Rheumatology 2001; 40: 944-945
© 2001 British Society for Rheumatology
Letters to the Editor |
Amyloidosis in a series of 964 Portuguese rheumatoid arthritis patients: comment on the article by Myllykangas-Luosujärvi et al.
Unit of Rheumatology, Service of Medicine IV, Santa Maria Hospital, Lisbon, Portugal
SIR, We read with great interest the article by Myllykangas-Luosujärvi et al. [1] about amyloidosis in a series of 1666 Finnish rheumatoid arthritis (RA) patients who died during 1989. In 1998 we carried out a review of 964 Portuguese RA patients which showed some remarkable results regarding the prevalence of secondary amyloidosis and the characteristics of this group of patients. This review included all patients satisfying the American College of Rheumatology (ACR) RA criteria [2], seen at the Rheumatology Unit of Santa Maria Hospital, Lisbon, during a 20-yr period (1977–1997). All cases were evaluated according to a protocol which included the assessment of extra-articular involvement, the presence of Sjögren's syndrome, rheumatoid factor detection, the presence of erosive disease, disease duration and patient functional class (ACR) [3]. The diagnosis of amyloidosis was established histologically (subcutis, rectum or renal biopsy). Biopsies were done in patients with a persistent raised erythrocyte sedimentation rate, proteinuria, hepatomegaly, splenomegaly, malabsortion or cardiac disease. The patients were considered to have extra-articular manifestations if at least one of the following clinical features could be detected: subcutaneous nodules, pulmonary fibrosis, pericardial effusion, pleural effusion, Felty's syndrome, cutaneous vasculitis and non-compressive neuropathy. The diagnosis of Sjögren's syndrome was based on the clinical symptoms of dry eyes and dry mouth and was confirmed by a positive result in Schirmer's test and/or by the diagnosis of keratoconjunctivitis sicca using Rose-Bengal staining, with involvement of salivary glands documented by positive findings on lip biopsy and/or salivary scintigraphy. Patients were considered seropositive if the Rose–Waaler test had a titre >64 on two or more occasions. Statistical analysis was carried out using the 
2 test.
We found 33 cases of amyloidosis (3.4%); 32 patients were female (97%) and one was male (3%). No time trend was noted in the occurrence of amyloidosis. The amyloidosis patients had a mean age [60.2 (S.D. 9.2) yr] and a disease duration [13.9 (8.6) yr] that were higher than the mean age [56.8 (14.2) yr] and disease duration [10.8 (9.6) yr] of the other RA patients studied. Eighty-eight per cent of the subjects with amyloidosis were positive for rheumatoid factor, 76% had erosive disease and 73% had erosive disease and were also positive for rheumatoid factor. These values were higher than those observed in the remainder of the RA population (respectively 68%, P<0.01; 50%, P<0.001; 41%, P<0.00001). In addition, patients with amyloidosis also had a higher prevalence of extra-articular manifestations (30 vs 12%, P<0.0001) and Sjögren's syndrome (39 vs 18%, P<0.0001) than the other RA patients. In accordance with these results, patient functional class (ACR) was worse in the amyloidosis group (class I, 60%; classes II and III, 22%; class IV, 18%) than in the other patients (class I, 82%, P<0.0001; class II and III, 15%, not significant; class IV, 3%, P<0.0001).
Our results confirm several important points suggested by the study of Myllykangas-Luosujärvi et al. In first place, amyloidosis is probably more common in Finland than in Western Europe (prevalence of 5.8% in the study of Myllykangas-Luosujärvi et al. vs 3.4% in our work), as has already been proposed by others [4]. On the other hand, this Finnish study showed that 84% of the subjects with amyloidosis were rheumatoid factor-positive, which is not in accordance with Maury et al. [5], who emphasized the high prevalence of rheumatoid factor negativity in such patients. Not only did we find a similar prevalence of rheumatoid factor positivity (88%) but we also found that this value was higher than the rheumatoid factor prevalence calculated for the rest of the RA population evaluated (68%, P<0.01). In addition to these aspects, we also found that amyloidosis occurred more frequently in women than in men, as reported by Myllykangas-Luosujärvi et al. and contrarily to other studies that have pointed to a higher risk in males [6, 7]. Finally, our data confirm the overall progressive physical disability of clinically established secondary amyloidosis observed in the Finnish patients.
Notes
Correspondence to: J. E. Cabral da Fonseca, Unidade de Reumatologia, Medicina IVc, Hospital de Santa Maria, Av. Prof. Egas Moniz, 1649–035 Lisbon, Portugal. 
Accepted 11 December 2000
References
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Myllykangas-Luosujärvi R, Aho K, Kautiainen H, Hakala M. Amyloidosis in a nationwide series of 1666 subjects with rheumatoid arthritis who died during 1989 in Finland. Rheumatology1999;38:576–9.
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Maury CPJ, Teppo AM, Wafin F, Wegelius O, Friman C, Koskimies S. Class-specific rheumatoid factors, DR antigens, and amyloidosis in patients with rheumatoid arthritis. Ann Rheum Dis1988;47:546–52.
[Abstract/Free Full Text] - Gertz MA, Kyle RA. Secondary systemic amyloidosis: response and survival in 64 patients. Medicine1991;70:246–56.[Medline]
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Reply
Department of Internal Medicine, Kuopio University Hospital, Kuopio,
1 National Public Health Institute, Helsinki and
2 Department of Internal Medicine, Oulu University Hospital, Oulu, Finland
We agree with the points made by Fonseca et al. Regarding the difference in the occurrence of amyloidosis in Finland and in Portugal, the true figure is probably higher than apparent from the data presented, as our series was population-based and that by Fonseca et al. was collected from a special rheumatological clinic. As pointed out by Fonseca et al., the development of amyloidosis is associated with severe disease with systemic manifestations. There is evidence suggesting that rheumatoid arthritis (RA) in Mediterranean countries has a milder course and fewer systemic manifestations compared with the disease in Northern Europe [1]. In this regard it is worth noting that >3% of the Portuguese RA patients had amyloidosis.
There is recent evidence that the incidence of new cases of amyloidosis is rapidly declining in Finland [2, 3]. This is certainly in part, but perhaps not entirely, attributable to advances in treatment. As we pointed out in our paper, the incidence of amyloidosis may be increasing in Japan [4]. Longitudinal studies from different areas are important to understand fully the background factors leading to this important and challenging complication of RA.
Notes
Correspondence to: R. Myllykangas-Luosujärvi, Kuopio University Hospital, P.O. Box 1777, FIN-70211 Kuopio, Finland.
References
- Vlachoyiannopoulos PG, Moutsopoulos HM. Rheumatoid arthritis in south-east Europe. Baillière's Clin Rheumatol1992;6:221–33.[Medline]
- Laiho K, Tiitinen S, Kaarela K, Helin H, Isomäki H. Secondary amyloidosis has decreased in patients with inflammatory joint disease in Finland. Clin Rheumatol1999;18:122–3.[Medline]
- Kaipiainen-Seppänen O, Myllykangas-Luosujärvi R, Lampainen E, Ikäheimo R. Intensive treatment slows progression of renal disease among rheumatoid arthritis patients with secondary amyloidosis. Arthritis Rheum1999;42(Suppl.):S239.
- Suzuki A, Ohosone Y, Obana M et al. Cause of death in 81 autopsied patients with rheumatoid arthritis. J Rheumatol1994;21:33–6.[Medline]
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