Immune Signature of Palmoplantar Pustulosis

I. SPECIFIC AIM

Specific Aim. To identify transcriptional signatures in the skin and blood of patients with palmoplantar pustulosis (PPP).

II. BACKGROUND AND SIGNIFICANCE

Despite major advances in elucidating the molecular pathways of chronic plaque psoriasis (CPP), the immunopathogenesis of PPP, a less common "variant" of psoriasis, remains elusive. It is characterized by the development of inflammatory sterile pustules on the palms and soles of affected individuals, which can be exceptionally painful, interfering with walking and manual activities and impinging significantly on quality of life. Current systemic and biologic treatments used to treat CPP have only a moderate effect in patients with PPP, supporting the suggestion that PPP is a separate disease entity with a distinct immunopathogenic basis. Moreover, the spontaneous paradoxical development of PPP is frequently observed in patients treated with anti-tumor necrosis factor-α therapies, agents typically used in the treatment of CPP. Genetic analysis also distinguishes patients with PPP from those with CPP.

At the investigators' institution, microarray analyses of blood transcriptional patterns have permitted crucial advances in characterizing the immunopathogenesis of immune-mediated conditions such as systemic lupus erythematosis and systemic-onset juvenile idiopathic arthritis. The investigators now wish to examine transcriptional profiles in the skin and blood of patients with PPP to identify the immunopathogenesis of this condition and identify potential therapeutic targets. The investigators will validate the findings at a cellular and protein level using flow cytometry, immunohistochemistry and measuring serum levels of proteins in the blood with Luminex or ELISA.

Inclusion criteria

• Subjects must give written informed consent.
• Subjects are age 18 years or older, with a diagnosis of palmoplantar pustulosis (PPP) or be a healthy control.
• Subjects must be able to adhere to the study visit schedule and other protocol requirements.
• Patient must be off systemic psoriasis therapies (e.g. retinoids, phototherapy, methotrexate, cyclosporine etc.) for at least 4 weeks, biologic therapies for 12 weeks (or 24 weeks in the case of ustekinumab) and off topical therapies (e.g. calcipotriene, topical steroids) for at least 2 weeks.

Exclusion criteria

• Inability to provide informed consent.
• Patient is unwilling to be off systemic psoriasis therapies for at least 4 weeks, biologic therapies for 12 weeks (or 24 weeks in the case of ustekinumab) or off topical therapies for at least 2 weeks.
• Unwilling to consent to skin biopsy or blood draw.
• Are pregnant, nursing, or planning a pregnancy while enrolled in the study.
• Uncontrolled medical conditions (diabetes, liver disease, renal disease).
• Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening or have had a non-tuberculous mycobacterial infection or opportunistic infection (e.g., cytomegalovirus, pneumocystosis, aspergillosis) within 6 months prior to screening.