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Muchtar E, Grogan M, Aus dem Siepen F, Waddington-Cruz M, Misumi Y, Carroll AS, Clarke JO, Sanchorawala V, Milani P, Caccialanza R, Da Prat V, Pruthi R, Quintana LF, Bridoux F. Supportive care for systemic amyloidosis: International Society of Amyloidosis (ISA) expert panel guidelines. Amyloid 2025; 32:93-116. [PMID: 39985185 DOI: 10.1080/13506129.2025.2463678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 01/25/2025] [Accepted: 02/02/2025] [Indexed: 02/24/2025]
Abstract
Systemic amyloidosis refers to a group of protein misfolding disorders resulting in organ deposition with amyloid, leading to organ dysfunction, ultimately resulting in organ failure and death if not successfully treated. Treatment is type-specific and aimed at the underlying source of the misfolded protein. In the past decades, treatments have become increasingly available across the various amyloidosis types with improved response rates and longer survival. Supportive care measures are an integral part of care for patients with systemic amyloidosis to improve symptom burden and quality of life, reduce healthcare costs, and potentially prolong survival while type-directed therapy takes effect. In these guidelines, we provide supportive care recommendations across eight areas of interest in systemic amyloidosis: cardiology, nephrology, peripheral neuropathy, central nervous system involvement, autonomic neuropathy, gastroenterology, coagulopathy and bleeding, nutrition and hematology. These guidelines were developed on behalf of the International Society of Amyloidosis (ISA) by experts in the above fields and provide the best available evidence and expertise for supportive care in these rare disorders.
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Affiliation(s)
- Eli Muchtar
- Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Martha Grogan
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Fabian Aus dem Siepen
- Department of Cardiology, Angiology and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany
| | - Marcia Waddington-Cruz
- National Amyloidosis Referral Center, CEPARM, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Yohei Misumi
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Antonia S Carroll
- Faculty of Medicine and Health, Brain and Mind Centre, Translational Research Collective University of Sydney, Sydney, Australia
- Department of Neurology, Royal Prince Alfred Hospital, Sydney, Australia
- Department of Neurology and Neurophysiology, St. Vincent's Amyloidosis Centre, St. Vincent's Hospital, Sydney, Australia
| | - John O Clarke
- Division of Gastroenterology and Hepatology, Stanford University, Redwood City, CA, USA
| | - Vaishali Sanchorawala
- Amyloidosis Center, Boston University Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston, MA, USA
| | - Paolo Milani
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
- Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo Pavia, Pavia, Italy
| | - Riccardo Caccialanza
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Valentina Da Prat
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Rajiv Pruthi
- Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Luis F Quintana
- Amyloidosis and Myeloma Unit, Nephrology Department, National Reference Center on Complex Glomerular Disease (CSUR), Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Frank Bridoux
- Department of Nephrology, Centre Hospitalier Universitaire, National Reference Center for AL amyloidosis, MGCS and MGRS, Université de Poitiers, Poitiers, France
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Bhatt S, Vaithiyam V, Teja Reddy R, Raghava Aneesh PS, Sachdeva S, Kumar A, Dalal A. Portal Hypertension as the First Manifestation of Primary Amyloidosis. J Clin Exp Hepatol 2025; 15:102502. [PMID: 39980576 PMCID: PMC11836503 DOI: 10.1016/j.jceh.2025.102502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 01/07/2025] [Indexed: 02/22/2025] Open
Affiliation(s)
- Shrey Bhatt
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002, India
| | - Venkatesh Vaithiyam
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002, India
| | - Ravi Teja Reddy
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002, India
| | - Payila S. Raghava Aneesh
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002, India
| | - Sanjeev Sachdeva
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002, India
| | - Ajay Kumar
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002, India
| | - Ashok Dalal
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002, India
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Stalker M, Garfall A, Cohen A, Vogl DT, Djulbegovic M, Susanibar‐Adaniya S, Stadtmauer E, Megherea O, Waxman AJ. Safety and Efficacy of Teclistamab in Patients With Relapsed or Refractory AL Amyloidosis. Eur J Haematol 2025; 114:443-447. [PMID: 39552142 PMCID: PMC11798760 DOI: 10.1111/ejh.14348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 10/30/2024] [Accepted: 10/31/2024] [Indexed: 11/19/2024]
Abstract
INTRODUCTION Teclistamab has demonstrated deep responses in patients with multiple myeloma in the MajesTEC-1 study. However, the safety and efficacy of teclistamab in patients with AL amyloidosis are unknown. METHODS We retrospectively analyzed patients with biopsy-proven relapsed/refractory AL amyloidosis who were treated with teclistamab from December 2022 to February 2024 at the University of Pennsylvania. The data cutoff was 2/29/24. Adverse events (AE) were extracted from the electronic medical record. Patients were assessed for hematologic and organ response per consensus guidelines. RESULTS Eight patients were included in this case series: median age 63 (range 59-67), 75% female, 88% White. All eight patients achieved at least very good partial response (VGPR) and had normalization of free light chains (FLC), and six (75%) patients achieved undetectable FLC levels. Of the six patients with immunofixation completed, all six (100%) achieved hematologic complete response (hCR). The median time to hematologic VGPR and hCR was 13 days (range 12-18 days) and 88 days (range 32-150 days), respectively. The median duration of follow-up was 8.5 months (range 1-14 months). Of the five patients with cardiac involvement, four (80%) achieved a cardiac response. Of the seven patients with renal involvement, two patients already achieved renal response prior to teclistamab, and of the remaining five, three (60%) achieved renal response. Six patients (75%) developed low-grade cytokine release syndrome (CRS). No patients developed ICANS. Neutropenia and AKI both occurred in 25% of patients, respectively. CONCLUSIONS In this series of patients, teclistamab showed outstanding depth of response and was well-tolerated. Teclistamab shows promise in treating patients with relapsed AL amyloidosis.
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Affiliation(s)
- Margaret Stalker
- Department of Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Alfred Garfall
- Division of Hematology and Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Adam Cohen
- Division of Hematology and Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Dan T. Vogl
- Division of Hematology and Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Mia Djulbegovic
- Division of Hematology and Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Sandra Susanibar‐Adaniya
- Division of Hematology and Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Edward Stadtmauer
- Division of Hematology and Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Oxana Megherea
- Division of Hematology and Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Adam J. Waxman
- Division of Hematology and Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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Bucurica S, Nancoff AS, Moraru MV, Bucurica A, Socol C, Balaban DV, Mititelu MR, Maniu I, Ionita-Radu F, Jinga M. Digestive Amyloidosis Trends: Clinical, Pathological, and Imaging Characteristics. Biomedicines 2024; 12:2630. [PMID: 39595194 PMCID: PMC11591665 DOI: 10.3390/biomedicines12112630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/12/2024] [Accepted: 11/14/2024] [Indexed: 11/28/2024] Open
Abstract
Amyloidosis is a group of diseases characterized by the extracellular deposition of abnormally folded, insoluble proteins that lead to organ dysfunction. While it commonly affects the cardiovascular system, gastrointestinal (GI) tract involvement is undetermined. Recent research has focused on understanding the pathophysiology, diagnostic challenges, and therapeutic approaches to GI amyloidosis, particularly in systemic amyloid light-chain (AL) and amyloid A (AA) forms. GI manifestations can include motility disorders, bleeding, and, in severe cases, bowel obstruction. This review highlights the importance of the early recognition of digestive symptoms and associated imagistic findings in GI amyloidosis by analyzing the research that included clinical, pathological, and endoscopic approaches to amyloidosis. A systematic search of the PubMed and Scopus databases identified 19 relevant studies. Our findings showed that amyloid deposits commonly affect the entire GI tract, with AL amyloidosis being the most predominant form. Endoscopic evaluations and biopsy remain key diagnostic tools, with Congo Red staining and mass spectrometry being used to confirm amyloid type. Although progress has been made in diagnosis, the absence of targeted therapies and the indistinct nature of GI symptoms continue to be challenging.
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Affiliation(s)
- Sandica Bucurica
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacology, 020021 Bucharest, Romania; (S.B.); (D.-V.B.); (M.J.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila”, 024185 Bucharest, Romania; (A.-S.N.); (M.V.M.)
| | - Andreea-Simona Nancoff
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila”, 024185 Bucharest, Romania; (A.-S.N.); (M.V.M.)
| | - Miruna Valeria Moraru
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila”, 024185 Bucharest, Romania; (A.-S.N.); (M.V.M.)
- General Medicine, Carol Davila University of Medicine and Pharmacology, 020021 Bucharest, Romania; (A.B.); (C.S.)
| | - Ana Bucurica
- General Medicine, Carol Davila University of Medicine and Pharmacology, 020021 Bucharest, Romania; (A.B.); (C.S.)
| | - Calin Socol
- General Medicine, Carol Davila University of Medicine and Pharmacology, 020021 Bucharest, Romania; (A.B.); (C.S.)
| | - Daniel-Vasile Balaban
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacology, 020021 Bucharest, Romania; (S.B.); (D.-V.B.); (M.J.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila”, 024185 Bucharest, Romania; (A.-S.N.); (M.V.M.)
| | - Mihaela Raluca Mititelu
- Department of Nuclear Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania
- Department of Nuclear Medicine, University Emergency Central Military Hospital, 010825 Bucharest, Romania
| | - Ionela Maniu
- Department of Mathematics and Informatics, Faculty of Sciences, Lucian Blaga University Sibiu, 550012 Sibiu, Romania;
- Research Team, Pediatric Clinical Hospital Sibiu, 550166 Sibiu, Romania
| | - Florentina Ionita-Radu
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacology, 020021 Bucharest, Romania; (S.B.); (D.-V.B.); (M.J.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila”, 024185 Bucharest, Romania; (A.-S.N.); (M.V.M.)
| | - Mariana Jinga
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacology, 020021 Bucharest, Romania; (S.B.); (D.-V.B.); (M.J.)
- Department of Gastroenterology, University Emergency Central Military Hospital “Dr. Carol Davila”, 024185 Bucharest, Romania; (A.-S.N.); (M.V.M.)
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Hudson D, Afzaal T, Bualbanat H, AlRamdan R, Howarth N, Parthasarathy P, AlDarwish A, Stephenson E, Almahanna Y, Hussain M, Diaz LA, Arab JP. Modernizing metabolic dysfunction-associated steatotic liver disease diagnostics: the progressive shift from liver biopsy to noninvasive techniques. Therap Adv Gastroenterol 2024; 17:17562848241276334. [PMID: 39553445 PMCID: PMC11565685 DOI: 10.1177/17562848241276334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 07/27/2024] [Indexed: 11/19/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern worldwide. Liver biopsy is the gold standard for diagnosing and staging MASLD, but it is invasive and carries associated risks. In recent years, there has been significant progress in developing noninvasive techniques for evaluation. This review article discusses briefly current available noninvasive assessments and the various liver biopsy techniques available for MASLD, including invasive techniques such as transjugular and transcutaneous needle biopsy, intraoperative/laparoscopic biopsy, and the evolving role of endoscopic ultrasound-guided biopsy. In addition to discussing the various biopsy techniques, we review the current state of knowledge on the histopathologic evaluation of MASLD, including the various scoring systems used to grade and stage the disease. We also explore current and alternative modalities for histopathologic evaluation, such as whole slide imaging and the utility of immunohistochemistry. Overall, this review article provides a comprehensive overview of the progress in liver biopsy techniques for MASLD and compares invasive and noninvasive modalities. However, beyond clinical trials, the practical application of liver biopsy may be limited, as ongoing advancements in noninvasive fibrosis assessments are expected to more effectively identify candidates for MASLD treatment in real-world settings.
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Affiliation(s)
- David Hudson
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Tamoor Afzaal
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Hasan Bualbanat
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Raaed AlRamdan
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Nisha Howarth
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Pavithra Parthasarathy
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Alia AlDarwish
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Emily Stephenson
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Yousef Almahanna
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Maytham Hussain
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, ON, Canada
| | - Luis Antonio Diaz
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
- MASLD Research Center, Division of MASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA
| | - Juan Pablo Arab
- Stravitz-Sanyal Institute of Liver Disease and Metabolic Health, Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, 1201 E. Broad St. P.O. Box 980341, Richmond, VA 23284, USA
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Zamarra GB, Sandu M, Caione N, Di Pasquale G, Di Berardino A, Di Ludovico A, La Bella S, Chiarelli F, Cattivera V, Colella J, Di Donato G. Amyloidosis in Childhood: A Review of Clinical Features and Comparison with Adult Forms. J Clin Med 2024; 13:6682. [PMID: 39597824 PMCID: PMC11594867 DOI: 10.3390/jcm13226682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 10/29/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024] Open
Abstract
Amyloidosis is a rare multisystem disorder characterized by extracellular accumulation of insoluble fibrils in various organs and tissues. The most common subtype in the pediatric population is systemic reactive amyloidosis, typically developing secondary to chronic inflammatory conditions and resulting in deposition of serum amyloid A protein in association with apolipoprotein HDL3. Clinical presentation is highly variable and is mostly influenced by specific organs involved, precursor protein type, and extent of amyloid deposition, often closely reflecting clinical features of the underlying disease. The most critical determinants of prognosis are cardiac and renal involvement. Diagnosis of amyloidosis is confirmed by tissue biopsy, which remains the gold standard, followed by precise amyloid fibril typing. The primary therapeutic approach is directed towards controlling underlying disease and reducing serum levels of precursor proteins to prevent further amyloid deposition. This study aims to highlight the main clinical characteristics of amyloidosis with onset in childhood, emphasizing the key differences compared to adult form.
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Affiliation(s)
- Giovanni Battista Zamarra
- Department of Pediatrics, L’Aquila University—UNIVAQ, 67100 L’Aquila, Italy; (G.B.Z.); (M.S.); (N.C.); (G.D.P.); (A.D.B.); (V.C.); (J.C.)
| | - Marina Sandu
- Department of Pediatrics, L’Aquila University—UNIVAQ, 67100 L’Aquila, Italy; (G.B.Z.); (M.S.); (N.C.); (G.D.P.); (A.D.B.); (V.C.); (J.C.)
| | - Nicholas Caione
- Department of Pediatrics, L’Aquila University—UNIVAQ, 67100 L’Aquila, Italy; (G.B.Z.); (M.S.); (N.C.); (G.D.P.); (A.D.B.); (V.C.); (J.C.)
| | - Gabriele Di Pasquale
- Department of Pediatrics, L’Aquila University—UNIVAQ, 67100 L’Aquila, Italy; (G.B.Z.); (M.S.); (N.C.); (G.D.P.); (A.D.B.); (V.C.); (J.C.)
| | - Alessio Di Berardino
- Department of Pediatrics, L’Aquila University—UNIVAQ, 67100 L’Aquila, Italy; (G.B.Z.); (M.S.); (N.C.); (G.D.P.); (A.D.B.); (V.C.); (J.C.)
| | - Armando Di Ludovico
- Department of Pediatrics, “G. D’Annunzio” University, 66100 Chieti, Italy; (A.D.L.); (S.L.B.); (F.C.)
| | - Saverio La Bella
- Department of Pediatrics, “G. D’Annunzio” University, 66100 Chieti, Italy; (A.D.L.); (S.L.B.); (F.C.)
| | - Francesco Chiarelli
- Department of Pediatrics, “G. D’Annunzio” University, 66100 Chieti, Italy; (A.D.L.); (S.L.B.); (F.C.)
| | - Valentina Cattivera
- Department of Pediatrics, L’Aquila University—UNIVAQ, 67100 L’Aquila, Italy; (G.B.Z.); (M.S.); (N.C.); (G.D.P.); (A.D.B.); (V.C.); (J.C.)
| | - Jacopo Colella
- Department of Pediatrics, L’Aquila University—UNIVAQ, 67100 L’Aquila, Italy; (G.B.Z.); (M.S.); (N.C.); (G.D.P.); (A.D.B.); (V.C.); (J.C.)
| | - Giulio Di Donato
- Department of Pediatrics, L’Aquila University—UNIVAQ, 67100 L’Aquila, Italy; (G.B.Z.); (M.S.); (N.C.); (G.D.P.); (A.D.B.); (V.C.); (J.C.)
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Singh A, Khanna T, Mahendru D, Kahlon J, Kumar V, Sohal A, Yang J. Insights into renal and urological complications of inflammatory bowel disease. World J Nephrol 2024; 13:96574. [PMID: 39351187 PMCID: PMC11439091 DOI: 10.5527/wjn.v13.i3.96574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/01/2024] [Accepted: 07/15/2024] [Indexed: 09/19/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract, which follows a relapsing and remitting course. Apart from affecting the gastrointestinal tract, IBD also has extra-intestinal manifestations (EIMs). While the etiology of extraintestinal manifestation remains unclear, it is theorized to be based on immunological responses influenced by genetic factors. Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn's disease. The renal manifestations in IBD patients encompass a range of conditions including nephrolithiasis, amyloidosis, tubulointerstitial nephritis, glomerulonephritis (GN), obstructive pathologies, and chronic kidney disease (CKD). The incidence of CKD in IBD patients varies from 5%-15%. The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury, or from complications like recurrent stones, amyloidosis, or GN. Additionally, nephrotoxic medications used in treating IBD, such as TNF-α inhibitors, calcineurin inhibitors, and aminosalicylates, can exacerbate the decline in renal function. Currently, there is a lack of consensus regarding these patients' screening and renal function monitoring. This review aims to assess the existing literature on the different renal complications among individuals with IBD, shedding light on their pathophysiology and management.
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Affiliation(s)
- Anmol Singh
- Department of Medicine, Tristar Centennial Medical Center, Nashville, TN 37203, United States
| | - Tejasvini Khanna
- Department of Medicine, Maulana Azad Medical College, New Delhi 110002, India
| | - Diksha Mahendru
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Jasraj Kahlon
- Department of Internal Medicine, Abrazo Medical Center, Phoenix, AZ 85015, United States
| | - Vikash Kumar
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Juliana Yang
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX 77555, United States
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Park D, Kővári B, Shimizu M. Miscellaneous conditions of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:347-358. [DOI: 10.1002/9781119423195.ch16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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9
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Emfietzoglou R, Muscogiuri G, Tsilingiris D, Kounatidis D, Stratigou T, Vallianou N, Karampela I, Basdra EK, Dalamaga M. Macroglossia in endocrine and metabolic disorders: current evidence, perspectives and challenges. Minerva Endocrinol (Torino) 2024; 49:335-350. [PMID: 39081187 DOI: 10.23736/s2724-6507.24.04219-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2024]
Abstract
Macroglossia is an uncommon condition characterized by chronic, painless and abnormal enlargement of the tongue. A multitude of medical conditions can cause macroglossia. Major endocrine and metabolic disorders associated with macroglossia include genetic, congenital and acquired conditions, such as mucopolysaccharidoses; acquired and congenital hypothyroidism and myxedema; transient neonatal diabetes mellitus; acromegaly and amyloidosis. Macroglossia is often associated (~57-60%) with all types of mucopolysaccharidoses, particularly type I (Hurler syndrome) and type II (Hunter syndrome), being a prominent feature of the disorder. It may also occur in patients with acquired and congenital hypothyroidism and myxedema, being a common sign of congenital hypothyroidism with an approximate prevalence of 12-25% at the time of diagnosis. Macroglossia is a predominant oral finding in subjects with transient neonatal diabetes mellitus (~44%), acromegaly (54-69%) and amyloidosis (10-25%), particularly AL amyloidosis (20-40%) whereas is considered a hallmark of the disease. Secondary to macroglossia various disturbances may occur, such as difficulty in speech or eating, orthodontic anomalies or even more serious conditions including upper airway obstruction or obstructive sleep apnea. Until now, no comprehensive review has been conducted focusing on macroglossia in endocrine and metabolic disorders. The objective of this review is to summarize literature on the etiology and epidemiology of macroglossia in major endocrine and metabolic disorders. It highlights key aspects such as pathophysiology, clinical presentation, diagnostic evaluation, management and prognosis of macroglossia in the context of endocrine and metabolic disorders.
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Affiliation(s)
- Rodopi Emfietzoglou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Private Dental Practice, Voula Attikis, Greece
| | - Giovanna Muscogiuri
- Unit of Endocrinology, Diabetology, and Andrology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
- Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O.), Unit of Endocrinology, Diabetology, and Andrology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
- Cattedra Unesco "Educazione alla Salute e allo Sviluppo Sostenibile", University of Naples Federico II, Naples, Italy
| | - Dimitrios Tsilingiris
- Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dimitrios Kounatidis
- Second Department of Internal Medicine, Hippokration General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Theodora Stratigou
- Department of Endocrinology, Evangelismos General Hospital, Athens, Greece
| | - Natalia Vallianou
- First Department of Internal Medicine, Sismanogleio General Hospital, Athens, Greece
| | - Irene Karampela
- Second Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Efthimia K Basdra
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece -
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Mirioglu S, Uludag O, Hurdogan O, Kumru G, Berke I, Doumas SA, Frangou E, Gul A. AA Amyloidosis: A Contemporary View. Curr Rheumatol Rep 2024; 26:248-259. [PMID: 38568326 PMCID: PMC11219434 DOI: 10.1007/s11926-024-01147-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/23/2024] [Indexed: 07/03/2024]
Abstract
PURPOSE OF REVIEW Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis. RECENT FINDINGS The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed.
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Affiliation(s)
- Safak Mirioglu
- Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
- Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
| | - Omer Uludag
- Division of Rheumatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ozge Hurdogan
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Gizem Kumru
- Division of Nephrology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - Ilay Berke
- Division of Nephrology, Marmara University School of Medicine, Istanbul, Turkey
| | - Stavros A Doumas
- Department of Medicine, MedStar Georgetown University Hospital, Washington, DC, USA
| | - Eleni Frangou
- Department of Nephrology, Limassol General Hospital, State Health Services Organization, Limassol, Cyprus
- University of Nicosia Medical School, Nicosia, Cyprus
| | - Ahmet Gul
- Division of Rheumatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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11
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Mancini M, Di Nardo G, Casciani E, Feudi ML, Bargiacchi L, Petraroli A, Della Casa F, Di Napoli A, Vecchione A. The Multifaceted Complexity of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS): A Case Report Highlighting Atypical Gastrointestinal Manifestations. Diagnostics (Basel) 2024; 14:1337. [PMID: 39001227 PMCID: PMC11241466 DOI: 10.3390/diagnostics14131337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/20/2024] [Accepted: 06/20/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder stemming from mutations in the TNFRSF1A gene affecting the tumor necrosis factor receptor (TNFR)-1. These mutations lead to dysregulated inflammatory responses, primarily mediated by augmented interleukin (IL)-1β release. CASE PRESENTATION We present the case of a 29-year-old woman with a history of recurrent febrile episodes, abdominal pain, and joint manifestations, eventually diagnosed with TRAPS following genetic testing revealing a heterozygous R92Q mutation in TNFRSF1A. Further genetic examinations unveiled additional clinically significant mutations, complicating the clinical picture. Our patient exhibited delayed colonic transit time and right colonic amyloidosis, a rare complication. Surgical intervention was required for overwhelming intestinal obstruction, revealing mucosal atrophy and dense lymphocytic infiltrates on histological examination. DISCUSSION Gastrointestinal involvement in TRAPS is common but can present diagnostic challenges. Following colon resection, histological examination revealed amyloid deposition, underscoring the importance of a comprehensive evaluation of these patients. Isolated colic amyloidosis has significant diagnostic and prognostic implications, warranting cautious monitoring and tailored management strategies. Treatment of TRAPS typically involves anti-inflammatory agents such as IL-1 inhibitors, with our patient experiencing clinical improvement on anakinra and canakinumab. CONCLUSION This case report emphasizes the diverse manifestations of TRAPS and the importance of recognizing gastrointestinal complications, particularly isolated colic amyloidosis. Comprehensive evaluation, including histological examination, is crucial for identifying atypical disease presentations and guiding management decisions. Continued research is needed to elucidate the underlying mechanisms and optimize treatment strategies for TRAPS and its associated complications.
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Affiliation(s)
- Massimiliano Mancini
- Morphologic and Molecular Pathology Unit, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.M.); (M.L.F.)
| | - Giovanni Di Nardo
- Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Pediatric Unit, Sant’Andrea University Hospital, 00189 Rome, Italy;
| | - Emanuele Casciani
- University of Rome Tor Vergata—Casa di Cura Pio XI, 00133 Rome, Italy;
| | - Maria Letizia Feudi
- Morphologic and Molecular Pathology Unit, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.M.); (M.L.F.)
| | - Lavinia Bargiacchi
- Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy;
| | - Angelica Petraroli
- Department of Translational Medical Sciences, University of Naples Federico II, 80133 Naples, Italy; (A.P.); (F.D.C.)
| | - Francesca Della Casa
- Department of Translational Medical Sciences, University of Naples Federico II, 80133 Naples, Italy; (A.P.); (F.D.C.)
| | - Arianna Di Napoli
- Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, 00189 Rome, Italy;
| | - Andrea Vecchione
- Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, 00189 Rome, Italy;
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12
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Asaad A, Ranjous Y, Hassan ZA, Alahmad N, Ghanimeh L, Ali A. Chronic underlying gastrointestinal amyloidosis was revealed by cardiac echography: a case report from Syria. Ann Med Surg (Lond) 2024; 86:2253-2255. [PMID: 38576978 PMCID: PMC10990300 DOI: 10.1097/ms9.0000000000001901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 02/25/2024] [Indexed: 04/06/2024] Open
Abstract
Introduction and importance Amyloidosis is an infiltrative disease caused by the deposition of abnormal proteins. While cardiac amyloidosis is relatively common, gastrointestinal (GI) tract involvement is less frequent. In this case, the authors report a delayed diagnosis of systemic amyloidosis presenting mainly with digestive symptoms. Case presentation An 81-year-old male presented with the complaint of persistent diarrhoea for over a year and the progressive development of edemas during the last 4 months. Echocardiogram findings revealed the presence of the characteristic sparkling sign. The diagnosis of amyloidosis was confirmed by histopathological biopsies taken from the duodenum. Serum electrophoresis findings strongly suggested the possibility of plasma cell dyscrasia. Clinical discussion What distinguishes this case is that the suspicion of amyloidosis as the underlying cause of the diarrhoea did not arise until an incidental echocardiogram revealed cardiac hypertrophy and a sparkling appearance. Conclusion This case reminds us to consider amyloidosis as a possible underlying cause for unexplained gastrointestinal symptoms such as diarrhoea, especially in bad economic situations where the diagnosis of rare diseases may be delayed.
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Affiliation(s)
| | - Yahia Ranjous
- Department of Gastroenterology, Faculty of Medicine, Damascus University, Damascus, Syria
| | - Zein Aldeen Hassan
- Department of Gastroenterology, Faculty of Medicine, Damascus University, Damascus, Syria
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13
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Habib MH, Tiger YKR, Dima D, Schlögl M, McDonald A, Mazzoni S, Khouri J, Williams L, Anwer F, Raza S. Role of Palliative Care in the Supportive Management of AL Amyloidosis-A Review. J Clin Med 2024; 13:1991. [PMID: 38610755 PMCID: PMC11012321 DOI: 10.3390/jcm13071991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/20/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
Light chain amyloidosis is a plasma-cell disorder with a poor prognosis. It is a progressive condition, causing worsening pain, disability, and life-limiting complications involving multiple organ systems. The medical regimen can be complex, including chemotherapy or immunotherapy for the disease itself, as well as treatment for pain, gastrointestinal and cardiorespiratory symptoms, and various secondary symptoms. Patients and their families must have a realistic awareness of the illness and of the goals and limitations of treatments in making informed decisions about medical therapy, supportive management, and end-of-life planning. Palliative care services can thus improve patients' quality of life and may even reduce overall treatment costs. Light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by the excessive secretion of light chains by an indolent plasma cell clone that gradually accumulates in vital organs as amyloid fibrils and leads to end-organ damage. With progressive disease, most patients develop diverse clinical symptoms and complications that negatively impact quality of life and increase mortality. Complications include cardiac problems including heart failure, hypotension, pleural effusions, renal involvement including nephrotic syndrome with peripheral edema, gastrointestinal symptoms leading to anorexia and cachexia, complex pain syndromes, and mood disorders. The prognosis of patients with advanced AL amyloidosis is dismal. With such a complex presentation, and high morbidity and mortality rates, there is a critical need for the establishment of a palliative care program in clinical management. This paper provides an evidence-based overview of the integration of palliative care in the clinical management of AL amyloidosis as a means of reducing ER visits, rehospitalizations, and in-hospital mortality. We also discuss potential future collaborative directions in various aspects of clinical care related to AL amyloidosis.
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Affiliation(s)
- Muhammad Hamza Habib
- Department of Palliative Care, Rutgers Robert Wood Johnson School of Medicine, New Brunswick, NJ 08901, USA
| | - Yun Kyoung Ryu Tiger
- Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA
| | - Danai Dima
- Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.D.); (A.M.); (S.M.); (J.K.); (L.W.); (F.A.); (S.R.)
| | - Mathias Schlögl
- Department of Geriatric Medicine, Clinic Barmelweid, 5017 Barmelweid, Switzerland;
| | - Alexandra McDonald
- Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.D.); (A.M.); (S.M.); (J.K.); (L.W.); (F.A.); (S.R.)
| | - Sandra Mazzoni
- Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.D.); (A.M.); (S.M.); (J.K.); (L.W.); (F.A.); (S.R.)
| | - Jack Khouri
- Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.D.); (A.M.); (S.M.); (J.K.); (L.W.); (F.A.); (S.R.)
| | - Louis Williams
- Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.D.); (A.M.); (S.M.); (J.K.); (L.W.); (F.A.); (S.R.)
| | - Faiz Anwer
- Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.D.); (A.M.); (S.M.); (J.K.); (L.W.); (F.A.); (S.R.)
| | - Shahzad Raza
- Department of Hematology & Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; (D.D.); (A.M.); (S.M.); (J.K.); (L.W.); (F.A.); (S.R.)
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14
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Karasawa Y, Nozawa K, Nakajima A. Potential drug-induced constipation: A retrospective study using a Japanese claims database. JGH Open 2024; 8:e13036. [PMID: 38361665 PMCID: PMC10867697 DOI: 10.1002/jgh3.13036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 12/29/2023] [Accepted: 01/28/2024] [Indexed: 02/17/2024]
Abstract
Background and Aim Detailed clinical information regarding drug-induced constipation (DIC) is limited. This study aimed to investigate the real-world situation of DIC. Methods This retrospective study used data from a Japanese claims database registered from 2014 to 2021. The constipation cohort included subjects with at least one record of treated constipation, while the non-constipation cohort was selected through random stratified sampling method, to match the constipation cohort by gender. The study population and control with at least one history of a known causative drug (CD) were matched 1:1 using propensity scores. The proportion of potential DIC (pDIC), the timing of diagnosis for pDIC, and the proportion of prescriptions by drug class for both the CDs and the laxatives were calculated, while logistic regression analysis was performed to explore additional associated factors. Results Of the 4 533 905 subjects, 178 852 were eligible in both the study population and the control. The pDIC group comprised of 19 485 patients, which accounted for 10.9% of all treated constipation subjects, while the non-constipation with CD group had 10 430 subjects. The median duration between the recorded CD prescription and treated constipation was 38.0 days. The most frequently prescribed CD was cardiovascular drugs (47.9%). All CD classes, being male, and some comorbidities were associated with the occurrence of pDIC. Conclusion The pDIC subjects accounted for about 11% of all treated constipation cases. Since DIC requires different treatment regimens compared to other constipation types, physicians should be cognizant to provide patients with optimized treatments.
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Affiliation(s)
- Yusuke Karasawa
- Medical Affairs, Viatris Pharmaceuticals Japan Inc.TokyoJapan
| | - Kazutaka Nozawa
- Medical Affairs, Viatris Pharmaceuticals Japan Inc.TokyoJapan
| | - Atsushi Nakajima
- Department of Gastroenterology and HepatologyYokohama City University Graduate School of MedicineYokohamaKanagawaJapan
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15
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Yadav AS, Malik S, De I, Pippal B, Singh M, Jain N, Yadav JK. Isolation of Amyloid-like Protein Aggregates (APA) from white bread and their characterisation. Biophys Chem 2023; 302:107097. [PMID: 37699275 DOI: 10.1016/j.bpc.2023.107097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/26/2023] [Accepted: 08/21/2023] [Indexed: 09/14/2023]
Abstract
High temperature, acidic pH, and physical agitation are commonly observed during cooking or industrial food processing, which are often considered as favorable conditions, at least for some proteins, to misfold and form amyloid-like protein aggregates (APA). The proteins in various bakery products generally experience high temperatures that might lead to the formation of APA. To test this hypothesis, the presence of APA in white bread was examined in this study. The APA isolated from white bread displayed typical characteristics of amyloids, like bathochromic shift in Congo red (CR) absorbance maxima, increased fluorescence of Thioflavin T (ThT) & 8-anilino-1-naphthalene sulfonic acid (ANS), fibrillar morphology of >200 nm long with average diameter of 10-12 nm and negative minima at 223 nm in Circular Dichroism (CD) spectrum. The SDS- and native PAGE revealed the presence of gliadin and glutenin as the constituent proteins in the isolated protein aggregates. Although, the presence of amyloid-like structures in white bread is evident, further studies would be essential to establish their functional role and health implications.
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Affiliation(s)
- Abhishek Singh Yadav
- Department of Biotechnology, Central University of Rajasthan, NH-8 Bandersindri, Kishangarh, Ajmer 305817, Rajasthan, India
| | - Shweta Malik
- Department of Biotechnology, Central University of Rajasthan, NH-8 Bandersindri, Kishangarh, Ajmer 305817, Rajasthan, India
| | - Indranil De
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali 140301, Punjab, India
| | - Bhumika Pippal
- Centre for Research and Development of Scientific Equipment (CRDSI), Indian Institute of Technology, Jodhpur 342030, Rajasthan, India
| | - Manish Singh
- Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali 140301, Punjab, India
| | - Neha Jain
- Centre for Research and Development of Scientific Equipment (CRDSI), Indian Institute of Technology, Jodhpur 342030, Rajasthan, India
| | - Jay Kant Yadav
- Department of Biotechnology, Central University of Rajasthan, NH-8 Bandersindri, Kishangarh, Ajmer 305817, Rajasthan, India.
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16
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Poli L, Labella B, Cotti Piccinelli S, Caria F, Risi B, Damioli S, Padovani A, Filosto M. Hereditary transthyretin amyloidosis: a comprehensive review with a focus on peripheral neuropathy. Front Neurol 2023; 14:1242815. [PMID: 37869146 PMCID: PMC10585157 DOI: 10.3389/fneur.2023.1242815] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 09/11/2023] [Indexed: 10/24/2023] Open
Abstract
Amyloidoses represent a group of diseases characterized by the pathological accumulation in the extracellular area of insoluble misfolded protein material called "amyloid". The damage to the tissue organization and the direct toxicity of the amyloidogenic substrates induce progressive dysfunctions in the organs involved. They are usually multisystem diseases involving several vital organs, such as the peripheral nerves, heart, kidneys, gastrointestinal tract, liver, skin, and eyes. Transthyretin amyloidosis (ATTR) is related to abnormalities of transthyretin (TTR), a protein that acts as a transporter of thyroxine and retinol and is produced predominantly in the liver. ATTR is classified as hereditary (ATTRv) and wild type (ATTRwt). ATTRv is a severe systemic disease of adults caused by mutations in the TTR gene and transmitted in an autosomal dominant manner with incomplete penetrance. Some pathogenic variants in TTR are preferentially associated with a neurological phenotype (progressive peripheral sensorimotor polyneuropathy); others are more frequently associated with restrictive heart failure. However, many mutations express a mixed phenotype with neurological and cardiological involvement. ATTRv is now a treatable disease. A timely and definite diagnosis is essential in view of the availability of effective therapies that have revolutionized the management of affected patients. The purpose of this review is to familiarize the clinician with the disease and with the correct diagnostic pathways in order to obtain an early diagnosis and, consequently, the possibility of an adequate treatment.
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Affiliation(s)
- Loris Poli
- Unit of Neurology, Azienda Socio-Sanitaria Territoriale Spedali Civili, Brescia, Italy
| | - Beatrice Labella
- Unit of Neurology, Azienda Socio-Sanitaria Territoriale Spedali Civili, Brescia, Italy
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Stefano Cotti Piccinelli
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy
| | - Filomena Caria
- NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy
| | - Barbara Risi
- NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy
| | - Simona Damioli
- NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy
| | - Alessandro Padovani
- Unit of Neurology, Azienda Socio-Sanitaria Territoriale Spedali Civili, Brescia, Italy
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Massimiliano Filosto
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- NeMO-Brescia Clinical Center for Neuromuscular Diseases, Brescia, Italy
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17
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Jaan A, Sarfraz Z, McFarland J, Okolo P, Dunnigan K, Gutman J. Emerging from the shadows: A rare case of gastrointestinal AL amyloidosis presenting as hematemesis. Proc AMIA Symp 2023; 36:758-760. [PMID: 37829217 PMCID: PMC10566416 DOI: 10.1080/08998280.2023.2257113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/05/2023] [Indexed: 10/14/2023] Open
Abstract
We document a unique presentation of light chain (AL) amyloidosis in a 62-year-old man exhibiting as acute hematemesis and chronic abdominal discomfort. Esophagogastroduodenoscopy disclosed marked thickening of gastric and duodenal folds, gastroduodenal nodularity, and friable ulcerations. Biopsy confirmed amyloidosis. Subsequent investigations ratified a diagnosis of systemic AL amyloidosis with cardiac involvement. Initiation of the cyclophosphamide, bortezomib, and dexamethasone (CyBorD) regimen, along with tafamidis and doxycycline for cardiac pathology, led to substantial improvement of abdominal symptoms. This case highlights the variability in amyloidosis presentations and the importance of early diagnosis.
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Affiliation(s)
- Ali Jaan
- Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA
| | - Zouina Sarfraz
- Department of Medicine, Fatima Jinnah Medical University, Lahore, Pakistan
| | - Joel McFarland
- Department of Gastroenterology, Rochester General Hospital, Rochester, New York, USA
| | - Patrick Okolo
- Department of Gastroenterology, Rochester General Hospital, Rochester, New York, USA
| | - Karin Dunnigan
- Department of Gastroenterology, Rochester General Hospital, Rochester, New York, USA
| | - Jason Gutman
- Department of Gastroenterology, Rochester General Hospital, Rochester, New York, USA
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18
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Deng Y(J, Othman B. A rare cause of colonic pseudo-obstruction due to light chain amyloidosis. J Surg Case Rep 2023; 2023:rjad517. [PMID: 37724062 PMCID: PMC10505509 DOI: 10.1093/jscr/rjad517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 08/14/2023] [Accepted: 08/30/2023] [Indexed: 09/20/2023] Open
Abstract
In this case report, we discuss the rare presentation of a 56-year-old-gentleman with a history of light chain amyloidosis (AL), causing colonic pseudo-obstruction and requiring open subtotal colectomy and end ileostomy. This should remain a differential diagnosis in patients with known light chain AL presenting with nonspecific gastrointestinal symptoms such as constipation and abdominal pain. This prompts early investigation, such as endoscopy and tissue biopsy, and surgical intervention may be warranted.
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Affiliation(s)
- Yunpeng (Jack) Deng
- Colorectal Surgical Department, Eastern Health, Box Hill, Victoria 3128, Australia
| | - Bushra Othman
- Colorectal Surgical Department, Eastern Health, Box Hill, Victoria 3128, Australia
- Department of Medicine Nursing and Health Sciences, Monash University, Box Hill, Victoria 3128, Australia
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19
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Luhn C, Agis H, Hütterer E, Simonitsch‐Klupp I, Dawoud C, Stift A, Harpain F. Teduglutide in amyloidosis-associated intestinal failure. Clin Case Rep 2023; 11:e7653. [PMID: 37601424 PMCID: PMC10433832 DOI: 10.1002/ccr3.7653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 06/19/2023] [Indexed: 08/22/2023] Open
Abstract
Amyloidosis is a heterogeneous disease characterized by tissue deposition of abnormally folded fibrillary proteins that can manifest itself by a wide variety of symptoms depending on the affected organs. GI involvement among amyloidosis patients is common. Its clinical manifestation often presents with nonspecific symptoms such as weight loss, diarrhea, and malabsorption. With no specific treatment existing for GI amyloidosis, therapy focuses on impeding amyloid deposition and managing the patients' symptoms with supportive measures. Here, we present an AL-amyloidosis patient with GI involvement and intestinal failure (IF) who was successfully treated with the glucagon-like peptide-2 (GLP-2) analogue teduglutide. Over the course of treatment with teduglutide, the patient was able to achieve independence from parenteral nutrition and experienced a significant improvement in quality of life (QoL) as stool frequency and consistency improved, urinary output was stabilized and body weight as well as body composition improved over the course of teduglutide therapy. With no longer being exposed to the burden and associated risks of parenteral nutrition, we were able to reduce the potential morbidity and mortality rate as well as to improve the patient's overall QoL. Intestinal tissue biopsy workup revealed a histopathological correlate for the clinical response; Congo-Red-positive intestinal depositions almost completely disappeared within 6 months of teduglutide therapy. Implementing intestinotrophic GLP-2 analogue teduglutide may enrich the spectrum of treatment options for amyloidosis patients with IF who are dependent on parenteral support.
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Affiliation(s)
- Clara Luhn
- Division of Visceral Surgery, Department of General SurgeryMedical University ViennaViennaAustria
| | - Hermine Agis
- Division of Hematology and Hemostaseology, Department of Internal Medicine IMedical University of ViennaViennaAustria
| | - Elisabeth Hütterer
- Division of Oncology, Department of Internal Medicine IMedical University of ViennaViennaAustria
| | | | - Christopher Dawoud
- Division of Visceral Surgery, Department of General SurgeryMedical University ViennaViennaAustria
| | - Anton Stift
- Division of Visceral Surgery, Department of General SurgeryMedical University ViennaViennaAustria
| | - Felix Harpain
- Division of Visceral Surgery, Department of General SurgeryMedical University ViennaViennaAustria
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20
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Raza D, Prajapati P, Bhavsar V, Raza SM, Papayannis I. Gastrointestinal (GI) Amyloidosis Presenting As Chronic Diarrhea: A Diagnostic Dilemma. Cureus 2023; 15:e41291. [PMID: 37539395 PMCID: PMC10393591 DOI: 10.7759/cureus.41291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2023] [Indexed: 08/05/2023] Open
Abstract
This case report describes a 63-year-old male patient with a four-year history of chronic diarrhea. Extensive diagnostic investigations failed to reveal a cause. Subsequent upper and lower gastrointestinal (GI) endoscopic procedures revealed the presence of amyloidosis in the GI tract. The patient was referred for further evaluation, but unfortunately, he presented with hypotension and shock, and ultimately succumbed to systemic amyloidosis involving multiple organs. GI amyloidosis, although rare, should be considered in patients presenting with chronic diarrhea, unexplained weight loss, or GI bleeding. Early recognition and appropriate management are crucial for optimizing patient outcomes. Healthcare providers should maintain a high index of suspicion for GI amyloidosis to ensure timely intervention and improve patient care.
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Affiliation(s)
- Daniyal Raza
- Internal Medicine, Louisiana State University Health Shreveport, Shreveport, USA
| | | | - Vatsa Bhavsar
- Internal Medicine, B.J. Medical College, Ahmedabad, IND
| | - Syed Musa Raza
- Gastroenterology, Louisiana State University Health Shreveport, Shreveport, USA
| | - Ioannis Papayannis
- Gastroenterology, Louisiana State University Health Shreveport, Shreveport, USA
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21
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Embry-Dierson M, Farrell MB, Schockling E, Warren J, Jerome S. Cardiac Amyloidosis Imaging, Part 1: Amyloidosis Etiology and Image Acquisition. J Nucl Med Technol 2023; 51:83-89. [PMID: 37268319 DOI: 10.2967/jnmt.123.265415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 02/16/2023] [Indexed: 06/04/2023] Open
Abstract
Cardiac amyloidosis is a systemic form of amyloidosis in which protein-based infiltrates are deposited in myocardial extracellular space. The accumulation of amyloid fibrils causes the myocardium to thicken and stiffen, leading to diastolic dysfunction and, eventually, heart failure. Until recently, cardiac amyloidosis was considered rare. However, the recent adoption of noninvasive diagnostic testing, including 99mTc-pyrophosphate imaging, has revealed a previously undiagnosed sizable disease prevalence. Light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), the 2 primary types, account for 95% of cardiac amyloidosis diagnoses. AL results from plasma cell dyscrasia and has a very poor prognosis. The usual treatment for cardiac AL is chemotherapy and immunotherapy. Cardiac ATTR is more chronic, usually resulting from age-related instability and misfolding of the transthyretin protein. ATTR is treated by managing heart failure and using new pharmacotherapeutic drugs. 99mTc-pyrophosphate imaging can efficiently and effectively distinguish between ATTR and cardiac AL. Although the exact mechanism of myocardial 99mTc-pyrophosphate uptake is unknown, it is believed to bind to amyloid plaque microcalcifications. 99mTc-pyrophosphate imaging has a 97% sensitivity and nearly 100% sensitivity for identifying cardiac ATTR when the AL form of the disease is ruled out through serum free light-chain and serum and urine protein electrophoresis with immunofixation testing. Although there are no published 99mTc-pyrophosphate cardiac amyloidosis imaging guidelines, the American Society of Nuclear Cardiology, Society of Nuclear Medicine and Molecular Imaging, and others have published consensus recommendations to standardize test performance and interpretation. This article, part 1 of a 3-part series in this issue of the Journal of Nuclear Medicine Technology, describes amyloidosis etiology and cardiac amyloidosis characteristics, including the types, prevalence, signs and symptoms, and disease course. It further explains the scan acquisition protocol. Part 2 of the series focuses on image/data quantification and technical considerations. Finally, part 3 describes scan interpretation, along with the diagnosis and treatment of cardiac amyloidosis.
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Affiliation(s)
| | | | - Eric Schockling
- Outpatient Cardiovascular Diagnostics, Norton Healthcare, LLC, Louisville, Kentucky
| | | | - Scott Jerome
- University of Maryland School of Medicine, Westminster, Maryland
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Abdullah KM, Alsuraimi A, Kagbo-Kue S, Vela M. Gastroparesis: an under-recognised manifestation of systemic amyloidosis. BMJ Case Rep 2023; 16:e254634. [PMID: 37130641 PMCID: PMC10163518 DOI: 10.1136/bcr-2023-254634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2023] [Indexed: 05/04/2023] Open
Abstract
Gastrointestinal (GI) amyloidosis can be acquired or genetic and is commonly caused by chronic inflammatory illnesses (AA amyloidosis), haematological malignancies (AL amyloidosis) and end-stage renal disease (beta-2 microglobulin amyloidosis). The accumulation of these aberrant proteins disrupts the structures and functions of many organs; the least common of which is the GI tract. GI presentations depend on the type, location and amount of amyloid deposition. Symptoms can range from nausea and vomiting to fatal GI bleeds. Pathological examination of the involved tissue with characteristic green birefringence under polarised light is used to confirm the diagnosis. Patients should be considered for further evaluation to rule out additional organ involvement, notably cardiac and renal. We present a patient with amyloidosis-induced gastroparesis, an under-recognised presentation of systemic amyloidosis in the gastroenterology system.
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Affiliation(s)
- Khaled M Abdullah
- Internal Medicine, University of California San Francisco, Fresno, California, USA
| | - Anas Alsuraimi
- Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA
| | - Suaka Kagbo-Kue
- Gastroenterology Department, Mayo Clinic, Scottsdale, Arizona, USA
| | - Marcelo Vela
- Gastroenterology Department, Mayo Clinic, Scottsdale, Arizona, USA
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Senecal JB, Abou-Akl R, Allevato P, Mazzetti I, Hamm C, Parikh R, Woldie I. Amyloidosis: a case series and review of the literature. J Med Case Rep 2023; 17:184. [PMID: 37081462 PMCID: PMC10120233 DOI: 10.1186/s13256-023-03886-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 03/10/2023] [Indexed: 04/22/2023] Open
Abstract
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.
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Affiliation(s)
| | - Romel Abou-Akl
- Schulich School of Medicine and Dentistry, London, ON, Canada
| | | | | | | | | | - Indryas Woldie
- Windsor Regional Hospital, Windsor, ON, Canada
- Karmanos Cancer Center, Detroit, MI, USA
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Kittleson MM, Ruberg FL, Ambardekar AV, Brannagan TH, Cheng RK, Clarke JO, Dember LM, Frantz JG, Hershberger RE, Maurer MS, Nativi-Nicolau J, Sanchorawala V, Sheikh FH. 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2023; 81:1076-1126. [PMID: 36697326 DOI: 10.1016/j.jacc.2022.11.022] [Citation(s) in RCA: 232] [Impact Index Per Article: 116.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Sakano H, Sumiyoshi T, Tomita Y, Uozumi T, Tokuchi K, Yoshida M, Fujii R, Minagawa T, Okagawa Y, Morita K, Yane K, Ihara H, Hirayama M, Kondo H. Localized Rectal Amyloidosis with Morphologic Changes from the Submucosal Tumor to the Ulcerative Lesion That Led to Hematochezia During Observation. Intern Med 2023; 62:733-738. [PMID: 35945025 PMCID: PMC10037022 DOI: 10.2169/internalmedicine.9648-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 75-year-old woman visited our hospital with constipation. Colonoscopy revealed a submucosal tumor in the rectum. She was followed up as a case of mucosal prolapse syndrome. Six years later, she was referred to our hospital due to hematochezia and abdominal pain. Colonoscopy revealed that the submucosal tumor had an ulcerative appearance with bleeding. Low anterior resection was performed. Amyloid protein deposition was detected from the submucosa to subserosa. Other organs showed no evidence of amyloidosis; we therefore diagnosed the patient with localized rectal amyloidosis. This is a rare case of symptomatic localized rectal amyloidosis whose long-term progression was able to be endoscopically observed.
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Affiliation(s)
- Hiroya Sakano
- Department of Gastroenterology, Tonan Hospital, Japan
| | | | - Yusuke Tomita
- Department of Gastroenterology, Tonan Hospital, Japan
| | | | - Kaho Tokuchi
- Department of Gastroenterology, Tonan Hospital, Japan
| | | | - Ryoji Fujii
- Department of Gastroenterology, Tonan Hospital, Japan
| | | | | | | | - Kei Yane
- Department of Gastroenterology, Tonan Hospital, Japan
| | | | | | - Hitoshi Kondo
- Department of Gastroenterology, Tonan Hospital, Japan
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Nigam N, Rastogi A, Bhatt P, Bihari C. Topographic Distribution Pattern in Hepatic Amyloidosis Presenting with Portal Hypertension. J Clin Exp Hepatol 2023; 13:259-264. [PMID: 36950500 PMCID: PMC10025754 DOI: 10.1016/j.jceh.2022.10.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 10/30/2022] [Indexed: 11/09/2022] Open
Abstract
Background/aims The liver is often involved in both primary and secondary forms of amyloidosis. Significant clinical evidence of portal hypertension is relatively uncommon and seems to be related to the reduced sinusoidal lumen and increased resistance to blood flow due to massive perisinusoidal amyloid deposits. The relationships between the pattern and extent of amyloid deposition in patients presenting with portal hypertension have not yet been clearly demonstrated. This study is focusing on the topographic distribution of amyloidosis in patients presenting with portal hypertension. Methods The study included biopsy-proven cases of hepatic amyloidosis. The clinical, biochemical, and serological data, involvement of the extrahepatic organs, and HVPG values were recorded. Tissue sections were re-evaluated for the distribution patterns of amyloid deposits. Results We had 41 patients with hepatic amyloidosis, of which, 32 were male. A mixed pattern (sinusoidal and vascular) was the most common (32/41; 78%). Hepatic venous pressure gradient was available in 21 cases. Portal hypertension was found in 14 patients (14/21; 67%). Cases of portal hypertension were found to have a sinusoidal pattern (3/14; 21.4%), vascular pattern (1/14; 7.1%), or a mixed sinusoidal and vascular pattern (10/14; 71.4%). Those not having portal hypertension showed hepatic artery (HA) involvement in 6/7 (85.7%) cases. A comparative analysis between portal hypertension (PTH) and non-PTH groups showed that HA amyloid deposition was dominant in the non-PTH group (6/7; 85.7%) and sinusoidal deposition in the PTH group (13/14; 92.8%). The difference was found to be significant (P < 0.05). Conclusion We found that portal hypertension was noted in cases with diffuse sinusoidal deposition or mixed sinusoidal with portal vein deposition. In the non-PHT group, the deposition was mainly in HA alone.
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Affiliation(s)
- Neha Nigam
- Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Pavni Bhatt
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Chhagan Bihari
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
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Karam S, Haidous M, Royal V, Leung N. Renal AA amyloidosis: presentation, diagnosis, and current therapeutic options: a review. Kidney Int 2023; 103:473-484. [PMID: 36502873 DOI: 10.1016/j.kint.2022.10.028] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 10/26/2022] [Accepted: 10/31/2022] [Indexed: 12/13/2022]
Abstract
Amyloid A amyloidosis is thought to be the second most common form of systemic amyloidosis behind amyloidosis secondary to monoclonal Ig. It is the result of deposition of insoluble fibrils in the extracellular space of tissues and organs derived from the precursor protein serum amyloid A, an acute phase reactant synthesized excessively in the setting of chronic inflammation. The kidney is the most frequent organ involved. Most patients present with proteinuria and kidney failure. The diagnosis is made through tissue biopsy with involvement of the glomeruli in most cases, but also often of the vessels and the tubulointerstitial compartment. The treatment usually targets the underlying etiology and consists increasingly of blocking the inflammatory cascade of cytokines with interleukin-1 inhibitors, interleukin-6 inhibitors, and tumor necrosis factor-α inhibitors to reduce serum amyloid A protein formation. This strategy has also shown efficacy in cases where an underlying etiology cannot be readily identified and has significantly improved the prognosis of this entity. In addition, there has been increased interest at developing effective therapies able to clear amyloid deposits from tissues, albeit with mitigated results so far.
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Affiliation(s)
- Sabine Karam
- Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA.
| | - Mohamad Haidous
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Virginie Royal
- Division of Pathology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Quebec, Canada
| | - Nelson Leung
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
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Fu Z, Lv J, Gao X, Zhang B, Li Y, Xu X, Zheng H, Wu H, Song Q. Research trends and hotspots evolution of cardiac amyloidosis: a bibliometric analysis from 2000 to 2022. Eur J Med Res 2023; 28:89. [PMID: 36805827 PMCID: PMC9940355 DOI: 10.1186/s40001-023-01026-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 01/20/2023] [Indexed: 02/22/2023] Open
Abstract
In the new century, cardiac amyloidosis has received more attention from many countries and institutions, leading to innovations in the essence of the pathology, biological markers, noninvasive tests, and staging diagnoses and treatments for this disease. However, few reviews have summarized the research trends and hotspots in cardiac amyloidosis. Bibliometrics analysis is a statistically based approach to research that visualizes the contributions of academic institutions and changes in research hotspots. Therefore, in this paper, we used Citespace and VOSviewer software to conduct co-occurrence analysis and collaborative network analysis on the countries, institutions, and authors in the articles related to cardiac amyloidosis since the new century. And further find out burst keywords and references to obtain the research history, disciplinary development, and new hotspots and topics.
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Affiliation(s)
- Zhenyue Fu
- grid.464297.aDepartment of General Internal Medicine, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China ,grid.24695.3c0000 0001 1431 9176Present Address: Beijing University of Chinese Medicine, Beijing, China
| | - Jiayu Lv
- grid.464297.aDepartment of General Internal Medicine, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiya Gao
- grid.464297.aDepartment of General Internal Medicine, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China ,grid.24695.3c0000 0001 1431 9176Present Address: Beijing University of Chinese Medicine, Beijing, China
| | - Bingxuan Zhang
- grid.464297.aDepartment of General Internal Medicine, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yumeng Li
- grid.464297.aDepartment of General Internal Medicine, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xia Xu
- grid.464297.aDepartment of General Internal Medicine, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haoran Zheng
- grid.464297.aDepartment of General Internal Medicine, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China ,grid.24695.3c0000 0001 1431 9176Present Address: Beijing University of Chinese Medicine, Beijing, China
| | - Huaqin Wu
- grid.410318.f0000 0004 0632 3409Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qingqiao Song
- Department of General Internal Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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Vieira RAL, S.P.R. Pereira L, Rocha RS, Muniz LB, de Ávila Almeida EX. Multidisciplinary Approach in Fabry Disease and Amyloidosis. AMYLOIDOSIS AND FABRY DISEASE 2023:449-465. [DOI: 10.1007/978-3-031-17759-0_39] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Endo H, Obara N, Mizuno S, Nakamura Y. Systemic AA Amyloidosis Secondary to Metastatic Renal Cell Carcinoma in a Hemodialysis Patient with Intractable Diarrhea. Case Rep Gastroenterol 2023; 17:275-280. [PMID: 37928968 PMCID: PMC10624937 DOI: 10.1159/000531066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 05/05/2023] [Indexed: 11/07/2023] Open
Abstract
We describe an autopsied case of systemic AA amyloidosis secondary to metastatic renal cell carcinoma presenting intractable diarrhea. Severe diarrhea was the major symptom for the diagnosis of AA amyloidosis. No renal symptoms which are common in AA amyloidosis secondary to renal cell carcinoma were shown because hemodialysis following bilateral nephrectomy had already been started 9 years before. Treatment against metastatic tumors as a solution of AA amyloidosis could not be performed because of bad performance status and the patient died 5 months after the diagnosis. Autopsy findings revealed that AA amyloid deposition was seen in multi-organs including the intestine. The metastatic tumors were histologically compatible as metastasis of renal cell carcinoma. There was no other cause of chronic inflammation such as inflammatory arthritis. We concluded that chronic inflammation provoked by the metastatic tumors of renal cell carcinoma was a major cause of systemic AA amyloidosis. Intestinal AA amyloidosis with malabsorption was the cause of death. Clinicians should keep it in mind that solid organ malignancy can be a cause of AA amyloidosis and renal cell carcinoma is the most common carcinomatous cause. This case is particularly instructive in that progression of amyloidosis may be missed in hemodialysis patients with anuria and that gastrointestinal symptoms can be the primary indicators of systemic amyloidosis. Endoscopic examination including biopsy is important for the diagnosis and early treatment of amyloidosis.
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Affiliation(s)
- Hiroyuki Endo
- Department of Gastroenterology, Japan Community Health Care Organization Sendai Hospital, Sendai, Japan
| | - Noriyuki Obara
- Department of Gastroenterology, Japan Community Health Care Organization Sendai Hospital, Sendai, Japan
| | - Shinichi Mizuno
- Department of Nephrology, Japan Community Health Care Organization Sendai Hospital, Sendai, Japan
| | - Yasuhiro Nakamura
- Division of Pathology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan
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Russe-Russe JR, Abramowitz C, Pellegrini JR, Alvarez Betancourt A, Cohen R, Baldino M, Crandall R, Kagolanu D, Mejia J, Rizvon K. COVID-19 Exposure Unmasking Systemic Amyloidosis With Hepatic Predominance. Cureus 2022; 14:e31092. [DOI: 10.7759/cureus.31092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2022] [Indexed: 11/06/2022] Open
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Barroso FA, Coelho T, Dispenzieri A, Conceição I, Waddington-Cruz M, Wixner J, Maurer MS, Rapezzi C, Planté-Bordeneuve V, Kristen AV, González-Duarte A, Chapman D, Stewart M, Amass L. Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS). Amyloid 2022; 29:175-183. [PMID: 35451899 DOI: 10.1080/13506129.2022.2043270] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
BACKGROUND Autonomic dysfunction is common in transthyretin amyloidosis (ATTR amyloidosis), but its frequency, characteristics, and quality-of-life (QoL) impact are not well understood. METHODS The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal survey of patients with ATTR amyloidosis, including patients with inherited (ATTRv) and wild-type (ATTRwt) disease and asymptomatic patients with TTR mutations (ClinicalTrials.gov: NCT00628745). In a descriptive analysis, characteristics and Norfolk QoL-DN total (TQoL) scores at enrolment were compared in patients with vs without autonomic dysfunction (analysis cut-off: 1 August 2020). RESULTS Autonomic dysfunction occurred in 1181/2922 (40.4%) symptomatic patients, and more commonly in ATTRv (1107/1181 [93.7%]) than ATTRwt (74/1181 [6.3%]) amyloidosis. Time (mean [SD]) from ATTR amyloidosis symptom onset to first autonomic dysfunction symptom was shorter in ATTRv (3.4 [5.7] years) than ATTRwt disease (9.7 [10.4]). In ATTRv disease, patients with vs without autonomic dysfunction had worse QoL (TQoL, 47.3 [33.2] vs 16.1 [18.1]); in ATTRwt disease, those with vs without autonomic dysfunction had similar QoL (23.0 [18.2] vs 19.9 [20.5]). CONCLUSIONS Autonomic dysfunction was more common and presented earlier in symptomatic ATTRv than ATTRwt amyloidosis and adversely affected QoL in ATTRv disease. These THAOS findings may aid clinicians in diagnosing and treating patients with ATTR amyloidosis. Trial registration: ClinicalTrials.gov: NCT00628745.
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Affiliation(s)
- Fabio A Barroso
- Institute for Neurological Research, FLENI, Buenos Aires, Argentina
| | - Teresa Coelho
- Unidade Corino Andrade, Hospital Santo António, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | | | - Isabel Conceição
- Hospital de Santa Maria-CHULN, FML Universidade de Lisboa, Lisbon, Portugal
| | - Marcia Waddington-Cruz
- CEPARM, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Jonas Wixner
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Mathew S Maurer
- Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Claudio Rapezzi
- Cardiological Center, University of Ferrara, Ferrara, Italy.,Maria Cecilia Hospital, GVM Care & Research, Cotignola (RA), Italy
| | - Violaine Planté-Bordeneuve
- Department of Neurology, East-Paris University, Hospital Henri Mondor, Assistance Publique Hopitaux de Paris, INSERM U955 Team 10 "Biology of the Neuro-Muscular System", Crétei, France
| | - Arnt V Kristen
- Department of Cardiology, Angiology, and Respiratory Medicine, Medical University of Heidelberg, Heidelberg, Germany
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Ding J, Huo L, Cui R, Luo Y. Secondary Gastrointestinal Amyloidosis With Increased 18 F-FDG Uptake as the Only Presentation in a Patient With Multiple Myeloma. Clin Nucl Med 2022; 47:721-722. [PMID: 35195581 DOI: 10.1097/rlu.0000000000004092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
ABSTRACT A 63-year-old woman presented with abdominal pain and hematochezia was referred for 18 F-FDG PET/CT for the underlying malignancy. PET/CT detected diffuse thickening of the bowel walls with intense radioactivity in the colons. She was later diagnosed with multiple myeloma and secondary gastrointestinal amyloidosis, and achieved complete response of myeloma and amyloidosis after 9 cycles of chemotherapy. This case highlighted that gastrointestinal abnormality caused by amyloidosis might be the only presenting symptoms and findings in 18 F-FDG PET/CT in patients with multiple myeloma.
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Affiliation(s)
- Jie Ding
- From the Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital; and Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China
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Ghazanfar H, Khaja M, Haider A, Yapor L, Kandhi S, Sulh M. Hepatic Amyloidosis as a Rare Cause of Liver Failure: A Case Report. Cureus 2022; 14:e27274. [PMID: 36039232 PMCID: PMC9403217 DOI: 10.7759/cureus.27274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2022] [Indexed: 11/05/2022] Open
Abstract
Amyloidosis is a systemic disease that results from the extracellular deposition of an abnormal protein called amyloid. The kidney and the heart are the most common organ affected by amyloidosis while in some cases liver involvement can be seen. Our patient is a 60-year-old African American male who presented to the emergency department because of multiple episodes of syncope over the past day. Chest x-ray and ultrasound chest were suggestive of pleural effusion for which thoracentesis was done. His hospital course was complicated with renal and liver failure. Computed tomography (CT) abdomen and pelvis was done which showed mild hepatomegaly. Liver biopsy was done which showed congo red stain positive for amyloid. The patient's clinical condition continued to worsen and he was started on hemodialysis. During hospital course, the patient developed liver failure. His family members opted for palliative care and the patient passed away during the same admission. Physicians need to be aware of the detrimental course and poor prognosis associated with hepatic and renal amyloidosis. High clinical suspicion is needed to make an early diagnosis and initiate prompt treatment. Although clinical, laboratory and radiological findings can help in suggesting amyloidosis, a tissue biopsy is needed to confirm the diagnosis of amyloidosis.
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Jensen CE, Byku M, Hladik GA, Jain K, Traub RE, Tuchman SA. Supportive Care and Symptom Management for Patients With Immunoglobulin Light Chain (AL) Amyloidosis. Front Oncol 2022; 12:907584. [PMID: 35814419 PMCID: PMC9259942 DOI: 10.3389/fonc.2022.907584] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/26/2022] [Indexed: 11/17/2022] Open
Abstract
Immunoglobulin light chain (AL) amyloidosis is a disorder of clonal plasma cells characterized by deposition of amyloid fibrils in a variety of tissues, leading to end-organ injury. Renal or cardiac involvement is most common, though any organ outside the central nervous system can develop amyloid deposition, and symptomatic presentations may consequently vary. The variability and subtlety of initial clinical presentations may contribute to delayed diagnoses, and organ involvement is often quite advanced and symptomatic by the time a diagnosis is established. Additionally, while organ function can improve with plasma-cell-directed therapy, such improvement lags behind hematologic response. Consequently, highly effective supportive care, including symptom management, is essential to improve quality of life and to maximize both tolerance of therapy and likelihood of survival. Considering the systemic nature of the disease, close collaboration between clinicians is essential for effective management.
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Affiliation(s)
- Christopher E. Jensen
- Division of Hematology, University of North Carolina School of Medicine, Chapel Hill, NC, United States
- Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, NC, United States
| | - Mirnela Byku
- Division of Cardiology, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Gerald A. Hladik
- Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Koyal Jain
- Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Rebecca E. Traub
- Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Sascha A. Tuchman
- Division of Hematology, University of North Carolina School of Medicine, Chapel Hill, NC, United States
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States
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Zhao Z, Jiao Y, Yue B, Wang W, Zhao G, Zhang S, Li P. Deep biopsy via endoscopic submucosal dissection for primary gastric amyloidosis. Endoscopy 2022; 54:E236-E237. [PMID: 34102683 DOI: 10.1055/a-1493-2081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Affiliation(s)
- Zheng Zhao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yue Jiao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Bing Yue
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wenjing Wang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guiping Zhao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Peng Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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A Case of Systemic AL Amyloidosis Diagnosed by Screening Colonoscopy. Case Rep Gastrointest Med 2022; 2022:5562281. [PMID: 35497055 PMCID: PMC9046006 DOI: 10.1155/2022/5562281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 04/02/2022] [Indexed: 11/26/2022] Open
Abstract
Amyloidosis encompasses several diseases associated with deposition of low-molecular-weight proteins in an abnormal configuration. In light-chain amyloidosis (AL), monoclonal free lambda (λ) or kappa (κ) light chains are the amyloid proteins involved and can deposit in almost any organ. Symptoms vary depending on presence and extent of organ involvement, and thus, clinical presentation varies. Diagnosis requires biopsy of the affected tissue, and sometimes, fat pad or bone marrow biopsy is completed initially. Prognosis of AL amyloidosis depends on the presence of cardiac involvement. Treatment of AL amyloidosis involves systemic chemotherapy and evaluation for autologous stem cell transplant. Herein, we present a case report of an asymptomatic middle-aged female who was diagnosed with AL amyloidosis during an average-risk screening colonoscopy, which is an unusual setting. We discuss the workup involved, clinical presentation, and gastroenterology-related organ involvement.
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Ke M, Li X, Wang L, Yue S, Zhao B. A stepwise data interpretation process for renal amyloidosis typing by LMD-MS. BMC Nephrol 2022; 23:144. [PMID: 35418036 PMCID: PMC9008935 DOI: 10.1186/s12882-022-02785-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 04/07/2022] [Indexed: 11/25/2022] Open
Abstract
Backgrounds Systemic amyloidosis is classified according to the deposited amyloid fibril protein (AFP), which determines its best therapeutic scheme. The most common type of AFP found are immunoglobulin light chains. The laser microdissection combined with mass spectrometry (LMD-MS) technique is a promising approach for precise typing of amyloidosis, however, the major difficulty in interpreting the MS data is how to accurately identify the precipitated AFP from background. Objectives The objective of the present study is to establish a complete data interpretation procedure for LMD-MS based amyloidosis typing. Methods Formalin-fixed paraffin-embedded specimens from patients with renal amyloidosis and non-amyloid nephropathies (including diabetic nephropathy, fibrillary glomerulonephritis, IgA nephropathy, lupus nephritis, membranous nephropathy, and normal tissue adjacent to tumors) were analyzed by LMD-MS. Forty-two specimens were used to train the data interpretation procedure, which was validated by another 50 validation specimens. Area under receiver operating curve (AUROC) analysis of amyloid accompanying proteins (AAPs, including apolipoprotein A-IV, apolipoprotein E and serum amyloid P-component) for discriminating amyloidosis from non-amyloid nephropathies was performed. Results A stepwise data interpretation procedure that includes or excludes the types of amyloidosis group by group was established. The involvement of AFPs other than immunoglobulin was determined by P-score, as well as immunoglobulin light chain by variable of λ-κ, and immunoglobulin heavy chain by H-score. This achieved a total of 88% accuracy in 50 validation specimens. The AAPs showed significantly different expression levels between amyloidosis specimens and non-amyloid nephropathies. Each of the single AAP had a AUROC value more than 0.9 for diagnosis of amyloidosis from non-amyloid control, and the averaged level of the three AAPs showed the highest AUROC (0.966), which might be an alternative indicator for amyloidosis diagnosis. Conclusions The proteomic data interpretation procedure for LMD-MS based amyloidosis typing was established successfully that has a high practicability in clinical application. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-022-02785-9.
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Affiliation(s)
- Ming Ke
- Guangzhou KingMed Center for Clinical Laboratory Co.,Ltd, Guangzhou, 510005, China
| | - Xin Li
- Guangzhou KingMed Center for Clinical Laboratory Co.,Ltd, Guangzhou, 510005, China
| | - Lin Wang
- Guangzhou KingMed Center for Clinical Laboratory Co.,Ltd, Guangzhou, 510005, China
| | - Shuling Yue
- Guangzhou KingMed Center for Clinical Laboratory Co.,Ltd, Guangzhou, 510005, China
| | - Beibei Zhao
- Guangzhou KingMed Center for Clinical Laboratory Co.,Ltd, Guangzhou, 510005, China.
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Modified Body Mass Index as a Novel Nutritional and Prognostic Marker in Patients with Cardiac Amyloidosis. CARDIOGENETICS 2022. [DOI: 10.3390/cardiogenetics12020017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The nutritional assessment is gaining clinical relevance since cardiac cachexia and malnutrition are emerging as novel markers of functional status and prognosis in many cardiovascular disorders, including cardiac amyloidosis (CA). This study aimed to evaluate the prognostic role of different nutritional indices for cardiovascular mortality in patients with CA and subgroups. Fifty CA patients (26 AL and 24 ATTR wild-type) were retrospectively analyzed. All patients underwent a comprehensive clinical and laboratory evaluation. Conventional body mass index (cBMI), modified BMI (mBMI), new BMI (nBMI) and prognostic nutritional index (PNI) were analyzed. Multivariate regression analysis was performed to identify the association between nutritional and other clinical-laboratory parameters with cardiovascular death. Compared to ATTRwt patients, those with AL showed lower mBMI values. No significant difference was observed for the other nutritional indices. During a median follow-up of 11.2 months, a lower mBMI quartile was associated with worse survival, in both groups. In multivariate analysis, mBMI emerged as an independent predictor for cardiovascular death. This study showed that mBMI is a novel index of malnutrition and an independent risk factor for cardiovascular mortality in patients with CA in both AL and ATTRwt form.
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40
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Fang H, Lin C, Yu Y, Chang M. Gastric amyloidosis associated with multiple myeloma: A rare cause of upper gastrointestinal bleeding. ADVANCES IN DIGESTIVE MEDICINE 2022. [DOI: 10.1002/aid2.13318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Huei‐Ling Fang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital New Taipei City Taiwan
| | - Cheng‐Kuan Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital New Taipei City Taiwan
| | - Yuan‐Bin Yu
- Division of Oncology and Hematology, Department of Internal Medicine, Far Eastern Memorial Hospital New Taipei City Taiwan
| | - Min‐Hsiang Chang
- Department of Anatomic Pathology, Far Eastern Memorial Hospital New Taipei City Taiwan
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Imamura T, Hori M, Tanaka S, Kinugawa K. Successful management of refractory constipation using Kampo medicine Mashiningan in a patient with wild-type ATTR cardiac amyloidosis. J Cardiol Cases 2022; 25:34-36. [PMID: 35024066 DOI: 10.1016/j.jccase.2021.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/01/2021] [Accepted: 06/04/2021] [Indexed: 10/20/2022] Open
Abstract
A wild-type ATTR amyloidosis is a systemic disease with multi-organ dysfunction, involving heart, kidney, skin, and gastrointestinal tract, due to deposition of wild-type transthyretin in each organ. We had a 76-year-old man diagnosed with wild-type ATTR cardiac amyloidosis, whose heart failure symptom improved by anti-heart failure medications but constipation refractory to multiple conventional medications persisted. Following the conversion from lubiprostone to Kampo medicine mashiningan, his average days per one evacuation decreased from around 7.0 days down to 1.6 days. Mashininigan might be an alternative option to improve refractory constipation in patients with cardiac amyloidosis. <Learning objective: Mashininigan might be an alternative option to improve refractory constipation in patients with cardiac amyloidosis.>.
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Affiliation(s)
- Teruhiko Imamura
- The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Masakazu Hori
- The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Shuhei Tanaka
- The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Koichiro Kinugawa
- The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
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Patel N, Das P, Jain D. Systemic Manifestations of Gastrointestinal Tract Diseases and Systemic Diseases Involving the Gastrointestinal Tract. SURGICAL PATHOLOGY OF THE GASTROINTESTINAL SYSTEM 2022:521-572. [DOI: 10.1007/978-981-16-6395-6_14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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DeMarco GB, Jiang Q, Fischer EA. POCUS Finding of Portal Venous Gas: An Unusual Consequence of an Amyloid Dysmotility Related Bezoar. POCUS JOURNAL 2022; 7:201-204. [PMID: 36896385 PMCID: PMC9983721 DOI: 10.24908/pocus.v7i2.15681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
A 73-year-old male with a recent finding of pericardial effusion and syncope was evaluated with point of care ultrasound for recurrent effusion. A thickened left ventricle and recurrent pericardial effusion were found. Unexpectedly, on scanning the inferior vena cava (IVC), extensive portal venous gas was identified, a finding previously described as a "meteor shower". Subsequent imaging by computed tomography (CT) identified gastric edema and peri-gastric vessel gas as the source of the portal gas, attributed to a large bezoar. The bezoar was later classified as a phytobezoar and the patient was found to have both cardiac and gastrointestinal manifestations of light chain amyloidosis. The gastrointestinal amyloidosis predisposed the patient to bezoar formation owing to associated dysmotility, a rare complication of an unusual manifestation of systemic amyloid.
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Affiliation(s)
- Grace B DeMarco
- Department of Medicine, MedStar Georgetown University Hospital Washington, DC
| | - Qiuchen Jiang
- Department of Medicine, MedStar Georgetown University Hospital Washington, DC
| | - Ernest A Fischer
- Department of Medicine, MedStar Georgetown University Hospital Washington, DC
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Abstract
Amyloidosis is a very rare condition, which, due to its rarity, is often missed or diagnosed in an advanced stage of the disease, causing significant morbidity and mortality. In this review we describe the existing types of amyloidosis focusing on the gastro-intestinal tract. Amyloidosis occurs when abnormal protein fibrils (amyloid) deposit in the muscularis mucosae. This can cause an array of symptoms ranging from (in order of occurrence): gastro-intestinal bleeding, heartburn, unintentional weight loss, early satiety, constipation, diarrhea, nausea, vomiting and fecal incontinence (1). Treatment is focused on the underlying condition (if any) causing the production and deposition of the abnormal fibrils, in combination of symptomatic treatment.
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Yumoto S, Doi K, Higashi T, Shimao Y, Ueda M, Ishihara A, Adachi Y, Ishiodori H, Honda S, Baba H. Intra-abdominal bleeding caused by amyloid transthyretin amyloidosis in the gastrointestinal tract: a case report. Clin J Gastroenterol 2021; 15:140-145. [PMID: 34797488 DOI: 10.1007/s12328-021-01551-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 10/30/2021] [Indexed: 11/28/2022]
Abstract
Diagnosis of gastrointestinal (GI) amyloidosis is often very difficult because of its nonspecific symptoms. However, a few reports have indicated that serious symptoms such as fatal GI bleeding and obstruction or perforation sometimes lead to a diagnosis of GI amyloidosis. A 79-year-old man was transported to our emergency department with a 1-week history of worsening abdominal pain. Abdominal contrast-enhanced computed tomography showed extravasation from part of the transverse colon wall and moderate ascites. Because intra-abdominal bleeding was suspected, the patient urgently underwent partial resection of the transverse colon, which was the source of the bleeding. Postoperative pathological examination of the tissue specimens led to a diagnosis of amyloid transthyretin amyloidosis. This is the first reported case in which intra-abdominal bleeding led to a diagnosis of GI amyloidosis. We should consider the possibility of GI amyloidosis when intraperitoneal bleeding is observed in elderly patients.
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Affiliation(s)
- Shinsei Yumoto
- Department of Surgery, Miyazaki Prefectural Nobeoka Hospital, Miyazaki, Japan
| | - Koichi Doi
- Department of Surgery, Miyazaki Prefectural Nobeoka Hospital, Miyazaki, Japan
| | - Takaaki Higashi
- Department of Surgery, Miyazaki Prefectural Nobeoka Hospital, Miyazaki, Japan
| | - Yoshiya Shimao
- Department of Pathology, Miyazaki Prefectural Nobeoka Hospital, 2-1-10 Shinkouji, Nobeoka, Miyazaki, 882-0835, Japan
| | - Mitsuharu Ueda
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Ishihara
- Department of Pathology, Junwakai Memorial Hospital, Miyazaki, Japan
| | - Yuki Adachi
- Department of Surgery, Miyazaki Prefectural Nobeoka Hospital, Miyazaki, Japan
| | - Hiroyuki Ishiodori
- Department of Surgery, Miyazaki Prefectural Nobeoka Hospital, Miyazaki, Japan
| | - Shinobu Honda
- Department of Surgery, Miyazaki Prefectural Nobeoka Hospital, Miyazaki, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
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Amyloidosis: A Rare Cause of Severe Cholestasis and Acute Liver Failure. ACG Case Rep J 2021; 7:e00479. [PMID: 34604435 PMCID: PMC8483873 DOI: 10.14309/crj.0000000000000479] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 07/17/2020] [Indexed: 11/17/2022] Open
Abstract
Although hepatic involvement in light chain–associated amyloidosis is common, clinical manifestations of hepatic amyloidosis are rare. In most cases, hepatomegaly serves as a clue to diagnosis. We report a unique case of a 48-year-old man from China with jaundice and noncirrhotic portal hypertension, with rapidly progressive liver failure, in the absence of hepatomegaly, secondary to systemic light chain–associated amyloidosis associated with multiple myeloma.
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Abstract
An 81-year-old male patient presented on the emergency ward for hematochezia, without any other complaints. Rectosigmoidoscopy showed a predominant patchy inflammation of the mucosa with several bluish blebs (submucosal hemorrhage) and small ulcerations. (Figure 1A). Subsequent elective colonoscopy (1) revealed multiple submucosal hematomas and mucosal lacerations throughout the entire colon in between normal mucosa. During the procedure spontaneous mucosal tears occurred. (Figure 1B). Multiple biopsies were taken.
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48
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Tanaka T, Naito T, Midori Y, Nosaka T, Takahashi K, Ofuji K, Matsuda H, Ohtani M, Hiramatsu K, Imamura Y, Yokoyama O, Naiki H, Nakamoto Y. Gastrointestinal AA amyloidosis secondary to chronic pyelonephritis presenting with refractory diarrhea and severe hypoalbuminemia. Clin J Gastroenterol 2021; 14:1642-1648. [PMID: 34468921 DOI: 10.1007/s12328-021-01508-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/24/2021] [Indexed: 10/20/2022]
Abstract
Secondary amyloidosis is a rare complication of chronic inflammatory diseases, such as collagen diseases, and is often difficult to treat. In addition, the gastrointestinal tract is frequently involved in amyloid deposition that often results in various disorders and symptoms. A 70-year-old woman was admitted to our hospital with refractory diarrhea and hypoalbuminemia. Abdominal computed tomography demonstrated extensive edematous wall thickening of the small intestine and colon. Video capsule endoscopy revealed multiple ulcerations with a white mossy appearance of the ileum. Double-balloon endoscopy showed severe circumferential ulcers in the entire ileum. Histological examination of ileum biopsy samples revealed severe amyloid deposition in the lamina propria and perivascular areas of the submucosa. The patient was diagnosed with gastrointestinal AA amyloidosis. The cause of AA amyloid deposition was presumed to be chronic pyelonephritis due to ureteral stones that had been left untreated for 35 years. After treatment with ureteral drainage and antibiotics, the patient's symptoms and serological abnormalities improved dramatically. Here, we describe a case of severe gastrointestinal AA amyloidosis secondary to chronic pyelonephritis. Clinicians should thoroughly investigate the entire gastrointestinal tract in patients with refractory diarrhea and severe hypoalbuminemia considering the possibility of gastrointestinal amyloidosis.
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Affiliation(s)
- Tomoko Tanaka
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Tatsushi Naito
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Yohei Midori
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Takuto Nosaka
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Kazuto Takahashi
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Kazuya Ofuji
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Hidetaka Matsuda
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Masahiro Ohtani
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Katsushi Hiramatsu
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan
| | - Yoshiaki Imamura
- Division of Diagnostic Pathology/Surgical Pathology, University of Fukui Hospital, Fukui, Japan
| | - Osamu Yokoyama
- Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan
| | - Hironobu Naiki
- Department of Molecular Pathology, University of Fukui, Fukui, Japan
| | - Yasunari Nakamoto
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.
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Roth B, Schiro DB, Ohlsson B. Diseases which cause generalized peripheral neuropathy: a systematic review. Scand J Gastroenterol 2021; 56:1000-1010. [PMID: 34214006 DOI: 10.1080/00365521.2021.1942542] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
PURPOSE Peripheral autonomic neuropathy, including enteric neuropathy, may be subtle and unrecognized for several years. Diagnosis of enteric neuropathy demands complicated examinations such as full-thickness bowel biopsy. We hypothesized that knowledge about simultaneous occurrence of different types of neuropathy would lead to faster recognition and diagnosis of autonomic/enteric neuropathy. The aim of the present systematic review was to increase the awareness of disease groups causing autonomic and enteric neuropathy along with sensorimotor neuropathy. METHODS A systematic search strategy was used in PubMed, Embase and Web of Science. First, 4978 articles were identified. Review of titles/abstracts rendered exclusion of animal studies, articles not written in English or full-length, case reports, conference abstracts and duplicates until 357 articles remained. The full-length evaluation resulted in 35 studies (27 non-systematic reviews) which described objectively verified peripheral autonomic, enteric and sensorimotor neuropathy within the same disease. RESULTS Diabetes is the most common disease in society rendering generalized peripheral neuropathy. Accumulation of tissue deposits in amyloidosis, Lewy body disorders and sarcoidosis lead to widespread peripheral neuropathy. Several autoimmune disorders such as systemic sclerosis and primary Sjögren's syndrome present themselves with neuropathy. Paraneoplastic neuropathy may appear prior to symptoms from the malignancy. Both the infection per se, as well as the autoimmune response to the infection, i.e., Guillain-Barré syndrome, may lead to widespread peripheral neuropathy. Hereditary disorders with disturbed metabolism lead to intermittent attacks of neuropathy. CONCLUSIONS The major causes of generalized peripheral neuropathy are diabetes, diseases with tissue deposits, autoimmunity, infections, malignancy and metabolic diseases.
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Affiliation(s)
- Bodil Roth
- Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.,Department of Clinical Sciences, Lund University, Malmö, Sweden
| | | | - Bodil Ohlsson
- Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.,Department of Clinical Sciences, Lund University, Malmö, Sweden
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Suggestive Diagnostic Process in a Case of Multiple Myeloma with Gastrointestinal Immunoglobulin Light-Chain Amyloidosis Accompanied by Protein-Losing Enteropathy. Case Rep Gastrointest Med 2021; 2021:5533993. [PMID: 34136288 PMCID: PMC8177977 DOI: 10.1155/2021/5533993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 05/22/2021] [Indexed: 11/18/2022] Open
Abstract
Multiple myeloma is a type of plasma cell neoplasm that produces monoclonal immunoglobulin. Multiple myeloma is known to cause immunoglobulin light-chain (AL) amyloidosis, which frequently involves the kidney and heart. Bone pain or fractures caused by osteolytic lesions and physical disorders related to renal or cardiac AL amyloidosis are major initial symptoms in multiple myeloma. Multiple myeloma diagnosed from the gastrointestinal symptoms is rare. We report a case of an 80-year-old man with multiple myeloma accompanied by gastrointestinal AL amyloidosis and secondary protein-losing enteropathy. The diagnostic process was suggestive, in that diarrhea and refractory leg edema related to protein-losing enteropathy were the primary symptoms and the trigger for making a sequential diagnosis of gastrointestinal AL amyloidosis and underlying multiple myeloma. This case is highly suggestive, in that multiple myeloma with gastrointestinal AL amyloidosis should be considered one of the background diseases of protein-losing enteropathy.
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