Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Mary N. Sheppard in Practical Cardiovascular Pathology, 2022
Amyloidosis is a heterogeneous disease that results from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. Amyloidosis can be acquired or hereditary, localized or systemic. Amyloid can accumulate in the liver, spleen, kidney, heart, nerves and blood vessels, causing different clinical syndromes, including cardiomyopathy, hepatomegaly, proteinuria, macroglossia, autonomic dysfunction, ecchymoses, neuropathy, renal failure, hypertension and corneal and vitreous abnormalities. In primary and secondary amyloidosis, interstitial infiltrative deposits replace normal myocardium, resulting in restrictive physiology. The most common types are IAA (isolated atrial amyloid), AL, ATTR (amyloid transport protein transthyretin) and dialysis-related amyloidosis (beta2M type).
Metabolic Myopathy
Maher Kurdi in Neuromuscular Pathology Made Easy, 2021
Amyloid myopathy is an uncommon metabolic disease characterized by abnormal deposition of amyloid proteins in muscle fibers. Patients may present with early peripheral neuropathy followed by myopathy. Widespread deposition of amyloid may cause systemic amyloidosis that ends with organ damage. The diagnosis is always difficult in clinical ground as amyloidosis is rarely suspected in clinician thoughts. Amyloidosis could be primary due to sporadic or inherited gene mutations or secondary, resulting from underlying chronic illness. A rare example of inherited or sporadic cases is amyloid deposition due to transthyretin. Muscle biopsy demonstrates perivascular and perimysial amyloid deposition. With using EM, the vessels and muscle fibers are lined with elongated and thin amyloid fibrils, frequently seen on the basal lamina.
Test Paper 7
Teck Yew Chin, Susan Cheng Shelmerdine, Akash Ganguly, Chinedum Anosike in Get Through, 2017
Amyloidosis is a rare condition, which can affect one specific organ, or present as a systemic illness. The disease is characterised by the deposition of proteinaceous material either in a focal, tumour-like lesion or an infiltrative fashion. Within the chest, cardiac involvement is the most commonly seen, with patients presenting with variable symptoms ranging from arrhythmias to cardiac failure. Pulmonary involvement is typically in the setting of multiple previous chest infections. Computed tomography often demonstrates ‘tree-in-bud’ opacity, usually in a peripheral location, at sites of previous pneumonia. Within the tracheo-bronchial tree, mass-like lesions are seen arising from the internal wall, often significantly compromising the airway lumen. While the other conditions listed could result in scattered intrapulmonary nodules, the additional endobronchial abnormality makes amyloidosis more likely.
Spontaneous periocular ecchymosis: a major review
Published in Orbit, 2023
Matthew J. Hartley, Pav Gounder, Huw Oliphant
Amyloidosis encompasses a group of rare diseases of abnormal synthesis and deposition of proteinaceous aggregates throughout the body.18 When these misfolded proteins accumulate, known as amyloid fibrils, they can become toxic to tissues within the kidneys and heart, liver, brain, gastrointestinal tract, and vascular architecture. Light-chain (AL) amyloidosis is the most common form, where dysplastic plasma cells of the bone marrow synthesize abnormal proteins. Although light-chain amyloidosis is not a true malignancy, multiple myeloma can co-exist in 10% of these patients due to a similar pathophysiological derivation.19 Despite improvements in recent decades, there is still significant mortality associated with amyloidosis, with overall survival being 48% at 5 years in one longitudinal study.20
Tissue biopsy for the diagnosis of amyloidosis: experience from some centres
Published in Amyloid, 2022
Merrill D. Benson, John L. Berk, Angela Dispenzieri, Thibaud Damy, Julian D. Gillmore, Bouke P. Hazenberg, Francesca Lavatelli, Maria M. Picken, Christoph Röcken, Stefan Schönland, Mitsuharu Ueda, Per Westermark
Diagnosis of amyloidosis is usually based on demonstration of amyloid deposits in a tissue biopsy. A definitive diagnosis has become increasingly important since a number of impactful treatment options have developed. The clinical and biologic diversity of amyloidosis conditions emphasises the need for refined and exact analysis of the deposited material. Evolution of such analyses has occurred independently at the relatively few different specialised centres around the world. In this way, a number of distinct but partially complementary methods have emerged. The purpose of this clinical practice summary of experts is to describe some important steps in biopsy procedures and diagnostic tools in the diagnostic work-up of amyloid and amyloidosis and provide examples of alternative methods. In addition, we wish to point out some challenges and pitfalls. The specific signs, symptoms and conditions warranting suspicion of amyloidosis that underlie the decision to obtain a biopsy fall beyond the scope of this article.
Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study#
Published in Amyloid, 2019
Josep Gamez, María Salvadó, Núria Reig, Pilar Suñé, Carles Casasnovas, Ricard Rojas-Garcia, Raúl Insa
Our study shows that tolcapone (SOM0226) is capable of stabilizing all TTR present in plasma samples in all the participants (ATTR patients, asymptomatic carriers and healthy individuals), supporting further development of this drug for the treatment of TTR amyloidosis. The possibility of new indications of drugs approved by the FDA (repurposing) can provide a faster route for new treatments owing to faster clinical development, a reduction in drug optimization, and failure rates due to pharmacokinetics and safety problems. Diflunisal is an example of a repurposed drug approved by the FDA that has shown its inhibiting capacity in the progression of hereditary ATTR amyloidosis in clinical trials. However, it has significant adverse gastrointestinal and cardiovascular effects, and is perhaps not the most suitable medication for a large patient subpopulation. Tolcapone (SOM0226) could be a repositioned drug for amyloidosis, including senile systemic amyloidosis, hereditary ATTR amyloidosis, hereditary amyloid cardiomyopathy, and the only one for TTR leptomeningeal amyloidosis [27]. It appears that TTR stabilizers may become the first-line therapeutic approach for patients with hereditary ATTR amyloidosis who do not meet the criteria for OLT. Consensus regarding the most appropriate therapeutic approach is still lacking for transplanted patients with progression of amyloidosis.
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