Running head: Radiological Modalities and Childhood Arthritis 1

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1 Running head: Radiological Modalities and Childhood Arthritis 1 Contemporary Radiological Modalities in the Diagnosis of Childhood Arthritis November 15 th, 2011

2 Radiological Modalities and Childhood Arthritis 2 ABSTRACT Today s world is filled with countless exciting and continuing advancements in technology. Imaging modalities are just one of many medical technologies in these advancements. Currently an uncertain area exists in which modalities are the most efficient in diagnosing specific diseases and the stage that disease is currently in. This gray area exists due to the fact not enough time has elapsed between advancements in technology and the time to perform numerous scientific tests. These tests are necessary to provide statistical information so that physicians, parents, and patients can make the best choice in imaging for the patient s disease. Childhood arthritis is one of many diseases caught up in this lag between advancements and knowledge. The ability to diagnose the correct childhood disease in early stage development is critical in the quality of a patient s complete life span.

3 Radiological Modalities and Childhood Arthritis 3 Modern Radiological Modalities in the Diagnosis of Childhood Arthritis Radiological imaging is a member of the health team in the diagnosis and stage of development in childhood arthritis. Childhood arthritis (CA) is commonly known as Juvenile Idiopathic Arthritis (JIA). According to Cahill et al. (2007), JIA occurs at a rate of about 1 per 1000 children in North America and may lead to morbidity and deformity (p.182). JIA has 7 subgroups known as Oligoarthritis, Extended oligoarthritis, Rheumatoid factor positive polyarthritis, Rheumatoid factor negative polyarthritis, Enthesitis-related arthritis (ERA), Psoriatic JIA, and Systemic-Onset JIA (Packam, 2008, as cited in McKay, 2010). JIA is very complicated due to the lack of ossification in the skeletal system. As a child skeleton matures, ossification of cartilage advances, and eventually becomes bone. Children develop at different rates and times; making it difficult to develop a standardized scale in which to measure cartilage. According to Spannow et al. (2009), a study that evaluated a healthy heterogeneous group of children up to the age of 16 years was performed. They were able to identify that boy s cartilage is significantly thicker than girls. Interestingly, during this study, a cartilage guideline was developed with age and sex categories. This guideline is one of the first steps in a protocol for cartilage thickness in children. This information combined with future studies should help to build a format to what is considered normal or diseased. The goal is to identify JIA in early stage development and then treatment can begin sooner. Early treatment can lead to a healthier long term outcome by slowing, or even placing the disease into remission. Acute arthritis often prompts consideration of commonly referred to disease-modifying anthiheumatic drugs (DMARDS), Tumor necrosis factor (TNF) inhibitor, Interleukin (IL) and Receptor antagonist, or IL-6 receptor antagonists (Lovell, 2000, as cited in Tateishi). Results can be devastating if JIA

4 Radiological Modalities and Childhood Arthritis 4 advances and permanent disabilities develop. The quality of life then becomes negatively impacted on the patient and their family. Magnetic Resonance Magnetic resonance imaging (MRI) combined with a gadolinium contrast enhancement is the most dependable form of MRI in the study of arthritis. There are presently some experimental contrasts that are being tested as an alternative replacement for gadolinium. Patients with severe kidney failure can be at risk of developing Nephrogenic Systemic Fibrosis by using Gadolinium. Nephrogenic Systemic Fibrosis causes thickening of the skin, organs, and other tissues. There's no effective treatment for this serious, debilitating disease. According to Kirkhus, Flato, Riise, Reiseter, and Smith (2011): A study was performed and was specifically designed to describe Magnetic Resonance Imaging (MRI) findings in synovium, bone marrow, joint fluid, soft tissue, and cartilage in children with recent onset arthritis recruited from a population - based study of the incidence of arthritis and to determine whether MRI characteristics can differentiate IA, PA/TA, and JIA from each other in early phase of the disease (p. 433). A strict scientific criterion for the study was followed that included 59 children. The children filled a rigid criteria base for possible arthritis or had recent- onset arthritis. Each child in the research had one joint or anatomical region scanned. Kirkhus et al. (2011) noted, 16 patients were classified clinically as having IA, 16 as having PA/TA and 27 as having JIA (p. 435). The study showed that JIA symptoms take much longer to become evident; therefore, it s a longer period of time before the child is seen by a physician. This delay makes JIA much more dangerous than IA or PA/TA. Kirkhus et al. discussed, JIA had synovium with irregular thickness and low signal intensity synovial tissue significantly more often than the children with

Radiological Modalities and Childhood Arthritis 5 IA and PA (p. 437). Illustrations of MRI findings of a young child with JIA are showing synovial thickening and low signal intensity tissue. (See Fig.

5 Radiological Modalities and Childhood Arthritis 5 IA and PA (p. 437). Illustrations of MRI findings of a young child with JIA are showing synovial thickening and low signal intensity tissue. (See Fig. 1) Fig.1 MRI of the knee of a 5-year-old boy with confirmed JIA. (a)coronal T1-W SE and (b) coronal STIR show thickened synovium with low signal intensity (arrows) and no bone marrow oedema or soft-tissue oedema. (c) Axial contrast-enhanced T1-W SE with FS shows irregularly thickened and intensely contrast-enhancing synovium, as well as low signal intensity synovial tissue with no contrast enhancement (white arrow), joint effusion and enlarged reactive lymph nodes (black arrow) Note. From Differences in MRI findings between subgroups of recent-onset childhood arthritis, by E. Kirkhus 2010, Pediatric Radiology, 41, p Copyright 2010 by The Author(s). Reprinted with permission In all appearances MRI seems to be an effective imaging device in conjunction with physicians in diagnosing and detecting early changes such as bone erosion, synovium thickening, and cartilage damage in childhood arthritis. Ultrasound Power Doppler Ultrasound Power Doppler (US-PD) is becoming popular with physicians in imaging synovial vascular flow. Vascular flow increases where synovitis is present due to the inflammation. Synovitis is one form of inflammation that can cause permanent synovial hypertrophy even after the disease is in remission. Another variety of inflammation according to Joulin et al. (2011), Enthesitis-related arthritis (ERA) is found in the enthuses, axial skeleton, and peripheral joints (p. 849). ERA is form of JIA that is difficult to detect in a clinical

6 Radiological Modalities and Childhood Arthritis 6 examination due to the fact it is often non-symptomatic. Sparchez, Fodor, and Miu (2010) found clinical and laboratory tests often fail to identify inflammation. Joulin et al. (2011), explained that ERA is most commonly involved entheses are plantar aponeurosis, calcaneal enthesis, and distal and proximal patellar ligament insertion in adults (p. 852). The illustration to the left shows how mild vascular flow can be seen and measured in US-PD. (See Fig. 2) ERA is associated with the insertion point of the enthesis into the bone and bursitis. The vasularizations at entheseal insertion points are Fig 2. Mild vascularisation on power Doppler (score 1). Active proliferative synovitis of the right ankle in a 10 years girl with polyarticular JIA. Note. From The role of Power Doppler ultrasonography in comparison with biological markers in the evaluation of disease activity in Juvenile Idiopathic Arthritis by M. Sparchez et al Medical Ultrasonography, 12(2), p. 99. Copyright 2010 by Medical Ultrasound. Reprinted with permission. far less than in the synovium. This makes diagnosis much more difficult because the inflamed vessels are few in number which makes them appear normal to the inexperienced eye. These complex problems make it necessary to have a well trained and experienced sonographer when imaging for ERA. According to Joulin et al. a study was performed to assess the diagnostic accuracy of US- PD for detecting enthesitis in children with JIA compared to the clinical examination (p. 849). The study was comprised of an equal ratio of males to females; with a total number of 26 children. All of the children were being treated for some form of JIA. The study also consisted of a control group of healthy children between the ages of approximately 3-16 years of age. The

7 Radiological Modalities and Childhood Arthritis 7 control group had a similar ratio of males to females. The results reported in the JIA Patients were approximately 9% had enthesitis at the cortical bone site, distal patellar ligament had 30%, Achilles tendon had 25%, quadriceps and proximal patellar ligament insertion were 20% and the plantar fascia was 10% (Joulin et al. 2011, p. 852). The illustration to the left show how marked vascular flow can be seen Fig. 3 Marked vascular on Power Dopplar (score 3). Active proliferative synovitis on the knee joint in a 15 year old patient with persistent oligoarthritis. Note. From The role of Power Doppler ultrasonography in comparison with biological markers in the evaluation of disease activity in Juvenile Idiopathic Arthritis by M. Sparchez et al Medical Ultrasonography, 12(2), p. 99. Copyright 2010 by Medical Ultrasound. Reprinted with permission. and measured in US-PD. (See Fig. 3) Combining physician s evaluation, laboratory tests, and US therapeutic decisions should be more successful due to advancing technology and team work. Overall it appears US-PD is filling a gap in diagnosing several subcategories of JIA. Further testing of children (not just adults) is needed to verify its effectiveness. Positron Emission Tomography A Positron Emission Tomography (PET) uses F-fluorodeoxyglucose (FDG) to search for inflammation in JIA patients. Tateishi et al. (2010) states, inflammation can be detected when FDG is taken up by macrophages and immature granulation tissue (p. 1782). According to Tateishi a study was completed with 28 children confirmed with JIA from Yokohama City University hospital in Yokohama. The purpose was to evaluate the correlation between FDG uptake and children with JIA. Plain radiographs, PET scans, and clinical evaluations were performed on each child using a set criterion. The results showed a positive relationship between

4) Clinical findings compared with F-FDG uptake results corresponded well to each other.

8 Radiological Modalities and Childhood Arthritis 8 F-FDG uptake and the other two tests. A Positron Emission Tomography Computed Tomography (PET/CT) image shows the different degrees of F-FDG uptake in a patient s anatomy. (See Fig. 4) Clinical findings compared with F-FDG uptake results corresponded well to each other. This relationship leads to the possibility that measurable uptake may be directly linked to determining the stage of synovitis. Another positive PET finding was radiographs and F-FDG Fig. 4 Image obtained using a combination of PET and CT imaging technology Note. From Positron Emission Tomography - Computed Tomography (PET/CT), by RadiologyInfo.Org 2011 by RadiologyInfo.org. Reprinted with permission. uptake did not correlate well. A possible reason for this may be PET is able to locate inflammation before erosion begins. Tateishi et al. commented on PET saying, F-FDG PET may underestimate erosive changes because chronic burnt-out erosion may be cold (p. 1787). The capability of differentiation between acute and chronic erosive changes on F-FDG PET is still unclear. Computed Tomography Computed tomography (CT) is one of the paramount ways to identify bone damage; including erosion. (See Fig. 5) Arthritis in the temporomandibular joint (TMJ) is commonly missed during routine clinical Fig.5 Photograph of a CT machine installed in a hospital. Note. kidneys&qpvt=ct+images+of+kidneys&form=igre#x0y2 8367

Radiological Modalities and Childhood Arthritis 9 evaluations unless; the general physician has become well educated on the field of arthritis.

9 Radiological Modalities and Childhood Arthritis 9 evaluations unless; the general physician has become well educated on the field of arthritis. Physicians need to be aware, arthritis of the Temporomandibular joint (TMJ) has been reported in association with all of the categories of Juvenile idiopathic arthritis (JIA), with prevalence as high as 75% according to (Pedersen, 2001 as cited in Ringold 2011, p. 1423). JIA children can be vulnerable to erosion of the mandible because the growth plate is below the fibrocartilage which can become inflamed. CT can verify erosion, narrowing, ossification, and condylar flattening in temporomandibular joint. These types of damage can be asymptotic or cause pain, stiffness, swelling, and difficulty opening or closing of the mandible. According to Ringold, CT was the first to diagnose TMJ but was unable to identify if ossification was present in the synovium. Endoscopy The intestines are not exempt from the attack of JIA. Inflammatory bowel disease (IBD) can cause fever, diarrhea, weight loss, and pain. Endoscopies, colonoscopies, and small bowel barium enemas are often ordered by physicians. These three procedures are not considered child friendly by the patient, parent, or health staff. Capsule endoscopy (CE) is bringing new hope to this problem. Lesions and ulcers Fig.6 Aphtous lesion of small bowel tract detected with video Capsule Note. Usefulness of wireless capsule endoscopy for detecting inflammatory bowel disease in children presenting with arthropathy, by Taddio et al. 2011, by Springer-Verlag. Reprinted with permission. were discovered by CE in the intestines tract (See Fig. 6 & 7).The child does not have to be initially exposed to radiation or traumatic exams with this non-invasive procedure. According to Taddio, the wireless CE called PillCam SB2 was used in their study for detecting

Radiological Modalities and Childhood Arthritis 10 intestinal inflammation. The PillCam SB2 video camera is placed inside a capsule that is small enough to be swallowed.

10 Radiological Modalities and Childhood Arthritis 10 intestinal inflammation. The PillCam SB2 video camera is placed inside a capsule that is small enough to be swallowed. The camera video s the intestines as it is being processed through the digestive system. It eventually is expelled by nature and the parents retrieve it. It is then returned to be evaluated by the radiologist. If the results look positive for IBD then a colonoscopy or small bowel follow through can be done to verify the PillCam s findings. Conclusion JIA is a challenging disease even with new and improving technologies. It is beginning to be found in earlier developmental stages because imaging modalities are factoring in to the medical field. New technologies are making it possible for children to receive lower doses of radiation, or in some cases no radiation in diagnosing Fig. 7 Typical cobblestone -like appearance of a small bowel tract detected with video capsule Note. Usefulness of wireless capsule endoscopy for detecting inflammatory bowel disease in children presenting with arthropathy, by Taddio et al. 2011, by Springer-Verlag. Reprinted with permission. JIA. Current studies that are being done are beginning to form statistical information and views to which diagnostic imaging modalities have superior performances with specific CA diseases. Many more studies are necessary before a final judgment can be made. It is possible that technological advances may continue to grow faster than scientific research can progress to catch up. It is evident that imaging will continue to grow and continue to be an indispensable component in the diagnosis of JIA and numerous other diseases.

11 Radiological Modalities and Childhood Arthritis 11 References Cahill, A.M., Baskin, K.M., Kay, R.D., Arabshahi, B., Cron, R.Q., Dewitt, E.M., Towbin, R.B. (2007). CT-Guided Percutaneous Steroid Injection for management of inflammatory Arthropathy of the temporomandibular joint in children. American Roentgen Ray, 188, doi: /ajr Joulin, S., Breton, S., Cangemi, C., Fenoll, B., Bressolette, L., Parsau, L., Pensec, V.D. (2011). Ultrasonography for detecting Enthesitis in Juvenile Idiopathic Arthritis. Arthritis Care & Research, 63(6), doi: /acr Kirkhus, E., Flato, B., & Riise, O., Smith, H. J. (2010). Differences in MRI findings between subgroups of recent-onset Childhood Arthritis. Pediatric radiology, 41, doi: /s y McKay, G.M., Cox, L.A., & Long, B.W. (2010). Imaging Juvenile Idiopathic Arthritis: Assessing the Modalities. Radiologic Technology, 81(4), Ringold, S., Thapa, M., Shaw, E.A., & Wallace, C.A. (2011). Heterotopic ossification of the Temporomandibular Joint in Juvenile Idiopathic Arthritis. Journal of Rheumatology, 38(8), doi: /jrheum ) Spannow, A.H., Jensen, M.P., Andersen, N.T., & Stenbog, E., & Herlin, T. (2009). Inter -and Intraobserver variation of Ultrasonographic Cartilage thickness assessments in small and large joints in healthy Children. Pediatric Rheumatology, 7(12). doi: / Spârchez, M., Fodor, D., & Miu, N. (2010). The role of Power Doppler ultrasonography in comparison with Biological Markers in the evaluation of disease activity in Juvenile Idiopathic Arthritis. Medical Ultrasonography, 12(2),

12 Radiological Modalities and Childhood Arthritis 12 Taddio, A., Simonini, G., Lionett, P., Lepore, L., Martelossi, S., Ventura, A., & Cimaz, R. (2011). Usefulness of Wireless Capsule Endoscopy for detecting inflammatory bowel disease in Children presenting with Arthropathy. European Journal of Pediatrics, doi: /s Tateishi, U., Imagawa, T., Kanezawa, N., Okabe, T., Shizukuishi, K., Inoue, T. et al. (2010). PET assessment of disease activity in children with Juvenile Idiopathic Arthritis. Pediatric Radiology, 40, doi: /s

8/29/2012. Outline Juvenile idiopathic arthritis. 1. Classification-ILAR. 1. Classification-clinical diagnosis. 1. JIA classification

8/29/2012. Outline Juvenile idiopathic arthritis. 1. Classification-ILAR. 1. Classification-clinical diagnosis. 1. JIA classification Outline Juvenile idiopathic arthritis 1. Classification and symptoms (ILAR-International league of Associations for Rheumatology) 2. Imaging J. Herman Kan, M.D. Section chief, musculoskeletal imaging Edward