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Circulation. Cardiovascular Imaging Jul 2023Apo AI amyloidosis (AApoAI) and Apo AIV amyloidosis (AApoAIV) are rare but increasingly recognized causes of cardiac amyloidosis (CA). We sought to define the cardiac...
BACKGROUND
Apo AI amyloidosis (AApoAI) and Apo AIV amyloidosis (AApoAIV) are rare but increasingly recognized causes of cardiac amyloidosis (CA). We sought to define the cardiac phenotype in AApoAI and AApoAIV using multimodality imaging.
METHODS
We identified all patients with AApoAI and AApoAIV assessed at our center between 2000 and 2021, and 2 cohorts of patients with immunoglobulin light-chain amyloidosis (AL) and transthyretin amyloidosis matched for age, sex, and cardiac involvement.
RESULTS
Forty-five patients had AApoAI, 13 (29%) of whom had cardiac involvement, 32 (71%) renal involvement, 28 (62%) splenic involvement, 27 (60%) hepatic involvement, and 7 (16%) laryngeal involvement. AApoAI-CA commonly presented with heart failure (n=8, 62%) or dysphonia (n=7, 54%). The Arg173Pro variant universally caused cardiac and laryngeal involvement (n=7, 100%). AApoAI-CA was associated with right-sided involvement, with a thicker right ventricular free wall (8.6±1.9 versus 6.3±1.3 mm versus 7.7±1.2 mm, =0.004), greater incidence of tricuspid stenosis (4 [31%] versus 0 [0%] versus 0 [0%], =0.012) and tricuspid regurgitation (6 [46%] versus 1 [8%] versus 2 [15%], =0.048) than AL-CA and transthyretin CA. Twenty-one patients had AApoAIV, and cardiac involvement was more common than in AApoAI (15 [71%] versus 13 [29%], =0.001). AApoAIV-CA most commonly presented with heart failure (n=12, 80%), and a lower median estimated glomerular filtration rate than AL-CA and transthyretin CA (36 mL/[min·1.73 m²] versus 65 mL/[min·1.73 m²] versus 63 mL/[min·1.73 m²], <0.001). All AApoAIV-CA patients had classical CA features on echocardiography/cardiac magnetic resonance, including an apical-sparing strain pattern, which was less common in AApoAI-CA (15 [100%] versus 7 [54%], =0.003), whereas cardiac uptake on bone scintigraphy was less common in AApoAIV-CA than AApoAI-CA (all grade 1) (14% versus 82%, <0.001). Patients with AApoAI and AApoAIV had a good prognosis (median survival >172 and >30 months, respectively), and a lower risk of mortality than matched patients with AL-amyloidosis (AL versus AApoAI: hazard ratio, 4.54 [95% CI, 2.02-10.14]; <0.001; AL versus AApoAIV: hazard ratio, 3.07 [95% CI, 1.27-7.44]; =0.013).
CONCLUSIONS
Dysphonia, multisystem involvement, or right-sided cardiac disease should raise suspicion of AApoAI-CA. AApoAIV-CA presents most commonly with heart failure and always displays classical CA imaging features, mimicking common forms of CA. Both AApoAI and AApoAIV are associated with a good prognosis and a lower risk of mortality than matched patients with AL-amyloidosis.
Topics: Humans; Apolipoprotein A-I; Dysphonia; Prealbumin; Amyloid Neuropathies, Familial; Immunoglobulin Light-chain Amyloidosis; Heart Failure; Echocardiography; Cardiomyopathies
PubMed: 37431665
DOI: 10.1161/CIRCIMAGING.123.015259 -
Journal of General Internal Medicine Aug 2021
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma; Tongue; Tongue Diseases
PubMed: 34027604
DOI: 10.1007/s11606-021-06890-7 -
Journal of Medical Case Reports Apr 2023Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light... (Review)
Review
BACKGROUND
Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis.
CASE PRESENTATIONS
In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a 69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges.
CONCLUSIONS
Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.
Topics: Male; Female; Humans; Aged; Adult; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Paraproteinemias; Heart
PubMed: 37081462
DOI: 10.1186/s13256-023-03886-1 -
BMJ Case Reports Jul 2011Primary localised bladder amyloidosis is a very rare entity, with only 200 cases reported worldwide. Our case illustrates the classical presentation of isolated bladder...
Primary localised bladder amyloidosis is a very rare entity, with only 200 cases reported worldwide. Our case illustrates the classical presentation of isolated bladder amyloidosis with frank painless haematuria and irritative voiding symptoms.
Topics: Aged; Amyloidosis; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Urinary Bladder Diseases
PubMed: 22689606
DOI: 10.1136/bcr.05.2011.4211 -
Hematology. American Society of... Dec 2021Systemic light chain (AL) amyloidosis is a protein misfolding disorder characterized by the deposition of abnormal immunoglobulin light chains in fibrillary aggregates,... (Review)
Review
Systemic light chain (AL) amyloidosis is a protein misfolding disorder characterized by the deposition of abnormal immunoglobulin light chains in fibrillary aggregates, resulting in end-organ damage. Several unique challenges face treating physicians, including delayed diagnosis, advanced vital organ involvement, and morbidity with treatment. Aggressive supportive care and risk-adapted application of plasma cell-directed therapies are the cornerstones of management. The therapeutic revolution in multiple myeloma will likely further expand the arsenal against plasma cells. Careful investigation of these agents will be critical to establish their role in this fragile population. The promise of fibril-directed therapies to restore organ function remains despite early disappointments. In this review, we discuss new therapies to tackle AL amyloidosis using a case-based approach.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Disease Management; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Teniposide
PubMed: 34889374
DOI: 10.1182/hematology.2021000305 -
The American Journal of Medicine Apr 2022Light chain (AL) amyloidosis is a potentially fatal disease of monoclonal plasma cells that leads to accumulation of light chain amyloid fibrils, organ damage, and the...
Light chain (AL) amyloidosis is a potentially fatal disease of monoclonal plasma cells that leads to accumulation of light chain amyloid fibrils, organ damage, and the manifestations of clinical disease. Meanwhile, coronavirus disease 2019 (COVID-19) is a disease caused by infection with the severe acute respiratory syndrome coronavirus 2 virus, with the potential to cause severe systemic illness and death. There is significant overlap in the demographics and comorbidities observed in AL amyloidosis and those associated with highest risk for severe morbidity and mortality due to COVID-19. This overlap creates unique challenges in caring for patients with AL amyloidosis, which are further compounded by the immunosuppressive nature of anti-plasma cell therapies, the need for frequent clinical assessments, and the exclusion of AL amyloidosis patients from initial COVID-19 vaccine trials. Herein, we highlight many of the relevant concerns related to COVID-19 and the treatment of AL amyloidosis, summarize a general approach for AL amyloidosis management amidst the ongoing COVID-19 pandemic, and discuss current guidance about COVID-19 vaccination of patients with AL amyloidosis.
Topics: Amyloidosis; COVID-19; COVID-19 Vaccines; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Pandemics
PubMed: 35081378
DOI: 10.1016/j.amjmed.2022.01.005 -
American Journal of Hematology Jul 2021
Topics: Aged; Bone Marrow; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Multiple Myeloma; Nail Diseases; Nails
PubMed: 33180338
DOI: 10.1002/ajh.26046 -
International Journal of Molecular... Jun 2022In amyloid light-chain (AL) amyloidosis, small B-cell clones (mostly plasma cell clones) present in the bone marrow proliferate and secrete unstable monoclonal free... (Review)
Review
In amyloid light-chain (AL) amyloidosis, small B-cell clones (mostly plasma cell clones) present in the bone marrow proliferate and secrete unstable monoclonal free light chains (FLCs), which form amyloid fibrils that deposit in the interstitial tissue, resulting in organ injury and dysfunction. AL amyloidosis progresses much faster than other types of amyloidosis, with a slight delay in diagnosis leading to a marked exacerbation of cardiomyopathy. In some cases, the resulting heart failure is so severe that chemotherapy cannot be administered, and death sometimes occurs within a few months. To date, many clinical studies have focused on therapeutics, especially chemotherapy, to treat this disease. Because it is necessary to promptly lower FLC, the causative protein of amyloid, to achieve a hematological response, various anticancer agents targeting neoplastic plasma cells are used for the treatment of this disease. In addition, many basic studies using human specimens to elucidate the pathophysiology of AL have been conducted. Gene mutations associated with AL, the characteristics of amyloidogenic LC, and the structural specificity of amyloid fibrils have been clarified. Regarding the mechanism of cellular and tissue damage, the mass effect due to amyloid deposition, as well as the toxicity of pre-fibrillar LC, is gradually being elucidated. This review outlines the pathogenesis and treatment strategies for AL amyloidosis with respect to its molecular mechanisms.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis
PubMed: 35683015
DOI: 10.3390/ijms23116336 -
Sao Paulo Medical Journal = Revista... May 2011Primary amyloidosis, also known as AL amyloidosis, is commonly caused by clonal expansion of plasma cells in the bone marrow, thereby segregating light chains of clonal... (Review)
Review
CONTEXT
Primary amyloidosis, also known as AL amyloidosis, is commonly caused by clonal expansion of plasma cells in the bone marrow, thereby segregating light chains of clonal immunoglobulin that settle in tissues in the form of insoluble amyloid fibrils. The aim of this study was to report a case of primary amyloidosis with renal failure, diagnosed in Hospital São João, Porto, Portugal, focusing on the diagnostic difficulties and presenting a literature review.
CASE REPORT
A 68-year-old Caucasian man was admitted to the Internal Medicine Department of the hospital with a condition of anasarca and nephrotic syndrome. After performing a renal biopsy that tested positive using Congo red and immunohistochemistry, lambda light chain amyloidosis was diagnosed. This evolved into terminal renal disease, which led to hemodialysis and several episodes of urinary and catheter infections. He was started on chemotherapy, consisting of bortezomib 0.7 mg/m(2) and dexamethasone 40 mg in six cycles. This led to clinical improvement, stabilization of the illness and good tolerance of the treatment.
CONCLUSION
Amyloidosis is a rare entity that is difficult to diagnose. This is because of the unspecific early clinical manifestations of the disease. The hypothesis of amyloidosis is only considered when specific organ failure occurs. This case consisted of primary amyloidosis with involvement of the kidneys as an initial presentation of the disease and its difficulties were shown, going from the clinical approach to the final diagnosis.
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Nephrotic Syndrome; Renal Insufficiency
PubMed: 21755253
DOI: 10.1590/s1516-31802011000300009 -
Advances in Therapy Nov 2023Systemic immunoglobulin light chain (AL) amyloidosis is a heterogeneous rare disease driven by a destructive monoclonal gammopathy and typified by misfolded... (Review)
Review
Systemic immunoglobulin light chain (AL) amyloidosis is a heterogeneous rare disease driven by a destructive monoclonal gammopathy and typified by misfolded immunoglobulin light and/or heavy chains which aggregate and deposit in organs as insoluble amyloid fibrils. Disease heterogeneity is driven by the degree of multi-systemic involvement; cardiac, renal, neurological, and gastrointestinal (GI) systems are affected to varying degrees in different patients. While prognosis is primarily driven by hematologic response to treatment and outcomes associated with cardiac events and overall survival, the involvement of the peripheral nervous, hepatic, and GI systems can also have a significant impact on patients. The Amyloidosis Forum ( https://amyloidosisforum.org ) is a public-private partnership between the nonprofit Amyloidosis Research Consortium ( www.arci.org ) and the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research formed to advance drug development for the treatment of systemic amyloid disorders. A series of virtual workshops focused on the development of novel, patient-relevant endpoint components and analytical strategies for clinical trials in AL amyloidosis. This review summarizes the proceedings and recommendations of the Multi-Systemic Working Group which identified, reviewed, and prioritized endpoints relevant to the impacts of AL amyloidosis on the peripheral nervous, hepatic, and GI systems. The Working Group comprised amyloidosis experts, patient representatives, statisticians, and representatives from the FDA, Medicines and Healthcare products Regulatory Agency (MHRA), and pharmaceutical companies. Prioritized neuropathy/autonomic endpoints included a modified form of the Neuropathy Impairment Score (NIS + 7) and the Composite Autonomic Symptom Score (COMPASS-31), respectively. Alkaline phosphatase was identified as the most relevant indicator of liver involvement and disease progression. Following extensive review of potential GI endpoints, the Working Group identified multiple exploratory endpoints. These recommended components will be further explored through evaluation of clinical trial datasets and possible integration into composite endpoint analysis.
Topics: United States; Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Amyloid; Immunoglobulin Light Chains; Liver
PubMed: 37658177
DOI: 10.1007/s12325-023-02637-4