo-controlled multicentre study we treated 58 PPP patients with placebo or cyclosporin at an initial dose of 1 mg/kg per day. Disease activity was calculated from the number of fresh pustules. Treatment success was defined as the number of fresh pustules not exceeding 50% of the patients' own baseline pustule number. In cases of treatment success the dose of the test medication was not increased and the treatment was kept blinded for a maximum of 12 months. Blinding was broken only on treatment failure of the initial test medication dose. The mean blinded treatment time was 5.1 months for the patients receiving cyclosporin and 2.1 months for placebo (P < 0.01). Treatment was kept blinded for 12 months for seven patients in the cyclosporin and two in the placebo group (P < 0.05). Patients whose treatment code was broken continued in an open dose-finding part of the study with dose adjustments of cyclosporin every second month. In cases of treatment failure the dose of cyclosporin was increased in steps of 1 mg/kg per day; in cases of treatment success the cyclosporin dose was decreased by 1 mg/kg per day. The minimum and maximum doses were 1 and 4 mg/kg per day, respectively. The mean effective dose during the dose-finding part was between 1.2 and 1.7 mg/kg per day. Two patients did not respond to the highest dose of 4 mg/kg per day. In two patients serum creatinine levels increased by > 30% of their own baseline. The other main adverse events were hypertension (seven patients) and hypertrichosis (six patients). After stopping cyclosporin treatment the mean number of fresh pustules showed a maximum after 2 weeks with a continuous decline after that. Twelve months after completing the treatment the mean number of pustules was reduced to 20.0 compared with 63.6 at baseline (P < 0.001); 11 patients were free from pustules and two of these were totally cleared. We conclude that cyclosporin at 1-2 mg/kg per day is an effective and well tolerated treatment for PPP in most patients. Twenty-two patients with bilaterally symmetrical persistent palmoplantar pustulosis were treated on one randomly selected side with oral psoralen and long-wave ultraviolet light. The treated side cleared completely in twelve patients, almost cleared in five patients and improved in four. One patient improved on both sides. Fifteen of the twenty-two patients were then treated with topical psoralen and long-wave ultraviolet light on the side that had previously been used as a control. Similar results were obtained. Seven patients cleared completely, six patients were much improved and two were improved. These results are significantly different from those liable to occur by chance (P < 0.001). Twenty patients with palmoplantar pustulosis (PPP) were treated with topical PUVA, oral etretinate (Re), or combined PUVA and etretinate (Re-PUVA). Re and Re-PUVA treated sites improved and/or cleared more rapidly than PUVA treated sites. Complete clearance was observed in six of ten sites treated with Re-PUVA, two of ten with Re, and one of ten sites with PUVA within 12 weeks. UVA-control sites failed to be cleared within 12 weeks. Remission periods after stopping the treatment were 1.5 +/- 0.5 weeks (n = 2) with Re, 10.5 +/- 11.4 weeks (n = 6) with Re-PUVA, and one year (n = 1) with PUVA. These results overall suggested that Re-PUVA is the most effective treatment for PPP. Tonsillar focal infection (TFI) and dental focal infection (DFI) were found in 6/20 and 17/20 patients, respectively. However, the presence of focal infection (FI), TFI and/or DFI, did not appear to interfere with the therapeutic activities of Re and/or PUVA, because the complete clearance rates and remission periods in FI(+) patients were comparable with those in FI(-) patients. nan The effect of grenz ray therapy in the treatment of pustulosis palmoplantaris was assessed in 15 patients by randomly allocating active treatment of the lesions of one side of the body, while the lesions on the other side, which received stimulated therapy, served as a control. Four Gy of grenz rays 10 kV were applied on 6 occasions at intervals of 1 week. A significantly better therapeutic result was recorded on the lesions which had received active grenz ray therapy. However, the therapeutic response was moderate. It is concluded that grenz ray therapy could be useful in pustulosis palmoplantaris mainly as an adjunct to other therapies. Thirty patients with severe pustulosis palmoplantaris completed a placebo-controlled comparative trial. Patients were randomly allocated to placebo or etretinate therapy; after two weeks, psoralen plus long-wave ultraviolet light (PUVA) treatment was instituted on one hand or foot, while the other hand or foot served as an untreated control. Fourteen of 18 hands or feet cleared with the combined treatment, compared with three of 18 with etretinate treatment and three of 12 with PUVA treatment. Follow-up showed a high relapse rate. Treatment of severe pustulosis palmoplantaris must be individualized to minimize short- and long-term side effects. 27 patients with pustulosis palmaris et plantaris were treated daily with colchicine 0.5 mg X 3 for four weeks in a double-blind study. Only ten patients experienced a halt of pustule formation, whereas redness, scaling, and subjective symptoms were unchanged. Colchicine seems of limited value in patients with pustulosis palmaris et plantaris. Sixty patients with persistent palmoplantar pustulosis (PPP) were treated with clomocycline (Megaclor) in a double-blind, cross-over trial in an attempt to establish whether the condition responds to tetracycline. Each patient received 3 months each of clomocycline and placebo in random order. Forty patients completed the trial. Twenty-two failed to respond to either treatment, fifteen improved on clomocycline, two improved on placebo and one placebo and one improbed on both treatments. These results are highly significant (P = 0-003) and suggest that clomocycline may suppress pustulation in some patients. The twenty-two 'non-responders' were compared with the eighteen 'responders' for sex, age, length of history and associated psoriasis but no significant differences were found. Difficulties in assessment and the possiblity of improvement deing due to spontaneous remission are discussed. Further follow-up of both groups suggested that clomocycline used over long periods favourably influenced the course of the disease in the 'responder' group.
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.