Estimation of The Prevalence of Extra-Articular Manifestations …… Muhammed Abdulsalam.
Estimation of The Prevalence of Extra-Articular Manifestations in Patients with Rheumatoid Arthritis. Muhammed Abdulsalam.* Summary: Rheumatoid Arthritis is a multi-systemic disease with a variety of extra-articular manifestations. On occasion, they may be the major evidence of disease activity and a source of morbidity, and require management per se. As a rule, these manifestations occur in patients with high titers of RF. This study was undertaken to determine the prevalence of the extraarticular manifestations in our clinic, and to compare it with figures from other countries. This study was performed on (115) patients who met the ARA criteria in 1987 for RA. Ninety-nine patients were females (86.08%), (16) patients were males (13.9%). Age ranged from (14-75 yrs) with a mean age of (41.5 yrs). One –hundred and thirteen patients were white (98.2%) and (2) patients (1.73%) were black. The RF was positive in (97) patients (84.3%), and negative in (18) patients (15.6%). These patients were assessed for extra-articular manifestations of RA clinically, using the appropriate laboratory investigations. Anaemia was the commonest manifestation, occurring in (44.3%). Secondary Sjogren’s syndrome was found in (8.6%). Carpal tunnel syndrome in (6.08%), and Raynaud”s phenomena in (5.2%). These results were comparable with the results of studies from other countries. The prevalence of gastritis and PUD (8.5%) was less than reported (14-31%); this probably due to the routine use of anti-acids as prophylaxis. The SC nodules were found in only (3.4%): this was much less than reported (28%). Among the pulmonary manifestations, pulmonary fibrosis was found in (2.6%) of the patients, this was much less than reported (21%). No other pulmonary complications were found. None of the patients had cardiac, renal, eye disorders or evidence of cuteneous vasculitis
Background: Although RA develops its central pathology within the synovium of diarthrodial joints, many nonarticular organs become involved, particularly in patients with severe joint disease It is becoming more clear that the same cytokines that drive synovial pathology are also responsible for generating pathology in extra-articular tissues.1 The most common of the cutaneous manifestations is rheumatoid nodules , which are present in 20-35% of the patients, and almost all these patients have a positive test for rheumatoid factor(RF).2 Eye involvement occurs in up to 5% of the patients, and Sjogrens syndrome in 15-25% of cases.3 Among respiratory system involvement ,pleural disease (pleurisy and pleural effusion) is the commonest occurring in up to 70% of cases. Other forms of lung involvement occurs with variable frequency.4,5 Cardiac disease occurs less frequently in patients with RA, with involvement of the pericardium, myocardium, and coronary arteries.6 Kidney disease is rare in RA and may be due to the * Rheumatology Unit.7th October Hospital .Benghazi-Libya.
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disease itself ,drug toxicity, or secondary amyloidosis.7,8 The CNS is generally spared in RA ,even when active vasculitis is present .Peripheral nervous system involvement in the form of mononeuritis multiplex,carpal tunnel syndrome, and peripheral neuropathy may occur.9 Various hematological abnormalities can occur in RA, including various types of anemia,13 leukocytosis,10 eosinophilia,11 and 12 thrombocytosis. Felty’s syndrome is rare and occurs in patients with late RA and a highly positive RF.14 Method And Patients: One hundred and fifteen patients diagnosed as RA according to American College of Rheumatology (ACR) criteria 1987 were studied at rheumatology clinic in the period from 1998-2001. Of these 99 (86%) were females and 16 (13.9%) were males. The age of patients ranges from 14-75 years, with a mean of 41.5 years. 113 of the patients
Estimation of The Prevalence of Extra-Articular Manifestations …… Muhammed Abdulsalam. were white 98.2%, 2 were black 1.7%. The RF was positive in 97 patients 84.3%, and negative in 18 patients 15.6%. The disease duration ranged from 2 months to 30 years, with a mean of 20.4 years. These patients were assessed for the presence of various extraarticular manifestations of RA. Results: Among the hematological manifestations normocytic-normochromic anemia was the commonest and was seen in (26) of the patients (22.6%); microcytic- hypochromic anemia was seen in (25) patients (21.7%). None of our patients had megaloblstic ,hemolytic anemia or Felty’s syndrome. Regarding the cutaneous manifestations of RA subcutaneous nodules (Sc) were seen in (4) patients (3.4%), Raynaud’s phenomenon was seen in (6) patients (5.2). None of our patients had rheumatoid vasculitis. Pleural effusion was seen in one patient (0.8%), and pulmonary fibrosis in (3) patients (2.6%). None of the patients had pulmonary nodules or Caplan’s syndrome. Carpal tunnel syndrome was seen in (7) patients (6.08%). Non of the patients had cord compression due to cervical sublaxation or mononeuritis multiplex. Scleromalicia was seen in(2) patients (1.7%), kerratoconjuctivitis sicca secondary to Sjogren’s syndrome was seen in (10) patients (8.6%). Non of the patients had scleritis or episcleritis. Gastritis was found in (7) patients (6.08%), and peptic ulcer disease (PUD) in (2) patients (l.7%). None of the patients had cardiac, renal, or muscle involvement. See table (1). Discussion: N-N anemia was the commonest hematological finding (22.6%) which correlates with disease activity and was less than reported (30-70%).10 M-H anemia was seen in (21 .7%) OF the patients which was less than reported (5075%). This is probably due to routine use of anti-acids.11 On the other hand megaloblastic anemia due to folate and vitamin B12 deficiency was not found in our study, whereas the reported was (29%) and (21%) respectively.12 Auto-immune hemolytic anemia
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and Feltys syndrome were not found in this study, both of which are reported rarely.14 Among the cutaneous manifestations, SC nodules was found in (3.4%) of the cases, this was much less than reported (20-35%), whereas Raynaud’s phenomenon was found in (5.2%) of the cases and this was as reported. None of our patients had rheumatoid vasculitis, which is also rarely reported.2 Pulmonary fibrosis was found in (2.6%) of the cases, this was far less than reported (2136%).4 Pleural effusion was found in only (0.8%) of cases compared to what have been reported (70%). None of our patients had pulmonary nodules or Caplan’s syndrome.4 Cardiac involvement was not seen in our study, apart from pericarditis which has been reported to occur in (10%) of cases; other cardiac involvement was rarely reported.6 None of our patients had renal involvement due to the disease, drugs, or secondary amyloidosis. Renal disease is rarely reported in patients with RA.7,8 CTS was the commonest neurological manifestation in our patients (6.08); this was comparable to the reported.9 (1.7%) of our patients had scleromalacia, and kerratoconjuctivitis sicca was found in (8.6%) of the cases; this was less than reported (1525%).3 Gastritis was found in (6.08%) of cases, and PUD in (1.7%) of the cases ,both of which was less than the reported. This is probably due to routine use of anti-acids. The overall lower prevalence of extra-articular manifestations in our study as compared to the results from other areas may be due to a lower incidence of certain HLA DR alleles which are associated with severe and aggressive disease, like DW4/DW 14, DW4/DRI.15,16 Conclusion: RA is a multi-systemic disease characterized by articular and extra- articular manifestations. In our study we find that the overall prevalence of the extra-articular manifestations of patients with RA was low as compared to what have been reported from other areas. This probably reflects the variation in HLA subtypes which are associated with severe disease.
Estimation of The Prevalence of Extra-Articular Manifestations …… Muhammed Abdulsalam. Table 1: Extra-articular manifestations of RA. Extra-Articular manifestations of RA 1. Hematological: - N-N anemia - M-H anemia - megaloblastic anemia - Hemolytic anemia - Felty’s ayndrome 2. Skin manifestations: - SC nodules - Raynaud’s phenomena - Vasculitic lesions 3. Respiratory system: - Pulmonary fibrosis - Pleural effusion - Pulomnary nodules - Caplan’s syndrome 4. Cardiac disease - Perocarditis - Myocarditis - Coronary artery disease 5. Renal involvement: 6. Nervous system involvement: - CTS 7. Ocular disease: - Scleromalacia - Kerratoconjuctivitis sicca - Episcleritis - Corneal melting 8. GIT disease: - Gastritis - PUD 9. Myositis and Myopathy:
Number of patients
Percentage %
26 25 0 0 0
22.6 21.7 0 0 0
4 6 0
3.4 5.2 0
3 1 0 0
2.6 0.8 0 0
0 0 0 0
0 0 0 0
7 2 10 0 0 0
6.08 1.7 8.6 0 0 0
7 2 0
6.08 1.7 0
References: 1. Edward D, Harris, Jr. Up-to-date, copy right 1999. 2. Ginsberg MH,Genant, HR, YU, TF, et al. Rheumatoid nodulosis: An unusual variant of rheumatoid disease. Arthritis Rheum, 1975, 18:49. 3. Thompson M, Eadie, T. Kerratoconjuctivitis sicca and RA. Ann Rheum Dis, 1956, 5:21. 4. Gabbay, E, Tarala, R, Will, R, et al. ILD in recent onset RA .Ann. J Respir crit care med. 1997,156:538. 5. Radoux, V, Menrad, HA, Bgin, R, et al, Airway disease in IRA patients. One element of a general exocrine dysfunction. Arthritis Rheum, 1987:30:249. 6. Halla, Jt, Koopman, WJ, F, Fallahi, et al. Rheumatoid myositis. Clinical and histological features and possible pathogenesis. Arthritis Rheum.
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1984:27:737. Helm, HJ, Korpela, MM .Mustonen, JT, Pasternack, AL. Renal biopsy finding and clinicopathologic correlations in RA. Arthritis Rheum. 1995,38:242. 8. Nakano, M, Ueno, M, Nishi, S, et al. Analysis of renal pathology and drug history in 158 Japanese patients with RA. Clin Nephrol 1998:50:154. 9. Lanzillo, B, Pappone, N, Crisci, C, et al. Sub clinical peripheral nerve involvement in patients with IRA. Arthritis Rheum, 1998,41:1196. 10. Hansen, NE. The anemia of chronic disorders: A bag of unsolved questions. Scand J Hematol, 1983:31:397. 11. Doube, A, Davis, M, Smith, JG, et al. Structured approach to the investigation of anemia in patients with IRA. Ann Rheum Dis 1992: 51:469. 7.
Estimation of The Prevalence of Extra-Articular Manifestations …… Muhammed Abdulsalam. 12. Vreugdenhil, G, Wagnum, AW, VC, Eijk, HG, et al. Anemia in RA, The role of iron, vit. B12, and folate deficiency and erythropoietin responsiveness. Ann Rheum Dis, 1990:49:43. 13. Hansen, OP, Hansen, TM, Jans, H, Hippe, E. Red blood cell membrane-bound IgG: Demonstration of antibodies in patients with autoimmune hemolytic anemia and immune complexes in patients with rheumatic disease, Clin Lab Hematol, 1984:6:341. 14. Rosenstien, ED, Kramer, N. Felty’S and
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pseudo- Felty’s syndrome. Semin Arthritis Rheum, 1991:21:129. 15. Lanchburg, JSS, Jaeger, EEM, Sansom, DM, et al. Strong primary selection for DW4 subtype of DR4 accounts for the HLA-DQW7 association with Felty’s syndrome. Human Immunol, 1991 :32:56. 16. Van Zeben, D, Hazes, Jmw, Zwiderfllafl, AH, et al. Association of HLA-DR4 with a more progressive disease course in patients with RA. Arthritis and Rheum, 1991 :34:822.
