Materiały źródłowe

• #1 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. […] Establishing a diagnosis of AL amyloidosis is often challenging because there is no single test that conclusively establishes the diagnosis, but testing performed in the correct clinical context is needed. Delay in arriving at a diagnosis has been reported to range from 6 months to 2 years from time of symptom onset.

• #2 Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-021-00483-7

  The ongoing rates of early mortality in newly diagnosed AL amyloidosis suggest there continue to be significant delays in diagnosis. […] An online survey from the Amyloid Research Consortium indicates that 37% of patients are diagnosed over 1 year from the onset of initial symptoms with a median of three physician visits before a diagnosis is established. […] If AL amyloidosis is suspected, particularly in patients who have multi-organ dysfunction, biopsies are not the first step in screening. […] The gold standard for typing is laser capture mass spectroscopic proteome analysis. […] Accurate typing of the protein subunit responsible for amyloid deposition is important since it directs treatment. […] The first step in assessing therapy for a patient with AL amyloidosis, as shown in our algorithm, is determination of their eligibility for stem cell transplantation. […] Physician alertness and suspicion to the possibility of amyloidosis is a critical first step in diagnosing AL amyloidosis. […] Once AL amyloidosis is suspected, the diagnosis can usually be made noninvasively, and organ biopsy is not generally required.

• #3 Amyloidosis Diagnosis | Stanford Health Care

  https://stanfordhealthcare.org/medical-conditions/blood-heart-circulation/amyloidosis/diagnosis.html

  Although amyloidosis is a rare disease, it is underdiagnosed. Many people die from complications of amyloidosis without ever receiving a diagnosis. […] At Stanford, your physician begins by conducting a complete medical history and physical exam. Tests for amyloidosis include: […] A biopsy that shows amyloid deposits is the best confirmation of amyloidosis. […] Once our specialists confirm a diagnosis of amyloidosis, we will discuss your treatment plan with you.

• #4 Amyloidosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/amyloidosis/diagnosis-treatment/drc-20353183

  Amyloidosis is often overlooked because the signs and symptoms can mimic those of more-common diseases. […] Early diagnosis can help prevent further organ damage. Precise diagnosis is important because treatment varies greatly, depending on your specific condition. […] Blood and urine may be analyzed for abnormal protein that can indicate amyloidosis. People with certain symptoms may also need thyroid and kidney function tests. […] A tissue sample can be checked for signs of amyloidosis. The biopsy may be taken from the fat under the skin on the abdomen or from bone marrow. Some people may need a biopsy of an affected organ, such as the liver or kidney. The tissue can be tested to see what type of amyloid is involved. […] Images of the organs affected by amyloidosis may include: Echocardiogram. This technology uses sound waves to create moving images that can show how well the heart is working. It can also show heart damage that can be specific to particular types of amyloidosis.

• #5 What Makes Diagnosing Amyloidosis So Difficult?

  https://www.everydayhealth.com/amyloidosis/diagnosis/

  Dr. Comenzo points out that there are roughly 30 different amyloid-producing proteins that can malfunction, each producing different types of amyloidosis as a result and each having potentially different symptoms. […] Plus, most symptoms of amyloidosis are what doctors term nonspecific, meaning they are not specific to amyloidosis and are linked to a number of different and unrelated medical conditions. […] Many individuals with amyloidosis will see multiple doctors to address their various symptoms, and it may take years before receiving an accurate diagnosis, according to Comenzo. Additionally, there are individuals with the condition who never manage to get diagnosed. […] If an individuals symptoms point to amyloidosis, the first step in confirming the presence of the disease would be either a urine test, a blood test, or both. High levels of protein in a persons urine can be caused by the buildup of amyloid in that persons kidneys. Protein in urine is a very powerful indicator of amyloidosis, Gertz says.

• #6 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. […] Establishing a diagnosis of AL amyloidosis is often challenging because there is no single test that conclusively establishes the diagnosis, but testing performed in the correct clinical context is needed. Delay in arriving at a diagnosis has been reported to range from 6 months to 2 years from time of symptom onset.

• #7 Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-021-00483-7

  The ongoing rates of early mortality in newly diagnosed AL amyloidosis suggest there continue to be significant delays in diagnosis. […] An online survey from the Amyloid Research Consortium indicates that 37% of patients are diagnosed over 1 year from the onset of initial symptoms with a median of three physician visits before a diagnosis is established. […] If AL amyloidosis is suspected, particularly in patients who have multi-organ dysfunction, biopsies are not the first step in screening. […] The gold standard for typing is laser capture mass spectroscopic proteome analysis. […] Accurate typing of the protein subunit responsible for amyloid deposition is important since it directs treatment. […] The first step in assessing therapy for a patient with AL amyloidosis, as shown in our algorithm, is determination of their eligibility for stem cell transplantation. […] Physician alertness and suspicion to the possibility of amyloidosis is a critical first step in diagnosing AL amyloidosis. […] Once AL amyloidosis is suspected, the diagnosis can usually be made noninvasively, and organ biopsy is not generally required.

• #8 The Amyloidoses: Clinical Features, Diagnosis and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3487569/

  Amyloidosis is a rare disorder in which insoluble amyloid proteins are deposited in body organs, causing abnormal protein build-up in tissues and eventually leading to organ dysfunction and death. […] Definitive determination of the underlying protein is critical since prognosis and treatment of amyloidosis can vary widely depending on the responsible protein. […] The diagnosis of AL amyloidosis can be made in several ways, although the first critical step is clinical suspicion. Serum protein electrophoresis with immunofixation electrophoresis (SPEP/IFE) is a frequently used screening test that can be deceptively normal in 25% of those with amyloidosis because either the pathogenic light chains are produced in small amounts or they are fully and completely filtered by the kidneys and therefore not present in quantities large enough to be detectable in the serum.

• #9 The Amyloidoses: Clinical Features, Diagnosis and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3487569/

  Even with abnormalities of these protein studies, tissue biopsy confirmation of the diagnosis is required. […] It is usually best to proceed with the least invasive procedures first. […] Effective therapy cannot be instituted unless the type of amyloid is correctly identified. […] This has become much more important as effective interventions have emerged for those with AL and other types of amyloidosis, and the success of therapeutic intervention is predicated on the earliest possible diagnosis.

• #10 Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-021-00483-7

  Immunoglobulin light chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea, and should be considered in patients presenting with these symptoms. […] The diagnosis of AL amyloidosis should be considered by physicians in any patient seen with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly, or diarrhea. […] The first screening test for these patients, as shown in the algorithm (Fig. 1), would be serum immunofixation and an immunoglobulin free light chain assay for k and immunoglobulin light chains. […] A simple subcutaneous fat aspirate and a bone marrow biopsy will demonstrate amyloid deposits in over 85% of patients with immunoglobulin light chain abnormalities and confirm a diagnosis of AL amyloidosis.

• #11 AA (Inflammatory) Amyloidosis Workup: Approach Considerations, Laboratory Studies, Biopsy

  https://emedicine.medscape.com/article/335559-workup

  The overwhelming factor in diagnosing amyloid A (AA) amyloidosis is considering the possibility that it is present. The development of proteinuria in any individual with chronic inflammatory disease or another associated condition should prompt a search for tissue AA deposition, most commonly in the kidney. […] The diagnosis of all forms of amyloidosis is confirmed by Congo red staining in a biopsy specimen. AA amyloidosis is then identified through immunohistochemical analysis and genetic testing. With respect to site selection, rectal biopsy is more useful than subcutaneous fat aspiration in AA amyloidosis. Biopsy of a clinically affected organ is the most sensitive method and may also detect concomitant pathologies, but is invasive and carries the risk of complications. […] For the detection of amyloid, biopsy of a clinically affected organ is the most sensitive method and may also detect concomitant pathologies. However, such a biopsy is invasive and carries the risk of complications, in particular bleeding. Thus, if amyloidosis is clinically suspected, a less invasive procedure may be desirable.

• #12 Diagnosis of Amyloidosis: Clinicopathological Advances and Challenges | IntechOpen

  https://www.intechopen.com/chapters/85657

  Critically, the management of amyloidosis is significantly different for various types of amyloid proteins, and it has become imperative to exactly subtype the amyloidosis for a targeted therapy as well as a guidance for determining its underlying cause. […] For example, neuropathy involving autonomous or peripheral nervous system is a common but early and non-specific manifestation of different types of amyloidosis. Once amyloid deposit is proven in tissue or cytology smears, further study with radiolabelled I123 administration and detection with radionuclide scintigraphy may help evaluate the distribution of amyloid in different organ systems and stage the extent of the disease. […] It is also important to know the correct clinical context in deciding the diagnostic workup, particularly at an early stage. Secondary amyloidosis type AA should be high in the clinical suspicion in a patient with long standing infections such as tuberculosis or chronic inflammatory conditions such as in Crohns disease or auto-immune conditions with long history of remission and relapses. Primary amyloidosis is most often sporadic but can be rarely familial. Among many causes of sporadic amyloidosis, AL type amyloidosis due to tissue deposition of amyloidogenic monoclonal light chains is most frequent and is often manifested by proteinuria. A high index of suspicion, leading to a kidney biopsy for tissue identification of amyloid deposition composed of monoclonal light chain revealed by IF is essential for diagnosis.

• #13 Amyloidosis – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-us/444

  Amyloidosis usually presents with unexplained weight loss, fatigue, and oedema resistant to diuretic therapy. […] Serum and urine immunofixation electrophoresis confirms the presence of monoclonal light chains in AL amyloidosis. Biopsy verification of amyloid deposits is essential for diagnosis. Accurate classification of amyloid deposit in tissues is necessary prior to initiating appropriate therapy. […] Diagnostic investigations include serum immunofixation electrophoresis, urine immunofixation electrophoresis (using 24-hour urine collection), and tissue biopsy.

• #14 Challenges in the Diagnosis of Amyloidosis: Unraveling the Complexity of a Heterogeneous Disease

  https://www.pelobiotech.com/news-details/challenges-in-the-diagnosis-of-amyloidosis-unraveling-the-complexity-of-a-heterogeneous-disease.html

  Amyloidosis comprises a spectrum of diseases characterized by the abnormal accumulation of amyloid fibrils derived from various precursor proteins. Although amyloidosis has been known for centuries, diagnosing the disease remains intricate due to its diverse clinical manifestations and overlapping symptoms with other conditions. Early and accurate diagnosis is crucial for appropriate treatment selection and improved patient outcomes. […] Physicians must maintain a high index of suspicion and consider amyloidosis in patients with unexplained organ dysfunction or characteristic findings such as proteinuria, nephrotic syndrome, heart failure with preserved ejection fraction, peripheral neuropathy, or hepatomegaly. […] One of the major challenges in amyloidosis diagnosis is the diverse range of precursor proteins that can contribute to amyloid fibril formation.

• #15 Neuromuscular Amyloidosis

  https://practicalneurology.com/diseases-diagnoses/neuromuscular/neuromuscular-amyloidosis/31815/

  The most common amyloidosis are both treatable; accurate diagnosis is paramount. […] Symptoms depend on which organs have the amyloid deposits, with a wide variety of symptoms and heterogeneous presentations, making diagnosis often a challenge. […] The progressive nature and autonomic dysfunction are 2 of the most important features of amyloid neuropathy. […] We recommend serum protein electrophoresis with immunofixation and plasma free light chain assay in every person presenting with polyneuropathy of unclear etiology. […] It is also essential to order a basic peripheral neuropathy workup with complete blood chemistry (CBC), vitamin B12 levels, serum A1c, thyroid stimulating hormone (TSH) and free thyroxine (T4) tests, liver enzyme levels, and renal function tests. […] In persons with features highly suggestive of amyloid neuropathy (ie, progressive polyneuropathy, autonomic dysfunction, hypertrophic cardiomyopathy, cardiac arrhythmia, proteinuria, concomitant myopathy, unexplained weight loss of 10 lbs, or family history of neuropathy), we recommend a minimally invasive tissue biopsy (eg, salivary gland biopsy, fat pad aspirate, or skin punch biopsy) with Congo red stain and TTR gene sequencing.

• #16 Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-021-00483-7

  Immunoglobulin light chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea, and should be considered in patients presenting with these symptoms. […] The diagnosis of AL amyloidosis should be considered by physicians in any patient seen with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly, or diarrhea. […] The first screening test for these patients, as shown in the algorithm (Fig. 1), would be serum immunofixation and an immunoglobulin free light chain assay for k and immunoglobulin light chains. […] A simple subcutaneous fat aspirate and a bone marrow biopsy will demonstrate amyloid deposits in over 85% of patients with immunoglobulin light chain abnormalities and confirm a diagnosis of AL amyloidosis.

• #17 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  The first step in diagnosing AL amyloidosis is to establish the presence of a monoclonal protein, because the absence of a monoclonal protein makes the diagnosis of AL amyloidosis extremely unlikely. […] Once a suspicion of AL amyloidosis is entertained, a biopsy demonstration of Congo red-positive amorphous deposits with apple green birefringence on polarized light microscopy is necessary. […] The importance of typing the amyloid fibrils cannot be overstated. This is true even when there is evidence of a monoclonal protein in the serum, because a monoclonal gammopathy may be unrelated to the amyloid process. Mass spectrometry-based proteomic assay is considered the gold standard testing to establish the type of amyloid fibril. […] Given that the heart is the most common organ involved in AL amyloidosis and cardiac involvement is the most important prognostic marker, assessing for heart involvement is crucial.

• #18 The Amyloidoses: Clinical Features, Diagnosis and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3487569/

  Amyloidosis is a rare disorder in which insoluble amyloid proteins are deposited in body organs, causing abnormal protein build-up in tissues and eventually leading to organ dysfunction and death. […] Definitive determination of the underlying protein is critical since prognosis and treatment of amyloidosis can vary widely depending on the responsible protein. […] The diagnosis of AL amyloidosis can be made in several ways, although the first critical step is clinical suspicion. Serum protein electrophoresis with immunofixation electrophoresis (SPEP/IFE) is a frequently used screening test that can be deceptively normal in 25% of those with amyloidosis because either the pathogenic light chains are produced in small amounts or they are fully and completely filtered by the kidneys and therefore not present in quantities large enough to be detectable in the serum.

• #19 Diagnosis, treatment and monitoring of AL amyloidosis – Myeloma Patients Europe

  https://www.mpeurope.org/what-we-do/educational-resources/qas/diagnosis-treatment-and-monitoring-of-al-amyloidosis/

  Diagnosing AL amyloidosis generally involves several tests, including blood tests, urine tests, imaging and biopsies. The following list outlines the most common tests that are performed to establish an AL amyloidosis diagnosis. […] These tests can also help determine the best treatment response once the diagnosis has been established. […] Biopsies are necessary to establish the diagnosis of amyloidosis and determine what type of amyloidosis you have. A biopsy involves taking a small piece of tissue from you. […] A bone marrow biopsy must be performed to find the cells producing the free light chains. […] An echocardiogram (or echo) is a type of ultrasound scan used to look at the heart and nearby blood vessels. […] ECG patterns can help differentiate between AL amyloidosis and TTR cardiac amyloidosis, another type of amyloidosis.

• #20 The Amyloidoses: Clinical Features, Diagnosis and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3487569/

  Amyloidosis is a rare disorder in which insoluble amyloid proteins are deposited in body organs, causing abnormal protein build-up in tissues and eventually leading to organ dysfunction and death. […] Definitive determination of the underlying protein is critical since prognosis and treatment of amyloidosis can vary widely depending on the responsible protein. […] The diagnosis of AL amyloidosis can be made in several ways, although the first critical step is clinical suspicion. Serum protein electrophoresis with immunofixation electrophoresis (SPEP/IFE) is a frequently used screening test that can be deceptively normal in 25% of those with amyloidosis because either the pathogenic light chains are produced in small amounts or they are fully and completely filtered by the kidneys and therefore not present in quantities large enough to be detectable in the serum.

• #21 Amyloidosis – Wikipedia

  https://en.wikipedia.org/wiki/Amyloidosis

  Amyloidosis symptoms are often vague and require different physician specialists for diagnosis. […] Diagnosis may be suspected when protein is found in the urine, organ enlargement is present, or problems are found with multiple peripheral nerves and it is unclear why. Diagnosis is confirmed by tissue biopsy. […] Diagnosis of amyloidosis generally requires tissue biopsy. The biopsy is assessed for evidence of characteristic amyloid deposits. The tissue is treated with various stains. The most useful stain in the diagnosis of amyloid is Congo red, which, combined with polarized light, makes the amyloid proteins appear apple-green on microscopy. […] A sample of tissue can be biopsied or obtained directly from the affected internal organ, but the first-line site of biopsy is subcutaneous abdominal fat, known as a „fat pad biopsy”, due to its ease of acquisition. An abdominal fat biopsy is not completely sensitive and may result in false negatives, which means a negative result does not exclude the diagnosis of amyloidosis. However, direct biopsy of the affected organ may still be unnecessary as other less invasive methods of biopsy can also be used, including rectal mucosa, salivary gland, lip, or bone marrow biopsy which can achieve a diagnosis in up to 85% of people.

• #22 Amyloidosis: Symptoms, Types & Treatments

  https://my.clevelandclinic.org/health/diseases/23398-amyloidosis

  Healthcare providers use a biopsy to identify the protein causing amyloidosis. They may remove a tissue sample from the affected organ or in places where fibrils often collect. These places include your bone marrow or the fat beneath the skin on your belly. […] Other tests you may need include: Blood and urine tests. Providers may test for abnormal protein levels in your blood or pee. They may also use these tests to see how affected organs are functioning. […] Healthcare providers stage amyloidosis to determine how advanced it is. The different types of this condition involve different staging systems. To stage amyloidosis, your provider may consider: The extent of organ damage. Blood test markers, or the amount of normal versus abnormal amyloid proteins. Your symptoms, including their severity.

• #23 AL Amyloidosis | Amyloidosis Foundation

  https://amyloidosis.org/facts/al

  In the United States, AL amyloidosis is the most common type, with approximately 4,500 new cases diagnosed every year. […] Diagnostic testing for AL amyloidosis involves blood tests, urine tests and biopsies. Blood and/or urine tests can indicate signs of the amyloid protein, but only bone marrow tests or other small biopsy samples of tissue or organs can positively confirm the diagnosis of amyloidosis. […] Blood and urine tests should be performed to help verify the diagnosis. They can also aid in discovering which organs are involved and how much they are compromised. […] These blood and urine tests can help with the diagnosis and used often while monitoring response to treatment. […] A tissue biopsy involves the removal of a small sample of tissue to find evidence of amyloid deposits.

• #24 Amyloidosis – Wikipedia

  https://en.wikipedia.org/wiki/Amyloidosis

  Amyloidosis symptoms are often vague and require different physician specialists for diagnosis. […] Diagnosis may be suspected when protein is found in the urine, organ enlargement is present, or problems are found with multiple peripheral nerves and it is unclear why. Diagnosis is confirmed by tissue biopsy. […] Diagnosis of amyloidosis generally requires tissue biopsy. The biopsy is assessed for evidence of characteristic amyloid deposits. The tissue is treated with various stains. The most useful stain in the diagnosis of amyloid is Congo red, which, combined with polarized light, makes the amyloid proteins appear apple-green on microscopy. […] A sample of tissue can be biopsied or obtained directly from the affected internal organ, but the first-line site of biopsy is subcutaneous abdominal fat, known as a „fat pad biopsy”, due to its ease of acquisition. An abdominal fat biopsy is not completely sensitive and may result in false negatives, which means a negative result does not exclude the diagnosis of amyloidosis. However, direct biopsy of the affected organ may still be unnecessary as other less invasive methods of biopsy can also be used, including rectal mucosa, salivary gland, lip, or bone marrow biopsy which can achieve a diagnosis in up to 85% of people.

• #25 AA (Inflammatory) Amyloidosis Workup: Approach Considerations, Laboratory Studies, Biopsy

  https://emedicine.medscape.com/article/335559-workup

  The overwhelming factor in diagnosing amyloid A (AA) amyloidosis is considering the possibility that it is present. The development of proteinuria in any individual with chronic inflammatory disease or another associated condition should prompt a search for tissue AA deposition, most commonly in the kidney. […] The diagnosis of all forms of amyloidosis is confirmed by Congo red staining in a biopsy specimen. AA amyloidosis is then identified through immunohistochemical analysis and genetic testing. With respect to site selection, rectal biopsy is more useful than subcutaneous fat aspiration in AA amyloidosis. Biopsy of a clinically affected organ is the most sensitive method and may also detect concomitant pathologies, but is invasive and carries the risk of complications. […] For the detection of amyloid, biopsy of a clinically affected organ is the most sensitive method and may also detect concomitant pathologies. However, such a biopsy is invasive and carries the risk of complications, in particular bleeding. Thus, if amyloidosis is clinically suspected, a less invasive procedure may be desirable.

• #26 AA (Inflammatory) Amyloidosis Workup: Approach Considerations, Laboratory Studies, Biopsy

  https://emedicine.medscape.com/article/335559-workup

  Rectal biopsy is more useful than subcutaneous fat aspiration in AA amyloidosis. It has been found to produce positive results (assuming that submucosa is included in the biopsy specimen) in 80-85% of patients ultimately found to have tissue amyloid at a clinically relevant site. […] Congo red stain continues to be the criterion standard for detection of amyloid deposits. In AL and AA amyloidosis, Congo red staining of aspirated subcutaneous abdominal fat has a sensitivity of 70-90% for the diagnosis. […] Once histological diagnosis of amyloidosis has been established, the amyloid type should be defined based on immunohistochemical analysis and genetic testing.

• #27 Amyloidosis – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/amyloidosis/amyloidosis

  Diagnosis is by biopsy of affected tissue; the amyloidogenic protein is typed using a variety of immunohistologic and biochemical techniques. […] Diagnosis of amyloidosis is made by demonstration of fibrillar deposits in an involved organ. Aspiration of subcutaneous abdominal fat detects amyloid deposits in approximately 80% of patients with AL but less than 25% of patients with ATTRwt. If the fat biopsy result is negative, a clinically involved organ should be biopsied. The diagnostic sensitivity of kidney and heart biopsies is nearly 100% when these organs are clinically involved. Tissue sections are stained with Congo red dye and examined with a polarizing microscope for characteristic birefringence. Nonbranching 10-nm fibrils can also be recognized by electron microscopy on biopsy specimens from the heart or kidneys.

• #28 AA (Inflammatory) Amyloidosis Workup: Approach Considerations, Laboratory Studies, Biopsy

  https://emedicine.medscape.com/article/335559-workup

  Rectal biopsy is more useful than subcutaneous fat aspiration in AA amyloidosis. It has been found to produce positive results (assuming that submucosa is included in the biopsy specimen) in 80-85% of patients ultimately found to have tissue amyloid at a clinically relevant site. […] Congo red stain continues to be the criterion standard for detection of amyloid deposits. In AL and AA amyloidosis, Congo red staining of aspirated subcutaneous abdominal fat has a sensitivity of 70-90% for the diagnosis. […] Once histological diagnosis of amyloidosis has been established, the amyloid type should be defined based on immunohistochemical analysis and genetic testing.

• #29 Amyloidosis – Wikipedia

  https://en.wikipedia.org/wiki/Amyloidosis

  Amyloidosis symptoms are often vague and require different physician specialists for diagnosis. […] Diagnosis may be suspected when protein is found in the urine, organ enlargement is present, or problems are found with multiple peripheral nerves and it is unclear why. Diagnosis is confirmed by tissue biopsy. […] Diagnosis of amyloidosis generally requires tissue biopsy. The biopsy is assessed for evidence of characteristic amyloid deposits. The tissue is treated with various stains. The most useful stain in the diagnosis of amyloid is Congo red, which, combined with polarized light, makes the amyloid proteins appear apple-green on microscopy. […] A sample of tissue can be biopsied or obtained directly from the affected internal organ, but the first-line site of biopsy is subcutaneous abdominal fat, known as a „fat pad biopsy”, due to its ease of acquisition. An abdominal fat biopsy is not completely sensitive and may result in false negatives, which means a negative result does not exclude the diagnosis of amyloidosis. However, direct biopsy of the affected organ may still be unnecessary as other less invasive methods of biopsy can also be used, including rectal mucosa, salivary gland, lip, or bone marrow biopsy which can achieve a diagnosis in up to 85% of people.

• #30 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  The first step in diagnosing AL amyloidosis is to establish the presence of a monoclonal protein, because the absence of a monoclonal protein makes the diagnosis of AL amyloidosis extremely unlikely. […] Once a suspicion of AL amyloidosis is entertained, a biopsy demonstration of Congo red-positive amorphous deposits with apple green birefringence on polarized light microscopy is necessary. […] The importance of typing the amyloid fibrils cannot be overstated. This is true even when there is evidence of a monoclonal protein in the serum, because a monoclonal gammopathy may be unrelated to the amyloid process. Mass spectrometry-based proteomic assay is considered the gold standard testing to establish the type of amyloid fibril. […] Given that the heart is the most common organ involved in AL amyloidosis and cardiac involvement is the most important prognostic marker, assessing for heart involvement is crucial.

• #31 Challenges in the Diagnosis of Amyloidosis: Unraveling the Complexity of a Heterogeneous Disease

  https://www.pelobiotech.com/news-details/challenges-in-the-diagnosis-of-amyloidosis-unraveling-the-complexity-of-a-heterogeneous-disease.html

  The gold standard for amyloidosis diagnosis is tissue biopsy followed by Congo red staining and confirmation through characteristic apple-green birefringence under polarized light microscopy. However, biopsies may not always be feasible or accessible, and sampling errors can occur due to the focal nature of amyloid deposition. […] Timely and accurate diagnosis is crucial for initiating appropriate treatment and improving patient outcomes.

• #32 Diagnosis of Amyloidosis: Clinicopathological Advances and Challenges | IntechOpen

  https://www.intechopen.com/chapters/85657

  Amyloidosis is a systemic disease with different subtypes of misfolded, insoluble proteins, which are deposited in viscera and thereby cause damage to the affected organs. Its clinical manifestations are highly variable depending on the organs and tissue affected and often require a high degree of clinical suspicion to achieve correct diagnosis. Development of proteomic tools, radioisotope scintigraphy, immunologic antibody targets by immunohistochemistry, immunofluorescence and microscopic techniques have improved the sensitivity of accurate detection of specific subtypes of amyloid proteins. The key to achieving success in better quality of life and overall survival in patients, is in early diagnosis and accurate subtyping of amyloidosis. […] Detection of amyloid protein has variable sensitivity in tissue sections and multiple variables affect its sensitivity such as the density of the amyloid deposits, thickness of the tissue section, quality of the histochemical staining, microscope illumination and quality of the polarizer. The importance of detecting amyloid early and in smaller quantities is essentially to diagnose the condition early, so that necessary treatment can be administered to stabilize and arrest the progression of end-organ damage.

• #33 The Amyloidoses: Clinical Features, Diagnosis and Treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3487569/

  Even with abnormalities of these protein studies, tissue biopsy confirmation of the diagnosis is required. […] It is usually best to proceed with the least invasive procedures first. […] Effective therapy cannot be instituted unless the type of amyloid is correctly identified. […] This has become much more important as effective interventions have emerged for those with AL and other types of amyloidosis, and the success of therapeutic intervention is predicated on the earliest possible diagnosis.

• #34 AL Amyloidosis | Amyloidosis Foundation

  https://amyloidosis.org/facts/al

  With combinations of these blood and urine tests and tissue biopsies, a positive diagnosis can be confirmed in a high percentage of patients. […] If any biopsy result shows a positive diagnosis for amyloidosis, then it is essential to also determine the accurate type of amyloid protein that is involved. In this case, the type of AL amyloidosis must be confirmed, showing a bone marrow disorder with light chain involvement, also known as a plasma cell dyscrasia. […] If your symptoms don’t stop, then keep asking questions of your medical team so they can give you an accurate diagnosis. […] Blood and/or urine tests can indicate signs of the amyloid protein, but only bone marrow tests or other small biopsy samples of tissue or organs can positively confirm the diagnosis of amyloidosis. […] Getting a quick and timely diagnosis is vital.

• #35 Amyloidosis – Wikipedia

  https://en.wikipedia.org/wiki/Amyloidosis

  The type of the amyloid protein can be determined in various ways: the detection of abnormal proteins in the bloodstream (on protein electrophoresis or light chain determination); binding of particular antibodies to the amyloid found in the tissue (immunohistochemistry); or extraction of the protein and identification of its individual amino acids.

• #36 Amyloidosis – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/amyloidosis/amyloidosis

  After amyloidosis has been confirmed by biopsy, the type is determined using a variety of techniques. For some types of amyloidosis, immunohistochemistry or immunofluorescence may be diagnostic, but false-positive typing results occur. Other useful techniques include gene sequencing for hereditary amyloidosis and biochemical identification by mass spectrometry to accurately identify protein variants in amyloid deposits (the most sensitive and specific method). […] If AL amyloidosis is suspected, patients should be evaluated for an underlying plasma cell disorder using quantitative measurement of serum free immunoglobulin light chains, qualitative detection of serum or urine monoclonal light chains using immunofixation electrophoresis, and a bone marrow biopsy with flow cytometry or immunohistochemistry to establish plasma cell clonality. […] Patients are screened for organ involvement beginning with noninvasive testing.

• #37 Diagnosis of Amyloidosis: Clinicopathological Advances and Challenges | IntechOpen

  https://www.intechopen.com/chapters/85657

  Testing for amyloid is very often performed in surrogate tissues such as abdominal fat pad, tongue, or rectal biopsies. The main reason is the easier accessibility and possibility of repeat testing when warranted. The draw-back of this approach is the limited sensitivity, when compared with testing in a potentially affected organ. […] Within the wide scope of the diagnostic approach for cardiac amyloidosis detailed elsewhere, cardiac amyloidosis is essentially detected by identifying low voltage QRS changes and a thick-walled non-dilated left ventricle in echocardiography. Serum marker studies for troponin proteins and N-terminal brain natriuretic peptide (NT-proBNP) are extremely useful markers in screening, detection and prognostication of patients with cardiac amyloidosis. […] The role of cardiac magnetic resonance (CMR) in the diagnosis of amyloid is still in evolution. Bone avid radio-isotope scan and technetium scintigraphy is a highly sensitive and specific method of detection of cardiomyopathy of ATTR type, in the absence of cardiac biopsy, in patients without light chain restriction as defined by work-up with free light chain assay (FLC) and negative serum and urine immunofixation electrophoresis.

• #38 Diagnosis of Amyloidosis: Clinicopathological Advances and Challenges | IntechOpen

  https://www.intechopen.com/chapters/85657

  While we emphasize on the high index of clinical suspicion for evaluation of amyloidosis, it is important to remember that clinical symptoms can be highly variable. For example, though proteinuria of sub-nephrotic or nephrotic range is the most common presentation of renal amyloidosis, newly identified ALECT2 amyloidosis, is known to present with bland urine sediments in the absence of or minimal proteinuria, in a setting of hypertension and chronic renal failure. […] Immunohistochemistry staining performed in formalin fixed paraffin embedded tissue sections is most useful in staining for type AA amyloid to detect secondary amyloidosis. It is particularly useful, as identifying the exact cause of secondary amyloidosis is not always straight-forward, as there may be several confounding diseases and factors influencing the condition in each patient. […] Immunofluorescence and immunohistochemistry will remain major diagnostic tools in basic subtyping of amyloidosis, due to their wider availability, better standardization, and reporting in most hospital-based pathology laboratories.

• #39 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  The first step in diagnosing AL amyloidosis is to establish the presence of a monoclonal protein, because the absence of a monoclonal protein makes the diagnosis of AL amyloidosis extremely unlikely. […] Once a suspicion of AL amyloidosis is entertained, a biopsy demonstration of Congo red-positive amorphous deposits with apple green birefringence on polarized light microscopy is necessary. […] The importance of typing the amyloid fibrils cannot be overstated. This is true even when there is evidence of a monoclonal protein in the serum, because a monoclonal gammopathy may be unrelated to the amyloid process. Mass spectrometry-based proteomic assay is considered the gold standard testing to establish the type of amyloid fibril. […] Given that the heart is the most common organ involved in AL amyloidosis and cardiac involvement is the most important prognostic marker, assessing for heart involvement is crucial.

• #40 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  The first step in diagnosing AL amyloidosis is to establish the presence of a monoclonal protein, because the absence of a monoclonal protein makes the diagnosis of AL amyloidosis extremely unlikely. […] Once a suspicion of AL amyloidosis is entertained, a biopsy demonstration of Congo red-positive amorphous deposits with apple green birefringence on polarized light microscopy is necessary. […] The importance of typing the amyloid fibrils cannot be overstated. This is true even when there is evidence of a monoclonal protein in the serum, because a monoclonal gammopathy may be unrelated to the amyloid process. Mass spectrometry-based proteomic assay is considered the gold standard testing to establish the type of amyloid fibril. […] Given that the heart is the most common organ involved in AL amyloidosis and cardiac involvement is the most important prognostic marker, assessing for heart involvement is crucial.

• #41 Amyloidosis diagnosis – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/amyloidosis/diagnosis/

  Further tests will then usually be arranged to establish whether the heart and kidneys or other organs of the body have been affected by the aggregation of the amyloid protein and by how much. These tests include blood and urine tests, ECGs, echo cardiograms and sometimes scans and nerve conduction tests. Not all of these will be necessary for every type of amyloidosis. These results will provide a baseline of your disease and general health which will be compared with later results to assess how well you are progressing and responding to treatment.

• #42 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  The first step in diagnosing AL amyloidosis is to establish the presence of a monoclonal protein, because the absence of a monoclonal protein makes the diagnosis of AL amyloidosis extremely unlikely. […] Once a suspicion of AL amyloidosis is entertained, a biopsy demonstration of Congo red-positive amorphous deposits with apple green birefringence on polarized light microscopy is necessary. […] The importance of typing the amyloid fibrils cannot be overstated. This is true even when there is evidence of a monoclonal protein in the serum, because a monoclonal gammopathy may be unrelated to the amyloid process. Mass spectrometry-based proteomic assay is considered the gold standard testing to establish the type of amyloid fibril. […] Given that the heart is the most common organ involved in AL amyloidosis and cardiac involvement is the most important prognostic marker, assessing for heart involvement is crucial.

• #43 Cardiac amyloidosis: epidemiology, diagnosis and therapy

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-19/cardiac-amyloidosis-epidemiology-diagnosis-and-therapy

  The diagnosis of cardiac amyloidosis depends on a high degree of clinical suspicion and is often delayed due to the lack of disease awareness and the heterogeneity of symptoms at presentation. […] The initial diagnostic evaluation of a patient with suspected cardiac amyloidosis includes a thorough clinical examination and history taking to identify and assess cardiac and extracardiac symptoms and signs of amyloidosis, as described in Table 1. […] Low QRS voltages in the electrocardiogram, discordant to left ventricular wall thickness, raise the suspicion of cardiac amyloidosis, whilst an echocardiogram is the initial cardiac imaging test for patients with suspected cardiac amyloidosis. […] Tissue characterisation with cardiovascular magnetic resonance (CMR) imaging may typically reveal diffuse subendocardial or transmural late gadolinium enhancement as well as increase in extracellular volume with T1 mapping.

• #44 Cardiac amyloidosis: epidemiology, diagnosis and therapy

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-19/cardiac-amyloidosis-epidemiology-diagnosis-and-therapy

  In the presence of cardiac and other findings suggestive of amyloidosis, the next step is to perform serum kappa/lamda free light chain ratio analysis, serum protein immunofixation and urine protein immunofixation. […] Bone tracer cardiac scintigraphy is a hallmark test for identifying ATTR amyloidosis, and the presence of grade 2 or 3 scintigraphy has high sensitivity and specificity for cardiac amyloidosis compared with tissue biopsy. […] Progress in diagnostic techniques, including echocardiography, cardiac magnetic resonance and bone scintigraphy, has led to a non-invasive diagnostic approach, thus limiting the need for endomyocardial biopsy.

• #45

  https://link.springer.com/article/10.1007/s00392-020-01799-3

  The cardiac biomarkers troponin T and NT-proBNP are part of the diagnostic criteria for the presence of cardiac involvement in all forms of amyloidosis. Biomarkers in the normal range virtually exclude relevant cardiac involvement, while elevated biomarkers may indicate cardiac involvement, but are not specific for amyloidosis and must be interpreted in the context of cardiac imaging. […] If light-chain amyloidosis is suspected, additional laboratory tests are necessary. First, an electrophoresis with determination of the M-gradient and immunofixation electrophoresis in serum and urine are performed, followed by quantitative determination of the free light-chain kappa and lambda in serum as well as the calculation of the ratio and the difference. […] The 12-lead resting ECG is part of every cardiac evaluation in patients with suspected cardiac amyloidosis as well as of every follow-up visit.

• #46

  https://link.springer.com/article/10.1007/s00392-020-01799-3

  Transthoracic echocardiography is the primary and most widely available cardiological diagnostic imaging tool for patients with suspected cardiac amyloidosis. […] In recent years, cardiovascular magnetic resonance imaging (CMR) has gained considerable importance in the diagnosis of amyloidosis and its distinction from other cardiomyopathies. […] Current scintigraphic methods rely on the use of radionuclides based on 99mTc phosphates. […] Today, endomyocardial biopsy (EMB) still remains the gold standard for the diagnosis of many non-ischemic heart diseases, such as (viral) myocarditis, cardiac storage diseases, and also for infiltrative or restrictive cardiomyopathies such as cardiac amyloidosis. […] The biopsy-proven extent of amyloidosis is of crucial therapeutic importance, particularly in AL amyloidosis: a bioptically quantified amyloid load of 20% (of the EMB sample considered) is associated with a lower probability of a therapeutic benefit from consecutive chemotherapy. […] In principle, the same general treatment recommendations apply to patients with symptomatic cardiac AL and ATTR amyloidosis as for patients with heart failure (HFrEF or HFpEF) due to other causes.

• #47 Diagnosis of cardiac amyloidosis: a systematic review on the role of imaging and biomarkers | BMC Cardiovascular Disorders | Full Text

  https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0952-8

  Endomyocardial biopsy remains the gold standard of CA amyloidosis diagnosis. Regarding AL, fat pad biopsy has been proven to have great sensitivity to confirm the diagnosis. A quick and efficient diagnostic approach in CA is of great significance given the accelerated deterioration observed in advanced stages of the disease. […] The diagnostic modalities that will be discussed below represent efforts to offer the clinicians with tools in order to minimize lost cases, significantly reduce the time needed for making the diagnosis, whilst simultaneously maintaining reasonable cost-effectiveness. […] CMR with LGE demonstrated 80% sensitivity and 90% specificity in detecting cardiac involvement in amyloidosis. […] The introduction of a new, high sensitivity assay for measuring cTnT, hs-cTnT, was thought that could improve the staging of AL amyloidosis.

• #48 Amyloidosis: The Path to Diagnosis | MyAmyloidosisTeam

  https://www.myamyloidosisteam.com/resources/amyloidosis-the-path-to-diagnosis

  If you know you have one of these conditions, your doctor may want you to undergo diagnostic tests if you develop a symptom of amyloidosis. This often includes looking at protein levels in the urine or taking a kidney biopsy. […] To figure out which one you have, your doctor can take a blood sample and use genetic testing to read the sequence of genes like transthyretin (TTR). […] Diagnosis often includes imaging tests, such as X-rays, to look for these signs.

• #49 Diagnosis of Amyloidosis: Clinicopathological Advances and Challenges | IntechOpen

  https://www.intechopen.com/chapters/85657

  Critically, the management of amyloidosis is significantly different for various types of amyloid proteins, and it has become imperative to exactly subtype the amyloidosis for a targeted therapy as well as a guidance for determining its underlying cause. […] For example, neuropathy involving autonomous or peripheral nervous system is a common but early and non-specific manifestation of different types of amyloidosis. Once amyloid deposit is proven in tissue or cytology smears, further study with radiolabelled I123 administration and detection with radionuclide scintigraphy may help evaluate the distribution of amyloid in different organ systems and stage the extent of the disease. […] It is also important to know the correct clinical context in deciding the diagnostic workup, particularly at an early stage. Secondary amyloidosis type AA should be high in the clinical suspicion in a patient with long standing infections such as tuberculosis or chronic inflammatory conditions such as in Crohns disease or auto-immune conditions with long history of remission and relapses. Primary amyloidosis is most often sporadic but can be rarely familial. Among many causes of sporadic amyloidosis, AL type amyloidosis due to tissue deposition of amyloidogenic monoclonal light chains is most frequent and is often manifested by proteinuria. A high index of suspicion, leading to a kidney biopsy for tissue identification of amyloid deposition composed of monoclonal light chain revealed by IF is essential for diagnosis.

• #50 Amyloidosis | Condition | UT Southwestern Medical Center

  https://utswmed.org/conditions-treatments/amyloidosis/

  Fat pad biopsy: Removal of a small sample of fat tissue from the abdomen to check for amyloid deposits […] Magnetic resonance imaging (MRI) scan: Test that uses a large magnet and radio waves to produce detailed images of the organs […] 24-hour urine collection: Checks for excess protein. […] Diagnostic tests for cardiac amyloidosis may include: […] Echocardiography (echo or cardiac ultrasound): Imaging test that uses sound waves to produce a video of the heart to look for thickened muscle and amyloid deposits. […] To confirm a diagnosis of amyloid neuropathy, our doctors may recommend: […] Electromyography and nerve conduction studies: Tests that evaluate the electrical activity of muscles and nerves […] Skin biopsy: Removal of a small sample of skin to check the distribution of nerves […] Nerve and muscle biopsy: Removal of small samples to check for amyloid deposits.

• #51 Neuromuscular Amyloidosis

  https://practicalneurology.com/diseases-diagnoses/neuromuscular/neuromuscular-amyloidosis/31815/

  The most common amyloidosis are both treatable; accurate diagnosis is paramount. […] Symptoms depend on which organs have the amyloid deposits, with a wide variety of symptoms and heterogeneous presentations, making diagnosis often a challenge. […] The progressive nature and autonomic dysfunction are 2 of the most important features of amyloid neuropathy. […] We recommend serum protein electrophoresis with immunofixation and plasma free light chain assay in every person presenting with polyneuropathy of unclear etiology. […] It is also essential to order a basic peripheral neuropathy workup with complete blood chemistry (CBC), vitamin B12 levels, serum A1c, thyroid stimulating hormone (TSH) and free thyroxine (T4) tests, liver enzyme levels, and renal function tests. […] In persons with features highly suggestive of amyloid neuropathy (ie, progressive polyneuropathy, autonomic dysfunction, hypertrophic cardiomyopathy, cardiac arrhythmia, proteinuria, concomitant myopathy, unexplained weight loss of 10 lbs, or family history of neuropathy), we recommend a minimally invasive tissue biopsy (eg, salivary gland biopsy, fat pad aspirate, or skin punch biopsy) with Congo red stain and TTR gene sequencing.

• #52 Diagnosis of Amyloidosis: Clinicopathological Advances and Challenges | IntechOpen

  https://www.intechopen.com/chapters/85657

  Testing for amyloid is very often performed in surrogate tissues such as abdominal fat pad, tongue, or rectal biopsies. The main reason is the easier accessibility and possibility of repeat testing when warranted. The draw-back of this approach is the limited sensitivity, when compared with testing in a potentially affected organ. […] Within the wide scope of the diagnostic approach for cardiac amyloidosis detailed elsewhere, cardiac amyloidosis is essentially detected by identifying low voltage QRS changes and a thick-walled non-dilated left ventricle in echocardiography. Serum marker studies for troponin proteins and N-terminal brain natriuretic peptide (NT-proBNP) are extremely useful markers in screening, detection and prognostication of patients with cardiac amyloidosis. […] The role of cardiac magnetic resonance (CMR) in the diagnosis of amyloid is still in evolution. Bone avid radio-isotope scan and technetium scintigraphy is a highly sensitive and specific method of detection of cardiomyopathy of ATTR type, in the absence of cardiac biopsy, in patients without light chain restriction as defined by work-up with free light chain assay (FLC) and negative serum and urine immunofixation electrophoresis.

• #53 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  Advances in plasma cell-directed therapies and improved supportive care have resulted in an improvement in overall survival (OS) for patients with AL amyloidosis over the past 2 decades. […] The Mayo 2004 prognostic model for AL amyloidosis incorporates NT-proBNP (N-terminal proB-type natriuretic peptide; 332 ng/L) and cardiac troponin T (cTnT; 0.035 mg/L), with 1 point for each biomarker above the mentioned thresholds. […] Establishing the diagnosis requires a high index of suspicion. Diagnosis confirmation requires biopsy-proven Congo red-positive material followed by accurate typing of the amyloid fibril.

• #54 Diagnosis of cardiac amyloidosis: a systematic review on the role of imaging and biomarkers | BMC Cardiovascular Disorders | Full Text

  https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0952-8

  The currently preferred staging system in AL amyloidosis is the Mayo Amyloidosis Staging System that utilizes the aforementioned biomarkers cTNT, NT-proBNP and dFLC to stratify disease severity in patients with AL. […] A timely diagnosis is thus critical but frequently proves difficult, as the symptoms are rarely indicative of the disease. The low cost, simplicity and lack of radiation render ultrasonographic protocols an almost ideal tool to rule in amyloidosis as a likely cause of congestive heart failure.

• #55 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  Advances in plasma cell-directed therapies and improved supportive care have resulted in an improvement in overall survival (OS) for patients with AL amyloidosis over the past 2 decades. […] The Mayo 2004 prognostic model for AL amyloidosis incorporates NT-proBNP (N-terminal proB-type natriuretic peptide; 332 ng/L) and cardiac troponin T (cTnT; 0.035 mg/L), with 1 point for each biomarker above the mentioned thresholds. […] Establishing the diagnosis requires a high index of suspicion. Diagnosis confirmation requires biopsy-proven Congo red-positive material followed by accurate typing of the amyloid fibril.

• #56 Diagnosis of cardiac amyloidosis: a systematic review on the role of imaging and biomarkers | BMC Cardiovascular Disorders | Full Text

  https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-018-0952-8

  The currently preferred staging system in AL amyloidosis is the Mayo Amyloidosis Staging System that utilizes the aforementioned biomarkers cTNT, NT-proBNP and dFLC to stratify disease severity in patients with AL. […] A timely diagnosis is thus critical but frequently proves difficult, as the symptoms are rarely indicative of the disease. The low cost, simplicity and lack of radiation render ultrasonographic protocols an almost ideal tool to rule in amyloidosis as a likely cause of congestive heart failure.

• #57

  https://link.springer.com/article/10.1007/s40265-022-01830-z

  Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. […] Circulating free light chain measurement in the diagnosis, prognostic assessment and evaluation of response of AL amyloidosis: comparison of Freelite and N latex FLC assays. […] Graded renal response criteria for light chain (AL) amyloidosis. […] Graded cardiac response criteria for AL amyloidosis: the impact of depth of cardiac response on survival.

• #58 Cardiac Amyloidosis Imaging, Part 3: Interpretation, Diagnosis, and Treatment | Journal of Nuclear Medicine Technology

  https://tech.snmjournals.org/content/51/2/102

  Cardiac amyloidosis was thought to be rare, undiagnosable, and incurable. However, recently it has been discovered to be common, diagnosable, and treatable. […] Diagnosing cardiac amyloidosis is complicated because typical signs and symptoms are nonspecific and usually attributed to other cardiac disorders. […] Several clinical and noninvasive diagnostic imaging (echocardiography and cardiac MRI) red flags have been identified that suggest a patient may have cardiac amyloidosis. […] One element in the diagnostic algorithm is to identify monoclonal proteins indicative of AL. […] Another element is identifying and grading cardiac amyloid deposition using 99mTc-pyrophosphate imaging. […] The absence of monoclonal proteins and a positive 99mTc-pyrophosphate scan is diagnostic for cardiac ATTR.

• #59 Cardiac amyloidosis: epidemiology, diagnosis and therapy

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-19/cardiac-amyloidosis-epidemiology-diagnosis-and-therapy

  In the presence of cardiac and other findings suggestive of amyloidosis, the next step is to perform serum kappa/lamda free light chain ratio analysis, serum protein immunofixation and urine protein immunofixation. […] Bone tracer cardiac scintigraphy is a hallmark test for identifying ATTR amyloidosis, and the presence of grade 2 or 3 scintigraphy has high sensitivity and specificity for cardiac amyloidosis compared with tissue biopsy. […] Progress in diagnostic techniques, including echocardiography, cardiac magnetic resonance and bone scintigraphy, has led to a non-invasive diagnostic approach, thus limiting the need for endomyocardial biopsy.

• #60 Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-021-00483-7

  The ongoing rates of early mortality in newly diagnosed AL amyloidosis suggest there continue to be significant delays in diagnosis. […] An online survey from the Amyloid Research Consortium indicates that 37% of patients are diagnosed over 1 year from the onset of initial symptoms with a median of three physician visits before a diagnosis is established. […] If AL amyloidosis is suspected, particularly in patients who have multi-organ dysfunction, biopsies are not the first step in screening. […] The gold standard for typing is laser capture mass spectroscopic proteome analysis. […] Accurate typing of the protein subunit responsible for amyloid deposition is important since it directs treatment. […] The first step in assessing therapy for a patient with AL amyloidosis, as shown in our algorithm, is determination of their eligibility for stem cell transplantation. […] Physician alertness and suspicion to the possibility of amyloidosis is a critical first step in diagnosing AL amyloidosis. […] Once AL amyloidosis is suspected, the diagnosis can usually be made noninvasively, and organ biopsy is not generally required.

• #61 Diagnostic Testing for Transthyretin Cardiac Amyloidosis | For HCPs

  https://transthyretincardiacamyloidosis.pfizerpro.com/diagnosis/diagnostic-testing

  Nuclear scintigraphy with 99mTechnetium pyrophosphate (99mTc-PYP) a noninvasive approach1 […] can identify ATTR cardiac amyloidosis with high sensitivity and specificity.2 […] A multicenter international study at amyloid centers of excellence demonstrated 100% positive predictive value for ATTR cardiac amyloidosis using visual grade 2 or 3 with concurrent testing to rule out immunoglobulin light chain (AL) amyloidosis.1,4 […] When cardiac amyloidosis is suspected, grade 2 or 3 myocardial uptake with concurrent testing to rule out AL is diagnostic of ATTR cardiac amyloidosis, as this degree of uptake is seen in 20% of patients with AL. […] Diagnosis of ATTR cardiac amyloidosis cannot be made solely based on heart-to-contralateral lung (H/CL) ratio alone. […] If clinical suspicion for cardiac amyloidosis remains high despite a negative or inconclusive scintigraphy scan, consider EMB, as biopsy with Congo red histology and apple-green birefringence can be used to diagnose ATTR cardiac amyloidosis. […] Genetic testing is used to determine if the disease is hereditary due to a mutation in the TTR gene or if it is wild-type. […] Diagnosis of hATTR-CM in an index patient should prompt genetic counseling and testing of family members.

• #62 Diagnostic Testing for Transthyretin Cardiac Amyloidosis | For HCPs

  https://transthyretincardiacamyloidosis.pfizerpro.com/diagnosis/diagnostic-testing

  Nuclear scintigraphy with 99mTechnetium pyrophosphate (99mTc-PYP) a noninvasive approach1 […] can identify ATTR cardiac amyloidosis with high sensitivity and specificity.2 […] A multicenter international study at amyloid centers of excellence demonstrated 100% positive predictive value for ATTR cardiac amyloidosis using visual grade 2 or 3 with concurrent testing to rule out immunoglobulin light chain (AL) amyloidosis.1,4 […] When cardiac amyloidosis is suspected, grade 2 or 3 myocardial uptake with concurrent testing to rule out AL is diagnostic of ATTR cardiac amyloidosis, as this degree of uptake is seen in 20% of patients with AL. […] Diagnosis of ATTR cardiac amyloidosis cannot be made solely based on heart-to-contralateral lung (H/CL) ratio alone. […] If clinical suspicion for cardiac amyloidosis remains high despite a negative or inconclusive scintigraphy scan, consider EMB, as biopsy with Congo red histology and apple-green birefringence can be used to diagnose ATTR cardiac amyloidosis. […] Genetic testing is used to determine if the disease is hereditary due to a mutation in the TTR gene or if it is wild-type. […] Diagnosis of hATTR-CM in an index patient should prompt genetic counseling and testing of family members.

• #63 Addressing the barriers to earlier amyloidosis diagnosis | AstraZeneca

  https://www.astrazeneca.com/media-centre/articles/2024/earlier-amyloidosis-diagnosis.html

  At AstraZeneca, we are committed to driving healthcare system transformation to improve outcomes for patients living with amyloidosis around the world. […] Our ambition is to halve the time to diagnosis by 2028 and double the diagnosis rates specifically of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a type of amyloidosis that often leads to heart failure (HF), by 2030. […] Early and accurate diagnosis in ATTR amyloidosis, leading to initiation of guideline-directed medical therapies (GDMT) and treatment, is essential to mitigate the impact of this disease on survival and quality of life (QoL). […] Barriers to early diagnosis include a lack of proactive screening in those with HF for amyloidosis and subsequent delay in specialist care. […] We are enabling proactive patient identification through different diagnostic tools such as artificial intelligence-assisted echocardiography, electronic medical record algorithms, biomarkers and genetic testing.

• #64 Diagnostic Algorithms for Cardiac Amyloidosis | Pathology and Laboratory Science | IU School of Medicine

  https://medicine.iu.edu/pathology/research/specialties/amyloid/diagnostic-algorithms

  The prevalence of cardiac amyloidosis is unknown because the condition often goes underdiagnosed. […] There is emerging evidence that cardiac amyloidosis may be a relatively common cause of heart failure, especially in older individuals. […] The two most common forms of amyloidosis that affect the heart are AL and ATTR amyloidosis. […] Red flags that may raise clinical suspicion for cardiac amyloidosis, a diagnostic algorithm to confirm or exclude a diagnosis of cardiac amyloidosis, lab/imaging ordering tips in the IU system, and FDA approved treatments are detailed below. […] Diagnosis: Early diagnosis and treatment may help preserve organ function. […] Rule out AL amyloidosis which is a medical emergency with serum free light chains (abnormal kappa/lambda ratio of 0.26 or 1.65) or a monoclonal protein on serum or urine immunofixation.

• #65 You must be logged in as a member to save to your library.

  https://www.acc.org/Latest-in-Cardiology/Articles/2024/04/01/00/42/Feature-Cardiac-Amyloidosis-and-How-to-Stop-Missing-the-Diagnosis

  Cardiac amyloidosis used to be considered an ultra-rare disease with no treatment options. No longer. Advances in noninvasive testing have led to greater awareness, earlier diagnosis and improved outcomes for patients. […] The disease is underdiagnosed. If clinicians don’t detect and diagnose the disease early, patients will continue to suffer, except now that suffering may be needless. […] „Every provider has probably seen patients with cardiac amyloidosis in their office several times over the years and never recognized it. Now that we have a noninvasive means of diagnosing it and a disease-specific treatment that works, it’s time to stop missing the diagnosis,” suggests Mathew S. Maurer, MD, FACC, at Columbia University Irving Medical Center in New York City. […] „The diagnosis of amyloidosis can be challenging, but it’s not as hard as people think. I believe any cardiologist should be able to diagnose and treat cardiac amyloidosis,” says Michelle Kittleson, MD, PhD, FACC, at Cedars-Sinai Medical Center in Los Angeles. What’s the trick? Be mindful of the red flags (Table).

• #66 You must be logged in as a member to save to your library.

  https://www.acc.org/Latest-in-Cardiology/Articles/2024/04/01/00/42/Feature-Cardiac-Amyloidosis-and-How-to-Stop-Missing-the-Diagnosis

  „When a patient presents with shortness of breath, leg swelling and a normal ejection fraction, don’t just diagnose HFpEF or write it off as not related to the heart. Look a bit further,” she adds. […] Once there is clinical suspicion for cardiac amyloidosis and a decision to screen has been made, it’s essentially a two-step process to a noninvasive diagnosis of ATTR-CM: a monoclonal protein screen and a nuclear scan (Figure). […] The serum free light chain assessment and the serum protein electrophoresis with immunofixation (not just a serum/urine protein electrophoresis) combined have a 99% sensitivity for identifying someone at risk for AL amyloidosis. […] If the lab tests are normal, the next step is imaging to evaluate for ATTR amyloidosis. Once AL is ruled out, the specificity of PYP bone scintigraphy for ATTR-CM approaches 100%.

• #67 Newly Diagnosed – Amyloidosis Research Consortium

  https://arci.org/patients-and-caregivers/newly-diagnosed/

  Being diagnosed with amyloidosis can be a scary, confusing, and anxious time. This is understandable as not many people have heard of amyloidosis before. […] It is important to learn as much about your disease as possible so you can make informed decisions and communicate effectively with your physicians, nurses, and other members of your care team. Available information can change very quickly as more research is done in amyloidosis. ARC is committed to ensuring that you stay informed. […] Amyloidosis is a multi-system disease, meaning it affects multiple organs. It is important to be seen at a center that has experience in diagnosing and treating your type of amyloidosis. These centers will have a group of different specialists (i.e., cardiologist, hematologist, neurologist) who will be able to provide a comprehensive evaluation and treatment plan.

• #68 Amyloidosis Diagnosis & Treatment | Mount Sinai – New York

  https://www.mountsinai.org/care/rheumatology/services/amyloidosis

  Amyloidosis can damage major organs such as the heart, kidney, gastrointestinal track, and nervous system. It can affect the quality of life and life expectancy. The term amyloidosis refers to a group of diseases in which too much fibrillary protein builds up in the tissues. […] It can be difficult to diagnose amyloidosis because its symptoms look like a variety of other conditions. This can delay diagnosis. The diagnosis evaluation includes a physical exam as well as blood and urine tests. The only way to be sure you have amyloidosis is by performing a biopsy of the involved tissue in patients with a high level of suspicion. The biopsy will be examined under the microscope to look for the amyloidosis fibrils. […] Mount Sinai has the resources to provide a comprehensive approach to the diagnosis and treatment of this condition including: Rheumatologists, Cardiologists, Dermatologists, Ear, nose, and throat (otolaryngology) experts, Gastroenterologists, Hematologists, Oncologists, Nephrologists, Neurologists, Pathologists.

• #69 Newly Diagnosed – Amyloidosis Research Consortium

  https://arci.org/patients-and-caregivers/newly-diagnosed/

  The treatment for your amyloidosis will depend on which type you have. That is why it is vital to establish which type of amyloidosis you have. Treatment may be aimed at halting the production of amyloid, or alleviating symptoms caused by organ damage. […] Seeking a second opinion can be a worthwhile option before beginning your treatment. Another opinion can provide you with a different perspective about your disease and potential treatments to consider, and it is important you feel confident in your decision before beginning treatment. […] It is important that the new doctor have access to all the records and tests performed leading up to and after your diagnosis. […] If you have health insurance It is important to work with your insurance company. Review the details of your policy: deductibles, preauthorizations, covered medications, limitations, etc. […] Finding the right support is critical so that you can navigate your amyloidosis care successfully. Connecting with people who will answer your questions and listen to your concerns is a necessary part of your well-being.

• #70 4 Things to Know About AL Amyloidosis Causes, Diagnosis & Treatment

  https://www.jnj.com/health-and-wellness/things-we-now-know-about-al-amyloidosis

  AL amyloidosis is caused by an overproduction of protein chains by the immune system. […] AL amyloidosis is rareDr. Weiss notes that it appears in roughly a dozen people out of every million in the United States. This means many general practitioners likely have never seen a case, which can make it harder to recognize and diagnose. […] Prognoses vary depending on factors like a patients age and the type and severity of organ involvement, but in general, early diagnosis and treatment have been shown to improve life expectancy. […] If we can treat people before their organs are damaged, they will be able to benefit from treatments and hopefully live longer and feel betterand thats a great goal. […] Most family docs dont know this disease, so patients have to be their own best advocate, he says. If something doesnt seem right to you, you have to speak up. Ask as many questions as possible. Drive your doctors crazy if you have to. And the doctors, if they cant answer, should say, I dont know, but Ill find out right away.

• #71 Cardiac Amyloidosis Imaging, Part 3: Interpretation, Diagnosis, and Treatment | Journal of Nuclear Medicine Technology

  https://tech.snmjournals.org/content/51/2/102

  When 99mTc-pyrophosphate imaging is normal, or grade 0 (no 99mTc-pyrophosphate myocardial uptake), and laboratory testing demonstrates monoclonal proteins, the likelihood of cardiac ATTR is low. […] A final cause of false-negative results is also related to a previous myocardial infarction but for a reason different from false-positive studies. […] In some situations, endocardial biopsy may be required to determine the amyloidosis subtype (e.g., AL or ATTR). […] The treatment of cardiac amyloidosis follows 2 parallel tracks: managing cardiac symptoms, such as heart failure and arrhythmias, and treating the underlying type of amyloidosis. […] The appropriate treatment of HFpEF in patients with cardiac amyloidosis is administration of loop diuretics. […] The use of 3 disease-modifying therapy pathways depends on the presence of cardiomyopathy, the presence of cardiomyopathy with polyneuropathy, and whether a patient has ATTRv or ATTRwt. […] These disease-modifying pathways for cardiac amyloidosis offer hope for treating a debilitating disease once thought incurable.

• #72 Cardiac amyloidosis: epidemiology, diagnosis and therapy

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-19/cardiac-amyloidosis-epidemiology-diagnosis-and-therapy

  Cardiac amyloidosis is an infiltrative cardiomyopathy caused by accumulation in the heart interstitium of amyloid fibrils formed by misfolded proteins. […] Heightened awareness of amyloid cardiomyopathy, the assessment of cardiac and extracardiac manifestations of amyloidosis, and the use of echocardiography and cardiac magnetic resonance are the mainstays of diagnosis of cardiac amyloidosis along with disease-specific modalities including bone scintigraphy, light chain assay and tissue biopsy. […] Advances in cardiac imaging and improved awareness among physicians have facilitated the diagnosis of cardiac amyloidosis over the last decade. […] Timely diagnosis is of the greatest importance for appropriate treatment modalities that may crucially modify the natural history of the disease.

• #73 Addressing the barriers to earlier amyloidosis diagnosis | AstraZeneca

  https://www.astrazeneca.com/media-centre/articles/2024/earlier-amyloidosis-diagnosis.html

  As scientific advancements improve our ability to identify patients, greater awareness of early disease manifestations and the constellation of red flags becomes essential. […] This increased awareness helps link patients to the appropriate diagnostic pathways and equips physicians with the necessary resources to support accurate diagnosis and guideline-directed care. […] Given the signs and symptoms of ATTR amyloidosis often mimic other diseases, leading to frequent misdiagnosis and delays, our goal is to enhance early diagnosis and treatment, ultimately improving the complex journey patients face in receiving timely care. […] Through the ACT on Amyloidosis programme, we aim to enhance cross-specialty collaboration, raise disease awareness, expedite referrals, and ensure earlier treatment.

• #74 Immunoglobulin Light Chain Amyloidosis: Diagnosis and Risk Assessment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10164359/

  Advances in plasma cell-directed therapies and improved supportive care have resulted in an improvement in overall survival (OS) for patients with AL amyloidosis over the past 2 decades. […] The Mayo 2004 prognostic model for AL amyloidosis incorporates NT-proBNP (N-terminal proB-type natriuretic peptide; 332 ng/L) and cardiac troponin T (cTnT; 0.035 mg/L), with 1 point for each biomarker above the mentioned thresholds. […] Establishing the diagnosis requires a high index of suspicion. Diagnosis confirmation requires biopsy-proven Congo red-positive material followed by accurate typing of the amyloid fibril.

• #75 Correct Diagnosis of Amyloidosis is Vital for Heart Patients | AdventHealth Celebration

  https://www.adventhealth.com/hospital/adventhealth-celebration/blog/correct-diagnosis-amyloidosis-vital-heart-patients

  Correct Diagnosis of Amyloidosis is Vital for Heart Patients […] Dr. Hazday emphasizes the need for prompt and accurate diagnosis since the sooner the treatment is instituted the better the clinical outcomes. […] It has been shown that the earliest you receive a diagnosis and start treatment, the better the outcome. […] Because amyloidosis is considered a rare disease, some cardiologists wont immediately consider it as a potential diagnosis. […] Dr. Hazday illuminates, I have had patients with what turned out to be amyloidosis mimicking hypertrophic cardiomyopathy, which illustrates the importance of multimodality imaging and of a willingness by physicians to consider an alternative diagnosis, even when the initial diagnosis seems clear and the alternative is rare. […] There are now FDA-approved medications that are effective in treating amyloidosis, so its important to receive the correct diagnosis to improve your chances of recovery.

• #76 Newly Diagnosed – Amyloidosis Research Consortium

  https://arci.org/patients-and-caregivers/newly-diagnosed/

  Being diagnosed with amyloidosis can be a scary, confusing, and anxious time. This is understandable as not many people have heard of amyloidosis before. […] It is important to learn as much about your disease as possible so you can make informed decisions and communicate effectively with your physicians, nurses, and other members of your care team. Available information can change very quickly as more research is done in amyloidosis. ARC is committed to ensuring that you stay informed. […] Amyloidosis is a multi-system disease, meaning it affects multiple organs. It is important to be seen at a center that has experience in diagnosing and treating your type of amyloidosis. These centers will have a group of different specialists (i.e., cardiologist, hematologist, neurologist) who will be able to provide a comprehensive evaluation and treatment plan.

• #77 Challenges in the Diagnosis of Amyloidosis: Unraveling the Complexity of a Heterogeneous Disease

  https://www.pelobiotech.com/news-details/challenges-in-the-diagnosis-of-amyloidosis-unraveling-the-complexity-of-a-heterogeneous-disease.html

  The gold standard for amyloidosis diagnosis is tissue biopsy followed by Congo red staining and confirmation through characteristic apple-green birefringence under polarized light microscopy. However, biopsies may not always be feasible or accessible, and sampling errors can occur due to the focal nature of amyloid deposition. […] Timely and accurate diagnosis is crucial for initiating appropriate treatment and improving patient outcomes.

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