secondary amyloidosis can occur as a complication of chronic systemic inflammatory and infectious diseases . until now there has been no report of secondary amyloidosis associated with ms .
we report herein a case of renal biopsy - proven secondary amyloidosis in a patient with ms .
a 41-year - old woman with ms was hospitalized due to aggravated quadriparesis and edema in both lower extremities .
a percutaneous renal biopsy procedure was performed , the results of which revealed secondary amyloid - a - type amyloidosis associated with ms .
multiple sclerosis ( ms ) is a demyelinating autoimmune disease of the central nervous system .
its pathological triad comprises central nervous system inflammation , demyelination , and gliosis.1 secondary amyloidosis , which develops secondarily to chronic inflammatory conditions such as rheumatoid arthritis , is now called amyloid - a ( aa ) amyloidosis because a major factor in the protein deposition process involves a cleaved product of the acute - phase protein , serum amyloid a ( saa).2 cerebrovascular amyloid deposits in the region of demyelinated plaques without systemic amyloidosis have been reported rarely in cases of ms;3 however , there is no report in the literature of ms related to aa amyloidosis .
this article presents a case of ms with secondary aa amyloidosis , presenting with nephrotic syndrome .
she had been diagnosed with ms at an age of 33 years . at 26 years of age , the patient experienced her first episode of quadriparesis with sensory changes in both lower extremities . at 33 years , she noticed decreased visual acuity for several days . at 40 years
, she was admitted to the hospital due to quadriparesis , dysarthria , and confusion , and her brain mri showed brain , medullary , and spinal cord lesions ( fig .
one year later , she was hospitalized again due to aggravated quadriparesis ; she also complained of edema in both lower extremities .
steroid pulse therapy was performed again and the motor weakness in her upper extremities improved , but she continued to complain of dyspnea , orthopnea , and peripheral edema .
her chest x - ray showed cardiomegaly with pulmonary edema , but her echocardiogram showed normal findings .
laboratory studies showed the following parameters : white blood cell count 6,500/mm , red blood cell count 2.9310/mm , hemoglobin 9.6 g / dl , hematocrit 28.1% , platelets 248,000/mm , serum sodium 144
meq / l , serum potassium 4.7 meq / l , serum chloride 109 meq / l , serum creatinine 1.2 mg / dl , serum blood urea nitrogen 78 mg / dl , serum albumin 2.5 g / dl , serum total protein 5.0 g / dl , serum cholesterol 218 mg / dl , and serum saa 44.4 g / ml ( reference level < 8 g / ml ) .
in addition , anti - nuclear antibody , anti - neutrophil cytoplasmic antibody , rheumatoid factor , and cryoglobulin were not detected in this patient 's serum , which was also negative for hepatitis b surface antigen and anti - hepatitis - c antibody .
a percutaneous renal biopsy procedure confirmed the presence of aa - type amyloidosis ( fig .
we performed immunofixation electrophoresis on her serum and urine to exclude a plasma - cell dyscrasia .
aa amyloidosis was confirmed in view of the positive immunohistochemical staining for amyloid a and negative staining for kappa and lambda ; however , with the exception of a past history of non - febrile asymptomatic bacteriuria and a short - lasting minor decubitus sore on the coccyx , there was no evidence of other systemic infection or inflammatory disease .
consequently , this case was diagnosed as secondary aa - type amyloidosis associated with ms .
we present herein the clinicopathological findings of a patient with ms who developed aa amyloidosis approximately 15 years after the onset of ms .
amyloidosis is caused by the extracellular deposition of pathologic , insoluble , fibrillar proteins in organs and tissues .
precursor proteins are known to change into fibrils through multiple mechanisms that differ among the various types of amyloid .
secondary amyloidosis is caused by the deposition of amyloid originating from saa , which is an acute - phase protein produced in response to inflammation4 and occurs most commonly among patients with chronic inflammatory diseases such as rheumatoid arthritis , juvenile rheumatoid arthritis , and inflammatory bowel disease.5 familial mediterranean fever ( fmf ) is also an inflammatory disease characterized by episodic fever and serositis .
livneh et al.6 reported the development of aa amyloidosis in up to 90% of untreated fmf patients . a high prevalence of fmf
was recently reported in one ms cohort in turkey.7 these data suggest that ms is related to secondary amyloidosis , although until now there have been no reports of secondary amyloidosis in patients with ms .
one previous study found that saa levels were increased in the peripheral blood of patients with relapsing - remitting type ms .
saa plays an important role in the conversion of innate immunity into the acquired immune response present during periods of acute and chronic inflammation.8 therefore , increases in levels of saa in ms patients may be considered evidence of the role of inflammation in ms , and may be a precursor of amyloid fibrils . however , there are no reports of increased levels of saa in asymptomatic bacteriuria or decubitus sores .
the clinical presentations and symptoms dependupon the distribution pattern and the amount of amyloid deposited .
the main treatment protocol for aa amyloidosis is management of the underlying inflammatory disease process , which usually focuses on the surgical debridement of inflammatory tissue , antibiotic treatment of infectious processes , anti - inflammatory medications ( colchicine and anti - tumor necrosis factor blockade ) , and immunosupp ressive ( cyclophosphamide ) agents.9 however , these treatments , have not yet been established in randomized controlled studies . in our case ,
disease - modifying agents for ms ( e.g. , interferon- , glatiramer acetate ) could be considered for the treatment of ms - associated secondary amyloidosis .
there have been two previous reports of localized amyloid deposits in ms;5 however , there have been no reported cases of associated systemic amyloidosis .
this is the first published case of secondary amyloidosis presenting as nephrotic syndrome associated with ms .
the findings of this case suggest strongly that ms is a chronic inflammatory disease and that secondary amyloidosis can develop in ms .
 backgroundmultiple sclerosis ( ms ) is a demyelinating disease of the central nervous system . 
 secondary amyloidosis can occur as a complication of chronic systemic inflammatory and infectious diseases . until now there has been no report of secondary amyloidosis associated with ms . 
 we report herein a case of renal biopsy - proven secondary amyloidosis in a patient with ms.case reporta 41-year - old woman with ms was hospitalized due to aggravated quadriparesis and edema in both lower extremities . 
 laboratory findings showed nephrotic - range proteinuria and hypoalbuminemia . 
 a percutaneous renal biopsy procedure was performed , the results of which revealed secondary amyloid - a - type amyloidosis associated with ms.conclusionsthis is the first report of secondary amyloidosis associated with ms . 
Background
Case Report
Conclusions
Introduction
Case Report
Discussion