Arthritis-associated syndromes.

There are a number of diseases characterized by inflammatory arthropathy that, although not as commonly seen as rheumatoid arthritis, often present to the family physician as difficult diagnostic problems. The diagnosis is frequently most difficult during the early course of these diseases. During recent years, new and altered concepts have arisen regarding both diagnostic and therapeutic management of this challenging group of arthropathies. This article presents a review of the more common arthritis-associated syndromes with emphasis on the differential diagnosis and medicinal therapeutics.

Recurrence of cervical spine instability in rheumatoid arthritis following previous fusion: can disease progression be prevented by early surgery?

In a retrospective study, 110 patients with rheumatoid arthritis who had cervical spine fusion were evaluated for recurrence of cervical spine instability and resultant need for further surgery. Recurrence of cervical instability was correlated with initial radiographic abnormality, primary surgical procedure and interval between the 2 surgeries. There were 55 patients who had atlantoaxial subluxation (AAS) and required C1-C2 fusion as primary surgery. Three of these patients (5.5%) developed subaxial subluxation (SAS) and had a second procedure after a mean interval of 9 years. Twenty-two patients had AAS with superior migration of the odontoid (AAS-SMO) and had initial surgery of occiput-C3 fusion. Eight of these patients (36%) developed SAS and had a second surgery after a mean interval of 2.6 years. Of the 19 patients with primary radiographic deformity of SAS, one required further surgery for subluxation of an adjacent superior vertebra after a period of 6 years. Fourteen patients had combined deformity of AAS-SMO-SAS, and one required further surgery for SAS after an interval of 22 months. Recurrence of cervical instability following a previous fusion occurred in 15% of these 110 patients. It was seen in 5.5% of patients with initial deformity of AAS vs 36% of patients with AAS-SMO. No patients with C1-C2 fusion for AAS progressed to develop superior migration of the odontoid. We conclude that early C1-C2 fusion for AAS before development of SMO decreases the risk of further progression of cervical spine instability. The pattern of progression of cervical spine involvement, as discussed in the literature, is reviewed.

Evidence for locally synthesized and clonally restricted immunoglobulin in the synovial fluid from rheumatoid arthritis patients.

In this study, we examined the immunoglobulin (Ig) present in synovial fluid (SF) from patients with rheumatoid arthritis (RA) to determine if it was locally produced and to assess the presence of clonally restricted (oligoclonal) immunoglobulin. We studied SF/serum pairs from 55 RA patients and 23 patients with degenerative joint disease (DJD). We found increases in total protein, IgG, IgA, and IgM in RA vs DJD SF (P less than 0.01). The immunoglobulin present in RA appeared to be locally produced as evidenced by significant increases (P less than 0.01) in the immunoglobulin indices. Regression analysis among the levels of IgG, IgA, and IgM RF and the Ig indices suggested that only a minority of the locally synthesized Ig present was specific for RF. To provide evidence of clonal restriction, we further analyzed the SF specimens by isoelectric focusing and assessed the presence of oligoclonal bands present only in RA SF. In 7/55 RA specimens (13%) we found unique SF IgG bands. All bands were of similar isoelectric point (pI), being quite cathodic with pI greater than 7.5. Our evidence supports synthesis of Ig within RA synovium, with a minority of patients showing prominent and unique SF Ig bands. This suggests an oligoclonal response in SF of some patients, but polyclonal Ig synthesis in most.

Soluble interleukin-2 receptor: elevated levels in serum and synovial fluid of patients with rheumatoid arthritis.

Soluble interleukin-2 receptor (sIL-2R) levels were quantitated in the serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and degenerative joint disease (DJD). A sandwich immunoassay, employing two monoclonal antibodies against distinct epitopes on the IL-2R, was utilized for measurement. We found a striking elevation of sIL-2R in RA SF as compared with DJD SF (RA, 1319 +/- 135; DJD, 416 +/- 59; p less than 0.001). RA serum sIL-2R levels were also significantly elevated over DJD levels. There was no interaction between rheumatoid factor (RF) and sIL-2R. RA patients with elevated sIL-2R levels had significantly longer disease duration, higher c-reactive protein (CRP) levels in serum and SF, and higher RF levels in serum and SF. The groups were similar in regard to other laboratory variables. The presence of elevated levels of sIL-2R in RA serum and SF confirms the presence of a heightened immune reactivity and in vivo activation of lymphocytes in RA.

Variable histopathology of discovertebral lesion (spondylodiscitis) of ankylosing spondylitis.

Extensive discovertebral lesion is an infrequent complication of long-standing ankylosing spondylitis. Reported histopathological descriptions vary from predominantly inflammatory to fibrous granulation with reactive bone formation. We report variable histological findings in four symptomatic patients with extensive discovertebral lesions who required spinal fusion.

Elevated soluble CD8 in the synovial fluid from patients with rheumatoid arthritis.

Suppressor/cytotoxic T cells express the surface marker CD8, which can be measured in a soluble form in culture supernatants of activated human lymphocytes. Using a sandwich immunoassay, we assessed the levels of soluble CD8 (sCD8) in serum from patients with rheumatoid arthritis (RA; n = 82), patients with degenerative joint disease (DJD; n = 40), and healthy controls. There were no differences in serum sCD8 levels among these groups. In contrast, the levels of soluble CD8 in the synovial fluid (SF) from patients with RA (n = 53) were significantly increased compared with the levels in 23 samples from patients with DJD (821 +/- 110 U/ml versus 213 +/- 13 U/ml, p less than 0.001). Synovial fluid sCD8 levels in the RA group were strikingly elevated, to a maximum value of 5,026 U/ml. In the majority of RA SF specimens (39 of 53), the values were significantly higher in the SF than the serum. Although the RA group had higher values of sCD8, such values were not significantly correlated with measured laboratory or clinical parameters. Current clinical and laboratory methods of evaluating patients may not be adequate in dealing with the complexity and heterogeneity of RA. Soluble CD8 values may be useful in further grouping patients with this disease.

Adult rheumatoid arthritis is associated with MC1, a new HLA-D encoded determinant.

We evaluated the association of a new HLA-D encoded determinant, MC1, with adult rheumatoid arthritis (RA). This determinant associates with DR1 and DR4 and can be defined by serological typing. We found MC1 in 83% of 80 patients with RA vs 43% of controls. Although the frequencies of DR1 and DR4 were both significantly increased in patients with RA compared with controls, MC1 had the highest relative risk (6.2) of any HLA-DR antigen tested. MC1 negative and positive populations were not significantly different in any of a variety of clinical and laboratory variables including age, sex, disease duration, age at onset, hours of morning stiffness, functional class, joint count, presence of subcutaneous nodules or bony erosions, frequency of side effects to gold or D-penicillamine, sedimentation rate, and antinuclear antibody.

Vasculitis in systemic sclerosis: association with Sjögren's syndrome and the CREST syndrome variant.

We describe 7 patients with established systemic sclerosis who developed clinical evidence of vasculitis 1 to 33 (mean 12.7) years after the first symptoms of scleroderma. Six had the CREST variant of systemic sclerosis and also had features of Sjögren's syndrome (SS). Five of 6 patients tested had serum anti-SSA (Ro) antibodies. Vasculitis presented primarily as cutaneous lesions with ulceration and/or mononeuritis multiplex, and 6 patients had severe systemic manifestations. Vasculitis was histopathologically documented in 6 cases in biopsies of skin (4 of 4), muscle (2 of 3) and sural nerve (3 of 3). Patients with systemic sclerosis with CREST syndrome and SS appear to be at increased risk to develop vasculitis.

Bilateral giant cyst of the shoulder.

The case of a 61 year old white female with a rapidly progressive rheumatoid arthritis who developed bilateral giant cyst of the shoulder is described here. Arthrographic investigation indicated that these giant cysts were true synovial cysts rather than "pseudocysts".