Dysautonomias in amyloidosis

2013 ◽  
Vol 32 (04) ◽  
pp. 192-196
Author(s):  
B. P. C. Hazenberg
Keyword(s):  
Cell Clone ◽  
Early Stage ◽  
Systemic Disease ◽  
Interdisciplinary Approach ◽  
Signs And Symptoms ◽  
Systemic Amyloidosis ◽  
Al Amyloidosis ◽  
Life Threatening ◽  
The Individual ◽  
Common Manifestation

SummarySystemic amyloidosis is a life-threatening and frequently unrecognized cause of dysautonomia. Autonomic neuropathy is a common manifestation of AL amyloidosis (caused by deposition of an immunoglobulin free light chain produced by an underlying plasma cell clone) and of autosomal dominant hereditary ATTR amyloidosis (caused by a transthyretin mutation). The following review aims to alert clinicians to look out for signs and symptoms of amyloidosis to enable the bioptic diagnosis at an early stage. Suspicion of systemic amyloidosis is usually raised by the systemic, multi-organ character of the disease. An interdisciplinary approach is needed in the individual patient in order to establish the diagnosis and to obtain a clear overview of the actual multitude of organ problems. This overview is necessary for risk management and for making a well-considered treatment choice. Collaboration of all medical specialists involved is necessary to deliver optimal treatment and care to the patient with this systemic disease.

Valuation of MCP-1 and VEGF Chemokines In Serum of Patients with AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1922-1922
Author(s):  
Alessandro Moscetti ◽  
Francesca Saltarelli ◽  
Maria Paola Bianchi ◽  
Guglielmo Bruno ◽  
Gerardo Salerno ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Inflammatory Process ◽  
Conflicts Of Interest ◽  
Systemic Disease ◽  
Inflammatory Cells ◽  
Mononuclear Phagocytes ◽  
Systemic Amyloidosis ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Localized Amyloidosis

Abstract Abstract 1922 AL amyloidosis is a pathology characterised by the deposition of fibrillary aggregates of immunoglobuline light chains with β-sheet conformation. The light chains are synthetized by neoplastic plasma cell and fibrils deposition can infiltrate tissues leading to multi systemic organ damage. To evaluate if vascular modifications are involved in AL amyloidosis, inflammatory activity of cytokines as MCP-1 and VEGF was investigated. MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte-endothelium binding and migration to sites of inflammation, while VEGF is an endothelial cell mitogen and permeability factor that is potently angiogenic in bone marrow of AL amyloidosis patients. Aim of this study is to evaluate serum cytokines MCP-1 and VEGF levels in patients with systemic or localized AL amyloidosis at presentation to find out potential differences useful to define a characteristic inflammatory pattern. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis and analyzed for serum MCP-1 and VEGF levels. Mann-Whitney test and Spearman correlation were used to compare results. MCP-1 level was significantly higher in the serum of patients with systemic disease (350.52±58.70 pg/ml) compared to the group of patients with localized amyloidosis (147.82±26.03; p=0.004); VEGF was also significantly increased in systemic disease group (p= 0.028). In addition, a positive correlation between MCP-1 and VEGF (r2= 0.755; p=0.031) has been found in the group of patients with systemic amyloidosis. Results seems to suggest a difference in serum cytokine MCP-1 and VEGF levels between AL systemic and localized amyloidosis. In systemic amyloidosis the neoplastic plasma cells interact with bone marrow microenvironment resulting in VEGF release leading to a new angiogenesis also supported by an inflammatory cells increase. The MCP-1 activates and promotes leukocyte-endothelium binding increasing the inflammatory process. The high correlation between MCP-1 and VEGF suggests a positive relationship between a new angiogenesis and a migration of inflammatory cells in the bone marrow stroma. On the basis of our results, MCP-1 and VEGF chemokines can be used to evaluate the inflammatory process in patient with systemic or localized AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk Factors for the Assessment of Patients with Pulmonary Embolism

2006 ◽  
Vol 4 (9) ◽  
pp. 871-880
Author(s):  
John Fanikos ◽  
Samuel Z. Goldhaber
Keyword(s):  
Pulmonary Embolism ◽  
Right Ventricular ◽  
Cancer Patients ◽  
Treatment Options ◽  
Rapid Assessment ◽  
Right Ventricular Dysfunction ◽  
Signs And Symptoms ◽  
Cardiac Biomarkers ◽  
Life Threatening ◽  
The Individual

Pulmonary embolism (PE) occurs frequently among cancer patients, with a spectrum ranging from small, clinically insignificant thrombi to life-threatening massive PE. It is fatal in as many as 14% of cancer patients, primarily by producing right ventricular heart failure and cardiogenic shock. PE diagnosis is difficult because the signs and symptoms imitate other commonly occurring diseases. Clinicians must be able to integrate a wide array of diagnostic imaging tools and laboratory tests to ensure rapid assessment and diagnosis. Risk stratification with the use of cardiac biomarkers and imaging tests to evaluate right ventricular function will identify treatment options. Hemodynamically stable patients can be treated effectively with anticoagulation alone, whereas those with right ventricular dysfunction require an aggressive strategy with thrombolysis, surgical embolectomy, or a catheter-based intervention. When anti-coagulation is contraindicated, a vena caval filter may be deployed. PE treatment must be customized to the individual and consider the existing thrombus burden, presence of underlying cardiopulmonary disease and right side heart dysfunction, and cancer status of the patient. Clinicians should focus on providing adequate thromboprophylaxis in hospitalized cancer patients to avoid PE treatment.

Heart Function In Systemic and Localized AL Amyloidosis: Role of NT-ProBNP and MPC-1

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5006-5006
Author(s):  
Francesca Saltarelli ◽  
Alessandro Moscetti ◽  
Guglielmo Bruno ◽  
Bruno Monarca ◽  
Gerardo Salerno ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Heart Function ◽  
Systemic Disease ◽  
Plasma Concentrations ◽  
Serum Levels ◽  
Mononuclear Phagocytes ◽  
Systemic Amyloidosis ◽  
Al Amyloidosis ◽  
Heart Involvement ◽  
Localized Amyloidosis

Abstract Abstract 5006 In AL amyloidosis typical sites of amyloid buildup are heart, skin, gastrointestinal tract, liver, kidneys, and blood vessels. To evaluate the heart involvement in systemic and localized amyloidosis proBNP, peptide (NT-proBNP; 76 amino acids) and MPC-1 were investigated. NT-proBNP have been described as useful marker for the diagnosis heart disease, and its plasma concentrations correlate with the functional classification of patients according to the New York Heart Association (NYHA). MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte–endothelium binding and migration to sites of inflammation. The MCP-1 levels seem to be related to the severity of cardiac alteration, as demonstrated by the coronary angiogram. NT-proBNP and MPC-1 serum levels were performed in systemic or localized AL amyloidosis to evaluate if there was a difference in the heart involvement. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. To analyze the results of NT-proBNP and MPC-1, Mann-Whitney test was performed. NT-proBNP serum values were significantly (p=0.007) increased in systemic disease. Also, MPC-1 serum levels were significantly (p=0.004) higher in the patients with systemic disease (350.52±58.70 pg/ml) if compared to the group of localized amyloidosis (147.82±26.03 pg/ml). On the basis of our results, the heart seem to be functionally more involved in AL systemic amyloidosis than in localized disease, as demonstrated by the higher NT-proBNP and MPC-1 serum values. Disclosures: No relevant conflicts of interest to declare.

Bilateral periorbital ecchymoses

2014 ◽  
Vol 34 (03) ◽  
pp. 249-252 ◽  
Author(s):  
L. Alberio ◽  
F. Biasiutti ◽  
B. Lämmle ◽  
G. Colucci
Keyword(s):  
Light Chain ◽  
Amyloid Fibrils ◽  
Cell Clone ◽  
Systemic Disease ◽  
Coagulation Factor ◽  
Al Amyloidosis ◽  
Factor X ◽  
The Face ◽  
One Year ◽  
Diagnostic Work

SummaryImmunoglobulin light chain (AL) amyloidosis is a systemic disease caused by a plasma cell clone synthesizing an unstable light chain, which forms amyloid fibrils. Deposition of amyloid fibrils affects primarily kidney, heart, nervous system, spleen, liver, gastrointestinal tract and the skin. Skin bleeding in these patients is called amyloid purpura. Classically, it occurs spontaneously and bilaterally in the periorbital region. Vessel wall fragility and damage by amyloid are the principal causes of periorbital and gastrointestinal bleeding. Additionally, coagulation factor inhibitory circulating paraprotein, hyperfibrinolysis, platelet dysfunction or isolated acquired factor X deficiency may contribute to even more severe, diffuse bleedings.Early diagnosis remains essential for improvsis. Although pictures of amyloid purpura have been often reported in the literature, the clinical diagnosis may be delayed. We report a case of cutaneous manifestation of AL amyloi-dosis diagnosed not until one year after the appearance of the first symptoms. Diagnostic work-up revealed that the patient suffered from multiple myeloma with secondary AL amyloidosis. Atraumatic ecchymoses at the face, particularly the eyelids as well as in the neck should raise the suspicion of AL amyloi-dosis.

scholarly journals Immunoglobulin light chain amyloidosis

2021 ◽  
Author(s):  
Hermine Agis ◽  
Maria T. Krauth
Keyword(s):  
Light Chain ◽  
Systemic Disease ◽  
Correct Diagnosis ◽  
Organ Damage ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Multiprofessional Team ◽  
Assessment And Treatment ◽  
Life Threatening ◽  
Immunoglobulin Light Chain Amyloidosis

SummaryImmunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed life-threatening systemic disease, primarily caused by insoluble depositions of misfolded monoclonal light chains. The monoclonal light chain paraprotein originates from a small clonal B‑cell or a clonal plasma cell population. If left undetected the paraprotein can induce a number of complications based on organ damage. The most dangerous and life-threatening organ dysfunction emerges from cardiac involvement. Thus, patients overall survival depends on early detection. Establishing the correct diagnosis and clear characterization of the amyloid-forming protein, staging, risk assessment and treatment are crucial and depend on a highly experienced interdisciplinary, multiprofessional team.

IL-4 and IL-1 Serum Levels In Systemic and Localized Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5000-5000
Author(s):  
Alessandro Moscetti ◽  
Francesca Saltarelli ◽  
Guglielmo Bruno ◽  
Bruno Monarca ◽  
Gerardo Salerno ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Conflicts Of Interest ◽  
Systemic Disease ◽  
Inverse Correlation ◽  
Serum Levels ◽  
Systemic Amyloidosis ◽  
Al Amyloidosis ◽  
Th2 Response ◽  
Localized Amyloidosis ◽  
Localized Disease

Abstract Abstract 5000 AL amyloidosis is a plasmacellular discrasia characterized by the deposition of light chains fibrils that infiltrate tissues leading to multisystemic organ involvement. Amyloidosis can be systemic or localized disease. No immunological markers are avaibable to distinguish the systemic from localized disease. IL-4 and IL-1 cytokines were performed to evaluate if there is a different inflammatory pattern between the two clinical forms. IL-4 is the central regulator of T helper 2 (Th2) immune responses, with also a major impact on innate immune cells. IL-1 is produced by macrophages, monocytes, fibroblasts and dendritic cells which play an important role in the inflammatory response, activating the Th1-mediated IL2 release. IL-1 increases the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes to sites of infection. The study was devoted to evaluate serum levels of IL-4 and IL-1 in systemic or localized AL amyloidosis at presentation and to find out potential Th1 and Th2 disequilibrium. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. Serum IL-4 and IL-1 levels were detected. Mann-Whitney test and correlation test were used to analyze results. IL-4 level was significantly (p < 0.05) higher in patients with localized disease compared to the group with systemic amyloidosis. IL-1 was instead significantly (p < 0.01) increased in systemic disease. In this, an inverse correlation between IL-4 and IL-1a was found (r2= –0.707; p = 0.05). In systemic amyloidosis, the regulatory mechanism of Th1/Th2 response was polarized versus Th1, as demonstrated by low serum level of IL-4 and high level of IL-1. The negative correlation between serum IL-4 and IL-1 levels demonstrates a disregulation of the immune system in systemic disease as supported by the increased activity of Th1. The results seem to hypothesize that IL-4 could be able to antagonize the diffusion of disease, as demonstrated by the higher IL-4 serum levels in localized amyloidosis. So IL-4 and IL-1 can be considered sensible markers for the inflammatory response assessment both in systemic and localized amyloidosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Supportive Care in AL Amyloidosis

2020 ◽  
Vol 143 (4) ◽  
pp. 335-342 ◽  
Author(s):  
M. Teresa Cibeira ◽  
José T. Ortiz-Pérez ◽  
Luis F. Quintana ◽  
Carlos Fernádez de Larrea ◽  
Natalia Tovar ◽  
...  
Keyword(s):  
Supportive Care ◽  
Light Chain ◽  
Amyloid Fibrils ◽  
Cell Clone ◽  
Systemic Disease ◽  
Complex Interventions ◽  
Al Amyloidosis ◽  
Salt Restriction ◽  
Organ Response

Immunoglobulin light-chain (AL) amyloidosis is a systemic disease characterized by the production and deposition of light chain-derived amyloid fibrils in different organs. Prompt treatment directed to the underlying plasma cell clone is crucial in order to achieve a rapid, deep and durable hematologic response. The decrease in the production of the amyloidogenic light chains is a required condition to obtain the organ response, which is commonly delayed. Meanwhile, supportive treatment is aimed to maintain quality of life of these patients and preserve their involved organs’ function. From simple measures, such as salt restriction or compressive stockings, to very complex interventions, such as heart transplantation in very selected patients with isolated severe cardiac involvement, this supportive care is essential and has to be necessarily included in the multidisciplinary management of this disease.

scholarly journals Scalp biopsy identifies systemic amyloidosis presenting as isolated telogen effluvium: A case report

2019 ◽  
Vol 7 ◽  
pp. 2050313X1984778
Author(s):  
Rory A Sutherland ◽  
Richard I Crawford
Keyword(s):  
Multiple Myeloma ◽  
Rare Case ◽  
Systemic Disease ◽  
Antibody Fragments ◽  
Systemic Amyloidosis ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Biopsy Finding ◽  
Scalp Biopsy ◽  
Underlying Pathology

AL amyloidosis is a complication of B-cell dyscrasias and multiple myeloma, manifest as deposition of antibody fragments in many different organs, including the skin. We describe a rare case of this systemic disease which presented with isolated scalp alopecia. Further investigation led to the diagnosis of an occult plasma-cell dyscrasia, showing the benefit of including systemic amyloidosis in the differential diagnosis of alopecia. The biopsy finding of cutaneous amyloidosis should prompt further workup to exclude an underlying pathology.

scholarly journals Non-Tuberculous Mycobacteria: Seven-Year Experience of a Tertiary Hospital

2019 ◽  
Vol 32 (3) ◽  
pp. 208
Author(s):  
Nuno Ferreira Monteiro ◽  
Susana Peres ◽  
Kamal Mansinho
Keyword(s):  
Diagnostic Criteria ◽  
Early Stage ◽  
Systemic Disease ◽  
Malignant Tumour ◽  
Tertiary Hospital ◽  
Precise Determination ◽  
Public Health Departments ◽  
Life Threatening ◽  
Clinical Records

Introduction: Non-tuberculous mycobacteria are ubiquitous organisms. Precise determination of infection numbers is difficult, since reporting them to public health departments is frequently not mandatory; furthermore, isolating a non-tuberculous mycobacteria does not necessarily translate into disease. The aims of this study were to ascertain non-tuberculous mycobacteria data of a tertiary hospital, determine the incidence and approach to colonization versus disease, and the incidence of predisposing comorbidities.Material and Methods: Retrospective study in a tertiary hospital, involving patients with positive cultural exam for non-tuberculous mycobacteria in any biological sample, from 2010 to 2017.Results: A total of 125 non-tuberculous mycobacteria isolates was identified, corresponding to 96 patients. Of these, 57.4% were male (n = 54); median age was 65 years (interquartile range = [50 - 82]). From these, 60.7% (n = 57) had some degree of immunosuppression, most frequently due to malignant tumour (49.0%) or HIV infection (39.2%). It was found that 29 patients (31.0%) had structural respiratory tract changes. Colonization was defined in 65.6% of patients (n = 63). While 71.0% of non-tuberculous mycobacteria infections were pulmonary, the remaining 29.0% presented as disseminated. According to available clinical records, 60.6% (n = 20) of the presumably infected patients fulfilled American Thoracic Society diagnostic criteria for non-tuberculous mycobacteria disease.Discussion: Several cases of non-tuberculous mycobacteria infection in this study presented as life-threatening, multi-systemic disease, highlighting the importance of accurate diagnosis and timely treatment. Other cases of presumed infection might instead have corresponded to colonization, possibly resulting in futile therapy.Conclusion: While there are diagnostic criteria for treatment of non-tuberculous mycobacteria infections, no such guidelines exist to assess colonization. One of the most challenging aspects remains the correct differentiation between colonization and early-stage infection.

scholarly journals AL amyloidosis

2012 ◽  
Vol 153 (15) ◽  
pp. 563-573
Author(s):  
Klára Gadó ◽  
Gyula Domján
Keyword(s):  
Plasma Cells ◽  
Cell Clone ◽  
Systemic Disease ◽  
Malignant Cell ◽  
High Dose Chemotherapy ◽  
The Body ◽  
High Dose ◽  
Al Amyloidosis ◽  
Amyloidogenic Protein ◽  
Plasma Cell Dyscrasias

AL amyloidosis is a systemic disease characterised by pathogenetic proteins produced by malignant plasma cells and the deposition of them in different organs of the body. Amyloidogenic protein is the light chain of the monoclonal immunoglobulin, which becomes water insoluble, precipitates and deposites in the extracellular space resulting damage of organ function. AL amyloidosis belongs to plasma cell dyscrasias or it can associate to other monoclonal B-cell diseases. Diagnosis – such as in case of other types of amyloidosis – is based on histology. Identification of the amyloidogenic protein often needs special examinations. The goal of the therapy is the eradication of the malignant cell clone. Therapeutical armamentarium has been largely flared in the past few decades, several drugs with new mechanisms of action are available (thalidomide, lenalidomide, bortezomib). The standard treatment is high dose chemotherapy followed by autologous stem cell transplantation in case of eligible patients. Transplantation uneligible patients can be treated with a low dose alkylating agent with or without dexamethasone, or with the new agents. The therapeutical decision must be preceded by very thorough risk assessment. Early diagnosis and the prompt beginning of the treatment has great significance because the evolving functional abnormalities of parenchymal organs (mainly cardiac failure) prevents the effectivity of the treatment. Amyloidosis is an orphan disease, special centers play a significant role in the field of clinical trials. Orv. Hetil., 2012, 153, 563–573.

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