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[Differential diagnosis of "rheumatoid nodules"].

Rheumatic nodules occur in some 20 to 25% of cases of chronic polyarthritis, and need special diagnostic, in particular differential diagnostic, consideration. They have to be differentiated from numerous other nodules in rheumatoid and non-rheumatoid diseases. To achieve this, palpation, a knowledge of the preferred sites, and the use of such technical means as laboratory and x-ray investigations are all useful.

Aged

Application of scanning electron microscopy in the characterization of Aschoff nodules in rheumatic heart disease.

Aschoff nodules (ANs) in excised atrial appendages from cases of rheumatic heart disease were examined with a scanning electron microscope (SEM). ANs could be identified with ease as nodular, fairly well defined cell aggregates lying in the subendocardium closely apposed to the myocardium. Cells comprising ANs were loosely packed in stacks. They were rectangular, oblong and angulated. The surface of some cells had fine ribbing while others were smooth having occasional blunt projections. SEM observations coupled with the findings of conventional and electron microscopy suggest that cells composing ANs are of mesenchymal origin having characters of epithelioid cells, reticular cells and/or fibroblasts.

Endocardium

Rheumatic Aschoff nodules revisited: an immunohistological reappraisal of the cellular component.

Rheumatic fever is still the leading cause of acquired heart disease in children and young adults in developing countries. Recent reports have documented a rising incidence of rheumatic fever in both the USA and Europe. The disease is characterized by specific lesions in the heart muscle and valves called Aschoff nodules. The Aschoff nodule has been neglected in the last few decades as most of the studies were conducted in the 1960s on autopsy tissues. This study examines Aschoff nodules using heart valve material obtained at valve surgery with updated commercially available immunohistochemical antibodies to determine the phenotypic characteristics of the cells involved in the formation of these lesions. Fifteen cases of rheumatic valvulitis, as indicated by the presence of Aschoff nodules, were examined. The Anitschkow and Aschoff cells stained prominently with macrophage markers. Three stages of nodules with Aschoff and Anitschkow cells were identified: stage 1, central fibrinoid necrosis without lymphocytes, stage 2 with occasional T lymphocytes (< 10) and stage 3 with lymphoid aggregates containing both T- and B-lymphocytes (with occasional admixed macrophages). We propose that the stage 1 lesion is the earliest granulomatous stage with the lymphoid aggregates being a later stage in the development of Aschoff nodules. The Aschoff and Anitschkow cells demonstrated mitotic activity and stained with antibodies to the proliferation cell nuclear antigen (PCNA) suggesting that the multinucleated giant cells may be formed, at least partially, by nuclear division rather than fusion.

Biomarkers

Subcutaneous nodules in rheumatic fever.

Acute rheumatic fever is described in a six year old Ethiopian male child who first presented with subcutaneous nodules and later developed carditis.

Acute Disease

Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages.

AIMS: A recent immunohistochemical analysis of the Aschoff lesions in rheumatic fever, combining immunohistochemical analysis with comparative morphology, permitted the division of the Aschoff nodules into three stages: (1) Aschoff nodule without admixed lymphocytes, (2) Aschoff nodules with a few T lymphocytes, and (3) Aschoff nodules containing many admixed lymphocytes of both B- and T-cell phenotype. It was postulated that the order of progression was from stage 1 with macrophages only, to accumulation of first T lymphocytes (stage 2) and then B lymphocytes (stage 3). This study was undertaken to determine the role and distribution of interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor alpha (TNF alpha) in the various stages of the rheumatic Aschoff nodule to investigate our hypothesis on the progression of these nodules. METHODS AND RESULTS: Sixteen fresh valve specimens from patients with acute rheumatic fever undergoing valve surgery were obtained. Tissue sections from 14 specimens identified as containing Aschoff nodules were subjected to immunohistochemistry for (1) T and B lymphocytes, to stage the lesions according to our previously proposed criteria; (2) IL-1, IL-2 and TNF alpha; and (3) CD4 and CD8 to phenotype the T lymphocytes. The stage 1 and 2 lesions expressed IL-1 and TNF alpha in the macrophages. The stage 3 lesions showed more variable expression of all three cytokines including IL-2 within T lymphocytes. CONCLUSION: TNF alpha and IL-1 secretion in macrophages is required for T and B lymphocytes activation and aggregation; suggesting that macrophages arrive at the scene of rheumatic injury prior to the lymphocytes. IL-2 is usually expressed later in the inflammatory process and was found only in the lymphoid aggregates. This study therefore produces corroborative evidence for our previously proposed developmental stages of the Aschoff nodule.

Acute Disease

Rheumatoid nodules of the larynx.

A 67-year-old woman with rheumatoid arthritis was hospitalized because of dysphagia and severe nodulosis. Over a two-year period the patient had been treated with methotrexate. A computed tomography (CT) scan of the neck showed a 2 x 2 cm large tumour behind the top left lateral thyroid cartilage. A biopsy taken during direct laryngoscopy showed it was a rheumatic nodule. Treatment with colchicine reduced the patient's dysphagia. As methotrexate is used increasingly in the treatment of rheumatoid arthritis and as this particular drug causes rheumatic nodules in five to 10 per cent of the patients, it must be foreseen that the incidence of nodules in the upper airways will increase.

Aged

Nodules, eosinophilia, rheumatism, dermatitis and swelling (NERDS): a novel eosinophilic disorder.

This study presents the clinical and laboratory findings of a novel syndrome associated with eosinophilia. Two young women presented with marked eosinophilia, and large, non-tender compressible articular nodules arising from the tenosynovium of extensor tendons, dermatitis, episodic swelling of the hands and/or feet and pain in adjacent muscles and joints. Tissue specimens were examined by routine haematoxylin and eosin staining, immunofluorescent staining for eosinophil granule major basic protein (MBP) and rhodamine-avidin or tryptase staining for mast cells. Plasma levels of MBP and eosinophil-derived neurotoxin (EDN) were quantitated by immunoassay. The first patient presented in 1967 at the age of 20 and had, in addition to nodules and eosinophilia, dermographism, recurrent episcleritis and axillary urticaria. Biopsy of a nodule showed tenosynovitis with necrotizing granulomas, non-specific vasculitis, eosinophils and eosinophil degranulation as shown by extracellular deposition of eosinophil granule MBP. Her symptoms responded to low-dose, alternate-day prednisone and have remained quiescent over the past 15 yr. The second patient presented in 1990 at the age of 28 with generalized pruritic dermatitis for 15 yr, eosinophilia for 2 yr, subcutaneous nodules and non-limiting pain in several joints. Biopsy of a nodule showed chronic mild tenosynovitis, numerous eosinophils and extracellular deposition of MBP. She remains untreated. Serum IgE values and plasma levels of MBP and EDN were elevated in both patients; mast cells were numerous in their synovial tissue. Based on their clinical courses, these patients reveal the existence of a distinctive, relatively benign eosinophilic disorder with good long-term prognosis.

Adult

[Does methotrexate induce "rheumatoid nodules"? Case report and discussion of the literature].

A 58-year-old woman with chronic polyarthritis rapidly developed a large number of rheumatic nodules under treatment with methotrexate. A comparison with other cases reported to date showed that the sudden onset of such nodules after initiation of treatment, and their disappearance again after discontinuation of the drug make the causal relationship highly likely. Although the predominantly anti-inflammatory actions of methotrexate control the chronic polyarthritis in almost all cases so far reported, they are unable to prevent the primarily immunological tissue necrosis (rheumatic nodules) and may even promote their development through the liberation of adenosine. Only in very rare cases does the severity or localisation of the nodules--e.g. vasculitis, pulmonary or cardial manifestation--necessitate the discontinuation of methotrexate.

Arthritis, Rheumatoid