Palmoplantar pustulosis (PPP) is a chronic recurrent skin condition characterized by the presence of pustules, erythema and hyperkeratosis on palms and soles. PPP can be a severe and disabling disease limiting the ability to walk or work. Although studies on the quality of life of patients with PPP are not available, a recent investigation showed that palmoplantar psoriasis (non pustular) has a more important impact on quality of life than plaque psoriasis. This important impact on quality of life is not surprising as palmoplantar psoriasis as well as palmoplantar pustulosis may limit the ability to work or conduct activities with hands or even impair walking. The disease is sometimes associated with psoriasis elsewhere on the body. Current treatments for PPP include topical corticosteroids, cyclosporine, PUVA therapy, methotrexate and acitretin. Response to topical corticosteroids and PUVA therapy is often disappointing presumably because the thickness of the stratum corneum on palms and soles prevents good penetration of topical medications and light. Cyclosporine and methotrexate are sometimes used with success for PPP but there are concerns with long term toxicity of both drugs. Therefore there is a need for new treatments for PPP.

This is a placebo-controlled double blind study. Patients will be randomized to receive etanercept versus placebo in a 2:1 fashion for the first 3 months. All patients will receive etanercept in the last 3 months.

Patients with active PPP will be included. A washout of 4 weeks for systemic medications and 2 weeks for Psoralen Ultra Violet A (PUVA) therapy will be required. A washout period of 2 weeks will be required for all other topical medications. The Palmoplantar pustulosis severity index (PPPASI) will be used to evaluate severity. Only patients with a severity score of 8 or more on hands and/or feet will be included. Safety will be assessed by performing physical examinations, evaluation of adverse events and biological parameters (complete blood count (CBC), chemistry, urinalysis).

High quality digital medical photographs will be taken at baseline, 3 months and 6 months.

Inclusion Criteria:

• Palmoplantar pustulosis with a severity score of at least 8 on hands and-or feet
• Age 18 years or older
• Patient who would benefit from systemic therapy
• Unless surgically sterile (or at least 1 year post-menopausal for women) patients (heterosexual men and women) must have used a effective method of contraception for at least 30 days before the start of the study drug and until at least 1 month after the last drug administration
• Informed consent obtained
• Normal or non clinically significant chest X ray taken within 6 months of screening
• Negative serum pregnancy test at screening and negative urine pregnancy test at day 0 for women of childbearing potential
• Negative personal history of tuberculosis
• Presence of PPP for more than 6 months
• Subject must be willing to inject themselves subcutaneously.
• Negative PPD results

Exclusion Criteria:

• Use of topical steroids, topical tar preparations, or other topical anti PPP or anti-psoriatic preparations within the past two weeks
• Unstable forms of psoriasis (acute guttate psoriasis, psoriatic erythroderma, generalized pustular psoriasis)
• At the investigator's discretion any significant infection within 30 days of screening or a patient at risk of septicemia
• Presence of acute forms of tinea pedis and other causes of pustular eruptions of the palms and soles apart from PPP based on clinical evaluation
• Evidence of any skin condition that would interfere with the evaluation of PPP
• Use of investigational drugs within the past four weeks
• Use of systemic anti-PPP or anti-psoriatic drugs such as steroids, retinoids, or methotrexate within the past four weeks
• Use of parenteral systemic antibiotics within the past four weeks
• Use of cyclosporine within the past four weeks
• Use of ultraviolet light therapy (UVB, nbUVB or PUVA) within the past two weeks
• An unstable or serious medical condition
• Known sero-positivity for the HIV virus
• Known hypersensitivity to etanercept or one of its components
• Receipt of live attenuated vaccines 12 weeks or less before Day 0 and during the course of the study
• Pregnant or breast feeding female subject
• Any significant medical condition that might cause this study to be detrimental to the patient
• At the investigator's discretion current or history of alcohol or drug abuse that would interfere with the ability to comply with the study protocol
• Presence of congestive heart failure
• Presence of a demyelinating disorder (optic neuritis, multiple sclerosis or other)