Ultrasound Assessment of Steroid Joint Injections in Juvenile Idiopathic Arthritis

AIM 1: The first aim will be a two-part cross-sectional study comparing US imaging of active
joints in 55 subjects with JIA to standardized clinical and functional measures, assuming
that each subject will have at least 1 active joint. Subjects less than 21 years diagnosed
with JIA per classification described by the International League Against Rheumatism (ILAR)
with large and medium joint synovitis will be eligible.

- Phase 1. A pediatric rheumatologist will examine 25 subjects with a spectrum of
arthritis severity after informed consent is obtained. Large and medium joints, such as
knees, ankles, wrists, and elbows, will be assessed for active arthritis, as defined by
swelling or limitation of motion with pain or warmth. Grading of clinical severity is
derived from the ACR Pediatric 30 and will assess for swelling on a scale of 0-3 and
limitation of motion with warmth or pain on motion on a scale of 0-3. Based on this
grading, a Clinical Severity Score for inactive, mild, moderate, or severe arthritis
will be obtained for each joint. Following the clinical evaluation, a pediatric
rheumatologist who has received training in musculoskeletal US (PI) will image the
joint. A portable US machine with a high frequency probe (6-18 MHz) and power Doppler
capability will be used to image the target joints and to identify anatomical signs
suggestive of arthritis. At least 2 views, coronal and transverse, of each joint will
be obtained and recorded per musculoskeletal US specifications as described by the
European League Against Rheumatism (EULAR). US images will be saved under a subject
code on the US machine hard drive. These images will be reviewed with a consulting
rheumatologist with expertise in musculoskeletal US (J. Nishio, MD). US determination
of synovitis (synovial thickness with Doppler enhancement), effusion, erosions, and
tenosynovitis will be based on definitions established by the Outcome Measures in
Rheumatoid Arthritis Clinical Trials (OMERACT) 7 consensus group for adults with
rheumatologic disease. An US score for arthritis will then be developed based on the
gold standard of clinical exam. The US score will assess for active arthritis as
defined by synovitis on a scale of 0-3 and/or effusion on a scale of 0-3. In addition,
other significant abnormalities in the joints will be evaluated, including absence or
presence of erosions and tenosynovitis. The result of this phase of Aim 1 will be the
creation of an US Severity Score for inactive, mild, moderate, or severe arthritis in a
single large or medium joint that is consistent with the Clinical Severity Score.

- Phase II. The US Severity Score developed as described above will be tested for
correlation with the Clinical Severity Score. An additional 30 subjects meeting
inclusion criteria will be enrolled and assessed for arthritis by physical exam
performed by a pediatric rheumatologist followed by an US exam performed by the PI. If
the subject has more than 1 large or medium joint with arthritis, a single joint will
be chosen by random selection. Based on the findings, the clinician will assign a
clinical score, and the PI and the consulting rheumatologist will assign an US score
based on the standardized US Severity Score obtained from Phase I. The PI and
consulting rheumatologist will be masked to physical exam findings and the Clinical
Severity Score. The US score will then be compared to the clinical score to assess how
the US scoring relates with the standardized clinical measures.

AIM 2: The second aim will study the use of US in imaging the placement of IAS and response
to this therapy in 20 subjects receiving IAS for treatment of active arthritis in large and
medium joints. Patients less than 21 years old with a diagnosis of JIA per ILAR
classification receiving IAS injections of the knee, wrist, elbow, or ankle as part of their
standard medical care will be eligible. Non-eligible patients include subjects with a
non-inflammatory diagnosis, such as mechanical joint disease, or a large joint effusion
requiring additional therapeutic procedures, such as arthrocentesis. Informed consent and
assent for children over 7 will be obtained. The targeted joint will be scored by a
rheumatologist other than the PI using the Clinical Severity Score described above. Sedation
may be provided per routine for joint injection. Routine process for joint injection will be
followed. The pediatric rheumatologist performing the injection will use standard external
clinical landmarks and palpation to identify the appropriate injection site. Triamcinolone
hexacetonide with 1% unbuffered lidocaine will then be shaken to allow the introduction of
air per GAS-graphy technique as described by Koski et al. and injected into the targeted
joint. The PI, who will not perform any injections in this study, will obtain US imaging
just prior and immediately following the joint injection. The rheumatologist performing the
injection will be masked to US images. Each image will be obtained and recorded using EULAR
specifications, saved under a subject code on the US machine hard drive, and scored by the
PI and the consulting rheumatologist using the US Severity Score described above. For the
second aim, I will also determine the presence or absence of steroid within the target joint
capsule. The physician performing the physical exam, the subject, and the subject's
guardian(s) will be masked regarding US results, including location of steroid within or
around the joint space and sonographic recordings of joint pathology. Patient outcomes will
be determined at 1 week, 4-6 weeks and 3-6 months by the Clinical Severity Score and by US
using the US Severity Score described and developed in Aim 1. The clinician performing the
physical exam and the sonographer will be masked to each other's scores.

Other variables will also be collected as part of both aims, including pain as assessed by a
standardized pain scale, physician assessment of global disease activity, and functional
status as determined by the childhood health assessment questionnaire (CHAQ), a validated,
reliable measure of functional status in JIA. These last assessments are 3 of the 6 measures
of the ACR Pediatric 30, a validated measure used in clinical trials in JIA (Giannini et
al., 1997). Other patient data that will be collected include JIA subtype, duration of
disease, age of onset, age at procedure, race/ethnicity, concurrent medications, and whether
the procedure required the use of general anesthesia.