Clin Rheumatol (2006) 25: 548–549DOI 10.1007/s10067-005-0048-6

BRIEF REPORT

Carolina Duarte . Clara Gomes . A Jorge Correia .Manuel Salgado

Renal amyloidosis: an uncommon complication of juvenileidiopathic arthritis

Received: 20 April 2005 / Accepted: 25 April 2005 / Published online: 1 November 2005# Clinical Rheumatology 2005

Abstract A 9-year-old girl presented with systemic-onsetjuvenile idiopathic arthritis, diagnosed at 3.5 of age andwhich was difficult to control despite several therapeutictrials. Five years after diagnosis of juvenile idiopathicarthritis, nephrotic proteinuria was noticed. Renal biopsyconfirmed the diagnosis of amyloidosis, and chlorambucilwas initiated, with general improvement of the disease andreduction of proteinuria.

Keywords Amyloidosis . Chlorambucil .Juvenile idiopathic arthritis . Proteinuria

Introduction

Amyloidosis represents a heterogeneous group of disordersof protein metabolism and is characterized by deposition offibrillar proteins in the intra- and extracellular spaces.Inflammatory causes of amyloidosis are the most commonin developed countries with systemic-onset juvenile idio-pathic arthritis (SOJIA) as the most prevalent cause amongchildren.

Case report

A 9-year-old girl was diagnosed with SOJIA at 3.5 years,with almost permanent active disease despite successivetherapy with prednisolone, and oral and subcutaneousadministration of methotrexate and cyclosporine. At 6 yearsof age, etanercept was tried, with clinical improvement,although she persisted to have high erythrocyte sedimen-

tation rate (ESR). After a period of 18 months with apparentimprovement, her condition worsened with recrudescenceof fever, polyarthritis, poor general condition and general-ized edema. Laboratory findings were remarkable forleukocytosis (23.54×103/ml), anemia (hemoglobin 10 g/dl),thrombocytosis (517,000/mm3), high ESR (125 mm/h),hypoalbuminemia (18 g/l), and nephrotic proteinuria (uri-nary protein/creatinine ratio 1,057 mg/mmol). Abdominalultrasound showed liver hyperechogenicity, and echocar-diography revealed pericardial thickness. Renal biopsyshowed focal and segmental deposits of amyloid A in someglomeruli, in some afferent arteriole walls, and in distaltubules, with minimal interstitial lesions.

Methotrexate and etanercept were discontinued, and shewas initiated on chlorambucil and prednisolone, withresolution of fever and articular complaints and improve-ment in laboratory parameters. At seventh month ofchlorambucil, prednisolone was given in an alternate dayscheme. Table 1 presents laboratorial evolution during 14months of therapy with chlorambucil.

Hematologic disturbances were the only adverse effect,leading to a slow reduction of chlorambucil dose. In the lastconsultation after 14 months of chlorambucil initiation, thegirl was asymptomatic, and had nonnephrotic range proteinsince the eighth month of chlorambucil therapy (Table 1).

Comments

Of 121 children with JIAwith follow-up of 5 years or morein our department, 21 have SOJIA. This girl is the only caseof renal amyloidosis (0.8%).

Reactive amyloidosis complicates between 1 and 2% ofJIA and is typically associated with systemic-onset disease.Amyloid A protein is the fibril constituent of amyloiddeposits. Its precursor, serum amyloid A, is a major acutephase reactant, therefore being raised in chronic inflamma-tory diseases. [1, 3].

Amyloidosis is suspected in setting of proteinuria and apoor general condition that is out of proportion of theinflammatory disease activity. Abdominal pain and distur-

C. Duarte (*) . C. Gomes . A. J. CorreiaUnidade de Nefrologia do Hospital Pediátrico de Coimbra,Avenida Bissaya Barreto,3000 Coimbra, Portugale-mail: carolduarte@netcabo.pt

M. SalgadoUnidade de Reumatologia do Hospital Pediátrico de Coimbra,Coimbra, Portugal

bance of gastrointestinal motility are common, and hepa-tosplenomegaly can occur [1, 2, 5]. Anemia, elevated ESR,hypergammaglobulinemia, hypoalbuminemia, and protein-uria are the main laboratory findings [2, 6].

Diagnosis confirmed the presence of amyloid deposits inaffected tissues. Rectal mucosa, subcutaneous fat, andgums are the safest sites to biopsy, but renal biopsy, despitehemorrhagic risk, is essential to characterize renal lesions.The light microscopic appearance of amyloid is an amor-phous eosinophilic material that stains with Congo red;under polarized light, it has a characteristic apple-greenbirefringence [2, 6]. The radionuclide imaging with sericamyloid P labeled with 123I provides a noninvasive meansof assessing the amyloid deposits and monitoring therapy[1, 6, 7], but probably it is rarely used.

As the aim of treatment is to suppress the inflammatorydisease activity, cytotoxic therapy is the choice. Chloram-bucil is used for amyloidosis complicating JIA since 1966,and it is the only drug with proven efficacy in this raresituation. The suggested dose varies between 0.07 and0.2 mg/kg/day, from months to years, and the side effectsare dependent on daily and cumulative doses. Bone marrowsuppression is the most common adverse effect, but riskof infertility and malignant neoplasms are also relevant [1,8-10].

As in other reports, our patient had a dramatic response tochlorambucil, with improvement of clinical and laboratoryfeatures of JIA and reduction of proteinuria.

This case shows the importance of diagnosing amyloid-osis in SOJIA as it is potentially treatable with changes inthe prognosis.

Acknowledgement The authors thank Dr. Fernanda Xavier for herexpert anatomopathological assistance.

References

1. David J (1991) Amyloidosis in juvenile chronic arthritis. ClinExp Rheumatol 9:73−78

2. Woo P (1992) Amyloidosis in pediatric rheumatic diseases.J Rheumatol Suppl 35:10−16

3. Grateau G (2003) Musculoskeletal disorders in secondaryamyloidosis and hereditary fevers. Best Pract Res Clin Rheu-matol 17:929−944

4. Elises JS, Griffiths PD, Hocking MD, Taylor CM, White RH(1988) Simplified quantification of urinary protein excretion inchildren. Clin Nephrol 30:225−229

5. Prieur AM (2000) Formes systémiques d’arthrite juvénileidiopatique. Aspects évolutifs. Presse Med 29:503−509

6. David J, Vouyiouka O, Ansell BM, Hall A, Woo P (1993)Amyloidosis in juvenile chronic arthritis: a morbidity andmortality study. Clin Exp Rheumatol 11:85−90

7. Hawkins PN et al (1993) Serum amyloid P componentscintigraphy and turnover studies for diagnosis and quantitativemonitoring of AA amyloidosis in juvenile rheumatoid arthritis.Arthritis Rheum 36:842−851

8. Savolainen HA (1999) Chlorambucil in severe juvenile chronicarthritis: longterm followup with special reference to amyloid-osis. J Rheumatol 26:898−903

9. Robles NR, Roncero F, ArrobasM, Vega JLA, Casado ES (1999)Tratamiento con clorambucilo de la amiloidosis renal secundariaa artritis reumatoide. Estudio de 6 casos. Med Clin 113:456−458

10. Tan SY, Pepys MB, Hawkins PN (1995) Treatment of amy-loidosis. Am J Kidney Dis 26:267−285

Table 1 Laboratory data since the beginning of therapy with chlorambucil

Month of therapy M0 M1 M2 M5 M7 M8 M9 M10 M12 M13 M14

TherapyChlorambucil (mg/kg+1/day−1) − 0.2 = = 0.1 = 0.08 = = = =Prednisolone (mg/kg−1/day−1) 1/0.75 1/0.75 1/0.5 0.5/0.125 0.5/0 0.125/0 0.25/0 = = = =Laboratory bloodHemoglobin (g/dl) 10 − 14.1 12 10.9 9.9 11.1 11.8 11.7 10.6 10.2Leukocytes (103/ml) 23.54 − 13.3 4.22 4.1 3.28 4.1 5.9 6.0 6.19Platelets (×103/mm3) 517 − 294 214 127 81 98 106 116 139ESR (mm/h) 125 − 15 37 − 75 60 33 29 27Creatinine (umol/l) − − − 36 44 35 42UrineProt/Creat (mg/l and mmol/l) 1,057 1,168 900 345 210 112 14.2 14 95 68 47

Prot/Creat Urinary protein/creatinine ratio (mg/l/mmol/l); normal <20; significant 20−200; nephrotic >200 [4]

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