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PubMed1989

Involvement of the central nervous system and its coverings in different forms of amyloidosis.

The list of human amyloidoses contains at least ten different types that might be differentiated on account of their pattern of distribution (localized or generalized), on the basis of their underlying diseases and above all on account of their different amyloidogenic proteins. According to WRIGHT it was already possible to differentiate two types of amyloid by pretreating the histologic tissue sections with KMnO4 before staining them with Congored. But now nearly all different types of amyloid can be determined immunohistologically by means of specific antibodies. In the human brain and in its coverings we found as well localized as generalized amyloidoses. The most frequent localized amyloidosis is the cerebral amyloidosis in Alzheimer's disease, in senile dementia of the Alzheimer type and in "normal" aging (type ASb). The endocrine type of amyloid could be detected in the anterior pituitary lobe of old people and sometimes in adenomas of the pituitary gland (type AE). In cases of generalized amyloidosis (e.g. amyloid type AA, type AF or type AL) the intracranial amyloid deposits or precipitations are only found in those regions where the blood brain barrier is insufficient. These regions are --choroid plexus --infundibulum (hypothalamus) --pineal gland (epiphysis) --area postrema --circumventricular organs --ganglion Gasseri and --dura mater. The other parts of the CNS (the leptomeninges, cortical grey matter, subcortical white matter and basal ganglia) are always free of amyloid in these cases of generalized amyloidosis. In cases of cerebral amyloidosis (type ASb) the typical berefringent Congored deposits are found in the leptomeninges and in cortical and subcortical grey matter; white matter and all other regions are always free of amyloid. We observed several cases with more than one type of amyloidosis: e.g. a generalized form and a second local amyloidosis, two generalized forms (AA and A beta 2M) or even several localized types (ASb, AE). By paying attention to the typical distribution pattern of the amyloid deposits in the CNS and its coverings and by using specific antibodies it is now possible to distinguish between two different amyloidoses even in the same body region, e.g. in the human brain.

Aged↗
PubMed1988

[Familial primary disseminated amyloidosis (a new clinical form?)].

This report concerns two siblings we observed, one male the other female, who presented with primary disseminated amyloidosis. Repeated blood and urine examinations failed to demonstrate dysglobulinaemia. The brother developed, at the age of 51, extensive cutaneous amyloidosis with xanthochromia of the entire upper part of his body. His dermis contained a potassium permanganate-resistant amyloid substance. One year later, he presented with amyloid cardiomyopathy confirmed by biopsy. Owing to the intractable cardiac failure, heart transplantation was performed, but the patient died post-operatively. At autopsy, amyloid deposits were found to be present in the heart, liver, spleen and adrenal glands. His sister developed, at the age of 40, cutaneous amyloidosis in the form of yellowish and purpuric papules and plaques disseminated over the upper part of her body. Histological examination and electron microscopy of the skin showed large potassium permanganate-resistant amyloid deposits. In addition, endoscopy and histology demonstrated the presence of amyloid substance deposits in her larynx, oesophagus and rectum. Echocardiography revealed amyloid cardiomyopathy. She now has moderate cardiac failure, and heart transplantation is being contemplated. Like her brother, she has no renal of neurological amyloid lesions. There is no abnormality of serum or urinary globulins, and her SAA protein is present in normal concentrations. These cases do not fit in with the known nosological framework of amyloidosis. Clinically, both patients had disseminated amyloidosis of the AL type, and their disease clearly differed from familial systemic amyloidosis with neuropathy or nephropathy. To our knowledge, no case of familial primary amyloidosis of the AL type without dysglobulinaemia has yet been reported.

Amyloidosis↗
PubMed1988

Immunoglobulin synthesis in primary and myeloma amyloidosis.

Bone marrow cells from 14 patients with primary amyloidosis and two patients with myeloma amyloidosis were studied by immunofluorescence and biosynthesis experiments after incorporation of radioactive amino acids. Cells from four patients affected with non-myeloma secondary amyloidosis were also studied as controls. In primary amyloidosis, monoclonal plasma cell populations were demonstrated by immunofluorescence in virtually every case, even in patients without serum and urine monoclonal immunoglobulin and with a normal percentage of bone marrow plasma cells. Biosynthesis experiments showed the secretion of large amounts of free light chains, most often of the lambda type, in every primary or myeloma amyloidosis case and the presence of light chain fragments in almost all cases. Special features in certain patients were the synthesis of short gamma chains (two cases), assembly block at the HL half molecule level of a monoclonal IgA (one case) and secretion of decameric abnormally large kappa chains (one case). This is in contrast with non-myelomatous secondary amyloidosis where the distribution of bone marrow plasma cells was normal by immunofluorescence and where normal sized immunoglobulins were synthesized, without free light chain secretion and fragments. These data confirm that primary amyloidosis belongs to plasma cell dyscrasias and emphasize the role of free light chains and light chain fragments in the pathogenesis of amyloid deposition.

Amyloidosis↗
PubMed1984

Pathology of amyloidosis and amyloid heart disease.

Amyloidosis is a family of disorders of the immune system. Each member of the family is characterized clinically by a unique syndrome and chemically by a specific amyloid fibril protein. The diagnosis of amyloidosis requires histopathologic identification of amyloid deposits in the affected tissues. Since none of the commonly used histochemical stains is specific for amyloid and their sensitivity is variable, application of a battery of staining methods (two or more) is essential for the histologic diagnosis of amyloidosis. The heart may be affected in any form of systemic amyloidosis and in senile amyloidosis. Cardiac amyloidosis is an important cause of progressive heart failure and refractory arrhythmia of obscure origin, especially in elderly persons. The average survival time of amyloid heart disease after the onset of symptoms is less than 3 years. Clinically, amyloid heart disease may mimic constrictive pericarditis, coronary artery disease, valvular heart disease, and idiopathic hypertrophic or congestive cardiomyopathy. A confirmatory biopsy is needed for diagnosis since cardiac amyloidosis has no pathognomonic symptoms and signs, nor diagnostic electrocardiographic, radiologic, cardioangiographic and echocardiographic findings.

Amyloid↗
PubMedDate not supplied

Immunoglobulin-related (AL) amyloidosis.

The amyloid fibril is the unique component of amyloid substances. Some amyloid fibrils (i.e. AL amyloid) are made up by homogeneous immunoglobulin light chains, and such fibrils are related to systemic and localized primary amyloidosis and amyloidosis associated with myelomatosis and Waldenstrøm's macroglobulinaemia. More lambda than kappa light chain proteins make up the amyloid in these cases, and it appears that lambda-chains are more prone to fibril formation than kappa-chains. Immunoglobulins are thus the precursor protein for AL amyloid, which shows that primary amyloidosis belongs to the plasma cell dyscrasias. Amyloid infiltration of the heart and the kidneys accounts for the most severe clinical consequences of AL amyloidosis. In addition, peripheral neuropathy, carpal tunnel syndrome, macroglossia, skin affections, amyloid arthropathy and autonomic disturbances (i.e. orthostatic hypotension) are characteristic features of the disease. Involvement of parenchymal organs (kidneys, liver, spleen, gastrointestinal tract and endocrine glands) are common to systemic AL amyloidosis and secondary amyloidosis. As protein AA is the major fibril constituent of secondary amyloid, this form of amyloid disease is not related to immunoglobulins. Like other forms of plasma cell dyscrasia, patients with AL amyloidosis are usually treated with cytotoxic drugs and corticosteroids, however, the prognosis is very poor with a reported survival time after diagnosis of less than two years.

Amyloid↗
PubMed1982

Amyloid A in systemic amyloidosis associated with cancer.

Amyloid fibrils from two cases of cancer-associated, systemic amyloidosis with renal cell carcinoma and mesothelioma as the respective underlying disorders were studied. The immunochemical studies suggested strongly that amyloid A comprised a principal fibril component in both cases of cancer-associated amyloidosis. This was definitively proven by amino acid sequence analyses, which revealed structural homology between a purified subcomponent of the amyloid fibrils from both of the two cases of cancer-associated amyloidosis and previously sequenced amyloid A proteins. The chemical composition of the amyloid fibrils from systemic amyloidosis associated with cancer thus corresponded to that seen in amyloidosis reactive to inflammatory diseases and Hodgkin's disease. Amyloid proteins of immunoglobulin light chain type, which are found associated with myelomatosis, macroglobulinemia, and idiopathic (primary) amyloidosis, were not found in the two amyloid preparations. Renal cell carcinoma appears to be an effective stimulator of amyloid formation, while only one case of amyloidosis associated with mesothelioma has been reported previously.

Adolescent↗
PubMed1994

[Amyloidosis in rheumatoid arthritis--clinical study of 124 histologically proven cases].

The diagnosis of secondary amyloidosis due to rheumatoid arthritis (RA) was confirmed by positive tissue staining using Congo-red and antiserum to amyloid A protein. Biopsied specimens were obtained mainly from gastro-intestinal tracts; small salivary glands of the lips as well as abdominal adipose tissues were also studied in a small number. The results were as follows: 1. Gastro-intestinal fiberscopies and biopsies were performed on 789 RA patients for the purpose of routine screening and follow-up for amyloidosis. Seventy-seven cases (10.5%) turned out positive for amyloid. Among the biopsied specimens taken from three different sites, the proportion of amyloid-positivity was 68.9% for gastric antrum, 76.5% for duodenal cap and 88.6% for the second portion of the duodenum, suggesting the higher sensitivity and efficacy of duodenal biopsy in studying secondary amyloidosis in RA. 2. 124 patients of RA complicated with secondary amyloidosis were studied clinically with special reference to its clinical characteristics and prognosis. (1) The mean duration of RA at diagnosis of amyloidosis was 15.4 years and all patients but two were in stage III or IV (Steinbrocker). (2) Gastro-intestinal symptoms were present in 58.1% of the cases, abnormal renal signs in 58.9%, cardiac symptoms in 39.5%, respectively. All of these findings had a significant association with poorer prognosis in secondary amyloidosis due to RA. (3) The 4-year survival rate of all the cases was 57.8%, while the 3-year survival rate for the group without symptoms and signs about amyloidosis was 100%. (4) The causes of death in 36 cases were renal failure (14 cases), infection (13 cases), cerebral bleeding (2 cases), myocardial infarction (1 case), pulmonary infarction (1 case), suicide (1 case) and unknown (4 cases). Patients with intractable diarrhea were mostly susceptible to the ensuing fatal bacterial infection.

Adult↗
PubMed1994

The clinicopathological spectrum of renal amyloidosis.

BACKGROUND: Renal amyloidosis is an uncommon cause of nephrotic syndrome. The clinical conditions in Chinese people remain obscure. This is a retrospective review of the clinicopathological spectrum of 12 cases diagnosed in Taichung Veterans General Hospital from October 1982 to November 1993. METHODS: Charts and renal pathological slides were reviewed retrospectively. A scoring system was set to evaluate the degree of amyloid deposition in the renal tissue. The clinical profile, immunological data, pathological picture and final outcomes are presented and discussed, with literature review. RESULTS: There were 12 cases of primary amyloidosis including 1 case of multiple myeloma. All were confirmed by renal biopsy. The cases were all male with mean age of onset as 53.3 +/- 11.3 (range: 32 to 65 years). The mean follow-up duration was 22.9 +/- 32.8 months. The initial average creatinine clearance was 66.7 +/- 42.7 ml/min; mean daily urine protein was 7.0 +/- 4.1 grams. Nephrotic syndrome was the main clinical manifestation, present in all 12 cases. Other presenting symptoms and signs included: malaise in 7 cases; hypertension and anorexia in 4 cases; limb numbness in 3 cases; low back pain, dizziness and microhematuria in 2 cases each; anemia, headache, stroke, restrictive cardiomyopathy, hepatomegaly, syncope, body weight loss, dysphagia and skin itching in one case individually. Amyloid cardiomyopathy was present in 4 of the 8 patients who received echocardiography. The mean serum albumin level was 1.9 +/- 0.7 mg/dl, globulin level 3.1 +/- 1.1 mg/dl. Urinary Bence-Jones protein examination was performed in 8 cases; none revealed positive response. The mean immunoglobulin (Ig) level for the patients included: IgG 1018 +/- 901 mg/dl, IgA 262.0 +/- 313.8 mg/dl, IgM 104.8 +/- 84.2 mg/dl. There were at least 4 cases with high levels of one Ig but depressed levels in the others. M-component was shown by immunoelectrophoresis (IEP) in 90% of the cases. IEP impression in 10 cases revealed 2 cases of IgA lambda, 2 cases IgA kappa, 3 cases IgG lambda and 1 case IgG kappa monogammopathy, 1 case free lambda myeloma and 1 case negative. The ratio of kappa to lambda chain was 3:6. Bone marrow biopsy performed in 8 cases found only 1 case with multiple myeloma, one with amyloidosis; the other 6 cases were unremarkable. Mesangium was the site of heaviest amyloid deposition, followed by tubular basement membrane, artery and interstitium. The median survival time for those whose total score was lower than 3 points was 97.5 months; 3 to 5 points, 14 months; 6 points or more, 18.5 months. The median survival time was 21.6 months and 3-year-survival rate was 32.7%. The 2 cases with long-term survival were of 111 months and 84 months. The possible reason included: 1) Organ-limited renal amyloidosis; 2) Light amyloid deposition; 3) Younger age; 4) Other undetected favorable factors. CONCLUSIONS: 1) Renal amyloidosis is not a frequent diagnosis of nephrotic syndrome in Taiwan, but it should be suspected in every patient over 50 years old with a recent onset of proteinuria. 2) Renal amyloidosis can be diagnosed only by renal biopsy. 3) Primary renal amyloidosis is a disease of poor prognosis.

Adult↗
PubMed1977

Cell-mediated immunity in amyloidosis secondary to lepromatous leprosy.

Cell-mediated immunity in lepromatous leprosy patients with and without amyloidosis has been studied. Amyloidosis occurred mostly in patients with a history of recurrent erythema nodosum leprosum (ENL) reactions. For this reason, two control groups of leprosy patients were included, one having a history of recurrent ENL and the other little or no ENL. The lack of responsiveness to lepromin in vivo and in vitro, characteristic of lepromatous leprosy, was not altered by the presence of amyloidosis or a history of ENL. No significant difference between the patient groups was observed in the response to PPD in vitro, but skin reactivity to PPD was significantly lower in the patients with amyloidosis than in those without amyloidosis. In contrast, the PHA responses of patients with amyloidosis were significantly higher than those of control patients without a history of ENL, but not significantly different from those of control patients with a history of recurrent ENL. Lepromatous leprosy patients who develop amyloidosis thus appear to belong to a group, susceptible to repeated attacks of ENL, whose PHA responses are higher than those of other lepromatous leprosy patients. The lower skin reactivity to PPD observed in the amyloid group may reflect a general impairment in delayed cutaneous hypersensitivity.

Adolescent↗
PubMed1996

Increased circulating serum amyloid A protein derivatives in rheumatoid arthritis patients with secondary amyloidosis.

Secondary amyloidosis, a serious complication of chronic inflammatory diseases, is caused by the deposition of amyloid fibrils in various organs. The major component of amyloid fibrils is derived from serum amyloid A protein (SAA) by proteolysis. To explore the mechanisms of amyloidogenesis, we measured SAA concentrations in the sera of 38 patients with rheumatoid arthritis (RA) without secondary amyloidosis and in the sera of 18 RA patients with secondary amyloidosis, using the latex agglutination immunoassay. We also determined whether SAA was present as a full-length protein in the sera of RA patients by immunoblotting. Although SAA concentrations were elevated in the sera, there were no significant differences in these concentrations between RA patients without amyloidosis (128.2 +/- 145.4 micrograms/ml) and RA patients with amyloidosis (165.0 +/- 162.9 micrograms/ml). To test for qualitative abnormalities of SAA, the isolated SAA proteins from individual RA patients were analyzed by anti-SAA immunoblot. In addition to full-length SAA protein, 6-kd and 4.5-kd SAA-derived fragments were detected in the sera of RA patients, and the ratio of these fragments to total SAA proteins was significantly higher in RA patients with amyloidosis (37.0% +/- 0.7%) compared with that of RA patients without amyloidosis (15.0% +/- 5.5%). Although a high serum level of SAA is a predisposing condition for amyloid formation in RA patients, our data suggest that the increased circulating proteolytic cleavage of SAA may potentially contribute to the development of AA-amyloid deposition.

Adult↗
PubMed1996

Renal amyloidosis--a clinicopathologic study.

A total of 19,075 necropsies and 1169 renal biopsies were scrutinised over a period of 20 years (1973-1992) retrospectively with an aim to study the incidence and pattern of renal amyloidosis in Nair Hospital. A total of 75 cases with amyloidosis were detected, 33 from the necropsy series (0.162%) and 42 from biopsies (3.59%). Secondary amyloidosis was seen in 82.66% and primary amyloidosis in 10.66%. Tuberculosis of various organs was the main cause of secondary amyloidosis (79.03%). Nephrotic syndrome was the common mode of presentation (52%). Besides kidney, which were involved in all cases, the liver, spleen and adrenals were other commonly involved organs at necropsy. Renal failure was the leading cause of death (51.51%). Thioflavine-T proved to be more sensitive technique than other conventional staining methods. The potassium permanganate test is a useful test to distinguish secondary amyloid fibrils from other amyloid fibrils. Abdominal fat aspiration may prove to be specific, sensitive and a routine procedure enabling the early diagnosis of amyloidosis leading to increased incidence of amyloidosis during life than at necropsy.

Adult↗
PubMed1997

Secondary amyloidosis in ankylosing spondylitis. A systematic survey of 137 patients using abdominal fat aspiration.

OBJECTIVE: To assess the frequency and clinical significance of amyloid deposits in abdominal fat in patients with ankylosing spondylitis (AS). METHODS: Abdominal subcutaneous fat aspiration (ASFA) by fine needle was performed in 137 unselected patients with AS of more than 5 years of disease evolution. A followup study was done of patients with amyloidosis in the abdominal fat (ASFA positive test) to evaluate the development of clinical amyloidosis. RESULTS: In 10 (9M/1F) patients with AS, the ASFA revealed amyloid deposits (prevalence of 7%). Patients with AS and an ASFA+ test were older and had more active and severe disease than those without AS. Only 2 ASFA positive test patients had clinical amyloidosis at the time of the test. After a followup period of 2-10 yrs (mean 5.4 +/- 3.2 yrs), 3 more patients developed symptomatology due to amyloidosis. All 5 patients with clinical amyloidosis showed nephropathy, and proteinuria was found in each. The remaining patients did not develop clinical amyloidosis during followup. CONCLUSION: Amyloid deposits in abdominal fat are not a rare finding in AS. A significant proportion of these patients do not develop clinical amyloidosis after a followup of several years. Thus, an ASFA + test in patients with AS is not always associated with a poor prognosis at least in the short term, although longer followup is required.

Adipose Tissue↗
PubMed1996

[Clinical and histologic findings in patients with renal amyloidosis].

Renal amyloidosis is a rare disease when compared to other kidney diseases. During the period of last fifteen years, at the Institute of Nephrology and Immunology in Sarajevo renal amyloidosis was diagnosed with 15 patients. The disease occurred more often with men than with women. Only during 1988, renal amyloidosis was revealed and followed up with five patients. The most common clinical manifestations of renal amyloidosis are nephrotic syndrome and chronic renal failure, with respective laboratory findings. Using immunofluorescent analysis of the kidney biopsy material, we discovered deposits of immunoglobulins of different intensity and deposits of lambda and kappa light chains of immunoglobulins. The intensity of lambda light chains is greater than that of kappa chains. The analysis of light microscopy showed nodular mesangial deposits and deposits along GBM without proliferation. The diagnosis of amyloidosis was confirmed by staining of amyloid. Application of therapy for amyloidosis was without any effect. Although renal amyloidosis is a rare disease, we want to point out disease as being an etiologic factor in nephrotic syndrome.

Adult↗
PubMed1996

Peripheral nerve amyloidosis.

Peripheral nerve amyloidosis is the cardinal feature of familial amyloid polyneuropathy (FAP) but can also be seen in primary light chain (AL) amyloidosis and dialysis (beta 2-microglobulin) related amyloidosis. The generalized neuropathy seen in all forms of peripheral nerve amyloidosis is similar, characterized by a severe progressive mixed neuropathy with autonomic dysfunction. Pathologically, amyloid is found in the peripheral nervous system as amorphous, eosinophilic, extracellular deposits. FAP is most commonly associated with variant plasma transthyretin (TTR), although it has also been described in association with mutant apolipoprotein A-1 and gelsolin. There are now at least 36 point mutations in the TTR gene associated with FAP and these continue to be described. Recent studies on the possible role individual point mutations in the TTR gene may play in amyloidosis have helped give us an insight into the mechanisms behind peripheral nerve amyloidosis. This article reviews the clinical and pathological features of the peripheral nerve amyloidosis and discusses theories of amyloidogenesis based on studies of FAP.

Amino Acid Sequence↗
PubMed2001

Is the Ala138Gly alteration of MEFV gene important for amyloidosis?

Progressive systemic amyloidosis is the most important complication of familial Mediterranean fever that inevitably leads to chronic renal failure. Initial studies have suggested that the presence of the Met694Val mutation carry a significant risk for the development of amyloidosis. On the contrary, our data revealed that there was no dominance of any MEFV mutation in relation to amyloidosis. The difference between our mutation data and others led us to study a polymorphism in Turkish population that might be a risk factor for the occurrence of amyloidosis. As some of the previously reported exonic polymorphisms in other disease states found to increase the genetic susceptibility, we aimed to study Ala138Gly of the MEFV gene. Our study group consisted of 124 FMF patients, of which 47 had amyloidosis. Eighty-one individuals without any familial history of FMF were included as control group. There was no statistically significant difference between healthy controls and FMF patients for the Ala138Gly polymorphism (p=0.9). However, when FMF/amyloidosis patients (n:47) were taken as another group, the difference was significant (p= 0.01) indicating that the carriers of 138Gly are more prone to amyloidosis [odds ratio 3.1 (CI 95% 1.57-5.75)].

Alanine↗
PubMed2001

A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis.

OBJECTIVE: To address whether the gamma haplotype at exon 3 of the SAA1 gene is directly associated with type AA amyloidosis or is merely in linkage with an unknown polymorphism that is primarily associated with disease risk, we examined the SAA1 gene for new polymorphisms. METHODS: We analyzed DNA samples from 44 rheumatoid arthritis (RA) patients with AA amyloidosis (amyloid group), 55 RA patients without AA amyloidosis (RA group), and 58 non-RA healthy subjects (non-RA group). We also examined DNA samples from 50 Caucasians to compare linkage disequilibrium relationships involving SAA1 region polymorphisms between Japanese and Caucasoid populations. RESULTS: We observed 3 novel single-nucleotide polymorphisms (SNPs) in the 5'-flanking region of SAA1: -61C/G, -13T/C, and -2G/A. Comparison of allele frequencies and ratios of individuals with particular alleles between the study groups revealed statistically significant differences between the amyloid and RA groups and between the amyloid and non-RA groups. Statistical analysis revealed that the -13T/C SNP was strongly associated with AA amyloidosis. In addition, we found tight linkage between the -13T allele and the alpha haplotype, rather than the beta haplotype, at exon 3 in the Caucasoid population, while -13T was closely linked to the gamma and beta haplotypes, rather than the alpha haplotype, in the Japanese population. Since the linkage disequilibrium relationship was reversed between the Japanese and Caucasoid populations, different exon 3 haplotypes of SAA1 are found to be associated with the risk of AA amyloidosis in different ethnic groups. CONCLUSION: Our data suggest that the SAA1 -13T allele, rather than SAA1 exon 3 haplotypes, is primarily associated with AA amyloidosis risk.

Amyloidosis↗
PubMed2003

Endothelial dysfunction precedes C-fiber abnormalities in primary (AL) amyloidosis.

Primary (AL; immunoglobulin light-chain associated) amyloidosis is characterized by the deposition of pathological proteins in the extracellular matrix of tissues and organs. Autonomic and sensory peripheral neuropathy is a common feature of this disorder. The pathogenesis of the neuropathy is poorly defined. The aims of this study were to investigate vascular and neural function in the cutaneous microcirculation of AL amyloidosis patients. Seven patients with AL amyloidosis and controls were studied. Acetylcholine and sodium nitroprusside were iontophoresed into the forearm skin. Endothelial, smooth muscle, and C-fiber-mediated cutaneous blood flow (CuBF) were recorded by laser Doppler flowmetry. Endothelial vasodilation in the forearm skin was attenuated in AL amyloidosis patients (p = 0.007). Maximum endothelium-mediated CuBF in the patient group was reduced (p = 0.047). No group differences could be detected in the C-fiber response or smooth muscle vasodilation (p value not significant). Maximum C-fiber and endothelium-independent CuBF did not differ between the two groups (p value not significant). Early in the disease, AL amyloidosis patients present with impaired endothelial function. At this stage, C-fiber and smooth muscle function are still preserved. These data suggest that endothelial abnormalities precede and may contribute to the pathogenesis of the neuropathy associated with AL amyloidosis.

Adult↗
PubMed2003

Anti-tumor necrosis factor alpha therapy in fifteen patients with AA amyloidosis secondary to inflammatory arthritides: a followup report of tolerability and efficacy.

OBJECTIVE: Because anti-tumor necrosis factor alpha (anti-TNF) has emerged as a highly effective treatment for numerous inflammatory arthritides, which are a common cause of AA amyloidosis, we retrospectively evaluated the safety and efficacy of anti-TNF in a nationwide study. METHODS: The rheumatology departments of all French teaching hospitals were contacted by mail to obtain the files of patients with histologically proven secondary AA amyloidosis and renal involvement who were treated with anti-TNF. Efficacy was assessed as a sustained decrease in 24-hour proteinuria and a stable/improved glomerular filtration rate (GFR). RESULTS: Among the 15 patients studied, the 24-hour proteinuria was 4.5 +/- 3.6 gm (mean +/- SD), creatininemia was 178.4 +/- 74.9 micromoles/liter, and GFR was 46 +/- 23 ml/minute before starting anti-TNF. Ten patients received infliximab, 4 received etanercept, and 1 received both types of treatment. The mean followup was 10.4 months. No severe adverse events were recorded; one episode of herpes zoster in the first branch of the trigeminal nerve occurred after one infusion of infliximab. Amyloidosis progressed in 7 patients and was stabilized in 5 patients. Three patients (receiving infliximab alone, infliximab plus methotrexate [MTX], or etanercept plus MTX) experienced rapid, dramatic, and sustained decreases in proteinuria (>or=80%), with the GFR increasing 15-78%. CONCLUSION: Anti-TNF was well-tolerated and safe in the 15 patients with AA amyloidosis and renal involvement. The pathogenic role of TNF in AA amyloidosis, the sustained proteinuria decrease in 3 patients, and the stabilization of renal parameters in 5 other patients make anti-TNF a promising candidate to treat AA amyloidosis secondary to inflammatory arthritides.

Adult↗