X linked agammaglobulinaemia and rheumatoid arthritis

BACKGROUND: Much interest has been shown recently in the pathogenic role of B cells in rheumatoid arthritis (RA) owing to the marked clinical responses to anti-CD20 treatment in RA. CASE REPORT: A patient with X linked agammaglobulinaemia (XLA) presented with an erosive symmetric polyarthritis with histological features of RA, including formation of a destructive pannus. Furthermore, the patient developed subcutaneous nodules that were histologically indistinguishable from rheumatoid nodules. Surprisingly, lymphocytic infiltrates in both the synovium and nodule consisted almost exclusively of CD8+ T cells. DISCUSSION: Although some peculiar B cell subsets have been described in patients with XLA, no B cell subsets could be demonstrated in synovial tissue or the subcutaneous nodule. This case illustrates that classical RA can develop in the absence of mature B cells.     

Inflammatory central nervous system involvement in rheumatoid arthritis

We describe a patient with seropositive rheumatoid arthritis who developed pachymeningitis resulting in optic atrophy. Clinical, histopathologic, and radiologic findings in 18 additional cases of inflammatory CNS disease associated with rheumatoid arthritis are reviewed. The three characteristic neuropathologic findings were rheumatoid nodules, pachymeningitis or leptomeningitis, and vasculitis. In most cases, more than one of these histopathologic processes were found. The typical host was middle-aged with long-standing severe nodular disease. However, contrary to previous reports, CNS disease occurred in a significant number of patients without active synovitis and extracranial vasculitis and nodules. Although no correlation between specific neurologic symptoms and neuropathology was noted, patients with CNS nodules tended to be asymptomatic more often than patients with vasculitis or meningitis. CSF analysis and computed axial tomography were helpful diagnostic tools, but diagnosis was ultimately made only by directed biopsy or at autopsy. Treatment with surgical decompression and/or corticosteroids has proved beneficial in several cases. Inflammatory CNS involvement in rheumatoid arthritis should be considered in any patient with neurologic symptoms in whom infectious and malignant processes are ruled out. An aggressive, invasive approach for diagnostic biopsies seems warranted.     

Complete reversal of rheumatoid nodulosis

A woman first seen in 1978 had a history of seropositive rheumatoid arthritis (RA) of 12 years' duration with attacks of palindromic rheumatism for 3 years. She was treated with D-penicillamine, pyridoxine and hydroxychloroquine and serial measurements of her grip strength and proximal interphalangeal joint circumference were taken. By 1987 all her nodules had resorbed completely. Hydroxychloroquine effects probably helped her improvement. Although spontaneous resorption of a rheumatoid nodule is not a rare event, to the best of our knowledge, this is the first instance of complete resolution of all nodules in a patient with RA with the nodulosis variant.     

Geode of the femur: an uncommon manifestation potentially reflecting the pathogenesis of rheumatoid arthritis

Geodes are noted frequently in rheumatoid arthritis (RA), but large geodes of the femur are uncommon. We describe a patient with RA and a large geode in his femur; histological findings were consistent with a rheumatoid nodule and chronically inflamed synovium. We review the literature of large femoral geodes and what this particular manifestation may reflect about the pathogenesis of RA.     

Nodular pulmonary opacities in patients with rheumatoid arthritis. A diagnostic dilemma

Nodular opacities are a well-known pulmonary manifestation of rheumatoid arthritis (RA), occurring most often in seropositive men who smoke and have subcutaneous nodules. In the past 15 years two cases of lung carcinoma presenting as pulmonary nodules have been reported in patients with rheumatoid disease. We present seven patients with seropositive RA and subcutaneous nodules who had new pulmonary nodule(s) noted on chest roentgenograms. All but one were current smokers. Carcinoma was found in all patients at bronchoscopy or thoracotomy. Four patients had solitary nodules (one was cavitary); the remaining three patients had multiple bilateral nodules that cavitated in one case. All patients had interstitial abnormality (peribronchial/vascular thickening) with basal predominance in three, and there was evidence of pleural thickening/fluid in three patients. These results strongly suggest that histologic proof of presumed rheumatoid pulmonary nodules be obtained.     

Multiple myeloma masquerading as severe seropositive rheumatoid arthritis with subcutaneous nodules and mononeuritis multiplex

Multiple myeloma can rarely mimic seronegative rheumatoid arthritis (RA). We report a 55‐year‐old woman who presented with longstanding deforming polyarthritis with extensive subcutaneous nodules, tenosynovitis, anti‐cyclic citrullinated peptide positivity and mononeuritis multiplex. Even though the clinical picture was consistent with seropositive RA, the absence of bone erosion or joint space narrowing on hand and knee radiographs led us to question the diagnosis of RA. Further investigation revealed a diagnosis of multiple myeloma with cutaneous amyloid deposits, based on serum immunofixation, bone marrow aspiration and biopsy of a subcutaneous nodule. The only clue to suspect myeloma from the basic investigations and clinical examination was mild hypercalcemia. This case serves to reiterate the need to maintain a heightened suspicion for other diagnoses even when RA appears most likely.     

The B cell repertoire in rheumatoid arthritis. III. Preferential homing of rheumatoid factor-producing B cell precursors in the synovial fluid.

OBJECTIVE. We sought to compare the frequencies of precursors producing IgM rheumatoid factors (IgM-RFs) in synovial fluid and peripheral blood B cells from patients with rheumatoid arthritis (RA). METHODS. We used limiting-dilution analysis of Epstein-Barr virus-activated B cells from seropositive and seronegative patients. B cell precursors producing IgM against insulin, an irrelevant autoantigen, were also assessed for comparison. RESULTS. On average, IgM-RF-producing precursors were 15-fold higher in the synovial fluid than in the peripheral blood of seropositive RA patients, but not in seronegative RA patients. The frequency of B cell precursors producing IgM against insulin was lower in the synovial fluid than in the peripheral blood of both the seropositive and the seronegative patient groups; moreover, the concentrations were similar in both groups. CONCLUSION. The findings provide evidence against a nonspecific accumulation of IgM-producing cells in the synovial fluid, and suggest that there is an active attraction of the RF-producing B cell precursors toward sites of inflammation in RA.     

False positive elevation of cardiac troponin I in seropositive rheumatoid arthritis.

Cardiac troponin I is a sensitive and specific biochemical marker for the diagnosis of acute myocardial injury. We describe a patient with seropositive rheumatoid arthritis (RA) in whom troponin I, measured with a microparticle enzyme immunoassay, was elevated falsely in the absence of acute myocardial infarction. Apparent elevation of troponin I concentration should be evaluated with care in patients with seropositive RA.     

Identification and prevalence of rheumatoid nodules in the finger tendons using high frequency ultrasonography.

OBJECTIVE: Rheumatoid nodules are classical diagnostic feature of rheumatoid arthritis (RA). The prevalence of rheumatoid nodules in the finger tendons is not known. We determined the prevalence of rheumatoid nodules of finger tendons in patients with RA, using high frequency linear transducers with high resolution ultrasonography. METHODS: The study comprised 54 consecutive patients with RA and 20 controls. Dynamic ultrasound examination of various tendons was performed using real-time equipment, the Apogee 800 ATL, with an 11 MHz linear array transducer. RESULTS: RA nodules were identified in 9 patients (16.66%); their sizes ranged from 0.21 to 0.95 cm (mean 0.35+/-0.12 cm), in 4 cases (7.4%) the nodules were intratendinous. The flexor tendons were affected in the 9 patients. The finger tendon ultrasonography identified RA nodules that had escaped routine clinical detection. CONCLUSION: The ultrasonography technique was valuable in the confirmation of rheumatoid nodule involvement of the finger tendons. The prevalence of rheumatoid nodule in finger tendons was 16.66%. We believe that ultrasonography should be the screening procedure of choice for diagnosis of RA nodules of the fingers.     

Production of agglutinators and rheumatoid factors in plasma cells of rheumatoid and nonrheumatoid synovial tissues

Immunohistochemical studies were performed in synovial tissues from 40 patients with rheumatoid arthritis (RA), 9 with juvenile rheumatoid arthritis (JRA), 7 with psoriatic arthritis, and 4 with various rheumatic diseases. Overall synthesis of IgG– and/or IgM–rheumatoid factor (RF) was found in all patients with seropositive RA and JRA, in 75% of patients with seronegative RA, and in 1 patient with psoriatic arthritis. Agglutinator producing cells were found in 77% of the samples from seropositive RA and in 44% and 56% from seronegative RA and JRA patients, respectively. The percentage of IgG plasma cells synthesizing one or more of the 5 types of agglutinators studied was approximately 10% of plasma cells synthesizing IgG–RF. Intercellular and intracellular immune complex deposits were also found in patients with seropositive and seronegative RA and JRA. These findings suggest that synthesis of agglutinators by synovial tissue plasma cells of RA and JRA patients is a distinct—but definitely less prominent—function than that of RF synthesis.     

Seronegative rheumatoid arthritis.

Measurement of serum rheumatoid factor (RF) by conventional methods in patients with rheumatoid arthritis (RA) has repeatedly identified a subpopulation of patients without detectable RF. Previous investigators have consistently confirmed the association of HLA–DR4 with seropositive RA, but studies of seronegative RA have been limited and contradictory. We studied 140 randomly selected patients from Alabama, all of whom had either classic or definite RA, and we were able to obtain complete HLA typing for 110 of these individuals. Eighty were consistently seropositive (on at least 2 separate occasions) and 30 were consistently seronegative (on at least 3 separate determinations). There was no statistically significant difference between the seronegative RA patients and 123 control subjects in the distribution of DR antigens. In seropositive RA, there was a significant increase in DR4 (P<0.001; relative risk = 8.02; attributable risk = 49.2%) and a significant decrease in DR3 (P<0.001; relative risk = 0.14) and DR7 (0.01>P>0.001; relative risk = 0.33). The clinical data also distinguished between seropositive RA and seronegative RA; subcutaneous nodules (37.5%) and vasculitis (6.3%) were present only in seropositive RA. DR4 positivity did not correlate with any of the clinical variables measured in the seropositive RA group. In contrast, DR4 in the seronegative RA group was associated with more destructive disease. The data suggest that seronegative RA represents a disease entity clinically and immunogenetically distinct from seropositive RA. Moreover, our results indicate that DR4 may be a previously undisclosed marker for disease severity in seronegative RA.     

Rheumatoid arthritis in a patient with sickle cell disease

Sickle cell disease has various articular manifestations. Coexistent rheumatoid arthritis (RA) and sickle cell disease has been reported rarely. We present a patient with sickle cell disease and seropositive erosive RA demonstrating characteristic radiographic findings of the 2 entities.     

Coexistence of rheumatoid arthritis and sarcoidosis: difficulties encountered in the differential diagnosis of common manifestations

Two patients with rheumatoid arthritis (RA) and sarcoidosis illustrate the dilemmas posed by their coexistence in the same patient. The first patient with classical RA developed iridocyclitis, interstitial lung disease and cranial neuropathies, initially attributed to extraarticular rheumatoid disease. Subsequent lung and skin biopsy revealed many granulomas consistent with sarcoidosis whereas synovium revealed changes typical for RA. In the second patient with cutaneous and pulmonary sarcoidosis development of persistent erosive polyarthritis and a subcutaneous nodule with typical pathology permitted the diagnosis of coexistent RA. These cases emphasize that uveitis alone or multiple cranial neuropathies are not features of RA and symptomatic interstitial lung disease in patients with RA warrants further investigation.     

ELISA determined IgM and IgA rheumatoid factors in seronegative rheumatoid and psoriatic arthritis

Previous studies have strongly suggested an association between rheumatoid factors (RF's), particularly IgA-RF, and the presence of erosions in rheumatoid arthritis (RA). The present study was aimed at studying this association in seronegative erosive arthritides. Forty-eight patients with seronegative arthritis were evaluated for the presence of IgM- and IgA-RFs using an enzyme linked immunosorbent assay (ELISA). Twenty-nine had seronegative RA and nineteen had psoriatic arthritis (PA). Twelve (41%) seronegative RA patients were found to be seropositive for IgM- or IgA-RF. Only 1 (7%) patient with PSA was positive for IgA-RF alone. Fifteen (51%) of the RA patients and eight (42%) of the PSA patients had erosive disease. A significant correlation between IgA-RF alone and erosive disease was found only in the seronegative RA patient (p less than 0.02). We conclude that in PSA patients there appears to be no need to define isotype specific RFs. On the other hand, our findings indicate that an early detection of IgA-RF can have clinical importance in seronegative rheumatoid arthritis, as it may constitute an indication for the timely institution of disease-modifying drugs in these patients.     

Examination of IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide antibody (anti-CCP Ab) in Japanese patients with palindromic rheumatism

We have studied the serology of 6 patients with palindromic rheumatism. None of the patients fulfilled the classification criteria for rheumatoid arthritis at the entry; however, 4 out of the 6 patients were seropositive for IgM rheumatoid factor (IgM-RF) at entry. Sequential serological study was performed in 4 patients; IgM-RF changed from seronegative to seropositive in one patient, and the titer increased in another patient. Anti-cyclic citrullinated peptide antibody (anti-CCP Ab) at the entry was detected in only one of the 6 patients; that patient later developed RA. Although follow-up is necessary, the present study may suggest the importance of serological examination, especially anti-CCP Ab, in patients with palindromic rheumatism.     

Seropositive,symmetric polyarthritis in a patient with poorly differentiated lung carcinoma: Carcinomatous polyarthritis,hypertrophic osteoarthropathy,or rheumatoid arthritis?

Polyarthritis resembling rheumatoid arthritis (RA) may be the presenting manifestation of occult malignancy. Hypertrophic osteoarthropathy (HOA) may also develop in association with pulmonary neoplasia and consists of clubbing, periostitis, and arthropathy We describe Q patient who presented with a seropositive, symmetric, inflammatory polyarthritis only 4 weeks before a lung tumor became clinically and radiographically apparent. After initiation of chemotherapy she developed features characteristic of HOA. It appears that the patient had both RA and HOA. We discuss the differential diagnosis and review the relationship of RA, HOA, carcinomatous polyarthritis, and malignancy.     

Recurrent pneumothorax associated with pulmonary nodules after leflunomide therapy in rheumatoid arthritis: a case report and review of the literature

Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterized by destructive synovitis and systemic extraarticular involvement. One of the most common pulmonary manifestations of RA is rheumatoid nodule. Spontaneous pneumothorax also very rare pulmonary finding and could be associated with pulmonary nodules. Antirheumatic drugs, methotrexate, leflunomide (LEF), infliximab and etanercept, were known as risk factors for developing rheumatoid nodule. However, there was no case report of rheumatoid nodule-associated pneumothorax with the use of LEF. We report, first, herein a case of 46-year-old woman with RA who suffered recurrent spontaneous pneumothorax associated with multiple bilateral subpleural cavitary nodules during treatment with LEF. We reviewed the cases of LEF-related pulmonary nodules developed in patients with RA. Thus, we suggested that pneumothorax can be a rare respiratory fatal complication in patients with RA with pulmonary nodules and LEF can be a rare cause of these manifestations.     

Increased frequency of Gm(1,2;21) phenotype in HLA-DR4 positive seropositive rheumatoid arthritis

Ninety-four patients with seropositive rheumatoid arthritis (RA) were typed for HLA-A, B, C and DR antigens and for immunoglobulin G (Gm) allotypes. Isolated IgG from patient serum was used to avoid interference of IgM rheumatoid factor (RF) with Gm typing in sera with high IgM-RF titer. Besides the association of seropositive RA with the antigen DR4 and an earlier disease onset in DR3/DR4 heterozygotes, we found the uncommon Gm phenotype Gm(1,2;21) significantly more often in our patient group than in healthy controls. Combination of HLA-DR and Gm data shows that individuals with both DR4 and Gm(1,2;21) are at a particularly high disease risk.     

A single pulmonary rheumatoid nodule masquerading as malignancy

We present a 54-year-old man, a heavy smoker, with clinical and laboratory evidence of familial hypercholesterolemia and an asymptomatic solitary pulmonary nodule (SPN) increasing in size on follow-up chest X–ray. Laboratory work-up revealed high titers of rheumatoid factor and the presence of acute phase reactants. Because of the patients age and history of smoking, open lung biopsy was performed to rule out malignancy. The biopsy showed histological features compatible with a rheumatoid nodule. Identical features were noted in the histological examination of the subcutaneous nodule. Usually, rheumatoid nodules occur in patients with active, long-standing rheumatoid arthritis (RA) with other extra-articular manifestations. The presence of a single pulmonary rheumatoid nodule as the first manifestation of RA is extremely rare. Histologic proof is often required since pulmonary carcinoma can present an identical clinical and radiological pattern. The diagnostic work-up and the differential diagnosis of an SPN, particularly in a heavy smoker, is a common clinical request and remains a diagnostic challenge.     

Isolation of cytomegalovirus from synovial cells of a patient with rheumatoid arthritis

Synovial cells from the joint of a patient with rheumatoid arthritis (RA) showed foci of cytopathic effects during their 3rd subculture in vitro. Electron microscopy of these cells revealed findings characteristic for cytomegalovirus (CMV), and immunofluorescent staining using antiserum specific for CMV was positive. The patient had classical seropositive RA, was not taking immunosuppressive agents, and had no clinical manifestations of CMV disease at the time of synovectomy 3 months earlier. Titers of antibodies to CMV were studied in the sera and synovial fluids of 3 additional patients with RA, and in 1, elevated IgM antibodies to CMV were found, indicating recent infection. Additional studies for CMV in RA are indicated.