-
Journal of Cutaneous Medicine and... 2022
Topics: Amyloidosis, Familial; Humans; Immunoglobulin Light-chain Amyloidosis; Skin Diseases, Genetic
PubMed: 34878924
DOI: 10.1177/12034754211064314 -
Acta Haematologica 2020Amyloidosis is a group of complex diseases caused by extracellular deposition of pathological insoluble fibrillary protein in organs and tissues and may result in severe... (Review)
Review
Amyloidosis is a group of complex diseases caused by extracellular deposition of pathological insoluble fibrillary protein in organs and tissues and may result in severe organ dysfunction. Despite the etiological heterogeneity of systemic amyloidosis, the clinical manifestations of the different forms of amyloidosis largely overlap and depend upon the effected organ. The signs and symptoms that should raise suspicion for the potential diagnosis of amyloidosis are usually nonspecific; therefore, establishing the diagnosis is difficult, and early diagnosis requires clinical suspicion. Light chain (AL) amyloidosis may present with highly specific signs such as macroglossia and periorbital purpura, but these signs are insensitive. Amyloidosis is still underdiagnosed, even though treatments are now available and are effective in improving patient's survival and quality of life. Cardiac amyloidosis is the major determinant of survival, and the earlier it is detected the better the survival. All MGUS patients should be routinely screened for AL amyloidosis by a focused history and physical examination and routine assessment of urine albumin. The aim of this review is to provide clinicians with knowledge about the signs and symptoms that raise the suspicion of amyloidosis, bearing in mind the importance of early diagnosis of this disease.
Topics: Amyloidosis; Animals; Diagnosis, Differential; Disease Susceptibility; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Organ Specificity; Phenotype
PubMed: 32340017
DOI: 10.1159/000506617 -
Medicina Clinica Aug 2016
Review
Topics: Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Organ Transplantation; Prognosis; Treatment Outcome
PubMed: 27085744
DOI: 10.1016/j.medcli.2016.02.018 -
Drugs Feb 2023Systemic light chain (AL) amyloidosis is caused by an usually small B cell clone that produces a toxic light chain forming amyloid deposits in tissue. The heart and... (Review)
Review
Systemic light chain (AL) amyloidosis is caused by an usually small B cell clone that produces a toxic light chain forming amyloid deposits in tissue. The heart and kidney are the major organs affected, but all others, with the exception of the CNS, can be involved. The disease is rapidly progressive, and it is still diagnosed late. Screening programs in patients followed by hematologists for plasma cell dyscrasias should be considered. The diagnosis requires demonstration in a tissue biopsy of amyloid deposits formed by immunoglobulin light chains. The workup of patients with AL amyloidosis requires adequate technology and expertise, and patients should be referred to specialized centers whenever possible. Stagings are based on cardiac and renal biomarkers and guides the choice of treatment. The combination of daratumumab, cyclophosphamide, bortezomib and dexamethasone (dara-CyBorD) is the current standard of care. Autologous stem cell transplant is performed in eligible patients, especially those who do not attain a satisfactory response to dara-CyBorD. Passive immunotherapy targeting the amyloid deposits combined with chemo-/immune-therapy targeting the amyloid clone is currently being tested in controlled clinical trials. Response to therapy is assessed based on validated criteria. Profound hematologic response is the early goal of treatment and should be accompanied over time by deepening organ response. Many relapsed/refractory patients are also treated with daratumumab combination, but novel regimens will be needed to rescue daratumumab-exposed subjects. Immunomodulatory drugs are the current cornerstone of rescue therapy, while immunotherapy targeting B-cell maturation antigen and inhibitors of Bcl-2 are promising alternatives.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Plaque, Amyloid; Bortezomib; Kidney; Cyclophosphamide
PubMed: 36652193
DOI: 10.1007/s40265-022-01830-z -
Seminars in Neurology Oct 2019Peripheral neuropathy occurs in the setting of both hereditary and acquired amyloidosis. The most common form of hereditary amyloidosis is caused by 1 of 140 mutations... (Review)
Review
Peripheral neuropathy occurs in the setting of both hereditary and acquired amyloidosis. The most common form of hereditary amyloidosis is caused by 1 of 140 mutations in the transthyretin (TTR) gene, which can lead to neuropathic hereditary transthyretin amyloidosis (hATTR; previously referred to as transthyretin familial amyloid polyneuropathy), whereas acquired immunoglobulin light chain (AL) amyloidosis is the most common acquired form. Patients typically present with a sensorimotor polyneuropathy, focal neuropathy such as carpal tunnel syndrome, or autonomic neuropathy. When neuropathy is the sole or dominant presenting symptom, the diagnosis is commonly delayed. With the advent of new drug therapies for AL amyloidosis and hATTR amyloidosis, including proteasome inhibitors, TTR silencers, and TTR protein stabilizers, the neurologist is uniquely positioned to diagnose neurologic manifestations of systemic amyloidosis, leading to earlier disease identification and treatment. This article reviews the epidemiology, clinical presentations, pathophysiology, diagnostic workup, and treatment of neuropathy in the setting of amyloidosis.
Topics: Amyloid Neuropathies, Familial; Humans; Immunoglobulin Light-chain Amyloidosis; Mutation; Nervous System Diseases; Prealbumin
PubMed: 31639841
DOI: 10.1055/s-0039-1688994 -
Nephrology, Dialysis, Transplantation :... Sep 2019AL amyloidosis (light chain; previously also called primary amyloidosis) is a systemic disease characterized by an amyloid deposition process affecting many organs, and... (Review)
Review
AL amyloidosis (light chain; previously also called primary amyloidosis) is a systemic disease characterized by an amyloid deposition process affecting many organs, and which still has unsatisfactory survival of patients. The monoclonal light chains kappa (κ) or lambda (λ) or their fragments form the fibrils that deposit and accumulate in different tissues. Renal involvement is very frequent in AL amyloidosis and can lead to the development of nephrotic syndrome followed by renal failure in some cases. AL amyloidosis ultimately leads to destruction of tissues and progressive disease. With recent advances in the treatment, the importance of an early diagnosis of amyloidosis and correct assessment of its type is high. Histologic confirmation is based on Congo red detection of amyloid deposits in tissues but AL amyloidosis must also be distinguished from other systemic forms of amyloidoses with renal involvement, such as AA amyloidosis, amyloidosis with heavy chain deposition, fibrinogen Aα or ALECT2 (leukocyte chemotactic factor 2) deposition. Immunofluorescence (IF) plays a key role here. IF on formalin-fixed paraffin-embedded tissue after protease digestion, immunohistochemistry or laser microdissection with mass spectrometry should complete the diagnosis in unclear cases. Standard treatment with melphalan and prednisolone or with cyclophosphamide and dexamethasone has been replaced with newer drugs used for the treatment of multiple myeloma-bortezomib, carfilzomib and ixazomib or thalidomide, lenalidomide and pomalidomide. High-dose melphalan supported by autologous stem cell transplantation remains the therapeutic option for patients with low-risk status. These new treatment options prolong survival from months to years and improve the prognosis in a majority of patients.
Topics: Combined Modality Therapy; Humans; Immunoglobulin Light-chain Amyloidosis; Prognosis
PubMed: 30299492
DOI: 10.1093/ndt/gfy291 -
Nature Reviews. Disease Primers Oct 2018Systemic immunoglobulin light chain amyloidosis is a protein misfolding disease caused by the conversion of immunoglobulin light chains from their soluble functional... (Review)
Review
Systemic immunoglobulin light chain amyloidosis is a protein misfolding disease caused by the conversion of immunoglobulin light chains from their soluble functional states into highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac damage and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the detection and quantification of organ involvement and damage is facilitating earlier diagnosis and improved evaluation of the efficacy of new and existing therapies. Treatment is guided by risk assessment, which is based on levels of cardiac biomarkers; close monitoring of clonal and organ responses guides duration of therapy and changes in regimen. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, along with high-dose chemotherapy and autologous haematopoietic stem cell transplantation, have led to rapid and deep suppression of amyloid light chain production in the majority of patients. However, effective therapies for patients with advanced cardiac involvement are an unmet need. Passive immunotherapies targeting clonal plasma cells and directly accelerating removal of amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease.
Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Doxycycline; Heart; Humans; Immunoglobulin Light-chain Amyloidosis; Kidney; Quality of Life; Risk Factors
PubMed: 30361521
DOI: 10.1038/s41572-018-0034-3 -
Blood Dec 2020In amyloid light chain (AL) amyloidosis, a small B-cell clone, most commonly a plasma cell clone, produces monoclonal light chains that exert organ toxicity and deposit... (Review)
Review
In amyloid light chain (AL) amyloidosis, a small B-cell clone, most commonly a plasma cell clone, produces monoclonal light chains that exert organ toxicity and deposit in tissue in the form of amyloid fibrils. Organ involvement determines the clinical manifestations, but symptoms are usually recognized late. Patients with disease diagnosed at advanced stages, particularly when heart involvement is present, are at high risk of death within a few months. However, symptoms are always preceded by a detectable monoclonal gammopathy and by elevated biomarkers of organ involvement, and hematologists can screen subjects who have known monoclonal gammopathy for amyloid organ dysfunction and damage, allowing for a presymptomatic diagnosis. Discriminating patients with other forms of amyloidosis is difficult but necessary, and tissue typing with adequate technology available at referral centers, is mandatory to confirm AL amyloidosis. Treatment targets the underlying clone and should be risk adapted to rapidly administer the most effective therapy patients can safely tolerate. In approximately one-fifth of patients, autologous stem cell transplantation can be considered up front or after bortezomib-based conditioning. Bortezomib can improve the depth of response after transplantation and is the backbone of treatment of patients who are not eligible for transplantation. The daratumumab+bortezomib combination is emerging as a novel standard of care in AL amyloidosis. Treatment should be aimed at achieving early and profound hematologic response and organ response in the long term. Close monitoring of hematologic response is vital to shifting nonresponders to rescue treatments. Patients with relapsed/refractory disease are generally treated with immune-modulatory drugs, but daratumumab is also an effective option.
Topics: Antibodies, Monoclonal; Bortezomib; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 33270858
DOI: 10.1182/blood.2020006913 -
BMC Gastroenterology Mar 2022Immunoglobulin light chain (AL) amyloidosis commonly affects the kidney or heart, but may also involve the liver at a histopathological level. Early diagnosis of AL... (Review)
Review
BACKGROUND
Immunoglobulin light chain (AL) amyloidosis commonly affects the kidney or heart, but may also involve the liver at a histopathological level. Early diagnosis of AL amyloidosis is important for proper management with desirable outcome. We reported here an unusual case of AL amyloidosis, presenting primarily with multiple serous cavity effusion, accompanied with rapidly progressive cholestasis.
CASE PRESENTATION
A previously healthy 63-year-old man presented with dysuria, frequent urination, oliguria and oedema of lower extremities for one month, accompanied with jaundice and hypoproteinemia. CT demonstrated multiple serous cavity effusion, focal hypodense lesions in the liver, and focal low-density in the spleen. Laparoscopy with liver biopsy revealed liver and spleen fibrosis with congestion, no visceral rupture, following haemorrhagic ascites from abdominocentesis. This patient was transferred to our (tertiary) hospital. The diagnosis of amyloidosis was confirmed with histopathology/immunohistochemistry. Haematopoietic stem cell transplantation was not applicable, however chemotherapy was advised, due to the patient's Mayo score 3. The patient declined chemotherapy and was self-discharged back to his hometown hospital with palliative care, however only lasted a further one-month.
DISCUSSION
The lesson we have learnt from this case that any patients with multiple serous cavity effusion and isolated hepatic involvement, primary amyloidosis should be considered. Multiple serous cavity effusion may serve as an indicator for poor prognosis of hepatic AL amyloidosis.
Topics: Amyloidosis; Cholestasis; Humans; Immunoglobulin Light-chain Amyloidosis; Liver Diseases; Male; Middle Aged
PubMed: 35303809
DOI: 10.1186/s12876-022-02201-4 -
Indian Journal of Dermatology,... 2016
Topics: Adult; Amyloidosis; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Skin Neoplasms
PubMed: 25994889
DOI: 10.4103/0378-6323.157454