Magnetic resonance imaging of rheumatoid arthritis in metacarpophalangeal joints.

OBJECTIVE: To report the development of high-resolution targeted magnetic-resonance imaging (MRI) techniques (not using injections of contrast media) to investigate and monitor rheumatoid arthritis (RA) in the metacarpophalangeal (MCP) joints. DESIGN AND PATIENTS: A total of 25 RA patients (age range 30-68 years) with varying degrees of disease severity ranging from early onset through active disease to the burnt-out stage, were imaged. (One patient subsequently underwent surgery and histological data was obtained.) A series of 10 control subjects were also studied--two for each 10-year age range. All the RA subjects were assessed for disease activity using standard clinical criteria and radiography as part of normal procedures. MRI was carried out using a targeted system and novel radiofrequency coil. Images of the MCP were performed at very high resolution with 1.5 mm slice thickness and in-plane resolution 130 microns. Standard gradient-echo (GE) sequences were used for anatomical imaging, multiple-echo GE sequences used to produce effective spin-spin relaxation time (T2*) maps and optimised binomialpulse presaturation used in conjunction with a GE sequence to generate magnetization-transfer (MT) ratio maps. RESULTS: High-quality high-resolution images of the MCP joints were obtained which highlighted normal anatomy and key features characterising the disease state (e.g. pannus, bone erosions, vascularity). Accurate measurements of T2* and MT with variations of +/- 4% and +/- 2% respectively were achieved. In active disease, variations in T2* and MT could be determined throughout areas of pannus, clearly demonstrating the heterogeneity of this erosive tissue. Pannus in MCP joints with active destruction was found to have high values of T2* varying from 25 ms to 40 ms with pockets up to 100 ms, whereas pannus present in chronic destruction, or burnt-out disease, had T2* values ranging from 21 to 29 ms. MT-active tissue was uniformly distributed in burnt-out disease, which was confirmed histologically in one case, compared with a more heterogeneous distribution in active disease. CONCLUSION: The MRI sequences and targeted system developed allow high-resolution studies of RA disease progression and activity. The data confirm the variable pattern of the disease and, in particular, heterogeneity of pannus.

Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group.

OBJECTIVE: Prednisolone reduced the progression of joint destruction over 2 yr in early, active rheumatoid arthritis. The response to discontinuation of prednisolone under double-blind conditions is now reported. METHODS: A randomized, double-blind, placebo-controlled trial of prednisolone 7.5 mg daily in addition to routine medication over 2 yr in 128 patients with early rheumatoid arthritis, using radiological progression (changes in the Larsen score) and the development of erosions as primary outcome measures. Study medication was blindly discontinued and follow-up maintained for a further year. Other assessments included disability, joint inflammation, pain and the acute-phase response. RESULTS: Similar results were obtained when all available radiographs were included for each year of assessment (maximum 114) and when only patients with radiographs at all time points were included (75 patients). In these 75, the mean progression in the prednisolone group was 0.21 Larsen units in year 1, 0.04 units in year 2 and 1.01 units in year 3 (P = 0.587, 0.913 and 0.039 for change within each year, respectively). The equivalent placebo group means were 2.34, 1.00 and 1.63 Larsen units (P = 0.001, 0.111 and 0.012; difference between groups: 2.13, 0.96 and 0.67 units, P = 0.082, 0.02 and 0.622). The percentage of hands which had erosions at each time point was: prednisolone group: 27.8, 29.2, 34.7 and 39.2; placebo group: 28.2, 48.7, 59.0 and 66.5. There was little evidence for a flare in clinical symptoms after discontinuation of prednisolone. CONCLUSION: Joint destruction resumed after discontinuation of prednisolone. This corroborates the previously reported therapeutic effect and challenges current concepts of disease pathogenesis.

Effect of a proprietary herbal medicine on the relief of chronic arthritic pain: a double-blind study.

Eighty-two subjects with chronic arthritic pain were randomly assigned for 2 months without cross-over to either Reumalex, a licenced over-the-counter (OTC) herbal medicine, or a placebo. Entry characteristics were determined by a previous survey of arthritic customers at pharmacy and healthfood shop outlets. The AIMS2 questionnaire was completed at monthly intervals throughout and for 2 months prior to the trial, and a modified Ritchie Index provided clinical scores. Subjects also completed diary recordings of their use of self-prescribed analgesics and events they considered significant. There was a small but statistically significant improvement in pain symptoms, less so in sufferers from osteoarthritis. There were no other significant changes in any other measures nor in the use of other self-prescribed analgesics. There were few side-effects noted. It is concluded that Reumalex has a mild analgesic effect in chronic arthritis at a level appropriate to self-medication.

Magnetic resonance imaging manifestations of idiopathic haemochromatosis in the wrist.

The magnetic resonance imaging features of the wrist of a patient suffering from the arthropathy of haemochromatosis are presented. It is apparent that the deposition of iron within the bone marrow is focal in origin and may be associated with cyst formation. In addition, changes in serum ferritin levels with treatment suggest that the deposition is irreversible. Studies of two other patients with haemochromatosis without cyst formation in the wrists did not yield similar artefacts, in spite of having high ferritin levels and arthritis.

High-resolution magnetic resonance imaging of the interphalangeal joints of the hand.

High-resolution magnetic resonance imaging (MRI) of the interphalangeal joints of the fingers is being employed to study arthritis. To facilitate this research, a clear understanding of the structures visualisable by MRI is necessary. A gradient echo (GE) sequence was developed that produced good contrast between cartilage and other joint structures. These detailed images, with an in-plane resolution of 200 x 100 microns, enable resolution of three cartilage zones which can be interpreted as a superficial layer at the cartilage/cartilage interface, an intermediate layer and calcified cartilage in contact with bone; these correlate well with known anatomy. Further analysis of the images indicates that although a chemical shift artifact causes changes in the images at the field strength used (0.5 T), it does not cause enough distortion to necessitate suppression of the effect. Furthermore, the only detectable susceptibility artifact at these low field strengths was a loss of signal in bone trabeculae at the bone/cartilage interface. There is clearly potential in the study of the articular structures, in particular cartilage, in detail, using high-resolution MRI.

Demonstration of a geode by magnetic resonance imaging: a new light on the cause of juxta-articular bone cysts in rheumatoid arthritis.

The magnetic resonance imaging (MRI) features of a rheumatoid arthritic geode are presented. Development of such a cyst from before x ray diagnosis to its coalescence with the wrist joint is described. The evidence suggests that these juxta-articular cysts are not merely an intrusion of the synovial cavity into the bone marrow but start as isolated structures beneath the subchondral bone.

Genes associated with rheumatoid arthritis and mild inflammatory arthritis. I. Major histocompatibility complex class I, II, and III allotypes.

Patients with mild inflammatory arthritis (IA) were compared with patients with definite rheumatoid arthritis (RA) for abnormal frequencies of major histocompatibility complex (MHC) antigens and haplotypes to determine whether a genetic predisposition either to RA or to mild self-limiting arthritis/arthralgia was present in the patients with IA. In general the MHC antigens with abnormal frequencies found in patients with IA differed from those in patients with RA and were mainly at the A and B loci. In patients with IA the frequencies of HLA-A24, A25, B27, and B35 antigens were significantly higher than those of controls and HLA-DR5 and C4A4 were slightly raised. In contrast, in patients with RA abnormal frequencies of the MHC antigens DR4 and DR2 and the extended haplotypes associated with them [B62 BfS C4A3 C4B3 DR4 GLO2] and [B7 BfS C4A3 C4B1 DR2] confirmed the observations reported on other white populations. Thus MHC antigen associations with IA and RA differ sufficiently to suggest a different genetic basis for the two conditions.

Genes associated with rheumatoid arthritis and mild inflammatory arthritis. II. Association of HLA with complement C3 and immunoglobulin Gm allotypes.

Associations were sought between major histocompatibility complex (MHC) genes on chromosome 6 and the complement component C3 and immunoglobulin genes located on other chromosomes which might contribute to susceptibility to mild inflammatory arthritis (IA) or definite rheumatoid arthritis (RA). Frequencies of the complement C3F allele were raised in patients with IA but were normal in patients with RA and controls. When associations between C3F and MHC genes were sought frequencies of some MHC genes were greater in patients with C3F than in those without--for example, HLA-B8 and DR3 in patients with RA and DR2 in patients with IA. Conversely, DR4 frequency was lower in patients with IA with C3F than in those without. Thus the C3F allele may act independently or exert an epistatic effect on MHC genes to increase susceptibility or protect against disease. The frequency of the immunoglobulin heavy chain allotype Glm(2) on chromosome 14 was increased in patients with RA but only in those with the phenotype Gm1,2,3,17;21,5; no significant associations were found between MHC genes and Gm phenotypes. Further, no associations of MHC, C3F, and immunoglobulin genes were shared by patients with RA and those with IA, indicating a different genetic basis for the two clinical entities.

Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee.

A multi-centre randomized, double-blind, parallel-group clinical trial was carried out in 63 patients with osteoarthritis of the knee to compare the efficacy and tolerability of a course of intra-articular injections of 20 mg sodium hyaluronate with a similar course of injections of placebo. Treatment consisted of up to 11 injections over a 23-week period. Evaluation was by means of subjective symptom and activity assessments, serially during the course of treatment and also 25 weeks thereafter. Ten patients (5 of 30 on active treatment; 5 of 33 on placebo) were withdrawn prematurely. Pain on movement, assessed by visual analogue scale (VAS) showed statistically significant (p less than 0.05 to p less than 0.0001) reductions in mean scores throughout the first 11 weeks of treatment with sodium hyaluronate but smaller, non-significant, reductions with placebo treatment. The difference between treatments was significant (p less than 0.05) at 5 weeks. Pain at rest, also assessed by VAS, showed little change in mean scores with placebo but with sodium hyaluronate there was a progressive reduction which was significant (p less than 0.01) throughout the period from 5 to 23 weeks. The difference between sodium hyaluronate and placebo was significant (p less than 0.05 to p less than 0.002) at Weeks 5, 11, 15, 19 and 23. 'Activities of daily living' were assessed using a standard scale. There were small improvements with both treatments, significant at some assessments and somewhat greater with sodium hyaluronate than placebo, but there were no statistically significant differences between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Human parvovirus infection in early rheumatoid and inflammatory arthritis.

Evidence of recent infection with human parvovirus B19 (HPV) was found in two patients with early rheumatoid arthritis (RA) and in four patients with acute inflammatory arthritis (IA). Both of the patients with RA but only one of the four patients with IA carried RA associated haplotypes. No evidence of persistent infection with HPV was found, but evidence of past infection with HPV was significantly more common in patients with RA than in controls. The results confirm the arthritogenic potential of HPV and are consistent with the hypothesis that rheumatoid arthritis may develop in a genetically predisposed patient after an arthritogenic insult such as an HPV infection.

Ankylosing spondylitis and trauma: the medicolegal implications. A comparative study of patients with non-specific back pain.

Ankylosing spondylitis (AS) arising as a result of injury was reported by five of 113 hospital patients who completed questionnaires on the historical and symptomatic features of their disease. Identical questionnaires were given to a group of 51 patients with non-specific back pain (NSBP) attending an orthopaedic clinic. Five of these patients developed their first symptoms after trauma. A further four patients with ankylosing spondylitis believed that their disease was initiated by injury, however, x-ray photographs showed that they had already developed AS at the time of their injuries. It is suggested that injury does not cause AS but brings it to the patient's attention, possibly through immobilisation, in 7% of hospital cases.

Synovial synthesis of rheumatoid factors and immune complex constituents in early arthritis.

Synovial synthesis of immune complex constituents and rheumatoid factors has been estimated in rheumatoid arthritis (RA) and in unclassifiable inflammatory arthritis (IA) and related to duration of symptoms. Within 6 months of onset of symptoms both RA and IA patients synthesised (or trapped) immune complexes locally. However, local synthesis of the rheumatoid factors was almost exclusive to RA patients and mainly in patients with symptoms of more than 6 months' duration. Thus all arthritis patients may respond immunologically to an initial trigger in the affected joint but only RA patients develop localised chronic autoimmunity later.

Immune complexes in early arthritis. II. Immune complex constituents are synthesized in the synovium before rheumatoid factors.

Synovial fluids and paired sera taken from patients either before, after or at the time of diagnosis of definite rheumatoid arthritis (RA) were compared with samples from patients with unclassified inflammatory arthropathies (IA). Raised levels of immune complexes (IC) were detected in some RA patients by C1q binding activity but in the majority of both RA and IA patients by the platelet aggregation test; levels were usually higher in joint fluids than in sera. IgM rheumatoid factors (RF) and IgA RFs were lower in synovial fluids but IgF RF levels were similar in matched samples. Synovial fluid to serum albumin ratios were used to estimate synovial permeability (inflammation) and then to calculate which patients synthesized macromolecules locally in the synovium. Local synthesis of RFs was detected in a greater proportion of RA than IA patients and only two patients formed RFs locally in the first months of symptoms. Half the patients in both groups however appeared to synthesize or trap IC constituents and in many patients there was evidence of local synthesis within 6 months after their symptoms had started. We conclude that local synthesis of large amounts of RFs is uncommon in the early stages of RA but that IC of unknown composition are synthesized or localized in the affected joints of many patients with RA and inflammatory arthropathies shortly after their symptoms appear.

The complement fixing properties and class distribution of rheumatoid factors (antiglobulins) in rheumatoid arthritis and other diseases.

The MRSPAH (mixed reverse solid-phase passive antiglobulin haemadherence) test for antiglobulins (Agbs) of IgA, IgG and IgM classes has been quantified and also modified to measure their C3 fixing activity. An alternative ELISA technique is also described. Levels of all Agbs and their C3 fixing activity were significantly raised in established rheumatoid arthritis (RA) patients, early RA patients and established SLE patients. Ankylosing spondylitis (AS) patients had normal levels of Agbs and C3 fixation. Patients with infectious mononucleosis (IM) had high levels of all Agbs, but these did not fix complement. Thus, C3 fixing activity of Agbs is heterogeneous and raised levels are associated with the presence of joint disease. Isolated IgA, IgG and IgM fractions showed examples of Agbs which fixed C3. The proportion of C3 fixed per unit weight of Agbs was no greater in 'hidden' Agbs from serum and synovial fluids (SFs) than in untreated serum, and Agbs in SF do not fix more C3 than in serum. We conclude that the C3 fixing activity of Agbs is not directly related to affinity.

Immune complexes in early arthritis. L Detection of immune complexes before rheumatoid arthritis is definite.

Fifty-three patients with early arthritis were studied longitudinally for up to 3 years. During this time, 24 developed sufficient features for definite rheumatoid arthritis (RA) to be diagnosed. The other (arthralgia patients) differed from the RA patients as, in the majority, C-reactive protein and ESR were normal and anti-nuclear antibodies or rheumatoid factors were rarely found. Moreover, in time their signs and symptoms improved or disappeared. Circulating immune complexes were detected in both groups of patients by the platelet aggregation test whereas complexes detected by abnormal Clq-binding activity were found mainly in the RA patients. Platelet-aggregating complexes were usually present in the first samples studied and disappeared in the arthralgia patients with recovery from their symptoms. In the RA patients, Clq-binding complexes appeared simultaneously or later than platelet-aggregating complexes but both tests were positive several months before RA could be diagnosed. These results suggest that immune complexes are one of the first immunological abnormalities to appear in patients with arthritis. Although the constituent antigen and antibody of complexes detected by either test are unknown, their possible nature is discussed.

Effect of homologous synovial membrane on adult human articular cartilage in organ culture, and failure to influence it with D-penicillamine.

Adult human articular cartilage has been maintained in organ culture for 8 days, and the culture medium, which was changed on alternate days, was pooled. Normal and rheumatoid cartilage was obtained from patients and 4 types of culture were prepared: (1) cartilage alone; (2) cartilage + D-penicillamine; (3) cartilage + homologous synovium; (4) cartilage, synovium, and D-penicillamine. The hexosamines and hexuronic acid were measured in the cartilage explants and in the medium. The quantity released was divided by the amount measured in the original cartilage explant and the different culture variables were compared. D-penicillamine did not alter the release of cartilage proteoglycan, but the addition of synovium did. The rheumatoid cartilage released significantly more proteoglycan than normal cartilage whether or not homologous synovium was present.