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Aims To evaluate different cardiovascular magnetic resonance (CMR) parameters for the differentiation of light chain amyloidosis (AL) and transthyretin-related amyloidosis (ATTR). Methods and results In total, 75 patients, 53 with cardiac amyloidosis {20 patients with AL [66 ± 12 years, 14 males (70%)] and 33 patients with ATTR [78 ± 5 years, 28 males (88%)]} were retrospectively analysed regarding CMR parameters such as T1 and T2 mapping, extracellular volume (ECV), late gadolinium enhancement (LGE) distribution patterns, and myocardial strain, and compared to a control cohort with other causes of left ventricular hypertrophy {LVH; 22 patients [53 ± 16 years, 17 males (85%)]}. One-way ANOVA and receiver operating characteristic analysis were used for statistical analysis. ECV was the single best parameter to differentiate between cardiac amyloidosis and controls [area under the curve (AUC): 0.97, 95% confidence intervals (CI): 0.89–0.99, P < 0.0001, cut-off: >30%]. T2 mapping was the best single parameter to differentiate between AL and ATTR amyloidosis (AL: 63 ± 4 ms, ATTR: 58 ± 2 ms, P < 0.001, AUC: 0.86, 95% CI: 0.74–0.94, cut-off: >61 ms). Subendocardial LGE was predominantly observed in AL patients (10/20 [50%] vs. 5/33 [15%]; P = 0.002). Transmural LGE was predominantly observed in ATTR patients (23/33 [70%] vs. 2/20 [10%]; P < 0.001). The diagnostic performance of T2 mapping to differentiate between AL and ATTR amyloidosis was further increased with the inclusion of LGE patterns [AUC: 0.96, 95% CI: (0.86–0.99); P = 0.05]. Conclusion ECV differentiates cardiac amyloidosis from other causes of LVH. T2 mapping combined with LGE differentiates AL from ATTR amyloidosis with high accuracy on a patient level. [ABSTRACT FROM AUTHOR]

Background: AA amyloidosis is a multisystem disease characterized by the deposition of serum amyloid A protein, which is secondary to chronic inflammation. Tocilizumab (an interleukin-6 inhibitor monoclonal antibody) was effective in suppressing inflammation, normalizing serum amyloid A protein levels, and inducing remission in patients with amyloidosis. Recently, tocilizumab treatment has been associated with the disappearance of amyloid deposits. Case presentation: A 61-year-old woman was referred to our hospital in 2011 due to oligoarthritis of both knees and elevation of acute-phase reactants. Corticosteroids and methotrexate were prescribed for the possibility of polymyalgia rheumatica, without clinical response. Two years later, the patient presented with foamy urine, nocturia, sweating, and dizziness. An elevated C-reactive protein (CRP), erythrocyte sedimentation rate, and nephrotic-range proteinuria were found. Autoantibodies and complements levels were normal. No signs of acute infections or cardiovascular disease were evidenced and amyloidosis was suspected. Rectal and oral mucosa biopsies were performed and amyloid AA deposits were detected in both. Magnetic resonance imaging (MRI) of the right knee showed arthropathy due to amyloid deposition. Intravenous monthly tocilizumab was prescribed with rapid improvement of CRP, proteinuria, and nephrotic syndrome symptoms. Arthritis also improved significantly. Two years later, a new biopsy of the rectal mucosa did not show amyloid deposits and the right knee MRI was normal, without evidence of amyloid synovitis. In 2017, isotopic synoviorthesis of both knees was performed due to repeated episodes of arthritis. Eight years after the start of Tocilizumab, the patient continues treatment and remains clinically stable, with no evidence of recurrence. Conclusions: Tocilizumab treatment controls chronic inflammatory disease and improves symptoms of AA amyloidosis. According to the latest evidence, long-term treatment with tocilizumab may remove amyloid deposits from tissues, leading to a definitive cure for this disease. To our knowledge, this is the first case of regression of amyloid deposits both in biopsy and magnetic resonance after treatment with tocilizumab. [ABSTRACT FROM AUTHOR]

Background: Ankylosing spondylitis (AS) is a chronic inflammatory condition primarily affecting the spine and sacroiliac joints, often associated with human leukocyte antigen B27 (HLA-B27) positivity. While musculoskeletal symptoms are typical manifestations, AS can also lead to systemic complications, including secondary systemic amyloidosis (SSA), also known as Amyloid A (AA) amyloidosis, involving multiple organs. Case presentation: We present a case of a 45-year-old Asian male with a complex medical history, including diabetes and hypertension, who developed AS complicated by SSA. The patient exhibited a diverse range of symptoms, including cardiac, renal, gastrointestinal, and musculoskeletal manifestations. He reported shortness of breath on exertion, orthopnea, pedal edema, generalized weakness, back pain, neck pain, low-grade fever, decreased appetite, frothy urine, and significant weight loss over the past year. Diagnostic evaluations revealed HLA-B27 positivity and histologically confirmed AA amyloidosis, providing a comprehensive understanding of the systemic involvement. Conclusion: This case report highlights the intricate interplay between AS and SSA, particularly AA amyloidosis, with a focus on its systemic impact beyond musculoskeletal symptoms. The tragic outcome, marked by severe cardiac involvement, underscores the challenges in managing such complex cases. This report emphasizes the importance of early diagnosis and treatment of AS to prevent severe complications, along with vigilant monitoring and individualized treatment plans, as well as the need for further research to enhance our understanding and improve management strategies for AS-related amyloidosis. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe the clinical spectrum of primary localized bladder amyloidosis (PLBA), its management options, outcomes, and follow-up. We retrospectively reviewed our medical records for patients with PLBA between April 2013 and April 2021. Patient's demographics, imaging, cystoscopic characteristics, treatment, and outcomes were recorded and analyzed. Serum and urine electrophoresis, abdominal fat aspiration, and rectal biopsy results where available were also recorded. We identified 20 patients with PLBA with a median age of 56 years. Hematuria (80%) was the most common symptom followed by irritative lower urinary tract symptoms (iLUTS) (50%). The bladder lesions were focal, multiple, and diffuse in 4 (20%), 14 (70%), and 2 (10%) patients, respectively. All patients had transurethral resection of the bladder tumor, except for 4 patients with exclusive iLUTS who had cold cup biopsy. At a median follow-up of 43.9 months, 4 patients (20%) developed recurrence with median time to recurrence being 19 months. All the recurrences were managed endoscopically by re-resection and none of the patients required radical surgery. PLBA is a rare entity with varied clinical presentations. Although histologically benign, recurrences can occur and require long-term cystoscopic surveillance. [ABSTRACT FROM AUTHOR]

Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow tract obstruction and is commonly associated with an underlying hypercoagulable state. Systemic amyloidosis is a disorder characterized by systemic deposition of misfolded proteins leading to end organ damage. Amyloidosis is commonly associated with coagulation abnormalities, mainly leading to increased bleeding diathesis. Here, we report a case of amyloid light chain (AL) amyloidosis presenting as BCS. A 40-year-old man presented with abdominal distension along with anorexia and weight loss. On evaluation, he had severe hypoalbuminemia, raised alkaline phosphatase, and non-visualization of hepatic veins on abdominal imaging. Further evaluation confirmed the diagnosis of AL amyloidosis with renal, cardiac, and hepatic involvement. AL amyloidosis rarely can present with BCS. A high index of suspicion is needed as symptoms can be variable and non-specific. [ABSTRACT FROM AUTHOR]

Secondary amyloidosis may complicate inherited dermatoses, but recessive dystrophic epidermolysis bullosa (RDEB) complicated by renal amyloidosis is rare. We report a case of a 12-year-old male child with RDEB presenting with progressive generalized anasarca for 20 days. Kidney biopsy showed diffuse expansion of mesangial matrix by pale acellular Periodic Acid-Schiff (PAS)-negative amorphous material, which was congophilic on Congo red stain and gave apple green birefringence on polarization and extending along the glomerular basement membrane, suggestive of amyloidosis. Genetic analysis showed a compound heterozygous pathogenic variant in the COL7A1 gene with autosomal recessive inheritance. [ABSTRACT FROM AUTHOR]

Amyloidosis can affect any organ in the body by deposition of amyloid fibrils. When these aggregate in the heart, it leads to cardiac amyloidosis a life-threatening and progressive disease. Although considered a rare condition, advances in imaging techniques and raised awareness have shown that it might be more frequent than has been historically estimated. Cardiac amyloidosis can be hereditary or occur as a consequence of the ageing process but, regardless of type, patients experience a heavy symptomatic burden. This article provides an overview of its pathophysiology, signs and symptoms and how any nurse can look for the main red flags in clinical practice. Early referral for specialist care can have a significant impact on disease progression and patient quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite a lack of standardization and some open questions, a growing body of evidence supports the use of frailty to optimize the clinical management of patients with hematological malignancies. Several scores have been applied particularly to multiple myeloma, an entity that shares many characteristics with AL amyloidosis, both being frequently associated. To date, no study has focused on frailty in patients with AL amyloidosis. We aimed to define a practical evaluation of frailty and estimate its impact in survival in patients with systemic AL amyloidosis. Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. ≥2) and NT-proBNP (<8500 vs. ≥8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. Multivariate analysis showed that the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario. [ABSTRACT FROM AUTHOR]

Primary mesenteric and/or retroperitoneal amyloidosis is a rare entity with only few cases described in literature. Herein we describe an unusual such case in a 56-year-old man who presented with long-standing vague abdominal pain and lump. Abdominopelvic CT revealed numerous nodular variably calcifying deposits that were diffusely involving the mesenteric and retroperitoneal fat. Resected specimen pathology showed extracellular amyloid deposits replacing the adipocytes that were congophilic and exhibited apple green birefringence under polarized light. Kappa light chain restriction was noted in amyloid deposits on immunohistochemical studies. Myeloma studies did not reveal any significant abnormality. In view of the primary AL amyloidosis, the patient was started on cyclophosphamide, thalidomide, and dexona (CTD regimen). The patient responded well to the treatment with no further progression of the lesions. After 7 years of follow-up, the patient is alive with no systemic complications. [ABSTRACT FROM AUTHOR]

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Amyloidosis is characterized by the extracellular accumulation of abnormal fibrillar proteins in various tissue and organs of the body. Systemic or localized involvement can be seen in various organs, often depending on the underlying disease such as plasma cell myeloma or chronic inflammatory and autoimmune diseases. Amyloid deposition in the breast is rare and may present similar appearance to areas of fat necrosis with fibroelastotic stromal changes in the breast. The amyloid tumor in the breast presented in a 49-year-old female patient diagnosed with multiple sclerosis is a good example of this. Therefore, since amyloid deposition in the breast is an entity that should be kept in mind, the case was deemed worth presenting. [ABSTRACT FROM AUTHOR]

Objective: To describe a 41‐year‐old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin‐1 receptor antagonist (IL‐1Ra) protein, anakinra, since the age of 28, who presented with golf‐ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation. Methods: Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo‐red staining and proteomic evaluation of microdissected Congo red–positive amyloid deposits by liquid chromatography‐tandem mass spectrometry. Results: The skin, stomach, and kidney biopsies all showed the presence of Congo red–positive amyloid deposits. Mass spectrometry‐based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL‐1Ra protein)‐type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P‐component) and the amyloidogenic IL‐1Ra protein, which were present in Congo red–positive areas and absent in Congo red–negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL‐1Ra (anakinra) and not endogenous wild‐type IL‐1Ra. Conclusion: This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra). [ABSTRACT FROM AUTHOR]

A 45-year-old man presented with an isolated sciatic mononeuropathy, which then evolved into a lumbosacral radiculoplexus neuropathy. His initial symptoms included lower limb pain, sensory disturbance and later weakness, without autonomic dysfunction. Neurophysiology suggested a postganglionic neuropathy. MR and ultrasound scans of the thighs showed right sciatic nerve thickening, and CSF analysis showed albuminocytological dissociation. Fluorodeoxyglucose positron emission tomography (FDG PET) was unremarkable. He then developed orthostatic symptoms and urinary disturbance, and was found to have an IgM paraprotein. Fat aspirate, cardiac and wholebody imaging found no amyloid deposition, and genetic testing for transthyretin amyloidosis was negative. A bone marrow biopsy was unremarkable. However, neuropathology review of a proximal, fascicular nerve biopsy identified a lambda chain-restricted plasma cell population with positive Congo red staining, leading to a diagnosis of peripheral nerve restricted amyloid light amyloidosis. We discuss the diagnostic approach to this case from the perspectives of neurology, neurophysiology, radiology and neuropathology. [ABSTRACT FROM AUTHOR]

Nuclear imaging techniques can detect and quantify pathophysiological processes underlying heart failure, complementing evaluation of cardiac structure and function with other imaging modalities. Combined imaging of myocardial perfusion and metabolism can identify left ventricle dysfunction caused by myocardial ischaemia that may be reversible after revascularization in the presence of viable myocardium. High sensitivity of nuclear imaging to detect targeted tracers has enabled assessment of various cellular and subcellular mechanisms of heart failure. Nuclear imaging of active inflammation and amyloid deposition is incorporated into clinical management algorithms of cardiac sarcoidosis and amyloidosis. Innervation imaging has well-documented prognostic value with respect to heart failure progression and arrhythmias. Emerging tracers specific for inflammation and myocardial fibrotic activity are in earlier stages of development but have demonstrated potential value in early characterization of the response to myocardial injury and prediction of adverse left ventricular remodelling. Early detection of disease activity is a key for transition from broad medical treatment of clinically overt heart failure towards a personalized approach aimed at supporting repair and preventing progressive failure. This review outlines the current status of nuclear imaging in phenotyping heart failure and combines it with discussion on novel developments. [ABSTRACT FROM AUTHOR]

Aim: Neuropathy is a frequent complication of Waldenström's macroglobulinemia (WM), the most common being a demyelinating polyneuropathy with anti‐myelin associated glycoprotein (MAG) antibodies, but also cryoglobulins, vasculitis, neurolymphomatosis, and amyloidosis. We describe a patient with IgM/kappa WM who presented with a severe, not length‐dependent, peripheral neuropathy as clinical onset of IgM/kappa‐related amyloidosis. Methods: A 69‐year‐old woman came to our attention for weight loss, gait imbalance and sensory loss at upper limbs. In her medical history, she was in hematological follow‐up for WM, and had undergone left carpal tunnel release. At neurological evaluation she had weakness and loss of sensation at upper limbs up to the elbows, more at the left side, gait was unsteady with right foot drop. Hypotrophy and areflexia were present at four limbs. Sensory loss and vibration sense were dramatically reduced. She underwent extensive diagnostic workup. Results: Laboratory workup revealed an IgM/kappa monoclonal paraprotein of 16 g/L and increased NT‐proBNP; anti‐MAG antibodies were absent. Bone marrow biopsy demonstrated a population of neoplastic B‐lymphocytes. Total‐body CT scan and echocardiogram were negative. Neurophysiology revealed a symmetric, no length dependent sensory‐motor polyneuropathy Periumbilical fat biopsy was positive for amyloid. Sural nerve biopsy detected amyloid in the wall of an epineurial vein. Conclusions: This case report describes a rare and unusual manifestation of IgM‐related AL amyloidosis in WM. The patient presented with a subacute clinically asymmetric neuropathy with no pain or dysautonomic features as clinical onset of IgM/kappa‐related amyloidosis. Sural nerve biopsy was crucial for the diagnosis. [ABSTRACT FROM AUTHOR]

Despite significant progress and improving outcomes in the management of plasma cell disorders, AL amyloidosis remains diagnostically and therapeutically challenging for clinicians across practice settings. There is, however, a reason for optimism with the advent of new combination therapy approaches and novel targets offering the promise of improvement in end organ function, survival, and quality of life. This review offers a clinically applicable overview of an approach to diagnosis, risk stratification, and clinical management of AL amyloidosis in an era of rapid therapeutic innovation. [ABSTRACT FROM AUTHOR]

Muscle involvement represents a well-recognized but rare manifestation of amyloidosis. Here, we report a 40-year-old female who presented with muscle weakness, musculoskeletal pain, and proteinuria, which was eventually diagnosed as myopathic amyloidosis based on muscle biopsy results. A multidisciplinary approach appears to be the cornerstone of the diagnostic work up for recognizing the unusual amyloid myopathy. [ABSTRACT FROM AUTHOR]

The characteristics of patients with pleural amyloidosis (PA) are poorly known. A systematic review was performed of studies reporting clinical findings, pleural fluid (PF) characteristics, and the most effective treatment of PA. Case descriptions and retrospective studies were included. The review included 95 studies with a total sample of 196 patients. The mean age was 63 years, male/female ratio was 1.6:1, and 91.9% of patients were >50 years. The most common symptom was dyspnea (88 patients). PF was generally serious (63%), predominantly lymphocytic, and with the biochemical characteristics of transudates (43.4%) or exudates (42.6%). Pleural effusion was generally bilateral (55%) and <1/3 of the hemithorax (50%), although in 21% pleural effusion (PE) exceeded 2/3. Pleural biopsy was performed in 67 patients (yield: 83.6%; 56/67) and was positive in 54% of exudates and 62.5% of unilateral effusions. Of the 251 treatments prescribed, only 31 were effective (12.4%). The combination of chemotherapy and corticosteroids was effective in 29.6% of cases, whereas talc pleurodesis was effective in 21.4% and indwelling pleural catheter in 75% of patients (only four patients). PA is more frequent in adults from 50 years of age. PF is usually bilateral, serous, and indistinctly a transudate or exudate. A pleural biopsy can aid in diagnosis if effusion is unilateral or an exudate. Treatments are rarely effective and there may be definitive therapeutic options for PE in these patients. [ABSTRACT FROM AUTHOR]

The article describes the case of an 83-year-old Hispanic female with hypertension, type 2 diabetes mellitus, hyperlipidemia, and hypothyroidism who underwent a screening mammogram which yielded posterior grouped heterogeneous and amorphous calcifications. The patient was referred to hematology for workup of systemic light chain (AL) amyloidosis versus possible myeloma. A discussion on amyloidosis of the breast is discussed.

Immunoglobulin light chain (AL) amyloidosis is the most common type of systemic amyloidosis in China and is associated with increased morbidity and a poor prognosis. However, the clinical characteristics of Chinese patients with AL amyloidosis have not been systematically investigated. This scoping review aimed to summarize the available literature regarding the clinical characteristics of patients with AL amyloidosis and identify potential knowledge gaps. We searched three electronic databases from inception to 7 February 2021. PICOS (Patient, Intervention, Comparison, Outcome and Study) design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R (version 3.6.0). Sixty-seven articles with 5022 patients were included. Results suggest Chinese patients were younger (57 years) at the time of diagnosis when compared with other patient populations and were predominantly male (61.2%). The time interval from the onset of symptoms to diagnosis was between 6 and 12 months. It was found that 41.1% of Chinese patients with AL amyloidosis were diagnosed with an advanced stage III disease when diagnosed, and 20.2% had a concurrent disease. The most involved organs were the kidneys (84.3%) and the heart (62.5%). In conclusion, our study shows some similarities and differences with other studies on the clinical characteristics of Chinese patients with AL amyloidosis, including the age at diagnosis, Mayo stage, and organ involvement. However, a nationwide epidemiological investigation is still needed to provide a comprehensive overview of this patient population in China. [ABSTRACT FROM AUTHOR]

Systemic light chain (AL) amyloidosis is caused by an usually small B cell clone that produces a toxic light chain forming amyloid deposits in tissue. The heart and kidney are the major organs affected, but all others, with the exception of the CNS, can be involved. The disease is rapidly progressive, and it is still diagnosed late. Screening programs in patients followed by hematologists for plasma cell dyscrasias should be considered. The diagnosis requires demonstration in a tissue biopsy of amyloid deposits formed by immunoglobulin light chains. The workup of patients with AL amyloidosis requires adequate technology and expertise, and patients should be referred to specialized centers whenever possible. Stagings are based on cardiac and renal biomarkers and guides the choice of treatment. The combination of daratumumab, cyclophosphamide, bortezomib and dexamethasone (dara-CyBorD) is the current standard of care. Autologous stem cell transplant is performed in eligible patients, especially those who do not attain a satisfactory response to dara-CyBorD. Passive immunotherapy targeting the amyloid deposits combined with chemo-/immune-therapy targeting the amyloid clone is currently being tested in controlled clinical trials. Response to therapy is assessed based on validated criteria. Profound hematologic response is the early goal of treatment and should be accompanied over time by deepening organ response. Many relapsed/refractory patients are also treated with daratumumab combination, but novel regimens will be needed to rescue daratumumab-exposed subjects. Immunomodulatory drugs are the current cornerstone of rescue therapy, while immunotherapy targeting B-cell maturation antigen and inhibitors of Bcl-2 are promising alternatives. [ABSTRACT FROM AUTHOR]

Although oral manifestations of amyloidosis are rare, it is important to exclude systemic involvement in patients who present with amyloidosis involving the oral cavity. Improved understanding of the oral manifestations of amyloidosis and the additional investigations required can lead to timely diagnosis and subsequent management. Treatment of localized forms of amyloidosis include resection, biologics, laser therapy and corticosteroids. [ABSTRACT FROM AUTHOR]

Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life-threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis. Delays in diagnosis and treatment remain the greatest challenge, necessitating physician awareness of the common clinical presentations that suggest amyloidosis. The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light-chain (AL) amyloidosis. While systemic AL amyloidosis was previously considered a death sentence with no effective therapies, significant improvement in patient survival has occurred over the past 2 decades, driven by greater understanding of the disease process, riskadapted adoption of myeloma therapies such as proteosome inhibitors (bortezomib) and monoclonal antibodies (daratumumab) and improved supportive care. ATTR amyloidosis is an underdiagnosed cause of heart failure. Technetium scintigraphy has made noninvasive diagnosis much easier, and ATTR is now recognised as the most common type of amyloidosis because of the increased identification of age-related ATTR. There are emerging ATTR treatments that slow disease progression, decrease patient hospitalisations and improve patient quality of life and survival. This review aims to update physicians on recent developments in amyloidosis diagnosis and management and to provide a diagnostic and treatment framework to improve the management of patients with all forms of amyloidosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Monoclonal gammopathy of clinical significance (MGCS) refers to a recently coined term describing a complex and heterogeneous group of nonmalignant monoclonal gammopathies. These patients are characterized by the presence of a commonly small clone and the occurrence of symptoms that may be associated with the clone or with the monoclonal protein through diverse mechanisms. This is an evolving, challenging, and rapidly changing field. Patients are classified according to the key organ or system involved, with kidneys, skin, nerves, and eyes being the most frequently affected. However, multiorgan involvement may be the most relevant clinical feature at the presentation or during the course. This review delves into the definition, history, differential diagnosis, classification, prognosis, and treatment of this group of entities by analyzing the evidence accumulated to date from a critical perspective. Monoclonal gammopathies of clinical significance (MGCSs) represent a group of diseases featuring the association of a nonmalignant B cells or plasma cells clone, the production of an M-protein, and singularly, the existence of organ damage. They present a current framework that is difficult to approach from a practical clinical perspective. Several points should be addressed in order to move further toward a better understanding. Overall, these entities are only partially included in the international classifications of diseases. Its definition and classification remain ambiguous. Remarkably, its real incidence is unknown, provided that a diagnostic biopsy is mandatory in most cases. In fact, amyloidosis AL is the final diagnosis in a large percentage of patients with renal significance. On the other hand, many of these young entities are syndromes that are based on a dynamic set of diagnostic criteria, challenging a timely diagnosis. Moreover, a specific risk score for progression is lacking. Despite the key role of the clinical laboratory in the diagnosis and prognosis of these patients, information about laboratory biomarkers is limited. Besides, the evidence accumulated for many of these entities is scarce. Hence, national and international registries are stimulated. In particular, IgM MGCS deserves special attention. Until now, therapy is far from being standardized, and it should be planned on a risk and patient-adapted basis. Finally, a comprehensive and coordinated multidisciplinary approach is needed, and specific clinical trials are encouraged. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine femoral cartilage thickness (FCT) in patients with familial Mediterranean fever (FMF) and healthy individuals and to assess the relationship of FCT with the development of amyloidosis and clinical features. Methods: Patients diagnosed with FMF according to the Tel-Hashomer criteria and healthy controls were included in the study. FCT of both knees was measured with a 7-12 MHz linear probe in maximum knee flexion. Three midpoint measurements were obtained from each knee: Lateral femoral condyle (LFC), intercondylar area (ICA), and medial femoral condyle (MFC). The patients' clinic characteristics include disease duration, medications, comorbid conditions, amyloidosis, chronic renal failure (CRF), FMF gene mutation, arthritis, sacroiliitis, PRAS score, and Physical Activity Questionnaire Short Form score were recorded. Results: A total of 46 patients with FMF (36 women) and 20 age-sex-body mass index-matched controls (14 women) were enrolled in this study. The patients and controls' mean age were 37±12.9 and 37.5±8.6 years, respectively. Amyloidosis occurred in 7 patients (15.2%), CRF in 3 (6.5%), and knee arthritis in 8 (17%). Disease activity was mild in 55.8%, moderate in 20.9%, and severe in 23.23% of the patients. The mean FCT in millimeter values in the FMF and control groups was as follows: On the right side, LFC 1.9±0.5 and 2±0.52, ICA 2.2±0.77 and 2.25±0.97, and MFC 2±0.47 and 2.25±0.72; on the left side, LFC 1.9±0.4 and 2.05±0.55, ICA 2.25±0.87 and 2.25±0.87, and MFC 1.85±0.5 and 2.25±0.6. Patients with FMF had decreased cartilage thickness at the lateral condyle of both knees (p<0.05) and medial condyle of the left knee (p<0.05) compared with controls. FCT measurements were similar in patients with or without arthritis, amyloidosis, and CRF (p>0.05). FCT scores were not different among the disease activity groups (p>0.05). Conclusion: These findings suggest that patients with FMF have decreased FCT compared with controls, and there is no significant relationship between the FCT and amyloidosis and disease activity. [ABSTRACT FROM AUTHOR]

The perspective on cardiac amyloidosis has deeply changed over the last 10 years following major advances in diagnosis and treatment options. This heterogeneous disease requires the interaction among experts of different specialties and subspecialties. Suspicion of disease, timely recognition and confirmation of final diagnosis, prognostic stratification, overall management and therapeutic strategies represent ongoing challenges in the clinical setting. Missing or delayed diagnosis may have significant impact on patient outcome, especially in light-chain amyloidosis. The present inter-society consensus document aims to provide a standardized approach to the diagnosis of cardiac amyloidosis in Italy, and to discuss the challenging clinical scenarios encountered in routine activity for cardiologists and physicians of different specialties dealing with patients with suspected or established cardiac amyloidosis. This document may be adapted to the setting of each specific region.

The ISA Nomenclature Committee met at the XIX International Symposium of Amyloidosis in Rochester, MN, 27 May 2024. The in-person event was followed by many electronic discussions, resulting in the current updated recommendations. The general nomenclature principles are unchanged. The total number of human amyloid fibril proteins is now 42 of which 19 are associated with systemic deposition, while 4 occur with either localised or systemic deposits. Most systemic amyloidoses are caused by the presence of protein variants which promote misfolding. However, in the cases of AA and ATTR the deposits most commonly consist of wild-type proteins and/or their fragments. One peptide drug, previously reported to create local iatrogenic amyloid deposits at its injection site, has been shown to induce rare instances of systemic deposition. The number of described animal amyloid fibril proteins is now 16, 2 of which are unknown in humans. Recognition of the importance of intracellular protein aggregates, which may have amyloid or amyloid-like properties, in many neurodegenerative diseases is rapidly increasing and their significance is discussed.

Cardiac Amyloidosis (CA) occurs when misfolded proteins accumulate in the heart muscle, leading to restrictive cardiomyopathy and possibly escalating to heart failure, impaired conduction system function, and sudden cardiac arrest. It is a significant clinical challenge due to its high rates of underdiagnosis and misdiagnosis. Research indicates that about 35% of individuals with CA have been incorrectly diagnosed with other prevalent cardiovascular diseases. CA is differentiated into various subtypes depending on the protein involved in its pathogenesis, with Transthyretin Amyloidosis (ATTR) and Light Chain Amyloidosis (AL) being the most common. A key diagnostic challenge is the subtle clinical presentation of CA, which often resembles other heart conditions such as restrictive cardiomyopathy with left ventricular hypertrophy or hypertrophic obstructive cardiomyopathy (HOCM). While several diagnostic methods are available for CA, many are expensive, invasive, and typically used after an initial clinical suspicion. Non-invasive tests like electrocardiography (ECG) are accessible but often have lower sensitivity in detecting CA. Given the limited expertise in recognizing CA symptoms in primary care settings, there is an urgent need for systems that can aid in early detection. It is crucial to develop systems that equip primary care providers with the tools and knowledge to recognize the subtle signs of cardiac amyloidosis, thereby enhancing patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Diagnosis of cardiac amyloidosis (CA) is often delayed due to variability in clinical presentation. The electrocardiogram (ECG) is one of the most common and widely available tools for assessing cardiovascular diseases. Artificial intelligence (AI) models analyzing ECG have recently been developed to detect CA, but their pooled accuracy is yet to be evaluated., Methods: We searched the Scopus, MEDLINE, and Cochrane CENTRAL databases until April 2024 for studies assessing AI-enhanced ECG diagnosis of CA. Studies reporting findings from derivation and validation cohorts were included. Studies combining other diagnostic modalities, such as echocardiography, were excluded. The outcome of interest was the area under the receiver operating characteristic curve (AUC) for overall CA and subtypes transthyretin amyloidosis (ATTR) and light chain amyloidosis (AL). Analysis was done using RevMan 5.4.1 general inverse variance random effects model, pooling data for AUC and 95 % confidence intervals (CI)., Results: Five studies comprising seven cohorts met the eligibility criteria. The total derivation and validation cohorts were 8,639 and 3,843, respectively, although one study did not describe this data. The AUC was 0.89 (95 % CI, 0.86-0.91) for cardiac amyloidosis, 0.90 (95 % CI, 0.86-0.95) for ATTR amyloidosis, and 0.80 (95 % CI, 0.80-0.93) for AL amyloidosis., Conclusion: AI-enhanced ECG models effectively detect CA and may provide a valuable tool for the early detection and intervention of this disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by the deposition of amyloid fibrils in the myocardium, presenting primarily as transthyretin cardiac amyloidosis (ATTR) and immunoglobulin light chain cardiac amyloidosis (AL). ATTR is further classified into wild-type (ATTRwt) and hereditary (ATTRv) based on transthyretin gene mutation. The disease is increasingly recognized as a significant cause of heart failure. Advances in diagnostic modalities, including electrocardiography, echocardiography, cardiac magnetic resonance imaging, and technetium pyrophosphate scintigraphy, have revolutionized the non-invasive diagnosis of CA. While ATTR can often be diagnosed with scintigraphy, AL typically requires histological confirmation. This review explores these diagnostic tools, emphasizing their role in early detection and quantification of disease burden, which are crucial for timely treatment and prognostication. This comprehensive overview aims to aid clinicians in efficiently diagnosing CA, ultimately improving patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Reliable typing of amyloid is essential. Amyloid extraction from tissue enables immunochemical typing of the precursor protein using an enzyme-linked immunosorbent assay (ELISA)., Objective: To assess the diagnostic accuracy of a panel of ELISAs for typing the four main types (AA, ATTR, AL-kappa and AL-lambda amyloid)., Methods: From 1996 to 2023 subcutaneous abdominal fat tissue aspirates were obtained from 1339 amyloidosis patients and 868 controls. Amyloid was visually graded 0-4+ in Congo red-stained smears. Amyloid extracted from tissue by Guanidine was typed using a panel comprising four ELISAs., Results: All amyloid protein concentrations in extracts correlated with amyloid grade in smears. Typing sensitivity was low (23.3%) in samples with grade 1+/2+ amyloid. Overall typing sensitivity of the panel was 81.6% for all easily visible amyloid (grade 3+/4+): high for AA (98.8%) and ATTR (96.8%) and fair for AL-kappa (66.7%) and AL-lambda (75.9). Overall typing specificity was 98.0% and the overall positive predictive value was 98.0%., Conclusions: We describe a highly specific ELISA panel for routine typing of the main amyloid types in fat tissue. Until more sensitive typing techniques will become generally available, typing easily visible amyloid in fat tissue using this ELISA panel is reliable, affordable and straightforward.

Amyloid myopathy often occurs in the context of systemic amyloidosis, as a rare manifestation of "light chain" (AL) amyloidosis, accounting for 1% of its incidence. A 58-year-old man with two years history of weakness and edema of lower extremity, elevated creatine kinase (CK), and inflammatory lesions from muscle biopsy which was misdiagnosed as inflammatory myopathy. After immunotherapy, the original symptoms worsened. We later confirmed the disease through MRI, Congo red staining and bone marrow puncture results. Our purpose is that to increase awareness of amyloid myopathy to minimize the risk of misdiagnosis and emphasize the importance of Congo red staining in diagnosing similar conditions., Competing Interests: Declarations. Ethics approval and consent to participate: The study involved human participants and was reviewed and approved by the Ethics Committee of Tongji Hospital of Huazhong University of Science and Technology. Patients provided written informed consent to participate in the study and to publish any potentially identifiable images or data contained in this article. Consent for publication: Written informed consent for publication was obtained from the patients and there legal guardians for publication of identifying information and images in an online open-access publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Current approaches for cardiac amyloidosis (CA) identification are time-consuming, labor-intensive, and present challenges in sensitivity and accuracy, leading to limited treatment efficacy and poor prognosis for patients. In this retrospective study, we aimed to leverage machine learning (ML) to create a diagnostic model for CA using data from routine blood tests. Our dataset included 6,563 patients with left ventricular hypertrophy, 261 of whom had been diagnosed with CA. We divided the dataset into training and testing cohorts, applying ML algorithms such as logistic regression, random forest, and XGBoost for automated learning and prediction. Our model's diagnostic accuracy was then evaluated against CA biomarkers, specifically serum-free light chains (FLCs). The model's interpretability was elucidated by visualizing the feature importance through the gain map. XGBoost outperformed both random forest and logistic regression in internal validation on the testing cohort, achieving an area under the curve (AUC) of 0.95 (95%CI: 0.92-0.97), sensitivity of 0.92 (95%CI: 0.86-0.98), specificity of 0.95 (95%CI: 0.94-0.97), and an F1 score of 0.89 (95%CI: 0.85-0.92). Its performance was also superior to the serum FLC-kappa and FLC-lambda combination (AUC of 0.88). Furthermore, XGBoost identified unique biomarker signatures indicative of multisystem dysfunction in CA patients, with significant changes in eGFR, FT3, cTnI, ANC, and NT-proBNP. This study develops a highly sensitive and accurate ML model for CA detection using routine clinical laboratory data, effectively streamlining diagnostic procedures, and providing valuable clinical insights and guiding future research into disease mechanisms., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Early diagnosis of cardiac amyloidosis (CA) is crucial due to the promising effect of disease-modifying treatment. This calls for screening strategies to identify CA patients with so-called "red flags", such as carpal tunnel syndrome (CTS)., Objectives: This study aims to assess Troponin-T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) as predictors for CA in patients with a history of surgery for bilateral carpal tunnel syndrome, a population suitable for systematic screening., Methods: Subjects with a history of surgery for bilateral CTS 5-15 years prior, identified using national registries were investigated for CA as per international recommendations. Sensitivity, specificity, positive and negative predictive values were assessed, and receiver operating curves were generated using logistic regression., Results: Among the 250 participants, 12 were diagnosed with CA, all with wild-type transthyretin amyloidosis. Elevated TnT levels (≥13 ng/L) were found in all CA patients and 25.6% (±2.8) of non-CA patients. The negative predictive value (NPV) of TnT <13 ng/L was 100%. For NT-ProBNP the NPV was 99.1% when age dependent cutoff levels were used. A combination of both biomarkers yielded an NPV of 99.1% and sensitivity of 99.7%. Early disease (Mayo or NAC stage 1) was found in 83% of identified patients with CA., Conclusion: This study demonstrates the utility of TnT and NT-ProBNP as negative predictors to exclude CA in a screening population with a history of surgery for CTS., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cardiac amyloidosis is a disease characterised by the accumulation of amyloid protein in the heart tissue. There are several types of amyloidosis, but the most common types affecting the heart are ATTR amyloidosis (caused by transthyretin protein) and AL amyloidosis (caused by abnormal immunoglobulin light chains). Cardiac amyloidosis causes typical signs and symptoms of heart failure. Diagnosis involves a combination of imaging tests such as echocardiography and cardiac magnetic resonance imaging, as well as nuclear imaging scans and tissue biopsies to confirm the presence of amyloid deposits in the heart. Treatment of cardiac amyloidosis depends on the type and severity of the disease and includes medications to manage symptoms as well as treatments targeting the underlying cause of amyloidosis. Importantly, cardiac amyloidosis is a serious condition requiring specialised care from a multidisciplinary team including cardiologists and haematologists as well as other specialists familiar with the management of this rare disease. This is crucial, as early diagnosis and treatment are important for improving outcomes.

Background: Wild-type and hereditary transthyretin-mediated amyloidosis (ATTRwt and ATTRv amyloidosis, respectively) are progressive, fatal diseases with a broad range of clinical presentations and multisystem effects. Despite having a higher prevalence, ATTRwt amyloidosis is less well characterized due to its non-hereditary nature, and its relatively poorer disease awareness delays diagnosis. Understanding of its natural history has evolved in recent years, but this is largely based on physician-collected data rather than patients' reports of their own experiences. A mixed methods approach was used to evaluate how the healthcare journeys of patients with ATTRv and ATTRwt amyloidosis compare., Methods: A quantitative survey was administered to US-patients diagnosed with both ATTRwt amyloidosis and ATTRv amyloidosis identified through a patient support group. Subsequent in-depth interviews with participants with ATTRwt amyloidosis were conducted. Quantitative data with related qualitative quotes from patients were produced to characterize their paths to diagnosis and the disease burden experienced., Results: A total of 47 respondents completed the survey (ATTRv, n = 20 and ATTRwt, n = 27) and a total of 14 survey respondents with ATTRwt amyloidosis were interviewed. Survey results reported a high disease burden for patients with both conditions, with patients with ATTRwt amyloidosis reporting more diagnoses and procedures prior to their final diagnosis. Interviews with participants with ATTRwt amyloidosis revealed that patients face a high symptomatic burden of disease. Diagnosis was often delayed due to three key factors: (1) early signs of ATTRwt amyloidosis were often assumed to be related to old age; (2) many medical specialists working in silos were involved in participants' diagnostic; and (3) there was a general lack of disease awareness. Early indicators such as carpal tunnel syndrome were often overlooked. Participants were typically diagnosed after the disease had progressed to include severe cardiac symptoms such as atrial fibrillation and severe shortness of breath. Sleep apnoea was also reported by a number of participants, with a considerable impact on quality of life., Conclusions: Our study provides insight into the overall impact of the patient journey on their quality of life and demonstrates how increased awareness of ATTRwt amyloidosis and more coordinated engagement with physicians could reduce the time to diagnosis., (© 2024. The Author(s).)

Pulmonary amyloidosis is an extremely rare disease, often detected incidentally because of its asymptomatic nature and potential to result in fatal outcomes. In this study, we aimed to present the clinical and radiological features of patients diagnosed with pulmonary amyloidosis by biopsy. This descriptive study included 21 patients with pathologically diagnosed pulmonary amyloidosis. Pulmonary amyloidosis was classified as diffuse alveolar-septal amyloidosis (DASA), cystic amyloidosis (CPA), tracheobronchial amyloidosis (TBA), nodular amyloidosis (NPA), and extraparenchymal pulmonary amyloidosis (pleural and mediastinal lymph node). Clinical, bronchoscopic, and radiological specific characteristics were presented in detail to be used for differential diagnosis. The median age of the patients was 63 (40-83) years, and 14 (66.7%) were male. Twenty patients (95.2%) presented with at least 1 comorbidity. All patients diagnosed with tracheobronchial amyloidosis were symptomatic at presentation, whereas those diagnosed with NPA/extraparenchymal amyloidosis were often asymptomatic. The patients included 1 case of DASA, 1 case of CPA, 10 cases of NPA, 6 cases of TBA, and 3 cases of extraparenchymal amyloidosis involving the mediastinal lymph node and pleura. Sixteen patients (76.2%) were classified as localized amyloidosis, while 5 patients (23.8%) were classified as systemic amyloidosis following the diagnosis of multiple myeloma, monoclonal gammopathy of undetermined significance, systemic lupus erythematosus, Sjogren's syndrome, and B-cell lymphoma. Bronchoscopic biopsies were sufficient for diagnosis, and notably, even transbronchial needle aspiration could be a useful diagnostic method. During the follow-up, we observed that the disease remained stable without progression. However, it is important to note that patients with concurrent malignancies experience fatal outcomes. In conclusion, it is crucial to distinguish pulmonary amyloidosis from other pulmonary diseases such as malignancies, infectious diseases, and interstitial lung diseases, which may have similar clinical and radiological findings. Bronchoscopic diagnostic methods are usually sufficient for the diagnosis. Although patients with pulmonary involvement mostly remain stable during long-term follow-up without progression, it is important to consider the risk of malignancy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Monoclonal immunoglobulins can form deposits other than amyloidosis in various tissues. Immunofluorescence is the key analysis for the identification of monoclonal immunoglobulin deposits. Pulmonary light chain deposition disease is a diagnosis to be considered when dealing with diffuse cystic lung disease., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives: The calculation of left ventricular mass varies in different studies, and reference values of the voltage-to-mass ratio for diagnosing cardiac amyloidosis (CA) are lacking. This study aimed to determine the value of the voltage-to-mass ratio in diagnosing CA and provide an optimal cut-off value for different calculation methods., Methods: We reviewed the electrocardiograms and echocardiograms of 213 consecutive biopsy-proven CA patients, 236 hypertrophic cardiomyopathy (HCM) patients, 100 hypertensive heart disease patients, and 181 healthy controls. Left ventricular mass was calculated using linear and cross-sectional area (CSA) methods. The voltage-to-mass ratios were compared between the CA group and other groups. The voltage-to-mass ratio obtained was used to build multivariate logistic regression models that predicted the log odds of developing CA., Results: The CA group had a significantly lower voltage-to-mass ratio than the HCM, hypertensive heart disease, and healthy control groups. The voltage-to-mass ratio was an independent factor significantly associated with the CA diagnosis after adjusting for baseline characteristics. Linear and CSA methods yielded areas under the ROC curve of 0.86 and 0.90, respectively. Using the CSA method, the optimal cut-off was 16.42 mV/mm 2 /m 2 , with 89.0% sensitivity and 80.8% specificity., Conclusion: The voltage-to-mass ratio could differentiate patients with CA, HCM, and hypertensive heart disease from healthy controls, potentially providing an accurate and non-invasive alternative to current expensive and invasive diagnostic techniques., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

The three most common varieties of systemic amyloidosis are transthyretin amyloidosis (ATTR), immunoglobulin amyloidosis (AL) and inflammatory amyloidosis (AA). There are two forms of transthyretin amyloidosis: the wild type, the most common, represents approximately 15% of heart diseases and the genetic, or "mutated" form, which is a rare disease and manifests mainly by peripheral neuropathy and heart disease. Major therapeutic advances have been made in recent years thanks to molecules that stabilize transthyretin and/or prevent its translation by destroying messenger RNA. Immunoglobulin amyloidosis (AL) is a hematological disease whose severity is due to the toxicity of immunoglobulin light chains forming amyloid deposits that are toxic to tissues, particularly the heart and kidneys. Treatments for immunoglobulin amyloidosis are increasingly effective, and target the plasma cell, leading to an overall improvement in the prognosis, with cardiac involvement being the most worrying condition. Inflammatory amyloidosis (AA) complicates chronic inflammatory diseases less often due to the effectiveness of anti-inflammatory biotherapies in inflammatory rheumatism, chronic inflammatory bowel diseases and genetic auto-inflammatory diseases. The causes of inflammatory amyloidosis are now more diverse with an increase in cases of unknown cause associated or not with obesity., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

As in other organs, the diagnosis of endogenous cutaneous overload diseases is based on histopathological analysis of the lesions using special stainings, even if the clinical appearance is sometimes very suggestive. The lesions are sometimes very subtle and can be included in the group of "invisible" dermatoses, such as primary macular cutaneous amyloidosis or calciphylaxis. Superficial dermal melanosis or pigmentary incontinence generally reflects the post-inflammatory stage of a chronic or recurrent interface dermatitis. Section levels should be systematically performed to look for active lesions of diagnostic interest: Alcian blue staining to identify dermal mucinosis (connectivitis) and pan-T markers (fixed pigmented erythema, lichenoid mycosis fungoides, and vitiligo). Some pathologies have a prognostic impact, either because they reflect an underlying disease, monoclonal gammopathies, in particular myeloma, being one of the most common conditions in this context (AL amyloidosis, xanthoma and xanthogranuloma, scleromyxedema), or because they can be associated with visceral damage (AL amyloidosis, scleromyxedema). The clinical-pathological comparison is mandatory to rule out differential diagnoses, especially for life-threatening diseases: nodular amyloidosis and primary cutaneous amyloidosis versus systemic AL amyloidosis, papular mucinosis versus scleromyxedema and calcific panniculitis versus calciphylaxis., (Copyright © 2024 The Author. Published by Elsevier Masson SAS.. All rights reserved.)

Localized orbital amyloidosis is a rare clinical entity. Periocular and orbital amyloid deposits are mainly located at the lacrimal apparatus, eyelid, conjunctiva, ocular adnexa, extraocular muscles, and levator palpebrae muscle. In this article, the authors report an unusual case of optic nerve amyloid deposition in an 82-year-old African American woman who presented with vertical diplopia. MRI revealed an enhancing mass from the optic nerve sheath, and CT showed foci of calcifications suggestive of optic nerve meningioma. However, an incisional biopsy demonstrated lymphoproliferative disease with focal optic nerve sheath amyloid deposition confirmed by histologic Congo red staining and immunohistochemistry., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: To present ocular clinical, histological, systemic, and genetic findings of a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency caused by a novel genetic variant of the LCAT gene associated with secondary corneal amyloidosis., Methods: Case report., Results: A 74-year-old woman presented with decreased visual acuity (VA), sensitivity to light, and progressive whitening of both corneas for approximately 20 years. The patient had undergone penetrating keratoplasty (PKP) on the right eye 6 years ago. Ophthalmologic examination revealed decreased VA in both eyes (OD: 0.05, OS: 0.3), and even further reduced glare VA (OD: 0.05, OS: 0.1), diffuse whitish corneal opacity involving the total thickness of the corneal stroma without crystalline deposits, and a marked peripheral diffuse arcus. Systemic examination revealed severely reduced plasma high-density lipoprotein cholesterol levels, target cells in blood smear, and chronic normochromic anemia. Clinically, LCAT deficiency was the most likely diagnosis. Further genetic analysis confirmed the diagnosis. The patient is homozygous for the novel variant c.943T>C (p.Trp315Arg) in the LCAT gene. Histologic examination of the cornea removed during the first keratoplasty revealed amyloid deposits. The cornea removed at the second keratoplasty had small vacuoles in the anterior stroma, indicating recurrence of lipid deposition., Conclusions: LCAT deficiency is a rare genetic disorder that can cause corneal opacities because of lipid deposition in the cornea. Systemic manifestations may help in the differential diagnosis to other diseases associated with severe high-density lipoprotein cholesterol reduction. Genetic analysis is employed to confirm the diagnosis. Some mutations in the LCAT gene seem to be associated with secondary corneal amyloidosis. Further investigation of this association is warranted. A recurrence of corneal opacity after PKP seems to occur mainly in the anterior corneal stroma., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Objective: Clinical manifestations secondary to amyloid deposition in connective tissue may allow early detection of amyloidosis. We sought to identify the prevalence of connective tissue amyloidosis in patients undergoing orthopedic surgery and evaluate for cardiac involvement., Material and Methods: Descriptive cross-sectional study that included patients >50 years referred for orthopedic surgery at our center. A sample of the affected connective tissue was taken during the intervention to evaluate the presence of amyloid material. Those with confirmed amyloidosis were further evaluated with complementary tests for cardiac involvement., Results: Forty-eight patients were included. Mean age was 65.4 years and 41.7% were women. The most frequent surgery was supraspinatus tendon rupture (50%). Transthyretin amyloid deposits were detected in 2 patients (4.2%). The absence of variants in the protein gene established the diagnosis of ATTRwt in both cases. None of them presented cardiac involvement., Conclusions: In this study, 4.2% of patients referred for orthopedic surgery presented transthyretin amyloidosis in the affected connective tissue., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Competing Interests: None.