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American Journal of Clinical Dermatology Oct 2017Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement.... (Review)
Review
BACKGROUND
Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement. Lichen amyloidosis, macular amyloidosis, and (primary localized cutaneous) nodular amyloidosis are different subtypes of PLCA.
OBJECTIVE
The aim of this study was to review the current reported treatment options for PLCA.
METHODS
This systematic review was based on a search in the PubMed database for English and German articles from 1985 to 2016.
RESULTS
Reports on the treatment of PLCA were limited predominantly to case reports or small case series. There were a few clinical trials but these lacked control groups. A variety of treatment options for PLCA were reported including retinoids, corticosteroids, cyclophosphamide, cyclosporine, amitriptyline, colchicine, cepharanthin, tacrolimus, dimethyl sulfoxide, vitamin D analogs, capsaicin, menthol, hydrocolloid dressings, surgical modalities, laser treatment, and phototherapy.
CONCLUSION
No definitive recommendation of preferable treatment procedures can be made based on the analyzed literature. Randomized controlled trials are needed to offer patients an evidence-based therapy with high-quality standardized treatment regimens for PLCA.
Topics: Amyloidosis, Familial; Bandages, Hydrocolloid; Dermatologic Agents; Dermatologic Surgical Procedures; Europe; Humans; Laser Therapy; Phototherapy; Practice Guidelines as Topic; Skin; Skin Diseases, Genetic
PubMed: 28342017
DOI: 10.1007/s40257-017-0278-9 -
JAMA Jul 2020Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis...
IMPORTANCE
Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis and 25% of patients with amyloid transthyretin (ATTR) amyloidosis die within 24 months of diagnosis. Effective therapy exists but is ineffective if end-organ damage is severe.
OBJECTIVE
To provide evidence-based recommendations that could allow clinicians to diagnose this rare set of diseases earlier and enable accurate staging and counseling about prognosis.
EVIDENCE REVIEW
A comprehensive literature search was conducted by a reference librarian with publication dates from January 1, 2000, to December 31, 2019. Key search terms included amyloid, amyloidosis, nephrotic syndrome, heart failure preserved ejection fraction, and peripheral neuropathy. Exclusion criteria included case reports, non-English-language text, and case series of fewer than 10 patients. The authors independently selected and appraised relevant literature.
FINDINGS
There was a total of 1769 studies in the final data set. Eighty-one articles were included in this review, of which 12 were randomized clinical trials of therapy that included 3074 patients, 9 were case series, and 3 were cohort studies. The incidence of AL amyloidosis is approximately 12 cases per million persons per year and there is an estimated prevalence of 30 000 to 45 000 cases in the US and European Union. The incidence of variant ATTR amyloidosis is estimated to be 0.3 cases per year per million persons with a prevalence estimate of 5.2 cases per million persons. Wild-type ATTR is estimated to have a prevalence of 155 to 191 cases per million persons. Amyloidosis should be considered in the differential diagnosis of adult nondiabetic nephrotic syndrome; heart failure with preserved ejection fraction, particularly if restrictive features are present; unexplained hepatomegaly without imaging abnormalities; peripheral neuropathy with distal sensory symptoms, such as numbness, paresthesia, and dysesthesias (although the autonomic manifestations occasionally may be the presenting feature); and monoclonal gammopathy of undetermined significance with atypical clinical features. Staging can be performed using blood testing only. Therapeutic decision-making for AL amyloidosis involves choosing between high-dose chemotherapy and stem cell transplant or bortezomib-based chemotherapy. There are 3 therapies approved by the US Food and Drug Administration for managing ATTR amyloidosis, depending on clinical phenotype.
CONCLUSIONS AND RELEVANCE
All forms of amyloidosis are underdiagnosed. All forms now have approved therapies that have been demonstrated to improve either survival or disability and quality of life. The diagnosis should be considered in patients that have a multisystem disorder involving the heart, kidney, liver, or nervous system.
Topics: Algorithms; Benzoxazoles; Dexamethasone; Diagnosis, Differential; Gene Silencing; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Liver Transplantation; Melphalan; Prognosis; Proteinuria; Stem Cell Transplantation
PubMed: 32633805
DOI: 10.1001/jama.2020.5493 -
Oxidative Medicine and Cellular... 2021Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still... (Meta-Analysis)
Meta-Analysis
Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still absent in the literature. Kefir is fermented milk resulting from the metabolism of a complex microbiota in symbiosis. Recent researches have investigated the bioactive compounds responsible for the preventive and therapeutic effects attributed to kefir. However, differences in functional potential between industrial and artisanal kefir are still controversial. Firstly, we identified differences in the microbial composition among both types of kefir. Available evidence concerning the action of different bioactive compounds from kefir on health, both from and studies, was subsequently summarized to draw a primary conclusion of the dose and the intervention time for effect, the producer microorganisms, the precursor in the milk, and the action mechanism. Meta-analysis was performed to investigate the statistically significant differences ( < 0.05) between intervention and control and between both types of kefir for each health effect studied. In summary, the bioactive compounds more commonly reported were exopolysaccharides, including kefiran, bioactive peptides, and organic acids, especially lactic acid. Kefir bioactive compounds presented antimicrobial, anticancer, and immune-modulatory activities corroborated by the meta-analysis. However, clinical evidence is urgently needed to strengthen the practical applicability of these bioactive compounds. The mechanisms of their action were diverse, indicating that they can act by different signaling pathways. Still, industrial and artisanal kefir may differ regarding functional potential-OR of 8.56 (95% CI: 2.27-32.21, ≤ .001)-according to the observed health effect, which can be associated with differences in the microbial composition between both types of kefir.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Biological Products; Fermentation; Humans; Immunomodulating Agents; Kefir; Milk
PubMed: 34745425
DOI: 10.1155/2021/9081738 -
Danish Medical Journal Nov 2013Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the... (Review)
Review
INTRODUCTION
Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised cutaneous amyloidosis (PLCA). The method of treatment was compared to the risk of local recurrence.
METHODS
A literature search produced 77 articles with localised cutaneous amyloidosis, 23 articles were excluded; thus, a total of 54 articles were included.
RESULTS
A total of 94 patients were included with a male:female ratio of 1.2:1.0. The median age was 57 years (range 24-87 years). The most common tumour localisation was in the head and neck region with a total of 38 lesions (34%), and 20 patients (22%) had two or more lesions in different locations. The nodular subtype was reported in 65 patients (69%). Only 29 patients received therapy with eight patients having two or more treatments (28%). Eight patients (9%) had local recurrence and all were nodular PLCA, which were mainly seen in males and localised in the face. One patient developed SA (1%); in fact, this was the only patient who was positive for monoclonal amyloid light chain amyloidosis by immunoelectrophoresis of the serum.
CONCLUSION
Our review suggests that PLCA is a benign disease that has a good prognosis and that it is associated with a low risk of developing SA (1%). The risk of developing local recurrence or developing new lesions was 9%, and no significant differences were found when compared to the primary treatment.
Topics: Amyloidosis, Familial; Disease Progression; Humans; Immunoglobulin Light Chains; Recurrence; Risk Assessment; Skin Diseases, Genetic
PubMed: 24192243
DOI: No ID Found -
The Journal of Allergy and Clinical... Feb 2021Primary immune deficiencies (PIDs) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections...
BACKGROUND
Primary immune deficiencies (PIDs) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections and immune dysregulation. The resulting chronic inflammation can induce long-term complications, including AA amyloidosis (AAA).
OBJECTIVES
To present the French cases of PID-related AAA and perform a systematic literature review to determine its main features and predisposing factors.
METHODS
A systematic literature review was performed by searching MEDLINE up until 2019. New French cases were identified with the help of the Reference Center for Auto-Inflammatory Diseases and AA Amyloidosis and the Reference Center for Hereditary Immune Deficiencies.
RESULTS
Forty patients were identified including 2 new French cases. PIDs were varied: immunoglobulin deficits (n = 30), chronic granulomatous disease (n = 3), hyper-IgM syndrome (n = 3), hereditary complete C4 deficiency (n = 1), leucocyte adhesion deficiency type 1 (n = 1), hyper-IgE syndrome (n = 1), and Chediak-Higashi syndrome (n = 1). The mean age at PID diagnosis was 22.2 ± 16.02 years. Renal involvement was the most common manifestation of AAA (80%). Infections were extremely heterogeneous; bacterial infection with pulmonary involvement was the most frequent. Bronchiectasis was particularly common (52.5%). The delay between the first symptoms of PID and AAA diagnosis was 16.18 ± 7 years. Thirteen concomitant diagnoses were made. Twenty patients died during follow-up.
CONCLUSION
AAA is a rare life-threatening complication of PID, especially in cases of long diagnostic and therapeutic delays. Bronchiectasis should be considered as a warning sign of chronic inflammation and increased risk of AAA.
Topics: Amyloidosis; Bronchiectasis; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
PubMed: 33007500
DOI: 10.1016/j.jaip.2020.09.023 -
Clinical Advances in Hematology &... Oct 2022Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal... (Review)
Review
BACKGROUND
Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal approach to AL-CA.
OBJECTIVE
We conducted this systematic review to summarize current evidence from published studies about the safety and efficacy of various treatment regimens for patients with AL-CA, mainly focusing on autologous stem cell transplant (ASCT) and heart transplant.
METHODS
An electronic literature search of PubMed, Web of Science, Scopus, EBSCO, and CINAHL Plus was conducted through December 2019 using the relevant keywords and prespecified MeSH terminology. Records were screened, and eligible studies were selected and narratively discussed. Data on the hematologic and cardiac responses as well as the safety of the treatment regimens were extracted and synthesized narratively in the context of the systematic review.
RESULTS
Thirty published articles were included in this systematic review. The most commonly used first-line treatment in the included studies was bortezomib-based therapy followed by high-dose melphalan and ASCT, with recent evidence of improved outcome with the addition of daratumumab. Heart transplant was found to extend survival for selected patients who were not eligible for ASCT; however, it was found to affect the patients' tolerance of further chemotherapy in some studies. Published data on longterm outcomes with immunomodulatory agents were scarce.
CONCLUSION
Current evidence suggests several possible regimens for the treatment of AL-CA. Effective treatment approaches for AL-CA include induction therapy with bortezomib-based or immunotherapy-based combinations in moderate/severe forms of cardiac involvement, followed by high-dose melphalan and ASCT in eligible patients, and heart transplant for selected severe cases. Therefore, we highlight the necessity of conducting well-designed, randomized controlled trials to provide evidence about the efficacy of these drugs with respect to ASCT.
Topics: Bortezomib; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Transplantation, Autologous; Treatment Outcome
PubMed: 36206073
DOI: No ID Found -
American Journal of Cardiovascular... 2022Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an... (Review)
Review
BACKGROUND
Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an underestimated phenotype. We aim to evaluate the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction.
METHODS
This meta-analysis was conducted according to PRISMA guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar to locate studies whose primary objective was to analyze the prevalence of transthyretin amyloidosis in heart failure preserved ejection fraction.
RESULTS
Of 271 studies initially identified, 5 studies comprising 670 patients were included in the final analysis. The prevalence of transthyretin amyloidosis was 11%. Patients with transthyretin amyloid cardiomyopathy were more likely to be males (RR 1.38; 95% CI 1.09 to 1.75; P<0.01; I=37%), and more likely to have low voltage criteria on ECG (RR 2.98; 95% CI 1.03 to 8.58; P=0.04; I=75%) compared with transthyretin negative group. They also have higher SMD of age (SMD 0.73; 95% CI 0.48 to 0.97; P<0.01; I=0%), and NT-proBNP (SMD 0.48; 95% CI 0.02 to 0.93; P=0.04; I=36%) compared with transthyretin negative group. On reported echocardiogram, they have higher SMD of mass index (SMD 0.77; 95% CI 0.27 to 1.27; P<0.01; I=65%), posterior wall thickness (SMD 0.92; 95% CI 0.62 to 1.21; P<0.01; I=0%), and septal wall thickness (SMD 1.49; 95% CI 0.65 to 2.32; P<0.01; I=87%) compared with transthyretin negative group.
CONCLUSION
Transthyretin amyloidosis affects 11% of HFpEF patients. Therefore, screening HFpEF patients at risk of cardiac amyloidosis is warranted.
PubMed: 35873185
DOI: No ID Found -
International Journal of Cardiology May 2024This systematic review aimed to assess the tolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with adverse... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aimed to assess the tolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with adverse outcomes.
METHODS
We performed a comprehensive search from January 1, 2000 to October 20, 2023. Studies examining BB use and tolerance or the relationship between BB use and outcomes in patients with CA were included. Pooled adjusted hazard ratios (aHRs) for all-cause mortality were calculated using random- and fixed-effects models.
RESULTS
Eight observational studies involving 4002 patients with CA (87.5% with transthyretin CA [ATTR-CA] and 12.5% with immunoglobulin light chain CA [AL-CA]) were assessed. BBs were used by 52.5% of the patients. However, 26.3% of the patients discontinued BBs because of hypotension, bradycardia, or fatigue. Regarding the association between BB use and all-cause death, four studies were identified that included 2874 patients with ATTR-CA and 16 patients with AL-CA. The meta-analysis revealed no apparent relationship between BB use and all-cause mortality (pooled aHR = 0.78, 95% confidence interval (CI) = 0.40-1.51). Two studies on patients with ATTR-CA found no impact of BB use on all-cause mortality in the subgroup with left ventricular ejection fraction (LVEF) > 40%, but conflicting results exist for those with LVEF ≤40% (pooled aHR = 0.78, 95% CI = 0.40-1.54).
CONCLUSION
The limited number of observational studies that predominantly enrolled patients with ATTR-CA showed that BBs were used in almost half of the patients with CA, with varying tolerability. However, no significant association was observed between BB use and all-cause mortality.
Topics: Humans; Amyloid Neuropathies, Familial; Stroke Volume; Ventricular Function, Left; Immunoglobulin Light-chain Amyloidosis; Prealbumin; Cardiomyopathies
PubMed: 38278490
DOI: 10.1016/j.ijcard.2024.131813 -
Biology of Blood and Marrow... Aug 2009Significant uncertainty exists regarding the efficacy of high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT) for the treatment of patients... (Comparative Study)
Comparative Study Meta-Analysis Review
Significant uncertainty exists regarding the efficacy of high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT) for the treatment of patients with primary systemic (AL) amyloidosis. We performed a systematic review and meta-analysis to evaluate the efficacy of AHCT versus conventional chemotherapy (CC) in patients with AL amyloidosis using methodology recommended by the Cochrane Collaboration. A comprehensive literature search yielded 820 studies. Twelve studies met the inclusion criteria: 1 randomized controlled trial (RCT), 2 other controlled studies, and 9 single-arm trials. The 1 RCT and 2 controlled studies compared AHCT and CC, and 9 single-arm studies assessed the efficacy of AHCT without a control. The pooled hazard ratio for overall survival (OS) in the 3 controlled studies was 1.79 (95% confidence interval [CI] = 1.11 to 2.91) favoring CC. The pooled proportion for mortality in the single-arm studies (n = 7) was 0.35 (95% CI = 0.25 to 0.46). The pooled odds ratio for complete hematologic response (CHR) from 2 controlled studies was 0.64 (95% CI = 0.25 to 1.64), indicating no difference between AHCT and CC. In the single-arm studies, the pooled proportion for CHR was 0.35 (95% CI = 0.26 to 0.44), and the pooled proportion for treatment-related mortality (TRM) was 0.12 (95% CI = 0.09 to 0.14). In the controlled studies, there was no heterogeneity for any outcome; however, in the single-arm studies, there was a significant heterogeneity for the outcomes of OS, CHR, renal response, and partial hematologic response. Our findings indicate that AHCT does not appear to be superior to CC in improving OS in patients with AL amyloidosis. But the quality of our evidence is low, indicating a need for well-designed and adequately powered RCTs to better address the role of AHCT in AL amyloidosis.
Topics: Amyloidosis; Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Odds Ratio; Proportional Hazards Models; Survival Rate; Transplantation, Autologous; Treatment Outcome
PubMed: 19589478
DOI: 10.1016/j.bbmt.2009.01.022 -
BMC Cardiovascular Disorders Dec 2018Cardiac Amyloidosis (CA) pertains to the cardiac involvement of a group of diseases, in which misfolded proteins deposit in tissues and cause progressive organ damage....
BACKGROUND
Cardiac Amyloidosis (CA) pertains to the cardiac involvement of a group of diseases, in which misfolded proteins deposit in tissues and cause progressive organ damage. The vast majority of CA cases are caused by light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). The increased awareness of these diseases has led to an increment of newly diagnosed cases each year.
METHODS
We performed multiple searches on MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. Several search terms were used, such as "cardiac amyloidosis", "diagnostic modalities cardiac amyloidosis" and "staging cardiac amyloidosis". Emphasis was given on original articles describing novel diagnostic and staging approaches to the disease.
RESULTS
Imaging techniques are indispensable to diagnosing CA. Novel ultrasonographic techniques boast high sensitivity and specificity for the disease. Nuclear imaging has repeatedly proved its worth in the diagnostic procedure, with efforts now focusing on standardization and quantification of amyloid load. Because the latter would be invaluable for any staging system, those spearheading research in magnetic resonance imaging of the disease are also trying to come up with accurate tools to quantify amyloid burden. Staging tools are currently being developed and validated for ATTR CA, in the spirit of the acclaimed Mayo Staging System for AL.
CONCLUSION
Cardiac involvement confers significant morbidity and mortality in all types of amyloidosis. Great effort is made to reduce the time to diagnosis, as treatment in the initial stages of the disease is tied to better prognosis. The results of these efforts are highly sensitive and specific diagnostic modalities that are also reasonably cost effective.
Topics: Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Echocardiography; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index; Tomography, Emission-Computed
PubMed: 30509186
DOI: 10.1186/s12872-018-0952-8