Prospective and serial study of primary amyloidosis with serum amyloid P component scintigraphy: from diagnosis to prognosis

doi:10.1016/S0002-9343(94)00054-9

The American Journal of Medicine

Volume 101, Issue 1, July 1996, Pages 77-87

https://doi.org/10.1016/S0002-9343(94)00054-9 Get rights and content

Objective

The purpose of this study was to assess the value of the serum amyloid P (SAP) component scintigraphy in patients with primary amyloidosis (AL).

Material and Methods

Pure human SAP labeled with iodine-123 (¹²³I-SAP) was given intravenously to 24 patients with biopsy-proven systemic amyloidosis (15 without multiple myeloma = group 1, and 9 with multiple myeloma = group 2) and to 6 patients with multiple myeloma without any clinical or biological signs of amyloidosis (group 3). Whole-body images as well as regional views and tissue retention levels were obtained after 24 hours. Our study was approved by the institutional review committee and all individuals gave informed consent and were prospectively studied (median 13 months, range 1 to 47 from the date of the scintigraphy to May 1995).

Results

Organ localization of ¹²³I-SAP, indicating the presence of substantial visceral amyloid deposits, was observed in all patients in group 1 and 2. The organ uptake of ¹²³I-SAP included the spleen (1 patient was splenectomized) in 20 of 23 cases (87%), the liver in 15 of 24 (60%), and the kidneys in 6 of 24 (25%). Myocardial ¹²³I-SAP was never seen although 13 out of the 24 patients had clinical or echographic data for amyloidosis. Twenty-four hour tissue retention was significantly elevated in all patients (group 1 and group 2): 55.66% ± 19.16% in group 1 and 34.37% ±24.92% in group 2, as compared with normal levels <24%. The sensitivity of the technique was 79% when only organ uptake was considered but reached 100% when tissue retention was also considered. The 24-hour tissue retention might be correlated with the severity of the amyloidosis: mean survival in patients with tissue retention greater than 50% was 11.3 months versus 24.5 months in patients with levels less or equal to 50%. Five of the 6 patients with multiple myeloma without evidence of amyloidosis had abnormal ¹²³I-SAP imaging and 24-hour tissue retention levels. In 2 of them, amyloidosis was secondly detected. In the 9 patients who had two scintigraphies, variations in 24-hour tissue retention values were in accordance with the clinical evaluation. Conclusions: Spleen and liver distribution of amyloidosis is mostly revealed by ¹²³I-SAP scintigraphy in patients with AL amyloidosis. The uptake of ¹²³I-SAP appeared in proportion to the quantity of amyloidosis present in different tissues, and the relative quantity of amyloid deposits in the myocardium, carpal tunnel, digestive tract, and kidneys was often small and seldom visualized by ¹²³I-SAP scintigraphy. In contrast 24-hour tissue retention levels were abnormal in all cases of known AL amyloidosis. This may be a positive argument for the diagnosis of amyloidosis when histopathological tests are normal. Tissue retention levels appear important as they may be correlated with survival.

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Cited by (46)

What do I need to know about immunoglobulin light chain (AL) amyloidosis?
2012, Blood Reviews
Citation Excerpt :
SAP scintigraphy is used to evaluate the extent and distribution of amyloid. Two studies demonstrate the prognostic utility of the extravascular retention of 123-I-SAP after 24 h in patients with AL.84,85 Hachulla and colleagues studied 24 patients with AL amyloidosis and found that 24 hour tissue retention was elevated in all patients. In addition, the mean survival in patients with tissue retention greater than 50% was 11.3 months versus 24.5 months in patients with levels less or equal to 50%.85
Immunoglobulin light chain (AL) amyloidosis is the most common acquired systemic amyloidoses. Its presentation is often insidious and progressive, which may delay diagnosis. The interval between first symptoms and actual diagnosis along the intrinsic heterogeneity of tissue tropism create a wide spectrum of presentations, both in terms of scope and depth of symptoms and signs and functional status of patients. In this review, the authors review the pathogenesis, diagnosis and differential diagnosis of AL amyloidosis along with the prognosis and state-of-the-art management for patients with this affliction.
Pulmonary amyloidosis and non-amyloid immunoglobulin deposits
2008, Revue des Maladies Respiratoires
Les amyloses sont caractérisées à l’histopathologie par des dépôts tissulaires de substance amyloïde fibrillaire spécifiquement colorée par le rouge Congo avec une biréfringence en lumière polarisée. Cette propriété est liée à une structure physique en feuillet torsadé bêta-plissé, dénominateur commun des amyloses dont plus de vingt protéines différentes peuvent être les précurseurs.
La plus fréquente des amyloses est l’amylose AL, d’origine immunoglobulinique, qui peut être limitée à un organe ou systémique (avec atteinte cardiaque prédominante).
L’amylose limitée à l’appareil bronchopulmonaire s’exprime sous forme de dépôts trachéobronchiques en plaques diffuses pouvant entraîner des sténoses, ou de nodules ou masses parenchymateuses. L’amylose interstitielle pulmonaire diffuse symptomatique est très rare, survenant dans le cadre d’une amylose systémique AL avec des dépôts amyloïdes atteignant la zone d’échanges gazeux alvéolocapillaire.
L’amylose peut se manifester également par une hypertension pulmonaire, des adénopathies amyloïdes hilaires et médiastinales, une atteinte pleurale.
L’amylose AL peut également être associée localement à un lymphome pulmonaire.
Plus rarement, des dépôts immunoglobuliniques non fibrillaires, non colorés par le rouge Congo, peuvent se produire au niveau pulmonaire sous forme de nodules ou de lésions kystiques. Exceptionnellement des dépôts immunoglobuliniques peuvent prendre une structure cristalline tissulaire ou intrahistiocytaire.
J.-F. Cordier
The amyloidoses are characterised histopathologically by the tissue deposition of fibrillar amyloid, specifically stained by Congo red and birefringent under polarised light. This characteristic is linked to a β-folded structural configuration that is the common denominator of the amyloidoses which may have more than twenty distinct protein precursors.
The most common is AL amyloidosis which is of immunoglobulin origin. It may be organ limited, or systemic (with predominant cardiac involvement). Limited bronchopulmonary amyloidosis, usually AL, may manifest itself as either tracheobronchial deposits or parenchymal nodules or masses. Diffuse interstitial pulmonary amyloidosis with clinical manifestations is rare and usually associated with systemic AL amyloidosis and deposits involving the alveolar-capillary gas exchange zone. Amyloidosis may also manifest itself as pulmonary hypertension, amyloid hilar and mediastinal adenopathy or pleural involvement. AL amyloidosis may be associated locally with pulmonary lymphoma.
Occasionally, non-fibrillar, Congo red-negative, immunoglobulin deposits may occur, presenting as parenchymal pulmonary nodules or cysts. Exceptionally immunoglobulin deposits may show a cellular or extra-cellular crystalline structure.
Diagnostic performance of <sup>123</sup>I-labeled serum amyloid P component scintigraphy in patients with amyloidosis
2006, American Journal of Medicine
Citation Excerpt :
Uptake of bone marrow and adrenal glands is particularly dissimilar: bone marrow uptake occurred only in AL in 21% of cases, whereas adrenal gland uptake was seen in this study only in AA in 20% of patients. Adrenal gland uptake, however, is not specific for AA amyloidosis and has been described in AL4,9 and ATTR patients.8 Within the group of AL patients, kappa light chain class was more frequently associated with uptake in joints and bone marrow than lambda, in contrast to the greater proportion of patients with AL amyloid of lambda type in general.
To assess the diagnostic accuracy and additional information provided by ¹²³I-labeled serum amyloid P component (SAP) scintigraphy in patients with systemic and localized amyloidosis.
¹²³I-labeled human SAP was injected intravenously into 20 controls and 189 consecutive patients with histologically proven amyloidosis: of AA type in 60 cases, AL type in 80, hereditary ATTR type in 27, and localized amyloidosis in 22 cases. SAP scintigrams were obtained 24 hours after tracer injection and were analyzed for abnormal patterns of uptake. Sensitivity and specificity were determined, and scintigraphic findings were compared with clinical data.
Diagnostic sensitivity of SAP scintigraphy for systemic AA, AL, and ATTR amyloidosis was 90%, 90%, and 48% respectively, and specificity was 93%. The distribution of amyloid was less diverse in AA than in AL type. Myocardial uptake was not visualized in any patient. Splenic amyloid was very frequent (80%) in AA and AL type but rarely detected clinically (14%). Abnormal tracer uptake in the liver and kidneys correlated with disturbed liver function and proteinuria, respectively. Bone marrow uptake was specific for AL (21%) and was more frequent in AL kappa than AL lambda. Localized amyloid deposits were not imaged.
SAP scintigraphy is diagnostic of amyloid in most patients with AA and AL type but fewer with hereditary ATTR type, relating to differing distributions and burdens of amyloid in these disorders. It usually reveals more widespread organ involvement than is identified clinically, and certain distributions of amyloid are characteristic of particular fibril types.
Hepatic amyloidosis
2005, EMC - Hepato-Gastroenterologie
L'amylose résulte du dépôt d'une protéine fibrillaire insoluble dans les espaces extracellulaires. L'atteinte histologique hépatique est très fréquente dans les amyloses AA et AL, mais il n'y a pas de parallélisme entre son importance et l'expression clinique. L'atteinte hépatique peut être un mode de révélation de la maladie : la présentation clinique la plus caractéristique est une hépatomégalie volumineuse, contrastant avec des perturbations enzymatiques modestes dont la plus évocatrice est une augmentation modérée des phosphatases alcalines. La biopsie hépatique est grevée d'un risque hémorragique accru, et doit être utilisée seulement si le diagnostic d'amylose n'a pu être obtenu à partir d'un autre tissu. En effet, l'atteinte hépatique ne semble pas modifier le pronostic dominé par les atteintes rénale et cardiaque. Les traitements spécifiques restent décevants avec une médiane de survie d'environ 1 an, sauf en cas d'amylose AA si la maladie causale peut être contrôlée.
Amyloidosis is a disease characterized by the extracellular deposition of insoluble fibrillar protein amyloid in organs or tissues. The liver is a common site of amyloidal deposition in amyloidosis AL and AA. There is a poor correlation between the amount of amyloid and the degree of hepatic impairment. Hepatomegaly is the most typical clinical feature, contrasting with mild liver tests abnormalities, the most common being an isolated elevation of alkaline phosphatase. Histological analysis of biopsy specimens is the only method to establish the diagnosis of amyloidosis but liver biopsy carries a risk of bleeding. Less invasive alternatives are rectal biopsy and subcutaneous fat aspiration or biopsy. Scintigraphy with radiolabeled serum amyloid (SAP) component is emerging as a non invasive technique for detecting, localizing, quantifying amyloid deposits and for monitoring treatment. The prognosis of amyloidosis AL is poor (median survival 9 months) despite systemic chemotherapy. Results of high dose chemotherapy associated with peripheral blood stem cell transplantation remain to assess. Prognosis of amyloidosis AA depends on treatment of the causal disease.
Renal response after high-dose melphalan and stem cell transplantation is a favorable marker in patients with primary systemic amyloidosis
2005, American Journal of Kidney Diseases
Background: Primary systemic (AL) amyloidosis is a rare plasma cell disorder characterized by soft-tissue deposition of monoclonal light chain fragments. High-dose melphalan followed by autologous stem cell transplantation currently has become the treatment of choice. Favorable outcome is ensured with achievement of hematologic response, but little is known about organ response. This study was undertaken to determine the prognostic importance of renal response after high-dose melphalan and stem cell transplantation. Methods: All patients with AL amyloidosis who underwent autologous stem cell transplantation between 1996 and December 2002 were selected for study. Renal response is defined as a 50% or greater reduction in proteinuria with less than 25% decline in renal function. Exclusion criteria included pretransplantation dialysis therapy or dialysis dependence posttransplantation, treatment mortality, lack of proteinuria assessment posttransplantation, and baseline proteinuria with protein less than 1 g/d. Results: Of 105 patients, 47 were excluded for stated reasons. Renal response was achieved in 60.3% of evaluated patients. Proteinuria was reduced by greater than 90% in 37.9% and returned to normal in 15.5%. Median response time was 12 months. Renal response was associated with a greater increase in serum albumin level (P = 0.001), maintenance of renal function (P < 0.001), and better survival (P = 0.0003). Renal responders had better survival regardless of hematologic response (P = 0.01 to 0.05). Conclusion: Currently, high-dose melphalan followed by stem cell transplantation is the most effective treatment for AL amyloidosis for those who are eligible. Our data show that renal response after high-dose melphalan followed by stem cell transplantation is associated with improved survival. Renal response is an independent marker of treatment success and can be used in cases in which determination of hematologic response is difficult.
Amyloidosis and Neuropathy
2005, Peripheral Neuropathy: 2-Volume Set with Expert Consult Basic

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Prospective and serial study of primary amyloidosis with serum amyloid P component scintigraphy: from diagnosis to prognosis

Objective

Material and Methods

Results

Arthritis Rheum.

Transfusion

Arthritis Rheum.

Amyloid deposits and amyloidosis: the β-fibrilloses

NEJM.

Amyloid deposits and amyloidosis: the β-fibrilloses

NEJM.

Circulating serum amyloid P component is the precursor of amyloid P component in tissue amyloid deposits

Clin Exp Immunol.

Quantitation of serum amyloid P by enzyme linked-immuno-sorbent assay

Clin Chem.

Response rates and survival in primary systemic amyloidosis

Blood

Diagnostic radionuclide imaging of amyloid: biological targeting by circulating human serum amyloid P component

Lancet