Výskyt monoklonální gamapatie (MG) stoupá s věkem. U jedinců starších 80 let můžeme diagnostikovat přítomnost monoklonálního imunoglobulinu až v 10 % případů. Nejen maligní onemocnění typu mnohočetného myelomu, ale i benigní formy jako MGUS (monoklonální gamapatie nejistého významu) mohou vést k postižení ledvin. Nejvíce ledviny poškozují lehké řetězce imunoglobulinů, protože ty se v důsledku své molekulové hmotnosti volně filtrují do moči. Detekce přítomnosti monoklonálního imunoglobulinu se opírá zejména o kombinaci imunofixační elektroforézy séra (IELFO) a moči a o stanovení volných lehkých řetězců kappa a lambda a jejich poměru (κ/λ) v séru. Kombinace těchto testů s 99% senzitivitou odhalí přítomnost monoklonálního imunoglobulinu. Poškození ledvin u MG může být způsobeno přímou depozicí monoklonálního imunoglobulinu v glomerulech (např. AL amyloidóza, nemoc z ukládání lehkých řetězců imunoglobulinů) či tubulech (v distálním tubulu jako myelomová ledvina nebo v proximálním tubulu jako Fanconiho syndrom či proximální tubulopatie). Typickým močovým nálezem u těchto chorob bývá velká proteinurie až nefrotický syndrom. Akutní poškození ledvin (AKI) lze očekávat zejména při zvýšení koncentrace volných lehkých řetězců v séru nad 500 mg/l. Pro stanovení přesné diagnózy, a tím i zahájení správné léčby, je klíčové provedení renální biopsie. Léčba těchto typů poškození ledvin zahrnuje stejné léčebné režimy, které se používají v léčbě mnohočetného myelomu, včetně inhibitorů proteasomu či daratumumabu.
The incidence of monoclonal gammopathy (MG) increases with age. In individuals over 80 years of age, we can diagnose the presence of monoclonal immunoglobulin (MIg) in up to 10 % of cases. Not only malignant diseases such as multiple myeloma (MM), but also benign forms such as MGUS (monoclonal gammopathy of undetermined significance) can lead to renal involvement. The light chains of immunoglobulins (LC) are the most damaging to the kidneys, as they are freely filtered into the urine due to their molecular weight. Detection of MIg relies mainly on a combination of immunofixation electrophoresis of serum (IELFO) and urine and determination of free light chains (FLC) of kappa and lambda and their ratio (κ/λ) in serum. The combination of these tests will detect the presence of MIg with 99 % sensitivity. Renal damage in MG may be caused by direct deposition of MIg in the glomeruli (e.g. AL amyloidosis, LC deposition disease) or tubules (in the distal tubule as a myeloma kidney or in the proximal tubule as Fanconi syndrome or proximal tubulopathy). Typical urinary findings in these diseases are moderate or severe proteinuria or nephrotic syndrome. Acute kidney injury (AKI) can be expected especially when serum FLC is >500 mg/l. Renal biopsy is crucial to establish an accurate diagnosis and thus initiate the correct treatment. Treatment of these types of renal damage involves the same treatment regimens used in the treatment of MM, including proteasome inhibitors or daratumumab.
- MeSH
- amyloidóza etiologie komplikace MeSH
- chronické selhání ledvin * etiologie MeSH
- dialýza ledvin metody MeSH
- imunoglobuliny škodlivé účinky MeSH
- lidé MeSH
- mnohočetný myelom * komplikace MeSH
- monoklonální gamapatie nejasného významu * etiologie komplikace MeSH
- plazmaferéza metody MeSH
- Check Tag
- lidé MeSH
Pojem amyloidóza zahrnuje skupinu poruch, při kterých dochází k ukládání proteinů, přirozených i mutovaných, do tkání. Z těchto proteinů vzniká uspořádaná vláknitá, špatně rozpustná matrix zvaná amyloid. Její ukládání poškozuje funkci postižených orgánů (1, 2). Diagnostika je obtížná a často pozdní (3). Postižení srdce je velmi časté a nejvíce limituje prognózu nemocného (4). Popisujeme případ pacientky, u které ani relativně časná diagnóza srdeční amyloidózy nezabránila jejímu náhlému úmrtí.
The term amyloidosis includes a group of disorders in which proteins, both native and mutated, are deposited in the tissues. These proteins form an ordered fibrous, poorly soluble matrix called amyloid. Its deposition impairs the function of the affected organs (1, 2). Diagnosis is difficult and often late (3). Heart involvement is very common and limits the prognosis of the patient (4). We describe the case of a patient in which even the relatively early diagnosis did not prevent her sudden death.
- MeSH
- amyloidóza * diagnóza komplikace patologie terapie MeSH
- echokardiografie metody MeSH
- fatální výsledek MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- nemoci srdce diagnóza etiologie MeSH
- primární amyloidóza diagnóza MeSH
- senioři MeSH
- srdeční selhání etiologie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or via imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.
- MeSH
- amyloidóza * komplikace diagnóza patologie MeSH
- lidé MeSH
- plíce diagnostické zobrazování patologie MeSH
- plicní nemoci * komplikace diagnóza patologie MeSH
- pneumotorax * diagnóza etiologie MeSH
- senioři nad 80 let MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. METHODS: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months. RESULTS: A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group. CONCLUSIONS: In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).
- MeSH
- amyloidóza * komplikace farmakoterapie genetika MeSH
- dvojitá slepá metoda MeSH
- familiární amyloidóza komplikace farmakoterapie genetika MeSH
- játra metabolismus MeSH
- kardiomyopatie * farmakoterapie etiologie genetika metabolismus MeSH
- lidé MeSH
- malá interferující RNA * terapeutické užití MeSH
- prealbumin * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys being the most commonly and earliest affected organ. Previously described amyloid A amyloidosis is linked to increased production and deposition of serum amyloid A proteins secondary to inflammatory conditions arising from infectious, metabolic, or genetic causes. Here we describe a family with primary amyloid A amyloidosis due to a chr11:18287683 T>C (human genome version19) mutation in the SAA1 promoter linked to the amyloidogenic SAA1.1 haplotype. This condition leads to a doubling of the basal SAA1 promoter activity and sustained elevation of serum amyloid A levels that segregated in an autosomal dominant pattern in 12 genetically affected and in none of six genetically unaffected relatives, yielding a statistically significant logarithm of odds (LOD) score over 5. Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed specifically of the SAA1.1 isoform. Tocilizumab (a monoclonal antibody against the interleukin-6 receptor) had a beneficial effect when prescribed early in the disease course. Idiopathic forms represent a significant and increasing proportion (15-20%) of all diagnosed cases of amyloid A amyloidosis. Thus, genetic screening of the SAA1 promoter should be pursued in individuals with amyloid A amyloidosis and no systemic inflammation, especially if there is a positive family history.
- MeSH
- amyloidóza * komplikace MeSH
- lidé MeSH
- mutace MeSH
- promotorové oblasti (genetika) MeSH
- sérový amyloid A genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- amyloidóza chirurgie farmakoterapie komplikace MeSH
- dospělí MeSH
- dýchací soustava chirurgie patologie MeSH
- granulomatóza s polyangiitidou komplikace MeSH
- imunosupresivní léčba metody MeSH
- kombinovaná farmakoterapie MeSH
- kyselina mykofenolová terapeutické užití MeSH
- lidé MeSH
- methylprednisolon terapeutické užití MeSH
- recidiva MeSH
- stenóza chirurgie diagnóza etiologie farmakoterapie komplikace MeSH
- trachea chirurgie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- abstrakt z konference MeSH
- kazuistiky MeSH
Transthyretinová amyloidóza je onemocněním, které donedávna bylo považováno za vzácné, ale nedávné studie ukazují, že se jedná o poddiagnostikované onemocnění. Klinický obraz tohoto onemocnění je variabilní, kardiální postižení může být izolované, ale dalším projevem bývá často polyneuropatie. V poslední době doznala diagnostika a léčba tohoto onemocnění řady změn. Do klinické praxe se zavádí nová léčiva, která nejenom příznivě ovlivňují mortalitu, ale také kvalitu života pacientů.
Transthyretin amyloidosis is a disease that has been considered as rare. However, recent studies have shown that this disorder is underdiagnosed. Clinical manifestation of this disease is variable, cardiac impairment can be isolated, but often manifestation of this disease is also polyneuropathy. Diagnostic and treatment have recently changed. New drugs that affect positively not only mortality, but also quality of life, have been introduced to clinical practice.
- Klíčová slova
- transthyretinová amyloidóza,
- MeSH
- amyloidóza * diagnostické zobrazování komplikace terapie MeSH
- histologické techniky MeSH
- lidé MeSH
- polyneuropatie etiologie MeSH
- prealbumin MeSH
- radioisotopová scintigrafie MeSH
- srdeční selhání * diagnostické zobrazování komplikace terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Amyloidosis is a heterogeneous group of diseases characterised by extracellular accumulation of amyloid in various tissues and organs of the body, leading to alteration and destruction of tissues. Heart involvement is the most important prognostic factor in patients with systemic amyloidosis and the diagnosis and typing of amyloid must be made properly. The clinical picture shows congestive heart failure with predominant right-sided heart failure symptoms in fully developed disease, various types of arrhythmias and characteristic electrocardiography and echocardiography findings. Blood and urine monoclonal protein studies and cardiac biomarkers belong to the spectrum of standard laboratory examinations. Cardiac cardiomyopathy is connected with amyloid based on immunoglobulin light chains, serum amyloid A, transthyretin, atrial natriuretic factor or apolipoprotein A1. In the routine diagnostic algorithm, biopsy specimens are examined using special histological staining, immunohistochemistry and immunofluorescence; proteomic analysis is only performed in specialised centres.
- MeSH
- amyloidóza komplikace diagnóza MeSH
- kardiomyopatie diagnóza etiologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Amyloidosis is a heterogeneous group of diseases characterized by the deposition of amyloid. It is caused by extracellular deposition of insoluble fibrils with beta-pleated sheet configuration. The protein misfolding abnormalities result in amyloid fibrils and may manifest as primary, secondary, or familial amyloidosis. Amyloid deposition can occur in multiple organs (eg, heart, liver, kidney, skin, eyes, lungs, nervous system) resulting in a variety of clinical manifestations. Cardiac involvement can occur as part of a systemic disease or as a localized phenomenon. Cardiac involvement in all types of amyloidosis represents a major negative prognostic factor. Early diagnosis, multi-disciplinary cooperation and proper therapy are key aspects of care for patients with amyloid cardiomyopathy. Early diagnosis is crucial, especially in AL amyloidosis, as patients with advanced heart disease are unsuitable candidates for modern, effective hematological treatment including autologous stem cell transplantation. Despite signal development in diagnostics and therapy, the prognosis for patients with advanced cardiac involvement remains poor. This article is an overview of amyloidosis, providing information about the characteristics of cardiac amyloidosis, and present a structured approach to diagnosis, treatment and prognosis of this condition.
Kazuistika popisuje kardiální symptomatologii jako dominantní příznak v klinickém obraze nově diagnostikované systémové AL amyloidózy. Definitivní diagnóza byla potvrzena histologicky po předchozí endomyokardiální biopsii. Následně byla zahájená systémová chemoterapie, jako základ léčby systémové AL amyloidózy.
This case report describes cardiac symptoms as a dominating feature in the clinical picture of newly diagnosed systemic AL amyloidosis. The definitive diagnosis was confirmed microscopically following endomyocardial biopsy. Subsequently, systemic chemotherapy was initiated as the basic treatment for systemic AL amyloidosis.
- MeSH
- amyloid analýza škodlivé účinky účinky léků MeSH
- amyloidóza * diagnóza farmakoterapie komplikace MeSH
- biopsie MeSH
- bortezomib aplikace a dávkování MeSH
- dexamethason aplikace a dávkování MeSH
- echokardiografie MeSH
- lidé MeSH
- myokard patologie MeSH
- senioři MeSH
- srdeční selhání etiologie krev patofyziologie MeSH
- terapie neúspěšná MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
