Premature osteoarthritis of the knee associated with cartilage hypertrophy and phalangeal dysgenesis.

A woman presented with premature knee osteoarthritis associated with marked femoral cartilage hypertrophy. She also exhibited phalangeal dysgenesis, suggesting this may be an unrecognised syndrome that may predispose to knee osteoarthritis.

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.

Mannosidosis: an unusual cause of a deforming arthropathy.

We report on a case of a deforming arthropathy in a young man with a lysosomal storage disorder. A 31-year-old man with a known diagnosis of mannosidosis presented with a painful swollen right elbow. Radiographs of his right elbow showed a disorganised joint with multiple fragments resembling the appearances of a neuropathic joint. This case provides further evidence that a deforming arthropathy may occur as part of the spectrum of skeletal abnormalities seen in mannosidosis.

A rapidly destructive amyloid arthropathy associated with myeloma.

Amyloid arthropathy is a known complication of multiple myeloma. Clinically, it can be confused with RA with a symmetrical swelling of small and large joints. However, radiologically it can produce bone cysts, but it is said to be distinguished from RA by preservation or even widening of the joint space. We describe a 53-year-old man with myeloma who developed a rapidly destructive rare form of amyloid arthropathy within months of his hematologic diagnosis. The myeloma was aggressive and only partially responsive to treatment; this may have influenced the severity of the joint disease. The arthritis had minimal improvement with the chemotherapy. Intraarticular injections with depot corticosteroids gave some symptomatic relief. Two other unusual features were an unexplained inflammatory arthritis of an elbow with associated soft tissue calcification. If other causes are excluded, amyloidosis may account for a more destructive arthritis than is generally recognized.

Osteoarthritis and magnetic resonance imaging: potential and problems.

To date, MRI has primarily been used to study anatomical changes, and at a resolution that makes detailed analysis of focal change difficult. This is primarily because cost limits the development and use of tailor made research systems. The detailed analysis of soft tissue, cartilage, and bone marrow images should provide a fruitful non-invasive method to study OA. However, the development of MRI methods to study movement, diffusion and perfusion, and the spatial localisation of spectroscopic information, promises a revolution in the study of the living joint in man.

Avascular necrosis of bone following intensified steroid therapy for acute lymphoblastic leukaemia and high-grade malignant lymphoma.

Five out of nine adults (55%) with lymphoblastic disease developed severe avascular necrosis of bone (AVN) when treated with a Berlin-Frankfurt-Munster (BFM) ALL protocol similar to the current joint MRC-ECOG ALL trial (UKALL XII). The principal purpose of these intensified regimens is to improve long-term disease-free survival without necessarily increasing toxicity and secondary morbidity. The presentation of all five was non-specific bone pain occurring after the re-intensification block of chemotherapy containing high doses of dexamethasone. Three types of diagnostic imaging were performed and magnetic resonance imaging (MRI) proved superior in demonstrating AVN and showed it at an earlier stage than plain radiographs or isotopic scans. We believe that the dose of corticosteroids was the major factor in the development of AVN. The five men in our series all remain in first remission with a median disease-free survival of 3.5 years (range 2-8 years) but with varying degrees of disability due to AVN. Clinicians involved in UKALL XII and similar trials should be aware of this debilitating and potentially crippling complication when using high-dose steroid-containing regimens, perform MRI scan early and modify treatment if necessary.

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.

Comparative study of C reactive protein and serum amyloid A protein in experimental inflammation.

The responses of C reactive protein, measured by radial immunodiffusion and radioimmunoassay, and serum amyloid A protein, measured by radial immunodiffusion, were compared in eight subjects with inflammation induced experimentally by intradermal injection of monosodium urate crystals. A significant increase in serum amyloid A was noted after a lag phase of eight hours, the increase in median concentration at 48 hours being about eightfold. A parallel but less marked increase was found in C reactive protein when measured by radioimmunoassay (fourfold increase in median concentration at 48 hours) after a small but significant decrease during the lag phase. The changes in C reactive protein remained within the reference range and were not detectable by radial immunodiffusion.

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.

Concentrations of glycosaminoglycans in synovial fluids and their relation with immunological and inflammatory mediators in rheumatoid arthritis.

The dimethylmethylene blue assay showed higher concentrations of glycosaminoglycans in many synovial fluids from patients with rheumatoid arthritis (RA) than in autologous sera or sera or synovial fluids from normal subjects. These results were taken to suggest that the glycosaminoglycans in RA synovial fluid were abnormally raised and derived from cartilage. To discover what stimulated such glycosaminoglycan release in RA joints relations were sought between synovial fluid concentrations of glycosaminoglycans and immunological and inflammatory mediators. It was shown that RA synovial fluid glycosaminoglycan concentrations correlated with synovial fluid C3d concentrations but not with synovial fluid rheumatoid factor concentrations, polymorphonuclear leucocyte numbers, myeloperoxidase concentrations, or the ability of the synovial fluids to release free radicals from normal polymorphonuclear leucocytes. A correlation was found between synovial fluid C3d and interleukin 1 concentrations as judged by both lymphocyte activating factor activity and immunoassay, but no significant correlation was detected between interleukin 1 and glycosaminoglycan concentrations. It is suggested that in the rheumatoid joint locally produced cytokines, in addition to interleukin 1, together stimulate glycosaminoglycan release from cartilage and render it vulnerable to attack by other processes.

Increased spontaneous production of interleukin-1 together with inhibitory activity in systemic sclerosis.

1. Increased spontaneous production of interleukin-1, measured as lymphocyte-activating factor activity, was seen in unstimulated monocytes from systemic sclerosis patients. 2. Inhibitory activity to interleukin-1 was seen in both normal and patient monocyte supernatants. 3. Inhibitory activity was significantly higher in unstimulated and stimulated monocyte supernatants from systemic sclerosis patients. 4. The net effect was an apparent decrease in lymphocyte-activating factor activity in the monocyte supernatants from systemic sclerosis patients. 5. These findings suggest a possible mechanism by which collagen deposition could be enhanced, thereby giving rise to the extensive fibrosis characteristic of systemic sclerosis.

Intra-articular apatite deposition in mixed connective tissue disease: crystallographic and technetium scanning characteristics.

An acute arthritis in a patient with mixed connective tissue disease (MCTD) was found to be associated with intra-articular deposition of carbonated hydroxyapatite crystals. A technetium hydroxymethylene diphosphonate bone scan showed intense uptake in the delayed phase scan of the affected joints. Synovial fluid analysis demonstrated uptake of the radiopharmaceutical drug directly onto the crystals.

Synovial fluid collagenase in patients with destructive arthritis of the shoulder joint.

We studied synovial fluid (SF) collagenase in 10 women with severe rheumatoid arthritis (RA), 10 with pyrophosphate arthropathy, and 10 with idiopathic destructive disease of the shoulder conforming to a pattern recently described. SF cell counts were highest in the RA group. Particles were detected by polarized light microscopy and alizarin red staining. Crystals were seen in fluids from all 3 groups; pyrophosphate predominated in the pyrophosphate arthropathy group and alizarin red-positive particles in the idiopathic disease group. Collagenase and tissue inhibitor of metalloproteinase levels were estimated in SF after gel filtration. Tissue inhibitor of metalloproteinase activity was detected in all fluids, but tended to be highest in the RA group. Collagenase activity was detected in 3 RA fluids only. In no sample was collagenase found in an active form. These findings support the clinical concept of an aggressive destructive process which sometimes occurs in the shoulder joints of elderly women. Because we were not able to detect free collagenase in SF from any of the patients with idiopathic shoulder disease, the data suggest that high levels of active collagenase are not characteristic of this group of patients.

The gut in the acute phase response: changes in colonic and hepatic enzyme activity in response to dermal inflammation in the rat.

1. Transient mild dermal inflammation was produced in rats by the subcutaneous injection of either carageenan or monosodium urate crystals. The activities of enzymes of the sialic acid metabolic pathway were measured in liver and colon at 8 h, 3 days and 7 days. 2. In both liver and colon the UDP-N-acetyl-D-glucosamine 2-epimerase and asialo-alpha 1-acid glycoprotein sialyltransferase activities increased relative to controls while that of CMP-sialic acid hydrolase decreased. Similar changes occurred for both carageenan and monosodium urate crystals. 3. These results indicate that the acute phase response to a relatively minor inflammatory lesion causes significant changes in a distant and apparently unrelated tissue.

Generalised osteoarthritis: an evolutionary problem?

Polyarticular osteoarthritis (OA) has a distinctive pattern of joint involvement. Some joints, such as the first metatarsophalangeal joint, are commonly affected, whereas others, such as the shoulder, are rarely involved. This distinct pattern of involvement may represent a subset of OA--generalised OA. Analysis of the pattern of change in joint function in the recent evolutionary development of man suggests a hypothesis that explains the pattern of joint involvement in generalised OA. Joints most commonly affected have undergone recent rapid evolutionary change to a new function that has resulted in increased loading. These joints are therefore relatively underdesigned, have little functional reserve, and are likely to fail often and early. Joints that are rarely affected have changed to a function with reduced loading. They are relatively overdesigned and have a large functional reserve, so fail rarely and late.