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.

[Regression of peripheral and pulmonary rheumatoid nodules under therapy with rituximab]. / Regression von peripheren und pulmonalen Rheumaknoten unter Rituximab-Therapie.

We report on a retrospective study of 16 rheumatoid arthritis (RA) patients with reduction in size of pulmonary and peripheral rheumatoid nodules following treatment with rituximab (RTX). The 8 female and 8 male patients had an average disease duration of 12.2 years, 88 % were anti-CCP positive and 94 % seropositive. Prior treatment included an average of 2.9 DMARD and 1.4 biological therapies. On average 6.1 rheumatoid nodules were found on hands and elbows and 5 patients had pulmonary nodules. In 6 out of 16 patients the nodules disappeared completely, in 2 patients a pulmonary nodule disappeared. In 10 out of 16 patients the size of the nodules decreased by approximately 50%, 1 out of the 16 patients with significant increase in size and number of nodules prior to RTX therapy showed a reduction in size but no new nodules occurred. The regression in size of the nodules occurred 34.2±39.1 weeks following RTX therapy, correlating with 1.3±0.59 RTX infusion cycles. Overall, increases in size or new nodules were reported in none of the patients. One nodule examined histologically following RTX therapy did not show any specific differences. RTX may lead to a marked reduction in size of rheumatoid nodules in RA patients. More studies are necessary to confirm whether this is an RTX-specific effect.

Exaggerated circulating Th-1 cytokine response in early rheumatoid arthritis patients with nodules.

BACKGROUND: Immunohistochemical studies of the rheumatoid nodule (RN) suggest it is a Th1 granuloma, with focal vasculitis, yet the pathogenesis remains unclear and little is known about circulating cytokines in these patients. OBJECTIVE: We studied circulating cytokines in DMARD-naïve RA patients to investigate associations with subcutaneous RN. METHODS: 149 DMARD-naïve adults with early RA (symptom duration ≤ 2 years) were assessed using the Simplified Disease Activity Index (SDAI), and hand and feet radiographs were scored using the modified Larsen method. Circulating cytokines and growth factors representative of T-helper cell 1(Th1) and Th2 cell, macrophages, and fibroblasts were measured using the Bio-Plex® suspension array system. RESULTS: Of 149 patients, 34 (22.8%) had subcutaneous RN, and these patients had more severe disease with higher mean swollen joint counts (p=0.02), SDAI (p=0.04) and modified Larsen scores (p=0.004). There were no differences in Rheumatoid Factor or anti-cyclic citrullinated peptide antibody positivity between patients with RN and those without RN. Patients with RN showed significantly higher levels of circulating IL-12 (p=0.02), IL-2 (p=0.048), and VEGF (p=0.033) levels, with a trend towards higher levels of IL-7 (p=0.056), IFN-γ (p=0.059) and IL-8 (p=0.074) compared to those without RN. CONCLUSIONS: DMARD-naïve early RA patients with RN had more severe disease than those without RN, and showed an exaggerated circulating Th1 and macrophage cytokine profile.

Smoking is a strong risk factor for rheumatoid nodules in early rheumatoid arthritis.

OBJECTIVE: To examine whether smoking is a risk factor for rheumatoid nodules in early rheumatoid arthritis, and if so to determine the quantitative effect of smoking. METHODS: From a cohort (n = 1589) in a structured programme for follow up of newly diagnosed cases of rheumatoid arthritis (symptoms of swollen joints < or =12 months), 112 individuals with rheumatoid nodules at inclusion were identified. Nodular patients were each compared with two age and sex matched controls without nodules from the same cohort. A detailed self administered tobacco use questionnaire was answered by 210 patients (63%). RESULTS: Seventy patients were current smokers, 71 former smokers, and 69 had never smoked. Current smoking and former smoking were more common in patients with rheumatoid nodules compared with controls (86% v 59%) in both sexes. Positive rheumatoid factor (RF) was found more often among cases with nodules than controls (78% v 64%). Using detailed information from the questionnaires with conditional logistic regression analyses, ever having smoked was associated with an increased risk of the presence of rheumatoid nodules (odds ratio (OR) = 7.3 (95% confidence interval, 2.3 to 23.6); p = 0.001). The risk of having nodules was not obviously dose dependent when smoking duration as well as smoking amount were examined. A stratified analysis showed that only RF positive smokers had an increased risk of rheumatoid nodules. Smoking was associated with rheumatoid nodules among both men (p = 0.006) and women (p = 0.001). Tobacco use other than smoking (n = 31) was not associated with an increased risk of nodules (OR = 0.8 (0.2 to 3.4); p = 0.813). CONCLUSIONS: There is a strong association between smoking and rheumatoid nodules in early seropositive rheumatoid arthritis.

Tumefactive necrobiotic granulomas (nodulosis) of the pancreas in an adult with long-standing rheumatoid arthritis.

Rheumatoid nodules are well-documented clinical and pathologic lesions in patients with seropositive rheumatoid arthritis (RA). The current report documents the occurrence of rheumatoid nodulosis of the pancreas in an adult woman with a 7-year history of seropositive RA who presented with upper abdominal pain and was found to have multiple masses in the body and tail of the pancreas by imaging studies. An elevated serum pancreatic polypeptide (PP) and the development of new lesions in the pancreas prompted a subsequent distal pancreatectomy. The lesions in the pancreas proved to be necrobiotic palisading and hyalinizing granulomas upon pathologic examination. Also, of interest, elevation of serum PP has been observed in patients with RA and other systemic noninfectious and infectious inflammatory disorders in the absence of a pancreatic or intestinal neuroendocrine neoplasm.

Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations.

BACKGROUND: Autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein antibodies can be detected in rheumatoid arthritis (RA) sera. OBJECTIVE: To determine the diagnostic values of RF, anticitrullinated protein antibodies, and the shared epitope (SE), and their associations with radiological progression rates and extra-articular manifestations. METHODS: Population 1 consisted of sera from 315 patients, consecutively sent for detection of anticitrullinated protein antibodies, of which 264 were used to determine the sensitivity and specificity of RF and of antibodies against three synthetic citrullinated peptides: peptide A (pepA), peptide B (pepB), and CCP2. Population 2 consisted of sera from 180 longstanding RA patients and was used to determine associations of RA associated antibodies and the SE with radiological progression rates and extra-articular manifestations. Antibodies to pepA and pepB were detected by line immunoassay, and antibodies to CCP2 by ELISA. HLA Class II typing was performed by LiPA. RESULTS: In population 1, we defined adapted cut offs corresponding to a specificity of >/=98.5%. This yielded the following sensitivities: RF 12.8%; anti-pepA antibodies 63.6%; anti-pepB antibodies 54.2%; and anti-CCP2 antibodies 73.7%. In population 2, significant differences in radiological progression rates were found between positive and negative patients for different RA antibodies and the SE. RF, but not anticitrullinated protein antibodies or the SE, were more frequent in patients with extra-articular manifestations. CONCLUSION: A valid comparison of RA associated antibodies shows superior sensitivity of the anticitrullinated protein antibodies compared with RF. The presence of RA associated antibodies and the SE are indicative for poorer radiological outcome, and presence of extra-articular manifestations is associated with RF but not with anticitrullinated protein antibodies.

Nodular disease in rheumatoid arthritis: association with cigarette smoking and HLA-DRB1/TNF gene interaction.

OBJECTIVE: To investigate the association of nodular disease in rheumatoid arthritis (RA) with smoking, seropositivity, and polymorphisms at HLA-DRB1 and TNF loci. METHODS: Consecutive patients with RA (n = 420) attending a hospital clinic were examined for the presence of subcutaneous nodules. Rheumatoid factor (RF) status and HLA-DRB1 genotype were determined on every patient, and their smoking history was recorded. TNFa microsatellite polymorphisms were examined in a subgroup of 144 patients. The relationships between smoking, RF status, HLA-DRB1 genotype, TNFa microsatellite polymorphism, and the presence of nodules were examined using chi-square tests and logistic regression analyses. RESULTS: Current smokers were more likely to have nodular disease than those who had never smoked (OR 1.8, 95% CI 1.0-2.9). An association was also found between RF positivity and nodular disease (OR 2.2, 95% CI 1.2-3.8) that remained significant after correction for current smoking. A combination of current smoking and seropositivity increased the risk of nodular disease (OR 3.9, 95% CI 1.7-9.1). Analysis of HLA-DRB1 genotypes in this RA population revealed that only DRB1*0401 homozygotes were associated with nodular disease, and that this was independent of the influence of smoking and seropositivity. Individual TNFa microsatellite alleles were not associated with the presence of nodules, but an interactive effect was found between the TNF a6 allele and homozygosity for DRB1*0401. CONCLUSION: Our data indicate that nodular disease in RA is independently associated with current cigarette smoking, seropositivity, and homozygosity for HLA-DRB1*0401. The latter association involves a possible interaction with the TNF a6 microsatellite allele.

Benign rheumatoid nodules of childhood.

The nodules associated with rheumatoid arthritis and rheumatic fever appear with other signs of active rheumatic disease. Rheumatoid nodule-like lesions irrelevant to rheumatoid disease occasionally occur in children who are well and have no complaints associated with rheumatoid diseases. Laboratory tests are normal. Children with benign rheumatoid nodule are not at increased risk for rheumatic disease. No therapy or prophylaxis is required. We present a two-year-old girl with a subcutaneous nodule on the right pretibial region who was diagnosed with clinical and histological findings.

[High titers of rheumatoid factor: clinical significance]. / Factor reumatoide a títulos elevados: significado clínico.

UNLABELLED: Rheumatoid factor (RF) is one of the most characteristic laboratory parameters in rheumatoid arthritis (RA), and its specificity for this disease increases when the titer is high. We investigated the diagnoses associated with high titers of RF and whether they are associated with a poor prognosis of RA. PATIENTS AND METHODS: Patients with RF titers higher than 300 IU/ml were studied (nephelometry) during a three-year period in a general hospital. Patients with RA were compared with other group of patients with RA and RF lower than 300 IU/ml regarding functional capacity, presence of nodules, HLA-DR4 and radiologic status, in a retrospective cohort study. RESULTS: RF was quantitated in 2,181 patients and was higher than 300 IU/ml in 79 cases; 63 among patients in this group (80%) had RA, and the remaining patients inflammatory diseases of the connective tissue (four patients), palindromic rheumatism (two), liver disease (two), infection (one) and neoplasm (one). In two cases the diagnosis was arthrosis and in one case arthralgia of unknown origin. RA with RF higher than 300 IU/ml had a higher frequency of rheumatoid nodules than RA with RF lower than 300 IU/ml (p = 0.01; RR: 2.26; 95% CI: 1.18-4.35). The index of functional capacity and rate of HLA-DR4 and erosions was similar in both RA groups. CONCLUSIONS: In a patient with a high RF titer, RA should be first ruled out, followed by other inflammatory diseases, collagenosis and liver diseases. The likelihood of finding a healthy patient with arthrosis or soft tissue rheumatism was very low. In RA, rheumatoid nodules were significantly associated with RF with titers higher than 300 IU/ml.

Raised IgA rheumatoid factor (RF) but not IgM RF or IgG RF is associated with extra-articular manifestations in rheumatoid arthritis.

In rheumatoid arthritis (RA) seropositivity has been associated with poor prognosis including bone erosions and extra-articular manifestations. However, findings have been conflicting on the association between individual rheumatoid factor (RF) isotypes and extra-articular manifestations. In this study the occurrence of extra-articular manifestations was examined in the context of the RF isotype patterns rather than individual RF isotypes. IgM, IgG and IgA RF was measured by ELISA in 74 patients with RA and the findings correlated with the presence or absence of extra-articular manifestations. Of the IgA RF positive patients 80% had one or more extra-articular manifestations. In contrast, only 21% of patients with raised IgM and/or IgG RF but normal IgA RF had some extra-articular manifestations and 27% of the seronegative patients. It is concluded that the previously reported association between raised RF and extra-articular manifestations in RA can largely be attributed to the IgA RF isotype.

Rheumatoid nodulosis: report of two new cases and discussion of diagnostic criteria.

Two patients with typical rheumatoid nodulosis are described and compared with 24 reported cases. Rheumatoid nodulosis is a particular variant of rheumatoid arthritis associated with palindromic rheumatism, subcutaneous rheumatoid nodules, mild or no systemic manifestation and a benign clinical course. Positive rheumatoid factor and radiologic subchondral bone cysts are usual, but their absence should not eliminate the diagnosis of rheumatoid nodulosis, particularly at the onset of the disease.

Rheumatoid markers in the absence of arthritis.

A 45-year-old man had high titer rheumatoid factor in his serum, marked elevation of his erythrocyte sedimentation rate, and a histologically proven rheumatoid nodule in the absence of other manifestations of rheumatoid disease. These findings are most unusual and emphasize that serologic and histologic markers of rheumatoid arthritis may be present without arthritis or other disease manifestations.