Eur Respir J, 1995, 8, 472Ð473 Copyright ERS Journals Ltd 1995 DOI: 10.1183/09031936.95.08030472 European Respiratory Journal Printed in UK - all rights reserved ISSN 0903 - 1936

CASE REPORT

Association of histologically proven rheumatoid with pulmonary

O. Menard*, N. Petit*, P. Gillet**, A. Gaucher**, Y. Martinet*+

Association of histologically proven with pulmonary sarcoidosis. O. *Clinique Pneumologique Médico-Chirur- Menard, N. Petit, P. Gillet, A. Gaucher, Y. Martinet. ERS Journals Ltd 1995. gicale, and **Service de Rhumatologie A, ABSTRACT: The association of rheumatoid arthritis proven by means of synovial Hôpital de Brabois, Vandoeuvre-les-Nancy, + with pulmonary sarcoidosis proven by means of bronchial biopsy, occurred France. INSERM U14, Vandoeuvre-les- in a 58 year old woman. Nancy, France. therapy resulted in complete resolution of sarcoidosis but only Correspondence: O. Menard, Clinique slight improvement of the rheumatoid arthritis, which was secondarily treated with Pneumologique Médico-Chirurgicale, CHU with a successful outcome. Only two similar cases have been reported Nancy, 54511 Vandoeuvre-les-Nancy, France with simultaneous histological proofs of both diseases. Keywords: Interstitial diseases, pul- Eur Respir J., 1995, 8, 472Ð473. monary sarcoidosis, rheumatoid arthritis Received: April 25 1994 Accepted after revision October 26 1994

Pulmonary involvement is common in rheumatoid nantly of the fingers. Pulmonary auscultation was nor- arthritis, and includes , pulmonary mal. Knee and hand radiographic examination revealed intraparenchymal rheumatoid nodules, and/ moderate demineralization. Chest roentgenogram and com- or interstitial lung disease with restrictive ventilatory puted tomography (CT) showed a diffuse bilateral reticulo- impairment. Furthermore, treatment of rheumatoid arth- nodular interstitial pattern with mediastinal ritis with gold salts, D-penicillamine or methotrexate can enlargement. Pulmonary function tests demonstrated mo- induce iatrogenic pulmonary interstitial diseases [1]. On derate hypoxaemia (arterial oxygen tension (PaO2) 10.3 the other hand, osteoarticular involvement by sarcoid- kPa (77.5 mmHg) and (arterial carbon dio- osis is rare, but can mimic rheumatoid arthritis disease xide tension (PaCO2) 4.7 kPa (35 mmHg)) with normal in some acute or chronic polyarthritic forms [2]. Differen- lung volumes and flows but diminished carbon mono- tial diagnosis is sometimes difficult when both pulmon- xide transfer factor (17.94 mlámmHg-1ámin-1; 72% of pred- ary and osteoarticular manifestations are present. The icted). association of rheumatoid arthritis or sarcoidosis with A moderate bronchial was observed on other connective diseases or vasculitis is relati- fibreoptic , and bronchial showed vely rare, but has been described. For an unknown reason, noncaseating epithelioid and . Cul- the association of rheumatoid arthritis with sarcoidosis tures and specific stains for fungal and acid-fast micro- seems to be exceptional, and histological proof has been organisms were negative. (BAL) obtained in only two previous cases of lung sarcoidosis analysis demonstrated a moderate hypercellularity (472,000 associated with RA, by simultaneous articular and pulmo- cellsámm-3), and a marked elevation of the lymphocyte nary positive biopsies [3, 4]. We report a further case count (56%), with a CD4/CD8 ratio of 2.5. with histological proof of both diseases, and with a Laboratory data showed: an elevated erythrocyte sedi- dissociated clinical course between the two diseases under mentation rate (28/68 mmáh-1 in first and second hour, treatment. respectively), a positive test, positive antinuclear antibodies (1/256), and normal serum and angiotensin converting enzyme levels. Human leu-

Case report cocyte antigen (HLA) phenotype was A2 A3 B35 Cw4 DR5 DR6. A 58 year old Caucasian woman was admitted, on Due to lung functional impairment and to severe poly- March 16, 1989 following a 3 month history of polyarth- arthritis, corticosteroid therapy ( 0.5 mgákg-1 ralgia with symmetrical inflammatory polysynovitis of daily) was initiated, resulting in rapid improvement of the proximal interphalangeal, metacarpophalangeal, wrist, both articular and pulmonary clinical symptoms. Six ankle and knee joints. She also complained of progressive months later, chest roentgenogram and CT scan, pulmon- dyspnoea on exertion. Clinical examination confirmed ary function tests and BAL revealed a complete resolu- inflammatory arthritis of the joints involved, predomi- tion of pulmonary sarcoidosis. Clinical remission of ASSOCIATION OF RHEUMATOID ARTHRITIS AND SARCOIDOSIS 473 osteoarticular signs was also observed. However, two acute or chronic polyarthritis, usually symmetrical, located months later the patient was readmitted following a new on knees, elbows, ankles, wrists and hands, and rarely episode of acute polysynovitis, predominant on both on sacroiliac joints [11Ð13]. wrists and fingers. After a complete clinical and radiolo- In our case, the dissociated clinical course of the gical examination, a combination of corticosteroid (pred- pulmonary and rheumatological manifestations raises the nisolone 1 mgákg-1 daily) and methotrexate (7.5 mgáweek-1) question of either a fortuitous association, or a noso- therapy was initiated, achieving a dramatic improvement logically related association of the two diseases, with of rheumatological symptoms within 3 weeks. Fourteen dissociated response to treatment due to different patho- months after initial admission, due to second and third physiological mechanisms and corticosteroid therapy metacarpophalangeal joint synovitis with associated responsiveness. In daily practice, formal diagnosis may retraction of the palmar aponeurosis, surgical palmar be difficult when pulmonary radiological and/or functional aponeurectomy and synovectomy of the second and third abnormalities are encountered in association with osteo- left metarcarpophalangeal joints were performed. His- articular manifestations. Although bronchial or transbron- tological examination of the synovial biopsy specimen chial biopsies through a flexible bronchoscope represent confirmed the presence of typical rheumatoid synovitis, a low invasive and successful technique for the diagnosis with hyperplasia of synovial fringes, hyperplasia of of sarcoidosis, osteoarticular biopsies for rheumatoid arth- synoviocytes, nodular perivascular lymphocytic and ritis diagnosis are much more invasive, explaining the plasmocytic inflammation, neoangiogenesis and mod- low rate of histological synovial proofs of rheumatoid erate fibrinoid necrosis. arthritis in the reported cases. Furthermore, disabling The patient was followed-up with regular clinical rheumatoid arthritis usually needs as first stage treatment examination, chest radiographs and pulmonary function strategy, the initiation of corticosteroid therapy, without tests. Four years after onset of symptoms, chest radio- the need of articular histological proof. graphs, chest CT scans and pulmonary function tests were normal. Osteoarticular status was assessed as being sta- Acknowledgements: The authors thank M. Gény for ble. Methotrexate (7.5 mgáweek-1) and low dose corti- preparation of the manuscript. costeroid therapy (prednisolone 20 mgáday-1) was continued. References

1. Prakash UBS. Rheumatological diseases. In: Murray Discussion JF, ed. Pulmonary Complications of Systemic Diseases. New York, Marcel Dekker 1992; pp. 384Ð393. We report a case of rheumatoid arthritis associated 2. James G, Neville E, Carstair LS. Bone and joint sarcoid- with pulmonary sarcoidosis in a female patient. Of osis. Semin Arthritis Rheum 1976; 6: 53Ð81. particular interest is the dissociated clinical course of 3. Fallahi S, Collins RD, Miller RK, Halla JT. Co-existence both diseases (resolution of pulmonary sarcoidosis, se- of rheumatoid arthritis and sarcoidosis: difficulties condary progression of rheumatoid arthritis) under corti- encountered in the of common costeroid therapy. manifestations. J Rheum 1984; 11: 526Ð529. 4. Kucera MRF. A possible association of rheumatoid A review of the literature disclosed only 10 previously arthritis and sarcoidosis. Chest 1989; 95: 604Ð606. reported cases of sarcoidosis associated with rheumatoid 5. Davis MW, Crotty RQ. Sarcoidosis associated with arthritis [3Ð9]. Of these 10 patients: eight had abnor- polyarthritis. Ann Intern Med 1952; 36: 1098Ð1106. mal chest roentgenograms and/or CT; 10 had histolo- 6. Putkonen T, Virkkunen M, Wager O. Joint involvement gical proof of sarcoidosis, but only four in the thorax in sarcoidosis with special reference to the co-existence (three on transbronchial biopsies and one on mediastinal of sarcoidosis and rheumatoid arthritis. Acta Rheum ); six had histological proof of rheum- Scand 1965; 11: 53Ð61. atoid arthritis (three on synovial biopsies and three on 7. Hillerdal O, Hultquist G, Linder L. A case of sarcoidosis, subcutaneous nodule biopsies); and no patient had syphilis and rheumatoid arthritis: an unusual combina- histological proof of osteoarticular sarcoidosis. Finally, tion of systemic diseases. Acta Tuberc Scand 1965; 46: 65Ð70. only two published cases have been reported with simul- 8. Thompson WR, Ferenzi GW. Sarcoidosis and rheumatoid taneous histological proof of rheumatoid arthritis and arthritis. Ill Med J 1966; 129: 239Ð242. pulmonary sarcoidosis [3, 4]. 9. Tane N, Hayashi M, Sakoda A, Mayeda A, Uda H. Extra- In the case reported by KUCERA [4] there was histologi- articular sarcoid lesions in a case treated as rheumatoid cal evidence of Sjögren's syndrome on lip biopsy. arthritis: a case report. Ryumachi 1980; 20: 358Ð367. Sarcoidosis and rheumatoid arthritis are relatively 10. Hunninghake GW, Fauci AS. Pulmonary involvement common diseases, but for unknown reasons, their associa- in the collagen vascular diseases. Am Rev Respir Dis tion seems to be rare. The main pulmonary manifestations 1979; 119: 471Ð503. of rheumatoid arthritis include , with or without 11. Sartoris DJ, Resnick D, Resnick C, Yaghmai I. Musculo- effusion, intraparenchymal necrobiotic nodules, Caplan's skeletal manifestations of sarcoidosis. Semin Roentgenol 1985; 20: 376Ð386. syndrome, diffuse interstitial with or with- 12. Mijiyawa M, Fereres M, Deutsch JP, Awada H, Dongado out fibrosis, obliterative bronchiolitis, pulmonary arteritis M, Amor B. Atteinte pelvirachidienne de la sarcoïdose. and/or [10]. Musculoskeletal manifesta- Rev Rhum 1989; 56: 529Ð532. tions of sarcoidosis include sarcoid myopathy, osseous 13. Kirkham B, Joban Putra P. Sarcoidosis and spondy- osteolytic lesions usually located in hands and feet bones, larthritis. Br J Rheum 1988; 27: 241Ð248.