scholarly journals Scalp biopsy identifies systemic amyloidosis presenting as isolated telogen effluvium: A case report

2019 ◽  
Vol 7 ◽  
pp. 2050313X1984778
Author(s):  
Rory A Sutherland ◽  
Richard I Crawford
Keyword(s):  
Multiple Myeloma ◽  
Rare Case ◽  
Systemic Disease ◽  
Antibody Fragments ◽  
Systemic Amyloidosis ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Biopsy Finding ◽  
Scalp Biopsy ◽  
Underlying Pathology

AL amyloidosis is a complication of B-cell dyscrasias and multiple myeloma, manifest as deposition of antibody fragments in many different organs, including the skin. We describe a rare case of this systemic disease which presented with isolated scalp alopecia. Further investigation led to the diagnosis of an occult plasma-cell dyscrasia, showing the benefit of including systemic amyloidosis in the differential diagnosis of alopecia. The biopsy finding of cutaneous amyloidosis should prompt further workup to exclude an underlying pathology.

A pharmacist’s review of the treatment of systemic light chain amyloidosis

2020 ◽  
pp. 107815522096353
Author(s):  
David M. Hughes ◽  
Andrew Staron ◽  
Vaishali Sanchorawala
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Case Reports ◽  
Evidence Base ◽  
Chemotherapeutic Agents ◽  
Plasma Cell Dyscrasia ◽  
High Dose ◽  
Al Amyloidosis ◽  
Tertiary Referral Center ◽  
Treatment Considerations

Objective Systemic light-chain (AL) amyloidosis is an uncommon hematologic plasma cell dyscrasia that is becoming increasingly recognized. Therapeutic agents used in AL amyloidosis overlap with those used in multiple myeloma; however, differences in disease features change treatment efficacy and tolerance. Pharmacists must be cognizant of these distinctions. Herein, this review article provides an up-to-date guide to treatment considerations for systemic AL amyloidosis in both the front-line and relapsed settings. Data sources: A comprehensive literature search was performed using the PubMed/Medline database for articles published through (June 2020) regarding treatments for AL amyloidosis. Search criteria included therapies that are FDA approved for multiple myeloma, as well as investigational agents. This review of chemotherapeutic agents reflects the current clinical practice guidelines endorsed by NCCN along with commentary based on the experience of pharmacists from a tertiary-referral center treating many patients with AL amyloidosis. Data consists of randomized controlled trials, observational cohorts, case reports, and ongoing clinical trials. Data summary: Frontline options discussed here include high-dose melphalan with autologous stem cell transplantation and bortezomib-based regimens. Regarding the relapsed setting, supporting data are compiled and summarized for: bortezomib, ixazomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, elotuzumab, isatuximab, venetoclax, NEOD001, and melflufen. Conclusions The treatment platform for AL amyloidosis is expanding with novel agents traditionally used in multiple myeloma being adopted and modified for use in AL amyloidosis. The pharmacist’s familiarity with the clinical evidence base for these agents and how they fit into standard protocols for AL amyloidosis is critical as dosing and monitoring recommendations are unique from multiple myeloma.

scholarly journals Cytogenetic intraclonal heterogeneity of plasma cell dyscrasia in AL amyloidosis as compared with multiple myeloma

2018 ◽  
Vol 2 (20) ◽  
pp. 2607-2618 ◽  
Author(s):  
Tilmann Bochtler ◽  
Maximilian Merz ◽  
Thomas Hielscher ◽  
Martin Granzow ◽  
Korbinian Hoffmann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Clonal Evolution ◽  
Statistical Significance ◽  
Hematologic Malignancies ◽  
Absolute Difference ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Clone Size

Abstract Analysis of intraclonal heterogeneity has yielded insights into the clonal evolution of hematologic malignancies. We compared the clonal and subclonal compositions of the underlying plasma cell dyscrasia in 544 systemic light chain amyloidosis (PC-AL) patients with 519 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or symptomatic MM; ie, PC–non-AL patients). Using interphase fluorescence in situ hybridization, subclones were stringently defined as clone size below two thirds of the largest clone and an absolute difference of ≥30%. Subclones were found less frequently in the PC-AL group, at 199 (36.6%) of 544 as compared with 267 (51.4%) of 519 in the PC–non-AL group (P < .001), and were not associated with the stage of plasma cell dyscrasia in either entity. In both groups, translocation t(11;14), other immunoglobulin heavy chain translocations, and hyperdiploidy were typically found as main clones, whereas gain of 1q21 and deletions of 8p21, 13q14, and 17p13 were frequently found as subclones. There were no shifts in the subclone/main clone ratio depending on the MGUS, SMM, or MM stage of plasma cell dyscrasia. In multivariate analysis, t(11;14) was associated with lower rates of subclone formation and hyperdiploidy with higher rates. PC-AL itself lost statistical significance, demonstrating that the lower subclone frequency in AL is a reflection of its exceptionally high t(11;14) frequency. In summary, the subclone patterns in PC-AL and PC–non-AL are closely related, implying that subclone formation depends on the main cytogenetic categories and is independent of disease entity and stage.

scholarly journals The plasma cell labeling index: a valuable tool in primary systemic amyloidosis

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1108-1111
Author(s):  
MA Gertz ◽  
RA Kyle ◽  
PR Greipp
Keyword(s):  
Multiple Myeloma ◽  
Median Survival ◽  
Plasma Cell ◽  
Poor Prognosis ◽  
Systemic Amyloidosis ◽  
Labeling Index ◽  
Cell Labeling ◽  
Plasma Cell Dyscrasia ◽  
Response To Chemotherapy

The plasma cell labeling index (LI) is of value in predicting prognosis in multiple myeloma. Primary systemic amyloidosis (AL) is a plasma cell dyscrasia that shares many features with myeloma. We obtained bromodeoxyuridine LI on 125 patients who presented with AL, 22 of whom also had overt multiple myeloma. Forty-six patients had a plasma cell LI greater than 0%. Of the 46 patients with an elevated LI, 19 (41%) had multiple myeloma as compared with three (4%) of the 79 patients with an LI = 0 (P less than .0001). A response to chemotherapy was seen in 14 (30%) of 46 patients with an LI greater than 0, as compared with ten (13%) of 79 patients with an LI of 0 (P = .015). The median survival of the high LI group was 14.6 months v 29.8 months for the low LI group (P = .02). In the low LI group, 29% are projected to be alive at 60 months, as compared with 20% in the high LI group. When patients with myeloma were excluded from the analysis, the LI did not predict response but continued to indicate a survival disadvantage (P less than .05). The major utility of the LI was in identifying those patients most likely to have multiple myeloma and those AL patients with a poor prognosis (median survival, 14.1 months).

Dysautonomias in amyloidosis

2013 ◽  
Vol 32 (04) ◽  
pp. 192-196
Author(s):  
B. P. C. Hazenberg
Keyword(s):  
Cell Clone ◽  
Early Stage ◽  
Systemic Disease ◽  
Interdisciplinary Approach ◽  
Signs And Symptoms ◽  
Systemic Amyloidosis ◽  
Al Amyloidosis ◽  
Life Threatening ◽  
The Individual ◽  
Common Manifestation

SummarySystemic amyloidosis is a life-threatening and frequently unrecognized cause of dysautonomia. Autonomic neuropathy is a common manifestation of AL amyloidosis (caused by deposition of an immunoglobulin free light chain produced by an underlying plasma cell clone) and of autosomal dominant hereditary ATTR amyloidosis (caused by a transthyretin mutation). The following review aims to alert clinicians to look out for signs and symptoms of amyloidosis to enable the bioptic diagnosis at an early stage. Suspicion of systemic amyloidosis is usually raised by the systemic, multi-organ character of the disease. An interdisciplinary approach is needed in the individual patient in order to establish the diagnosis and to obtain a clear overview of the actual multitude of organ problems. This overview is necessary for risk management and for making a well-considered treatment choice. Collaboration of all medical specialists involved is necessary to deliver optimal treatment and care to the patient with this systemic disease.

Valuation of MCP-1 and VEGF Chemokines In Serum of Patients with AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1922-1922
Author(s):  
Alessandro Moscetti ◽  
Francesca Saltarelli ◽  
Maria Paola Bianchi ◽  
Guglielmo Bruno ◽  
Gerardo Salerno ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Inflammatory Process ◽  
Conflicts Of Interest ◽  
Systemic Disease ◽  
Inflammatory Cells ◽  
Mononuclear Phagocytes ◽  
Systemic Amyloidosis ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Localized Amyloidosis

Abstract Abstract 1922 AL amyloidosis is a pathology characterised by the deposition of fibrillary aggregates of immunoglobuline light chains with β-sheet conformation. The light chains are synthetized by neoplastic plasma cell and fibrils deposition can infiltrate tissues leading to multi systemic organ damage. To evaluate if vascular modifications are involved in AL amyloidosis, inflammatory activity of cytokines as MCP-1 and VEGF was investigated. MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte-endothelium binding and migration to sites of inflammation, while VEGF is an endothelial cell mitogen and permeability factor that is potently angiogenic in bone marrow of AL amyloidosis patients. Aim of this study is to evaluate serum cytokines MCP-1 and VEGF levels in patients with systemic or localized AL amyloidosis at presentation to find out potential differences useful to define a characteristic inflammatory pattern. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis and analyzed for serum MCP-1 and VEGF levels. Mann-Whitney test and Spearman correlation were used to compare results. MCP-1 level was significantly higher in the serum of patients with systemic disease (350.52±58.70 pg/ml) compared to the group of patients with localized amyloidosis (147.82±26.03; p=0.004); VEGF was also significantly increased in systemic disease group (p= 0.028). In addition, a positive correlation between MCP-1 and VEGF (r2= 0.755; p=0.031) has been found in the group of patients with systemic amyloidosis. Results seems to suggest a difference in serum cytokine MCP-1 and VEGF levels between AL systemic and localized amyloidosis. In systemic amyloidosis the neoplastic plasma cells interact with bone marrow microenvironment resulting in VEGF release leading to a new angiogenesis also supported by an inflammatory cells increase. The MCP-1 activates and promotes leukocyte-endothelium binding increasing the inflammatory process. The high correlation between MCP-1 and VEGF suggests a positive relationship between a new angiogenesis and a migration of inflammatory cells in the bone marrow stroma. On the basis of our results, MCP-1 and VEGF chemokines can be used to evaluate the inflammatory process in patient with systemic or localized AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

Role of laboratory tests in diagnosis of multiple myeloma and other plasmocytes dyscrasia patients

2015 ◽  
Vol 51 (1) ◽  
pp. 43-52
Author(s):  
Anna Rodziewicz-Lurzyńska ◽  
Dagna Bobilewicz
Keyword(s):  
Multiple Myeloma ◽  
Serum Protein ◽  
Laboratory Tests ◽  
Plasma Cells ◽  
Pathological Condition ◽  
Protein Pattern ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Monoclonal Protein ◽  
Single Clone

Plasma cell dyscrasia is a group of diseases characterized by uncontrolled proliferation of single clone of plasma cells producing monoclonal protein – immunoglobulin and/or its subunits (light and heavy chains). Monoclonal protein most often can be detected as an extra band on serum protein pattern, nevertheless if it is lacking pathological condition cannot be excluded. Multiple myeloma is the most common gammapathy and the diagnostic criteria are well précised and updated. In case of the others like AL amyloidosis many problems with interpretation of laboratory results exist. For solving them besides of well established laboratory tests like serum protein electrophoresis the others like serum free light chains are being introduced. The own results illustrating laboratory picture of discrasia are presented.

Heart Function In Systemic and Localized AL Amyloidosis: Role of NT-ProBNP and MPC-1

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5006-5006
Author(s):  
Francesca Saltarelli ◽  
Alessandro Moscetti ◽  
Guglielmo Bruno ◽  
Bruno Monarca ◽  
Gerardo Salerno ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Heart Function ◽  
Systemic Disease ◽  
Plasma Concentrations ◽  
Serum Levels ◽  
Mononuclear Phagocytes ◽  
Systemic Amyloidosis ◽  
Al Amyloidosis ◽  
Heart Involvement ◽  
Localized Amyloidosis

Abstract Abstract 5006 In AL amyloidosis typical sites of amyloid buildup are heart, skin, gastrointestinal tract, liver, kidneys, and blood vessels. To evaluate the heart involvement in systemic and localized amyloidosis proBNP, peptide (NT-proBNP; 76 amino acids) and MPC-1 were investigated. NT-proBNP have been described as useful marker for the diagnosis heart disease, and its plasma concentrations correlate with the functional classification of patients according to the New York Heart Association (NYHA). MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte–endothelium binding and migration to sites of inflammation. The MCP-1 levels seem to be related to the severity of cardiac alteration, as demonstrated by the coronary angiogram. NT-proBNP and MPC-1 serum levels were performed in systemic or localized AL amyloidosis to evaluate if there was a difference in the heart involvement. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. To analyze the results of NT-proBNP and MPC-1, Mann-Whitney test was performed. NT-proBNP serum values were significantly (p=0.007) increased in systemic disease. Also, MPC-1 serum levels were significantly (p=0.004) higher in the patients with systemic disease (350.52±58.70 pg/ml) if compared to the group of localized amyloidosis (147.82±26.03 pg/ml). On the basis of our results, the heart seem to be functionally more involved in AL systemic amyloidosis than in localized disease, as demonstrated by the higher NT-proBNP and MPC-1 serum values. Disclosures: No relevant conflicts of interest to declare.

scholarly journals An Unusual Cause of Generalized Swelling

2018 ◽  
Vol 26 (2) ◽  
pp. 173-177
Author(s):  
Sabrina Shahrin ◽  
Md Aminul Islam ◽  
Md Ehsan Uddin Khan ◽  
Parvez Iftekhar Ahmed ◽  
Md Nazrul Islam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Systemic Disease ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Medical College ◽  
Multiple Organs ◽  
Single Clone ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Amyloidosis and multiple myeloma are included in the same spectrum of clonal plasma cell disorder. Amyloidosis can present with localized deposits or manifest as systemic disease involving multiple organs such as kidney, heart, intestine. Free Ig subunits ,mostly light chains secreted by a single clone of B cells, are the cause of the most frequent and severe amyloidosis affecting the kidney. The incidence of AL amyloidosis is nine per 1 million populations per year. Amyloid deposists are found in approximately 10% of all patients with myeloma and in 20% of those with pure light chain myeloma[1].Here we are reporting a case who initially presented with generalized swelling and subsequently found to have AL amyloidosis involving multiple organs due to multiple myeloma.J Dhaka Medical College, Vol. 26, No.2, October, 2017, Page 173-177

scholarly journals Multiple myeloma with primary systemic amyloidosis affecting cutaneous, gastro intestinal and cardio-vascular system

2019 ◽  
Vol 6 (3) ◽  
pp. 982
Author(s):  
Mohammed Feros A. S. ◽  
Lokesh Shanmugam
Keyword(s):  
Multiple Myeloma ◽  
Cardiac Amyloidosis ◽  
Vascular System ◽  
Systolic Function ◽  
Restrictive Cardiomyopathy ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Systemic Amyloidosis ◽  
Plasma Cell Dyscrasia ◽  
Cardio Vascular

Amyloidosis refers to a group of disorders characterized by extracellular deposition of protein fibrils. Primary systemic amyloidosis is commonly due to an underlying plasma cell dyscrasia. Infiltrative amyloid cardiomyopathy is a rare cause of predominantly diastolic myocardial disease. Restrictive cardiomyopathy is the main finding in cardiac amyloidosis and results from the replacement of normal myocardial contractile elements by infiltration and interstitial deposits of amyloid, leading to alterations in cellular metabolism, calcium transport, receptor regulation, and cellular edema. Injury can also occur from circulating light chains in the absence of amyloid fibril formation. Cardiac amyloidosis should be considered in any patient presenting with congestive heart failure, preserved systolic function, and a discrepancy between a low QRS voltage on electrocardiography and an apparent left ventricular hypertrophy on sonogram. The pattern of left ventricular diastolic dysfunction changes during the course of amyloidosis and the classically described restrictive physiology occurs only in advanced stages of the disease. This is a case report where an unusual extensive cutaneous and cardiac involvement provided the sign of widespread systemic deposition of amyloid protein which eventually led to the diagnosis of multiple myeloma.

IL-4 and IL-1 Serum Levels In Systemic and Localized Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5000-5000
Author(s):  
Alessandro Moscetti ◽  
Francesca Saltarelli ◽  
Guglielmo Bruno ◽  
Bruno Monarca ◽  
Gerardo Salerno ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Conflicts Of Interest ◽  
Systemic Disease ◽  
Inverse Correlation ◽  
Serum Levels ◽  
Systemic Amyloidosis ◽  
Al Amyloidosis ◽  
Th2 Response ◽  
Localized Amyloidosis ◽  
Localized Disease

Abstract Abstract 5000 AL amyloidosis is a plasmacellular discrasia characterized by the deposition of light chains fibrils that infiltrate tissues leading to multisystemic organ involvement. Amyloidosis can be systemic or localized disease. No immunological markers are avaibable to distinguish the systemic from localized disease. IL-4 and IL-1 cytokines were performed to evaluate if there is a different inflammatory pattern between the two clinical forms. IL-4 is the central regulator of T helper 2 (Th2) immune responses, with also a major impact on innate immune cells. IL-1 is produced by macrophages, monocytes, fibroblasts and dendritic cells which play an important role in the inflammatory response, activating the Th1-mediated IL2 release. IL-1 increases the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes to sites of infection. The study was devoted to evaluate serum levels of IL-4 and IL-1 in systemic or localized AL amyloidosis at presentation and to find out potential Th1 and Th2 disequilibrium. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. Serum IL-4 and IL-1 levels were detected. Mann-Whitney test and correlation test were used to analyze results. IL-4 level was significantly (p < 0.05) higher in patients with localized disease compared to the group with systemic amyloidosis. IL-1 was instead significantly (p < 0.01) increased in systemic disease. In this, an inverse correlation between IL-4 and IL-1a was found (r2= –0.707; p = 0.05). In systemic amyloidosis, the regulatory mechanism of Th1/Th2 response was polarized versus Th1, as demonstrated by low serum level of IL-4 and high level of IL-1. The negative correlation between serum IL-4 and IL-1 levels demonstrates a disregulation of the immune system in systemic disease as supported by the increased activity of Th1. The results seem to hypothesize that IL-4 could be able to antagonize the diffusion of disease, as demonstrated by the higher IL-4 serum levels in localized amyloidosis. So IL-4 and IL-1 can be considered sensible markers for the inflammatory response assessment both in systemic and localized amyloidosis. Disclosures: No relevant conflicts of interest to declare.

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