Figure 5 - uploaded by Jenny Pinney
Content may be subject to copyright.
(a) Extensive peri-orbital bruising in a patient with AL amyloidosis. (b) Macroglossia with dental indentations in a patient with AL amyloidosis
Source publication
The term amyloid describes the deposition in the extracellular space of certain proteins in a highly characteristic, insoluble fibrillar form. Amyloidosis describes the various clinical syndromes that occur as a result of damage by amyloid deposits in tissues and organs throughout the body. The clinical significance of amyloid varies enormously, ra...
Context in source publication
Context 1
... features late on in the disease process and is associated with a poor prognosis. 51 Soft tissue involvement is pathognomonic for AL amyloidosis; macroglossia is not seen in other forms of amyloid ( Figure 5). The prognosis in untreated AL amyloidosis is very poor with a median survival of only 6 -15 months and a 10-year survival rate of ,5%. ...
Similar publications
Cerebral amyloid angiopathy is commonly associated with normal aging and Alzheimer's disease and it is also the principal feature of hereditary cerebral hemorrhage with amyloidosis Dutch type, a familial condition associated to a point mutation G to C at codon 693 of the amyloid β (Aβ) precursor protein gene resulting in a Glu to Gln substitution a...
Citations
... Proteins, under pathological conditions, tend to misfold and aggregate, leading to the formation of abnormal fibrillary conformation called amyloid fibrils [1]. Amyloid fibrils are insoluble, several microns long, and 5-18 nm wide based on protein, sharing characteristic highly organized cross-β-sheet structure, with β-strands ordered perpendicular to the fibril axis [2]. ...
... Amyloid fibrils are insoluble, several microns long, and 5-18 nm wide based on protein, sharing characteristic highly organized cross-β-sheet structure, with β-strands ordered perpendicular to the fibril axis [2]. Due to their insolubility, they create deposits in the intra-or extracellular space that cause cytotoxicity characteristic of disrupting tissues' structure and function [1,2]. Even today, it is problematic to cope with amyloidoses since the diversity of misfolded species precludes an accurate description of the toxicity initiators. ...
... Lysozyme, an antibacterial enzyme expressed by different immune cells, such as monocytes, granulocytes, or bone marrow precursor cells, is part of the innate immune system. It is present in the liver, articular surfaces, tears, and saliva [1]. However, lysozyme may create amyloid deposits in the kidneys, spleen, and liver [4], as part of a rare autosomal dominant condition known as hereditary non-neuropathic systemic lysozyme amyloidosis (Ostertag-type) [3]. ...
Amyloidoses represent a group of pathological conditions characterized by amyloid fibrils accumulating in the form of deposits in intra- or extracellular space, leading to tissue damage. The lysozyme from hen egg-white (HEWL) is often used as a universal model protein to study the anti-amyloid effects of small molecules. The in vitro anti-amyloid activity and mutual interactions of green tea leaf constituents: (-)-epigallocatechin gallate (EGCG), (-)-epicatechin (EC), gallic acid (GA), caffeine (CF) and their equimolar mixtures were studied. The inhibition of HEWL amyloid aggregation was monitored by a Thioflavin T fluorescence assay and atomic force microscopy (AFM). The interactions of the analyzed molecules with HEWL were interpreted by ATR-FTIR and protein-small ligand docking studies. EGCG was the only substance efficiently inhibiting amyloid formation (IC50 ~ 193 μM), slowing the aggregation process, reducing the number of fibrils and partially stabilizing the secondary structure of HEWL. Compared to EGCG alone, EGCG-containing mixtures displayed lower overall anti-amyloid efficacy. The decrease in efficiency results from (a) the spatial interference of GA, CF and EC with EGCG while binding to HEWL, (b) the propensity of CF to form a less active adduct with EGCG, which participates in interactions with HEWL in parallel with pure EGCG. This study confirms the importance of interaction studies, revealing the possible antagonistic behavior of molecules when combined.
... However, amyloid deposits can be seen in the liver, spleen, gastrointestinal tract, and adrenals without leading to any organ dysfunction. [3] The involvement of the heart and nerves is infrequent. In India, the estimated biopsy incidence of amyloid nephropathy is 1.9%. ...
... The diagnosis of amyloidosis involves a multidisciplinary approach which starts with a high index of suspicion on clinical evaluation, hematological, and biochemical investigations, various imaging techniques, histopathology of the biopsied tissue, characteristic apple-green birefringence under polarized light on Congo red staining, and immunohistochemistry (IHC) for identifying the specific type of amyloid protein and genetic analysis. [3] Serum amyloid P component (SAP) scintigraphy is an imaging technique that uses 123 iodine SAP to image the visceral amyloid, and it also quantifies the load of amyloid deposits, which can be monitored serially. However, limited availability is the reason why it has not gained popularity. [10] Our patient had a history of childhood-onset JIA-ERA with poor compliance to treatment and multiple flares in childhood. ...
The prevalence of Juvenile idiopathic arthritis (JIA) in India is 0.001% among the population under 16 years old and 0.00029% among the total population. Of the total JIA population, enthesitis-related arthritis (ERA) constitutes 35% of the cases. In the past, chronic infections, mainly, tuberculosis were the most common cause of AA amyloidosis in India; however, chronic inflammatory arthropathies have become the most common cause of AA amyloidosis in India over the past three to four decades. In 95% of the patients with AA amyloidosis, the kidney is the most affected organ presenting as proteinuria of nephrotic syndrome. The prevalence of AA amyloidosis in JIA is estimated to be 7.7% and 3.1% among the ERA group, making it an infrequent association. This translates to one case of AA amyloidosis secondary to ERA per 1,00,000,00 population in India. Similarly, the incidence of pulmonary thromboembolism in patients with nephrotic syndrome is 7.8%. We present a case of a young male who was diagnosed with JIA-ERA at the age of 13 years with multiple flares in childhood had now developed nephrotic syndrome secondary to AA amyloidosis demonstrated on renal biopsy complicated by acute pulmonary embolism and occult hepatitis B infection. He was managed with anti-tumor necrosis factor inhibitor therapy with a favorable outcome. This is the first such case of multiple rare associations occurring together in a single patient to the best of our knowledge.
... Amyloidosis is a disorder of protein folding in which various proteins automatically aggregate into a highly abnormal fibrillar conformation (1). Amyloidosis is classified according to the type of protein deposited and can be either systemic (i.e., fibrils are deposited in various organs and tissues throughout the body) or localized (i.e., fibrils are produced only in one organ or site in the body) (2,3). ...
Amyloidosis is a disorder of protein folding in which various proteins automatically aggregate into a highly abnormal fibrillar conformation. Amyloidosis is classified into systemic and localized forms depending on whether the abnormal proteins deposited in several different organs or only a single organ. In localized amyloidosis of the head and neck regions, laryngeal amyloidosis is common; however, localized amyloidosis of the nose is extremely rare. We herein report a case of localized amyloidosis of the nose and review the relevant literature on localized sinonasal amyloidosis. A 41-year-old man presented with a history of severe nasal obstruction, which had persisted for two decades. Nasal endoscopy and imaging studies showed extensive thickening of the bilateral nasal mucosa and diffuse submucosal deposition of calcification. After histopathological and systemic examinations, he was diagnosed with localized amyloidosis of the nasal mucosa. Septoplasty and bilateral inferior turbinoplasty, which consisted of mucosal resection using an ultrasonic bone curette, was performed and his symptoms markedly improved. Localized sinonasal amyloidosis has a good prognosis and surgical resection should be selected as a first-line treatment; however, clinicians should recognize the high probability of recurrence.
... Definitive diagnosis relies on tissue biopsy demonstrating the characteristic finding of apple green birefringence under polarizing light microscopy with Congo red stain, then identification of the precursor protein using liquid chromatography-tandem mass spectrometry on samples of the congophilic material isolated by microdissection. 1,2 Amyloidosis can be a localized or systemic disease process and is classified into subtypes based on the dominant amyloid precursor protein. The most common types of amyloidosis include primary (AL type, precursor is usually immunoglobulin light chain from a clonal plasma cell or B-cell disorder), secondary (AA type, precursor is serum amyloid A from a systemic inflammatory disorder), hereditary (most common precursor is mutant ATTR), and wild-type ATTR/Senile. ...
Objective
To evaluate the pattern of presentation and management of laryngotracheobronchial amyloidosis at a tertiary care academic center over a 27 year period.
Methods
In a retrospective review, the electronic medical record at a tertiary care academic center was queried for encounters with 3 laryngologists between 1996 and 2019 which included the ICD-9 or ICD-10 diagnosis of amyloidosis. Demographics, clinical presentation, referral diagnoses, medical history, family history, laboratory values, radiology studies, and treatment modalities of subjects were collated. Results were analyzed using standard univariate descriptive statistics.
Results
Seventeen subjects were identified with an average age at diagnosis of 58 years (range 26-76 years). The most common amyloid type on biopsy was immunoglobulin light chain (AL) subtype. The most common location of laryngeal amyloid at diagnosis was the glottis and disease was more likely to be bilateral at the time of diagnosis in this location. Supraglottic disease more often had a unilateral presentation and had a tendency to spread to additional laryngeal subsites. Nearly 25% of subjects had associated systemic disease, including multiple myeloma, auto-immune disease, and familial ATTR mutation.
Conclusions
The overall rate of associated systemic disease was low in our study cohort; however, it is higher than typically referenced in extant literature. Our cohort demonstrates that while laryngeal amyloidosis is a chronic condition, the behavior is generally indolent with a low treatment burden.
... Most cross-β aggregates are insoluble and are often almost irreversible. Thus, they are notorious as markers of neurodegenerative diseases (including Aβ fibrils in Alzheimer's disease, alpha-synuclein aggregates in Parkinson's disease, prions in Creutzfeldt-Jakob Disease and scrapie, and others [4,16,17]). Interestingly, as opposed to these pathogenic amyloids, there are also functional amyloids, in which cross-β aggregates are essential for function of proteins [18][19][20][21][22]. ...
Amyloid structures assemble through a repeating type of bonding called "cross-β", in which identical sequences in many protein molecules form β-sheets that interdigitate through side chain interactions. We review the structural characteristics of such bonds. Single cell force microscopy (SCFM) shows that yeast expressing Als5 adhesin from Candida albicans demonstrate the empirical characteristics of cross-β interactions. These properties include affinity for amyloid-binding dyes, birefringence, critical concentration dependence, repeating structure, and inhibition by anti-amyloid agents. We present a model for how cross-β bonds form in trans between two adhering cells. These characteristics also apply to other fungal adhesins, so the mechanism appears to be an example of a new type of cell-cell adhesion.
... Серьезной проблемой пожилых людей является спорадическая форма старческого (сенильного) системного амилоидоза, причиной развития которого являются транстиретин дикого типа (ATTRwt). Его обнаруживают 25% людей старше 80 лет [54] и у 90% старше 90 лет [58]. ...
... Частота встречаемости амилоидоза миокарда (%) в зависимости от возраста� График построен по данным Л�В� Козловской и др�[58]� ...
Amyloidosis is a pathological process caused by various environmental and hereditary etiological factors. It develops according to its own rules, regardless of the primary events that caused it. Systematization of information about amyloid disease epidemiology is a challenging task due to differences in the methods used for statistical analysis, the lack of a unified worldwide classification of this pathology, and differences in the description of this pathology by clinicians and pathologists. Despite a WHO classification of amyloidosis based on a pathogenetic principle, statistics on some amyloidosis cases are performed by individual nosological forms. Therefore, some amyloidosis cases are not included in statistical analyses. In general, this creates an incorrect impression that amyloidosis is much less common than it actually is.
The aim of this study is to analyze the available literature data on the epidemiology of amyloidosis in order to approximate the correct prevalence of this pathology.
Results. The published data on the epidemiology of amyloidosis, Alzheimer’s disease, AL- and AA-amyloidoses, LECT2 amyloidosis, hereditary amyloidoses, pharmacological amyloidosis, and narcotic drug induced amyloidosis were analyzed. Also the relationship of amyloidosis with age and sex was taken into account. Differences were identified in research methods for the epidemiology of amyloidosis that led to incompatible data. Since different authors use different methods for assessing the epidemiology of amyloidosis, data obtained in the same geographical area sometimes differed by an order of magnitude. Own classification of amyloidosis by origin is proposed for discussion. Since amyloidosis is not a diagnosis, but a pathological process, it is proposed to abandon the nosological principle of statistical accounting of amyloidosis cases in favor of the WHO pathogenetic classification.
Conclusion. There are no uniformly comparable data on the prevalence and incidence of amyloidosis. For this reason, mandatory staining with Congo red of biopsy and autopsy material for the presence of amyloid is required. It is also necessary to create a digital national registry of patients with amyloidosis and to develop methods for early lifetime diagnosis of amyloidosis, possibly based on proteomic analysis of blood plasma.
... AA amyloidosis is characterized by the extracellular tissue deposition of fibrils that are composed of fragments of and/or intact serum amyloid A protein (SAA), a hepatic acute phase reactant (4,5). Apart from the kidneys, which is the organ most commonly affected by systemic amyloidosis, involvement of the heart, the liver, the gastrointestinal tract and the peripheral nervous system should be considered. ...
... The optimal treatment strategy of AA amyloidosis includes control of the underlying inflammatory disease and complete suppression of SAA production (5). Similarly to C-reactive protein (CRP), SAA constitutes an acute-phase reactant synthesized by hepatocytes but also by other cells, including macrophages, endothelial cells, and smooth muscle cells, under the transcriptional regulation of proinflammatory cytokines, particularly tumor necrosis factor (TNF) alpha, interleukin-1 (IL-1) beta, and IL-6 (4, 6, 7). ...
Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.
... Optimalno lečenje pacijenata zahteva ranu dijagnozu (3). Najosetljivija metoda za potvrdu oboljenja je biopsija zahvaćenog organa, ali manje invazivne su biopsija kostne srži i potkožnog masnog tkiva, čemu se najčešće i pribegava (5). Za dokazivanje zahvaćenosti srca koristi se određivanje srčanih markera: B-natriuretskog peptida (engl. ...
... Amiloidoza lakih lanaca predstavlja najčešći tip stečene amiloidoze koja se javlja u adultnoj populaciji, prema literaturi često u uzrasnoj grupi 50 -60 godina. Prosečna starost naših ispitanika je iznosila 59 godina, što odgovara podacima iz literature (5)(6)(7)(8). U našoj studiji najčešće zahvaćeni organi su bubrezi i srce, zatim gastrointestinalni trakt, jetra, autonomni nervni sistem i perifireni nervni sistem, što se u potpunosti poklapa sa već poznatim podacima o učestalosti zahvaćenih organa (4)(5)(6)(7)(8). Imajući u vidu mali broj obolelih, svega 30 u periodu od januara 2012. ...
... Prosečna starost naših ispitanika je iznosila 59 godina, što odgovara podacima iz literature (5)(6)(7)(8). U našoj studiji najčešće zahvaćeni organi su bubrezi i srce, zatim gastrointestinalni trakt, jetra, autonomni nervni sistem i perifireni nervni sistem, što se u potpunosti poklapa sa već poznatim podacima o učestalosti zahvaćenih organa (4)(5)(6)(7)(8). Imajući u vidu mali broj obolelih, svega 30 u periodu od januara 2012. ...
Introduction: Light chain amyloidosis (AL) is a plasma cell neoplasia characterized by deposition of a pathological insoluble fibrillary protein, i.e. light chain immunoglobulin. Aim: To show clinical and laboratory characteristics of patients, course, treatment modalities, prognosis etc. Material and methods: A number of 30 newly diagnosed patients with AL amyloidosis were analyzed. Histopathological diagnosis was made by identifying Congo red positive deposits in the affected organs. Results: A number of 30 patients(pts) was analyzed, 21 male / 9 female, with average age of 59 years. Paraprotein was found in 26 (86.7%). The most frequent monoclonal protein was immunoglobulin light chain (14pts, 46.7%), Lambda isotope was more common (21pts, 70%). Organ involvement: heart (21pts, 70%), kidney (21pts, 70%), sub cutis (18pts, 60%), bone marrow (12pts, 40%), liver (7pts, 23.3%) and 9pts(30%) had unusual localization (lung, skin, uterus); 18pts (60%) had more than one parenchymal organ involved. Biomarkers of cardiac involvement: BNP in 8pts (26.7%), NTproBNP in 13pts (43.3%), and troponin 7pts (23.3). Elevation of LDH was found in 7pts (23.3%). Anemia was observed in 3 (10%) and thrombocytopenia in 1 pts (3.3%). With conventional chemotherapy 21pts(70%) were treated, bortezomib was applied in 9pts (30%). With ASCT was performed on 2pts (6.7%). Overall treatment response (ORR, ≥PR) was achieved in 21pts (70%). All pts treated with bortezomib based HT had treatment response (≥PR). In transplant ineligible patients, treatment modality did not affect PFS (Log Rank = 1.675, p = 0.196), but showed statistically significant effect on OS (Log Rank = 3.834, p = 0.05). Number of parenchymal organ involvement (1 vs. ≥ 2) did not show influence neither of PFS or OS (PFS: Log Rank = 0.017, p = 0.895; OS: Log Rank = 0.739, p = 0.390). Although the most important negative prognostic factor, cardiac involvement had no effect on OS (Log Rank = 2.480, p = 1.410). Conclusion: Heart involvement indicated a worse prognosis for patients. Bortezomib based protocols and HDT with ASCT are essential for maintaining long-term remission and improving OS.
... The most significant complication of FMF that may cause cardiac disease is secondary systemic AA amyloidosis [4] . Cardiac deposition of amyloid, which causes increased morbidity and mortality in FMF patients, may lead to cardiovascular mortality [5] . Cardiac manifestations related to FMF may genarally be associated with secondary AA amyloidosis. ...
KEY WORDS: cardiac, cardiac problem, familial mediterranean fever, MEFV gene, recurrent chest pain
... Most SAA in plasma is produced by hepatocytes under transcriptional regulation by cytokines, especially interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF). Its circulating concentration can rise from normal levels with an acute inflammatory stimulus and can remain persistently high in chronic inflammation [1][2][3]. ...
Secondary amyloid A (AA) amyloidosis is a late and serious complication of poorly controlled, chronic inflammatory diseases. Rheumatoid arthritis (RA) patients with poorly controlled, longstanding disease and those with extra-articular manifestations are under risk for the development of AA amyloidosis. Although new drugs have proven to be significantly effective in the treatment of secondary AA amyloidosis, no treatment modality has proven to be ideal. To date, only in small case series preliminary clinical improvement have been shown with rituximab therapy for AA amyloidosis secondary to RA that is refractory to TNF-α inhibitors (TNF-i) therapy. In these case series, we assessed the efficacy and safety of rituximab therapy for patients with RA and secondary amyloidosis. Hacettepe University Biologic Registry was developed at 2005. The data of the RA patients who were prescribed a biological drug were recorded regularly. Patients with biopsy proven AA amyloidosis patients were screened. Of 1022 RA patients under biologic therapy, 0.7% patients had clinically apparent histologically confirmed amyloidosis. Four of seven patients who were prescribed rituximab at least one infusion enrolled to those case series. Two of four patients showed significant clinical improvement and one of them also had decrease in proteinuria and the other one had stable renal function and proteinuria. The main goal for the treatment of AA amyloidosis is to control the activity of the underlying disorder. In this study, we showed that rituximab may be an effective treatment in RA patients with amyloidosis who were unresponsive to conventional disease modifying anti-rheumatic drugs (DMARDs) and/or TNFi.
