Mechanistically-based Optimization of UV Radiation Therapy in Psoriasis

The characteristic lesion of psoriasis is a sharply demarcated erythematous papule or plaque
with excessive scaling due to hyperproliferating keratinocytes, infiltrating granulocytes,
and a dense mononuclear infiltrate with activated T cells. To date, no one mechanism has
been explanatory for the panoply of changes that occur in both the dermis and epidermis of
psoriasis patients. Several key findings have shown that cutaneous T cells play a key role
in the propagation of the disease; memory-type T cells home to the skin, specifically due to
expression of cutaneous lymphocyte antigen (CLA), and are the main effector cells in
psoriatic tissue responsible for the production of cytokines that result in exacerbated
cutaneous inflammation. T cell recruitment is thought to occur in psoriasis, in part, as a
result of cytokine and chemokine release from keratinocytes, macrophages, and endothelial
cells. CLA-positive T cells migrate into the tissues where memory-effector T cells are
activated and expand. This migration is critical to maintenance of the psoriasis lesions,
because anti-LFA-1 antibodies (efalizumab) are effective in treating psoriasis, resulting in
blood lymphocytosis and tissue depletion of T cells. Despite many years of using UVB
phototherapy in the treatment of psoriasis, its mechanism of action is based mainly on in
vitro exposures of isolated cells and on extrapolations from UV effects on normal skin, with
little direct data from lesional skin.

Previously, our studies determined optimal single efficacious dose using the Excimer laser,
refined the mechanism of UVB action in psoriasis, developed key cytokine quantitative meth
-ods to assess targeted mRNA levels in psoriatic tissue after treatment, demonstrated that
regulatory T cells from psoriasis tissue and blood appear to have a functional defect, and
demonstrated that UVA component of solar radiation is a critical and significant contributor
to UV-induced in vivo immuno-suppression. All of these previous findings lead us to our
current hypothesis that direct selective apoptotic effects on the T mem/Teff cells may
result in decreased APC activation and IL-12 over-riding of Treg suppression and a
re-balanced Tre:Tmem/eff cell ratio which in turn may have a sustained remittive effect
(high duration multi-month clearing of a psoriasis lesion after a single UVB laser light
treatment.)

Inclusion Criteria:

- The presence of plaque-type psoriasis in areas of the trunk, buttocks, or extremities
that are amenable to biopsy and evaluable disease in at least 2 cm target treatment
sites separated by 1 cm

- Age 18-80, both genders, all ethnicities

- No contraindications to phototherapy or biopsy procedures

- No topical steroid, tar, phototherapy, Vitamin D, or retinoid therapy to target
lesions for at least 1 week prior to the study

- No systemic psoriasis therapy for at least four weeks prior to the study

- Able to give informed consent under IRB approval procedures

Exclusion Criteria:

- Photosensitivity disorders

- Active untreated diseases or medication usage which may interfere with UVB, wound
healing, or immune function

- Hypersensitivity to local anesthetic

- Inability to provide informed consent

- Pregnancy and /or lactating