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Sample records for systemic al amyloidosis

  1. AL Amyloidosis

    PubMed Central

    2012-01-01

    Definition of the disease AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils. Epidemiology AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50. Clinical description The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis. Diagnostic methods The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and/or immunofluorescence. Due to the

  2. Systemic amyloidosis.

    PubMed

    Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N

    2016-06-25

    Tissue deposition of protein fibrils causes a group of rare diseases called systemic amyloidoses. This Seminar focuses on changes in their epidemiology, the current approach to diagnosis, and advances in treatment. Systemic light chain (AL) amyloidosis is the most common of these conditions, but wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly being diagnosed. Typing of amyloid fibrils, a critical determinant of therapy, has improved with the wide availability of laser capture and mass spectrometry from fixed histological tissue sections. Specific and accurate evaluation of cardiac amyloidosis is now possible using cardiac magnetic resonance imaging and cardiac repurposing of bone scintigraphy tracers. Survival in AL amyloidosis has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Early diagnosis, a key to better outcomes, still remains elusive. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilisers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise to transform outcomes in systemic amyloidoses. PMID:26719234

  3. AL Amyloidosis and Agent Orange

    MedlinePlus

    ... for survivors' benefits . Research on AL amyloidosis and herbicides The Health and Medicine Division (formally known as ... to the compounds of interest found in the herbicide Agent Orange and AL amyloidosis." VA made a ...

  4. Primary (AL) amyloidosis in plasma cell disorders.

    PubMed

    Müller, Antonia M S; Geibel, Annette; Neumann, Hartmut P H; Kühnemund, Alexander; Schmitt-Gräff, Annette; Böhm, Joachim; Engelhardt, Monika

    2006-01-01

    Primary (AL) amyloidosis is the most common form of systemic amyloidosis. The morbidity arises from extracellular deposition of immunoglobulin light chain (LC) fibrils in major organs, such as the kidneys, heart, and bowel. Organ dysfunction contributes to a high mortality and poor prognosis, with a median survival time of 1-2 years from diagnosis. Here, we present a 46-year-old man with an exceptional clinical course of an LC multiple myeloma with generalized amyloidosis, causing renal insufficiency, congestive heart failure, and complete intestinal necrosis. We have summarized recent knowledge on AL amyloidosis, its association with monoclonal gammopathies, clinical presentations, diagnostic tools, and treatment strategies. Our comprehensive overview of this rare and often fatal disease aims to increase the awareness of AL amyloidosis. This may facilitate earlier diagnosis, and thus allow initiation of prompt and specific therapies, which are indispensable in order to improve disease prognosis. PMID:16880241

  5. Clinical profile and treatment outcome of older (>75 years) patients with systemic AL amyloidosis

    PubMed Central

    Sachchithanantham, Sajitha; Offer, Mark; Venner, Christopher; Mahmood, Shameem A.; Foard, Darren; Rannigan, Lisa; Lane, Thirusha; Gillmore, Julian D.; Lachmann, Helen J.; Hawkins, Philip N.; Wechalekar, Ashutosh D.

    2015-01-01

    Systemic AL amyloidosis, a disease with improving outcomes using novel therapies, is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied in this group of patients in whom comorbidities and frailty may compound morbidity and mortality. We report the outcomes of 295 patients with systemic AL amyloidosis ≥75 years seen at the UK National Amyloidosis Centre from 2005–2012. The median age was 78.5 years. The median overall survival was 20 months. Two hundred and thirty-eight patients received chemotherapy and 57 elected for supportive care only (overall survival – 24 and 8.4 months, respectively). On intention-to-treat analysis, 44% achieved a hematologic response including a very good partial response or better in 23%. The median overall survival was 6.2 years in patients achieving very good partial response or better at the 6-month landmark analysis and 1.5 years in non-responders. Factors independently indicating a poor prognosis were: cardiac involvement, performance status ≥2; systolic blood pressure <100 mmHg and, on landmark analysis, achieving less than a very good partial response. Treatment of systemic AL amyloidosis in the elderly is challenging. Deep clonal responses are associated with excellent survival and organ responses. Achieving a response to the first-line regimen appears particularly important as outcomes of non-responders are similar to those of untreated patients. Prospective trials with lower toxicity, outpatient treatment regimens are needed. PMID:26294730

  6. Immunomodulatory drugs in AL amyloidosis.

    PubMed

    Jelinek, T; Kufova, Z; Hajek, R

    2016-03-01

    Immunoglobulin light chain amyloidosis (AL amyloidosis) is indeed a rare plasma cell disorder, yet the most common of the systemic amyloidoses. The choice of adequate treatment modality is complicated and depends dominantly on the risk stratification of these fragile patients. Immunomodulatory drugs (IMiDs) are currently used in newly diagnosed patients as well as in salvage therapy in relapsed/refractory patients. IMiDs have a pleiotropic effect on malignant cells and the exact mechanism of their action has been described recently. Thalidomide is the most ancient representative, effective but toxic. Lenalidomide seems to be more effective, nevertheless the toxicity remains high, especially in patients with renal insufficiency. Pomalidomide is the newest IMiD used in this indication with a good balance between efficacy and tolerable toxicity and represents the most promising compound. This review is focused on the evaluation of all three representatives of IMiDs and their roles in the treatment of this malignant disorder. PMID:26806146

  7. Systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency.

    PubMed

    Taniyama, H; Yamamoto, S; Sako, T; Hirayama, K; Higuchi, H; Nagahata, H

    2000-01-01

    Histopathologic and immunohistochemical examinations were conducted on a 5-year-old Holstein-Friesian cow with systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency. Amyloid deposits were present in the perivascular and intercellular spaces of the visceral organs, such as the liver, kidneys, pancreas, adrenal glands, and upper alimentary tract. Amyloid was stained positively with Congo red with or without 5% potassium permanganate pretreatment and had green birefringence observed under polarized light. Immunohistochemically, amyloid reacted strongly against anti-bovine IgG (H+L) and anti-bovine kappa-light chain and reacted weakly against bovine X-light chain antibodies but was negative for anti-human amyloid AA antibody. This is the first description of AL amyloidosis immunohistochemically related to immunoglobulin kappa-light chains of precursor protein in cattle. PMID:10643989

  8. Secondary systemic amyloidosis

    MedlinePlus

    ... occurs as a result of chronic infection or chronic inflammatory disease. Primary amyloidosis means there is no disease that is causing the condition. Systemic means that the disease affects the entire body. Causes ... fibrosis Familial Mediterranean fever Hairy cell ...

  9. [Purpura: primary systemic amyloidosis manifestation].

    PubMed

    Lestre, Sara; Gonçalves, Andreia; João, Alexandre; Ferreira, Ana; Apetato, Margarida

    2009-01-01

    Primary Systemic Amyloidosis (AL) is the most frequent form of systemic amyloidosis and its morbilility is associated with immunoglobulin light chains deposition in vital organs. The mucocutaneous manifestations occur in about 30-40% of the cases and are important in diagnostic suspicion, once they appear in early stages of disease. We report a 71-years-old female patient, with disseminated purpura and cutaneous fragility with 6 months of evolution, accompanied by recent complaints of dysphagy. The first laboratory evaluation didn't show any alterations. The histological and immunohistochemical study of subcutaneous abdominal fat and skin biopsy showed lambda type amyloid protein. In the systemic work-up, we highlight a proteinúria > 1g/24h with Bence Jones proteins and the presence of monoclonal immunoglobulin light chain (lambda type) in serum immunoelectrophoresis. With the diagnosis of primary systemic amyloidosis, treatment with prednisolone and melphalan was started. PMID:19686633

  10. Systemic AL amyloidosis due to non-Hodgkin's lymphoma: an unusual clinicopathologic association.

    PubMed

    Cohen, A D; Zhou, P; Xiao, Q; Fleisher, M; Kalakonda, N; Akhurst, T; Chitale, D A; Moscowitz, C; Dhodapkar, M V; Teruya-Feldstein, J; Filippa, D; Comenzo, R L

    2004-02-01

    Systemic AL amyloidosis (AL) is a disorder in which light chains form fibrillar deposits, leading to organ dysfunction and death. Rarely, AL has been associated with non-Hodgkin's lymphoma (NHL), although this association has not been well characterized. We report a series of six patients with AL associated with NHL, primarily lymphoplasmacytic lymphoma. Organ involvement was variable, with frequent bulky lymphadenopathy and visceral cavity deposits, but no cardiac involvement. Positron emission tomography scans were negative. Bone marrow and lymph node biopsies showed a mixed population of CD20+ lymphoid and CD138+ plasma cells. Serum free light chains were elevated, and correlated with response to therapy. Immunoglobulin light chain variable region (Ig VL) germline gene use was typical for AL, reflecting previously observed correlations between germline gene use and organ tropism. Five patients received rituximab-based therapies with two responses. Two patients underwent autologous stem cell transplantation with one complete haematological response. Four patients survive at 10-132 months from diagnosis. AL with NHL has distinctive clinical features but employs the same Ig VL gene repertoire as AL with clonal plasma cell dyscrasias. Serial serum free light chain levels are useful for tracking response to therapy. Treatments aimed at both lymphoid and plasma cell components appear warranted. PMID:14717777

  11. Oral purpura as the first manifestation of primary systemic amyloidosis.

    PubMed

    McCormick, Robert Stuart; Sloan, Philip; Farr, David; Carrozzo, Marco

    2016-07-01

    Oral blood blisters and purpura are rare features of primary systemic amyloidosis (amyloid light-chain (AL) amyloidosis). We report a case in which these unusual presentations led to a diagnosis of amyloidosis, which enabled effective treatment before organ failure. PMID:26708800

  12. 77 FR 6466 - Schedule for Rating Disabilities; AL Amyloidosis (Primary Amyloidosis)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-08

    ... 22, 2010, VA published in the Federal Register (75 FR 65279) a proposed rule that would add AL... decision was published in the Federal Register at 74 FR 21258, which amended 38 CFR 3.309(e) by adding AL... hemic and lymphatic systems to include AL amyloidosis. This regulatory action is necessary to add...

  13. Systemic AA amyloidosis: epidemiology, diagnosis, and management

    PubMed Central

    Real de Asúa, Diego; Costa, Ramón; Galván, Jose María; Filigheddu, María Teresa; Trujillo, Davinia; Cadiñanos, Julen

    2014-01-01

    The term “amyloidosis” encompasses the heterogeneous group of diseases caused by the extracellular deposition of autologous fibrillar proteins. The global incidence of amyloidosis is estimated at five to nine cases per million patient-years. While amyloid light-chain (AL) amyloidosis is more frequent in developed countries, amyloid A (AA) amyloidosis is more common in some European regions and in developing countries. The spectrum of AA amyloidosis has changed in recent decades owing to: an increase in the median age at diagnosis; a percent increase in the frequency of primary AL amyloidosis with respect to the AA type; and a substantial change in the epidemiology of the underlying diseases. Diagnosis of amyloidosis is based on clinical organ involvement and histological evidence of amyloid deposits. Among the many tinctorial characteristics of amyloid deposits, avidity for Congo red and metachromatic birefringence under unidirectional polarized light remain the gold standard. Once the initial diagnosis has been made, the amyloid subtype must be identified and systemic organ involvement evaluated. In this sense, the 123I-labeled serum amyloid P component scintigraphy is a safe and noninvasive technique that has revolutionized the diagnosis and monitoring of treatment in systemic amyloidosis. It can successfully identify anatomical patterns of amyloid deposition throughout the body and enables not only an initial estimation of prognosis, but also the monitoring of the course of the disease and the response to treatment. Given the etiologic diversity of AA amyloidosis, common therapeutic strategies are scarce. All treatment options should be based upon a greater control of the underlying disease, adequate organ support, and treatment of symptoms. Nevertheless, novel therapeutic strategies targeting the formation of amyloid fibrils and amyloid deposition may generate new expectations for patients with AA amyloidosis. PMID:25378951

  14. 75 FR 65279 - Schedule for Rating Disabilities; AL Amyloidosis (Primary Amyloidosis)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... INFORMATION: A final rule was published in the Federal Register at 74 FR 21258 amending 38 CFR 3.309(e) by... the schedule of ratings for the hemic and lymphatic systems to include AL amyloidosis. This regulatory... period, comments are available online through the Federal Docket Management System (FDMS) at...

  15. Rare and unusual clinicopathologic presentation of renal AL amyloidosis

    PubMed Central

    Zuppan, Craig; Pi, Alexander; Zhang, Zhiwei; Jaipaul, Navin

    2016-01-01

    Lesson Rarely, renal light chain (AL) amyloidosis may present without significant proteinuria owing to glomerular sparing and amyloid deposition confined to the vasculature and tubulointerstitium. PMID:27186381

  16. Hereditary amyloidosis

    MedlinePlus

    ... of the blood cells (myeloma) Specific conditions include: Cardiac amyloidosis Cerebral amyloidosis Secondary systemic amyloidosis Treatment A liver transplant may be helpful. Talk to your health care ...

  17. Systemic Amyloidosis and Extraocular Muscle Deposition.

    PubMed

    Shah, Veeral S; Cavuoto, Kara M; Capo, Hilda; Grace, Sara F; Dubovy, Sander R; Schatz, Norman J

    2016-06-01

    Isolated amyloid deposition in an extraocular muscle is a rare event but can be a presenting feature of systemic amyloidosis. A 67-year-old woman with an acquired exotropia and hypertropia was found to have unilateral diffuse extraocular muscle enlargement on magnetic resonance imaging. Owing to the progressive nature of her strabismus and the negative laboratory testing for thyroid disease, she underwent an extraocular muscle biopsy that revealed amyloid deposition. Further workup demonstrated a monoclonal gammopathy consistent with systemic amyloidosis. This case demonstrates the need to consider amyloidosis in the differential diagnosis of patients presenting with an atypical acquired strabismus. We review other reports of isolated amyloid deposition in extraocular muscles and its association with systemic amyloidosis, emphasizing the importance of the ophthalmologist in the early recognition of this disease to prevent irreversible, life-threatening end organ damage. PMID:26967574

  18. Recurrent Syncope and Cardiac Arrest in a Patient with Systemic Light Chain Amyloidosis Treated with Bortezomib.

    PubMed

    Jaipaul, Navin; Pi, Alexander; Zhang, Zhiwei

    2016-05-10

    About 10-15% of patients with multiple myeloma develop light chain (AL) amyloidosis. AL amyloidosis is a systemic disease that may involve multiple organs, often including the heart. It may present clinically with bradyarrhythmia and syncope. The proteasome inhibitor bortezomib has been used with clinical efficacy in treating patients with AL amyloidosis but also implicated as a possible cause of cardiomyocyte injury. We report a case of a 48-year-old man with AL amyloidosis and increased frequency of syncope and cardiac arrest after starting bortezomib. The biologic and clinical plausibility of a heightened risk for cardiac arrest in patients with cardiac AL amyloidosis and history of syncope being treated with bortezomib is a possibility that is not well documented in the medical literature and warrants further investigation. PMID:27499835

  19. Recurrent Syncope and Cardiac Arrest in a Patient with Systemic Light Chain Amyloidosis Treated with Bortezomib

    PubMed Central

    Jaipaul, Navin; Pi, Alexander; Zhang, Zhiwei

    2016-01-01

    About 10-15% of patients with multiple myeloma develop light chain (AL) amyloidosis. AL amyloidosis is a systemic disease that may involve multiple organs, often including the heart. It may present clinically with bradyarrhythmia and syncope. The proteasome inhibitor bortezomib has been used with clinical efficacy in treating patients with AL amyloidosis but also implicated as a possible cause of cardiomyocyte injury. We report a case of a 48-year-old man with AL amyloidosis and increased frequency of syncope and cardiac arrest after starting bortezomib. The biologic and clinical plausibility of a heightened risk for cardiac arrest in patients with cardiac AL amyloidosis and history of syncope being treated with bortezomib is a possibility that is not well documented in the medical literature and warrants further investigation. PMID:27499835

  20. Cholestasis and liver failure with lambda-AL amyloidosis.

    PubMed Central

    Konikoff, F; Mor, C; Stern, S; Shaklai, M; Halevy, J; Theodor, E

    1987-01-01

    Clinically significant liver involvement in systemic amyloidosis, especially with cholestasis, is rare. We report a case of primary amyloidosis with severe intrahepatic cholestasis leading to terminal liver failure. The present case is the first of its kind reported involving Lambda light chains only as the associated paraprotein. Conventional treatment and a therapeutic trial with dimethyl sulphoxide were unsuccessful. Images Fig. 1 Fig. 2 PMID:3115870

  1. Diagnosis of systemic amyloidosis and amyloidosis mediated cardiomyopathy by VATS pleural biopsy for chronic pleural effusion.

    PubMed

    Harvey-Taylor, Jessica; Zhang, Yanhong; Kuderer, Valerie; Cooke, David T

    2013-06-01

    Amyloidosis is a family of diseases characterized by the extracellular accumulation of amyloid protein, causing altered physiology based on its abnormal deposition in an organ. The etiology of persistent pleural effusions in patients with systemic amyloidosis is unknown. Endomyocardial biopsy is the gold standard of diagnosis for patients with cardiac involvement in systemic amyloidosis. We present the case of a patient with systemic amyloidosis whose diagnosis was made by pleural pathology collected via video-assisted thoracic surgery after a false negative endomyocardial biopsy. PMID:23825783

  2. CVID Associated with Systemic Amyloidosis.

    PubMed

    Esenboga, Saliha; Çagdas Ayvaz, Deniz; Saglam Ayhan, Arzu; Peynircioglu, Banu; Sanal, Ozden; Tezcan, Ilhan

    2015-01-01

    Common variable immunodeficiency (CVID) is a frequent primary immune deficiency (PID), which consists of a heterogeneous group of disorders and can present with recurrent infections, chronic diarrhea, autoimmunity, chronic pulmonary and gastrointestinal diseases, and malignancy. Secondary amyloidosis is an uncommon complication of CVID. We report an unusual case of a 27-year-old male patient who presented with recurrent sinopulmonary infections, chronic diarrhea, and hypogammaglobulinemia and was diagnosed with CVID. The patient was treated with intravenous immunoglobulin (IVIg) therapy once every 21 days and daily trimethoprim-sulfamethoxazole for prophylaxis. Two years after initial diagnosis, the patient was found to have progressive decline in IgG levels (as low as 200-300 mg/dL) despite regular Ig infusions. The laboratory tests revealed massive proteinuria and his kidney biopsy showed accumulation of AA type amyloid. We believe that the delay in the diagnosis of CVID and initiation of Ig replacement therapy caused chronic inflammation due to recurrent infections in our patient and this led to an uncommon and life-threatening complication, amyloidosis. Patients with CVID require regular follow-up for the control of infections and assessment of adequacy of Ig replacement therapy. Amyloidosis should be kept in the differential diagnosis when managing patients with CVID. PMID:26346511

  3. CVID Associated with Systemic Amyloidosis

    PubMed Central

    Esenboga, Saliha; Çagdas Ayvaz, Deniz; Saglam Ayhan, Arzu; Peynircioglu, Banu; Sanal, Ozden; Tezcan, Ilhan

    2015-01-01

    Common variable immunodeficiency (CVID) is a frequent primary immune deficiency (PID), which consists of a heterogeneous group of disorders and can present with recurrent infections, chronic diarrhea, autoimmunity, chronic pulmonary and gastrointestinal diseases, and malignancy. Secondary amyloidosis is an uncommon complication of CVID. We report an unusual case of a 27-year-old male patient who presented with recurrent sinopulmonary infections, chronic diarrhea, and hypogammaglobulinemia and was diagnosed with CVID. The patient was treated with intravenous immunoglobulin (IVIg) therapy once every 21 days and daily trimethoprim-sulfamethoxazole for prophylaxis. Two years after initial diagnosis, the patient was found to have progressive decline in IgG levels (as low as 200–300 mg/dL) despite regular Ig infusions. The laboratory tests revealed massive proteinuria and his kidney biopsy showed accumulation of AA type amyloid. We believe that the delay in the diagnosis of CVID and initiation of Ig replacement therapy caused chronic inflammation due to recurrent infections in our patient and this led to an uncommon and life-threatening complication, amyloidosis. Patients with CVID require regular follow-up for the control of infections and assessment of adequacy of Ig replacement therapy. Amyloidosis should be kept in the differential diagnosis when managing patients with CVID. PMID:26346511

  4. Neuroarthropathy of the foot revealing primary systemic amyloidosis: case report and literature review.

    PubMed

    Andrei, Irina Adriana; Kuntzer, Thierry; Lobrinus, Johannes Alexander; Jaccard, Arnaud; Zufferey, Pascal

    2016-02-01

    The aims of this review were to describe the case of a patient with debilitating neuroarthropathy of the ankles and feet and reveal a primary systemic (amyloid light chain, AL) amyloidosis and to review the relevant literature concerning the peripheral neuropathy and neuroarthropathy due to amyloidosis. We will emphasize the diagnostic pitfalls and discuss prognosis and treatments of both the peripheral neuropathy and the arthropathy related to AL amyloidosis. This is a descriptive case report of a patient with neuroarthropathy of the lower limbs due to AL amyloidosis. A review and discussion of relevant literature were conducted, based on a PubMed search from 1973 to December 2013. A 51-year-old female was diagnosed with AL amyloidosis after 20 months of investigation of small painful deformities of the feet. Chronic peripheral neuropathy occurs as a manifestation of AL amyloidosis in 25 % of cases. It may exceptionally be complicated by neuroarthropathy. In this case, the paucity of clinical and electrophysiological signs of the neuropathy delayed the diagnosis, leading to a severe arthropathy. The massive destruction of the joints dominated the clinical and the poor functional outcome. Diagnosis of AL amyloidosis should be considered in the presence of a mild peripheral neuropathy and a distal destructive and painless arthropathy. The two key diagnostic procedures are serum protein electrophoresis and nerve biopsy. Delay in treatment worsens the prognosis. PMID:25227773

  5. Independent Predictors of Survival in Primary Systemic (AL) Amyloidosis, Including Cardiac Biomarkers and Left Ventricular Strain Imaging: An Observational Cohort Study

    PubMed Central

    Bellavia, Diego; Pellikka, Patricia A.; Al-Zahrani, Ghormallah B.; Abraham, Theodore P.; Dispenzieri, Angela; Miyazaki, Chinami; Lacy, Martha; Scott, Christopher G.; Oh, Jae K.; Miller, Fletcher A.

    2014-01-01

    Background The prognostic value of Doppler myocardial imaging, including myocardial velocity imaging, strain, and strain rate imaging, in patients with primary (AL) amyloidosis is uncertain. The aim of this longitudinal study was to identify independent predictors of survival, comparing clinical data, hematologic and cardiac biomarkers, and standard echocardiographic and Doppler myocardial imaging measures in a cohort of patients with AL amyloidosis. Methods A total of 249 consecutive patients with AL amyloidosis were prospectively enrolled. The primary end point was all-cause mortality, and during a median follow-up period of 18 months, 75 patients (30%) died. Clinical and electrocardiographic data, biomarkers (brain natriuretic peptide and cardiac troponin T) and standard echocardiographic and longitudinal systolic and diastolic Doppler myocardial imaging measurements for 16 left ventricular segments were tested as potential independent predictors of survival. Results Age (hazard ratio [HR], 1.03; P = .03), New York Heart Association class III or IV (HR, 2.47; P = .01), the presence of pleural effusion (HR, 1.79; P = .08), brain natriuretic peptide level (HR, 1.29; P = .01), ejection time (HR, 0.99; P = .13), and peak longitudinal systolic strain of the basal anteroseptal segment (HR, 1.05; P = .02) were independent predictors in the final model. Conclusions Multivariate survival analysis identified independent predictors of clinical outcome in patients with AL amyloidosis: New York Heart Association class III or IV, presence of pleural effusion, brain natriuretic peptide level > 493 pg/mL, ejection time < 273 ms, and peak longitudinal systolic basal anteroseptal strain less negative than or equal to −7.5% defined a high-risk group of patients. PMID:20434879

  6. Soluble suppression of tumorigenicity 2 (sST2), but not galactin-3, adds to prognostication in patients with systemic AL amyloidosis independent of NT-proBNP and troponin T.

    PubMed

    Dispenzieri, Angela; Gertz, Morie A; Saenger, Amy; Kumar, Shaji K; Lacy, Martha Q; Buadi, Francis K; Dingli, David; Leung, Nelson; Zeldenrust, Steven; Hayman, Suzanne R; Kapoor, Prashant; Grogan, Martha; Hwa, Lisa; Russell, Stephen J; Go, Ronald S; Rajkumar, S Vincent; Kyle, Robert A; Jaffe, Allan

    2015-06-01

    The use of soluble cardiac biomarkers such as N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin has revolutionized prognostication for patients with AL amyloidosis. Soluble ST2 (sST2) and galectin-3 have also been reported to have prognostic value in other cardiac patient populations. We identified 502 patients with AL amyloidosis, who provided a research sample and consent to review their medical records between 1/1/2006-12/31/2010 within 90 days of their diagnosis. Samples were assayed for sST2 and galectin-3. Within this AL amyloidosis population, overall survival (OS) was 25.5 months (95% CI 18, 35.7 months). Receiver operating curve analyses were done to detect the best cut-points for sST2 and galectin-3 to predict both 1- and 5-year OS. The respective cut points for sST2 were 30 and 29.7 ng/mL, while the median sST2 for the entire population was 31 ng/mL (IQR 19.8, 53.6). The respective cut points for galectin-3 were 11 and 10.4 ng/mL while the median for the entire population was 16.6 ng/mL (IQR 11.5, 24.0). Although on univariate analysis, both sST2 and galectin-3 were prognostic, upon multivariate analysis, only sST2 was independent of troponin, NT-proBNP, serum immunoglobulin free light chain, and blood pressure. Not only did sST2 add to previously reported prognostication systems, but a novel prognostication 5-point system including sST2 was possible. The addition of sST2 - but not galectin-3 - to existing prognostication systems for patients with AL amyloidosis strengthens the ability to predict for death. PMID:25753178

  7. Systemic Amyloidosis: Lessons from β2-Microglobulin*

    PubMed Central

    Stoppini, Monica; Bellotti, Vittorio

    2015-01-01

    β2-Microglobulin is responsible for systemic amyloidosis affecting patients undergoing long-term hemodialysis. Its genetic variant D76N causes a very rare form of familial systemic amyloidosis. These two types of amyloidoses differ significantly in terms of the tissue localization of deposits and for major pathological features. Considering how the amyloidogenesis of the β2-microglobulin mechanism has been scrutinized in depth for the last three decades, the comparative analysis of molecular and pathological properties of wild type β2-microglobulin and of the D76N variant offers a unique opportunity to critically reconsider the current understanding of the relation between the protein's structural properties and its pathologic behavior. PMID:25750126

  8. Primary systemic amyloidosis: A rare cause for pleural effusion.

    PubMed

    George, Sunny; Ravindran, M; Anandan, P T; Kiran, V N

    2014-01-01

    Pleural effusion is a common problem dealt by most of the practicing clinicians. Some causes for pleural effusion are less often considered as a differential diagnosis owing to its rarity. Here we report a case of renal amyloidosis on alternate day haemodialysis for about two months time presenting with left sided pleural effusion. On evaluation this turned out to be a case of amyloidosis on thoracoscopic pleural biopsy suggesting the possibility of Primary systemic amyloidosis. PMID:26029558

  9. Quantitative analysis of interstitial mast cells in AA and AL renal amyloidosis.

    PubMed

    Danilewicz, Marian; Wagrowska-Danilewicz, Małgorzata

    2002-01-01

    Eighteen renal biopsy specimens obtained from patients with AA-type renal amyloidosis (AA) and 11 from patients with AL-type renal amyloidosis (AL), for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available, were examined quantitatively. The cases were selected on the basis of immunohistochemical studies. As a control, we used 10 biopsy specimens from the kidneys removed because of trauma. Morphometric investigations were carried out by a computer image analysis system to find an answer to the question of whether mast cells can correlate with tubulointerstitial fibrosis in AA and AL renal amyloidosis, and to examine the relationship between mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression and interstitial infiltrates. The morphometric study revealed that the mean values of the interstitial tryptase-positive cells, expression of alpha-SMA, interstitial volume, CD68+, CD45RB+, CD43+ and CD20+ cells were increased in AA as compared with the AL group, most of them significantly. Most of these parameters were also significantly increased in both AA and AL patients as compared with the control group. In both the AA group and the AL group, there existed some significant positive correlations between interstitial tryptase-positive cells and interstitial expression of alpha-SMA, interstitial volume and CD68+ cells. Interestingly, in AA cases, but not in AL cases, we noted a significant relationship between interstitial tryptase-positive cells and CD43+ cells. Our findings demonstrate that mast cells belong to the constitutive cell types in the interstitium in renal amyloidosis, in particular in amyloid type A. In addition, in both the AA group and the AL group, the significant positive correlations between interstitial mast cell count and relative interstitial volume and interstitial expression of alpha-SMA suggest that these cells play a role in the development of interstitial

  10. Idiopathic systemic AA-amyloidosis in a skunk (Mephitis mephitis).

    PubMed

    Elhensheri, Mohamed; Linke, Reinhold P; Blankenburg, Anja; Beineke, Andreas

    2012-03-01

    This report describes a case of systemic amyloidosis in a captive striped skunk. At necropsy, bilateral alopecia, as well as reno-, hepato-, and splenomegaly were present. Congo red staining and immunohistochemistry revealed depositions of AA-amyloid in different organs. The lack of a predisposing disease is suggestive of idiopathic systemic AA-amyloidosis. PMID:22448530

  11. Association of acquired von Willebrand syndrome with AL amyloidosis.

    PubMed

    Kos, Cynthia A; Ward, Jennifer E; Malek, Karim; Sanchorawala, Vaishali; Wright, Daniel G; O'Hara, Carl; Connors, Lawreen; Skinner, Martha; Seldin, David C

    2007-05-01

    Acquired loss of functional von Willebrand factor (VWF) has been termed the acquired von Willebrand syndrome (AVWS). AVWS is a rare adult-onset bleeding diathesis that is clinically similar to congenital von Willebrand disease (VWD), and occurs with a variety of autoimmune, lymphoproliferative, or myeloproliferative disorders. We have identified four patients with AVWS in association with immunoglobulin light chain (AL) amyloidosis. These patients, lacking any pre-existing or family history of abnormal bleeding, developed cutaneous, mucosal, or gastrointestinal bleeding in the course of their disease without deficiency of clotting factor X or other factors; the activated partial thromboplastin time (aPTT) was prolonged in three out of the four cases. Despite normal VWF antigen levels, VWF ristocetin cofactor activity (VWF:RCo) was low. Electrophoresis patterns of high molecular weight (HMW) VWF multimers were abnormal in two of the four cases. Two of the patients were treated with high-dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) and achieved hematologic remission. In these two patients, the bleeding diathesis improved and the coagulation parameters normalized, confirming a causal relationship between the plasma cell dyscrasia and the AVWS. AVWS should be considered in AL amyloidosis patients with hemorrhagic diatheses and normal clotting factor levels. PMID:17205535

  12. Systemic AA amyloidosis in the common marmoset.

    PubMed

    Ludlage, E; Murphy, C L; Davern, S M; Solomon, A; Weiss, D T; Glenn-Smith, D; Dworkin, S; Mansfield, K G

    2005-03-01

    The common marmoset (Callithrix jacchus) is a small New World primate native to Brazil that has been used extensively in biomedical research. A retrospective analysis of archived hematoxylin and eosin-stained tissue sections and clinical records was conducted at the New England Primate Research Center on 86 marmosets more than 1 year of age that were euthanized during the past decade because of morbidity and failure to thrive. Approximately 17% (15 of 86) were found to have amyloid deposits in one or more organs, including the liver, adrenal glands, kidneys, and intestine. This material was shown by amino acid sequence analysis to be composed of serum amyloid A (SAA)-related protein. This type of amyloidosis, designated AA or "secondary," is associated typically with an inflammatory process that induces elevated levels of the SAA amyloidogenic precursor molecule. Notably, there were no significant pathologic differences or other distinguishing features in animals with amyloid versus those without; furthermore, on the basis of the limited number of serum specimens available for analysis, the SAA concentrations in the two groups were comparable, thus suggesting the possible inheritable nature of the disorder. In this respect, the common marmoset provides a unique experimental model for study of the pathogenesis and treatment of AA and other forms of systemic amyloidosis. PMID:15753464

  13. (99m)Tc-HMDP scintigraphy rectifies wrong diagnosis of AL amyloidosis.

    PubMed

    Galat, Arnault; Van Der Gucht, Axel; Colombat, Magali; Attias, David; Itti, Emmanuel; Meignan, Michel; Lebras, Fabien; Molinier-Frenkel, Valérie; Benhaiem, Nicole; Guellich, Aziz; Rosso, Jean; Damy, Thibaud

    2015-08-01

    A 71-year-old African man without history of cardiac disease was referred to our center for dyspnea. Transthoracic echocardiogram and cardiac MRI were suggestive of cardiac amyloidosis (CA). The diagnosis of the light-chain cardiac amyloidosis (AL-CA) was made after a first endomyocardial biopsy. Accordingly chemotherapy was started. Systematic 99mTc-HMDP scintigraphy showed moderate cardiac uptake (visual score of 2), unusual for AL-CA, and permitted to rectify the diagnosis. Hereditary transthyretin cardiac amyloidosis was confirmed by a second endomyocardial biopsy with a positive Congo-red and anti-transthyretin antibody stainings, mass spectrometry and genetic analysis (Val122Ile mutation). PMID:26002815

  14. Transmission of systemic AA amyloidosis in animals.

    PubMed

    Murakami, T; Ishiguro, N; Higuchi, K

    2014-03-01

    Amyloidoses are a group of protein-misfolding disorders that are characterized by the deposition of amyloid fibrils in organs and/or tissues. In reactive amyloid A (AA) amyloidosis, serum AA (SAA) protein forms deposits in mice, domestic and wild animals, and humans that experience chronic inflammation. AA amyloid fibrils are abnormal β-sheet-rich forms of the serum precursor SAA, with conformational changes that promote fibril formation. Extracellular deposition of amyloid fibrils causes disease in affected animals. Recent findings suggest that AA amyloidosis could be transmissible. Similar to the pathogenesis of transmissible prion diseases, amyloid fibrils induce a seeding-nucleation process that may lead to development of AA amyloidosis. We review studies of possible transmission in bovine, avian, mouse, and cheetah AA amyloidosis. PMID:24280941

  15. Clinical benefits of bortezomib-containing regimens for newly diagnosed AL amyloidosis with severe cardiac impairment.

    PubMed

    Tsukune, Yutaka; Yahata, Yuriko; Sasaki, Makoto; Hiki, Makoto; Tsutsui, Miyuki; Hamano, Yasuharu; Itoh, Seigo; Miyazaki, Tetsuro; Dohi, Tomotaka; Maruyama, Masaki; Gotoh, Akihiko; Komatsu, Norio

    2016-08-01

    Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis. PMID:27599413

  16. Alopecia in Systemic Amyloidosis: Trichoscopic-Pathologic Correlation

    PubMed Central

    Miteva, Mariya; Wei, Erin; Milikowski, Clara; Tosti, Antonella

    2015-01-01

    Alopecia in systemic amyloidosis is very rare and has been described as individual cases of diffuse nonscarring alopecia and a case of alopecia universalis. We report the trichoscopic findings in alopecia associated with systemic amyloidosis. The most prominent feature was a salmon colored halo (0.3-1 mm in diameter) surrounding the follicular ostia. Other features included broken hairs and black dots. The salmon colored halo correlated on pathology with the perifollicular deposition of amyloid. The horizontal sections showed that the sebaceous glands were preserved which supports the nonscarring pattern of the alopecia. PMID:26903748

  17. Presumptive service connection for disease associated with exposure to certain herbicide agents: AL amyloidosis. Final rule.

    PubMed

    2009-05-01

    This document amends the Department of Veterans Affairs (VA) adjudication regulations concerning presumptive service connection for a certain disease based on the most recent National Academy of Sciences (NAS) Institute of Medicine committee report, "Veterans and Agent Orange: Update 2006" (Update 2006). This amendment is necessary to implement a decision of the Secretary of Veterans Affairs that there is a positive association between exposure to herbicides used in the Republic of Vietnam during the Vietnam era and the subsequent development of AL amyloidosis. The intended effect of this amendment is to establish presumptive service connection for AL amyloidosis based on herbicide exposure. PMID:19507326

  18. Nonsecretory Multiple Myeloma and AL Amyloidosis Presenting with Nephrotic Range Proteinuria

    PubMed Central

    Beyler Kilic, Ozlem; Oguz, Ali Kemal; Ergun, Ihsan; Baydar, Dilek Ertoy; Ayli, Meltem

    2015-01-01

    Nonsecretory multiple myeloma (NSMM) is the absence of a detectable monoclonal protein in serum and urine of a multiple myeloma (MM) patient and immunoglobulin light chain (AL) amyloidosis is a significantly rare complication. A case of NSMM with AL amyloidosis and nephrotic range proteinuria is presented. Sharing clinical, therapeutic, and prognostic characteristics with MM, real challenge may be during initial diagnosis of NSMM and assessment of treatment response. In elderly patients with unexplained renal dysfunction, MM should be in the differential diagnosis and the absence of a monoclonal protein should not rule out MM but should remind us of the possibility of NSMM. PMID:26090243

  19. Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis.

    PubMed

    Kastritis, Efstathios; Papassotiriou, Ioannis; Terpos, Evangelos; Roussou, Maria; Gavriatopoulou, Maria; Komitopoulou, Anna; Skevaki, Chrysanthi; Eleutherakis-Papaiakovou, Evangelos; Pamboucas, Constantinos; Psimenou, Erasmia; Manios, Efstathios; Giannouli, Stavroula; Politou, Marianna; Gakiopoulou, Harikleia; Papadopoulou, Elektra; Stamatelopoulos, Kimon; Tasidou, Anna; Dimopoulos, Meletios A

    2016-07-21

    Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which endothelium function is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction, whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease. We measured the serum levels of VWF (VWF:Ag) and ADAMTS-13 antigens in 111 newly diagnosed patients with AL amyloidosis. The levels of VWF:Ag were significantly higher than in healthy controls; 76% of patients with AL had VWF:Ag levels higher than the upper levels of controls. There was no significant association of VWF:Ag levels with patterns of organ involvement, free light-chain levels, the levels of cardiac biomarkers, or renal dysfunction but correlated with low systolic blood pressure. VWF:Ag levels ≥230.0 U/dL were associated with higher probability of early death and poor survival independently of cardiac biomarkers and low systolic blood pressure (SBP). Moreover, among patients with Mayo stage III or stage IIIB (that is stage III with N-terminal pro-brain natriuretic peptide [NTproBNP] >8500 pg/mL) disease, VWF:Ag identified subgroups of patients with very poor outcome. Low ADAMTS-13 levels correlated with high levels of NTproBNP but had no independent prognostic significance. In conclusion, high VWF:Ag levels, probably representing endothelial dysfunction, are associated with prognosis in patients with AL amyloidosis, independently of other features of the disease or cardiac biomarkers. PMID:27166361

  20. Primary systemic amyloidosis as a real diagnostic challenge – case study

    PubMed Central

    Jerzykowska, Sonia; Gil, Lidia A.; Balcerzak, Andrzej; Pupek-Musialik, Danuta; Komarnicki, Mieczysław A.

    2014-01-01

    Primary amyloidosis (AL) is a rare variety of plasma cell dyscrasia, the diagnosis of which is often difficult to establish. Pathogenesis of amyloidosis involves extracellular deposition of insoluble protein fibrils in tissues, leading to insufficiency of affected organs. According to various sources, mean survival rate of patients with primary amyloidosis ranges from 12 to 24 months, making primary amyloidosis a disease with a very poor prognosis. Survival rate is significantly lowered in case of cardiac manifestation of amyloidosis (about 6 months survival in untreated patients). In recent years a considerable progress in AL treatment has been observed. Nowadays we are able not only to delay progression of amyloidosis, but also to improve the function of the affected organs. Unfortunately as first signs and symptoms of AL are usually nonspecific, the diagnosis of AL is often delayed, resulting in late introduction of optimal therapy. There are many diagnostic tests which can be used in diagnostic process of amyloidosis, i.e. electrophoresis, serum and urine immunofixation or affected organs and bone marrow biopsy. On establishing the diagnosis in a patient with suspected amyloidosis it should be remembered that particular diagnostic methods vary considerably in sensitivity. The aim of this paper is to present a case report of a 27-year-old patient with primary amyloidosis focusing on diagnostic aspect of this condition. On the basis of this case, the authors would like to emphasize the value of precise diagnostic process, with immunological techniques playing undoubtedly a crucial role. PMID:26155101

  1. Cardiac Amyloidosis

    MedlinePlus

    ... abbreviation AL stands for Amyloidosis formed from Light chains, and it is a disease of the bone ... proteins that make up antibodies, known as light chains. These light chains circulate in the blood and ...

  2. Bilateral kidney infarction due to primary Al amyloidosis: a first case report.

    PubMed

    Mihout, Fabrice; Joseph, Laure; Brocheriou, Isabelle; Leblond, Véronique; Varnous, Shaïda; Ronco, Pierre; Plaisier, Emmanuelle

    2015-05-01

    Primary Amyloid Light-chain (AL) amyloidosis is a rare form of plasma cell dyscrasia characterized by tissue deposition of monoclonal immunoglobulin light chain. Kidney involvement is the most frequent manifestation, and patients usually present with glomerular disease.We report an exceptional case of bilateral kidney infarcts caused by AL amyloidosis. A 34-years-old man presented with progressive dyspnea, loin pain, recurrent macroscopic hematuria, and acute kidney injury. Computed tomography showed bilateral kidney infarcts.The diagnosis of AL amyloidosis was established on the kidney biopsy with the characterization of major vascular amyloid deposits that selectively stained with antilambda light chain antibody. An amyloid restrictive cardiomyopathy was also present, responsible for the life-threatening conduction disturbance, but without patent cardioembolic disease. The patient then underwent emergency heart transplantation, followed by a conventional chemotherapy with bortezomib, melphalan, and dexamethasone. More than 3 years later, the patient has subnormal renal function, a well-functioning heart transplant, and a sustained hematologic response.In addition to the very uncommon presentation, this case illustrates the tremendous progress that has occurred in the management of severe forms of AL amyloidosis. PMID:25929920

  3. Marked shrinkage of amyloid lymphadenopathy after an intensive chemotherapy in a patient with IgM-associated AL amyloidosis.

    PubMed

    Tazawa, Ko-Ichi; Katoh, Nagaaki; Shimojima, Yasuhiro; Matsuda, Masayuki; Ikeda, Shu-Ichi

    2009-12-01

    A male patient with primary AL amyloidosis who had been suffering from systemic lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab followed by autologous peripheral blood stem cell transplantation. Four years after complete hematological remission he showed marked reduction in size of the amyloid-laden lymph nodes. Deposits of AL amyloid may regress from the tissue if the chemotherapy succeeds in persistent inhibition of the production of an amyloidogenic immunoglobulin light chain. PMID:19922338

  4. Marked shrinkage of amyloid lymphadenopathy after an intensive chemotherapy in a patient with IgM-associated AL amyloidosis.

    PubMed

    Tazawa, Ko-Ichi; Katoh, Nagaaki; Shimojima, Yasuhiro; Matsuda, Masayuki; Ikeda, Shu-Ichi

    2009-01-01

    A male patient with primary AL amyloidosis who had been suffering from systemic lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab followed by autologous peripheral blood stem cell transplantation. Four years after complete hematological remission he showed marked reduction in size of the amyloid-laden lymph nodes. Deposits of AL amyloid may regress from the tissue if the chemotherapy succeeds in persistent inhibition of the production of amyloidogenic immunoglobulin light chains. PMID:19590992

  5. Primary amyloidosis

    MedlinePlus

    ... Swelling in the arms and legs Weak hand grip Weight loss Other symptoms that may occur with ... kidney involvement may lead to organ failure and death. Body-wide ( systemic ) amyloidosis can lead to death ...

  6. A patient with AL amyloidosis with negative free light chain results.

    PubMed

    Milani, Paolo; Valentini, Veronica; Ferraro, Giovanni; Basset, Marco; Russo, Francesca; Foli, Andrea; Palladini, Giovanni; Merlini, Giampaolo

    2016-06-01

    The detection and quantification of amyloidogenic monoclonal light chains are necessary for the diagnosis and evaluation of response to treatment in AL amyloidosis. However, the amyloid clone is often small and difficult to detect. We report the case of a 68-year-old man who was referred to our Center in April 2013 after syncope and the identification of left ventricular hypertrophy at echocardiography, suspected for amyloidosis. A commercial agarose gel electrophoresis immunofixation (IFE) did not reveal monoclonal components in serum and urine. The κ serum free light chain (FLC) concentration was 21.5 mg/L, λ 33 mg/L (κ/λ ratio 0.65), NT-proBNP 9074 ng/L (u.r.l. <332 ng/L) and an echocardiogram confirmed characteristic features of amyloidosis. The abdominal fat aspiration was positive and the amyloid typing by immune-electron microscopy revealed λ light chains deposits. A high-resolution (hr) IFE of serum and urine showed a faint monoclonal λ component in the urine. A bone marrow biopsy showed 8% plasma cells (BMPC) and a kappa/lambda light-chain restriction with λ light chain on immunofluorescence. The diagnosis of AL (λ) amyloidosis with cardiac involvement was made. In May 2013, patient was started on cyclophosphamide, bortezomib and dexamethasone. After six cycles, serum and urine hr-IFE were negative, the bone marrow biopsy showed 3% BMPC without light chain restriction by immunofluorescence, and a decrease of NT-proBNP was observed (5802 ng/L).Thus, treatment was discontinued. In this patient the amyloid clone could be detected only by in house hr-IFE of urine and bone marrow examination. The detection of the small dangerous amyloidogenic clone should be pursued with a combination of high-sensitivity techniques, including assessment of BMPC clonality. Studies of novel tools, such as mass spectrometry on serum and next-generation flow cytometry analysis of the bone marrow, for detecting plasma cell clones in AL amyloidosis and other monoclonal light

  7.  Liver transplantation followed by autologous stem cell transplantation for acute liver failure caused by AL amyloidosis. Case report and review of the literature.

    PubMed

    Elnegouly, Mayada; Specht, Katja; Zoller, Heinz; Matevossian, Edouard; Bassermann, Florian; Umgelter, Andreas

    2016-01-01

     Hepatic involvement in AL amyloidosis may present as acute liver failure. Historically, liver transplantation in these cases has achieved poor outcomes due to progress of amyloidosis and non-hepatic organ damage. In the era of bortezomib treatment, the prognosis of AL amyloidosis has been markedly improved and may also result in better post-transplant outcomes. We present a case of isolated acute liver failure caused by AL amyloidosis, bridged to transplantation with bortezomib and treated with sequential orthotopic liver transplantation (OLT) and autologous stem cell transplantation. The patient is in stable remission 3 years after OLT. PMID:27236160

  8. Undiagnosed light chain systemic amyloidosis: does it matter to anesthesiologists? -a case report-.

    PubMed

    Kim, Gwan Ho; Lee, Woo Kyung; Na, Se Hee; Lee, Jong Seok

    2013-11-01

    Light chain systemic amyloidosis is rare but may accompany laryngeal or pulmonary involvement, which may increase the risk in airway management. We present a case of a patient planned for resection of cervical epidural mass. The patient had face and neck ecchymoses and purpuras with an unknown cause. Mask ventilation and intubation were successful, but the operation was cancelled to evaluate bleeding from facial skin lesions. A diagnosis of light chain systemic amyloidosis prompted evaluation of involvement of other organs and treatment. This case shows the importance of preoperative evaluation and careful airway management in patients with systemic amyloidosis. PMID:24363850

  9. Primary Systemic Amyloidosis with Unusual Dermatological Manifestations: A Rare Case Report

    PubMed Central

    Vyas, Kapil; Morgaonkar, Manjaree; Gupta, Savera; Jain, Suresh Kumar

    2016-01-01

    Amyloidosis is a group of heterogeneous diseases characterized by pathological deposition of proteinaceous substance extracellularly in various tissues. The clinical presentation depends on the site of amyloid deposition, with predominant involvement of mesenchymal elements and cutaneous findings in 30–40% of patients in case of primary systemic amyloidosis. We present a case of idiopathic primary systemic amyloidosis presenting with an unusual finding of nodulo-ulcerative lesion over tongue along with multiple skin-colored nodules, mimicking squamous cell carcinoma of tongue with secondary cutaneous metastasis, as well as lacking the classical presentation of purpura, macroglossia, waxy papules, and plaques. PMID:27057028

  10. Primary Systemic Amyloidosis and High Levels of Angiotensin-Converting Enzyme: Two Case Reports

    PubMed Central

    Praena-Segovia, J.; Sanchez-Gastaldo, A.; Bernabeu-Wittel, M.; Ocete-Pérez, R.; Ávila-Polo, R.; Martino, M. L.

    2013-01-01

    Infiltrative heart diseases are caused by a heterogeneous group of disorders; amyloidosis and sarcoidosis are two frequent causes of myocardial infiltration, which differ in clinical and biological outcome and treatment issues. The presence of high levels of angiotensin-converting enzyme (ACE) in a patient with infiltrative heart disease may increase suspicion of sarcoidosis. Nevertheless, no mention about increased ACE levels in extracerebral primary systemic amyloidosis is available. We present two cases of primary systemic amyloidosis, which are cardiac involvement and elevated ACE levels. PMID:24826302

  11. Utility of Doppler Myocardial Imaging, Cardiac Biomarkers and Clonal Immunoglobulin Genes to Assess Left Ventricular Performance and Stratify Risk Following Peripheral Blood Stem Cell Transplantation in Patients with Systemic Light Chain Amyloidosis (AL)

    PubMed Central

    Bellavia, Diego; Abraham, Roshini S.; Pellikka, Patricia A.; Dispenzieri, Angela; Burnett, John C.; Al-Zahrani, Ghormallah B.; Green, Tammy D.; Manske, Michelle K.; Gertz, Morie A.; Miller, Fletcher A.; Abraham, Theodore P.

    2011-01-01

    Cardiac dysfunction is a well-recognized complication of light chain amyloidosis (AL). Autologous stem cell transplant (auto-SCT) has emerged as a successful treatment modality for AL patients. In this study, we examined the effect of clonal immunoglobulin light chain genes (VL), which encodes the immunoglobulin light chain protein that ultimately forms amyloid, on cardiac function, in the context of auto-SCT and its impact on overall survival. Longitudinal Doppler myocardial imaging parameters along with cardiac biomarkers were used to assess for cardiac function pre and post auto-SCT. VL gene analysis revealed that Vλ genes, in particular VλVI, were associated with worse cardiac function parameters than Vκ genes. Clonal VL genes appeared to have an impact on left ventricular (LV) function post-transplant and also influenced mortality, with specific VL gene families associated with lower survival. Another key predictor of mortality in this report was change in tricuspid regurgitant flow velocity following auto-SCT. Correlations were also observed between systolic strain rate, systolic strain and VL genes associated with amyloid formation. In summary, clonal VL gene usage influences global cardiac function in AL, with patients having VλVI and VλII-III-associated amyloid more severely affected than those having Vκ or VλI amyloid. Pulsed wave tissue Doppler imaging along with immunoglobulin gene analysis offers novel insights into prediction of mortality and cardiac dysfunction in AL after auto-SCT. PMID:21315556

  12. Immunohistochemical identification of heparan sulphate proteoglycan in secondary systemic amyloidosis.

    PubMed Central

    Norling, B; Westermark, G T; Westermark, P

    1988-01-01

    The distribution of proteoglycans in kidneys from patients with secondary (AA) systemic amyloidosis was investigated. Antisera reacting with the protein cores of chondroitin sulphate proteoglycan (CSPG), dermatan sulphate proteoglycan (DSPG) and heparan sulphate proteoglycan (HSPG) were used in conjunction with the peroxidase-antiperoxidase (PAP) method. HSPG was the only proteoglycan found to be specifically localized to the amyloid deposits. The staining was most intense on the endothelial side of the deposits in both the glomeruli and in the vessel walls. No staining was observed after absorption of the HSPG antiserum with a fraction of the amyloid preparations, corresponding in size to that reported for glomerular HSPG. The possible role of HSPG and endothelial cells in the pathogenesis of the amyloid deposits is discussed. Images Fig. 1 Fig. 2 Fig. 3 PMID:3052949

  13. Nodular immunocyte-derived (AL) amyloidosis in the trachea of a dog.

    PubMed

    Besancon, M Faulkner; Stacy, Brian A; Kyles, Andrew E; Moore, Peter F; Vernau, William; Smarick, Sean D; Rasor, Liberty A

    2004-04-15

    A 7-year-old castrated male Miniature Schnauzer was examined because of labored breathing and episodes of respiratory distress that progressed to collapse. On cervical radiographs, a focal soft tissue mass in the caudal cervical portion of the trachea was observed, and during tracheoscopy, a 1 x 1 cm, pedunculated, multinodular, pink, intraluminal mass extending from the dorsal tracheal membrane and obstructing approximately 80% of the tracheal lumen was seen. Tracheal resection and anastomosis was performed to remove the mass, and the dog recovered without complications. On histologic examination, the mass consisted of a large accumulation of homogeneous, faintly fibrillar eosinophilic material admixed with a predominantly plasma cell infiltrate; examination of sections stained with thioflavin T and Congo red stain confirmed that the eosinophilic material was amyloid. A diagnosis of nodular, immunocyte-derived (AL) amyloidosis was made. Seventeen months after surgery, the dog had a relapse of respiratory distress because of an extramedullary plasmacytoma involving the trachea. PMID:15112779

  14. Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

    PubMed Central

    Vrana, Julie A.; Theis, Jason D.; Dasari, Surendra; Mereuta, Oana M.; Dispenzieri, Angela; Zeldenrust, Steven R.; Gertz, Morie A.; Kurtin, Paul J.; Grogg, Karen L.; Dogan, Ahmet

    2014-01-01

    Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis. PMID:24747948

  15. T1 mapping and survival in systemic light-chain amyloidosis

    PubMed Central

    Banypersad, Sanjay M.; Fontana, Marianna; Maestrini, Viviana; Sado, Daniel M.; Captur, Gabriella; Petrie, Aviva; Piechnik, Stefan K.; Whelan, Carol J.; Herrey, Anna S.; Gillmore, Julian D.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Hawkins, Philip N.; Moon, James C.

    2015-01-01

    Aims To assess the prognostic value of myocardial pre-contrast T1 and extracellular volume (ECV) in systemic amyloid light-chain (AL) amyloidosis using cardiovascular magnetic resonance (CMR) T1 mapping. Methods and results One hundred patients underwent CMR and T1 mapping pre- and post-contrast. Myocardial ECV was calculated at contrast equilibrium (ECVi) and 15 min post-bolus (ECVb). Fifty-four healthy volunteers served as controls. Patients were followed up for a median duration of 23 months and survival analyses were performed. Mean ECVi was raised in amyloid (0.44 ± 0.12) as was ECVb (mean 0.44 ± 0.12) compared with healthy volunteers (0.25 ± 0.02), P < 0.001. Native pre-contrast T1 was raised in amyloid (mean 1080 ± 87 ms vs. 954 ± 34 ms, P < 0.001). All three correlated with pre-test probability of cardiac involvement, cardiac biomarkers, and systolic and diastolic dysfunction. During follow-up, 25 deaths occurred. An ECVi of >0.45 carried a hazard ratio (HR) for death of 3.84 [95% confidence interval (CI): 1.53–9.61], P = 0.004 and pre-contrast T1 of >1044 ms = HR 5.39 (95% CI: 1.24–23.4), P = 0.02. Extracellular volume after primed infusion and ECVb performed similarly. Isolated post-contrast T1 was non-predictive. In Cox regression models, ECVi was independently predictive of mortality (HR = 4.41, 95% CI: 1.35–14.4) after adjusting for E:E′, ejection fraction, diastolic dysfunction grade, and NT-proBNP. Conclusion Myocardial ECV (bolus or infusion technique) and pre-contrast T1 are biomarkers for cardiac AL amyloid and they predict mortality in systemic amyloidosis. PMID:25411195

  16. Bortezomib-based induction for transplant ineligible AL amyloidosis and feasibility of later transplantation.

    PubMed

    Cornell, R F; Zhong, X; Arce-Lara, C; Atallah, E; Blust, L; Drobyski, W R; Fenske, T S; Pasquini, M C; Rizzo, J D; Saber, W; Hari, P N

    2015-07-01

    Recent studies support the use of bortezomib-based therapies in light chain amyloidosis (AL). We performed a retrospective analysis of the safety, efficacy and long-term survival (median follow-up 3 years) after bortezomib-based treatment in 28 consecutive patients with de novo AL deemed ineligible at initial presentation. The first 14 patients received bortezomib and dexamethasone (VD), and the second 14 patients received cyclophosphamide, bortezomib and dexamethasone (CVD; CyBorD). Both regimens were well tolerated with no treatment-related mortality. The overall hematological response (HR) rate was 93% in both the groups. Median time to response was shorter in the CVD group (39 days vs 96 days in the VD group; P=0.002). Hematological and organ responses induced with bortezomib-based therapy enabled 8 (33%) of initially transplant ineligible patients to undergo autologous hematopoietic stem cell transplantation (AHCT), including 4 patients with cardiac stage III or IV. Seven of the eight patients (88%) who underwent subsequent AHCT achieved sustained HR at a median of 33 months posttransplant. These data suggest that bortezomib-based induction followed by AHCT is a viable therapeutic strategy for transplant-ineligible AL. Larger, multicenter prospective trials are necessary to confirm our findings. PMID:25915809

  17. Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis): Severity and Risk Factors.

    PubMed

    Gaffney, P M; Witte, C; Clifford, D L; Imai, D M; O'Brien, T D; Trejo, M; Liberta, F; Annamalai, K; Fändrich, M; Masliah, E; Munson, L; Sigurdson, C J

    2016-05-01

    Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum AA (SAA) from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli (98% [n= 78 of 80] vs 56% [n= 45], respectively;P< .0001), and medullary deposition was more commonly severe (19% [n= 20 of 105]) as compared with glomeruli (7% [n= 7];P= .01). Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes as compared with free-ranging foxes (ORs = 3.2, 3.7, respectively; overall P= .05) and for females as compared with males (OR = 2.9;P= .05). Multivariable logistic regression revealed that independent risk factors for amyloid development were increasing age class (OR = 3.8;P< .0001), San Clemente Island subspecies versus San Nicolas Island subspecies (OR = 5.3;P= .0003), captivity (OR = 5.1;P= .0001), and nephritis (OR = 2.3;P= .01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis. PMID:26419399

  18. Cardiac amyloidosis

    MedlinePlus

    ... heart signals Prednisone, an anti-inflammatory medicine A heart transplant may be considered for people with some types of amyloidosis who have very poor heart function. People with hereditary amyloidosis may need a liver transplant.

  19. A rare case of acute lymphoblastic leukemia in a patient with light chain (AL) amyloidosis treated with lenalidomide

    PubMed Central

    Nair, Ranjit; Gheith, Shereen; Popescu, Dan; Agostino, Nicole M

    2014-01-01

    Lenalidomide belongs to a novel class of drugs called Immunomodulators which are now being used for the treatment of plasma cell dyscrasias with variable degrees of efficacy and toxicity. Though Second Primary Malignancies (SPM) have been a concern with its use, the benefits of the treatment outweigh the risks. The leukemogenic risk seems to be potentiated especially when combined with alkylating agents and the SPMs documented are predominantly myeloblastic. To date there are no reported cases of new lymphocytic leukemias in AL amyloidosis, regardless of whether undergone treatment or not. We present a case of AL amylodosis who was treated with lenalidomide and subsequently developed acute lymphoblastic leukemia. PMID:24966987

  20. Nodular amyloidosis derived from keratinocytes: an unusual type of primary localized cutaneous nodular amyloidosis.

    PubMed

    Cornejo, Kristine M; Lagana, Frances J; Deng, April

    2015-11-01

    Primary, localized cutaneous amyloidosis includes macular, lichen, and nodular (tumefactive) types in which the amyloid deposits are limited to the dermis without systemic involvement. The material in lichen and macular amyloidosis is derived from epidermal keratinocytes [keratinocyte-derived amyloid (AK)], whereas that in nodular amyloidosis is derived from immunoglobulin light-chains amyloid (AL). Primary, localized cutaneous nodular amyloidosis (PLCNA) is a form of primary, localized cutaneous amyloidosis that has been associated with a risk of progression to systemic amyloidosis. We report an unusual case of nodular AK-type amyloid deposited in the dermis of the feet. The patient is a 60-year-old woman with asymptomatic verrucoid-like lesions present around the medial and lateral aspects of the bilateral heels for 1-2 years. A biopsy showed massive deposition of eosinophilic amorphous material in the papillary and reticular dermis. The material stained positive for Congo red with apple-green birefringence on polarized light. It was also positive for pan-cytokeratin and negative for kappa and lambda light-chain immunostains. An extensive workup was negative for systemic involvement. Lipid chromatography tandem mass spectrometry confirmed that the deposition was AK-type amyloid. We believe that this is the first case of PLCNA with AK deposition. This entity should be included in the differential diagnosis of PLCNA so that an extensive systemic workup may be avoided. PMID:26485243

  1. Serum transthyretin levels in senile systemic amyloidosis: effects of age, gender and ethnicity.

    PubMed

    Buxbaum, Joel; Koziol, James; Connors, Lawreen H

    2008-12-01

    Serum transthyretin (TTR) levels are reduced in familial amyloidotic polyneuropathy (FAP). A single study of patients with senile systemic amyloidosis (SSA) in Sweden found that those individuals also had a significantly lower mean serum TTR concentration than age- and gender-matched controls. To determine if the same phenomenon prevailed in an ethnically more heterogeneous population, we compared the serum TTR levels, as determined by ELISA, in 45 documented SSA patients with congestive heart failure, 20 AL patients with congestive heart failure and population controls. Serum TTR concentrations in the controls were influenced in a statistically significant manner by age, gender and ethnicity. Although it is unlikely that such differences are clinically relevant, they must be considered when assessing the meaning of serum TTR concentrations in any clinically defined population. The serum concentrations in patients with SSA did not differ from age, gender and ethnically matched controls or from a group of AL patients with significant clinical cardiac involvement. We also compared TTR concentrations in 12 African-Americans carrying the TTR V122I allele with those in 826 African-Americans who were homozygous wild type at the TTR locus. The TTR V122I carriers had significantly lower serum TTR concentrations than appropriate controls even though the majority of such individuals had not reached the age of clinical or anatomic risk, i.e. over 60. Thus, as in carriers of other TTR mutations the serum TTR level is lower than normal, despite having a much later appearance of clinical disease. PMID:19065297

  2. [The concurrence of light-chain deposition disease, AL-amyloidosis, and cast nephropathy in a patient with multiple myeloma].

    PubMed

    Rekhtina, I G; Zakharova, E V; Stoliarevich, E S; Sinitsina, M N; Denisova, E N

    2015-01-01

    Despite of the fact that their clinical manifestations are similar, AL-amyloidosis (AL-A) and light chain deposition disease (LCDD) are individual nosological entities in view of considerable differences in their pathogenesis and pathomorphology. The paper describes a rare case of the concurrence of LCDD and AL-A in a patient with multiple myeloma. Clinically, there was dialysis-dependent renal failure, flail leg syndrome, myocardiopathy, and rhabdomyolysis. At the disease onset, his nephrobiopsy specimen could diagnose LCDD and myeloma or cast nephropathy. The disease was characterized by an aggressive course. Despite the administration of innovative agents, the patient had a short-term remission and died from disease progression. Autopsy additionally revealed amyloid deposition in the heart and kidney. The development of AL-A in the presence of prior LCDD may reflect the progression of the tumor and the appearance of an additional subclone of plasma cells that produce amyloidogenic light chains. The uncommonness of this case is that renal amyloid was found in the tubular casts and absent in the glomeruli, which may be considered as a special form--tubular AL-amyloidosis. PMID:26281203

  3. Extracorporeal Membrane Oxygenation as Bridge-to-Decision in Acute Heart Failure due to Systemic Light-Chain Amyloidosis

    PubMed Central

    Silva, Jennifer Mancio; Fontes-Carvalho, Ricardo; Valente, Dília; Almeida, Cristiana; Cruz, António José; Tente, David; Coelho, Henrique; Oliveira, Marco; Albuquerque, Aníbal; Ribeiro, Vasco Gama

    2015-01-01

    Patient: Female, 58 Final Diagnosis: Acute hear failure Symptoms: Dispnoea • edema • fatigue Medication: — Clinical Procedure: Bone marrow biopsy • endomyocardial biopsy • abdominal subcutaneous fat biopsy under ECMO support Specialty: Cardiology Objective: Rare disease Background: Cardiac amyloidosis results from the amyloid deposition in heart tissue, either in the context of a systemic disease or as a localized form. Several pro-amyloid proteins can produce amyloid deposits in the heart. Each of these amyloidoses has characteristic clinical (cardiac and extracardiac) features, and a specific diagnosis and treatment. Case Report: A 58-year-old woman who presented with acute heart failure and echocardiographic findings strongly suggestive of infiltrative cardiomyopathy needed percutaneous veno-arterial extracorporeal membrane oxygenation (ECMO) as bridge-to-decision. Amyloid deposition was found on endomyocardial and bone marrow biopsies. Bone marrow plasma cell infiltrate with acute renal lesion and hypercalcemia confirmed the diagnosis of multiple myeloma-associated systemic light-chain amyloidosis (AL). Refractory shock with multi-organic failure syndrome persisted and no improvements in left ventricular function and structure were seen. After extensive discussion by a multidisciplinary team, and with the patients’ family, she was not considered eligible for high-dose chemotherapy and/or autologous stem cell transplantation, heart transplantation, or sequential heart with autologous stem cell transplantation. The patient died a few hours after ECMO withdrawal. During the 14 days of ECMO support no major bleeding or thrombotic complications occurred. Conclusions: The clinician must consider a diagnosis of cardiac amyloidosis in patients with heart failure, a restrictive type of cardiomyopathy with ventricular hypertrophy in the absence of valve abnormalities, or uncontrolled arterial hypertension. Although developments in chemotherapy have greatly

  4. [Light Chain Amyloidosis: an Update for Treatment].

    PubMed

    Shen, Kai-Ni; Li, Jian

    2015-06-01

    Systemic light chain amyloidosis (AL amyloidosis) is the most common type of amyloidosis, in which deposition of misfolded monoclonal light chain secreted by underlying clonal plasma cells leads to organ dysfunction. Tissue biopsy of involved organ is needed to confirm the type of amyloid deposits, thus proper treatment could be applied. Laser microdissection followed by mass spectrometry, performed on formalin-fixed paraffin-embedded specimens, has been proven superior to traditional methods on accurate diagnosis of amyloidosis. Prognosis depends on the extent of cardiac involvement. The Mayo staging system using NT-ProBNP, cardiac troponin-T and free light chain, is the most robust method for risk stratification and treatment guidance. The introduction of autologous stem cell transplantation (auto-ASCT) resulted in long-term survival in responders, while treatment-related toxicity substantially limited the number of eligible candidates. Novel agents, especially bortezomib, thalidomide and lenalidomide hold promise to achieve comparable hematological responses with auto-ASCT, which might play significant role in treatment of recurrent or refractory AL amyloidosis. PMID:26117060

  5. Primary Amyloidosis Presenting as Upper Limb Multiple Mononeuropathies

    PubMed Central

    Tracy, Jennifer A.; Dyck, Peter J.; Dyck, P. James B.

    2010-01-01

    Peripheral neuropathy in primary (AL) amyloidosis is usually lower limb predominant, length-dependent, symmetrical, and affects small (pain and autonomic) fibers, as much or more than large fibers. We report a patient with step-wise progressive, multiple upper limb mononeuropathies that were due to nerve biopsy-proven primary amyloidosis (lambda light chain), with no systemic or autonomic features. Recognition that light chain amyloidosis may be the cause of a multiple mononeuropathy pattern adds to the differential diagnosis of this clinical phenotype. PMID:20405503

  6. An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis.

    PubMed

    Sanchorawala, V; Wright, D G; Seldin, D C; Dember, L M; Finn, K; Falk, R H; Berk, J; Quillen, K; Skinner, M

    2001-10-01

    Primary or AL amyloidosis results from a plasma cell dyscrasia in which fibrillar light chain protein deposition leads to organ failure and death. Standard treatment for AL amyloidosis has been oral melphalan and prednisone. However, this form of treatment modifies the natural history of this lethal disease only marginally, extending median survival from 13 months following diagnosis to 17 months. At Boston University Medical Center, we have developed treatment protocols using high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) to treat AL amyloidosis, and we have treated over 200 patients with HDM/SCT during the past six years. This extensive experience has shown that patients with AL amyloidosis, despite multisystem involvement and compromised organ function can tolerate this aggressive form of treatment. Furthermore, HDM/SCT results in durable hematologic responses in a substantial proportion of patients, and such responses are associated with clinical improvement, decreased amyloid-related organ dysfunction, and prolonged survival. However, toxicity from treatment is high (overall peri-transplant mortality, 14%), particularly for those patients with clinically significant cardiac involvement. For this reason, we believe a multidisciplinary management approach is essential when using HDM/SCT for treatment of AL amyloidosis. Based on our experience, we believe that HDM/SCT is the treatment of choice for patients with AL amyloidosis who have a good performance status and limited cardiac involvement at the time of diagnosis. HDM/SCT offers the best chance for hematologic remission, prolongation of survival, and reversal of amyloid-related disease. At the same time, we believe that HDM/SCT should continue to be examined in the context of clinical trials, directed at developing approaches to broaden the applicability of this therapy by minimizing toxicity and to increase the likelihood of complete hematologic responses

  7. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip

    PubMed Central

    Arahata, Masahisa; Shimadoi, Shigeru; Yamatani, Satosi; Hayashi, Shin-ichi; Miwa, Shigeharu; Asakura, Hidesaku; Nakao, Shinji

    2016-01-01

    Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. PMID:27540285

  8. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip.

    PubMed

    Arahata, Masahisa; Shimadoi, Shigeru; Yamatani, Satosi; Hayashi, Shin-Ichi; Miwa, Shigeharu; Asakura, Hidesaku; Nakao, Shinji

    2016-01-01

    Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. PMID:27540285

  9. Pulmonary arterial hypertension in primary amyloidosis

    PubMed Central

    Emerson, Lyska L.; Bull, David A.; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C.; Ryan, John J.

    2016-01-01

    Abstract Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852

  10. Pulmonary arterial hypertension in primary amyloidosis.

    PubMed

    Cirulis, Meghan M; Emerson, Lyska L; Bull, David A; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C; Ryan, John J

    2016-06-01

    Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852

  11. Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis

    PubMed Central

    Sun, Yijuan; Sandhu, Amarpreet; Gabaldon, Darlene; Danaraj, Jonathan; Servilla, Karen S.; Tzamaloukas, Antonios H.

    2012-01-01

    AL amyloidosis complicating monoclonal gammopathy of undetermined significance (MGUS) has usually a predominant glomerular deposition of lambda light chain. Heavy proteinuria is one of its cardinal manifestations. A 78-year-old man with a 9-year history of IgG kappa light-chain-MGUS and normal urine protein excretion developed severe renal failure. Serum levels of kappa light chain and serum IgG had been stable while proteinuria was absent throughout the nine-year period. For the first eight years, he had stable stage III chronic kidney disease attributed to bladder outlet obstruction secondary to prostatic malignancy. In the last year, he developed progressive serum creatinine elevation, without any increase in the serum or urine levels of paraproteins or any sign of malignancy. Renal ultrasound and furosemide renogram showed no evidence of urinary obstruction. Renal biopsy revealed AL amyloidosis, with reactivity exclusive for kappa light chains, affecting predominantly the vessels and the interstitium. Glomerular involvement was minimal. Melphalan and prednisone were initiated. However, renal function continues deteriorating. Deposition of AL kappa amyloidosis developing during the course of MGUS predominantly in the wall of the renal vessels and the renal interstitium, while the involvement of the glomeruli is minimal, leads to progressive renal failure and absence of proteinuria. Renal biopsy is required to detect both the presence and the sites of deposition of renal AL kappa light chain amyloidosis. PMID:24555136

  12. [Treatment of amyloidosis with dimethyl sulfoxide (DMSO)].

    PubMed

    Morassi, P; Massa, F; Mesesnel, E; Magris, D; D'Agnolo, B

    1989-01-01

    In this study we have investigated the role of oral dimethylsulfoxide (DMSO) therapy in 2 patients with primary amyloidosis (AL) and in 2 patients with secondary amyloidosis (AA) to long-standing rheumatoid arthritis. DMSO treatment produced no beneficial effects in the patients with idiopathic amyloidosis. Instead the patients with secondary amyloidosis experienced a subjective improvement, a decrease of inflammatory activity of the rheumatoid arthritis and an unequivocal improvement of renal function following 3-6 months of DMSO therapy. No serious side effects of DMSO were observed except for unpleasant breath odour. We conclude that a treatment with oral DMSO may prolong life of patients with secondary amyloidosis. PMID:2915815

  13. Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis.

    PubMed

    Sečník, Peter; Honsová, Eva; Jabor, Antonín; Lavríková, Petra; Franeková, Janka

    2016-06-01

    The objective of this study was to demonstrate the necessity of using different methods for amyloidogenic light chain detection. Serum and urine agarose gel electrophoresis and immunofixation, as well as serum free light chain (FLC) immunoassay measurements, were evaluated in a patient with verified multiple myeloma and consequent AL amyloidosis confirmed by Congo red staining and immunofluorescence techniques. Conventional chemistry tests [serum and urine electrophoresis (SPE and UPE); serum and urine immunofixation (SIFE and UIFE)] were inconclusive. Only quantitative FLC immunoassay (serum free light chain immunoanalysis, SFLC) provided correct diagnostic information. A combination of gel-based SIFE and UIFE with more novel quantitative FLC immunoassays appears necessary when searching for monoclonal immunoglobulin light chain-related diseases. PMID:26760309

  14. Sinonasal Globular Amyloidosis Simulating Malignancy: A Rare Presentation.

    PubMed

    Kumar, Binay; Pant, Bhawna; Kumar, Vikrant; Negi, Meghna

    2016-09-01

    Primary localized amyloidosis in the head and neck region is a rare entity. The most commonly involved organ is larynx. Primary amyloidosis localized to the sinonasal tract is extremely rare. We report one such case along with a brief review of the associated literature. The aim of reporting this case is to emphasize the fact that sometimes nasal amyloidosis can also present with signs and symptoms of nasal and nasopharyngeal malignancy. The definitive diagnosis in such cases depends upon histopathology and further confirmed by immunohistochemistry. A 55-year old male presented with recurrent episodes of nasal bleed, bilateral nasal obstruction, and bilateral hearing loss from last 7 years. On clinical examination a mass was found in the nasal cavity on both sides reaching up to the nasopharynx. Contrast enhanced CT scan revealed that the mass was extending up to the skull base and destroying bony landmarks of the nasal cavity and paranasal sinuses. Mass was proved to be amyloidosis after histopathological examination. It showed multiple blotches of globular submucosal deposit of amyloid, on staining with Congo red. Immunohistochemistry confirmed AL amyloidosis with expression of mixed kappa and lambda light chain immunoglobulin (κ > λ). No evidence of systemic amyloidosis was found after proper work up. It was managed by conservative surgery. PMID:26780770

  15. Colchicine Treatment for Tracheobronchial Amyloidosis.

    PubMed

    Morales, Arturo; Pari, Marizell; López-Lisbona, Rosa; Cubero, Noelia; Dorca, Jordi; Rosell, Antoni

    2016-01-01

    Tracheobronchial amyloidosis is an infrequent disease characterized by the deposition of proteinaceous material in the tracheobronchial tree. The disease generally has a high morbidity and variable mortality in the years following diagnosis. There is no consensus on the optimal treatment. We report a case of a 63-year-old woman who presented with a diffuse tracheobronchial amyloidosis associated with laryngeal involvement, which required a percutaneous tracheostomy due to high-grade subglottic stenosis, with no evidence of systemic amyloidosis. After treatment exclusively with colchicine, she had a complete resolution of the stenotic area, with a very good response from the tracheobronchial amyloidosis disease, with only minor yellow plaques persisting. The patient has remained asymptomatic in the next 4 years of follow-up, with no evidence of endoscopic progression. This is the first documented case of this kind of response of tracheobronchial amyloidosis to colchicine treatment alone. A review of the available literature is presented. PMID:26855229

  16. Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis.

    PubMed

    Sahota, T; Berges, A; Barton, S; Cookson, L; Zamuner, S; Richards, D

    2015-02-01

    The amyloid deposits that cause disease in systemic amyloidosis always contain the normal plasma protein, serum amyloid P (SAP) component. SAP is the target of a novel immunotherapy approach now being developed to eliminate amyloid deposits. The treatment is enabled by, and critically depends on, the use of the drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, GSK2315698, Ro 63-8695), which depletes circulating SAP almost completely but leaves some SAP in amyloid deposits for specific recognition by subsequently administered therapeutic anti-SAP antibodies. Herein, we report a mechanistic model that predicts, with clinically acceptable precision, the exposure-response relationship for CPHPC, both in healthy individuals and in patients with systemic amyloidosis. The model covariates are gender, renal function, total amyloid load, and presence of hepatic amyloid, all of which are known at baseline. The model is being used to predict individualized dosing regimens in an ongoing, first-in-human study with anti-SAP antibodies. PMID:26225229

  17. Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis

    PubMed Central

    Sahota, T; Berges, A; Barton, S; Cookson, L; Zamuner, S; Richards, D

    2015-01-01

    The amyloid deposits that cause disease in systemic amyloidosis always contain the normal plasma protein, serum amyloid P (SAP) component. SAP is the target of a novel immunotherapy approach now being developed to eliminate amyloid deposits. The treatment is enabled by, and critically depends on, the use of the drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, GSK2315698, Ro 63-8695), which depletes circulating SAP almost completely but leaves some SAP in amyloid deposits for specific recognition by subsequently administered therapeutic anti-SAP antibodies. Herein, we report a mechanistic model that predicts, with clinically acceptable precision, the exposure-response relationship for CPHPC, both in healthy individuals and in patients with systemic amyloidosis. The model covariates are gender, renal function, total amyloid load, and presence of hepatic amyloid, all of which are known at baseline. The model is being used to predict individualized dosing regimens in an ongoing, first-in-human study with anti-SAP antibodies. PMID:26225229

  18. The relationship between the antioxidant system, oxidative stress and dialysis-related amyloidosis in hemodialysis patients.

    PubMed

    Celik, Gulperi; Capraz, Irfan; Yontem, Mustafa; Bilge, Murat; Unaldi, Mustafa; Mehmetoglu, Idris

    2013-11-01

    End-stage renal disease (ESRD) is associated with several complications that are partly due to excess amounts of reactive oxygen species and/or decreased antioxidant activity. Dialysis-related amyloidosis (DRA) has also been linked to increased oxidative stress. The aim of this study was to investigate the relationships between the antioxidant system, including superoxide dismutase (SOD), malonyldialdehyde (MDA), various biochemical parameters and shoulder amyloidosis, in hemodialysis patients. We studied 107 non-diabetic chronic dialysis patients. The SOD levels correlated with right and left biceps tendon thickness (r = -0.219, P = 0.048 and r = -0.236, P = 0.031, respectively), MDA (r = -0.429, P = 0.000) and albumin levels (r = -0.319, P = 0.001). MDA levels correlated with right and left biceps thickness (r = 0.291, P = 0.006 and r = 0.337, P = 0.001, respectively) and β2 microglobulin levels (r = 0.455, P = 0.000). We also identified the statistically significant relationships between MDA levels and supraspinatus tendon thickening (greater than 7 mm) and right and left biceps tendon thickness (P = 0.022, P = 0.040 and P = 0.005, respectively). Our data suggest the complex relationship between antioxidants and oxidative stress and further support the roles of oxidative stress and antioxidants in DRA. PMID:24231477

  19. Systemic amyloidosis involving the diaphragm and acute massive hydrothorax during peritoneal dialysis.

    PubMed

    Gagnon, R F; Thirlweil, M; Arzoumanian, A; Mehio, A

    2002-06-01

    Hydrothorax secondary to trans-diaphragmatic fluid leakage through a peritoneo-pleural communication is an occasional, potentially serious complication of peritoneal dialysis. The etiology of this condition is not clear, being thought to be due either to congenital or acquired diaphragmatic fenestrations or acquired scarcity of muscle fibers in the tendinous part of the diaphragm which are compounded by increased intra-abdominal pressure during the dwell period of peritoneal dialysis. We report a 54-year-old woman who developed irreversible acute renal failure from adjuvant chemotherapy for ovarian cancer previously resected surgically. Three days after the onset of continuous ambulatory peritoneal dialysis, she developed acute respiratory distress associated with a massive right hydrothorax secondary to a peritoneo-pleural communication demonstrated by scintigraphy. At autopsy 2 weeks later, systemic amyloidosis was surprisingly found and histologic examination of the right hemidiaphragm showed the presence of amyloid, among sparse muscle fibers. This is the first case report of a distinct pathological process, i.e. amyloidosis, involving the diaphragm associated with a peritoneo-pleural communication causing massive hydrothorax at the onset of peritoneal dialysis. PMID:12078953

  20. Nuclear Imaging of Amyloidosis

    PubMed Central

    Cytawa, Wojciech; Teodorczyk, Jacek; Lass, Piotr

    2014-01-01

    Summary Amyloidosis is a clinical condition caused by deposition of various protein fibrills in extracellular space. The presented symptoms depend on the type of deposits and the organ or organs involved. The correct diagnosis is often difficult, due to lack of nonivasive imaging techniques and insufficiency of morphological imaging procedures delievered by radiology. We presented a list of potential radiopharmaceuticals that can be used in detecting various types of amyloidoses. 123I-SAP proved to have high sensitivity in imaging of AA and AL amyloidosis in visceral organs. 99mTc-Aprotinin was found to be useful in detecting cardiac amyloidosis. A couple of classical radiotracers, such as 201Tl, 123I-mIBG, together with 111In-antimyosin were also tested for accuracy in cardiac imaging, however the main problem was low specificity. Potential applicability was also found in case of some bone-seeking agents and other radiotracers, e.g. 67Ga-citrate and 99mTc-penta-DMSA. High sensitivity and specificity was achieved with β2-microglobulin labeled with 131I or 111In. Among PET tracers, 11C-PIB deserves more attention, because it may have an important role in diagnosing of AD in the near future. Further clinical studies are expected to take place, because noninvasive diagnosing and monitoring of amyloidosis is still a challenge. PMID:25071873

  1. Amyloidosis and Kidney Disease

    MedlinePlus

    ... body has fewer red blood cells than normal. Dialysis-related Amyloidosis People who suffer from kidney failure ... weight loss [ Top ] What are the symptoms of dialysis-related amyloidosis? The symptoms of dialysis-related amyloidosis ...

  2. Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study.

    PubMed

    Bochtler, Tilmann; Hegenbart, Ute; Kunz, Christina; Benner, Axel; Kimmich, Christoph; Seckinger, Anja; Hose, Dirk; Goldschmidt, Hartmut; Granzow, Martin; Dreger, Peter; Ho, Anthony D; Jauch, Anna; Schönland, Stefan O

    2016-07-28

    Cytogenetic aberrations detected by interphase fluorescence in situ hybridization (iFISH) of plasma cells are routinely evaluated as prognostic markers in multiple myeloma. This long-term follow-up study aimed to assess the prognosis of systemic light chain amyloidosis (AL) patients treated with high-dose melphalan (HDM) chemotherapy and autologous stem cell transplantation, depending on iFISH results. Therefore, we analyzed a consecutive cohort of 123 AL patients recruited from 2003 to 2014. HDM was safe, with only 1 of 123 patients dying as a result of treatment-related mortality, and effective, with a complete remission (CR) rate of 34%. Translocation t(11;14) as the most prevalent aberration (59%) led to an improved CR rate after high-dose therapy (41.2% vs 20.0%; P = .02), translating into a prolonged hematologic event-free survival (hemEFS; median, 46.1 vs 28.1 months; P = .05) and a trend for better overall survival (median, not reached vs 93.7 months; P = .07). In multivariate analysis, t(11;14) was confirmed as a favorable prognostic factor regarding hemEFS along with lower values for the difference between involved and uninvolved free light chains. Conversely, deletion 13q14, gain of 1q21, and hyperdiploidy had no significant prognostic impact. The high-risk cytogenetic aberrations t(4;14), t(14;16), and del(17p13) conferred an unfavorable prognosis, although statistical significance was reached only for univariate CR analysis in this small group of 9 patients. Thus, t(11;14) positivity in HDM-treated AL patients conferred superior CR rates and hemEFS. In view of the reduced response of t(11;14) to bortezomib, this highlights the impact of therapy on the prognostic role of cytogenetic aberrations. PMID:27257181

  3. A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype.

    PubMed

    Tougaard, Birgitte G; Pedersen, Katja Venborg; Krag, Søren Rasmus; Gilbertson, Janet A; Rowczenio, Dorota; Gillmore, Julian D; Birn, Henrik

    2016-09-01

    Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion. It is a form of systemic amyloidosis, but at presentation, can also mimic localized amyloidosis. The renal presentation generally involves interstitial and medullary deposition of apo A-I amyloid protein. We describe the identification of apo A-I amyloidosis by mass spectrometry in a 52-year old male, with no family history of amyloidosis, presenting with nephrotic syndrome and associated with heterozygosity for a novel APOA1 mutation (c.220 T > A) which encodes the known amyloidogenic Trp50Arg variant. Renal amyloid deposits in this case were confined to the glomeruli alone, and the patient developed progressive renal impairment. One year after diagnosis, the patient had a successful kidney transplant from an unrelated donor. Pathogenic mutations in the APOA1 gene are generally associated with symptoms of amyloidosis. In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations. PMID:27240838

  4. 18F-fluorodeoxyglucose positron emission tomography might be useful for diagnosis of hepatic amyloidosis

    PubMed Central

    Tawada, Akinobu; Kanda, Tatsuo; Oide, Takashi; Tsuyuguchi, Toshio; Imazeki, Fumio; Nakatani, Yukio; Yokosuka, Osamu

    2014-01-01

    We report on a woman with hepatic involvement of primary systemic (immunoglobulin light chain, AL) amyloidosis. Her diagnosis was confirmed by liver biopsy. Clinical symptoms of hepatic amyloidosis are generally mild at its first stage, with most frequent findings being hepatomegaly and alkaline phosphatase elevation. Recent advances in the understanding of the pathophysiology of systemic amyloidosis have made several treatments available. However, its prognosis is occasionally poor. Because liver biopsy is not always safe, other modalities for the diagnosis are needed. Of interest was that fluorodeoxyglucose (FDG) uptake into the liver was observed, compared with that into the spleen, in this patient, indicating that FDG positron emission tomography and computed tomography might be useful for the diagnosis of hepatic amyloidosis with mild liver dysfunction. PMID:25018655

  5. Ocular Myasthenia Gravis Associated With Thymic Amyloidosis.

    PubMed

    Chapman, Kristin O; Beneck, Debra M; Dinkin, Marc J

    2016-03-01

    A 45-year-old woman with ptosis and diplopia was found to have myasthenia gravis (MG) associated with amyloidosis of the thymus gland. Systemic MG is frequently associated with thymomas or thymic hyperplasia but has only once previously been reported in association with amyloidosis of the thymus. This case demonstrates that isolated ocular MG rarely may also be associated with amyloidosis of the thymus. PMID:25822660

  6. Genetic factors in amyloidosis.

    PubMed Central

    Thomas, P K

    1975-01-01

    In the absence of biochemical distinctions, the nosography of the inherited amyloidoses must at present depend largely upon clinical subdivisions. In the broad classification adopted here, the disorders have for convenience been grouped according to the anatomical system that is predominantly affected. It is evident that the amyloid syndromes display considerable heterogeneity. However, they overlap. Thus in the Iowa type classified with the hereditary amyloid neuropathies (van Allen et al, 1969; Gimeno et al, 1974), renal involvement was frequent and was the usual cause of death. In the English (Zalin et al, 1974) and Scandinavian (Andersson, 1970) families with neuropathy as the predominant feature, cardiac involvement was a common finding. In certain of the conditions discussed, such as medullary carcinoma of the thyroid and Down's syndrome, amyloid deposition is merely an incidental aspect of the disorder. In those conditions in which generalized or localized amyloid deposition occupies a more central position in the clinical syndrome, an autosomal dominant inheritance has been established or suggested in the majority. An autosomal recessive inheritance has so far only been recognized in familial Mediterranean fever. In the family with hereditary amyloid heart diseases reported by Fredricksen et al (1962), the disorder was confined to a single sibship, raising the possibility of recessive inheritance. This could also be true in sporadic examples of primary amyloidosis. The dominantly inherited amyloidoses comprise a number of geographically widely scattered families with clinical pictures that do not show consistent differences between some families. The families that do not show consistent differences are not necessarily harbouring nutations at the same locus, or the same mutation at any particular locus. However, many of these dominantly inherited clinical syndromes are sufficiently different from each other and the clinical manifestations of each

  7. Cardiac Amyloidosis Presenting With Cardiogenic Shock.

    PubMed

    Afzal, Ashwad; Brener, Sorin J; Narula, Navneet; Worku, Berhane; Gulkarov, Iosif

    2016-01-01

    Cardiac amyloidosis is an infiltrative disorder of the myocardium. It is the result of one of 4 types of amyloidosis: primary systemic (immunoglobulin light chain), secondary, familial (hereditary), or senile. Cardiac amyloidosis ultimately causes congestive heart failure due to irreversible restrictive cardiomyopathy. Because of the rapid progression of the disease, early recognition and determination of underlying etiology are important for tailored therapy. Current interventions range from conservative heart failure management to autologous stem cell and heart transplantation. We present a case of cardiac amyloidosis accompanying undiagnosed multiple myeloma to illustrate the rapid progression of the disease and the complexities of diagnosing and treating this disorder. PMID:26177555

  8. Current perspectives on cardiac amyloidosis

    PubMed Central

    Guan, Jian; Mishra, Shikha; Falk, Rodney H.

    2012-01-01

    Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either local tissue or systemic amyloidosis, with nine of them manifesting in cardiac deposition and resulting in a syndrome termed “cardiac amyloidosis” or “amyloid cardiomyopathy.” Although cardiac amyloidosis has been traditionally considered to be a rare disorder, as clinical appreciation and understanding continues to grow, so too has the prevalence, suggesting that this disease may be greatly underdiagnosed. The most common form of cardiac amyloidosis is associated with circulating amyloidogenic monoclonal immunoglobulin light chain proteins. Other major cardiac amyloidoses result from a misfolding of products of mutated or wild-type transthyretin protein. While the various cardiac amyloidoses share a common functional consequence, namely, an infiltrative cardiomyopathy with restrictive pathophysiology leading to progressive heart failure, the underlying pathophysiology and clinical syndrome varies with each precursor protein. Herein, we aim to provide an up-to-date overview of cardiac amyloidosis from nomenclature to molecular mechanisms and treatment options, with a particular focus on amyloidogenic immunoglobulin light chain protein cardiac amyloidosis. PMID:22058156

  9. A hepatitis C-positive patient with new onset of nephrotic syndrome and systemic amyloidosis secondary to common variable immunodeficiency.

    PubMed

    Turkmen, Kultigin; Anil, Melih; Solak, Yalcin; Atalay, Huseyin; Esen, Hasan; Tonbul, Halil Z

    2010-01-01

    Common variable immunodeficiency (CVID) is a heterogenous group of predominantly antibody-deficiency disorders that make up the greatest proportion of patients with symptomatic primary hypogammaglobulinemia. The rare coincidence of amyloidosis and hypogammaglobulinemia has been reported previously. Contrary to the usual insidious, slowly progressive disease following hepatitis C infection, a rapidly progressive cirrhotic form can develop in hypogammaglobulinemic patients. We report a HCV-positive patient with a new onset of nephrotic syndrome and systemic amyloidosis secondary to CVID. Blood analyses showed serum creatinine of 1.8 mg/dL and serum albumin of 3.1 gm/dL; 24-h urinary protein was 11 800 mg/day. Serum immunoglobulin levels were IgG 340 mg/dL, IgM 18 mg/dL, IgA 11 mg/dL. Duodenal biopsy revealed AA-type amyloidosis with potassium permanganate and Congo red staining. After a month of antiproteinuric therapy, the proteinuria was reduced to 3350 mg/day. PMID:20697163

  10. Nephrotic Syndrome Associated with Lung Cancer: A Rare Case of Malignancy Associated with AA Amyloidosis

    PubMed Central

    Gueutin, Victor; Langlois, Anne-Lyse; Shehwaro, Nathalie; Elharraqui, Ryme; Rouvier, Philippe; Izzedine, Hassane

    2013-01-01

    Nonhematologic malignancies are rarely reported to be associated with AA amyloidosis. Although the association between renal cell carcinoma and systemic AA amyloidosis has been established, the evidence linking pulmonary cancer to AA amyloidosis is scarce. Here, a case of biopsy-proven renal AA amyloidosis complicated with nephrotic syndrome associated with lung carcinoma is reported. PMID:24558629

  11. Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone +/- thalidomide for systemic light-chain amyloidosis: results of a phase II trial.

    PubMed

    Cohen, Adam D; Zhou, Ping; Chou, Joanne; Teruya-Feldstein, Julie; Reich, Lilian; Hassoun, Hani; Levine, Beth; Filippa, Daniel A; Riedel, Elyn; Kewalramani, Tarun; Stubblefield, Michael D; Fleisher, Martin; Nimer, Stephen; Comenzo, Raymond L

    2007-10-01

    High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. We performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients (n = 45) with newly diagnosed AL involving < or =2 organ systems were assigned to MEL 100, 140, or 200 mg/m(2) with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). Organ involvement was kidney (67%), heart (24%), liver/GI (22%) and peripheral nervous system (18%), with 31% having two organs involved. TRM was 4.4%. Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement in haematological response. By intention-to-treat, overall haematological response rate was 71% (36% complete response), with 44% having organ responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients. PMID:17897298

  12. AA amyloidosis in vaccinated growing chickens.

    PubMed

    Murakami, T; Inoshima, Y; Sakamoto, E; Fukushi, H; Sakai, H; Yanai, T; Ishiguro, N

    2013-01-01

    Systemic amyloid-A (AA) amyloidosis in birds occurs most frequently in waterfowl such as Pekin ducks. In chickens, AA amyloidosis is observed as amyloid arthropathy. Outbreaks of systemic amyloidosis in flocks of layers are known to be induced by repeated inflammatory stimulation, such as those resulting from multiple vaccinations with oil-emulsified bacterins. Outbreaks of fatal AA amyloidosis were observed in growing chickens in a large scale poultry farm within 3 weeks of vaccination with multiple co-administered vaccines. This study documents the histopathological changes in tissues from these birds. Amyloid deposits were also observed at a high rate in the tissues of apparently healthy chickens. Vaccination should therefore be considered as a potential risk factor for the development of AA amyloidosis in poultry. PMID:23570943

  13. The clinical spectrum of IgM-related amyloidosis: a French nationwide retrospective study of 72 patients.

    PubMed

    Terrier, Benjamin; Jaccard, Arnaud; Harousseau, Jean-Luc; Delarue, Richard; Tournilhac, Olivier; Hunault-Berger, Mathilde; Hamidou, Mohamed; Dantal, Jacques; Bernard, Marc; Grosbois, Bernard; Morel, Pierre; Coiteux, Valérie; Gisserot, Olivier; Rodon, Philippe; Hot, Arnaud; Elie, Caroline; Leblond, Véronique; Fermand, Jean-Paul; Fakhouri, Fadi

    2008-03-01

    Immunoglobulin M (IgM)-related amyloidosis remains a rare and little-known complication of monoclonal IgM-associated disorders. We sought to determine the clinical and laboratory presentation, response to treatment, and outcome of patients with IgM-related amyloidosis in the era of new therapeutic approaches. We conducted a retrospective study in 29 French centers to identify patients with monoclonal IgM and biopsy-proven amyloidosis; we reviewed patients' records and collected relevant clinical and laboratory data. We identified 72 patients with IgM-related amyloidosis. Systemic primary amyloidosis (AL) was present in 64, peritumoral AL in 5, and systemic secondary amyloidosis (AA) in 3 patients. A peculiar pattern of relatively frequent lymph node (31%) and lung (17%) involvement was noted in patients with systemic AL amyloidosis. Response to alkylating agents was poor, with a hematologic response in 37%, a complete remission in 0%, and an organ response in 21%. Response to hematopoietic stem cell transplantation showed a hematologic response in 100% with complete remission in 75% and an organ response in 75%. Purine analogs and rituximab induced a hematologic response in 73% and 60%, respectively, with complete remission in 9% and 0% and an organ response in 55% and 0%, respectively. In multivariate analysis, prognostic factors for survival were serum albumin level < or =3.5 g/dL (p = 0.018) and heart involvement (p = 0.0034). Further prospective studies are needed in patients with IgM-related amyloidosis, with special emphasis on treatment options: hematopoietic stem cell transplantation and purine analogs could represent the most effective therapies. The identification of adverse prognostic factors of survival could be useful for those managing and making treatment decisions for these patients. PMID:18344807

  14. Current trends in diagnosis and management of cardiac amyloidosis.

    PubMed

    Esplin, Brandt L; Gertz, Morie A

    2013-02-01

    Amyloidosis is a rare disease in which insoluble extracellular protein fibrils in β-pleated sheets infiltrate multiple organs, causing organ dysfunction and failure. Amyloidoses are generally classified into light chain or primary systemic amyloidosis, hereditary amyloidosis (most commonly, transthyretin amyloidosis), senile systemic amyloidosis, secondary amyloidosis, and isolated atrial amyloidosis. At least 100 different amyloidogenic proteins have been identified in humans and can be differentiated by mass spectroscopy after laser capture microdissection and genetic testing. Organ involvement can include kidneys, skin, blood vessels, central and peripheral nervous systems, lungs, liver, intestines, and heart. Developments in noninvasive techniques are facilitating earlier and more accurate diagnosis. Management depends on the specific disease type, thus early and accurate diagnosis is imperative. Prognosis generally correlates with degree of cardiac involvement but varies widely with specific amyloid protein type. New treatment strategies involving chemotherapy and organ transplantation are improving survival, but prognosis is guarded. PMID:23337445

  15. Diagnosis and typing of systemic amyloidosis: The role of abdominal fat pad fine needle aspiration biopsy

    PubMed Central

    Halloush, Ruba A; Lavrovskaya, Elena; Mody, Dina R; Lager, Donna

    2009-01-01

    Introduction: Systemic amyloidosis (SA) has a broad nonspecific clinical presentation. Its diagnosis depends on identifying amyloid in tissues. Abdominal fat pad fine needle aspiration (FPFNA) has been suggested as a sensitive and specific test for diagnosing SA. Materials and Methods: Thirty-nine FPFNA from 38 patients (16 women and 20 men, age range 40–88 years) during a 15-year period were reviewed. Smears and cell blocks were stained with Congo red (CR). A panel of antibodies (serum amyloid protein, serum amyloid A, albumin, transthyretin, kappa light chain and lambda light chain) was used on six cell blocks from five patients. The FNA findings were correlated with clinical and histological follow-up. Results: FPFNAs were positive, confirmed by CR in 5/39 (13%), suspicious in 1/39 (3%), negative in 28/39 (72%), and insufficient for diagnosis in 5/39 (13%) of cases. In all the positive cases, SA was confirmed within 2–16 weeks. Among the 28 negative cases, SA was diagnosed in 21, the rest were lost to follow-up. Among the insufficient cases, SA was diagnosed in four and one was lost to follow-up. Specificity was 100%, whereas sensitivity was 19%. SA typing using cell block sections was successful in three, un-interpretable in one, and negative in two cases. Conclusion: FPFNA for SA is not as good as previously reported. This may be due to different practice setting, level of experience, diagnostic technique, or absence of abdominal soft tissue involvement. A negative result of FPFNA does not exclude SA. Immune phenotyping of amyloid is possible on cell block. PMID:20165547

  16. Coexistent asymptomatic myeloma and hereditary cardiac amyloidosis: an unusual case of heart failure.

    PubMed

    Lee, Lydia; Aziz, Michael; Wechalekar, Ashutosh; Rabin, Neil

    2011-11-01

    A 76-year-old Afro-Caribbean man presenting with heart failure was diagnosed with isolated cardiac amyloid. He had evidence of myeloma on bone marrow biopsy suggesting AL amyloid, the commonest type of systemic amyloidosis, as the underlying cause. He had no other myeloma-related organ damage. However, endocardial biopsy revealed amyloid fibrils composed of transthyretin and genetic typing established heterozygozity for the valine to isoleucine mutation at position 122 (Val122Ile). The diagnosis was therefore hereditary systemic amyloidosis as a result of a genetic transthyretin variant (ATTR) causing cardiac amyloidosis and coexistent asymptomatic myeloma. This requires symptomatic treatment of heart failure only. This article discusses a rare cause of heart failure and uses this case to illustrate that histological confirmation of the amyloid-causing protein is essential. Mistaken assumption of AL amyloid could have resulted in inappropriate cytotoxic therapy targeting the plasma cell clone. PMID:22083004

  17. Emerging Advances in the Management of Cardiac Amyloidosis.

    PubMed

    Vranian, Michael N; Sperry, Brett W; Valent, Jason; Hanna, Mazen

    2015-11-01

    Amyloidosis is a disease in which proteins misfold, aggregate into fibrils, and deposit extracellularly disrupting organ architecture and function. There are two main types which affect the heart: light chain (AL) amyloidosis and transthyretin cardiac amyloidosis (ATTR). There is a misconception that cardiac amyloidosis has no effective treatment options. However, over the past decade, there has been extensive research and drug development. Outcomes are improving in AL amyloidosis with evolving chemotherapeutic regimens and novel monoclonal antibodies. In ATTR, therapies that decrease protein production, prevent dissociation, and promote clearance have the potential to slow or even halt a disease which is uniformly fatal. Selected patients may be candidates for heart and/or stem cell transplant and should be promptly referred to an experienced amyloid program. Herein, we discuss the emerging advances for the treatment of cardiac amyloidosis. PMID:26374453

  18. Recent advances in the diagnosis and management of cardiac amyloidosis.

    PubMed

    Sher, Taimur; Gertz, Morie A

    2014-01-01

    The heart is commonly involved in various forms of amyloidosis and cardiomyopathy is a major cause of morbidity and mortality in these patients. Diagnosis of cardiac amyloidosis is often delayed due to nonspecific presenting symptoms and failure to recognize early signs of amyloid heart disease on routine cardiac imaging. Treatment of cardiac amyloidosis depends upon the type of amyloid protein. Systemic chemotherapy with or without stem cell transplantation is used to treat immunoglobulin-related amyloidosis and liver transplantation is used for familial transthyretin amyloidosis in select patients. Clinical trials with siRNA for the treatment of transthyretin amyloid cardiomyopathies and amyloid protein stabilizers are ongoing. Prognosis depends on the type of amyloid protein with poorer outcomes noted in immunoglobulin light-chain amyloidosis. Supportive care forms the cornerstone of management and advancements in cardiac imaging and proteomics are expected to positively impact our ability to diagnose, prognosticate and treat cardiac amyloidosis. PMID:24344669

  19. Does AL amyloidosis have a unique genomic profile? Gene expression profiling meta-analysis and literature overview.

    PubMed

    Kryukov, Fedor; Kryukova, Elena; Brozova, Lucie; Kufova, Zuzana; Filipova, Jana; Growkova, Katerina; Sevcikova, Tereza; Jarkovsky, Jiri; Hajek, Roman

    2016-10-15

    Immunoglobulin light chain amyloidosis (ALA) is a plasma cell dyscrasia characterized by deposition of amyloid fibrils in various organs and tissues. The current paper is devoted to clarify if ALA has a unique gene expression profile and to its pathogenetic argumentation. The meta-analysis of ALA patients vs. healthy donors, monoclonal gammopathy of undetermined significance, smoldering and multiple myeloma patients' cohorts have revealed molecular signature of ALA consists of 256 genes representing mostly ribosomal proteins and immunoglobulin regions. This signature appears pathogenetically supported and elucidates for the first time the role of ribosome dysfunction in ALA. In summary of our findings with literature overview, we hypothesize that ALA development is associated not only with changes in genes, coding amyloidogenic protein itself, but with post-transcriptional disbalance as well. Based on our data analysis in ALA, ribosome machinery is impaired and the affected link mainly involves translational initiation, elongation and co-translational protein folding. PMID:27288311

  20. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a common form of renal amyloidosis among Egyptians.

    PubMed

    Larsen, Christopher P; Ismail, Wesam; Kurtin, Paul J; Vrana, Julie A; Dasari, Surendra; Nasr, Samih H

    2016-04-01

    Large case series of renal amyloidosis subtypes have recently been published in the United States and Europe showing AL amyloidosis to be the predominant subtype in this part of the world. However, the most common subtypes of renal amyloidosis throughout the rest of the world are unknown. We present here the first large case series detailing the subtypes of renal amyloidosis among Egyptians. In this population, AA amyloidosis was the most common type of amyloidosis on renal biopsy at 48%. The newly described leukocyte chemotactic factor 2 amyloidosis (ALECT2) was the second most common type and represented nearly one-third of renal amyloid cases at 31%. AL accounted for only 20% of cases. The pathologic findings in ALECT2 cases were similar to those previously described in other case series. Thus ALECT2, which was initially thought to affect mainly Hispanics in the United States, appears to represent an important and likely underrecognized etiology of chronic kidney disease among Egyptians and probably in other ethnic groups around the world. PMID:26867784

  1. [Amyloidosis and familial Mediterranean fever].

    PubMed

    Pras, M

    1986-01-01

    Familial Mediterranean Fever (F. M. F.) is an autosomal recessive disorder occurring most commonly in Sepharadi Jews and Armenians. Two phenotypic features characterize the disease: brief episodic febrile attacks of peritonitis, pleuritis or synovitis recurring from childhood or adolescence and the development of systemic amyloidosis. Attacks are accompanied by striking elevations of acute phase proteins, including serum amyloid A protein. The amyloidosis of Familial Mediterranean Fever is of the AA type, and manifest clinically as a nephropathy that passes through proteinuria, nephrotic and uremic stages to renal death. Although there is ethnic variation in the incidence of amyloidosis of F. M. F. in our patient population--predominantly Sepharadi Jews of North African extraction--an amyloidotic death at an early age is their genetic destiny. Since the introduction in 1972 of colchicine to prevent the febrile attacks, the drug has been proven and become the main stay of therapy. Today, colchicine has been shown to be effective in preventing amyloidosis as well as the febrile attacks in Familial Mediterranean Fever. End stage renal disease is not the end of the road for patients with F.M.F. because of improving outlook for dialysis and renal transplantation in these patients. PMID:2943362

  2. Amyloidosis in Retinal Neurodegenerative Diseases.

    PubMed

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer's disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer's patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer's patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a "window" to the brain. PMID:27551275

  3. Amyloidosis in Retinal Neurodegenerative Diseases

    PubMed Central

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275

  4. Laboratory assessment of transthyretin amyloidosis.

    PubMed

    Benson, Merrill D; Yazaki, Masahide; Magy, Nadine

    2002-12-01

    Mutations in transthyretin (TTR) are the most common cause of autosomal dominant systemic amyloidosis. To date, more than 80 TTR mutations have been associated with amyloidosis in humans. A high prevalence of some mutations like Val122Ile which is identified in 3% of African Americans indicates the necessity of thorough investigation of patients suspected of having, or to be at risk of developing, TTR amyloidosis. Laboratory tests available for evaluation of TTR amyloidosis include both DNA and protein assays. In the case of a known mutation DNA analysis is realized by restriction fragment length polymorphism (RFLP), polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA), single strand confirmation polymorpism (SSCP) or nucleotide sequencing. SSCP, PCR-non-isotopic RNAse cleavage assay (NIRCA) or nucleotide sequencing are used to identify an unknown mutation. At the protein level, two techniques are used, isoelectric focusing and mass spectrometry, in both cases (known or unknown mutation). The identification of a previously unknown mutation requires a combination of clinical, pathological and molecular studies. PMID:12553428

  5. Gastrointestinal amyloidosis: a case of chronic diarrhoea.

    PubMed

    Fonnesu, C; Giovinale, M; Verrecchia, E; De Socio, G; Cerquaglia, C; Curigliano, V; Soriano, A; Obici, L; Grieco, A; Lauriola, L; Gasbarrini, G; Manna, R

    2009-03-01

    Amyloidosis is a rare disease caused by extracellular deposits of insoluble fibrillar proteins in various organs and tissues. There are different forms of amyloidosis distinguished by the type of protein fibrils, by the sites of deposition and by associated conditions. Gastrointestinal involvement is common both in primary and secondary amyloidosis, while isolated gastrointestinal amyloidosis is rare. We describe a case of AL amyloidosis with a gastrointestinal involvement and restrictive cardiomiopathy. A 64 year old woman came to our attention with a history of chronic diarrhoea and weight loss, associated with dysphagia, dry mouth, xerophtalmia, chronic gastritis and depression. Clinical diagnosis has been difficult because of aspecificity of symptoms that mimed other more common diseases, like gastro-paresis, epigastric discomfort, gastric or duodenal ulcers, perforation, malabsorption, intestinal pseudo-obstruction. There is an important risk of misunderstanding and diagnostic delay. Indeed in this patient a diagnosis of irritable colon syndrome was erroneously established two years before admission in our hospital. Therefore gastrointestinal amyloidosis should be considered among differential diagnoses of chronic diarrhoea and weight loss when other more common diseases have been excluded. PMID:19530511

  6. Amyloidosis presenting as priapism.

    PubMed

    Lapan, D I; Graham, A R; Bangert, J L; Boyer, J T; Conner, W T

    1980-02-01

    A sixty-five-year-old white man presented with sudden onset of painful, priapism. Review of pathologic specimens at the time of surgical decompression revealed massive amyloid infiltration. Purpura, organ enlargement, gastrointestinal bleeding, and congestive heart failure developed subsequently. Postmortem examination revealed widespread amyloidosis. To our knowledge this is the first report of amyloidosis presenting with priapism. PMID:7355542

  7. Isolated Tricuspid Regurgitation: Initial Manifestation of Cardiac Amyloidosis

    PubMed Central

    Yoon, Dong Woog; Park, Byung-Jo; Kim, In Sook; Jeong, Dong Seop

    2015-01-01

    Amyloid deposits in the heart are not exceptional in systemic amyloidosis. The clinical manifestations of cardiac amyloidosis may include restrictive cardiomyopathy, characterized by progressive diastolic and eventually systolic bi-ventricular dysfunction; arrhythmia; and conduction defects. To the best of our knowledge, no previous cases of isolated tricuspid regurgitation as the initial manifestation of cardiac amyloidosis have been reported. We describe a rare case of cardiac amyloidosis that initially presented with severe tricuspid regurgitation in a 42-year-old woman who was successfully treated with tricuspid valve replacement. Unusual surgical findings prompted additional evaluation that established a diagnosis of plasma cell myeloma. PMID:26665112

  8. Anterior Orbit and Adnexal Amyloidosis

    PubMed Central

    Al Hussain, Hailah; Edward, Deepak P.

    2013-01-01

    Purpose: To describe six cases of anterior orbital and adnexal amyloidosis and to report on proteomic analysis to characterize the nature of amyloid in archived biopsies in two cases. Materials and Methods: The clinical features, radiological findings, pathology, and outcome of six patients with anterior orbit and adnexal amyloidosis were retrieved from the medical records. The biochemical nature of the amyloid was determined using liquid chromatography/mass spectroscopy archived paraffin-embedded tissue in two cases. Results: Of the six cases, three had unilateral localized anterior orbit and lacrimal gland involvement. Four of the six patients were female with an average duration of 12.8 years from the time of onset to presentation eyelid infiltration by amyloid caused ptosis in five cases. CT scan in patients with lacrimal gland involvement (n = 3) demonstrated calcified deformable anterior orbital masses and on pathological exmaintionamyloid and calcific deposits replaced the lacrimal gland acini. Ptosis repair was performed in three patients with good outcomes. One patient required repeated debulking of the mass and one patient had recurrenct disease. Proteomic analysis revealed polyclonal IgG-associated amyloid deposition in one patient and AL kappa amyloid in the second patient. Conclusion: Amyloidosis of the anterior orbit and lacrimal gland can present with a wide spectrum of findings with good outcomes after surgical excision. The nature of amyloid material can be precisely determined in archival pathology blocks using diagnostic proteomic analysis. PMID:24014979

  9. [Progress in the diagnosis and treatment of cardiac amyloidosis].

    PubMed

    Jurczyszyn, Artur; Engel, Anna; Rajzer, Marek; Czepiel, Jacek; Mazurs, Grzegorz

    2014-01-01

    The heart is an organ often occupied by various forms of amyloidosis; cardiomyopathies are the leading cause of mortality in patients with amyloidosis. Cardiac amyloidosis is often diagnosed late because of nonspecific symptoms and missed early signs in the imaging routine. A method for treating cardiac amyloidosis depends on the type of amyloid protein. In the treatment of amyloidosis associated with immunoglobulins systemic chemotherapy is used without transplant or stem cell transplantation and in the treatment of familial transthyretin amyloidosis liver transplantation is used. There are still clinical studies on the use of siRNA for the treatment of cardiomyopathy associated with transthy retin amyloidosis, and on the use of amyloid protein stabilizers. The prognosis depends on the type of amyloid protein; worse results observed in the case of light chain amyloidosis. Care support is the cornerstone of treatment; it is expected that advances in cardiac imaging and proteomics positive impact on our ability to diagnosis, prognosis and treatment outcomes of amyloidosis of the heart. PMID:25344976

  10. Cardiac amyloidosis

    MedlinePlus

    ... the way electrical signals move through the heart (conduction system). This can lead to abnormal heart beats ( ... due to medication) Sick sinus syndrome Symptomatic cardiac conduction system disease (arrhythmias related to abnormal conduction of ...

  11. Soft-tissue uptake of 99mTc-diphosphonate and 99mTc-pyrophosphate in amyloidosis.

    PubMed

    Janssen, S; Piers, D A; van Rijswijk, M H; Meijer, S; Mandema, E

    1990-01-01

    This study describes the results of scintigraphy with 99mTc-labeled methylene-diphosphonate (99mTc-MDP) and pyrophosphate (99mTc-PYP) as a noninvasive test for the distribution of organ involvement in five different types of amyloidosis. Scintigraphy with 99mTc-labeled phosphates appeared to be a sensitive noninvasive screening test for the extent and the distribution of organ involvement in systemic AA and systemic AL amyloidosis as well as in local bronchial amyloid, local dermal amyloid, and familial amyloidotic polyneuropathy. Echocardiography, however, was more sensitive for demonstrating cardiac involvement in systemic amyloidosis than 99mTc-MDP or 99mTc-PYP scintigraphy. 99mTc-MDP images showed a better contrast than 99mTc-PYP images, although there was no difference in the extent or the intensity of soft-tissue uptake. PMID:2166666

  12. Amyloidosis cutis dyschromica in two female siblings: cases report

    PubMed Central

    2011-01-01

    Background Cutaneous amyloidosis has been classified into primary cutaneous amyloidosis (PCA, OMIM #105250), secondary cutaneous amyloidosis and systemic cutaneous amyloidosis. PCA is the deposition of amyloid in previously apparent normal skin without systemic involvement. Amyloidosis cutis dyschromica (ACD) is a rare distinct type of PCA. Here, the unique clinical and histological findings of two Chinese female siblings with ACD were described. Cases presentations Patient 1 was a 34-year-old female, presented with mildly pruritic, diffuse mottled hyperpigmentation and hypopigmentation. The lesions involved all over the body since she was 10 years old. There were a few itchy blisters appearing on her arms, lower legs and truck, especially on the sun-exposed areas in summer. Some hypopigmented macules presented with slight atrophy. Patient 2 was 39-year-old, the elder sister of patient 1. She had similar skin lesions since the same age as the former. The atrophy and blisters on the skin of the patient with amyloidosis cutis dyschromica have not been described in previous literature. Histological examinations of the skin biopsies taken from both patients revealed amyloid deposits in the whole papillary dermis. Depending on the histological assessment, the two cases were diagnosed as amyloidosis cutis dyschromica. Conclusion The two cases suggest that the atrophy and blisters may be the uncommon manifestations of amyloidosis cutis dyschromica. It alerts clinicians to consider the possibility of ACD when meeting patients with cutaneous dyschromia. Skin biopsy is essential and family consultation of genetic investigation is very important in such cases. PMID:21320354

  13. Cardiac amyloidosis: updates in diagnosis and management.

    PubMed

    Mohty, Dania; Damy, Thibaud; Cosnay, Pierre; Echahidi, Najmeddine; Casset-Senon, Danielle; Virot, Patrice; Jaccard, Arnaud

    2013-10-01

    Amyloidosis is a severe systemic disease. Cardiac involvement may occur in the three main types of amyloidosis (acquired monoclonal light-chain, hereditary transthyretin and senile amyloidosis) and has a major impact on prognosis. Imaging the heart to characterize and detect early cardiac involvement is one of the major aims in the assessment of this disease. Electrocardiography and transthoracic echocardiography are important diagnostic and prognostic tools in patients with cardiac involvement. Cardiac magnetic resonance imaging better characterizes myocardial involvement, functional abnormalities and amyloid deposition due to its high spatial resolution. Nuclear imaging has a role in the diagnosis of transthyretin amyloid cardiomyopathy. Cardiac biomarkers are now used for risk stratification and staging of patients with light-chain systemic amyloidosis. Different types of cardiac complications may occur, including diastolic followed by systolic heart failure, atrial and/or ventricular arrhythmias, conduction disturbances, embolic events and sometimes sudden death. Senile amyloid and hereditary transthyretin amyloid cardiomyopathy have better prognoses than light-chain amyloidosis. Cardiac treatment of heart failure is usually ineffective and is often poorly tolerated because of its hypotensive and bradycardiac effects. The three main types of amyloid disease, despite their similar cardiac appearance, have specific new aetiological treatments that may change the prognosis of this disease. Cardiologists should be aware of this disease to allow early treatment. PMID:24070600

  14. A homozygous transthyretin variant associated with senile systemic amyloidosis: evidence for a late-onset disease of genetic etiology.

    PubMed Central

    Jacobson, D R; Gorevic, P D; Buxbaum, J N

    1990-01-01

    Senile systemic amyloidosis (SSA) is a late-onset disease characterized by deposition of amyloid fibrils containing transthyretin (TTR). Amino acid sequencing of protein isolated from the amyloid fibrils of a patient with SSA identified TTR containing a position - 122 isoleucine-for-valine substitution. This change led to the prediction of a genomic G-to-A transition, destroying an MaeIII restriction site. We confirmed the presence of the variant DNA fragment both by Southern blotting and by visualization of MaeIII digests of DNA amplified around codon 122, by using the polymerase chain reaction. The patient's DNA was entirely resistant to MaeIII cleavage; therefore, only the mutant sequence was present. DNA from none of either 24 controls or six other SSA patients contained the variant. Quantitative Southern blotting demonstrated that the patient's DNA contained two copies of the TTR gene per genome; the mutation was therefore homozygous rather than hemizygous. In the present case, the homozygous mutation TTR (122 Val----Ile) is associated with SSA, a finding which is consistent with autosomal recessive inheritance of this condition. Images Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2349941

  15. Amyloidosis and Reiter's syndrome: report of a case and review of the literature.

    PubMed

    Anderson, C J; Gregory, M C; Groggel, G C; Clegg, D O

    1989-10-01

    Reiter's syndrome is classically described as the triad of urethritis, conjunctivitis, and arthritis, It has many manifestations and has rarely been reported to occur in association with amyloidosis. Four cases of systemic amyloidosis have previously been reported. This case describes a patient who developed progressive renal amyloidosis after a 17-year history of severe Reiter's syndrome. Immunofluorescent staining of the renal biopsy was strongly positive for AA protein, the type of protein found in secondary amyloidosis. This is the first case in which amyloidosis has been proven to be secondary to Reiter's syndrome and not merely the coincidental occurrence of two rare diseases. PMID:2679059

  16. A case of multicentric Castleman's disease associated with advanced systemic amyloidosis treated with chemotherapy and anti-CD20 monoclonal antibody.

    PubMed

    Gholam, Dany; Vantelon, Jean-Marie; Al-Jijakli, Ahmad; Bourhis, Jean-Henri

    2003-12-01

    Multicentric Castleman's disease (MCD) is a rare systemic lymphoproliferative disorder with too few patient series reported in the literature to have a clear idea about the etiology, outcome and the best treatment available. Systemic reactive amyloidosis is a very rare complication of MCD and its presence worsens the prognosis. We report a case of a 28-year-old patient with plasma-cell type, human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative MCD who responded to treatment with chemotherapy and the anti-CD20 monoclonal antibody, rituximab. Anti-CD20 therapy could be an interesting adjunctive treatment in MCD. PMID:12898190

  17. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments.

    PubMed

    Sekijima, Yoshiki

    2015-09-01

    Transthyretin (ATTR) amyloidosis is a life-threatening, gain-of-toxic-function disease characterised by extracellular deposition of amyloid fibrils composed of transthyretin (TTR). TTR protein destabilised by TTR gene mutation is prone to dissociate from its native tetramer to monomer, and to then misfold and aggregate into amyloid fibrils, resulting in autosomal dominant hereditary amyloidosis, including familial amyloid polyneuropathy, familial amyloid cardiomyopathy and familial leptomeningeal amyloidosis. Analogous misfolding of wild-type TTR results in senile systemic amyloidosis, now termed wild-type ATTR amyloidosis, characterised by acquired amyloid disease in the elderly. With the availability of genetic, biochemical and immunohistochemical diagnostic tests, patients with ATTR amyloidosis have been found in many nations; however, misdiagnosis is still common and considerable time is required before correct diagnosis in many cases. The current standard first-line treatment for hereditary ATTR amyloidosis is liver transplantation, which allows suppression of the main source of variant TTR. However, large numbers of patients are not suitable transplant candidates. Recently, the clinical effects of TTR tetramer stabilisers, diflunisal and tafamidis, were demonstrated in randomised clinical trials, and tafamidis has been approved for treatment of hereditary ATTR amyloidosis in European countries and in Japan. Moreover, antisense oligonucleotides and small interfering RNAs for suppression of variant and wild-type TTR synthesis are promising therapeutic approaches to ameliorate ATTR amyloidosis and are currently in phase III clinical trials. These newly developed therapies are expected to be effective for not only hereditary ATTR amyloidosis but also wild-type ATTR amyloidosis. PMID:25604431

  18. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis

    PubMed Central

    Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A.; Banypersad, Sanjay M.; Maestrini, Viviana; Barcella, William; Rosmini, Stefania; Bulluck, Heerajnarain; Sayed, Rabya H.; Patel, Ketna; Mamhood, Shameem; Bucciarelli-Ducci, Chiara; Whelan, Carol J.; Herrey, Anna S.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Manisty, Charlotte H.; Schelbert, Eric B.; Kellman, Peter; Gillmore, Julian D.; Hawkins, Philip N.

    2015-01-01

    Background— The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Methods and Results— Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1–13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3–13.1; P<0.05). Conclusions— There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after

  19. Optimization of Serum Immunoglobulin Free Light Chain Analysis for Subclassification of Cardiac Amyloidosis.

    PubMed

    Halushka, Marc K; Eng, George; Collins, A Bernard; Judge, Daniel P; Semigran, Marc J; Stone, James R

    2015-06-01

    Accurate and rapid classification of cardiac amyloidosis is important for patient management. We have optimized the use of serum free light chain kappa and lambda values to differentiate immunoglobulin light chain amyloid (AL) amyloidosis from transthyretin amyloid and amyloid A using 85 cases of tissue-proven cardiac amyloidosis, in which there was direct classification of amyloidosis by mass spectrometry or immunofluorescence. The serum free light chain kappa/lambda ratios were non-overlapping for the three major groups: AL-lambda (0.01-0.41, n = 30), non-AL (0.52-2.7, n = 43), and AL-kappa (6.7-967, n = 12). A kappa/lambda ratio value between 0.5 and 5.0 had 100 % sensitivity and 100 % specificity for distinguishing AL amyloidosis from non-AL amyloidosis. This optimized range for serum light chain kappa/lambda ratio provides extremely robust classification of cardiac amyloidosis. Cases of cardiac amyloidosis in which the serum kappa/lambda free light chain ratio falls close to these new cutoff values may benefit most from direct amyloid subtyping. PMID:25925232

  20. Amyloidosis and Kidney Disease

    MedlinePlus

    ... Foundation Genetic and Rare Diseases Information Center MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... PDF, 345 KB)​​​​​ Alternate Language URL Amyloidosis and Kidney Disease Page Content On this page: What is ...

  1. Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis)

    PubMed Central

    Kiuru-Enari, Sari; Salonen, Oili; Kaipainen, Markku; Hokkanen, Laura

    2014-01-01

    Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the patient group, although the number of findings was small. Our study shows that AGel amyloidosis can be associated with visuoconstructional problems and depression, but severe neuropsychiatric involvement is not characteristic. The gelsolin mutation may even induce cerebrovascular fragility, but further epidemiological and histopathological as well as longitudinal follow-up studies are needed to clarify gelsolin-related vascular pathology and its clinical consequences. PMID:25097823

  2. [Truss-induced macular amyloidosis].

    PubMed

    Abels, C; Karrer, S; Landthaler, M; Szeimies, R M

    2001-10-01

    A 80-year-old male presented with a long time history of a localized red-brown macule with superficial lichenification and slight scaling in the right groin. An earlier skin biopsy revealed the presence of amyloid deposits. The patient therefore had a complete internal checkup including a rectal biopsy for exclusion of systemic amyloidosis. However, the laboratory data did not reveal any specific abnormalities including immunoglobulins and Bence-Jones protein. The rectal biopsy was also nonspecific. After skin examination, a rebiopsy was performed at our department showing acanthosis and spongiosis of the epidermis with parakeratosis. A homogenous eosinophilic deposit was present in the upper dermis and stained positive with thioflavine. At the second visit the patient wore a truss for a right inguinal hernia, perfectly matching the area of the skin lesion. Thus, the diagnosis of a localized macular amyloidosis was confirmed very likely due to permanent local friction. The classification of localized cutaneous amyloidoses should include local trauma as a cause to avoid unnecessary and exhausting internal checkups to exclude systemic involvement. PMID:11715396

  3. Systemic senile amyloidosis. Identification of a new prealbumin (transthyretin) variant in cardiac tissue: immunologic and biochemical similarity to one form of familial amyloidotic polyneuropathy.

    PubMed Central

    Gorevic, P D; Prelli, F C; Wright, J; Pras, M; Frangione, B

    1989-01-01

    Isolated amyloid fibrils from three cases of systemic senile amyloidosis (SSA) contained subunit proteins with molecular masses of 14 (10-20%), 10-12 (60-80%), and 5-6 kD (5-10%) when fractionated under reducing and dissociating conditions. This grouping was identical to that seen in SKO, a case of familial amyloidotic polyneuropathy (FAP) studied earlier. Amino acid sequencing confirmed that SSA subunit proteins were in fact prealbumin (transthyretin). Complete sequence analysis of one SSA preparation revealed the presence of a new variant Pa (TTr) molecule with a single amino acid substitution of isoleucine for valine at position 122. Further studies used an antiserum specific for SKO IV, a subunit protein of SKO previously shown to correspond to carboxy-terminal 78 residues (positions 49-127) of (TTr). Anti-SKO IV reacted with SSA in tissue at equivalent dilutions to anti-Pa (TTr) and with the 10-12-kD fraction of SSA on Western blots; reactivity was blocked by SKO IV, but not by Pa (TTr). SSA is a form of systemic amyloidosis caused by tissue deposition of Pa (TTr) and its fragments, with shared conformational or subunit antigenicity to at least one form of FAP. Identification of a new variant Pa (TTr) molecule in one case suggests further that SSA may be a genetically determined disease expressed late in life. Images PMID:2646319

  4. What is new in diagnosis and management of light chain amyloidosis?

    PubMed

    Palladini, Giovanni; Merlini, Giampaolo

    2016-07-14

    Light chain (AL) amyloidosis is caused by a usually small plasma cell clone producing a misfolded light chain that deposits in tissues. Survival is mostly determined by the severity of heart involvement. Recent studies are clarifying the mechanisms of cardiac damage, pointing to a toxic effect of amyloidogenic light chains and offering new potential therapeutic targets. The diagnosis requires adequate technology, available at referral centers, for amyloid typing. Late diagnosis results in approximately 30% of patients presenting with advanced, irreversible organ involvement and dying in a few months despite modern treatments. The availability of accurate biomarkers of clonal and organ disease is reshaping the approach to patients with AL amyloidosis. Screening of early organ damage based on biomarkers can help identify patients with monoclonal gammopathy of undetermined significance who are developing AL amyloidosis before they become symptomatic. Staging systems and response assessment based on biomarkers facilitate the design and conduction of clinical trials, guide the therapeutic strategy, and allow the timely identification of refractory patients to be switched to rescue therapy. Treatment should be risk-adapted. Recent studies are linking specific characteristics of the plasma cell clone to response to different types of treatment, moving toward patient-tailored therapy. In addition, novel anti-amyloid treatments are being developed that might be combined with anti-plasma cell chemotherapy. PMID:27053535

  5. Mitral valve involvement as a predominant feature of cardiac amyloidosis

    PubMed Central

    Viswanathan, Girish; Williams, James; Slinn, Simon; Campbell, Philip

    2010-01-01

    Cardiac involvement in systemic amyloidosis carries poor prognosis with a median survival of 5 months.1 The authors report an unusual presentation of cardiac amyloidosis in the form of predominant mitral regurgitation. The patient responded very well to medical therapy with subsequent improvement of mitral valve dysfunction. The authors would like to highlight this multisystem involvement and the presence of a complex overlap of systemic features. PMID:22767536

  6. Amyloidosis of the renal pelvis: a harbinger of mammary carcinoma?

    PubMed

    Grigor, Thomas; Munro, Nicolas

    2015-01-01

    We describe a rare case of light chain immunoglobulin amyloid (AL) accumulation in the central and lower pole renal calyces. Our patient, a woman aged 60, presented with several episodes of gross haematuria. Radiological imaging detected a filling defect in the left renal pelvis. Rigid ureteroscopy showed a corresponding mucosal abnormality resembling transitional cell carcinoma. A definitive preoperative tissue diagnosis could not be reached. Laparoscopic-assisted left nephroureterectomy was indicated. Histopathological examination excluded malignancy, revealing congophilic deposits of submucosal amyloid. A constellation of findings confirmed localised or primary amyloidosis with an AL immunophenotype but no evidence of clonal B-cell disease in the amyloid-associated lymphoplasmacytic cell infiltrate. Investigation for systemic plasma cell dyscrasia and echocardiography and scintigraphy for visceral amyloid deposits were negative for systemic disease. At a follow-up period of 30 months, there is no recurrence. However, our patient was diagnosed with breast cancer 21 months ago. PMID:25596296

  7. Amyloidosis in alkaptonuria.

    PubMed

    Millucci, Lia; Braconi, Daniela; Bernardini, Giulia; Lupetti, Pietro; Rovensky, Josef; Ranganath, Lakshminaryan; Santucci, Annalisa

    2015-09-01

    Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces an HGA-melanin ochronotic pigment, of hitherto unknown composition. Besides the accumulation of HGA, the potential role and presence of unidentified proteins has been hypothesized as additional causal factors involved in ochronotic pigment deposition. Evidence has been provided on the presence of serum amyloid A (SAA) in several AKU tissues, which allowed classifying AKU as a novel secondary amyloidosis. In this paper, we will briefly review all direct and indirect lines of evidence related to the presence of amyloidosis in AKU. We also report the first data on abnormal SAA serum levels in a cohort of AKU patients. PMID:25868666

  8. Cardiac amyloidosis in a heart transplant patient - A case report and retrospective analysis of amyloidosis evolution.

    PubMed

    Kintsler, Svetlana; Jäkel, Jörg; Brandenburg, Vincent; Kersten, Katrin; Knuechel, Ruth; Röcken, Christoph

    2015-02-01

    Cardiac amyloidosis is a very rare cause of heart failure in heart transplant recipients but an important differential diagnosis in cases of progressive cardiac failure. We report a 72-year-old male patient with the diagnosis of senile systemic amyloidosis (SSA) in a transplanted heart 15 years after transplantation by the initial diagnosis of the dilated cardiomyopathy. Additionally performed immunohistochemical analysis with anti-transthyretin antibody of the cardiac biopsies of the last 15 years enabled the possibility to show the evolution of this disease with characteristic biphasic pattern. PMID:25674390

  9. The many guises of amyloidosis. Clinical presentations and disease associations.

    PubMed

    Vogelgesang, S A; Klipple, G L

    1994-10-01

    Amyloidosis occurs in association with many diseases and can also be idiopathic. It is usually a systemic disease with variable presentations. The diagnosis should be suspected in patients with unexplained proteinuria, cardiomyopathy, congestive heart failure, peripheral neuropathy, carpal tunnel syndrome, macroglossia, or hepatosplenomegaly. Amyloidosis generally has a poor prognosis and responds poorly to therapy. Much needs to be learned about its pathogenesis and treatment possibilities. PMID:7937410

  10. Why are some amyloidoses systemic? Does hepatic “chaperoning at a distance” prevent cardiac deposition in a transgenic model of human senile systemic (transthyretin) amyloidosis?

    PubMed Central

    Buxbaum, Joel N.; Tagoe, Clement; Gallo, Gloria; Walker, John R.; Kurian, Sunil; Salomon, Daniel R.

    2012-01-01

    In the human systemic amyloidoses caused by mutant or wild-type transthyretin (TTR), deposition occurs at a distance from the site of synthesis. The TTR synthesized and secreted by the hepatocyte circulates in plasma, then deposits in target tissues far from the producing cell, a pattern reproduced in mice transgenic for multiple copies of the human wild-type TTR gene. By 2 yr of age, half of the transgenic males show cardiac deposition resembling human senile systemic amyloidosis. However, as early as 3 mo of age, when there are no deposits, cardiac gene transcription differs from that of nontransgenic littermates, primarily in the expression of a large number of genes associated with inflammation and the immune response. At 24 mo, the hearts with histologically proven TTR deposits show expression of stress response genes, exuberant mitochondrial gene transcription, and increased expression of genes associated with apoptosis, relative to the hearts without TTR deposition. These 24-mo-old hearts with TTR deposits also show a decrease in transcription of inflammatory genes relative to that in the younger transgenic mice. After 2 yr of expressing large amounts of human TTR, the livers of the transgenic mice without cardiac deposition display chaperone gene expression and evidence of an activated unfolded protein response, while the livers of animals with cardiac TTR deposition display neither, showing increased transcription of interferon-responsive inflammatory genes and those encoding an antioxidant response. With time, in animals with cardiac deposition, it appears that hepatic proteostatic capacity is diminished, exposing the heart to a greater load of misfolded TTR with subsequent extracellular deposition. Hence systemic (cardiac) TTR deposition may be the direct result of the diminution in the distant chaperoning capacity of the liver related to age or long-standing exposure to misfolded TTR, or both.—Buxbaum, J. N., Tagoe, C., Gallo, G., Walker, J. R

  11. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile.

    PubMed

    Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A; Relini, Annalisa; Talmud, Philippa J; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D; Kalopissis, Athina D; Bellotti, Vittorio

    2016-01-01

    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

  12. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

    PubMed Central

    Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P. Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A.; Relini, Annalisa; Talmud, Philippa J.; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N.; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D.; Kalopissis, Athina D.; Bellotti, Vittorio

    2016-01-01

    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

  13. Leukocyte Cell-Derived Chemotaxin 2-Associated Amyloidosis: A Recently Recognized Disease with Distinct Clinicopathologic Characteristics.

    PubMed

    Nasr, Samih H; Dogan, Ahmet; Larsen, Christopher P

    2015-11-01

    Amyloidosis derived from leukocyte cell-derived chemotaxin 2 is a recently recognized form of amyloidosis, and it has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of kidney and liver. The disease has a strong ethnic bias, affecting mainly Hispanics (particularly Mexicans). Additional ethnic groups prone to develop amyloidosis derived from leukocyte cell-derived chemotaxin 2 include Punjabis, First Nations people in British Columbia, and Native Americans. Most patients are elderly who present with chronic renal insufficiency and bland urinary sediment. Proteinuria is variable, being absent altogether in about one third of patients. Liver involvement is frequently an incidental finding. Amyloidosis derived from leukocyte cell-derived chemotaxin 2 deposits shows a characteristic distribution: in the kidney, there is consistent involvement of cortical interstitium, whereas in the liver, there is a preferential involvement of periportal and pericentral vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and IgA nephropathy being the most common. Patient survival is excellent, likely because of the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease. There is currently no efficacious therapy for amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis. Renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft. The pathogenesis of amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis has not yet been elucidated. It could be a result of leukocyte cell-derived chemotaxin 2 overexpression by hepatocytes either constitutively (controlled by yet-uncharacterized genetic defects) or secondary to hepatocellular damage. It is critical not to misdiagnose amyloidosis

  14. Diagnostic approach to cardiac amyloidosis.

    PubMed

    Amin, Hilman Zulkifli; Mori, Shumpei; Sasaki, Naoto; Hirata, Kenichi

    2014-01-01

    Amyloidosis is a relatively rare disease that may be underdiagnosed and could affect the entire human body. Many organs may be affected, which could increase the morbidity and mortality. Cardiac involvement is the leading cause of poor prognosis. Patients with cardiac amyloidosis are usually admitted with heart failure. The clinical presentation varies greatly, and using the correct approach is important in identifying cardiac amyloidosis. A 51-year-old man was diagnosed with chronic heart failure. He had increased brain natriuretic peptide levels, a low ejection fraction, and left and right ventricular hypertrophy with granular sparkling as seen by echocardiography. These findings led us to perform a cardiac biopsy that confirmed the diagnosis of cardiac amyloidosis. Further investigation revealed that the patient had amyloid light-chain type amyloidosis due to multiple myeloma. He is now undergoing the 3rd phase of chemotherapy. Congo-red stain is usually used by physicians to histologically confirm amyloidosis, with which apple-green birefringence indicates amyloid deposits. Other stains such as direct fast scarlet (DFS) and hematoxylin-eosin (HE) can also confirm the presence of amyloid deposits. In the present case, DFS and HE were used, both of which suggested amyloid deposits surrounding myocardial cells. The use of a combination of stains can increase the diagnostic sensitivity and specificity of amyloidosis. However, the typical echocardiographic appearances would be enough to diagnose cardiac amyloidosis when it is impossible for the patient to undergo a cardiac biopsy, if an additional histological specimen from another tissue such as abdominal fat confirms amyloidosis. PMID:25011639

  15. Cardiac amyloidosis: pathology, nomenclature, and typing.

    PubMed

    Maleszewski, Joseph J

    2015-01-01

    Amyloidosis is an increasingly recognized cause of heart disease, caused by the deposition of misfolded protein within the heart. These proteins may deposit systemically and include the heart or deposit only within the heart muscle itself. In either case, cardiac symptoms may be the primary manifestation. The diagnosis is usually made by the pathologist identifying amyloid within a tissue sample. The diagnosis, however, does not end with such visual recognition of the presence of amyloid. Newer generation pharmacotherapeutic agents that are protein specific necessitate a closer evaluation to determine the type of protein being deposited and accurately conveying this to the treating clinician. Herein, the gross and histopathologic features of cardiac amyloidosis are reviewed along with a review of amyloid typing strategies (both direct and indirect) that may be employed in the diagnostic workup as well as the nomenclature standards for reporting. PMID:26361138

  16. Light chain amyloidosis - current findings and future prospects.

    PubMed

    Baden, Elizabeth M; Sikkink, Laura A; Ramirez-Alvarado, Marina

    2009-10-01

    Systemic light chain amyloidosis (AL) is one of several protein misfolding diseases and is characterized by extracellular deposition of immunoglobulin light chains in the form of amyloid fibrils [1]. Immunoglobulin (Ig) proteins consist of two light chains (LCs) and two heavy chains (HCs) that ordinarily form a heterotetramer which is secreted by a plasma cell. In AL, however, a monoclonal plasma cell population produces an abundance of a pathogenic LC protein. In this case, not all of the LCs pair with the HCs, and free LCs are secreted into circulation. The LC-HC dimer is very stable, and losing this interaction may result in an unstable LC protein [2]. Additionally, somatic mutations are thought to cause amyloidogenic proteins to be less stable compared to non-amyloidogenic proteins [3-5], leading to protein misfolding and amyloid fibril formation. The amyloid fibrils cause tissue damage and cell death, leading to patient death within 12-18 months if left untreated [6]. Current therapies are harsh and not curative, including chemotherapy and autologous stem cell transplants. Studies of protein pathogenesis and fibril formation mechanisms may lead to better therapies with an improved outlook for patient survival. Much has been done to determine the molecular factors that make a particular LC protein amyloidogenic and to elucidate the mechanism of amyloid fibril formation. Anthony Fink's work, particularly with discerning the role of intermediates in the fibril formation pathway, has made a remarkable impact in the field of amyloidosis research. This review provides a general overview of the current state of AL research and also attempts to capture the most recent ideas and knowledge generated from the Fink laboratory. PMID:19538145

  17. [Localized nodular pulmonary amyloidosis; report of a case].

    PubMed

    Shimada, Kazuyoshi; Tsubochi, H; Isogami, K; Kobayashi, S

    2006-12-01

    A 66-year-old female was admitted to our hospital because of chest abnormal shadow. Chest X-ray and chest computed tomography (CT) on admission showed a nodule in the right middle lobe. The nodule was not diagnosed preoperatively by a bronchoscopy. She underwent partial lung resection including the nodule with video-assisted thoracoscopic surgery. The pathological diagnosis was amyloidosis, and we diagnosed her illness as localized nodular pulmonary amyloidosis, since the amyloid substance was type AL. In addition, electron microscopy showed amyloid as straightly fibrous materials in alveolus. It is difficult to differentiate amyloidosis from lung cancer by radiology, and the lung biopsy with video-assisted thoracoscopic surgery is useful and a safety way to establish diagnosis. PMID:17163218

  18. Corneal amyloidosis associated with keratoconus.

    PubMed

    Stern, G A; Knapp, A; Hood, C I

    1988-01-01

    Nodular, gray-white, central corneal opacities which extended from the subepithelial zone through the anterior four fifths of the stroma developed in a 50-year-old man with a longstanding history of hard contact lens wear for keratoconus. Results of histopathologic analysis of the corneal button obtained at the time of penetrating keratoplasty disclosed that the opacities were composed of amyloid. Corneal amyloidosis is rarely found in association with keratoconus. Although there were some similarities in the pattern of amyloid deposition to that seen in primary familial amyloidosis of the cornea, the authors believe that their patient is more likely to have had a secondary amyloidosis. Corneal amyloidosis should be considered in keratoconus patients with development of unusual forms of central corneal opacification. PMID:3278260

  19. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    PubMed Central

    Meng, Ling-Chao; Lyu, He; Zhang, Wei; Liu, Jing; Wang, Zhao-Xia; Yuan, Yun

    2015-01-01

    Background: Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods: Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results: The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions: Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis. PMID:26521788

  20. Amyloidosis in black-footed cats (Felis nigripes).

    PubMed

    Terio, K A; O'Brien, T; Lamberski, N; Famula, T R; Munson, L

    2008-05-01

    A high prevalence of systemic amyloidosis was documented in the black-footed cat (Felis nigripes) based on a retrospective review of necropsy tissues (n = 38) submitted as part of ongoing disease surveillance. Some degree of amyloid deposition was present in 33 of 38 (87%) of the examined cats, and amyloidosis was the most common cause of death (26/38, 68%). Amyloid deposition was most severe in the renal medullary interstitium (30/33, 91%) and glomeruli (21/33, 63%). Other common sites included the splenic follicular germinal centers (26/31, 84%), gastric lamina propria (9/23, 39%), and intestinal lamina propria (3/23, 13%). Amyloid in all sites stained with Congo red, and in 13 of 15 (87%) cats, deposits had strong immunoreactivity for canine AA protein by immunohistochemistry. There was no association with concurrent chronic inflammatory conditions (P = .51), suggesting that amyloidosis was not secondary to inflammation. Adrenal cortical hyperplasia, a morphologic indicator of stress that can predispose to amyloid deposition, was similarly not associated (P = .09) with amyloidosis. However, adrenals were not available from the majority of cats without amyloidosis; therefore, further analysis of this risk factor is warranted. Heritability estimation suggested that amyloidosis might be familial in this species. Additionally, tissues from a single free-ranging black-footed cat had small amounts of amyloid deposition, suggesting that there could be a predilection for amyloidosis in this species. Research to identify the protein sequence of serum amyloid A (SAA) in the black-footed cat is needed to further investigate the possibility of an amyloidogenic SAA in this species. PMID:18487501

  1. [Hereditary transthyretin amyloidosis].

    PubMed

    Hund, E

    2014-10-01

    Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied. PMID:25123367

  2. Transthyretin Amyloidosis: Chaperone Concentration Changes and Increased Proteolysis in the Pathway to Disease

    PubMed Central

    Ribeiro, Raquel; Gilberto, Samuel; Gomes, Ricardo A.; Ferreira, António; Mateus, Élia; Barroso, Eduardo; Coelho, Ana V.; Freire, Ana Ponces; Cordeiro, Carlos

    2015-01-01

    Transthyretin amyloidosis is a conformational pathology characterized by the extracellular formation of amyloid deposits and the progressive impairment of the peripheral nervous system. Point mutations in this tetrameric plasma protein decrease its stability and are linked to disease onset and progression. Since non-mutated transthyretin also forms amyloid in systemic senile amyloidosis and some mutation bearers are asymptomatic throughout their lives, non-genetic factors must also be involved in transthyretin amyloidosis. We discovered, using a differential proteomics approach, that extracellular chaperones such as fibrinogen, clusterin, haptoglobin, alpha-1-anti-trypsin and 2-macroglobulin are overrepresented in transthyretin amyloidosis. Our data shows that a complex network of extracellular chaperones are over represented in human plasma and we speculate that they act synergistically to cope with amyloid prone proteins. Proteostasis may thus be as important as point mutations in transthyretin amyloidosis. PMID:26147092

  3. Case report: isolated cardiac amyloidosis: an enigma unravelled.

    PubMed

    Khalid, Umair; Awar, Omar; Verstovsek, Gordana; Cheong, Benjamin; Yellapragada, Sarvari Venkata; Jneid, Hani; Deswal, Anita; Virani, Salim S

    2015-01-01

    Amyloidosis is a rare, multisystem disease characterized by deposition of fibrils in extracellular tissue involving kidney, liver, heart, autonomic nervous system, and several other organs. This report discusses a 75-year-old male who presented with worsening dyspnea on exertion, orthopnea, and lower-extremity edema. On physical exam, he had elevated jugular venous pressure and lower-extremity edema. Electrocardiogram depicted low voltage in limb leads and a prolonged PR interval. Echocardiogram revealed left ventricular hypertrophy, severe biatrial dilatation, and restrictive filling physiology. Coronary angiography showed absence of significant epicardial coronary artery disease. On right heart catheterization, a "dip-and-plateau sign" was noted on right ventricular pressure tracings. A diagnosis of cardiac amyloidosis was considered, but a complete hematology work-up for systemic amyloidosis was negative. Cardiac magnetic resonance imaging was pursued, showing delayed gadolinium enhancement, and this ultimately led to the myocardial biopsy confirming the diagnosis of isolated cardiac amyloidosis. Further genetic analyses confirmed isolated cardiac amyloid caused by mutant transthyretin protein (Val-122-Ile). Isolated cardiac amyloidosis is an extremely rare entity, and diagnosis may be difficult despite the use of multimodality imaging. If the index of suspicion is high, then myocardial biopsy should be considered. PMID:25793032

  4. Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis

    PubMed Central

    Treibel, Thomas A.; Bandula, Steve; Fontana, Marianna; White, Steven K.; Gilbertson, Janet A.; Herrey, Anna S.; Gillmore, Julian D.; Punwani, Shonit; Hawkins, Philip N.; Taylor, Stuart A.; Moon, James C.

    2015-01-01

    Background Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. Objectives To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. Methods Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). Results ECVCT and ECVCMR results were well correlated (r2 = 0.85 vs r2 = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001). Conclusion Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis. PMID:26209459

  5. Dynamic Modeling of ALS Systems

    NASA Technical Reports Server (NTRS)

    Jones, Harry

    2002-01-01

    The purpose of dynamic modeling and simulation of Advanced Life Support (ALS) systems is to help design them. Static steady state systems analysis provides basic information and is necessary to guide dynamic modeling, but static analysis is not sufficient to design and compare systems. ALS systems must respond to external input variations and internal off-nominal behavior. Buffer sizing, resupply scheduling, failure response, and control system design are aspects of dynamic system design. We develop two dynamic mass flow models and use them in simulations to evaluate systems issues, optimize designs, and make system design trades. One model is of nitrogen leakage in the space station, the other is of a waste processor failure in a regenerative life support system. Most systems analyses are concerned with optimizing the cost/benefit of a system at its nominal steady-state operating point. ALS analysis must go beyond the static steady state to include dynamic system design. All life support systems exhibit behavior that varies over time. ALS systems must respond to equipment operating cycles, repair schedules, and occasional off-nominal behavior or malfunctions. Biological components, such as bioreactors, composters, and food plant growth chambers, usually have operating cycles or other complex time behavior. Buffer sizes, material stocks, and resupply rates determine dynamic system behavior and directly affect system mass and cost. Dynamic simulation is needed to avoid the extremes of costly over-design of buffers and material reserves or system failure due to insufficient buffers and lack of stored material.

  6. Acute liver failure due to primary amyloidosis in a nephrotic syndrome: a swiftly progressive course.

    PubMed

    Cardoso, Brigite Aguiar; Leal, Rita; Sá, Helena; Campos, Mário

    2016-01-01

    AL amyloidosis is a clonal plasma cell proliferative disorder characterised by extracellular tissue deposits of insoluble fibrils derived from κ or λ immunoglobulin light chains. The most common organs affected by AL amyloidosis are the kidney, presenting with nephrotic syndrome and/or progressive renal dysfunction, and the heart, with restrictive cardiomyopathy. Hepatic deposition of fibrils occurs in half the cases but the liver is rarely the predominantly affected organ. The most common presentation of hepatic amyloidosis is hepatomegaly with elevated alkaline phosphatase. Acute liver failure with cholestasis and jaundice is a rare complication, with a prevalence of approximately 5%, and is usually associated with a worse prognosis. We report a case of a 39-year-old man admitted to our nephrology department with an unusual presentation of primary amyloidosis with nephrotic syndrome and acute liver failure, complicated by obstructive cholestasis resulting in death 2 months after diagnosis. PMID:26965175

  7. Renal AA amyloidosis: survey of epidemiologic and laboratory data from one nephrology centre.

    PubMed

    Potysová, Z; Merta, M; Tesar, V; Jancová, E; Honsová, E; Rysavá, R

    2009-12-01

    Renal amyloid involvement results, especially, from AL (primary) or AA (secondary) amyloidosis. The extent of amyloid tissue deposits in the kidneys and the clinical course of amyloidosis not only depend on the type of basic process but also reflect the time of diagnosis and the ability to affect the underlying disease. We analyzed laboratory and clinical data from patients with bioptically proven renal amyloidosis. Renal amyloidosis was found in 99 patients (4.65%) from an overall number of 2,128 renal biopsies (RB) performed in our department during a period of 11 years (from 1995 to 2006). AA amyloidosis was diagnosed in 46 patients. Nephrotic syndrome was diagnosed in 27 patients (59%) with AA amyloidosis; all these patients had different degrees of proteinuria. Impaired renal function was discovered in 24 patients (52%); in three of these patients (6.5%) we had to start renal replacement therapy. Patients were treated with corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biological therapy in various regimens. Nine patients (19.5%) died during the one-year follow-up period; complications such as sepsis and cardiac failure were the leading causes of death. Median survival in the AA group was 54 months. Although for approximately half of patients different treatment regimens can lead to a partial remission or disease stabilization, the prognosis of patients with amyloidosis could be regarded as unsatisfactory. PMID:19184513

  8. The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave-Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis.

    PubMed

    Sun, Weiyi; Sun, Jian; Zou, Lili; Shen, Kaini; Zhong, Dingrong; Zhou, Daobin; Sun, Wei; Li, Jian

    2015-01-01

    Laser microdissection followed by mass spectrometry has been successfully used for amyloid typing. However, sample contamination can interfere with proteomic analysis, and overnight digestion limits the analytical throughput. Moreover, current quantitative analysis methods are based on the spectrum count, which ignores differences in protein length and may lead to misdiagnoses. Here, we developed a microwave-assisted filter-aided sample preparation (maFASP) method that can efficiently remove contaminants with a 10-kDa cutoff ultrafiltration unit and can accelerate the digestion process with the assistance of a microwave. Additionally, two parameters (P- and D-scores) based on the exponentially modified protein abundance index were developed to define the existence of amyloid deposits and those causative proteins with the greatest abundance. Using our protocol, twenty cases of systemic amyloidosis that were well-typed according to clinical diagnostic standards (training group) and another twenty-four cases without subtype diagnoses (validation group) were analyzed. Using this approach, sample preparation could be completed within four hours. We successfully subtyped 100% of the cases in the training group, and the diagnostic success rate in the validation group was 91.7%. This maFASP-aided proteomic protocol represents an efficient approach for amyloid diagnosis and subtyping, particularly for serum-contaminated samples. PMID:25984759

  9. The Successful Diagnosis and Typing of Systemic Amyloidosis Using A Microwave-Assisted Filter-Aided Fast Sample Preparation Method and LC/MS/MS Analysis

    PubMed Central

    Zou, Lili; Shen, Kaini; Zhong, Dingrong; Zhou, Daobin; Sun, Wei; Li, Jian

    2015-01-01

    Laser microdissection followed by mass spectrometry has been successfully used for amyloid typing. However, sample contamination can interfere with proteomic analysis, and overnight digestion limits the analytical throughput. Moreover, current quantitative analysis methods are based on the spectrum count, which ignores differences in protein length and may lead to misdiagnoses. Here, we developed a microwave-assisted filter-aided sample preparation (maFASP) method that can efficiently remove contaminants with a 10-kDa cutoff ultrafiltration unit and can accelerate the digestion process with the assistance of a microwave. Additionally, two parameters (P- and D-scores) based on the exponentially modified protein abundance index were developed to define the existence of amyloid deposits and those causative proteins with the greatest abundance. Using our protocol, twenty cases of systemic amyloidosis that were well-typed according to clinical diagnostic standards (training group) and another twenty-four cases without subtype diagnoses (validation group) were analyzed. Using this approach, sample preparation could be completed within four hours. We successfully subtyped 100% of the cases in the training group, and the diagnostic success rate in the validation group was 91.7%. This maFASP-aided proteomic protocol represents an efficient approach for amyloid diagnosis and subtyping, particularly for serum-contaminated samples. PMID:25984759

  10. A simple screening test for variant transthyretins associated with familial transthyretin amyloidosis using isoelectric focusing.

    PubMed

    Connors, L H; Ericsson, T; Skare, J; Jones, L A; Lewis, W D; Skinner, M

    1998-09-30

    Variant forms of the plasma protein transthyretin (TTR) are associated with the most frequently occurring type of familial systemic amyloidosis. Organ system involvement in transthyretin type amyloidosis (ATTR) is often similar to that which occurs in light chain amyloid disease (AL). The proper diagnosis of ATTR is important since treatment (liver transplantation) differs from that in AL (chemotherapy). We present a two-step test to screen sera for variant TTRs using non-denaturing gel electrophoresis performed in 7.5% acrylamide (PAGE) followed by isoelectric focusing (IEF) between pH 4.0 and 7.0 in 2.5 M urea. Serum samples from 110 patients with amyloidosis and their relatives were tested using this IEF technique and compared to genetic mutation results. Sera from patients with ATTR who underwent liver transplantation were also examined prior to and following surgery. IEF analysis showed the presence of both wild-type and variant TTR in 74 of the 110 serum samples tested. Genomic DNA from peripheral blood was used to identify TTR gene mutations in 77 of the 110 patients. Fifteen variants including Val122Ile, preponderant in the African-American population, could be demonstrated by IEF. The sensitivity of IEF was 96% (74/77) and the specificity was 100% (33/33). The predictive values for a positive or negative result were 100% (74/74) and 92% (33/36), respectively. There were no false-positive results and 4% (3/77) false-negative results. In sera from patients with ATTR who underwent liver transplantation, variant TTR was detected by IEF before, but not after, surgery. A simple, accurate, sensitive method is presented as a useful screening test for variant transthyretins associated with ATTR. PMID:9748569

  11. Nodular Cutaneous Amyloidosis at the Temple.

    PubMed

    Schucht, Kathrin; Schröder, Josef; Siegmund, Heiko; Grafe, Claudia; Schreml, Stephan

    2016-01-01

    A 52-year-old woman presented with a large partially yellow and erythematous tumor on her right temple. She reported that it had grown over the last 4 years. Regional lymph nodes were impalpable. A punch biopsy showed eosinophilic material in the dermis and subcutis. Immunohistochemistry showed positive staining for kappa and lambda light chains. Electron microscopy showed the typical amyloid fibrils (7-10 nm in diameter). There was no evidence of systemic amyloidosis, paraproteinemia or underlying plasmacytoma. The tumor was completely removed via curettage. At follow-up, the patient presented in good health with no signs of relapse. PMID:27504090

  12. Nodular Cutaneous Amyloidosis at the Temple

    PubMed Central

    Schucht, Kathrin; Schröder, Josef; Siegmund, Heiko; Grafe, Claudia; Schreml, Stephan

    2016-01-01

    A 52-year-old woman presented with a large partially yellow and erythematous tumor on her right temple. She reported that it had grown over the last 4 years. Regional lymph nodes were impalpable. A punch biopsy showed eosinophilic material in the dermis and subcutis. Immunohistochemistry showed positive staining for kappa and lambda light chains. Electron microscopy showed the typical amyloid fibrils (7–10 nm in diameter). There was no evidence of systemic amyloidosis, paraproteinemia or underlying plasmacytoma. The tumor was completely removed via curettage. At follow-up, the patient presented in good health with no signs of relapse. PMID:27504090

  13. Coexistent Multiple Myeloma or Increased Bone Marrow Plasma Cells Define Equally High-Risk Populations in Patients With Immunoglobulin Light Chain Amyloidosis

    PubMed Central

    Kourelis, Taxiarchis V.; Kumar, Shaji K.; Gertz, Morie A.; Lacy, Martha Q.; Buadi, Francis K.; Hayman, Suzanne R.; Zeldenrust, Steven; Leung, Nelson; Kyle, Robert A.; Russell, Stephen; Dingli, David; Lust, John A.; Lin, Yi; Kapoor, Prashant; Rajkumar, S. Vincent; McCurdy, Arleigh; Dispenzieri, Angela

    2013-01-01

    Purpose There is consensus that patients with light chain (AL) amyloidosis with hypercalcemia, renal failure, anemia, and lytic bone lesions attributable to clonal expansion of plasma cells (CRAB criteria) also have multiple myeloma (MM). The aim of this study was to examine the spectrum of immunoglobulin AL amyloidosis with and without MM, with a goal of defining the optimal bone marrow plasma cell (BMPC) number to qualify as AL amyloidosis with MM. Patients and Methods We identified 1,255 patients with AL amyloidosis seen within 90 days of diagnosis between January 1, 2000, and December 31, 2010. We defined a population of patients with coexisting MM on the basis of the existence of CRAB criteria (AL-CRAB). Receiver operating characteristic analysis determined the optimal BMPC cut point to predict for 1-year mortality in patients with AL amyloidosis without CRAB to produce two additional groups: AL only (≤ 10% BMPCs) and AL plasma cell MM (AL-PCMM; > 10% BMPCs). Results Among the 1,255 patients, 100 (8%) had AL-CRAB, 476 (38%) had AL-PCMM, and 679 (54%) had AL only. Their respective median overall survival rates were 10.6, 16.2, and 46 months (P < .001). Because the outcomes of AL-CRAB and AL-PCMM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, pooled AL-CRAB and AL-PCMM retained negative prognostic value independent of age, Mayo Clinic AL amyloidosis stage, prior autologous stem-cell transplantation, and difference between the involved and uninvolved free light chain. Conclusion Patients with AL amyloidosis who have more than 10% BMPCs have a poor prognosis, similar to that of patients with AL-CRAB, and should therefore be considered together as AL amyloidosis with MM. PMID:24145344

  14. Cardiac Amyloidosis: Typical Imaging Findings and Diffuse Myocardial Damage Demonstrated by Delayed Contrast-Enhanced MRI

    SciTech Connect

    Sueyoshi, Eijun Sakamoto, Ichiro; Okimoto, Tomoaki; Hayashi, Kuniaki; Tanaka, Kyouei; Toda, Genji

    2006-08-15

    Amyloidosis is a rare systemic disease. However, involvement of the heart is a common finding and is the most frequent cause of death in amyloidosis. We report the sonographic, scintigraphic, and MRI features of a pathologically proven case of cardiac amyloidosis. Delayed contrast-enhanced MR images, using an inversion recovery prepped gradient-echo sequence, revealed diffuse enhancement in the wall of both left and right ventricles. This enhancement suggested expansion of the extracellular space of the myocardium caused by diffuse myocardial necrosis secondary to deposition of amyloid.

  15. THE AUTOIMMUNE CONSTELLATION IN LICHEN AMYLOIDOSIS.

    PubMed

    Andrese, Elena; Vâţă, D; Ciobanu, Delia; Stătescu, Laura; Solovăstru, Laura Gheucă

    2015-01-01

    Localized cutaneous amyloidosis is a rare disease among white people, being more common in South-Asia, China and South America. The disease is characterized by deposition of amyloid material in the papillary dermis without visceral involvement. Nevertheless, there is a growing list of immune-mediated disorders that have been linked to cutaneous amyloidosis. We present two cases of concomitant occurrence of lichen amyloidosis and autoimmune thyroiditis/atopic dermatitis in two Caucasian women. PMID:26793847

  16. Single Nodular Pulmonary Amyloidosis: Case Report

    PubMed Central

    Ko, Young Chun; Jeong, Jong Pil; Park, Chan Woo; Seo, Seok Ho; Kim, Jong Taek; Park, Dae Won; Bak, Cheol Min; Moon, Seung Ki; Jo, Shin Hyoung; Kim, Se Mi; Jung, Ah Lon

    2015-01-01

    Amyloidosis is defined as the presence of extra-cellular deposits of an insoluble fibrillar protein, amyloid. The pulmonary involvement of amyloidosis is usually classified as tracheobronchial, parenchymal nodular, or diffuse alveolar septal. A single nodular lesion can mimic various conditions, including malignancy, pulmonary tuberculosis, and fungal infection. To date, only one case of nodular pulmonary amyloidosis has been reported in Korea, a case involving multiple nodular lesions. Here, we report and discuss the case of a patient having single nodular amyloidosis. PMID:26508930

  17. [Amyloidosis in infected Didelphis marsupialis].

    PubMed

    Roa, Diana Milena; Sarmiento, Ladys; Rodríguez, Gerzaín

    2002-09-01

    A male opossum, Didelphis marsupialis, captured in Teruel (Huila), Colombia, was inoculated intraperitoneally with 1 x 10(6) promastigotes of Leishmania chagasi (MHOM/CO/84/CL044B). The animal died 5 weeks after inoculation. Autopsy revealed signs of visceral leishmaniasis along with amastigote parasite form in Kupffer cells and spleen macrophages. Amyloid deposits in liver and spleen were demonstrated by histological staining and electron microscopy. The rapid death was considered a consequence of a secondary, reactive amyloidosis. PMID:12404923

  18. Isolated heart transplantation for familial transthyretin (TTR) V122I cardiac amyloidosis.

    PubMed

    Thenappan, Thenappan; Fedson, Savitri; Rich, Jonathan; Murks, Catherine; Husain, Aliya; Pogoriler, Jennifer; Anderson, Allen S

    2014-06-01

    Transthyretin (TTR) cardiac amyloidosis is characterized by deposition of either mutant or wild type TTR amyloid protein in the myocardium ultimately leading to progressive cardiomyopathy and heart failure. The most common TTR gene mutation that leads to TTR cardiac amyloidosis is the valine-to-isoleucine substitution at position 122 (V122I or Ile122). Currently, the only definitive treatment suggested for mutant TTR cardiac amyloidosis is the combined or sequential liver-heart transplantation in eligible patients, since liver is the source of TTR production. Here, we report a case of heterozygous Val122L mutated TTR-related cardiac amyloidosis treated with isolated heart transplantation with no recurrence of amyloid in the cardiac allograft and no systemic abnormalities 5 years after heart transplantation. Abbreviations MMF mycophenolate mofetil NYHA New York Heart Association TTR transthyretin VE minute ventilation. PMID:24818650

  19. A renal transplant recipient with delayed gastric emptying in amyloidosis due to familial Mediterranean fever improved with erythromycin: a case report.

    PubMed

    Saglam, F; Celik, A; Cavdar, C; Sifil, A; Atila, K; Kaya, G C; Bora, S; Gulay, H; Camsari, T

    2008-01-01

    Patients with systemic amyloidosis often have symptoms related to impared gastrointestinal motility due to delayed gastric emptying, which results from autonomic nerve or smooth muscle infiltration with amyloid. There is no current report about gastric delaying secondary to amyloidosis due to familial Mediterranean fever. In this report, we have described a renal transplant recipient with delayed gastric emptying secondary to amyloidosis due to familial Mediterranean fever, which improved with erithromycin treatment. PMID:18261613

  20. Duodenal Amyloidosis Masquerading as Iron Deficiency Anemia

    PubMed Central

    Hurairah, Abu

    2016-01-01

    The present study is a unique illustration of duodenal amyloidosis initially manifesting with iron deficiency anemia. It underscores the importance of clinical suspicion of amyloidosis while performing upper gastrointestinal endoscopy with a biopsy to establish the definite diagnosis in patients with unexplained iron deficiency anemia. PMID:27625911

  1. Pathophysiology and treatment of cardiac amyloidosis.

    PubMed

    Gertz, Morie A; Dispenzieri, Angela; Sher, Taimur

    2015-02-01

    Amyloid cardiomyopathy should be suspected in any patient who presents with heart failure and preserved ejection fraction. In patients with echocardiographic evidence of ventricular thickening and without a clear history of hypertension, infiltrative cardiomyopathy should be considered. If imaging suggests the presence of amyloid deposits, confirmation by biopsy is required, although endomyocardial biopsy is generally not necessary. Assessment of aspirated subcutaneous fat and bone-marrow biopsy samples verifies the diagnosis in 40-80% of patients, dependent on the type of amyloidosis. Mass spectroscopy can be used to determine the protein subunit and classify the disease as immunoglobulin light-chain amyloidosis or transthyretin-related amyloidosis associated with mutant or wild-type TTR (formerly known as familial amyloid cardiomyopathy and senile cardiac amyloidosis, respectively). In this Review, we discuss the characteristics of cardiac amyloidosis, and present a structured approach to both the assessment of patients and treatment with emerging therapies and organ transplantation. PMID:25311231

  2. Tissue distribution of amyloid deposits in Abyssinian cats with familial amyloidosis.

    PubMed

    DiBartola, S P; Tarr, M J; Benson, M D

    1986-07-01

    The tissue distribution of amyloid deposits was studied in 15 related Abyssinian cats with familial amyloidosis. There was interstitial medullary amyloidosis in the kidneys of all 15 cats but only 11 had detectable glomerular involvement. The thyroid glands, stomach and colon were affected in all cats examined. Most of the cats also had amyloid deposits in the small intestine, spleen, heart, adrenals, pancreas, liver, lymph nodes and bladder. In 50 per cent or fewer of the cats examined, there was involvement of the parathyroids, lung and gonads. The central nervous system was not involved in any of the 3 cats evaluated. In 8 of the cats, no concurrent inflammatory disease could be detected. The tissue distribution of amyloid deposits resembled that found in other breeds of domestic cats with systemic amyloidosis. Despite the wide tissue distribution of amyloid deposits, clinical signs were related to renal amyloidosis. Familial amyloidosis in the Abyssinian cat may represent a valuable spontaneous animal model for the study of Familial Mediterranean Fever in man and the pathogenesis of reactive amyloidosis in general. PMID:3734172

  3. Nuclear imaging modalities for cardiac amyloidosis

    PubMed Central

    Bokhari, Sabahat; Shahzad, Reehan; Castaño, Adam; Maurer, Mathew S.

    2015-01-01

    Amyloidosis is a heterogeneous group of diseases characterized by localized or systemic deposition of insoluble extracellular fibrillary proteins in organs and tissues. Several types of amyloid can infiltrate the heart resulting in a restrictive cardiomyopathy, heart failure, and atrial and ventricular arrhythmias. Scintigraphy is a noninvasive method that may facilitate early diagnosis, distinguish various forms of cardiac amyloid, and may be useful in following disease burden. The amyloid-specific tracers presented in this article have been used with planar imaging and/or single-photon emission computed tomography. To date, there are no approved cardiac amyloid tracers although investigational tracers are currently under examination. This article serves to review the current nuclear imaging modalities available in the detection of cardiac amyloid. PMID:24162886

  4. Primary amyloidosis and severe intrahepatic cholestatic jaundice.

    PubMed Central

    Peters, R A; Koukoulis, G; Gimson, A; Portmann, B; Westaby, D; Williams, R

    1994-01-01

    Liver involvement in systemic amyloidosis is frequent but is rarely of clinical importance. Five patients with severe cholestatic jaundice are described and an additional 20 from published reports are reviewed. The most frequent presenting symptoms were lethargy and abdominal pain, which were present for a median of 11 months before the onset of jaundice. Hepatomegaly, usually marked, was present in 92%, with ascites in 56% of the cases. The serum bilirubin concentration was noticeably high and the serum globulin low. Histology of the liver showed considerable perisinusoidal deposition with a slight predilection for the periportal area. Two patients presented with predominant centrilobular deposition. Congo red staining was not uniformly positive. A variety of treatment regimens was tried but median survival was only three months from the onset of jaundice. PMID:7959246

  5. Diflunisal for ATTR Cardiac Amyloidosis

    PubMed Central

    Castaño, Adam; Helmke, Stephen; Alvarez, Julissa; Delisle, Susan; Maurer, Mathew S.

    2013-01-01

    Transthyretin (TTR) cardiac amyloidosis is an important, often under-recognized and potentially modifiable cause of heart failure with a preserved ejection fraction. The only proven treatment is liver or combined heart/liver transplantation, which, although effective, is not suitable for the vast majority of older adults with this condition. Diflunisal, a nonsteroidal anti-inflammatory drug, can stabilize the TTR tetramer in vitro and may prevent misfolding monomers and dimers from forming amyloid deposits in the heart. It is one of two small molecules assessed in animal safety studies and human clinical trials of TTR polyneuropathy. The authors conducted a single-arm, open-label investigation with a mean follow-up of 0.9±0.3 years to determine the safety and efficacy of diflunisal administration in a cohort of 13 patients with confirmed wild-type or mutant TTR cardiac amyloidosis. Diflunisal was well tolerated from a hematologic standpoint, although a 6% decline in estimated glomerular filtration rate was noted. Therapy was discontinued in one patient who rapidly developed volume overload. There was no significant mean change in cardiac structure (left ventricular mass: −53 g/m2 change, P=.36), function (ejection fraction: −2% change, P=.61), or biomarkers (Troponin I: +0.03 ng/mL, P=.08; BNP: +93 pg/mL change, P=.52) during the course of therapy. These data suggest that at low dosages and with careful monitoring, diflunisal can be safely administered to compensated patients with cardiac TTR amyloidosis. Further study in a randomized placebo-controlled trial is warranted. PMID:22747647

  6. Tracheobronchial amyloidosis and confocal endomicroscopy.

    PubMed

    Newton, Richard C; Kemp, Samuel V; Yang, Guang-Zhong; Darzi, Ara; Sheppard, Mary N; Shah, Pallav L

    2011-01-01

    Tracheobronchial amyloidosis is one of many causes of endobronchial stenosis and nodularity, the concrete diagnosis of which currently requires the finding of apple-green birefringence from endobronchial biopsies. Bronchoscopic probe-based confocal endomicroscopy (pCLE) is a novel optical biopsy technique which provides real-time images of the lattice structure of the bronchial basement membrane - a finding lost in malignancy. This case study outlines the imperfect, essentially palliative management of this rare disease, and shows for the first time the unusual dappled in vivo pCLE images of amyloid-affected endobronchium. PMID:21430359

  7. Renal amyloidosis--a clinicopathologic study.

    PubMed

    Shah, V B; Phatak, A M; Shah, B S; Kandalkar, B M; Haldankar, A R; Ranganathan, S

    1996-07-01

    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. PMID:8972145

  8. Laryngeal amyloidosis causing hoarseness and airway obstruction.

    PubMed

    Gallivan, Gregory J; Gallivan, Helen K

    2010-03-01

    Amyloidosis constitutes a fraction of 1% of benign localized laryngeal tumors and may occasionally be associated with systemic disease. A chronic, insidious, progressive, recurrent disease characterized by hoarseness, dyspnea, and stridor, it is caused by extracellular deposition of insoluble, abnormal tissue injurious fibrils. Submucosal lesions occur frequently in the vestibular folds and ventricles, less commonly in the subglottis and aryepiglottic folds and least on the vocal folds. Apple green birefrigence under polarized light after Congo red staining, electron microscopic fibrillar structure, and a beta-pleated sheet structure observed by x-ray diffraction are confirmatory. Two presented cases add to the small literature review of similar patients. Case 1 was a 70-year-old man with severe hoarseness, incomplete glottic closure, ovoid concentric stenosis of the inferior glottis and subglottis, who initially was not diagnosed by several laryngologists and speech therapists. He required multiple microlaryngoscopic excisions and dilations. Because low dose radiation induces plasma cell apoptosis in other diseases, external beam radiation therapy (EBRT) was hypothesized to eliminate amyloidogenic plasma cells. Case 2 was a 46-year-old welder with progressive dyspnea for 2-3 years and hoarseness, voice loss, and stridor over 6-7 months. Masses caused airway obstruction of the anterior commissure, vestibular, and vocal folds, with extension to the subglottis. Two phonomicrosurgical CO(2) laser-assisted resections relieved upper airway obstruction and restored voice. Conservative surgical intervention and long-term followup are essential. Further studies are needed to determine if a radiation dose response relationship exists to control laryngeal amyloidosis. PMID:19111441

  9. Magnetic resonance imaging in cardiac amyloidosis

    SciTech Connect

    O'Donnell, J.K.; Go, R.T.; Bott-Silverman, C.; Feiglin, D.H.; Salcedo, E.; MacIntyre, W.J.

    1984-01-01

    Primary amyloidosis (AL) involves the myocardium in 90% of cases and may present as apparent ischemia, vascular disease, or congestive heart failure. Two-dimensional echocardiography (echo) has proven useful in the diagnosis, particularly in differentiating AL from constrictive pericarditis. The findings of thickened RV and LV myocardium, normal LV cavity dimension, and a diffuse hyperrefractile ''granular sparkling'' appearance are virtually diagnostic. Magnetic resonance (MR) imaging may improve the resolution of anatomic changes seen in cardiac AL and has the potential to provide more specific information based on biochemical tissue alterations. In this preliminary study, the authors obtained both MR and echo images in six patients with AL and biopsy-proven myocardial involvement. 5/6 patients also had Tc-99 PYP myocardial studies including emission tomography (SPECT). MR studies utilized a 0.6 Tesla superconductive magnet. End diastolic gated images were obtained with TE=30msec and TR=R-R interval on the ECG. 6/6 pts. showed LV wall thickening which was concentric and included the septum. Papillary muscles were identified in all and were enlarged in 3/6. 4/6 pts. showed RV wall thickening but to a lesser degree than LV. Pericardial effusions were present in 4 cases. These findings correlated well with the results of echo although MR gave better RV free wall resolution. PYP scans were positive in 3 pts. but there was no correlation with degree of LV thickening. The authors conclude that there are no identifiable MR findings in patients with cardiac AL which encourage further attempts to characterize myocardial involvement by measurement of MR relaxation times in vivo.

  10. Pneumatosis intestinalis due to gastrointestinal amyloidosis: A case report & review of literature

    PubMed Central

    Khalid, Filza; Kaiyasah, Hadiel; Binfadil, Wafa; Majid, Maiyasa; Hazim, Wessam; ElTayeb, Yousif

    2016-01-01

    Introduction Pneumatosis intestinalis (PI) is not a disease but a radiological finding with a poorly understood pathogenesis. It can be divided into primary/idiopathic (15%) or secondary (85%) Kim et al. 2007, based on the factors thought to play a role in its development. Amongst the rare causes of secondary PI is gastrointestinal (GI) amyloidosis. Presentation of the case We report a case of a 46-year-old gentleman who presented with a one month history of acute on chronic abdominal pain, associated with one episode of melena. Upon further investigation, he was found to have pneumoperitoneum. He was taken to the operating theatre, where he was noted to have features of pneumatosis intestinalis of the small bowel with no evidence of bowel perforation. Postoperatively, he underwent an upper GI endoscopy with biopsies that revealed GI amyloidosis. Discussion One of the rare causes that can lead to secondary PI is GI amyloidosis as proven in our case. Patients with symptomatic gastrointestinal amyloidosis usually present with one of four syndromes: gastrointestinal bleeding, malabsorption, protein-losing gastroenteropathy, and, less often, gastrointestinal dysmotility. Conclusion GI amyloidosis is a rare cause of secondary pneumatosis intestinalis. The presentation of the disease varies from patient to patient, therefore, the management should be tailored accordingly. PMID:27085104

  11. AA-negative and Kappa-positive Amyloidosis in a Patient with Rheumatoid Arthritis.

    PubMed

    Ueno, Toshiharu; Sumida, Keiichi; Hoshino, Junichi; Suwabe, Tatsuya; Mise, Koki; Hazue, Ryo; Hayami, Noriko; Hiramatsu, Rikako; Kawada, Masahiro; Imafuku, Aya; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Kinowaki, Keiichi; Ohashi, Kenichi; Fujii, Takeshi; Nishida, Aya; Ubara, Yoshifumi

    2016-01-01

    A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain. Combination therapy with high-dose melphalan and autologous stem cell transplantation was performed according to the regimen for AL amyloidosis. Her proteinuria and RA subsided, but relapsed after 3 years. This is the first report regarding kappa light chain amyloidosis in an RA patient. PMID:27580556

  12. Oral primary localized amyloidosis in HIV-infected patients: the oral face of a described skin lesion.

    PubMed

    Anaya-Saavedra, Gabriela; Ramírez-Amador, Velia; Valencia-Mayoral, Pedro

    2015-12-01

    Oral primary localized amyloidosis should be considered in the diagnosis of oral white lesions such as hyperplastic candidosis, lichen planus and lichenoid reactions; it is not associated with antiretroviral therapy use, systemic involvement or malignant transformation. PMID:25586447

  13. In situ characterization of protein aggregates in human tissues affected by light chain amyloidosis: a FTIR microspectroscopy study.

    PubMed

    Ami, Diletta; Lavatelli, Francesca; Rognoni, Paola; Palladini, Giovanni; Raimondi, Sara; Giorgetti, Sofia; Monti, Luca; Doglia, Silvia Maria; Natalello, Antonino; Merlini, Giampaolo

    2016-01-01

    Light chain (AL) amyloidosis, caused by deposition of amyloidogenic immunoglobulin light chains (LCs), is the most common systemic form in industrialized countries. Still open questions, and premises for developing targeted therapies, concern the mechanisms of amyloid formation in vivo and the bases of organ targeting and dysfunction. Investigating amyloid material in its natural environment is crucial to obtain new insights on the molecular features of fibrillar deposits at individual level. To this aim, we used Fourier transform infrared (FTIR) microspectroscopy for studying in situ unfixed tissues (heart and subcutaneous abdominal fat) from patients affected by AL amyloidosis. We compared the infrared response of affected tissues with that of ex vivo and in vitro fibrils obtained from the pathogenic LC derived from one patient, as well as with that of non amyloid-affected tissues. We demonstrated that the IR marker band of intermolecular β-sheets, typical of protein aggregates, can be detected in situ in LC amyloid-affected tissues, and that FTIR microspectroscopy allows exploring the inter- and intra-sample heterogeneity. We extended the infrared analysis to the characterization of other biomolecules embedded within the amyloid deposits, finding an IR pattern that discloses a possible role of lipids, collagen and glycosaminoglycans in amyloid deposition in vivo. PMID:27373200

  14. In situ characterization of protein aggregates in human tissues affected by light chain amyloidosis: a FTIR microspectroscopy study

    PubMed Central

    Ami, Diletta; Lavatelli, Francesca; Rognoni, Paola; Palladini, Giovanni; Raimondi, Sara; Giorgetti, Sofia; Monti, Luca; Doglia, Silvia Maria; Natalello, Antonino; Merlini, Giampaolo

    2016-01-01

    Light chain (AL) amyloidosis, caused by deposition of amyloidogenic immunoglobulin light chains (LCs), is the most common systemic form in industrialized countries. Still open questions, and premises for developing targeted therapies, concern the mechanisms of amyloid formation in vivo and the bases of organ targeting and dysfunction. Investigating amyloid material in its natural environment is crucial to obtain new insights on the molecular features of fibrillar deposits at individual level. To this aim, we used Fourier transform infrared (FTIR) microspectroscopy for studying in situ unfixed tissues (heart and subcutaneous abdominal fat) from patients affected by AL amyloidosis. We compared the infrared response of affected tissues with that of ex vivo and in vitro fibrils obtained from the pathogenic LC derived from one patient, as well as with that of non amyloid-affected tissues. We demonstrated that the IR marker band of intermolecular β-sheets, typical of protein aggregates, can be detected in situ in LC amyloid-affected tissues, and that FTIR microspectroscopy allows exploring the inter- and intra-sample heterogeneity. We extended the infrared analysis to the characterization of other biomolecules embedded within the amyloid deposits, finding an IR pattern that discloses a possible role of lipids, collagen and glycosaminoglycans in amyloid deposition in vivo. PMID:27373200

  15. Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis.

    PubMed

    Gertz, Morie A; Benson, Merrill D; Dyck, Peter J; Grogan, Martha; Coelho, Terresa; Cruz, Marcia; Berk, John L; Plante-Bordeneuve, Violaine; Schmidt, Hartmut H J; Merlini, Giampaolo

    2015-12-01

    Transthyretin amyloidosis is a fatal disorder that is characterized primarily by progressive neuropathy and cardiomyopathy. It occurs in both a mutant form (with autosomal dominant inheritance) and a wild-type form (with predominant cardiac involvement). This article guides clinicians as to when the disease should be suspected, describes the appropriate diagnostic evaluation for those with known or suspected amyloidosis, and reviews the interventions currently available for affected patients. PMID:26610878

  16. A rare cause of secondary amyloidosis: common variable immunodeficiency disease.

    PubMed

    Kadiroğlu, Ali Kemal; Yıldırım, Yaşar; Yılmaz, Zülfükar; Kayabaşı, Hasan; Avcı, Yahya; Yıldırım, M Serdar; Yılmaz, M Emin

    2012-01-01

    The common variable immunodeficiency disease (CVID) is the most common symptomatic primary antibody deficiency. It is the most frequently observed cause of panhypogammaglobulinemia in adults. Here, we present a case of systemic amyloidosis that developed secondary to the common variable immunodeficiency disease causing recurrent infections in a young female patient. A 24-year-old female patient, who was under treatment at the gynecology and obstetrics clinic for pelvic inflammatory disease, was referred to our clinic when she was observed to have swellings in her legs, hands, and face. She had proteinuria at a rate of 3.5 gr/day, and her serum albumin was 1.5 gr/dl. The levels of immunoglobulins are IgG: 138 mg/dl, IgA: 22,6 mg/dl, and IgM: 16,8 mg/dl. The renal USG revealed that the kidneys were observed to be enlarged. Since the patient had recurrent infections, hypogammaglobulinemia, nephrotic range proteinuria, and enlarged kidneys in the renal USG, she was thought to have type AA amyloidosis and therefore underwent a renal biopsy. The kidney biopsy revealed amyloid (+). So the patient was diagnosed with AA type of amyloidosis secondary to common variable immunodeficiency disease. A treatment regimen (an ACE inhibitor and a statin) with monthly administration of intravenous immunoglobulin was started. PMID:24558615

  17. Amyloidosis: an unusual cause of portal hypertension

    PubMed Central

    Laborda, Lorena Silva; Bernardelli, Raquel; Pinesi, Henrique Trombini; Silva, Marilia Polo Minguete e; Chiavelli, Viviane; Simões, Angélica Braz; Felipe-Silva, Aloisio

    2016-01-01

    Amyloidosis comprises a group of diseases that occurs in five to nine cases per million patients per year worldwide irrespective of its classification. Although the hepatic involvement in primary amyloidosis is frequent, the clinical manifestations of liver amyloidosis are mild or even absent. The authors report the case of an aged man who complained of diffuse abdominal pain and marked weight loss and presented clinical signs of hepatopathy. Clinical workup revealed portal hypertension with ascites, hemorrhoids, and esophageal varices. The laboratory tests showed the cholestatic pattern of liver enzymes, hyperbilirubinemia, renal insufficiency and massive proteinuria accompanied by the presence of serum pike of monoclonal lambda light chain protein. The outcome was unfavorable, and the patient died. The autopsy findings revealed the diagnosis of amyloidosis predominantly involving the liver and kidneys. The bone marrow examination demonstrated the deposition of amyloid material associated with clonal plasma cells infiltration. The authors call attention to portal hypertension as a rare manifestation of primary amyloidosis. Meanwhile, this diagnosis should be taken into account whenever the hepatopathy is accompanied by laboratory abnormalities consistent with hepatic space-occupying lesions concomitantly with other organs involvement. In the case reported herein, kidney involvement was also present with renal failure, massive proteinuria with monoclonal serum gammopathy, what reinforced the diagnostic possibility of primary amyloidosis. PMID:27547738

  18. Amyloidosis: an unusual cause of portal hypertension.

    PubMed

    Takayasu, Vilma; Laborda, Lorena Silva; Bernardelli, Raquel; Pinesi, Henrique Trombini; Silva, Marilia Polo Minguete E; Chiavelli, Viviane; Simões, Angélica Braz; Felipe-Silva, Aloisio

    2016-01-01

    Amyloidosis comprises a group of diseases that occurs in five to nine cases per million patients per year worldwide irrespective of its classification. Although the hepatic involvement in primary amyloidosis is frequent, the clinical manifestations of liver amyloidosis are mild or even absent. The authors report the case of an aged man who complained of diffuse abdominal pain and marked weight loss and presented clinical signs of hepatopathy. Clinical workup revealed portal hypertension with ascites, hemorrhoids, and esophageal varices. The laboratory tests showed the cholestatic pattern of liver enzymes, hyperbilirubinemia, renal insufficiency and massive proteinuria accompanied by the presence of serum pike of monoclonal lambda light chain protein. The outcome was unfavorable, and the patient died. The autopsy findings revealed the diagnosis of amyloidosis predominantly involving the liver and kidneys. The bone marrow examination demonstrated the deposition of amyloid material associated with clonal plasma cells infiltration. The authors call attention to portal hypertension as a rare manifestation of primary amyloidosis. Meanwhile, this diagnosis should be taken into account whenever the hepatopathy is accompanied by laboratory abnormalities consistent with hepatic space-occupying lesions concomitantly with other organs involvement. In the case reported herein, kidney involvement was also present with renal failure, massive proteinuria with monoclonal serum gammopathy, what reinforced the diagnostic possibility of primary amyloidosis. PMID:27547738

  19. Primary localized cutaneous nodular amyloidosis of the feet: a case report and review of the literature.

    PubMed

    Ritchie, Simon A; Beachkofsky, Thomas; Schreml, Stephan; Gaspari, Anthony; Hivnor, Chad M

    2014-02-01

    Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare disorder that manifests as the cutaneous formation of nodules composed of light-chain amyloid. Although the type of amyloid deposit is similar to primary systemic amyloidosis, there seems to be little, if any, crossover between the 2 diseases. Because reports of PLCNA are sparse, there is no established protocol for treating this disease. This case report presents a 42-year-old man with a visually striking presentation of PLCNA on both feet with some of the lesions possibly being secondary to trauma, a rare phenomenon. The lesions had been present for more than 4 years, and there were no signs or symptoms of systemic amyloidosis. The lesions responded well to a combination of complete curettage followed by CO2; laser ablation. Primary localized cutaneous nodular amyloidosis is rare and difficult to treat, with high rates of recurrence and a concern for progression to systemic amyloidosis. The diagnosis, workup, treatment, and monitoring of PLCNA also are discussed. PMID:24605345

  20. Novel drugs targeting transthyretin amyloidosis.

    PubMed

    Hanna, Mazen

    2014-03-01

    Transthyretin amyloidosis (ATTR) is either a hereditary disease related to a mutation in the transthyretin gene that leads to neuropathy and/or cardiomyopathy or an acquired disease of the elderly that leads to restrictive cardiomyopathy. The prevalence of this disease is higher than once thought and awareness is likely to increase amongst physicians and in particular cardiologists. Until recently there have been no treatment options for this disease except to treat the heart failure with diuretics and the neuropathy symptomatically. However, there are several emerging pharmacologic therapies designed to slow or stop the progression of ATTR. This article reviews novel therapeutic drugs that work at different points in the pathogenesis of this disease attempting to change its natural history and improve outcomes. PMID:24464360

  1. Localized amyloidosis of the stomach mimicking a superficial gastric cancer.

    PubMed

    Kagawa, Miwako; Fujino, Yasuteru; Muguruma, Naoki; Murayama, Noriaki; Okamoto, Koichi; Kitamura, Shinji; Kimura, Tetsuo; Kishi, Kazuhiro; Miyamoto, Hiroshi; Uehara, Hisanori; Takayama, Tetsuji

    2016-06-01

    A 73-year-old man was referred to our hospital for further examination of a depressed lesion in the stomach found by cancer screening gastroscopy. A barium upper gastrointestinal series showed an area of irregular mucosa measuring 15 mm on the anterior wall of the gastric body. Esophagogastroduodenoscopy revealed a 15 mm depressed lesion on the anterior wall of the lower gastric body. We suspected an undifferentiated adenocarcinoma from the appearance and took some biopsies. However, histology of the specimens revealed amyloidal deposits in the submucosal layer without malignant findings. Congo red staining was positive for amyloidal protein and green birefringence was observed under polarized light microscopy. Congo red staining with prior potassium permanganate incubation confirmed the light chain (AL) amyloid type. There were no amyloid deposits in the colon or duodenum. Computed tomography of the chest, abdomen, and pelvis showed no remarkable findings. Thus, this case was diagnosed as a localized gastric amyloidosis characterized by AL type amyloid deposition in the mucosal or submucosal layer. As the clinical outcome of gastric AL amyloidosis seems favorable, this case is scheduled for periodic examination to recognize potential disease progression and has been stable for 2 years. PMID:27170299

  2. Outcomes of heart transplantation for cardiac amyloidosis: subanalysis of the spanish registry for heart transplantation.

    PubMed

    Roig, E; Almenar, L; González-Vílchez, F; Rábago, G; Delgado, J; Gómez-Bueno, M; Crespo-Leiro, M G; Arizón, J M; de la Fuente, L; Manito, N

    2009-06-01

    Amyloidosis (Am), a systemic disease, has poor prognosis because of organ damage produced by protein deposition in the extracellular space. Although heart transplantation (HTx) is possible, donor availability concerns and high mortality make this approach controversial. The Spanish Registry for Heart Transplantation includes 25 Am patients (54 +/- 9 years): 13 with AL type, 2 with AA and 10 with TTR mutation. Fifteen patients (60%) died during follow-up (4.9 +/- 1.3 years): 9 AL-Am patients, both AA-Am patients and 4 with TTR-Am. HTx survival for Am patients was similar to patients without Am at 1 month but significantly worse at 5 years: 46% versus 78% (p < 0.02). Of 10 AL-Am patients undergoing successful HTx, 4 died of systemic Am. Stem cell transplantation was performed in 3 (1 died of acute rejection). Five of 10 patients with TTR-Am underwent liver transplant; 4 remained alive at the last follow-up. Findings include poor outcome for AL-Am patients despite HTx and better survival for TTR-Am patients if HTx is associated with liver transplantation. Given the shortage of donors and poor outcome for Am patients, we would recommend that HTx be reserved for patients without or with mild systemic Am and be supplemented by additional therapies as indicated. PMID:19459811

  3. Wild-Type Transthyretin Cardiac Amyloidosis: Novel Insights From Advanced Imaging.

    PubMed

    Narotsky, David L; Castano, Adam; Weinsaft, Jonathan W; Bokhari, Sabahat; Maurer, Mathew S

    2016-09-01

    Amyloidosis is caused by extracellular deposition of abnormal protein fibrils, resulting in destruction of tissue architecture and impairment of organ function. The most common forms of systemic amyloidosis are light-chain and transthyretin-related (ATTR). ATTR can result from an autosomal dominant hereditary transmission of mutated genes in the transthyretin or from a wild-type form of disease (ATTRwt), previously known as senile cardiac amyloidosis. With the aging of the worldwide population, ATTRwt will emerge as the most common type of cardiac amyloidosis that clinicians encounter. Diagnosis of systemic amyloidosis is often delayed, either because of the false assumption that it is a rare disease, or because of misdiagnosis as a result of mistaking it with other conditions. Clinicians must integrate clinical clues from history, physical examination, and common diagnostic tests to raise suspicion for ATTRwt. The historical gold standard for diagnosis of cardiac amyloid is endomyocardial biopsy analysis with pathological distinction of precursor protein type, but this method often results in delayed diagnosis because of the limited availability of expertise to perform and interpret the endomyocardial biopsy specimen. Emerging noninvasive imaging modalities provide easier, accurate screening for ATTRwt. These modalities include advanced echocardiography, using strain imaging and the myocardial contraction fraction; nuclear scintigraphy, which can differentiate between ATTR and light-chain cardiac amyloid; and cardiac magnetic resonance imaging, using extracellular volume measurement, late gadolinium enhancement, and distinct T1 mapping. These novel approaches reveal insights into the prevalence, clinical course, morphological effects, and prognosis of ATTRwt. PMID:27568874

  4. Systems Engineering Techniques for ALS Decision Making

    NASA Technical Reports Server (NTRS)

    Rodriquez, Luis F.; Drysdale, Alan E.; Jones, Harry; Levri, Julie A.

    2004-01-01

    The Advanced Life Support (ALS) Metric is the predominant tool for predicting the cost of ALS systems. Metric goals for the ALS Program are daunting, requiring a threefold increase in the ALS Metric by 2010. Confounding the problem, the rate new ALS technologies reach the maturity required for consideration in the ALS Metric and the rate at which new configurations are developed is slow, limiting the search space and potentially giving the perspective of a ALS technology, the ALS Metric may remain elusive. This paper is a sequel to a paper published in the proceedings of the 2003 ICES conference entitled, "Managing to the metric: an approach to optimizing life support costs." The conclusions of that paper state that the largest contributors to the ALS Metric should be targeted by ALS researchers and management for maximum metric reductions. Certainly, these areas potentially offer large potential benefits to future ALS missions; however, the ALS Metric is not the only decision-making tool available to the community. To facilitate decision-making within the ALS community a combination of metrics should be utilized, such as the Equivalent System Mass (ESM)-based ALS metric, but also those available through techniques such as life cycle costing and faithful consideration of the sensitivity of the assumed models and data. Often a lack of data is cited as the reason why these techniques are not considered for utilization. An existing database development effort within the ALS community, known as OPIS, may provide the opportunity to collect the necessary information to enable the proposed systems analyses. A review of these additional analysis techniques is provided, focusing on the data necessary to enable these. The discussion is concluded by proposing how the data may be utilized by analysts in the future.

  5. THAOS: Gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease

    PubMed Central

    2014-01-01

    Background Transthyretin amyloidosis is a systemic disorder caused by amyloid deposits formed by misfolded transthyretin monomers. Two main forms exist: hereditary and wild-type transthyretin amyloidosis, the former associated with transthyretin gene mutations. There are several disease manifestations; however, gastrointestinal complications are common in the hereditary form. The aim of this study was to explore the prevalence and distribution of gastrointestinal manifestations in transthyretin amyloidosis and to evaluate their impact on the patients’ nutritional status and health-related quality of life (HRQoL). Methods The Transthyretin Amyloidosis Outcomes Survey (THAOS) is the first global, multicenter, longitudinal, observational survey that collects data on patients with transthyretin amyloidosis and the registry is sponsored by Pfizer Inc. This study presents baseline data from patients enrolled in THAOS as of June 2013. The modified body mass index (mBMI), in which BMI is multiplied with serum albumin, was used to assess the nutritional status and the EQ-5D Index was used to assess HRQoL. Results Data from 1579 patients with hereditary transthyretin amyloidosis and 160 patients with wild-type transthyretin amyloidosis were analyzed. Sixty-three percent of those with the hereditary form and 15% of those with the wild-type form reported gastrointestinal symptoms at enrollment. Unintentional weight loss and early satiety were the most frequent symptoms, reported by 32% and 26% of those with transthyretin gene mutations, respectively. Early-onset patients (<50 years) reported gastrointestinal complaints more frequently than those with a late onset (p < 0.001) and gastrointestinal symptoms were more common in patients with the V30M mutation than in those with other mutations (p < 0.001). For patients with predominantly cardiac complications, the prevalence of gastrointestinal manifestations was not evidently higher than that expected in the general

  6. Macular Amyloidosis and Epstein-Barr Virus.

    PubMed

    Nahidi, Yalda; Tayyebi Meibodi, Naser; Meshkat, Zahra; Nazeri, Narges

    2016-01-01

    Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV) DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group). There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8%) and control (23.8%) groups (P = 0.08). Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis. PMID:26981113

  7. Macular Amyloidosis and Epstein-Barr Virus

    PubMed Central

    Nahidi, Yalda; Tayyebi Meibodi, Naser; Meshkat, Zahra; Nazeri, Narges

    2016-01-01

    Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV) DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group). There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8%) and control (23.8%) groups (P = 0.08). Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis. PMID:26981113

  8. Primary localized amyloidosis presenting as diffuse amorphous calcified mass in both orbits: case report.

    PubMed

    Gonçalves, Allan Christian Pieroni; Moritz, Rodrigo Bernal da Costa; Monteiro, Mário Luiz Ribeiro

    2011-01-01

    Primary localized amyloidosis is rare in the orbit. We report the case of a 63-year-old woman that presented with bilateral proptosis and ophthalmoplegia. A computed tomography scan revealed an infiltrative amorphous and markedly calcified mass in both orbits while a magnetic resonance scan showed a heterogeneous hypointense signal on T2-weighted images. A biopsy was performed through an anterior orbitotomy. Microscopy revealed extracellular amorphous and eosinophilic hyaline material which stained pink with Congo red and displayed green birefringence on polarized microscopy, leading to a diagnosis of amyloidosis. The results of the systemic workup were completely normal. A two-year follow-up period without any treatment disclosed no worsening of the condition. While calcification of nonvascular orbital lesions has often been regarded as suggestive of malignant disease, our case is a reminder that it can also be a characteristic presenting sign of orbital amyloidosis. PMID:22184002

  9. Tracheobronchial Amyloidosis Mimicking Tracheal Tumor.

    PubMed

    Tanrıverdi, Elif; Özgül, Mehmet Akif; Uzun, Oğuz; Gül, Şule; Çörtük, Mustafa; Yaşar, Zehra; Acat, Murat; Arda, Naciye; Çetinkaya, Erdoğan

    2016-01-01

    Tracheobronchial amyloidosis is a rare presentation and accounts for about 1% of benign tumors in this area. The diagnosis of disease is delayed due to nonspecific pulmonary symptoms. Therapeutic approaches are required to control progressive pulmonary symptoms for most of the patients. Herein, we report a case of a 68-year-old man admitted with progressive dyspnea to our institution for further evaluation and management. He was initially diagnosed with and underwent management for bronchial asthma for two years but had persistent symptoms despite optimal medical therapy. Pulmonary computed tomography scan revealed severe endotracheal stenosis. Bronchoscopy was performed and showed endotracheal mass obstructing 70% of the distal trachea and mimicking a neoplastic lesion. The mass was successfully resected by mechanical resection, argon plasma coagulation (APC), and Nd-YAG laser during rigid bronchoscopy. Biopsy materials showed deposits of amorphous material by hematoxylin and eosin staining and these deposits were selectively stained with Congo Red. Although this is a rare clinical condition, this case indicated that carrying out a bronchoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma is very important. PMID:27594885

  10. Cardiac amyloidosis: the great pretender.

    PubMed

    Rapezzi, Claudio; Lorenzini, Massimiliano; Longhi, Simone; Milandri, Agnese; Gagliardi, Christian; Bartolomei, Ilaria; Salvi, Fabrizio; Maurer, Mathew S

    2015-03-01

    Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic "red flags" (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition. PMID:25758359

  11. Tracheobronchial Amyloidosis Mimicking Tracheal Tumor

    PubMed Central

    Özgül, Mehmet Akif; Uzun, Oğuz; Yaşar, Zehra; Acat, Murat; Arda, Naciye; Çetinkaya, Erdoğan

    2016-01-01

    Tracheobronchial amyloidosis is a rare presentation and accounts for about 1% of benign tumors in this area. The diagnosis of disease is delayed due to nonspecific pulmonary symptoms. Therapeutic approaches are required to control progressive pulmonary symptoms for most of the patients. Herein, we report a case of a 68-year-old man admitted with progressive dyspnea to our institution for further evaluation and management. He was initially diagnosed with and underwent management for bronchial asthma for two years but had persistent symptoms despite optimal medical therapy. Pulmonary computed tomography scan revealed severe endotracheal stenosis. Bronchoscopy was performed and showed endotracheal mass obstructing 70% of the distal trachea and mimicking a neoplastic lesion. The mass was successfully resected by mechanical resection, argon plasma coagulation (APC), and Nd-YAG laser during rigid bronchoscopy. Biopsy materials showed deposits of amorphous material by hematoxylin and eosin staining and these deposits were selectively stained with Congo Red. Although this is a rare clinical condition, this case indicated that carrying out a bronchoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma is very important. PMID:27594885

  12. Localisation of the gene for X-linked reticulate pigmentary disorder with systemic manifestations (PDR), previously known as X-linked cutaneous amyloidosis

    SciTech Connect

    Gedeon, A.K.; Mulley, J.C.; Kozman, H.; Donnelly, A.; Partington, M.W.

    1994-08-01

    X-linked reticulate pigmentary disorder (PDR), previously reported as X-linked cutaneous amyloidosis (MIM No. 301220), is characterized by brown pigmentation of the skin which follows the lines of Blaschko in females but appears as reticulate sheets in males. Males may suffer severe gastrointestinal disorders in infancy with failure to thrive and early death. Nowadays symptomatic treatment allows survival and other manifestations may appear such as corneal dystrophy with severe photophobia or chronic respiratory disease. Amyloid deposition in the skin may be no more than an age-dependent secondary manifestation. The PDR gene was localized by linkage analysis to Xp21-p22. The background genetic map is Xpter-DXS996-22.5-DXS207-3.3-DXS999-3.3-DXS365-14.2-DXS989-4.1-3`DMD-3.5-DXS997-1.0-STR44-9.3-DYSI-2.3-DXS1068-11.0-DXS228 with distances between markers given in cM. Recombinants detected with DXS999 distally and DXS228 proximally, define the limits to the localization. Linkage was found with several markers within this interval. Peak lod scores of 3.21 at {theta} = 0.0 were obtained between PDR and DXS989 and between PDR and 5`DYSI within the dystrophin locus. 29 refs., 2 figs., 2 tabs.

  13. Transthyretin Cardiac Amyloidosis in Black Americans.

    PubMed

    Shah, Keyur B; Mankad, Anit K; Castano, Adam; Akinboboye, Olakunle O; Duncan, Phillip B; Fergus, Icilma V; Maurer, Mathew S

    2016-06-01

    Transthyretin-related cardiac amyloidosis is a progressive infiltrative cardiomyopathy that mimics hypertensive and hypertrophic heart disease and often goes undiagnosed. In the United States, the hereditary form disproportionately afflicts black Americans, who when compared with whites with wild-type transthyretin amyloidosis, a phenotypically similar condition, present with more advanced disease despite having a noninvasive method for early identification (genetic testing). Although reasons for this are unclear, this begs to consider the inadequate access to care, societal factors, or a biological basis. In an effort to improve awareness and explore unique characteristics, we review the pathophysiology, epidemiology, and therapeutic strategies for transthyretin amyloidosis and highlight diagnostic pitfalls and clinical pearls for identifying patients with amyloid heart disease. PMID:27188913

  14. Primary Pulmonary Amyloidosis with Mediastinal Lymphadenopathy

    PubMed Central

    Kim, Dohun; Lee, Yong-Moon; Kim, Si-Wook; Kim, Jong-Won; Hong, Jong-Myeon

    2016-01-01

    We report a case of inadvertent hoarseness after surgery for primary pulmonary amyloidosis. A 55-year-old male was transferred to our facility due to a lung mass. Chest computed tomography revealed a solitary pulmonary nodule. Positron emission tomography–computed tomography showed fluorodeoxyglucose uptake in the main mass and in the mediastinal lymph nodes. To confirm the pathology of the mass, wedge resection and thorough lymph node dissection were performed via video-assisted thoracic surgery (VATS). No complications except for hoarseness were observed; hoarseness developed soon after surgery and lasted for 3 months. The main mass was diagnosed as amyloidosis, but this was not found in the lymph nodes. In conclusion, VATS wedge resection for peripheral amyloidosis is a feasible and safe procedure. However, mediastinal lymph node dissection is not recommended unless there is evidence of a clear benefit. PMID:27298804

  15. Colchicine use in isolated renal AA amyloidosis.

    PubMed

    Meneses, Carlos F; Egües, César A; Uriarte, Miren; Belzunegui, Joaquín; Rezola, Marta

    2015-01-01

    We present the case of a 45-year-old woman, with two-year history of chronic renal insufficiency and proteinuria. A kidney biopsy showed the presence of AA amyloidosis (positive Congo red staining and immunohistochemistry). There was no evidence of amyloid deposits in other organs and there was no underlying disease. AA amyloidosis normally is secondary to chronic inflammatory or infectious diseases. High levels of IL-1, IL-6 and TNF-α play a role in the pathogenesis of amyloidosis and induce the synthesis of serum amyloid A protein (SAA), a precursor of tissue amyloid deposits. We empirically treated the patient with a low dose colchicine. The patient responded well. Colchicine has been used for the treatment of Familiar Mediterranean Fever and related auto-inflammatory diseases. To monitor treatment responses, we measured SAA finding low titers. Soon after treatment onset there were signs of improvement pertaining to proteinuria and stabilization of renal function. PMID:25453598

  16. Renal amyloidosis in leprosy, an infrequent cause of nephrotic syndrome in Europe.

    PubMed

    Sanz-Martín, Noelia; Samillán-Sosa, Kelly Del Rocío; De Miguel, Julio; Martínez-Miguel, Patricia

    2016-01-01

    Leprosy is a chronic infectious disease caused by Mycobacterium leprae The main clinical manifestations involve the skin and the peripheral nervous system. Several types of nephropathy have been described in leprosy. One frequent form of renal involvement is amyloidosis, especially in patients with lepromatous leprosy. In these patients, end-stage renal disease is an important contributor to morbidity and mortality. Here, we present the case of a patient with nephrotic syndrome caused by secondary amyloidosis, chronic peripheral neuropathy and a history of leprosy. The patient was correctly treated in her youth, which is the best way to avoid renal pathology, but she developed a nephrotic syndrome years later. PMID:27489069

  17. Light-chain cardiac amyloidosis with neuropathy: a case report

    PubMed Central

    Xu, Zhan-Wen; Li, Ya-Qin; Liu, Li-xia; Zhou, Bing-Juan

    2015-01-01

    Light-chain amyloidosis is a relatively rare multisystem disorder. The disease often is normally difficult to diagnose due to its broad range of characters without specific symptoms. A 62-year-old male patient presented with heart failure after experiencing a long period of unexplained and untreated gastrointestinal symptoms. Clinical examination and laboratory findings indicated a systemic process with cardiac involvement. Echocardiography revealed concentric left ventricular hypertrophy with enhanced echogenicity and preserved ejection fraction. Rectum biopsy confirmed amyloid deposition. The side effect of delayed diagnosis on prognosis and the appropriate diagnostic strategy has been discussed. PMID:26257516

  18. Study on epidemiology of cutaneous amyloidosis in northern India and effectiveness of dimethylsulphoxide in cutaneous amyloidosis

    PubMed Central

    Krishna, Arvind; Nath, Bhola; Dhir, G. G.; Kumari, Ranjeeta; Budhiraja, Virendra; Singh, Kalpana

    2012-01-01

    Context: Amyloidosis, which is characterized by the extracellular deposition of a proteinaceous substance, is usually associated with considerable tissue dysfunction. However, the etiology of the disease remains uncertain and the treatment disappointing. Aim: 1. To know the epidemiology of cutaneous amyloidosis 2. To evaluate the effect of dimethylsulphoxide on cutaneous amyloidosis. Settings and Design: Data was collected from patients attending the Outpatient Department (OPD) over a period of one year. Material and Methods: Patients were screened on the basis of signs and symptoms and then confirmed histologically. A total of 62 patients who were suspected to be suffering from amyloidosis on the basis of clinical signs and symptoms and 38 patients who were further confirmed histopathologically underwent the treatment. Statistical Analysis Used: Chi-square test was used for testing the significance of proportions. Results: 63.15 percent of the patients had macular amyloidosis and the interscapular area was the most common area involved (52.63%). Pruritus, pigmentation, and papules responded excellently to dimethylsulphoxide after one month of treatment. Conclusions: Cutaneous amyloidosis is a disease found in middle-aged persons, with a female preponderance, and dimethylsulphoxide seems to be an effective therapy. PMID:23189250

  19. Growth Hormone and Cerebral Amyloidosis.

    PubMed

    Benvenga, S; Guarneri, F

    2016-08-01

    Great interest has recently been focused on a paper reporting characteristic deposits of amyloid-β protein associated with Alzheimer's disease in brains of adults who died of Creutzfeldt-Jakob disease. As they had contracted such disease after treatment with prion-contaminated human growth hormone extracted from cadaver-derived pituitaries, the authors have suggested that interhuman transmission of Alzheimer's disease had occurred. Our previous research led us to find that amyloid-forming peptides share amino acid sequence homology, summarized by a motif. Here, we probed the amino acid sequence of human growth hormone for such a motif, and found that 2 segments fit the motif and are potentially amyloid-forming. This finding was confirmed by Aggrescan, another well-known software for the prediction of amyloidogenic peptides. Our results, taken together with data from the literature that are missing in the aforementioned paper and associated commentaries, minimize the contagious nature of the iatrogenically-acquired coexistence of Creutzfeldt-Jakob disease and Alzheimer's disease. In particular, the above mentioned paper misses literature data on intratumoral amyloidosis in growth hormone- and prolactin-secreting adenomas, tumors relatively frequent in adults, which are often silent. It cannot be excluded that some pituitaries used to extract growth hormone contained clinically silent microadenomas, a fraction of which containing amyloid deposits, and patients might had received a fraction of growth hormone (with or without prolactin) that already was an amyloid seed. The intrinsic amyloidogenicity of growth hormone, in the presence of contaminating prion protein (and perhaps prolactin as well) and amyloid-β contained in some cadavers' pituitaries, may have led to the observed co-occurring of Creutzfeldt-Jakob disease and Alzheimer's disease. PMID:27214308

  20. Role of imaging in the diagnosis and management of patients with cardiac amyloidosis: state of the art review and focus on emerging nuclear techniques.

    PubMed

    Aljaroudi, Wael A; Desai, Milind Y; Tang, W H Wilson; Phelan, Dermot; Cerqueira, Manuel D; Jaber, Wael A

    2014-04-01

    Amyloidosis is an infiltrative disease characterized by deposition of amyloid fibrils within the extracellular tissue of one or multiple organs. Involvement of the heart, cardiac amyloidosis, is recognized as a common cause of restrictive cardiomyopathy and heart failure. The two major types of cardiac amyloidosis are cardiac amyloid light-chain (AL) and transthyretin-related cardiac amyloidosis (ATTR, mutant and wild types) (Nat Rev Cardiol 2010;7:398-408). While early recognition of cardiac amyloidosis is of major clinical importance, so is the ability to differentiate between subtypes. Indeed, both prognosis and therapeutic options vary drastically depending on the subtype. While endomyocardial biopsy with immunostaining is considered the gold standard, advances in imaging provide an attractive non-invasive alternative. Currently, electrocardiography, echocardiography, and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy. Yet, none of these modalities can effectively differentiate the cardiac amyloid subtypes. Recent data with (99m)Tc-phosphate derivatives, previously used as bone seeking radioactive tracers, have shown promising results; these radiotracers selectively bind ATTR, but not AL subtype, and can differentiate subtypes with high diagnostic accuracy. This review will initially present the non-radionuclide imaging techniques and then focus on the radionuclide imaging techniques, particularly (99m)Tc-DPD and (99m)Tc-PYP, mechanism of action, performance and interpretation of the study, diagnostic accuracy, prognostic value, future clinical perspective, and outlook. PMID:24347127

  1. Macular amyloidosis complicating macroprolactinoma--a novel clinical association.

    PubMed

    Dutta, Deep; Ahuja, Arvind; Sharma, Lokesh; Bhardwaj, Minakshi; Kulshreshtha, Bindu

    2015-01-01

    Amyloid deposition in the pituitary gland is a rare localised form of amyloidosis, and most commonly reported with prolactinoma. Macular amyloidosis is a rare form of localised cutaneous amyloidosis of obscure aetiology. In contrast to most localised amyloidosis, the precursor protein(s) of both macular amyloidosis and prolactinoma are unknown. A 35-year-old man with chronic headache (six years), blurring of vision (three years), and hyperpigmented macular lesion involving arms, legs, and back (two years) was diagnosed to have hyperprolactinaemia (8927 ng/mL) and secondary adrenal insufficiency. MRI revealed pituitary macroadenoma compressing the optic chiasma, encasing the right carotid artery and extending into the sphenoid sinus. A biopsy of skin from the right upper arm revealed thickened stratum corneum, acanthosis, and deposition of pale eosinophilic material in papillary dermis that gave a rose pink colour under methyl-violet and appeared congophilic with Congo red stain, which under polarised light showed green birefringence, diagnostic of macular amyloidosis. Headache, bitemporal haemianopia, and skin lesion improved following cabergoline therapy. Temporal profile of the disease characterised by symptoms of macroprolactinoma preceding onset of macular amyloidosis with resolution of symptoms of macroprolactinoma, accompanied by reductions in prolactin, and concomitant improvement in macular amyloidosis with cabergoline therapy may suggest some link between macroprolactinoma and macular amyloidosis. This report intends to highlight this novel association of macular amyloidosis and macroprolactinoma. PMID:26662655

  2. The ALS Storage Ring RF System

    SciTech Connect

    Taylor, B.; Lo, C.C.; Baptiste, K.; Guigli, J.; Julian, J.

    1993-05-01

    The ALS Storage Ring RF System is characterized by the use of the following features: (1) High power loading of two single cell cavities. (2) The use of a tubular ceramic input window employing aperture coupling. (3) The use of waveguide filters and matchers designed for HOM absorption. (4) A comprehensive HOM monitoring system. (5) The use of waveguide water-wedge loads for the magic tee and circulator loads. The results of cavity measurements and high power tests are reported together with the performance of the system during the commissioning and operation phases of the ALS project. Plans for future window development are discussed.

  3. Long-term follow-up after surgery in localized laryngeal amyloidosis.

    PubMed

    Hazenberg, Aldert J C; Hazenberg, Bouke P C; Dikkers, Frederik G

    2016-09-01

    To study effectiveness of surgery and watchful waiting in localized laryngeal amyloidosis, retrospective case series. This retrospective study comprises all consecutive patients with localized laryngeal amyloidosis surgically treated in a tertiary hospital between 1994 and February 2016. Recurrence rate, revision surgery, progression to systemic amyloidosis, and changes in voice were monitored yearly. Eighteen patients were included. Seven women and eleven men had a median age 50 years (range 21-77 years) and median follow-up 6.4 years (2.4-17 years). Amyloid was located in subglottis (5), glottis (8), false vocal folds (8) and other supraglottic areas (5), in more than one laryngeal region (13) and bilaterally (12). Cold steel excision was used at the glottis; CO2 laser excision, sometimes assisted by microdebrider, at other laryngeal areas. Eleven patients needed revision surgery, ten within the first 4 years after surgical treatment. One patient needed his first revision surgery after 11 years. Five patients needed a second revision within 6 years after initial diagnosis. Two patients needed a third revision. Indications for first revision surgery were progression (8) with dysphonia (7), dyspnea (2), dysphagia (1), exclusion of malignancy (1), and aphonia (1). No patient developed systemic amyloidosis during follow-up. Although local progression of amyloid necessitates revision surgery once or twice in the first 4-6 years, progression slows down thereafter. Late progression, however, remains possible. PMID:27156084

  4. Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis.

    PubMed

    Butler, James S; Chan, Amy; Costelha, Susete; Fishman, Shannon; Willoughby, Jennifer L S; Borland, Todd D; Milstein, Stuart; Foster, Donald J; Gonçalves, Paula; Chen, Qingmin; Qin, June; Bettencourt, Brian R; Sah, Dinah W; Alvarez, Rene; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Fitzgerald, Kevin; Meyers, Rachel E; Nochur, Saraswathy V; Saraiva, Maria J; Zimmermann, Tracy S

    2016-06-01

    ATTR amyloidosis is a systemic, debilitating and fatal disease caused by transthyretin (TTR) amyloid accumulation. RNA interference (RNAi) is a clinically validated technology that may be a promising approach to the treatment of ATTR amyloidosis. The vast majority of TTR, the soluble precursor of TTR amyloid, is expressed and synthesized in the liver. RNAi technology enables robust hepatic gene silencing, the goal of which would be to reduce systemic levels of TTR and mitigate many of the clinical manifestations of ATTR that arise from hepatic TTR expression. To test this hypothesis, TTR-targeting siRNAs were evaluated in a murine model of hereditary ATTR amyloidosis. RNAi-mediated silencing of hepatic TTR expression inhibited TTR deposition and facilitated regression of existing TTR deposits in pathologically relevant tissues. Further, the extent of deposit regression correlated with the level of RNAi-mediated knockdown. In comparison to the TTR stabilizer, tafamidis, RNAi-mediated TTR knockdown led to greater regression of TTR deposits across a broader range of affected tissues. Together, the data presented herein support the therapeutic hypothesis behind TTR lowering and highlight the potential of RNAi in the treatment of patients afflicted with ATTR amyloidosis. PMID:27033334

  5. Proteomic Analysis of Highly Prevalent Amyloid A Amyloidosis Endemic to Endangered Island Foxes

    PubMed Central

    Gaffney, Patricia M.; Imai, Denise M.; Clifford, Deana L.; Ghassemian, Majid; Sasik, Roman; Chang, Aaron N.; O’Brien, Timothy D.; Coppinger, Judith; Trejo, Margarita; Masliah, Eliezer; Munson, Linda; Sigurdson, Christina

    2014-01-01

    Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins. PMID:25429466

  6. Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis

    PubMed Central

    Butler, James S.; Chan, Amy; Costelha, Susete; Fishman, Shannon; Willoughby, Jennifer L. S.; Borland, Todd D.; Milstein, Stuart; Foster, Donald J.; Gonçalves, Paula; Chen, Qingmin; Qin, June; Bettencourt, Brian R.; Sah, Dinah W.; Alvarez, Rene; Rajeev, Kallanthottathil G.; Manoharan, Muthiah; Fitzgerald, Kevin; Meyers, Rachel E.; Nochur, Saraswathy V.; Saraiva, Maria J.; Zimmermann, Tracy S.

    2016-01-01

    Abstract ATTR amyloidosis is a systemic, debilitating and fatal disease caused by transthyretin (TTR) amyloid accumulation. RNA interference (RNAi) is a clinically validated technology that may be a promising approach to the treatment of ATTR amyloidosis. The vast majority of TTR, the soluble precursor of TTR amyloid, is expressed and synthesized in the liver. RNAi technology enables robust hepatic gene silencing, the goal of which would be to reduce systemic levels of TTR and mitigate many of the clinical manifestations of ATTR that arise from hepatic TTR expression. To test this hypothesis, TTR-targeting siRNAs were evaluated in a murine model of hereditary ATTR amyloidosis. RNAi-mediated silencing of hepatic TTR expression inhibited TTR deposition and facilitated regression of existing TTR deposits in pathologically relevant tissues. Further, the extent of deposit regression correlated with the level of RNAi-mediated knockdown. In comparison to the TTR stabilizer, tafamidis, RNAi-mediated TTR knockdown led to greater regression of TTR deposits across a broader range of affected tissues. Together, the data presented herein support the therapeutic hypothesis behind TTR lowering and highlight the potential of RNAi in the treatment of patients afflicted with ATTR amyloidosis. PMID:27033334

  7. A Rare Case of Ascites due to Peritoneal Amyloidosis

    PubMed Central

    Stofer, Fernanda; Barretto, Maria Fernanda; Gouvea, Ana Luisa; Ribeiro, Mario; Neves, Marcio; Gismondi, Ronaldo Altenburg; Mocarzel, Luís Otavio

    2016-01-01

    Patient: Male, 65 Final Diagnosis: Peritoneal amyloidosis Symptoms: Anasarca • Dyspnea • Orthopnea Medication: — Clinical Procedure: Paracentesis and peritoneal biopsy Specialty: Gastroenterology and Hepatology Objective: Unusual clinical course Background: The clinical manifestations of amyloidosis depend on the type of insoluble protein as well as the location of amyloid deposits in tissues or organs. In the gastrointestinal tract, the small intestine is the most common site of amyloid deposits, whereas peritoneal involvement and ascites are rare. Case Report: We report on a case of ascites due to peritoneal amyloidosis. A 65-year-old patient was admitted to our institution due to anasarca and pulmonary congestion, mimicking heart failure. We started the patient on diuretics and vasodilators. Despite improvement in pulmonary congestion and peripheral edema, his ascites was not reduced. Echocardiogram revealed restrictive cardiomyopathy and a speckle-tracking pattern suggestive of cardiac amyloidosis. Subcutaneous and peritoneal biopsies revealed amyloidosis. Conclusions: Amyloidosis is rare in the peritoneum and is usually asymptomatic. Ascites occurs in only 20% of patients with peritoneal amyloidosis. We searched PubMed using “ascites” and “amyloidosis” and identified only eight case reports of amyloidosis with ascites. Physicians should be particularly careful in heart failure and anasarca cases when ascites is disproportional or not responsive to diuretic treatment. To date, there is no specific treatment for peritoneal amyloidosis. PMID:27353538

  8. Gastrointestinal Amyloidosis Presenting with Multiple Episodes of Gastrointestinal Bleeding

    SciTech Connect

    Kim, Sang Hyeon Kang, Eun Ju; Park, Jee Won; Jo, Jung Hyun; Kim, Soo Jin; Cho, Jin Han; Kang, Myong Jin; Park, Byeong Ho

    2009-05-15

    Amyloidosis is characterized by the extracellular deposition of amyloid protein in various organs. Gastrointestinal involvement in amyloidosis is common, but a diagnosis of amyloidosis is often delayed. Severe gastrointestinal hemorrhage in amyloidosis is rare but can be fatal in some cases. We experienced a case of a 49-year-old man who presented with recurrent massive hematochezia. Although embolization was performed eight times for bleeding from different sites of the small intestine, hematochezia did not cease. We report the case, with a review of the literature.

  9. A Rare Case of Ascites due to Peritoneal Amyloidosis.

    PubMed

    Stofer, Fernanda; Barretto, Maria Fernanda; Gouvea, Ana Luisa; Ribeiro, Mario; Neves, Marcio; Gismondi, Ronaldo Altenburg; Mocarzel, Luís Otavio

    2016-01-01

    BACKGROUND The clinical manifestations of amyloidosis depend on the type of insoluble protein as well as the location of amyloid deposits in tissues or organs. In the gastrointestinal tract, the small intestine is the most common site of amyloid deposits, whereas peritoneal involvement and ascites are rare. CASE REPORT We report on a case of ascites due to peritoneal amyloidosis. A 65-year-old patient was admitted to our institution due to anasarca and pulmonary congestion, mimicking heart failure. We started the patient on diuretics and vasodilators. Despite improvement in pulmonary congestion and peripheral edema, his ascites was not reduced. Echocardiogram revealed restrictive cardiomyopathy and a speckle-tracking pattern suggestive of cardiac amyloidosis. Subcutaneous and peritoneal biopsies revealed amyloidosis. CONCLUSIONS Amyloidosis is rare in the peritoneum and is usually asymptomatic. Ascites occurs in only 20% of patients with peritoneal amyloidosis. We searched PubMed using "ascites" and "amyloidosis" and identified only eight case reports of amyloidosis with ascites. Physicians should be particularly careful in heart failure and anasarca cases when ascites is disproportional or not responsive to diuretic treatment. To date, there is no specific treatment for peritoneal amyloidosis. PMID:27353538

  10. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations.

    PubMed

    Rowczenio, Dorota M; Noor, Islam; Gillmore, Julian D; Lachmann, Helen J; Whelan, Carol; Hawkins, Philip N; Obici, Laura; Westermark, Per; Grateau, Gilles; Wechalekar, Ashutosh D

    2014-09-01

    Hereditary systemic amyloidosis comprises a group of rare monogenic diseases inherited in an autosomal dominant fashion. It is associated with mutations in genes encoding eight different proteins, including transthyretin, apolipoprotein AI, apolipoprotein AII, lysozyme, fibrinogen A α-chain, cystatin C, gelsolin and beta-2-microglobulin. With support from the EU FP6 EURAMY project we have designed an online registry of genes and mutations in hereditary amyloidosis including their associated clinical phenotypes, with a view to having a single free online portal for the collection and distribution of this information. Users can search the registry by either mutation, phenotype or authors who have published or submitted mutations. It provides a submission form for reporting newly identified mutations. We also wanted to introduce nomenclature which complies with recommendations set out by Human Genome Variation Society and HUGO Gene Nomenclature Committee for description of new and known genetic variants. We hope this registry would be a useful and convenient tool for the medical and scientific community. PMID:25044787

  11. Nodular pulmonary amyloidosis associated with asbestos exposure.

    PubMed

    Hiroshima, K; Ohwada, H; Ishibashi, M; Yamamoto, N; Tamiya, N; Yamaguchi, Y

    1996-01-01

    A 71 year old man was admitted for the purpose of diagnosis of a right solitary pulmonary nodule. The size of the nodule was 18 x 18 mm in diameter 2 years ago, but it has become large, 25 x 25 mm in diameter. The nodule was resected by thoracotomy. Microscopically, eosinophilic amorphous, acellular substances were surrounded by inflammatory infiltrates. It stained with Congo red stain and showed green birefringence with polarizing microscopy. Amyloid fibrils were observed electron microscopically. Asbestos bodies were observed in the lung parenchyma around the nodule. This case shows that a nodule in nodular pulmonary amyloidosis can grow gradually and suggests the possibility of asbestos fibers as one of the etiologic factors in nodular pulmonary amyloidosis. PMID:10846552

  12. Poikiloderma-like cutaneous amyloidosis - a rare presentation of primary localized cutaneous amyloidosis.

    PubMed

    Heng, Jun Khee; Ho, Sue Ann; Tan, Kong Bing

    2016-01-01

    Poikiloderma-like cutaneous amyloidosis (PCA) is a rare variant of primary cutaneous amyloidosis. It was first described in 1929 and there are two clinical forms of PCA, the ordinary type and PCA syndrome. The characteristics of PCA include poikiloderma-like skin changes, lichenoid papules, blister formation, and cutaneous amyloid deposits on histological examination. These skin lesions usually occur at the extremities, consistent with the few cases that have been reported. We present a case of a 62-year-old man who presented with the features of poikiloderma-like cutaneous amyloidosis. Diagnosis of this unique condition is a challenge and a skin biopsy is necessary in such instances. A discussion of the differential diagnosis of this condition is also included. PMID:26990468

  13. Response to oral acitretin in lichen amyloidosis

    PubMed Central

    Vasani, Resham J.

    2014-01-01

    We report the therapeutically challenging case of a patient with severe and extensive lichen amyloidosis (LA) who responded to oral acitretin and topical corticosteroids. Colloid milia and terra firma-forme dermatoses were noted post healing of the lesions of LA. There has been no recurrence of lesions post 8 months of follow-up. We recommend that acitretin should be used more often in severe and recalcitrant cases of LA. PMID:25593815

  14. Update on treatment of light chain amyloidosis

    PubMed Central

    Mahmood, Shameem; Palladini, Giovanni; Sanchorawala, Vaishali; Wechalekar, Ashutosh

    2014-01-01

    Light chain amyloidosis is the most common type of amyloidosis as a consequence of protein misfolding of aggregates composed of amyloid fibrils. The clinical features are dependent on the organs involved, typically cardiac, renal, hepatic, peripheral and autonomic neuropathy and soft tissue. A tissue biopsy or fat aspirate is needed to confirm the presence/type of amyloid and prognostic tools are important in a risk stratified approach to treatment. Autologous stem cell transplant eligibility should be assessed at baseline, weighing the reversible or non-reversible contraindications, toxicity of treatment and chemotherapy alternatives available. Chemotherapy options include melphalan, thalidomide, bortezomib, lenalidomide, bendamustine in combination with dexamethasone. Many studies have explored these treatment modalities, with ongoing debate about the optimal first line and sequential treatment thereafter. Attaining a very good partial response or better is the treatment goal coupled with early assessment central to optimizing treatment. One major challenge remains increasing the awareness of this disease, frequently diagnosed late as the presenting symptoms mimic many other medical conditions. This review focuses on the treatments for light chain amyloidosis, how these treatments have evolved over the years, improved patient risk stratification, toxicities encountered and future directions. PMID:24497558

  15. Yield of noncardiac biopsy for the diagnosis of transthyretin cardiac amyloidosis.

    PubMed

    Fine, Nowell M; Arruda-Olson, Adelaide M; Dispenzieri, Angela; Zeldenrust, Steven R; Gertz, Morie A; Kyle, Robert A; Swiecicki, Paul L; Scott, Christopher G; Grogan, Martha

    2014-05-15

    Transthyretin (ATTR) cardiac amyloidosis may be because of mutant transthyretin causing familial amyloid cardiomyopathy (FAC) or wild-type transthyretin causing systemic senile amyloidosis (SSA). Histologic confirmation is often challenging and may require endomyocardial biopsy (EMB). The purpose of this study was to determine the frequency of amyloid protein deposition in positive noncardiac organ biopsy or fat aspiration in patients with ATTR cardiac amyloidosis. The medical records of 286 patients (mean age 66 ± 11, 85% men) with a diagnosis of ATTR cardiac amyloidosis at our institution who underwent noncardiac biopsy or subcutaneous fat aspiration were reviewed, including 186 patients (65%) with FAC and 100 patients (35%) with SSA. One hundred and thirty-one patients (46%) had EMB, all of which were positive. There were 210 patients (73%) with positive noncardiac tissue sampling, including 175 patients (94%) with FAC and 35 patients (35%) with SSA (p <0.001). There were 141 patients (76%) with FAC and 84 patients (84%) with SSA who underwent fat aspiration, and 67% and 14% were positive, respectively, whereas 100 (54%) and 64 (64%) underwent bone marrow biopsy, and 41% and 30% were positive, respectively. Rectal and sural nerve biopsies were performed in 52 (28%) and 54 (29%) patients with FAC and were positive in 81% and 83%, respectively. Biopsy of other noncardiac sites was performed with relatively lower frequency. In conclusion, although EMB is more commonly required to establish the diagnosis of SSA than FAC, noncardiac biopsy or fat aspiration could be considered as initial testing in patients evaluated for ATTR cardiac amyloidosis with characteristic echocardiography findings. PMID:24698461

  16. Transthyretin cardiac amyloidosis: an under-diagnosed cause of heart failure

    PubMed Central

    Molina O, Gabriela; Judge, Daniel; Campbell, Wayne; Chahal, Harjit; Mugmon, Marc

    2014-01-01

    Introduction Cardiac amyloidosis is the most common cause of infiltrative cardiomyopathy and is associated with a poor prognosis. Transthyretin cardiac amyloidosis, particularly the type caused by the mutation that replaces the amino acid valine with the amino acid isoleucine at position 122 (Val122Ile), is most common among African- Americans above 65 years of age. Evidence suggests that this mutation is an important, though under-diagnosed, cause of heart failure in this population. Case presentation A 74-year-old African American male with a diagnosis of non-ischemic cardiomyopathy for several years, presented with gradually worsening dyspnea on exertion and lower extremity edema. There is no known cardiac disease in his family. An echocardiogram was done showing a decrease in ejection fraction to 30% from 45% in the span of a year. An endomyocardial biopsy analysis identified transthyretin amyloid with the Val122Ile mutation, confirming the diagnosis of familial transthyretin cardiomyopathy. Discussion Systemic amyloidosis is a group of diseases caused by the deposition of an abnormally folded, insoluble protein that can accumulate in multiple organs causing progressive and irreversible dysfunction. The mutations that most commonly induce variant transthyretin cardiac amyloidosis are Val122Ile, Val30Met and Thr60Ala. The Val122Ile mutation has been found to be present in 3–4% of the African American/Caribbean population. Conclusions Familial amyloid cardiomyopathy is an uncommonly recognized cause of heart failure in the population, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. Patients that meet the high-risk profile criteria – male gender, age 65 years and older, heart failure symptoms, symmetric left ventricular (LV) hypertrophy, and moderately depressed LV function – should likely undergo additional testing for cardiac amyloidosis. PMID:25432650

  17. Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant.

    PubMed Central

    Hesse, A; Altland, K; Linke, R P; Almeida, M R; Saraiva, M J; Steinmetz, A; Maisch, B

    1993-01-01

    Cardiac amyloidosis is caused by amyloid deposits derived from different human plasma proteins. It can lead to cardiac conduction disturbances, restrictive cardiomyopathy, and low output heart failure. The heart is variably involved during the development of systemic amyloidosis and seems to be more frequently affected in immunoglobulin (primary) than in reactive (secondary) amyloidosis. Amyloid is common in the elderly. Isolated atrial amyloid, for which a major subunit is the atrial natriuretic peptide, seems to be three times more frequent than senile cardiac amyloid, which is derived from normal prealbumin (transthyretin). Like polyneuropathy, cardiac amyloidosis is a prominent clinical feature of hereditary amyloidosis, namely of the autosomal dominant transthyretin (TTR) type. All 28 cases of TTR amyloidoses reported so far were heterozygotes for a single nucleotide change in the gene for TTR that resulted in amino acid substitutions in the mature protein. A new TTR genetic variant is reported in a German family where the index patient presented at the age of 63 with anginal pain and arrhythmia. Electrocardiography was suggestive of a pseudoinfarction pattern, and echocardiography and cardiac catheterisation showed signs of hypertrophic nonobstructive cardiomyopathy with increased ventricular filling pressures and a prominent "a" wave. Amyloid of the TTR type was identified by immunohistochemistry in the endomyocardial biopsy specimen. Hybrid isoelectric focusing established heterozygosity by showing normal TTR protein and an electrically neutral TTR variant differing from all known TTR variants so far. The patient died in an accident before investigations were complete. Electrophoretic analysis of the plasma from his first degree relatives (son, daughter, brother, and mother) identified the asymptomatic 22 year old son as an apparently heterozygous carrier of the mutant TTR protein. Comparative tryptic peptide mapping and sequencing showed that isoleucine at

  18. AA protein-related renal amyloidosis in drug addicts.

    PubMed Central

    Menchel, S.; Cohen, D.; Gross, E.; Frangione, B.; Gallo, G.

    1983-01-01

    Reports of renal amyloidosis occurring among narcotic addicts have been limited, for the most part, to case reports. In a prospective survey of 150 addicts examined at autopsy in the Office of the Chief Medical Examiner of the City of New York, 7 cases of renal amyloidosis were found. Immunohistologic examination demonstrated that in all of the 7 cases, the amyloid was AA protein-related. The amyloid extracted from the kidneys of two addicts and analyzed biochemically did not differ from the AA amyloid secondary to chronic infectious and inflammatory diseases. The combined data of previous reports and the present survey demonstrate that addicts who are subcutaneous users with skin infections most frequently develop amyloidosis. Our data demonstrating renal amyloidosis in 26% of addicts with chronic suppurative skin infections suggest that such addicts are at high risk for the development of amyloidosis. Images Figure 1 Figure 2 PMID:6881286

  19. A Case of Amyloidosis Presenting as Chronic Cholecystitis, Misdiagnosed as Polymyalgia Rheumatica.

    PubMed

    Um, Yoo Jin; Kim, Hyoun Ah; Jung, Jin Hee; Cho, Hundo; Kang, Joon Koo

    2016-07-25

    Amyloidosis is a rare disease defined by extracellular deposits of amorphous fibrillar proteins, derived from aggregations of misfolded proteins. Localization of amyloidosis in the gallbladder is uncommon; only eight cases have been reported. We describe a case of amyloidosis diagnosed by cholecystectomy, which possibly also affected the liver and kidney. The patient was misdiagnosed with polymyalgia rheumatica, but after a cholecystectomy to treat chronic cholecystitis, we ultimately diagnosed him with amyloidosis. We review amyloidosis with gallbladder involvement in the literature. PMID:27443625

  20. Late gadolinium enhancement in cardiac amyloidosis: attributable both to interstitial amyloid deposition and subendocardial fibrosis caused by ischemia.

    PubMed

    Hashimura, Hiromi; Ishibashi-Ueda, Hatsue; Yonemoto, Yumiko; Ohta-Ogo, Keiko; Matsuyama, Taka-Aki; Ikeda, Yoshihiko; Morita, Yoshiaki; Yamada, Naoaki; Yasui, Hiroki; Naito, Hiroaki

    2016-06-01

    Gadolinium contrast agents used for late gadolinium enhancement (LGE) distribute in the extracellular space. Global diffuse myocardial LGE pronounced in the subendocardial layers is common in cardiac amyloidosis. However, the pathophysiological basis of these findings has not been sufficiently explained. A 64-year-old man was admitted to our hospital with leg edema and nocturnal dyspnea. Bence Jones protein was positive in the urine, and an endomyocardial and skin biopsy showed light-chain (AL) amyloidosis. He died of ventricular fibrillation 3 months later. 9 days before death, the patient was examined by cardiac magnetic resonance (CMR) imaging on a 3-T system. We acquired LGE data at 2, 5, 10, and 20 min after the injection of gadolinium contrast agents, with a fixed inversion time of 350 ms. Myocardial LGE developed sequentially. The myocardium was diffusely enhanced at 2 min, except for the subendocardium, but LGE had extended to almost the entire left ventricle at 5 min and predominantly localized to the subendocardial region at 10 and 20 min. An autopsy revealed massive and diffused amyloid deposits in perimyocytes throughout the myocardium. Old and recent ischemic findings, such as replacement fibrosis and coagulative myocyte necrosis, were evident in the subendocardium. In the intramural coronary arteries, mild amyloid deposits were present within the subepicardial to the mid layer of the left ventricle, but no stenotic lesions were evident. However, capillaries were obstructed by amyloid deposits in the subendocardium. In conclusion, the late phase of dynamic LGE (at 10 and 20 min) visualized in the subendocardium corresponded to the interstitial amyloid deposition and subendocardial fibrosis caused by ischemia in our patient. PMID:25794983

  1. [Hereditary gelsolin amyloidosis--40 years of Meretoja disease].

    PubMed

    Kiuru-Enari, Sari; Haltia, Matti

    2010-01-01

    Hereditary gelsolin amyloidosis is an autosomally dominantly inherited systemic disease, first described in 1969 by the Finnish ophthalmologist Jouko Meretoja. The estimated number of disease carriers in Finland is almost 1 000, and the disease has subsequently been found in many other countries as well. It's typical initial manifestation is lattice corneal dystrophy, detected at biomicroscopic examination of the eye by the age of 25 to 30 years, followed by slowly progressing cranial neuropathy with bilateral facial palsy, polyneuropathy and generalized cutis laxa. Meretoja's disease is caused by mutations of the gelsolin gene, leading to the production and aberrant processing of variant gelsolin and deposition of its fragments in various tissues in the form of amyloid fibrils. PMID:20597346

  2. Prevalence of amyloid deposition in mature healthy chickens in the flock that previously had outbreaks of vaccine-associated amyloidosis

    PubMed Central

    IBI, Kanata; MURAKAMI, Tomoaki; GODA, Wael Mohamed; KOBAYASHI, Naoki; ISHIGURO, Naotaka; YANAI, Tokuma

    2015-01-01

    Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic inflammation, such as that caused by bacterial infection. We previously described vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of amyloid deposition was measured in mature healthy chickens that survived a previous outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the amyloid deposition in mature chickens and compared the prevalence of amyloid deposition with juvenile chickens obtained in our previous study (Murakami et al., 2013). We found that: 1) amyloid deposition in the liver was absent in mature chickens, while juvenile chickens had a rate of 24%; 2) amyloid deposition in the spleen was observed in 36% of juvenile chickens and in 40% of mature chickens; 3) amyloid deposition in the pectoral muscle of mature chickens (43.75%) was approximately half that of juvenile chickens (88%). These results suggest that additional amyloid deposition in chickens previously exposed to AA amyloidosis may not worsen with age. Further, amyloid deposition in chickens may tend to regress when causative factors, such as vaccinations and/or chronic inflammation, are absent. PMID:25985816

  3. Prevalence of amyloid deposition in mature healthy chickens in the flock that previously had outbreaks of vaccine-associated amyloidosis.

    PubMed

    Ibi, Kanata; Murakami, Tomoaki; Goda, Wael Mohamed; Kobayashi, Naoki; Ishiguro, Naotaka; Yanai, Tokuma

    2015-10-01

    Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic inflammation, such as that caused by bacterial infection. We previously described vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of amyloid deposition was measured in mature healthy chickens that survived a previous outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the amyloid deposition in mature chickens and compared the prevalence of amyloid deposition with juvenile chickens obtained in our previous study (Murakami et al., 2013). We found that: 1) amyloid deposition in the liver was absent in mature chickens, while juvenile chickens had a rate of 24%; 2) amyloid deposition in the spleen was observed in 36% of juvenile chickens and in 40% of mature chickens; 3) amyloid deposition in the pectoral muscle of mature chickens (43.75%) was approximately half that of juvenile chickens (88%). These results suggest that additional amyloid deposition in chickens previously exposed to AA amyloidosis may not worsen with age. Further, amyloid deposition in chickens may tend to regress when causative factors, such as vaccinations and/or chronic inflammation, are absent. PMID:25985816

  4. Unusual Combination of Tracheobronchopathia Osteochondroplastica and AA Amyloidosis

    PubMed Central

    Kırbaş, Gökhan; Dağlı, Canan Eren; Tanrıkulu, Abdullah Çetin; Yıldız, Fetin; Bükte, Yaşar; Kıyan, Esen

    2009-01-01

    Tracheobronchopathia osteochondroplastica (TO) is a rare disorder of unknown cause characterized by the presence of multiple submucosal osseous and/or cartilaginous nodules that protrude into the lumen of the trachea and large bronchi. A simultaneous diagnosis of TO and amyloidosis is rarely reported. In this report, a case initially suspected to be asthma bronchiole that could not be treated, was radiologically diagnosed as TO, and also secondary amyloidosis is presented. A 53 years, man patient reported a 3 years history of dyspnea. Pulmonary function tests (PFTs) showed an obstructive pattern. Chest X-rays revealed right middle lobe atelectasis. FOB and CT detected nodular lesions in the trachea and in the anterior and lateral walls of the main bronchi. AA amyloidosis was confirmed by endobronchial biopsy. In the abdominal fat pad biopsy, amyloidosis was not detected. Asthma bronchiole was excluded by PFTs. This case illustrates that it is possible for TO and amyloidosis to masquerade as asthma. TO and amyloidosis should be suspected in patients of older ages with asthma and especially with poorly treated asthmatic patients. Although nodular lesions in the anterior and lateral tracheobronchial walls are typical for TO, a biopsy should be obtained to exclude amyloidosis. PMID:19881980

  5. Genetics Home Reference: transthyretin amyloidosis

    MedlinePlus

    ... a loss of sensation in the extremities (peripheral neuropathy). The autonomic nervous system, which controls involuntary body ... peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. Impairments in bodily ...

  6. Cerebral β-Amyloidosis in Mice Investigated by Ultramicroscopy

    PubMed Central

    Jährling, Nina; Becker, Klaus; Wegenast-Braun, Bettina M.; Grathwohl, Stefan A.; Jucker, Mathias; Dodt, Hans-Ulrich

    2015-01-01

    Alzheimer´s disease (AD) is the most common neurodegenerative disorder. AD neuropathology is characterized by intracellular neurofibrillary tangles and extracellular β-amyloid deposits in the brain. To elucidate the complexity of AD pathogenesis a variety of transgenic mouse models have been generated. An ideal imaging system for monitoring β-amyloid plaque deposition in the brain of these animals should allow 3D-reconstructions of β-amyloid plaques via a single scan of an uncropped brain. Ultramicroscopy makes this possible by replacing mechanical slicing in standard histology by optical sectioning. It allows a time efficient analysis of the amyloid plaque distribution in the entire mouse brain with 3D cellular resolution. We herein labeled β-amyloid deposits in a transgenic mouse model of cerebral β-amyloidosis (APPPS1 transgenic mice) with two intraperitoneal injections of the amyloid-binding fluorescent dye methoxy-X04. Upon postmortem analysis the total number of β-amyloid plaques, the β-amyloid load (volume percent) and the amyloid plaque size distributions were measured in the frontal cortex of two age groups (2.5 versus 7-8.5 month old mice). Applying ultramicroscopy we found in a proof-of-principle study that the number of β-amyloid plaques increases with age. In our experiments we further observed an increase of large plaques in the older age group of mice. We demonstrate that ultramicroscopy is a fast, and accurate analysis technique for studying β-amyloid lesions in transgenic mice allowing the 3D staging of β-amyloid plaque development. This in turn is the basis to study neural network degeneration upon cerebral β-amyloidosis and to assess Aβ -targeting therapeutics. PMID:26017149

  7. Vulvar amyloidosis mimicking giant condylomata acuminata in a patient with multiple myeloma.

    PubMed

    Konig, A; Wennemuth, G; Soyer, H P; Hoffmann, R; Happle, R; Krause, W

    1999-01-01

    We report a case of unusual cutaneous amyloidosis involving the vulva in a patient with multiple myeloma. Genital examination revealed a dense agglomeration of verrucous papules and pedunculated condyloma-like tumors. The correct diagnosis was established by immunohistochemical examinations that visualized large amounts of lambda light chains, whereas no reaction was detected for kappa light chains or human papilloma virus. In this way, the differential diagnosis of condylomata acuminata could be ruled out. Condyloma-like lesions have been described in patients suffering from multiple myeloma, but the present case is unusual because of the extensive involvement. Vulvar amyloidosis should be added to the list of possible presentations of myeloma-associated systemic amyloidoses. PMID:9920983

  8. Heart transplantation for homozygous familial transthyretin (TTR) V122I cardiac amyloidosis.

    PubMed

    Hamour, I M; Lachmann, H J; Goodman, H J B; Petrou, M; Burke, M M; Hawkins, P N; Banner, N R

    2008-05-01

    Heart failure is the usual cause of death in patients with amyloid cardiomyopathy. The commonest form of hereditary cardiac amyloidosis is associated with the Val122Ile variant of transthyretin (TTR), which is carried by 3-4% of the African American population. Here, we report the outcome of the first cardiac transplantation in a patient with TTR V122I. A 59-year-old Caribbean man presented with biventricular failure. Other than previous bilateral carpel tunnel syndrome, he had been well and had no evidence of extracardiac amyloidosis. An endomyocardial biopsy demonstrated amyloid of TTR type. Sequencing of TTR gene indicated homozygosity for V122I. He underwent cardiac transplantation and 3 years later, remains well with no evidence of allograft or systemic amyloid deposition. PMID:18318779

  9. Renal amyloidosis due to familial mediterranean fever misdiagnosed

    PubMed Central

    Hama, Iman; Ilham, Ratbi; Ouzeddoun, Naima; Alhamany, Zaitouna; Bayahia, Radia; Sefiani, Abdelaziz

    2012-01-01

    Familial Mediterranean fever (FMF, MIM 249100) is an autosomal recessive disease affecting mainly patients of the Mediterranean basin. It is an autoinflammatory periodic disorder characterized by recurrent episodes of fever and abdominal pain, synovitis, and pleuritis. The major complication of FMF is the development of renal AA amyloidosis. Treatment with colchicine prevents the occurrence of recurrent seizures and renal amyloidosis. The disease is caused by mutations in the MEFV gene. We report here the cases of two unrelated patients, who have been late diagnosed with FMF complicated by renal amyloidosis. We focus on the importance of early diagnosis of FMF, both to start rapidly treatment with colchicine and avoid renal amyloidosis, and to provide genetic counseling to families. PMID:23716950

  10. Rituximab therapy in nephrotic syndrome due to AH amyloidosis.

    PubMed

    Katoh, Nagaaki; Matsuda, Masayuki; Miyazaki, Daigo; Gono, Takahisa; Yazaki, Masahide; Ikeda, Shu-Ichi

    2009-01-01

    We report a patient with AH amyloidosis associated with lymphoplasmacytic leukemia that has remained in a stable state with a nephrotic syndrome for 17 months since the commencement of cyclic rituximab therapy aimed at suppression of pathogenetic gamma heavy chains. Free light chains in serum and CD20-positive cells in peripheral blood were useful as hematological markers in the patient. Rituximab might be a potent therapeutic option for AH amyloidosis associated with a B-cell lymphoproliferative disorder. PMID:19590993

  11. Polymerization of intact beta 2-microglobulin in tissue causes amyloidosis in patients on chronic hemodialysis.

    PubMed Central

    Gorevic, P D; Munoz, P C; Casey, T T; DiRaimondo, C R; Stone, W J; Prelli, F C; Rodrigues, M M; Poulik, M D; Frangione, B

    1986-01-01

    Systemic amyloidosis with a predilection for bone and synovium may complicate the course of patients on long-term hemodialysis. This form of amyloidosis can be typed as distinct from other amyloid diseases by using small tissue samples obtained by bone biopsy and at postmortem. Immunoblot analysis of two-dimensional gels of partially solubilized amyloid fibrils established that tissue deposits are composed of monomers, dimers, and higher polymers of beta 2-microglobulin (beta 2m) and that amyloid P component was also present. Anti-beta 2m antiserum recognized fibrils, as shown by immunoelectron microscopy. Purified monomer isolated from dissociated fibrils yielded peptides corresponding to the entire known sequence of beta 2m. Virtually all serum beta 2m, as well as that present in tissue fluid bathing amyloid fibrils, was monomeric. Hemodialysis-related amyloidosis is an example of a deposition disease occurring in hemodialysis patients. We have shown conclusively that, in this amyloid disease, polymerization of an intact normal serum protein to a fibrillar configuration may occur without proteolysis. We propose the designation A beta 2m for this form of amyloid fibril subunit protein. Images PMID:3532124

  12. Multiple myeloma-associated skin light chain amyloidosis: A case of misdiagnosis

    PubMed Central

    XIAO, LI; LIN, FENGXIA; XIAO, RONG; HU, CHUN; DENG, MINGYANG; LI, DAIQIANG; SHE, XIAOLING; LIU, FUYOU; SUN, LIN

    2016-01-01

    The present study reports the case of a 42-year-old male with multiple myeloma (MM)-associated skin light chain amyloidosis who presented with skin purpura as the initial symptom, which was misdiagnosis as Henoch-Schönlein purpura nephritis prior to admission to the Second Xiangya Hospital (Changsha, Hunan, China). The patient presented with purpura, papules petechiae and spontaneous ecchymosis, which was located scattered around the neck, chest and limbs, accompanied by a small amount of bleeding in the conjunctival and oral mucosa, and a swollen tongue. Upon laboratory examination, the serum immunological change showed increased serum immunoglobulin G and λ light chain levels, and a urine Bence Jones protein level of >1 g/24 h. This was accompanied with an abnormal result for immunofixation electrophoresis, and positive staining with Congo red showing apple-green birefringence in skin biopsy specimens. Thus, the patient was diagnosed with MM-associated skin amyloidosis with the initial symptom of skin purpura. Following treatment with chemotherapy consisting of prednisone and bortezomib, the skin lesions markedly improved. The present study indicates that the presentation of skin purpura in systemic amyloidosis associated with MM may be an important aid in the diagnosis and direct treatment of this disease in the clinic. PMID:27284363

  13. Treatment of primary cutaneous amyloidosis with laser: a review of the literature.

    PubMed

    Al Yahya, Rand S

    2016-07-01

    Primary cutaneous amyloidosis (PCA) is a condition characterized by tissue deposition of misfolded proteins. PCA can present in different forms, namely macular, lichen, and nodular amyloidosis. These lesions can be of cosmetic concern and are difficult to treat. Many therapeutic modalities have been suggested for the treatment of PCA, with variable efficacy, including topical and systemic medications, phototherapy, electrodessication, dermabrasion, cryosurgery, and lasers. Over the past decade, several studies have reported successful treatment of PCA with different types of lasers; however, a review of these studies has never been reported in the dermatologic literature. The aim of this study was to review the efficacy and safety of lasers in the treatment of PCA. A search of the National Library of Medicine's PubMed Database was performed. Studies were considered for inclusion based on their relevance, and specific data were extracted from all included studies. Eleven studies, comprising 64 patients, were included in this review. Significant improvements were observed in macular and lichen amyloidosis patients treated with carbon dioxide laser in two studies, while a number of case series and case reports showed good results with other types of laser in the treatment of PCA. This review was limited by the lack of large double-blinded randomized controlled trials and the overall small sample size. Laser treatment is a promising option in the treatment of PCA. Future randomized controlled trials are needed to compare the efficacy of different types of lasers and to select the best parameters for different types of PCA. PMID:26984345

  14. AA amyloidosis as a complication of primary lymphedema.

    PubMed

    Beloncle, François; Sayegh, Johnny; Eymerit-Morin, Caroline; Duveau, Agnès; Augusto, Jean-François

    2014-03-01

    Primary lymphedema is a rare disease caused by a disorder of lymphangiogenesis. Clinical presentation and age at onset are variable. AA amyloidosis is usually due to chronic inflammatory diseases, malignant tumors or less frequently chronic infectious diseases. We report here the first two cases of AA amyloidosis present with renal failure and nephrotic syndrome in patients with primary lymphedema-induced chronic leg ulcers. The first patient was a 62-year-old female who presented with chronic untreated leg ulcers for 8 years secondary to primary lymphedema. A kidney biopsy done for nephrotic syndrome allowed the diagnosis of AA amyloidosis. The second patient was a 54-year-old male who presented with hereditary lymphedema and elephantiasis since the age of 12. A salivary gland biopsy allowed the diagnosis of AA amyloidosis. Renal function deteriorated progressively needing chronic haemodialysis. Chronic leg ulcers have been rarely reported to induce AA amyloidosis. Only five other cases have been reported in the literature, but none of them with chronic lymphedema. We believe that the relation between lymphedema, chronic leg ulcers and AA amyloidosis is underestimated. PMID:23964754

  15. Senile systemic amyloidosis--a case report.

    PubMed

    Shah, V B; Pathak, A M; Mandke, J V; Kandalkar, B M; Chitale, A R

    1999-07-01

    An 85 years old female presented with acute pain and weakness in left lower extremity and doppler evidence of femoropopliteal block was made which subsequently proved fatal. Necropsy revealed extensive amyloid deposition in the heart and amyloid angiopathy in rest of the organs. PMID:10862300

  16. Thermal Properties in the MgAl2O4-Al2O3 System

    SciTech Connect

    Wilkerson, Dr. Kelley R.; Smith, Jeffrey D; Hemrick, James Gordon

    2013-01-01

    Compositional effects on the thermal diffusivity in the MgAl2O4-Al2O3 system were studied. The lowest thermal diffusivity, 0.0258 +/-5% cm/s, was measured between 79.8 and 83.9 wt% Al2O3 quenched from various temperatures between 1500 and 1700C. All of the chemistries in this range extend past the solvus, but still form a singe super-saturated spinel solid solution, regardless of quenching tempeature. A super-saturated metastable solid solution region was observed at 1500, 1600, and 1700C extending to 83.9, 85.2, and 87.1 wt% Al2O3, respectively. Beyond 83.9% Al2O3 a significant increase in thermal diffusivity, 11.7%, was observed and its attributed to precipiation of Al2O3 through spinodal decomposition.

  17. Evolving landscape in the management of transthyretin amyloidosis.

    PubMed

    Hawkins, Philip N; Ando, Yukio; Dispenzeri, Angela; Gonzalez-Duarte, Alejandra; Adams, David; Suhr, Ole B

    2015-01-01

    Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTR(Rx), an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease. PMID:26611723

  18. Evolving landscape in the management of transthyretin amyloidosis

    PubMed Central

    Hawkins, Philip N.; Ando, Yukio; Dispenzeri, Angela; Gonzalez-Duarte, Alejandra; Adams, David; Suhr, Ole B.

    2015-01-01

    Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be significantly reduced with ISIS-TTRRx, an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease. PMID:26611723

  19. Induced Pluripotent Stem Cell Modeling of Multisystemic, Hereditary Transthyretin Amyloidosis

    PubMed Central

    Leung, Amy; Nah, Shirley K.; Reid, Whitney; Ebata, Atsushi; Koch, Clarissa M.; Monti, Stefano; Genereux, Joseph C.; Wiseman, R. Luke; Wolozin, Benjamin; Connors, Lawreen H.; Berk, John L.; Seldin, David C.; Mostoslavsky, Gustavo; Kotton, Darrell N.; Murphy, George J.

    2013-01-01

    Summary Familial transthyretin amyloidosis (ATTR) is an autosomal-dominant protein-folding disorder caused by over 100 distinct mutations in the transthyretin (TTR) gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. Here, we describe the directed differentiation of ATTR patient-specific iPSCs into hepatocytes that produce mutant TTR, and the cardiomyocytes and neurons normally targeted in the disease. We demonstrate that iPSC-derived neuronal and cardiac cells display oxidative stress and an increased level of cell death when exposed to mutant TTR produced by the patient-matched iPSC-derived hepatocytes, recapitulating essential aspects of the disease in vitro. Furthermore, small molecule stabilizers of TTR show efficacy in this model, validating this iPSC-based, patient-specific in vitro system as a platform for testing therapeutic strategies. PMID:24286032

  20. [Nodular pulmonary amyloidosis with bullae; report of a case].

    PubMed

    Ishibashi, H; Akamatsu, H; Sunamori, M; Ishibashi, T; Iwata, T

    2002-11-01

    A 53-year-old male was admitted to the hospital because of progressive paralysis of inferior limb. Chest X-ray film and chest computed tomography (CT) on admission showed a small nodule with bullae in the right lower lung field. After CT-guided marking, partial lung resection including the nodule was performed. The cut surface of the resected specimen showed a tumor (10 mm in diameter) in a bullae measuring 14 mm in diameter. The tumor was diagnosed as amyloidosis. Fourty-six cases of primary localized pulmonary amyloidosis were reported in Japan. However, primary localized pulmonary amyloidosis with bullae is extremely rare, only 3 cases have been reported. PMID:12428345

  1. Amyloidosis Cutis Dyschromica: A Rare Reticulate Pigmentary Dermatosis

    PubMed Central

    Verma, Shyam; Joshi, Rajiv

    2015-01-01

    We are reporting a rare case of amyloidosis cutis dyschromica in a 41-year-old man. This is a rare form of primary cutaneous amyloidosis characterized by reticulate pigmentation with hypopigmented and hyperpigmented macules, onset in childhood, familial tendency in some, occasional mild itching and deposition of amyloid in the papillary dermis. Our case also had multiple bilaterally symmetrical hyperpigmented keratotic papules abutting the axillary vault resembling those seen in Dowling–Deogs disease. The other unusual feature in this patient was the strong family history of vitiligo, which we are unable to explain. We have also tried to explain the mechanism leading to the hyperpigmentation and hypopigmentation in amyloidosis cutis dyschromica. PMID:26288409

  2. Recurrent Pleural Effusions Occurring in Association with Primary Pulmonary Amyloidosis

    PubMed Central

    Tada, Lauren; Anjum, Humayun; Linville, W. Kenneth; Surani, Salim

    2015-01-01

    Recurrent pleural effusions occurring in association with immunoglobulin light chain amyloidosis and not associated with amyloid cardiomyopathy are rare. These portend an overall poor prognosis with mean survival time of approximately 1.8 months. We hereby report a case of a 59-year-old Caucasian female with recurrent pleural effusions and an ultimate diagnosis of pulmonary amyloidosis in association with plasma cell myeloma. The optimal treatment for recurrent pleural effusions in amyloidosis has not been determined; however, our patient responded to therapy with Cyclophosphamide-Bortezomib- (Velcade-) Dexamethasone (CyBorD) and had no repeat hospitalizations or recurrence of pleural effusion at four-month follow-up after initiation of therapy. PMID:26448893

  3. Guideline of transthyretin-related hereditary amyloidosis for clinicians.

    PubMed

    Ando, Yukio; Coelho, Teresa; Berk, John L; Cruz, Márcia Waddington; Ericzon, Bo-Göran; Ikeda, Shu-ichi; Lewis, W David; Obici, Laura; Planté-Bordeneuve, Violaine; Rapezzi, Claudio; Said, Gerard; Salvi, Fabrizio

    2013-01-01

    Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand transthyretin amyloidosis--and, specifically, familial amyloidotic polyneuropathy--so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials. PMID:23425518

  4. Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience

    PubMed Central

    Grogan, Martha; Gertz, Morie; McCurdy, Arleigh; Roeker, Lindsey; Kyle, Robert; Kushwaha, Sudhir; Daly, Richard; Dearani, Joseph; Rodeheffer, Richard; Frantz, Robert; Lacy, Martha; Hayman, Suzanne; McGregor, Christopher; Edwards, Brooks; Dispenzieri, Angela

    2016-01-01

    AIM: To determine the outcome of orthotopic heart transplantation (OHT) in immunoglobulin light chain (AL) amyloidosis. METHODS: The medical records of patients with AL who underwent orthotopic heart transplantation at the Mayo Clinic in Rochester Minnesota from 1992 to 2011 were reviewed. Patients met at least one of the following at: New York Heart Association class IV heart failure, ventricular thickness > 15 mm, ejection fraction < 40%. Selection guidelines for heart transplant included age < 60 years, absence of multiple myeloma and significant extra-cardiac organ involvement. Baseline characteristics including age, gender, organ involvement, and New York Heart Association functional class were recorded. Laboratory data, waiting time until heart transplant, and type of treatment of the underlying plasma cell disorder were recorded. Survival from the time of OHT was calculated using Kaplan-Meier survival curves. Survival of patients undergoing OHT for AL was compared to that of non-amyloid patients undergoing OHT during the same time period. RESULTS: Twenty-three patients (median age 53 years) with AL received OHT. There were no deaths in the immediate perioperative period. Twenty patients have died post OHT. For the entire cohort, the median overall survival was 3.5 years (95%CI: 1.2, 8.2 years). The 1-year survival post OHT was 77%, the 2-year survival 65%, and the 5-year survival 43%. The 5-year survival for non-amyloid patients undergoing OHT during the same era was 85%. Progressive amyloidosis contributed to death in twelve patients. Of those without evidence of progressive amyloidosis, the cause of death included complications of autologous hematopoietic stem cell transplantation for 3 patients, post-transplant lymphoproliferative disorder for 2 patients; and for the remaining one death was related to each of the following causes: acute rejection; cardiac vasculopathy; metastatic melanoma; myelodysplastic syndrome; and unknown. Eight patients had

  5. 'Abd al-Rahman al-Sufi's 3-Step Magnitude System

    NASA Astrophysics Data System (ADS)

    Hafez, Ihsan; Stephenson, F. Richard; Orchiston, Wayne

    'Abd al-Rahmān al-ūfī's Book of the Fixed Stars dates from around AD 964 and is one of the most important medieval Arabic treatises on astronomy. In this paper we begin with a very brief introduction to the Book of the Fixed Stars. This book contains an extensive star catalogue that lists star coordinates and magnitude estimates for all of the Ptolemaic stars. However, in his book al-hūfī utilized three distinct intermediate magnitude values whereas Ptolemy only mentioned two. We believe that al-hūfī used what we have termed a '3-step intermediate magnitude system,' which is more accurate than Ptolemy's 2-step intermediate system. In this paper we examine in detail the accuracy of this unique 3-step system in comparison with Ptolemy's and modern magnitude values.

  6. Experimental induction and oral transmission of avian AA amyloidosis in vaccinated white hens.

    PubMed

    Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Yanai, Tokuma; Goryo, Masanobu; Ishiguro, Naotaka

    2013-06-01

    Avian AA amyloidosis is commonly observed in adult birds afflicted with bacterial infections or chronic inflammatory disorders. Experimental AA amyloidosis in birds can be induced by repeated inflammatory stimulation, such as injection with casein or vaccination with oil-emulsified bacterins. However, the transmission of amyloidosis among avian species has not been studied well to date. In the present study, we confirm the potential induction of avian AA amyloidosis by inoculation of Salmonella enteritidis (SE) vaccine or Mycoplasma gallisepticum vaccine. To determine the transmission of chicken AA amyloidosis among white hens, we induced experimental AA amyloidosis in vaccinated chickens by intravenous or oral administration of chicken AA fibrils. Amyloid deposits were observed in chickens injected with SE and inoculated with chicken AA fibrils intravenously (21/26: 81%) and orally (8/12: 67%). These results suggest that chicken AA amyloidosis can be induced by vaccinations, and may be transmitted among like species by oral administration. PMID:23548152

  7. UNUSUAL PRESENTATION OF GENERALIZED MACULAR AMYLOIDOSIS IN A YOUNG ADULT

    PubMed Central

    Kudur, Mohan H; B, Sathish Pai; H, Sripathi; Prabhu, Smitha

    2008-01-01

    Macular amyloidosis is a common problem seen dermatology out-patient department. Generalized macular amyloidosis presenting with a poikilodermatous appearance is rare. In our case, an 18-year-old male presented with generalized hypopigmented macules with a poikilodermatous appearance of 10-year duration. His developmental milestones were normal with negative family history of similar complaints. Histopathology of hyperpigmented lesions revealed hyperkeratosis and acanthosis of epidermis and hypopigmented lesion showing only hyperkeratosis. Both lesions were showing the deposition of amorphous, hazy material in the tips of papillary dermis with perivascular inflammatory infiltrate. Congo red staining of the amorphous material was positive for amyloid. PMID:19882037

  8. Retroperitoneal amyloidosis as the presenting manifestation of Waldenstrom's macroglobulinaemia

    PubMed Central

    Franco-Palacios, Domingo; Tama, Maher; Samaddar, Suprotim; Yang, Jay

    2013-01-01

    Retroperitoneal amyloidosis has been described in a few case reports and is typically a secondary manifestation of inflammation or malignancy. We present the case of a 69-year-old man who presented with a large pleural effusion and an incidental retroperitoneal mass in the CT imaging. Further investigation confirmed the diagnosis of amyloid amyloidosis involving the retroperitoneum as well as a concurrent Waldenstrom's macroglobulinaemia. Chemotherapy consistent of drugs active against both the lymphoid and plasma cell components of the disease is the proposed therapy for Waldenstrom's macroglobulinaemia in those patients amenable to receive chemotherapy and can make a difference in the survival. PMID:23616327

  9. Severe hidradenitis suppurativa complicated by renal AA amyloidosis.

    PubMed

    Utrera-Busquets, M; Romero-Maté, A; Castaño, Á; Alegre, L; García-Donoso, C; Borbujo, J

    2016-04-01

    Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease affecting the skin folds. Multiple therapeutic options have been proposed for severe cases, but persistent responses are rarely seen. Important complications of HS are uncommon, and usually seen only in severe and unresponsive disease. Amyloid A (AA) amyloidosis is secondary to inflammatory chronic diseases, and is an uncommon complication of dermatological diseases. Only a few cases related with HS have been reported. We report the case of a 37-year-old patient who developed AA amyloidosis secondary to severe HS. PMID:26206410

  10. Imaging of experimental amyloidosis with /sup 131/I-labeled serum amyloid P component

    SciTech Connect

    Caspi, D.; Zalzman, S.; Baratz, M.; Teitelbaum, Z.; Yaron, M.; Pras, M.; Baltz, M.L.; Pepys, M.B.

    1987-11-01

    /sup 131/I-labeled human serum amyloid P component, which was injected into mice with experimentally induced systemic AA amyloidosis and into controls, became specifically localized and was retained in amyloidotic organs. In comparison, it was rapidly and completely eliminated from unaffected tissues and from control animals. Distinctive images of this amyloid-specific deposition of labeled serum amyloid P component were derived from whole body scanning, in vivo, of amyloidotic mice. These findings suggest that such imaging may have applications for the diagnosis and quantitation of amyloid deposits in humans.