A giant rheumatoid nodule

Subcutaneous rheumatoid nodules occur commonly in advanced cases of rheumatoid arthritis and are the most common extra-articular lesion of this disease. We present a case of a very unusual giant rheumatoid nodule that developed on the lateral side of a knee. The case was devoid of systemic symptoms of arthritis and the lesion was limited to a rheumatoid nodule. The nodule was successfully treated by surgical excision. However, other new nodules developed in her hand. Her clinical course has not been satisfactory.     

Pulmonary Nodule and Aggressive Tibialis Posterior Tenosynovitis in Early Rheumatoid Arthritis

We report the case of a 34-year-old man with a rheumatoid pulmonary nodule preceding the development of articular symptoms of rheumatoid arthritis. Pulmonary nodules are a well known feature of rheumatoid arthritis and are mostly seen in severe established rheumatoid factor-positive cases. To differentiate between benign and malign pulmonary nodules we discuss the use of positron emission tomography (PET). Despite intensive therapy with steroids and methotrexate in our patient, within months he developed a severe tibialis posterior tendinitis, with partial rupture and evolution to a planovalgus deformity requiring surgery. Both these symptoms are rare but demonstrate the need for close follow-up in early rheumatoid arthritis. Received: 18 October 1999 / Accepted: 22 March 2000     

Chronic active hepatitis presenting with rheumatoid nodules and arthritis

Chronic active hepatitis is often accompanied by extrahepatic rheumatic symptoms of mild or moderate severity. We report a 16-year-old girl with this disorder who presented with severe polyarthritis and rheumatoid nodules mimicking juvenile rheumatoid arthritis. Rheumatoid nodules have not previously been described in chronic active hepatitis, and the severity of the rheumatic symptoms in our patient led to a delay in the recognition of the underlying liver disease. Our report provides support for an autoimmune etiology in some patients with chronic active hepatitis, notes the occurrence of rheumatoid nodules in the disorder, and emphasizes that severe extrahepatic symptoms may obscure the diagnosis and institution of therapy in some individuals.     

Broadening of the T cell receptor spectrum among rheumatoid arthritis synovial cell-lines in relation to disease duration

OBJECTIVE: The aim of the study was to evaluate the T cell receptor (TCR) family usage in T cell-lines from subcutaneous nodules and synovium from patients with rheumatoid arthritis (RA), with specific reference to the duration of symptoms. In vitro adherence characteristics of nodular T cells was studied as well. METHODS: Monoclonal antibodies were used to determine the distribution of TCR families in T cell-lines from synovium of patients with early and long-standing RA, from rheumatoid nodules and control tissues. An in vitro binding assay with T cell-lines from 2 rheumatoid nodules was performed. RESULTS: In early RA synovium, a restricted TCR family usage was observed in 5 out of 8 patients, contrary to long-standing disease, peripheral blood, ileum and colon. In RA nodules, a similar degree of restriction was noted. Moreover, the same TCR family was overexpressed by T cell-lines from different nodules derived from the same patient. T cell-lines from rheumatoid nodules demonstrated a preferential in vitro adherence to rheumatoid synovium and rheumatoid nodules, while no binding was observed on skin or tonsil. CONCLUSION: The TCR spectrum among RA synovial cell-lines broadens in relation to the disease duration. The overexpression of the same TCR family in different rheumatoid nodules from the same patients, and the in vitro adherence of T cell-lines from rheumatoid nodules may be indicative for recirculation between the different disease manifestations in RA.     

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.     

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.     

Multicentric reticulohistiocytosis with hydrarthrosis in both knee joints: disease stabilization with synovectomy, and medication with a steroid and low-dose methotrexate

 Multicentric reticulohistiocytosis is a rare systemic disease characterized by the infiltration of histiocytes and multinucleated giant cells with cutaneous nodules, and severe destructive arthritis. It is commonly the peripheral joints which are affected, and therefore symptoms in large joints have not been fully investigated. We describe the case of a 44-year-old woman with multicentric reticulohistiocytosis, who was suffering from swelling in both knee joints and cutaneous nodules, in addition to arthritis in the elbow, hip, and peripheral joints. Magnetic resonance imaging of both knee joints showed hydrarthrosis associated with a tumor-like overgrowth of synovial tissue. These symptoms were reduced following a resection of the synovial tissue and subsequent medication with prednisone and low-dose methotrexate. It should be noted that swelling in the knee joints can be one of the symptoms caused by multicentric reticulohistiocytosis, in addition to cutaneous nodules and arthritis in the peripheral joints. Resection of synovial tissue, and medication with prednisone and low-dose methotrexate were effective in the present case. Received: May 23, 2001 / Accepted: November 19, 2001     

Rheumatoid-like nodules presenting as “pump bumps” in a patient without rheumatoid arthritis

Bilateral “pump bumps” removed from the heels of a 23-year-old woman had the histologic appearance of rheumatoid nodules. The patient had no symptoms, physical signs or laboratory evidence of rheumatoid arthritis.     

Esophago-bronchial fistula in a patient with rheumatoid arthritis

A 58-year-old woman with active rheumatoid arthritis developed an esophago-bronchial fistula in close temporal proximity to the eruption of subcutaneous nodules and a worsening of her joint symptoms. Possible mechanisms to explain the fistula formation are discussed.     

Knee joint destruction driven by residual local symptoms after anti-tumor necrosis factor therapy in rheumatoid arthritis

In patients with rheumatoid arthritis who had symptomatic knee joints at the start of anti-tumor necrosis factor (TNF) therapy, the relationship between local symptoms and knee joint destruction at 94 weeks was retrospectively investigated. Among the patients with rheumatoid arthritis and received anti-TNF therapy, the 32 patients (52 joints) having swollen and/or tender knee joints were included in this study. Changes of disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) and knee joint destruction using Larsen’s grading system 94 weeks after anti-TNF therapy were evaluated. Furthermore, the differences of the DAS28-CRP, swollen and tender knee joints between the patients who showed progression of joint destruction (Progression group) and those who did not (Non-progression group) were investigated. DAS28-CRP showed time-dependent, favorable results. However, progression of joint destruction was observed in 12 out of 52 joints. DAS28-CRP at 0 and 94 weeks after anti-TNF therapy were not different between Progression and Non-progression groups. However, the rate of swollen knee joints was higher in Progression group from 0 week. In addition, the ratio of swollen and/or tender knee joints was higher in Progression group from 22 to 94 weeks after anti-TNF therapy. The disease activity evaluated using DAS28-CRP was improved by anti-TNF therapy, but residual local symptoms in the knee joints were associated with a high incidence of joint destruction progression. We should treat rheumatoid arthritis patients with consideration for the possibility of joint destruction in the knee joints having residual local symptoms to progress.     

Intra-articular rheumatoid nodules of the knee joint

Intra-articular rheumatoid nodules found in 6 knee joints of 4 patients with rheumatoid arthritis were reported with histological findings. All patients were women, ranging in age from 32 to 61 years, with 6 to 41-year history of rheumatoid arthritis. The masses were exclusively in the anterolateral aspect of the joint. Snapping occurred when the joint was flexed by 20 degrees in four joints and by 60 degrees in two. The masses had the sizes of a thumb tip to index-finger tip, and were elastic and soft. Histologic examination of the masses revealed the typical formation of rheumatoid nodule in two joints. Myxomatous degeneration and granulation tissue consistent with rheumatoid arthritis were found in two joints. Perivascular fibrosis and myxomatous degeneration were mainly demonstrated in two joints which had developed masses two months before excision.     

Benign rheumatoid nodules in a woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy.

OBJECTIVES--To report benign rheumatoid nodules in a woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy and to summarise the features of the patients with adult onset benign rheumatoid nodules. METHODS--A 66 year old woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy who presented with subcutaneous elbow nodules, which were at first suspected to represent either progression of her haematological disease or leprosy, is described. The clinical characteristics of our patient and previous reports of another 24 subjects with adult onset benign rheumatoid nodules are reviewed. RESULTS--Biopsy of the patient's subcutaneous lesion disclosed the histopathology of a rheumatoid nodule; serological and clinical evaluations for rheumatoid arthritis and other rheumatoid nodule associated systemic diseases were negative. Adult onset benign rheumatoid nodules are clinically and histologically identical to those found in patients with rheumatoid arthritis. They often appeared in women during their 20s, frequently resolved spontaneously or were adequately treated by excision, and recurred in about one third of patients. The lesions were located in the ocular adnexa in 60% of patients. The most common lesional sites in patients with non-ocular benign rheumatoid nodules were the elbows, feet, and knees. None of these patients subsequently developed rheumatoid arthritis or other rheumatoid nodule associated diseases during follow up periods of as long as 20 years. CONCLUSION--The appearance of subcutaneous nodules is often the harbinger of an associated systemic disorder. Although benign rheumatoid nodules occur infrequently in adults, they should be considered in the differential diagnosis of new nodular lesions.     

An account of pleural effusions, pulmonary nodules and cavities attributable to rheumatoid disease.

Nine case histories and references to published reports are used to illustrate the manifestations and management of pleural effusions, lung nodules and lung cavities which may occur in cases of rheumatoid disease. Repeated aspiration of effusions seldom is useful. They often are chronic and symptomless. What is taking place in some turbid and purulent effusions is debatable, since there can be an associated leucocytosis without infection. In the presence of acute symptoms, such as rigors, careful evaluation of such effusions is required, since there have been fatal examples with rather uncertain bacteriological findings. Lung nodules ordinarily cause a radiographic blemish without symptoms but may predispose to small haemoptyses or may rupture into the pleural cavity to cause a pneumothorax, usually requiring surgical resection of the nodule, whether or not a pleural effusion is present. Some nodules and lung cavities do not have the histology of the typical necrobiotic nodule but it is unlikely that they are fundamentally different. Large cavitated lung lesions which closed on azothioprine treatment are described, together with similar untreated cavities which became secondarily infected with a fatal outcome. It is suggested that the history of possible rheumatoid disease, even of 'aches and pains' must be sought if this aetiology for pleural effusions, lung nodules and unusual lung cavities is not to be overlooked, with the penalty of diagnostic thoracotomy or wrong treatment for the patient.     

Pulmonary rheumatoid nodules demonstrating features usually associated with rheumatoid synovial membrane

OBJECTIVES: To describe the unusual immunohistological characteristics of two pulmonary rheumatoid nodules showing ectopic lymphoid follicles and the features normally associated with rheumatoid synovial membrane, and to discuss the implications of this novel observation. METHODS: Two formalin-fixed wax-embedded pulmonary rheumatoid nodules were processed for immunohistology. RESULTS: The central structure of the pulmonary nodules was typical of that uniformly expected in a rheumatoid nodule with central necrosis surrounded by a palisade of macrophages. However, a feature not previously observed in nodules was the presence of lymphoid aggregates containing B lymphocytes and, in some cases, showing characteristic features of lymphoid follicles. CONCLUSIONS: The presence of B lymphocytes and the development of ectopic lymphoid follicles in rheumatoid nodules have not been described previously. It is similar to synovial membrane, and contrasts with the expected structure of subcutaneous nodules where B cells and lymphoid follicles are normally absent. These observations establish that the morphology of rheumatoid nodules can vary in different tissues. They further suggest that the inflammatory process in the nodule and synovial membrane are likely to be similar, and that the characteristics of different tissues may be an important determinant of apparent differences between inflammatory lesions in synovial membrane and extra-articular nodules in rheumatoid arthritis.     

Necrobiotic pulmonary nodule leading to pyopneumothorax in a case of rheumatoid arthritis--a rare clinical presentation

A 49-year-old male patient, an active case of sero positive rheumatoid arthritis involving multiple joints with bilateral necrobiotic pulmonary nodules is presented. Initial symptoms were of progressively increasing dyspnoea. The nodule in the right lung subsequently cavitated leading to pyopneumothorax. The diagnosis of rheumatoid lung was confirmed by post-mortem.     

IgG and IgM rheumatoid factor in active seronegative nodular rheumatoid arthritis and in children with benign rheumatoid nodules

Summary Rheumatoid nodules in rheumatoid arthritis are usually associated with high levels of IgM rheumatoid factors and aggressive disease. IgM, IgG, and C3 have been identified in tissue sections of rheumatoid nodules, suggesting pathogenetic importance. The role of IgM and IgG rheumatoid factors in sero-negative RA is poorly understood. Seven patients with active seronegative RA and rheumatoid nodules and 10 seronegative children with the syndrome of benign rheumatoid nodules were studied for the presence of IgG and IgM rheumatoid factors by radioimmunoassay and for complement-fixing IgM rheumatoid factor by haemolytic assay. Elevated titres of hidden complement fixing IgM rheumatoid factor were found in 60 % of the patients with benign rheumatoid nodules studied but in none of the patients with active seronegative nodular RA. Serum IgG and IgM rheumatoid factor levels by radioimmunoassay and circulating immune complex levels in both groups were not significantly different from normal controls. These data suggest IgG and IgM rheumatoid factors do not participate in the pathogenesis of active seronegative rheumatoid arthritis with rheumatoid nodules.     

Tumour necrosis factor alpha independent disease mechanisms in rheumatoid arthritis: a histopathological study on the effect of infliximab on rheumatoid nodules

BACKGROUND: It has been suggested that the immunopathology of rheumatoid nodules parallels that of inflamed synovium in rheumatoid arthritis (RA). OBJECTIVE: To analyse the effect of infliximab on the immunopathology of rheumatoid nodules in order to provide new insights into the relationship between synovial inflammation and rheumatoid nodules. MATERIALS AND METHODS: Nodules were present at baseline in six patients with RA and after infliximab treatment in five patients, including paired nodules before and after treatment in three patients. In one patient, the nodule appeared during treatment. Paraffin sections were used for histological analysis. Frozen sections were stained by immunohistochemistry for cellular markers (CD3, CD4, CD8, CD16, CD20, CD68), blood vessels (CD146, vWF, alphavbeta3), and adhesion molecules (E-selectin, VCAM-1, ICAM-1). RESULTS: No manifest immunopathological differences were found between the nodules before and after infliximab treatment. All nodules depicted the classical structure with a central necrotic zone, surrounding the palisade layer, and an outer connective tissue zone. Immunohistochemistry showed the presence of CD68+ and CD16+ macrophages in the palisade and the connective tissue zone, as well as a small number of CD3+, CD4+ T lymphocytes in the perivascular areas. Small vessels were seen in the connective tissue and were sometimes positive for the neovascularisation marker alphavbeta3. They expressed no VCAM-1, E-selectin weakly, but ICAM-1 strongly. ICAM-1 was also strongly expressed on palisade cells. CONCLUSIONS: Despite an improvement of articular symptoms, infliximab treatment had no distinct effect on the histopathology of rheumatoid nodules, suggesting that different pathogenetic mechanisms mediate the two disease manifestations in RA.     

Benign Rheumatoid Nodules

Summary: Nine cases in which subcutaneous rheumatoid nodules were observed in the absence of any evidence of rheumatoid arthritis are recorded. In four of these cases, the nodules appeared during adolescence or adult life, a very rare phenomenon. Synovitis occurred in only one patient, after an interval of 15 years, but it did not persist and other features of rheumatoid arthritis were not present. The siting of the nodules in the sub-cutaneous tissue, the absence of features suggestive of rheumatic fever, necrobiosis lipiodica or fungal infection, and lack of any history of trauma, together with the histological appearance, supported a diagnosis of rheumatoid nodules. In all cases, serological tests for rheumatoid factor were negative but in the only case investigated with immunofluorescent staining, IgG and IgM were demonstrated in the biopsy material.
It is important to recognise the fact that these benign nodules do not necessarily indicate that the patient has rheumatoid arthritis, or will develop rheumatoid arthritis in the future. The possible relationship of such nodules to granuloma annulare is discussed.     

Polychondritis and rheumatoid arthritis. Case report and review of the literature

Summary We present the case history of a 50-year-old man with seropositive erosive rheumatoid arthritis of 30-years standing who developed polychondritis simultaneously with several extra-articular rheumatoid manifestations, such as anaemia, subcutaneous nodules, pericarditis and episcleritis. The relevant literature is reviewed. Gradually, all symptoms and signs disappeared after start of treatment with 30 mg prednisone and 100 mg azathioprine daily. We suggest that the polychronditis in this patient was also an extra-articular manifestation of rheumatoid arthritis.     

A case of rheumatoid nodule formation within the central nervous system and review of the literature

We describe nodule formation within the central nervous system (CNS) in a patient with seropositive rheumatoid arthritis (RA). Review of 13 previous reports of CNS rheumatoid nodule formation suggests that the clinical course is usually one of longstanding seropositive disease. Correlation of neurologic signs and symptoms with anatomic lesions has frequently been tenuous. We conclude that CNS nodules are a rare extraarticular feature of RA which, although often of uncertain clinical significance, should be considered as a possible etiology when neurologic dysfunction occurs in the RA patient.