Patients and Methods
Clinical records of patients with PPPP from the dermatological outpatient clinic of the Hospital de la Santa Creu i Sant Pau university-affiliated reference hospital in Barcelona, Spain, were reviewed. Patients with other forms of nonpustular palmoplantar psoriasis (hyperkeratotic or erythematous forms) and classic PPP were not included. This study was previously approved by the Hospital Ethics Committee.
Five patients (two men and three women, age range 30–50 years) with severe refractory PPPP have been treated with ustekinumab, according to a pre-established protocol, since December 2010. Their demographic and clinical data, as well as their response to treatment and duration of follow-up, are summarized in Table 1.
Infections, malignancies, drug hypersensitivity or other contraindications were ruled out before starting administration of ustekinumab. Tuberculin skin tests and/or QuantiFERON®-TB Gold tests (Cellestis, Chadstone, Australia), and chest X-ray films were also routinely performed for screening of latent tuberculosis. Blood-cell count and liver and renal function test results were obtained before starting treatment, and every 3 months thereafter. A 45-mg dose of ustekinumab (patient weight was < 100 kg in all cases) was administered subcutaneously, followed by a 45-mg dose 4 weeks later and every 12 weeks thereafter. The severity of involvement and the therapeutic outcome were evaluated in every patient by measuring the affected body surface area (BSA) and using the Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), PPP PASI (Table 2) and the Dermatology Life Quality Index (DLQI) at the beginning of treatment, and then every 1–3 months thereafter, at the time of injections. The injections were administered at the hospital.
At the beginning of treatment, two patients (patients 3 and 4) had concomitant psoriasis vulgaris with a BSA involvement < 3%, and in the other three patients the BSA involvement was > 10%. In all five patients, PPPP had failed to respond to multiple topical and systemic treatments (including phototherapy, acitretin, leflunomide, methotrexate and ciclosporin), and four of them (patients 1, 2, 3 and 5) had previously been treated with other biological agents (efalizumab, etanercept and adalimumab). In patients 1 and 5, PPPP was the main sign of a paradoxical reaction to anti-TNF-α treatment, previously prescribed for psoriasis and psoriatic arthritis, respectively. The average duration of follow-up under ustekinumab treatment was 15·2 months, with a range of 11–23 months.
Patient 1 has had plaque psoriasis since 2000. His lesions responded completely to efalizumab treatment for 2 years. Following market withdrawal of this biological agent, he presented a severe flare in February 2009, which was not controlled with topical corticosteroids or etanercept 50 mg twice each week. The patient's lesions cleared after the initiation of 80 mg adalimumab, followed by 40 mg after 1 week, and then every 2 weeks thereafter. One year later, while on treatment with adalimumab, the patient presented a moderate flare of psoriasis and severe PPPP. He developed extensive pustules, severe hyperkeratosis and fissuring on both the palms and soles, with a PPP PASI of 12, PASI 14.8, BSA 18%, PGA 4 and DLQI 15. Monotherapy with ustekinumab 45 mg was started in December 2011, and 5 months later there was marked improvement in his psoriasis and a complete clearance of the palmoplantar lesions: PPP PASI 0, PASI 5, BSA 6%, PGA 1 and DLQI 3.
Patient 2 has had psoriasis since 2003 and PPPP since January 2011. He had been treated with topical corticoids and ciclosporin without response. Treatment with 50 mg etanercept every week was started in March 2011 with only minor improvement. In December 2011, he presented pustules, severe hyperkeratosis and fissures on both the palms and soles; PPP PASI was 14, PASI 8.5, BSA 11%, PGA 4 and DLQI 13, and a decision was made to switch to ustekinumab 45 mg. Five months later, a full recovery was seen, with no remaining lesions on the soles or palms: PPP PASI 0, PASI 0, BSA 0% and DLQI 0.
Patient 3 has had PPPP since May 2010. Her disease had shown a refractory response to methotrexate 10 mg weekly, ciclosporin 200 mg daily, acitretin 25 mg daily, plus topical psoralen ultraviolet A photochemotherapy (tPUVA) and leflunomide 20 mg daily. The patient decided to stop her treatment (acitretin 25 mg daily plus tPUVA) in January 2011 because of lack of efficacy. In March 2011 she showed a severe, handicapping flare of PPP: PPP PASI 6, BSA < 1% (corresponding to minimal compromise of the scalp and eyebrows), PGA 3 and DLQI 15. Treatment with ustekinumab 45 mg was started in March 2011, and a good response was seen 1 month after the first injection. A full recovery was obtained 5 months later, and has been maintained for 20 months: PPP PASI 0, PASI 0, PGA 0 and DLQI 0.
Patient 4 has had PPPP since March 2011; she also showed isolated lesions of psoriasis vulgaris on the pubic area and legs, with a BSA of 2%. She started treatment with acitretin 25 mg per day with no response. In December 2011 she developed extensive palmoplantar affectation with pustules and erythematous desquamative plaques: PPP PASI 11.7, PGA 4 and DLQI 18. Acitretin was stopped and treatment with ustekinumab 45 mg was started. Two months later, there was complete resolution of PPP and the psoriasis vulgaris lesions: PPP PASI 0, DLQI 0. She remains asymptomatic 11 months after the initiation of ustekinumab.
Patient 5 (Figs 1 and 2) has had psoriasis and psoriatic arthritis since 2006. She developed PPPP and a moderate flare of psoriasis as a paradoxical reaction during treatment with adalimumab, in October 2010. We decided to stop adalimumab and to start etanercept 50 mg biweekly plus methotrexate 15 mg every week, but there was no response after 1 month. In December 2010 the patient presented a severe flare of psoriasis (PASI 14.8, BSA 23%, PGA 5 and DLQI 19) and palmoplantar pustules, with PPP PASI 17.6. In addition, pustules could be observed locally on psoriasis lesions. Ustekinumab 45 mg was started 1 week after discontinuation of etanercept and methotrexate. Three months later, there was a complete resolution of PPPP lesions, with PASI 3, DLQI 5, and significant improvement of her arthritis, which had worsened following discontinuation of adalimumab. Twenty-one months after the initiation of ustekinumab, the patient has no PPPP lesions; PPP PASI 0, PASI 0 and DLQI 0. This patient has been the subject of an independent publication.
Hands of patient 5 prior to ustekinumab treatment.
Hands of patient 5 after 16 weeks of ustekinumab treatment.
The British Journal of Dermatology. 2013;168(4):820-824. © 2013 Blackwell Publishing