Multiple intrapulmonary rheumatoid nodules]

A 66-year-old woman who had been treated at a nearby hospital since 1977 for rheumatoid arthritis complained of cough. Chest X-ray films disclosed multiple nodular shadows with cavitation in the fields of both lungs. The patient was admitted to our hospital and a thoracoscopic lung biopsy was performed. Histologically, the nodule consisted of necrotizing granuloma, indicating a necrobiotic nodule. Rheumatoid nodule was diagnosed because the patient exhibited rheumatoid arthritis. The chest X-ray shadow disappeared without medication. Rheumatoid nodules without coniosis are uncommon, but should be considered in the differential diagnosis of lung nodular lesions in patients with rheumatoid arthritis.     

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.     

Gutes Ansprechen eines pulmonalen Rheumaknoten auf Rituximab

Pulmonary rheumatoid nodules can be found in over 4% of patients with rheumatoid arthritis. Diagnostically they have to be differentiated from malignant and infectious processes. The present article describes a case of pulmonary rheumatoid nodule which responded well to Rituximab therapy.     

Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty tophi and rheumatoid nodules

Summary The mononuclear phagocyte infiltrate which occupies the gout tophus has been compared with that of the subcutaneous rheumatoid nodule. In the gout tophus, macrophage migration appears to be at a relatively low level and effectively terminates once these cells have been recruited into the corona. In the nodule the evidence suggests that both macrophage and granulocyte populations continuously migrate towards, and are progressively incorporated into, the necrotic centres. These observations indicate that chemotactic activity in rheumatoid nodules is at a higher level than in gout tophi, or that the rheumatoid mononuclear phagocyte is more responsive to such stimuli.     

Immunological and immunohistochemical analysis of rheumatoid nodules.

An attempt was made to examine the pathophysiology of the rheumatoid nodule. Significant amounts of interleukin 1-like activity and prostaglandin E2 were detected in the supernatants from in vitro organ cultures of rheumatoid nodule tissue. When fresh (but not old) rheumatoid nodules were minced and cultured in vitro prominent outgrowths of cells were observed. These cells expressed both HLA-DR and CD14 antigens but lacked conventional differentiation antigens for T cells and B cells, suggesting that they are of monocyte-macrophage origin. These data suggest that interleukin 1 and prostaglandin E2 may be deeply involved in the formation of rheumatoid nodules.     

Constitutive production of angiotensin converting enzyme from rheumatoid nodule cells under serum free conditions.

Angiotensin converting enzyme was assayed in serum free culture supernatants from unstimulated rheumatoid nodule cells. Angiotensin converting enzyme was released spontaneously and the angiotensin converting enzyme derived from rheumatoid nodule cells was suppressed in a dose and time dependent manner by the protein synthesis inhibitor cycloheximide. These data suggest the constitutive de novo synthesis of angiotensin converting enzyme by rheumatoid nodule cells.     

MRI appearance of retrocalcaneal bursitis and rheumatoid nodule in a patient with rheumatoid arthritis

Rheumatoid arthritis is an autoimmune disorder of unknown etiology characterized by symmetric, erosive synovitis and sometimes multisystem involvement. Rheumatoid nodules have been reported in as many as 20–30% of patients with rheumatoid arthritis; however, they are not commonly seen in the feet. We present magnetic resonance (MR) findings of a rarely seen case of rheumatoid bursitis in the retrocalcaneal bursa associated with a subcutaneous rheumatoid nodule inferior to the calcaneus which histologically confirmed the rheumatoid arthritis. To the best of our knowledge, this is the first case that rheumatoid bursitis in the retrocalcaneal bursa associated with the rheumatoid nodule in the foot was revealed by MR imaging.     

Fluorodeoxyglucose (FDG) uptake in pulmonary rheumatoid nodules diagnosed by video-assisted thoracic surgery lung biopsy: two case reports and a review of the literature

Two cases of rheumatoid nodules evaluated by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and video-assisted thoracic surgery (VATS) biopsy are reported. The first case was that of a 44-year-old woman who presented with a cavitated nodule with intense standardized uptake values (SUVs) both in the early (max 3.4) and delayed (max 4.4) phases, suggesting malignancy. However, after VATS biopsy, she was diagnosed as having a rheumatoid nodule with vasculitis. The second case was that of a 74-year-old woman admitted with bilateral lung nodules, two of which showed intense early (max 2.2) and delayed (max 6.0) phase SUVs, and mild early (max 0.6) and delayed (max 0.9) phase SUVs. These two nodules were finally proven to be a lung cancer and rheumatoid nodule without vasculitis, respectively. These cases show that rheumatoid nodules with an enhanced inflammatory process, such as vasculitis, can appear false-positive for malignancy on FDG-PET/CT scan images.     

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.     

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.     

Rheumatoid nodule and complete heart block: diagnosis by transesophageal echocardiography

We report a case of 48 years old women with a 8 years history of rheumatoid arthritis and severe articular deformation treated during the last 6 months by prednisone (5 mg daily) and chloroquine (200 mg daily), admitted in the emergency room because of syncope. The electrocardiogram showed a complete atrioventricular block. Transesophageal echocardiography was performed and revealed an hyperechogenic mass (6 x 2.5 mm) in the interventricular septum probably related to a fibrous rheumatoid nodule. This potentially explain the atrioventricular block by infiltration of the conduction pathways. A permanent double chamber pacemaker was inserted. The chloroquine, another factor of conduction disturbances was not incriminated in this case. The conduction disturbances should be systematically detected in case of severe rheumatoid arthritis. Therefore, every patient must be submitted to a transthoracic echocardiography. Transesophageal echocardiography may be helpful to detect rheumatoid nodule.     

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.     

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.     

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.     

Cells expressing dendritic cell markers are present in the rheumatoid nodule

OBJECTIVE: To determine if dendritic antigen-presenting cells (DC) are present in rheumatoid nodules, as has been reported in the synovial lesions of rheumatoid arthritis. METHODS: Nodules (n = 14) were examined with monoclonal antibodies (Mab) recognizing the DC differentiation/activation markers CD83, CMRF44, and CMRF56 and an antibody recognizing the CD1a antigen present on epithelial tissue associated DC. Results. Cells expressing CMRF44 were common in rheumatoid nodules, comprising 22% of nucleated cells versus 13% in synovial membranes (n = 10). Cells positive for CD1a (5%) and CD83 (2%) were less common. A majority (86%) of CMRF44 positive cells were also positive for the macrophage marker CD14. This left a significant minority of putative DC that were single stained with CMRF44. CONCLUSION: Cells bearing DC markers are as frequent in the rheumatoid nodule as in the synovial lesions. A majority are "indeterminate" cells that are CD14 positive but a proportion are single stained putative DC. The lack of lymphoid collections containing DC and T and B lymphocytes in the nodule suggests that local presentation of antigen may not occur in the rheumatoid nodule, as is thought to be the case in synovial membranes containing lymphoid follicles. This difference could potentially be explained by different states of activation, and differentiation of DC within the 2 lesions.     

Rheumatoid lung disease, pneumothorax, and eosinophilia.

Four cases of the triad of rheumatoid lung disease, spontaneous pneumothorax, and peripheral blood eosinophilia are reported. Cavitation of a rheumatoid lung nodule caused the pneumothorax in at least 1 case. The significance of eosinophilia and its value as a marker of extra-articular manifestations of rheumatoid disease are discussed.     

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.     

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.     

Immunohistology of rheumatoid nodules and rheumatoid synovium.

The immunohistological features of rheumatoid nodules and rheumatoid synovium were examined using monoclonal and polyclonal antibodies raised against macrophages, HLA-DR, leucocyte common antigen, and immunoglobulin components. The palisading cells surrounding the necrotic centre of the rheumatoid nodule were shown to be HLA-DR positive leucocytes, mostly histiocytes. The inflammatory infiltrate associated with rheumatoid nodules showed many immunohistochemical similarities to that of rheumatoid synovium, including a preponderance of IgG positive plasma cells, and a similar number and microanatomical pattern of distribution of HLA-DR positive cells. The significance of these findings for the cellular immunopathology and aetiology of the rheumatoid lesion is discussed.     

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