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Annals of Internal Medicine Mar 2023Amyloidosis is a pathologic and clinical condition resulting from the accumulation of insoluble aggregates of misfolded proteins in tissues. Extracellular deposition of... (Review)
Review
Amyloidosis is a pathologic and clinical condition resulting from the accumulation of insoluble aggregates of misfolded proteins in tissues. Extracellular deposition of amyloid fibrils in the myocardium leads to cardiac amyloidosis, which is often overlooked as a cause of diastolic heart failure. Although cardiac amyloidosis was previously believed to have a poor prognosis, recent advances in diagnosis and treatment have emphasized the importance of early recognition and changed management of this condition. This article provides an overview of cardiac amyloidosis and summarizes current screening, diagnosis, evaluation, and treatment options.
Topics: Humans; Cardiomyopathies; Myocardium; Amyloidosis; Prognosis
PubMed: 36913688
DOI: 10.7326/AITC202303210 -
Protoplasma Sep 2020Amyloidosis is a diverse group of protein conformational disorder which is caused by accumulation and deposition of insoluble protein fibrils in vital tissues or organs,... (Review)
Review
Amyloidosis is a diverse group of protein conformational disorder which is caused by accumulation and deposition of insoluble protein fibrils in vital tissues or organs, instigating organ dysfunction. Renal amyloidosis is characterized by the acellular Congo red-positive pathologic deposition of amyloid fibrils within glomeruli and/or the interstitium. It is generally composed of serum amyloid A-related protein or an immunoglobulin light chain; other rare forms lysozyme, gelsolin, fibrinogen alpha chain, transthyretin, apolipoproteins AI/AII/AIV/CII/CIII; and the recently identified form ALECT2. This disease typically manifests with heavy proteinuria, nephrotic syndrome, and finally progression to end-stage renal failure. Early diagnosis of renal amyloidosis is arduous as its symptoms appear in later stages with prominent amyloid deposition. The identification of the correct type of amyloidosis is quite troublesome as it can be confused with another related form. Therefore, the exact typing of amyloid is essential for prognosis, treatment, and correct management of renal amyloidosis. The emanation of new techniques of proteomic analysis, for instance, mass spectroscopy/laser microdissection, has provided greater accuracy in amyloid typing. This in-depth review emphasizes on the clinical features, renal pathological findings, and diagnosis of the AL and non-AL forms of renal amyloidosis.
Topics: Amyloidosis; Humans; Kidney; Prognosis
PubMed: 32447467
DOI: 10.1007/s00709-020-01513-0 -
Brazilian Journal of Medical and... 2022Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical... (Review)
Review
Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical management depends on the subtype of the protein deposited and the affected organs. Systemic amyloidosis may stem from anomalous proteins, such as immunoglobulin light chains or serum amyloid proteins in chronic inflammation or may arise from hereditary disorders. Hereditary amyloidosis consists of a group of rare conditions that do not respond to chemotherapy, hence the identification of the amyloid subtype is essential for diagnosis, prognosis, and treatment. The kidney is the organ most frequently involved in systemic amyloidosis. Renal amyloidosis is characterized by acellular pathologic Congo red-positive deposition of amyloid fibrils in glomeruli, vessels, and/or interstitium. This disease manifests with heavy proteinuria, nephrotic syndrome, and progression to end-stage kidney failure. In some situations, it is not possible to identify the amyloid subtype using immunodetection methods, so the diagnosis remains indeterminate. In cases where hereditary amyloidosis is suspected or cannot be excluded, genetic testing should be considered. Of note, laser microdissection/mass spectrometry is currently the gold standard for accurate diagnosis of amyloidosis, especially in inconclusive cases. This article reviews the clinical manifestations and the current diagnostic landscape of renal amyloidosis.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Amyloidosis, Familial; Congo Red; Humans; Immunoglobulin Light Chains
PubMed: 36197414
DOI: 10.1590/1414-431X2022e12284 -
The Journal of Hand Surgery Oct 2019Carpal tunnel syndrome (CTS) can be caused by the deposition and accumulation of misfolded proteins called amyloid and is often an early manifestation of systemic... (Review)
Review
Carpal tunnel syndrome (CTS) can be caused by the deposition and accumulation of misfolded proteins called amyloid and is often an early manifestation of systemic amyloidosis. In patients undergoing surgery for idiopathic CTS, a recent study identified amyloidosis by tenosynovial biopsy in 10.2% of men older than 50 years and women older than 60 years; all positive patients had bilateral symptoms. These findings have led to a renewed interest in amyloidosis as an etiology of CTS. The 2 most common systemic amyloidoses, immunoglobulin light chain and transthyretin amyloidosis, affect the heart, nerves, and other organ systems throughout the body including the soft tissues. Patients with cardiac involvement of amyloidosis have an especially poor prognosis if the disease remains unrecognized and untreated. Early diagnosis is paramount, and patients classically present with cardiac disease several years after being operated on by a hand surgeon for carpal tunnel release. Herein, we present a review of amyloidosis as it pertains to CTS and an algorithm for the detection of amyloidosis in patients undergoing carpal tunnel release. Implementation of this straightforward algorithm will allow for early diagnosis of amyloidosis, a group of progressive and lethal diseases.
Topics: Algorithms; Amyloidosis; Biopsy; Carpal Tunnel Syndrome; Connective Tissue; Early Diagnosis; Humans; Plaque, Amyloid; Reoperation; Rupture; Synovial Membrane; Tendon Injuries; Tendons; Trigger Finger Disorder
PubMed: 31400950
DOI: 10.1016/j.jhsa.2019.06.016 -
Pathology Oncology Research : POR 2023Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant... (Review)
Review
Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.
Topics: Male; Humans; Aged, 80 and over; Pneumothorax; Amyloidosis; Lung; Lung Diseases
PubMed: 37808084
DOI: 10.3389/pore.2023.1611390 -
European Respiratory Review : An... Sep 2017Amyloidosis is a disorder caused by misfolding of autologous protein and its extracellular deposition as fibrils, resulting in vital organ dysfunction and eventually... (Review)
Review
Amyloidosis is a disorder caused by misfolding of autologous protein and its extracellular deposition as fibrils, resulting in vital organ dysfunction and eventually death. Pulmonary amyloidosis may be localised or part of systemic amyloidosis.Pulmonary interstitial amyloidosis is symptomatic only if the amyloid deposits severely affect gas exchange alveolar structure, thus resulting in serious respiratory impairment. Localised parenchymal involvement may be present as nodular amyloidosis or as amyloid deposits associated with localised lymphomas. Finally, tracheobronchial amyloidosis, which is usually not associated with evident clonal proliferation, may result in airway stenosis.Because the treatment options for amyloidosis are dependent on the fibril protein type, the workup of all new cases should include accurate determination of the amyloid protein. Most cases are asymptomatic and need only a careful follow-up. Diffuse alveolar-septal amyloidosis is treated according to the underlying systemic amyloidosis. Nodular pulmonary amyloidosis is usually localised, conservative excision is usually curative and the long-term prognosis is excellent. Tracheobronchial amyloidosis is usually treated with bronchoscopic interventions or external beam radiation therapy.
Topics: Amyloidosis; Animals; Humans; Lung; Lung Diseases, Interstitial; Prognosis; Tomography, X-Ray Computed
PubMed: 28877975
DOI: 10.1183/16000617.0046-2017 -
Archives of Pathology & Laboratory... Feb 2017-Amyloidosis is a heterogeneous group of diseases characterized by the deposition of congophilic amyloid fibrils in the extracellular matrix of tissues and organs. To... (Review)
Review
CONTEXT
-Amyloidosis is a heterogeneous group of diseases characterized by the deposition of congophilic amyloid fibrils in the extracellular matrix of tissues and organs. To date, 31 fibril proteins have been identified in humans, and it is now recommended that amyloidoses be named after these fibril proteins. Based on this classification scheme, the most common forms of amyloidosis include systemic AL (formerly primary), systemic AA (formerly secondary), systemic wild-type ATTR (formerly age-related or senile systemic), and systemic hereditary ATTR amyloidosis (formerly familial amyloid polyneuropathy). Three different clinicopathologic forms of amyloidosis can be seen in the lungs: diffuse alveolar-septal amyloidosis, nodular pulmonary amyloidosis, and tracheobronchial amyloidosis.
OBJECTIVE
-To clarify the relationship between the fibril protein-based amyloidosis classification system and the clinicopathologic forms of pulmonary amyloidosis and to provide a useful guide for diagnosing these entities for the practicing pathologist.
DATA SOURCES
-This is a narrative review based on PubMed searches and the authors' own experiences.
CONCLUSIONS
-Diffuse alveolar-septal amyloidosis is usually caused by systemic AL amyloidosis, whereas nodular pulmonary amyloidosis and tracheobronchial amyloidosis usually represent localized AL amyloidosis. However, these generalized scenarios cannot always be applied to individual cases. Because the treatment options for amyloidosis are dependent on the fibril protein-based classifications and whether the process is systemic or localized, the workup of new clinically relevant cases should include amyloid subtyping (preferably with mass spectrometry-based proteomic analysis) and further clinical investigation.
Topics: Amyloidosis; Humans; Lung Diseases
PubMed: 28134587
DOI: 10.5858/arpa.2016-0102-RA -
American Journal of Kidney Diseases :... Dec 2015AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a... (Review)
Review
AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a single class of immunoglobulin heavy chain. We report a case of AH amyloidosis with immunoglobulin G (IgG) λ monoclonal gammopathy that was diagnosed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunostaining of renal tissue for immunoglobulin heavy chain gave negative results. The molecular weight of the purified renal amyloid protein was ∼11kDa, which was determined by LC-MS/MS analysis to correspond to an amino acid sequence comprising the variable region and a truncated portion of the constant region of IgG heavy chain. The exact same truncated heavy chain was detected by LC-MS/MS of a protein isolated from the patient's serum, suggesting that the truncated serum protein was the precursor of the amyloid protein. Because antibodies to immunoglobulin heavy chain recognize the Fc portion, the large deletion in the constant region could explain the negative results upon immunostaining. Direct protein detection by LC-MS/MS is a powerful aid to diagnose renal AH amyloidosis, particularly when the findings of immunoglobulin staining are inconsistent with the background monoclonal gammopathy.
Topics: Aged; Amyloidosis; Female; Humans; Immunoglobulin Heavy Chains; Kidney; Kidney Diseases
PubMed: 26362695
DOI: 10.1053/j.ajkd.2015.08.016 -
Annual Review of Pathology Jan 2017Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction,... (Review)
Review
Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction, particularly in the heart, kidneys, and nerves. There are at least 30 different proteins that can cause amyloidosis. The clinical management depends entirely on the type of protein deposited, and thus on the underlying pathogenesis, and often requires high-risk therapeutic intervention. Application of mass spectrometry-based proteomic technologies for analysis of amyloid plaques has transformed the way amyloidosis is diagnosed and classified. Proteomic assays have been extensively used for clinical management of patients with amyloidosis, providing unprecedented diagnostic and biological information. They have shed light on the pathogenesis of different amyloid types and have led to identification of numerous new amyloid types, including ALECT2 amyloidosis, which is now recognized as one of the most common causes of systemic amyloidosis in North America.
Topics: Amyloidosis; Animals; Humans; Proteome; Proteomics
PubMed: 27959636
DOI: 10.1146/annurev-pathol-052016-100200 -
Amyloid : the International Journal of... Jun 2008We report a 67-year-old male patient who suffered from nephrotic syndrome and progressive renal dysfunction with monoclonal gammopathy (IgMkappa). Renal biopsy... (Review)
Review
We report a 67-year-old male patient who suffered from nephrotic syndrome and progressive renal dysfunction with monoclonal gammopathy (IgMkappa). Renal biopsy demonstrated amyloid deposition in glomeruli. Immunohistochemical studies of the renal amyloid using a number of antibodies, including anti-lambda and anti-kappa light chains, AA, beta(2)-microglobulin, and transthyretin, showed negative findings. Biochemical analysis of the deposited amyloid fibrils in gastroduodenal mucosa revealed that the amyloid fibrils were composed of an immunoglobulin heavy chain variable region (VH) fragment belonging to the VH1 subgroup, and a diagnosis of AH amyloidosis was made. In our institute, three patients with AH amyloidosis including the present one have been identified during the past 2 years, so AH amyloidosis seems to be by no means a rare disorder.
Topics: Aged; Amino Acid Sequence; Amyloid; Amyloidosis; Gastric Mucosa; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; Intestinal Mucosa; Kidney; Male; Nephrotic Syndrome; Paraproteinemias
PubMed: 18484339
DOI: 10.1080/13506120802006229