Neuropathic osteoarthropathy: diagnostic dilemmas and differential diagnosis.

The purpose of this pictorial essay is to illustrate the radiologic spectrum of imaging findings of neuropathic osteoarthropathy. Typical findings include joint destruction, disorganization, and effusion with osseous debris. A variety of other imaging findings related to neuropathic osteoarthropathy such as resorption of the ends of tubular bones and neuropathic fracture are shown. The two prevailing theories for the pathophysiology of neuropathic bone and joint disease, the neurovascular and neurotraumatic theories, are briefly described. Examples of osteoarthropathy from diverse causes are presented including syringomyelia, spinal cord injury, meningomyelocele, diabetes mellitus, congenital insensitivity to pain, steroid injections, syphilis, leprosy, and others. The discussion focuses on key imaging features with emphasis on disease patterns and differential diagnosis, which vary by skeletal location.

Serodiagnosis and immune profile in rheumatoid arthritis.

One hundred and seventy-five cases of clinically diagnosed rheumatoid arthritis, 82 non-rheumatoid cases suffering from various other diseases and 40 healthy normal controls were investigated for detection of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of antinuclear antibody (ANA) and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor (RF) showed 64% positivity in rheumatoid group and 1.2% positivity in non-rheumatoid group. All three immunoglobulins (IgG, IgM, IgA) were found to be raised in serum of patients with rheumatoid arthritis, whereas only IgA level was elevated in serum of patients with non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 3.4% and 2.8% cases respectively in cases of clinically diagnosed rheumatoid arthritis who had been suffering from severe active rheumatoid arthritis. In non-rheumatoid group RF was positive in significant titre in only one case of leprosy. Synovial fluid and synovium were found to be heavily infiltrated by plasma cells and lymphocytes. RF appears first in synovial fluid and then in serum. Hence RF titre in blood may not attain significant level for the first several months.

Antibodies to 65Kd heat-shock protein were elevated in rheumatoid arthritis.

Antibodies to 65Kd heat-shock protein (hsp) of mycobacterium leprae were measured by enzyme-linked immunosorbent assay (ELISA) in the three immunoglobulin classes in paired sera and synovial fluids of patients with rheumatoid arthritis (RA). Titers of anti-hsp antibody were expressed by optical density (OD) values for sera or indexes (OD values divided by amounts of immunoglobulin in each class) for synovial fluids and for their paired sera. Indexes of anti-hsp antibody were higher in synovial fluids than those in sera at 15/18 for IgG, 17/18 for IgA and 16/18 for IgM class. These results suggest the participation of anti-hsp antibodies to synovitis in RA.

Synovial fluid antigen-presenting cell function in rheumatoid arthritis.

We have previously demonstrated enhanced synovial fluid (SF) antigen-presenting cell (APC) function in inflammatory arthritis patients selected on the basis of marked SF mononuclear cell (MNC) responsiveness to reactive arthritis-associated bacteria (Clin Exp Immunol 1990; 79:189-94). In this study we have assessed whether similarly enhanced synovial APC function is present in other inflammatory arthritis patients by using two assay systems to study 18 rheumatoid arthritis patients whose MNC responsiveness had not been determined in advance. We demonstrate that rheumatoid SF APC are much more potent than peripheral blood (PB) APC in stimulating the responses of autologous PB T cells to a range of recall antigens. In addition, SF APC are shown to be efficient stimulators of the antigen-specific responses of MHC-compatible, cloned T cells. Enhanced synovial APC function is thus likely to be a general feature of inflammatory arthritis and may play an important role in its pathogenesis.

Limiting dilution analysis of proliferative T cell responses to mycobacterial 65-kDa heat-shock protein fails to show significant frequency differences between synovial fluid and peripheral blood of patients with rheumatoid arthritis.

Recent evidence has pointed to the mycobacterial 65-kDa heat-shock protein (hsp 65) as an antigen that may be important in the pathogenesis of rheumatoid arthritis (RA). Using limiting dilution analysis the frequency of purified protein derivative of tuberculin (PPD) and hsp 65-responsive T cells was measured in paired peripheral blood and synovial fluid samples of patients with RA. There was no increase in the anti-PPD or anti-hsp 65 frequency in synovial fluid compared with peripheral blood. In addition, no difference was found between peripheral blood of RA patients and healthy controls. These results do not support the idea of an important pathogenic role of T cells responding to hsp 65, or a cross-reacting antigen, in RA.

Epitope specificity and MHC restriction of rheumatoid arthritis synovial T cell clones which recognize a mycobacterial 65 kDa heat shock protein.

CD4+ T cell clones specific for the mycobacterial hsp 65 were obtained from synovial fluid of a DR4 homozygous rheumatoid arthritis (RA) patient. A stimulatory epitope was defined using both deletion mutants of the mycobacterial hsp 65 and synthetic peptides and proved to be in a highly conserved region of the molecule. Despite this, however, there was no recognition by these clones of either the recombinant human homologue of mycobacterial hsp 65, P60, nor of a synthetic peptide containing an amino acid sequence from P60 corresponding to the epitope defined in the mycobacterial hsp 65. When the pattern of HLA restriction shown by the hsp-65-specific T cell clones was investigated, all clones tested proved to be restricted by HLA-DP rather than the more usual HLA-DR. Inhibition experiments suggested that this restriction also applied to the polyclonal synovial T cell response to hsp 65, but not to other antigens. Exclusive restriction of T cell recognition of an antigen by HLA-DP has not been reported previously, and strongly suggests that in this case the T cell repertoire for recognizing hsp 65 in the context of DR4 is deficient. Such an association between DR4 and the inability to respond to an immunodominant bacterial antigen may have implications for the pathogenesis of RA.

In vitro responses to a 65-kilodalton mycobacterial protein by synovial T cells from inflammatory arthritis patients.

Bacterial Ag, especially those of mycobacteria, have been implicated in the pathogenesis of experimental inflammatory arthritis in rodents, while in man, reactive arthritis has a clear temporal relationship to infection with particular bacteria. To investigate the role of immune responses to bacterial Ag in inflammatory arthritis, we have examined the proliferative responses of paired synovial fluid and PBMC when stimulated with 1) suspensions of irradiated or heat-killed bacteria associated with reactive arthritis (ReA), 2) purified protein derivative, 3) a recombinant 65-kDa heat shock protein of Mycobacterium leprae. The 65-kDa Ag was stimulatory to synovial fluid mononuclear cells, but not PBMC, from patients with different arthropathies, including most of those with ReA, but also some with rheumatoid arthritis. Furthermore, the magnitude of these responses correlated more closely with responses to ReA-associated bacteria (such as Salmonella), than with responses to the mycobacterial Ag represented in purified protein derivative. These results suggest that the 65-kDa molecule, which is common to a wide range of bacteria, may be an important immunogen for the T cell-mediated immune responses within the joint in different clinically defined inflammatory arthropathies.

Congenital contractural deformities of the fingers and arthropathy

Four patients are described who presented with congenital finger contractures and arthropathy. There was synovial cell hyperplasia and giant cells but no inflammatory process. Radiographs showed flattening of the metacarpal and metatarsal heads and the proximal femoral ossification centres. In the oldest patient the process had subsided leaving slight contractures but severe impairment of hip mobility. In another the arthropathy was still prominent in the early teens. In a third, finger contractures had failed to respond to conservative or surgical measures.

Synovial swellings over wrist in leprosy.

Soft cystic swellings are noticed in leprosy patients during the course of disease and are seen all through the spectrum. The commonest site for these is the dorsum of wrist. At times these are seen over the dorsum and the lateral aspects of ankle as well. These contain straw colored sticky but clear fluid. On exploration these appear to arise from the synovial covering of the extensor tendons of wrist and fingers and have no communication with the wrist joint. Histology of the synovium suggests these swellings to be of inflammatory nature.

Manifestations articulaires au cours de deux cas de lèpre

Deux observations d'arthrosynovite survenant au cours d'une > sont rapportées: l'une concerne un cas de lèpre nerveuse où une monoarthrite d'un genou succède à une intradermo-réaction de lépromine; l'autre un cas de lèpre lépromateuse où, quelques mois après l'administration de disulone, survient une atteinte polyarticulaire au cours d'un érythème noueux. Divers cas relevés dans la littérature sont analysés. Les désorders immunitaires observés au cours de la réaction lépreuse fournissent l'explication la plus satisfaisante. La rifampicine, utilisée avec succès dans l'un des cas rapportés, completè lers moyens thérapeutiques de la réaction lépresuse où corticoides, thalidomide, lamprène, sont doués d'une réelle efficacité.

Complement determinations in the synovial fluid and serum of a patient with Erythema nodosum leprosum.

Simultaneous serum and synovial fluid CH50, C1, C4, C2, C1 esterase inhibitor and C3 protein were determined in a patient with acute erythema nodosum leprosum. The pattern of synovial fluid complement activity coupled with the demonstration of multiple lepra bacilli free and within histiocytes is more consistent with an infectious than an immune complex induced synovitis.