Magnetic resonance imaging and bone scintigraphy in the differential diagnosis of unclassified arthritis.

OBJECTIVES: To investigate the value in clinical practice of hand magnetic resonance imaging (MRI) and whole body bone scintigraphy in the differential diagnosis of patients with unclassified arthritis. METHODS: 41 patients with arthritis (> or = 2 swollen joints, > 6 months' duration) which remained unclassified despite conventional clinical, biochemical and radiographic (hands and feet) examinations were studied. Patients who fulfilled the ACR criteria for rheumatoid arthritis (RA) or had radiographic bone erosions were excluded. Contrast enhanced MRI of the wrist and metacarpophalangeal joints of the most symptomatic hand and whole body bone scintigraphy were performed. Two rheumatologists agreed on the most likely diagnosis and the patients were treated accordingly. A final diagnosis was made by another specialist review 2 years later. RESULTS: Tentative diagnoses after MRI and bone scintigraphy were: RA (n = 13), osteoarthritis (n = 8), other inflammatory diseases (n = 11), arthralgias without inflammatory or degenerative origin (n = 9). Two years later 11 of 13 patients with an original tentative diagnosis of RA had fulfilled the ACR criteria while two were reclassified (one to psoriatic arthritis (RF negative + psoriasis); one to non-specific self-limiting arthritis). No patients classified as non-RA at baseline had fulfilled the ACR criteria after 2 years. The presence of MRI synovitis, MRI erosion and bone scintigraphic pattern compatible with RA showed 100% specificity for a diagnosis of RA at 2 year follow-up. CONCLUSIONS: In patients with arthritis unclassified despite conventional clinical, biochemical and radiographic examinations, MRI and scintigraphy allowed correct classification as RA or non-RA in 39 of 41 patients when fulfilment of ACR criteria 2 years later was considered the standard reference.

Magnetic resonance imaging for accelerated assessment of drug effect and prediction of subsequent radiographic progression in rheumatoid arthritis: a study of patients receiving combined anakinra and methotrexate treatment.

OBJECTIVES: By MRI to assess the efficacy of addition of anakinra for controlling synovitis and stopping erosive progression in patients with clinically active RA despite receiving methotrexate, and to determine the predictive value of MRI for subsequent radiographic erosive progression. METHODS: 100 mg anakinra subcutaneously/day was added to the treatment of 17 patients with clinically active RA despite methotrexate. MRI of the non-dominant wrist and 2nd-5th MCP joints (OMERACT evaluation) was performed at weeks 0, 12, and 36, and radiography of both hands and wrists (modified Sharp evaluation) at weeks 0 and 36. RESULTS: MRI synovitis scores were not significantly changed. Radiography of both hands and wrists after 36 weeks showed erosive progression in 11 patients, and MRI after 12 weeks in 10 patients. Nine of 10 patients with MRI progression at 12 weeks had radiographic progression at 36 weeks. Baseline MRI synovitis and erosion scores, but no clinical/biochemical parameters, correlated significantly with subsequent erosive progression. CONCLUSION: Addition of anakinra did not significantly reduce MRI signs of synovitis, and most patients had progressive joint destruction. Baseline MRI findings predicted subsequent radiographic erosive progression. Unilateral wrist and MCP joint MRI after 12 weeks had a similar sensitivity for detection of erosive progression as bilateral hand and wrist radiography after 36 weeks.

Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: a single-blinded, open-label pilot study.

BACKGROUND: Autism is a severe developmental disorder with poorly understood etiology. A recently published case series describes 3 autistic children with gastrointestinal symptoms who underwent endoscopy and intravenous administration of secretin and were subsequently noted by their parents to demonstrate improved language skills over a 5-week period. This report sparked tremendous public interest, and investigators at several sites moved quickly to design controlled trials to test the efficacy of secretin as a therapy for autistic children. However, this is the first effort specifically designed to replicate the initial reported findings in terms of patient age, presenting symptoms, and drug administration. OBJECTIVE: To rigorously apply the scientific method by assessing the reproducibility of the reported effects of intravenous secretin on the language of young children with autism and gastrointestinal symptoms. METHODS: We performed a single-blinded, prospective, open-label trial by conducting formal language testing and blinded behavioral rating both before and repeatedly after a standardized infusion of secretin. We selected autistic children who were similar in age and profile to those described in the published retrospective case review. Inclusion criteria for study participation included age (3-6 years), confirmed diagnosis of autism, and reported gastrointestinal symptoms (16 had chronic diarrhea, 2 had gastroesophageal reflux, and 2 had chronic constipation). Twenty children (18 male) were admitted to the Pediatric Clinical Research Center at the University of California, San Francisco after administration of the Preschool Language Scale-3 (PLS-3). A 3 CU/kg dose of secretin (Secretin-Ferring) was administered intravenously (upper endoscopy was not performed). Behavioral ratings were derived using the Autism Observation Scale applied to a 30-minute time sample of the child's behavior consisting of a videotape of the PLS-3 (structured setting) and a second free play session with a standard set of developmentally appropriate toys. Participants then returned for follow-up evaluations, with readministrations of the PLS-3 at 1, 2, 3, and 5 weeks' postinfusion, and videotaping of each session for later blinded review by 2 independent observers using the Autism Observation Scale, uninformed about week of posttreatment. We also surveyed parents of our study children about their impressions of the effects of secretin using a 5-point Likert scale for parents to rate changes seen in their child. RESULTS: With a total study completion rate across all participants of 96%, repeated measures analyses of variance revealed no significant increases in children's language skills from baseline across all 5 study time periods after a single infusion of secretin. Similarly, neither significant decreases in atypical behaviors nor increases in prosocial behaviors and developmentally appropriate play skills emerged. Furthermore, no relationship was found between parental reports of change and observable improvement in the sample. Despite the objective lack of drug effect, 70% of parents in our study reported moderate to high change in their child's language and behavior. Furthermore, 85% of parents reported that they felt that their child would obtain at least some additional benefits from another infusion of secretin. CONCLUSIONS: The results of our pilot study indicate that intravenous secretin had no effects in a 5-week period on the language and behavior of 20 children with autism and gastrointestinal symptoms. The open-label, prospective design of our study with blinded reviews of patients both before and after secretin administration follows the scientific method by seeking to reproduce an observed phenomenon using validating and reliable outcome measures. Pilot studies remain a mandatory step for the design of future randomized, clinical trials investigating potential treatments for children with autism.