A 66 year old white woman was referred to us for further evaluation of pulmonary nodules. Her medical history was as follows: in July 2001 multiple pulmonary nodules were recorded on a chest x ray examination as well as computed tomographic (CT) scan (fig 1). Cancer of unknown origin with multiple lung metastases was suspected. The patient showed no pulmonary symptoms at any time, was a non‐smoker, and had not been exposed to any environmental toxins. She underwent an intensive search for the primary tumour, but all investigations were unsuccessful. Thus anterolateral thoracotomy was performed for histological evaluation of the nodules, which were classified as disseminated rheumatoid nodules (fig 2).
Figure 1 Chest x ray (A) of the patient in 2001 (depicting multiple pulmonary nodules) and chest CT scan (B).
Figure 2 Histology of the nodules (haematoxylin and eosin staining, magnification ×2.5).
On presentation at our clinic, the patient reported extreme dryness of mouth and eyes, as well as Raynaud's phenomenon. She did not have any history of fever, night sweats, weight loss, thrombosis, arthralgias, or morning stiffness.
Clinical examination at that time (November 2001) showed extreme dryness of mouth and eyes, confirmed by pathological Saxon and Schirmer tests. There was no evidence of parotid swelling or enlarged lymph nodes. No tender or swollen joints, no functional deficits or joint deformities, no subcutaneous rheumatoid nodules or rashes were documented on clinical examination.
Laboratory values were as follows: rheumatoid factor was strongly positive with 156 U/ml (normal <20 U/ml). Indirect immunofluorescent assay for antinuclear antibodies on Hep‐2 cells showed a titre of 1/640, and serological testing was positive for anti‐SSA and anti‐SSB antibodies; antibodies against Sm, RNP/Sm, U1‐snRNP, Scl‐70, Jo‐1, CENP‐B, dsDNA, and histones were negative, as were antineutrophil cytoplasmic antibodies. The C3 and C4 complement fractions and C reactive protein were in the normal range.
Serum electrophoresis showed polyclonal hypergammaglobulinaemia with a γ globulin fraction of 24%. IgG was raised at 22.6 g/l (normal 7–16 g/l); IgA and IgM were within the normal range.
An x ray examination of the hands and feet showed no pathological finding; in particular, no signs of destructive lesions were seen.
Symptomatic treatment of the sicca syndrome and Raynaud's phenomenon was started and led to good relief of the symptoms. In addition, steroid treatment was started and gradually tapered to a low dose of 5 mg prednisolone/day. The patient has been seen regularly as an outpatient during the past 4 years. She has not developed any clinical signs or symptoms of rheumatoid arthritis (RA) since her first visit in November 2001 and a recently repeated Tc99m scintigraphy again showed no signs of arthritis. Remarkably, the size and number of the pulmonary nodules has been stable since then.
Disseminated pulmonary nodules as a primary manifestation of a disease present a challenge for the clinician because a wide range of differential diagnoses have to be considered1,2,3 (box 1). In this case histological analysis finally showed the typical features of rheumatoid nodules.
Box 1 Differential diagnosis of pulmonary nodules.
| Malignant tumours |
| Bronchial carcinoma |
| Metastases |
| Pulmonary lymphoma |
| Benign tumours |
| Hamartoma |
| Chondroma |
| Infections |
| Tuberculosis |
| Bacterial infections |
| Fungal infections |
| Autoimmune diseases |
| Sarcoidosis |
| Rheumatoid arthritis |
| Wegener's granulomatosis |
| Churg‐Strauss syndrome |
| Goodpasture syndrome |
| Rare causes |
| Myloidosis |
| Connective tissue diseases (SS, SLE, PM/DM) |
Pulmonary rheumatoid nodules are detected in only 1% of patients with RA on chest radiographs, while they are found in 22% of subjects on high resolution CT.4 They often correlate with the presence of subcutaneous nodules and are mostly asymptomatic.4,5
However, although most frequently found in RA, rheumatoid nodules are not specific for this disease. Subcutaneous rheumatoid nodules have also been described in connective tissue diseases—for example, in 5–7% of patients with systemic lupus erythematosus and systemic sclerosis.6 In addition, rheumatoid nodules have occasionally been reported in association with Sharp's syndrome and dermatomyositis.
To our knowledge, this is the first case in which pulmonary rheumatoid nodules have been reported in a patient with primary Sjögren's syndrome (SS). Their occurrence can be explained by the same pathophysiological mechanism as in RA.
Pulmonary manifestations other than nodules were found to be present in about 10% of patients with SS, with most patients developing interstitial lung disease such as lymphocytic interstitial pneumonia or more rarely pseudolymphoma.7 Our observation of pulmonary rheumatoid nodules in primary SS further enlarges the spectrum of potential pleuropulmonary manifestations in patients with primary SS.
Acknowledgements
We thank Professor Dr Heine, Institute of Pathology, Schweinfurt, for providing the histological pictures.
Footnotes
Competing interest: None
References
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