Systemic lupus erythematosus (SLE) affects joints in up to 95% of SLE patients in general, and 11.7% of lupus patients develop permanent joint damage. Additionally, clinical trials involving SLE patients find arthritis present in 70%-80% of SLE patients. Lupus-related joint involvement is inconsistently defined in classification criteria and activity measures and characterized by a wide heterogeneity in presentations and severities, ranging from persistent joint pain without evidence of swelling to joint deformities (also known as Jaccoud’s arthropathy) and bone destruction. There is continued debate as to whether tenderness in the absence of swelling constitutes active lupus arthritis and should be scored on activity instruments. The confusion over arthritis scoring impacts both clinical care and trials. There is a clear unmet need for a simple, reliable, non- invasive, and low-cost imaging modality that can objectively assess and monitor arthritis progress in lupus patients.

Optical tomographic imaging (OTI) has the potential to address this need. Studies have shown its utility for diagnosing rheumatoid arthritis (RA) joints. OTI measures the intensities of transmitted and reflected light of different wavelengths that illuminate tissues in order to evaluate arthritis. Changes in the measured light intensity reflect physiologic or pathologic changes, which enable this technology to diagnose and monitor arthritis activity. Overall, OTI has the potential to provide inexpensive, non-invasive, rapid, and quantitative measurements of arthritis without the use of radiation in a patient-friendly setting.

The first aim of this study is to design and build a rapid and ergonomic, low-cost, full imaging system to evaluate all the finger joints of SLE patients. A prototype device was tested in a pilot study of 20 SLE patients. The proposed imaging hardware development will be based on our experience from the pilot study and will use highly flexible bands that can be wrapped around the fingers and contain the electronic components, lasers, and light detectors. Eventually, we hope to develop a single unit glove that can simultaneously diagnose all finger joints. Lights in different wavelengths emitted from the lasers will illuminate the joints and allow visualization of bones, tendons, muscles, and vessels. Imaging reconstruction software will be developed to produce cross- sectional images of the joints.

In the second aim, we will evaluate 50 SLE patients and 20 healthy volunteers in order to validate OTI as a measure of lupus arthritis. Patients will be assessed over a period of 6 months both before and after treatment of their lupus arthritis. We will compare results of OTI evaluation to the “ground truth,” which is a combination of all arthritis measures: swollen/tender joint counts, musculoskeletal ultrasound assessment, and MRI evaluation for each joint. In addition, we will correlate OTI evaluation results from the baseline visit with the results from follow-up assessments to determine the measure’s test-retest reliability (in patients in whom arthritis is stable) and its ability to detect changes (in patients that improve or worsen).

The third aim is to characterize SLE arthritis by evaluating plasma soluble inflammation proteins, called cytokines, and gene transcription. Plasma cytokine profiles, genes, arthritis characteristics (tender, swollen, deformed), and the results of imaging modalities will be interpreted in a comprehensive manner to differentiate different types of SLE arthritis and search for the molecular changes that correlate with SLE arthritis flare and/or resolution.

This proposal addresses the challenges of diagnosing lupus arthritis and evaluating patient’s response to therapy – given the wide heterogeneity of SLE arthritis – by using a cost-effective, objective, and reliable method. The aims will provide essential data to allow the development of OTI, a novel optics-based technology, to be applied in accurate diagnosis and evaluation of SLE arthritis. Based upon our findings, we hope to expand the use of OTI in SLE arthritis to clinical practices, lupus research, and clinical trials. Ultimately, we hope to produce a wearable and portable imaging device incorporating OTI technology that would allow real-time and at-home monitoring of lupus arthritis, with the potential to improve the quality of care for SLE patients.