The events that underlie the conversion from Psoriasis to Psoriatic Arthritis (PsA) are not
well understood. This conversion occurs 30% of the time within the first 10 years of
psoriasis diagnosis. PsA patients have about a 50% chance of developing joint damage within
the first 2 years of disease. A biomarker that identifies subclinical joint inflammation in
psoriasis patients would allow for a diagnostic tool to allow for earlier intervention in
psoriasis patients and provide a better understanding of the underlying molecular
pathogenesis that may lead to development of new therapeutic targets in PsA.
Our long-term goals are to: 1) develop arthritis biomarkers in psoriasis patients that will
facilitate early treatment interventions; and, 2) identify new therapeutic targets in PsA
through better understanding of the underlying molecular pathogenesis. PsA, an inflammatory
arthritis associated with psoriasis, affects approximately 650,000 adults in the United
States and is associated with increased morbidity and mortality. Joint inflammation and
damage arise within the first 2 years of disease in 50% of patients who manifest bone
erosions and joint space narrowing on plain x-rays. The advent of Tumor Necrosis Factor
antagonists (TNFi) for treatment of PsA has dramatically improved clinical response and
slowed bone and cartilage degradation. Nevertheless, up to 45% of patients do not meet
primary endpoints in clinical trials, which underscores the need for new therapeutic options.
Another approach to improve treatment response is early PsA diagnosis, and recent data
indicate that treatment soon after disease onset can improve outcomes. Relevant to the
potential for early intervention and prevention, psoriatic skin plaques typically precede PsA
by 10 years. Moreover, a significant percentage of these psoriasis patients have subclinical
musculoskeletal imaging findings. These findings provide an unparalleled opportunity for
early intervention that could potentially limit or halt joint inflammation and damage.
Regrettably, despite the obvious advantages of early diagnosis and treatment, this goal
remains elusive because the clinical significance of imaging abnormalities in psoriasis
remains unknown. Furthermore, investigators have limited understanding of the mechanisms that
underlie the transition from psoriasis to PsA, and investigators lack the disease specific
biomarkers necessary to identify psoriasis patients with new onset arthritis or sub-clinical
disease. Lastly, up to a third of psoriasis patients with moderate to severe skin disease
report they are undertreated and many are on topical agents unlikely to have a significant
effect on subclinical or clinically apparent joint inflammation.
Up to 150 subjects will be consented and studied in this cross-sectional study - 125 subjects
with Psoriasis (Ps) and 25 Healthy controls. Power Doppler Ultrasound (PDUS) in joints and
entheses will be analyzed to find at least 35 subjects with positive US findings defined as
synovitis, effusion, joint erosions, or increased vascularity otherwise known as a signal. Up
to 50 Ps patients with positive PDUS results will be followed prospectively and contacted at
intervals to update medication history indefinitely. Ps patients will be asked for a follow
up PDUS 4 months post start of biologic, DMARD therapy or phototherapy if the patient decides
to go on such therapies to study longitudinally.
Up to 30 bone marrow aspirations on healthy and PDUS positive Psoriasis subjects will be
performed. A bone marrow aspiration post start of biologic or DMARD standard of care therapy
will be assessed as well.
Research assays: serum will be used to measure biomarker 14-3-3η levels, which may be
analyzed by an external company. Peripheral blood will be used to measure the frequency of
DC-STAMP+ cells (CD14+DC-STAMP+ CD4+DCSTAMP+DC-STAMP+IL-17+). Using multichromatic flow
cytometry, we will measure DC-STAMP expression on peripheral blood cells and on bone marrow
cells. To determine if elevated BM DC-STAMP expression by stromal cells, T cells and/or
monocytes promotes OC formation, co-cultures of bone marrow stromal and hematopoietic cells
with peripheral blood cells will be analyzed for OCPs.
- All Subjects
1. Ability to provide written informed consent
2. Subjects must be 18 years old or older
- Psoriasis Subjects
1. Patients with self-diagnosed Psoriasis. These subjects may present with thick,
scaly, silvery and/or red skin, without ever having been diagnosed by a
- Starting either a DMARD or biologic standard of care for their psoriasis OR
- Currently started taking a DMARD within the last two weeks of study visit
- Currently not using a DMARD or biologic treatment, subjects may be using
topical creams or UV therapy
2. Willing to be studied longitudinally with a 4 month follow-up blood draw and PDUS
if initial PDUS demonstrates positive findings.
- Bone Marrow Aspiration:
1. Willing to undergo procedure.
2. Psoriasis: positive findings on Power Doppler Ultra Sound (PDUS+) such as joint
erosion, effusion, synovitis or increased vascularity, otherwise known as a
- All Subjects
1. Unable to donate blood because of poor venous access or intolerance of
2. Chronic pain syndrome, autoimmune or active inflammatory conditions other than
the conditions being studied. (i.e., chronic infection with hepatitis B or
hepatitis C, inflammatory arthritis, etc) which in the investigator's opinion may
confound the study results.
- Healthy subjects:
1. Musculoskeletal conditions such as joint pains or swelling, fracture, tendonitis
or trauma in the past 3 months, gout, or any arthritis which in the
investigator's opinion may confound the study results.
2. Illness in the last month which in the investigator's opinion may confound the
3. Taking systemic steroids or immunosuppressants
- Psoriasis Subjects:
1. Evidence of inflammatory arthritis.
2. Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire score greater
than or equal to 47.
3. Meet CASPAR criteria for PsA.
- Bone Marrow Aspiration:
1. Side effect to local anesthetics such as lidocaine or novocain.
2. Bleeding disorders or conditions requiring treatment with, NSAID, aspirin,
anti-coagulants or anti-platelet agent, unless a physician investigator
determines it to be safe to hold these agents for 2 weeks.
3. Known thrombocytopenia (< 100,000) or clinically significant PT or PTT outside
the normal range.
4. Pregnant women should not participate; Pregnancy tests will not be performed.