adult onset still s disease ( aosd ) is a chronic systemic inflammatory disorder in which high spiking fever , typical skin rash , and polyarthritis occur .
the main biological features are neutrophilic leukocytosis , hyperferritinemia , and negative rheumatoid factor ( rf ) or antinuclear antibodies ( ana ) .
others may include splenomegaly , pleuritis , pericarditis , and hepatic abnormalities . even though functional prognosis essentially depends on articular involvement , life - threatening prognosis depends on serious complications , such as hepatic failure , disseminated intravascular coagulopathy , hemophagocytosis , infections , amyloidosis , and cardiomyopathy . in this article
we suggest a successful combined therapy of prednisolone ( pd ) , colchicine ( col ) , and cyclophosphamide ( ctx ) and review the literature .
a 25-year - old korean woman was diagnosed with aosd four years ago after experiencing a high spiking fever , maculopapular rash , and polyarthritis in her hands , elbows and knees . in laboratory findings ,
the leukocyte count was 19,900/ l , the serum ferritin level was 719.3 ng / ml ( 10240 ) , and rf and ana were negative . during a follow - up , typical skin rash had disappeared after administration of pd , sulfasalazine or hydroxychloroquine and methotraxate ( mtx ) , but either high fever or polyarthitis was wax and wane , and occasionally , intra - articular injections of corticosteroid were administered . in july 1998 , she was admitted to our hospital because of slowly increasing proteinuria over a 7 month period without pitting edema or hypertension .
she was single and had no family history of any rheumatic disease or drug history , such as gold or d - penicilliamine .
the results of laboratory data showed that the white - cell count ( wbc ) was 12,800 / l , hemoglobin ( hb ) was 10.6 g / dl , platelet was 610,000 / l , esr was 61 mm / hr , and c - reactive protein ( crp ) was 9.50 mg / dl ( < 0.8 ) . the serum protein and albumin had decreased to 4.5 g / dl ( 6.48.5 ) and 2.1 g / dl ( 3.25.5 ) , respectively .
twenty - four hour urine protein excretion was 6.9 g / day , and urine creatine clearance was 93.3 ml / min . in radiographic findings ,
chest pa was normal and bony erosions were detected in both wrist joints . in the sonography , the sizes of both kidneys were 11.5 cm on the right and 11 cm on the left side with increased renal parenchymal echogenicity .
renal biopsy showed amorphous deposits in the mesangial areas , some glomerular capillary walls and in the vascular poles ( figure 1 ) .
the amyloid deposit stained with congored displayed apple - green birefringence under the polarizing light .
immunofluorescence study for igg , igm , iga , c3 , c1 , c4 , fibrinogen , albumin , and light chains showed segmental positive staining for igm and c3 in the mesangium and trace (  ) positive staining for light chain .
electron microscopic examination confirmed amyloid deposits in the mesangial areas , which were characterized by non - branching fibrils arranged in a random array ( figure 2a , 2b ) .
serum protein electrophoresis showed a decrease in both total protein and total albumin without a monoclonal spike .
urine protein electrophoresis showed an elevated total protein level and an elevated total albumin level .
we maintained a high oral daily dose of pd ( 45 mg / day , 1 mg / kg ) , ctx ( 100 mg / day ) , and col ( 1.2 mg / day ) .
a follow - up 15 months later , laboratory tests showed that the wbc was 6,000 /ul , hb 13.2 g / dl , platelet 297,000 / l , esr 11 mm / hr , crp 0.11 mg / dl , and the serum protein and albumin had increased to 6.2 g / dl and 4.2 g / dl , respectively .
the serum ferritin was 24.3 ng / ml . the urine protein clearance was decreased from 6.9 g / day to 92 mg / day .
currently , she is taking pd 7.5 mg , ctx 50 mg , and col 1.2 gm orally .
the association of amyloid deposits and aosd is rather unusual and should be considered a serious complication .
the development of amyloidosis often occurs in patients with longstanding persistent inflammatory diseases . according to previous histopathologic reports on aosd
we have experienced 45 patients with aosd in our hospital and so far , found one case ( 2.2% ) associated with renal amyloidosis , which had developed four years after the onset of aosd .
when this complication occurs , amyloid material is preferentially deposited in the glomeruli , and proteinuria and nephrotic syndrome are the most common initial manifestations .
helin et al . demonstrated in a retrospective study of nephropathy in rheumatoid arthritis ( ra ) that the most common histopathologic finding was mesangial glomerulonephritis ( gn ) , followed by amyloidosis .
amyloidosis was the most common finding in nephrotic syndrome . in a patient with isolated proteinuria , amyloidosis , membranous gn , and mesangial gn were almost equally common .
membranous gn was closely related to gold or d - penicillamine therapies , whereas mesangial gn probably was related to ra itself .
biopsy is thus a valuable tool in differential diagnosis , assessment of prognosis , and decision - making with regard to treatment . although either nsaid or an oral steroid is usually effective in aosd , some patients with complications of the renal amyloidosis may require sustained therapy with corticosteroid and a cytotoxic agent .
the col was also effective in a patient with severe ankylosing spondylitis and nephrotic syndrome due to amyloidosis .
in review of 10 cases with aosd complicated by renal amyloidosis , combined drug therapy with pd , col , ctx , azathioprine , and mtx were used . in two of those cases ,
they were treated with steroids and dialysis due to renal failure . in our experience , it has persistently decreased proteinuria as well as recovered polyarthritis or fever , without any severe complications , during the combined therapy of pd , col , and ctx ( table 1 ) . in conclusion
although the mechanism of renal amyloid deposition is unknown , early diagnosis and treatment with pd , col , ctx may produce excellent results .
 we report a 25-year - old korean woman with adult onset still s disease ( aosd ) presented with renal amyloidosis , which had developed four years after disease onset . 
 we successfully treated her with prednisolone , colchicine and cyclophosphamide . a review of the literature uncovered about 10 cases , most of which were treated by various regimens that resulted in poor outcomes . 
 renal amyloidosis should be suspected in patients with aosd who have unexplained proteinuria . 
 although the mechanism of renal amyloid deposition is not well known , earlier histopathologic diagnosis and choice of regimen may affect prognosis . 
INTRODUCTION
CASE
DISCUSSION