Scandinavian Journal of Rheumatology

ISSN: 0300-9742 (Print) 1502-7732 (Online) Journal homepage: http://www.tandfonline.com/loi/irhe20

Amyloidosis of Juvenile Chronic Arthritis in Turkish Children N. Besbas, U. Saatci, A. Bakkaloglu & S. Ozen To cite this article: N. Besbas, U. Saatci, A. Bakkaloglu & S. Ozen (1992) Amyloidosis of Juvenile Chronic Arthritis in Turkish Children, Scandinavian Journal of Rheumatology, 21:5, 257-259, DOI: 10.3109/03009749209099235 To link to this article: http://dx.doi.org/10.3109/03009749209099235

Published online: 12 Jul 2009.

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Date: 24 April 2016, At: 03:46

SHORT REPORT

Amyloidosis of Juvenile Chronic Arthritis in Turkish Children N. Besbas, U. Saatci, A. Bakkaloglu and S. Ozen Department of Pediatric Nephrology, Hacettepe University, Faculty of Medicine, Sihhiye, Ankara, Turkey

Besbas N, Saatci U, Bakkaloglu A , Ozen S. Amyloidosis of Juvenile Chronic Arthritis in Tbrkish Children. Scand J Rheumatol 1992; 21: 257-259.

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Key words: juvenile chronic arthritis, amyloidosis

Amyloidosis is a syndrome characterized by the deposition of an insoluble proteinaceous material in the extracellular matrix of one or several organs (1). Secondary amyloidosis occurs as a potentially fatal complication of long-standing or poorly controlled inflammation (1-3). Juvenile chronic arthritis (JCA) has received the most attention among the chronic inflammatory states predisposing to amyloidosis. The incidence of secondary amyloidosis varies from 1% to 10%. It has been reported to be 0.1% in North America, 4% in Great Britain, 0.25% in France, 3.2% in Germany and 10.6% in Poland (2,3). Although JCA most often has a favourable prognosis; once amyloidosis develops the survival is estimated to be reduced to 8 years. In this report we present six Turkish JCA patients who developed secondary amyloidosis between the years 1980 to 1990. Patients and Methods

During this time period 286 patients have been followed-up with a diagnosis of JCA in our pediatric department. Three boys and three girls have developed amyloidosis secondary to JCA (Table 1). The mean age of onset of JCA was 3.6 years and the mean age at the time of diagnosis of amyloidosis was 8.1 years. Three of these secondary amyloisosis cases had systemic onset, and the other three had a polyarticular JCA onset. A complete physical examination was performed, and laboratory tests including biological Seza Ozen, Kuleli sok. 9/2, Gazi Osman Pasa, 06700, Ankara, Turkey Received 3 December 1991 Accepted 22 May 1992

inflammatory criteria (erythrocyte sedimentation rate, c-reactive protein) and renal parameters (blood urea nitrogen, creatinine and albumin, creatinine clearance, proteinuria) were evaluated in all six patients (Table 2). The diagnosis of amyloidosis was based on renal biopsy in 5 and rectal biopsy in one of the cases. In all of these six patients the therapy for JCA started with salicylates, was continued with nonsteroidal anti-inflammatory drugs (NSAID) and all had ended up with oral corticosteroids because of the non-responsive activity of their diseases. All except case no. 3 had heavy proteinuria, cases 1, 2, 4 and 5 had a full-blown nephrotic syndrome at the time of diagnosis of amyloidosis. Case no. 2, who was the only one with diminished renal function, had the most rapid course with a fatal end in 6 months. On the other hand case no. 3 who had only mild clinical and laboratory abnormalities, and who was presumably at an earlier stage of the deposition of amyloid material, was the only one who entered full remission. She is in remission for 3 years and is now off treatment. Case nos. 1 and 4 received dimethyl sulfoxide (DMSO) for a limited time in addition to colchicine. In our last patient we have recently discontinued colchicine and started chlorambucil therapy. This case who had mild proteinuria at the time of diagnosis is alive 2.5 years after the diagnosis. The patient has heavy proteinuria, but normal renal function at present. The other three patients (cases 1, 4, 5) died due to infections, complicated with thromboembolic complications in one. The mean survival after the onset of amyloidosis was 2 years in our fatal cases. Secondary amyloidosis constituted the sole reason of mortality in our JCA patients. Thus the overall mortality in our JCA patients in this time period was 1.4%.

N . Besbas et al. Table I(Characteristics and therapy of our patients Case no. (sex)

Onset of JRA (age)

1 IM)

2.5

2 IF)

Onset of Renal disease (age)

Type of JRA

Therapy for JRA

Therapy for Amyloidosis

6

Systemic

Salicylate, Tolmetin, Corticosteroid

DMSO, Colchicine

4

9

Polyarticular

Salicylate, Tolmetin, Hydrochloroquine, Corticosteroid

Colchicine

3 (F)

2.5

11.5

4 (MI

4

Polyarticular

Salicylate, Ibuprofon, Corticosteroid

Colchicine

6

Systemic

Salicylate, Tolmetin, Corticosteroid

Colchicine, DMSO

10

Systemic

Salicylate, Corticosteroid

Colchicine

Polyarticular

Salicylate, Tolmetin

Colchicine, Chlorambucil

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7

Discussion

Secondary amyloidosis is one of the most serious and fatal complications of juvenile arthritis in our country. The incidence of secondary amyloidosis in our pediatric JCA group has been found to be 2.1%. This is similar to the European figures for this complication (2). Amyloidosis has developed within 2 to 9 years after the onset of JCA. In the patient group reported by Smith et al. (4)the onset of JCA was at 1 to 11 years of age and secondary amyloidosis had developed within 9 months to 19 years. It is generally accepted that secondary amyloidosis is uncommon within the first 2 years of the diagnosis of JCA (1). The form of JCA also influences the development of amyloidosis; it developes usually in the systemic form and occasionally in the polyarticular type as in our patients (3). The pathogenesis of secondary amyloidosis has not been clarified. In secondary amyloidosis the amyloid protein is of AA type and its synthesis is induced in the chronic inflammatory processes ( 3 ) . Initially drugs, especially steroids, have been accused of predisposing for the development of secondary amyloidosis. At present it is suggested that steroids will protect the child from amyloidosis in JCA by suppressing the acute phase of the inflammatory process. Cytotoxic agents used in the treatment may improve survival partly due to this effect (1). Dimethyl sulfoxide (DMSO) is a drug reported to have some success in secondary amyloidosis ( 5 ) . It is thought to break down amyloid fibrils. We have attempted to use this drug in two of our patients, but had to discontinue due to its side effects. Once amyloidosis develops colchicine used to be our choice of treatment due to the beneficial experience in our amyloidosis cases secondary to familial Mediterranean fever (FMF). FMF is known to 258

be common among Turks; in fact Turkish decent has been reported to be an important criteria for the differential diagnosis of JCA versus FMF in Germany (6). Although colchicine is effective in preventing amyloidosis in FMF, the amyloidosis of JCA does not appear to respond to colchicine ( 3 ) . Colchicine seemed to be successful only in one case where it might have stopped the further progression of amyloidosis at an early stage of the disease. It did not change the outcome in the other patients. Thus it may be suggested that colchicine should not be used in these cases once the nephrotic syndrome has developed. Daily chlorambucil therapy appears to improve survival in these secondary amyloidosis cases (3,7). Deschenes et al. (2) have reported beneficial results with the use of this drug over 5 to 192 months. In our last patient chlorambucil treatment has been only recently instituted. JCA as well as other chronic inflammatory diseases should be dynamically treated to suppress the acute phase response. We believe that such patients should be carefully followed up for the detection of early signs of amyloidosis and that the patient should be worked up when persistent proteinuria is noted, since a probably better prognosis may be achieved if the deposition of amyloid fibrils Table II. Some laboratory features of our patients Case no.

Proteinuria (gr/day/m2)

Serum albumin Igrldl)

1 2 3 4 5 6

5 10 0.8 2.6 4.6 2.8

2.1 2.2 3.4 2.4 1.5 3.6

Creatine Erythrocyte clearance sedimentation (ml/min/l.73 m2) rate 88 6 82 109 100 101

110 68 48 130 125 12

Juvenile Chronic Arthritis

is at an earlier stage. We suggest that a biopsy should be done when a persistent proteinuria of more than 0.5 gr/day/m2 is noted. 123 I-SAP scanning is a new and non-invasive method that may facilitate the evaluation of this complication (3). References

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1. Cathcart ES. Amyloidosis. In: Kelley WN, Harris E D , Rubby S, Sledge CB (eds). Textbook of Rheumatology. 3rd ed. Philadelphia: WB Saunders. 1989: 152344. 2. Deschenes G , Prieur AM, Hayem F, Broyer M, Gubler MC. Renal amyloidosis in juvenile chronic arthritis: evolution after chlorambucil treatment. Pediatr Nephrol 1990; 4: 463-9.

3. David J. Amyloidosis in juvenile chronic arthritis. Clin Exp Rheumatol 1991; 9: 73-8. 4. Smith ME, AnseIl BM, Waters EGL. Mortality and prognosis related to the amyloidosis of Still’s disease. Ann Rheum Dis 1968; 27: 137. 5. van Rijswijk MH, Donker AJM, Ruinen L, Marrink J. Treatment of renal amyloidosis with dimethylsylphoxide (DMSO). Proc EDTA 1979; 16: 500-5. 6. Michels H , Hafner R, Vogel P. Das familiare Mittelmeerfieber - eine withtige Differentialdiagnose zur systemischen juvenilen chronischen Arthritis. Z Rheumatol 1989; 48: 143-6. 7. Schnitzer TJ, Ansell BM. Amyloidosis in juvenile chronic arthritis. Arthritis Rheum 1977; 20: 245.

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Amyloidosis of juvenile chronic arthritis in Turkish children.

Scandinavian Journal of Rheumatology ISSN: 0300-9742 (Print) 1502-7732 (Online) Journal homepage: http://www.tandfonline.com/loi/irhe20 Amyloidosis...
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