Ocular Involvement in Hereditary Amyloidosis.

The term amyloidosis describes a group of rare diseases caused by protein conformation abnormalities resulting in extracellular deposition and accumulation of insoluble fibrillar aggregates. So far, 36 amyloid precursor proteins have been identified, and each one is responsible for a specific disease entity. Transthyretin amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, due to the deposition of transthyretin (TTR), which is a transport protein mainly synthesized in the liver but also in the retinal pigment epithelial cells. ATTRv amyloidosis may be misdiagnosed with several other conditions, resulting in a significant diagnostic delay. Gelsolin and keratoepithelin are other proteins that, when mutated, are responsible for a systemic amyloid disease with significant ocular manifestations that not infrequently appear before systemic involvement. The main signs of ocular amyloid deposition are in the cornea, irido-corneal angle and vitreous, causing complications related to vasculopathy and neuropathy at the local level. This review aims at describing the main biochemical, histopathological and clinical features of systemic amyloidosis associated with eye involvement, with particular emphasis on the inherited forms. We discuss currently available treatments, focusing on ocular involvement and specific ophthalmologic management and highlighting the importance of a prompt treatment for the potential sight-threatening complications derived from amyloid deposition in ocular tissues.

[Update on immunohistological classification of amyloidoses]. / Update--Immunhistologische Klassifikation der Amyloidosen.

The exact classification of amyloid in surgical pathology specimens is complicated by the increasing number of amyloid diseases, with more than 25 different currently known amyloid proteins. Special attention has to be paid to distinguishing hereditary amyloidosis from AL amyloidosis. For this reason we started several years ago to search specifically for hereditary amyloidoses by improving the immunohistochemical classification of amyloid with new antibodies and by applying molecular biology. Since then we have found various cases of systemic and local amyloid diseases in Germany, including, AApoAI-, AFib-, AKer-, ALys- and ATTR-amyloidosis, as well as hitherto unknown amyloidoses. Based on an increasing number of referrals we also collected substantial numbers of cases, which allowed a direct comparison of the prevalences of the various amyloid diseases in organ biopsies.

[Amyloid centers in Europe: the EURAMY project]. / Amyloidose-Zentren in Europa: Das EURAMY-Projekt.

The systemic amyloidoses comprise a large group of serious protein deposition diseases. Although rather rare, the disorders are spread all over the world. Increasing understanding of pathogenic mechanisms and recent hope for treatment options demand further research and development of diagnostic procedures. The European Union Framework 6 program EURAMY (http://www.EURAMY.org) is devoted to all aspects of research on systemic amyloidoses, from molecular aspects to treatment of patients.

[Hereditary and non-hereditary cutaneous amyloidoses]. / Hereditäre und nichthereditäre kutane Amyloidosen.

Amyloid and amyloidosis describes a heterogeneous group of diseases which are characterized by the pathological extracellular deposition of autologous proteins. Basically, amyloidoses can be divided into systemic or organ-limited (e.g. cutaneous) forms and can be acquired or hereditary in nature. The subclassification discriminates between primary amyloidosis (in the absence of an obvious predisposing disease) and secondary amyloidosis (if caused by a certain underlying disease). The subclassification of amyloidoses is based on the main protein constituent and therefore on the chemical composition of the amyloid fibrils. However, the exact etiopathogenesis of amyloid formation remains unclear. In addition to the clinical presentation, histology, electron microscopy and biochemical-immunological differentiation are also decisive for a proper diagnosis. In cutaneous amyloidosis the deposition of amyloid either occurs along reticulin fibers and the basal membrane (perireticulary amyloidoses) or along collagen fibers (pericollagenous amyloidosis). The purpose of this article is to provide an up-to-date overview on the different kinds of cutaneous amyloidoses.

[Amyloid and amyloidoses]. / Amyloid und Amyloidosen.

Amyloid is a pathologic fibrillar aggregation of polypeptides in a cross-beta-sheet conformation. Amyloidoses are caused by the deposition of amyloid and may occur as cerebral and extracerebral disease. More than 29 different amyloid proteins have been identified. Analysis of a Congo red-stained tissue section by polarization microscopy is the gold standard for diagnosing amyloid. Subsequent classification of the amyloid is mandatory and is increasingly supported by molecular biological analyses. In Germany, this recently led to the discovery of several hereditary amyloid diseases. The correct classification of amyloid is of paramount importance. This helps to asses the prognosis and plan patient treatment.

[Amyloidoses]. / Amyloidosen.

Amyloidoses make up a group of diseases caused by misfolded proteins. These misfolded proteins are insoluble and are deposited in various tissues and organs, ultimately resulting in severe organ dysfunction. The majority of patients with amlyoidoses suffer from chronic inflammatory, infectious or malignant diseases. Moreover, unexplained nephropathy, cardiomyopathy, neuropathy, enteropathy, arthropathy or macroglossia with or without periorbital bleeding should include an amyloidosis in the differential diagnosis. The latter is facilitated by histological examination of abdominal adipose tissue, the rectum or affected organs. Therapy focuses predominantly on reduction of activity of the underlying disease and specific organ protection. More recent therapeutic strategies include interleukin-1 inhibition, as well as inhibitors of protein misfolding.

Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management.

Amyloidosis comprises a unique group of diseases that share in common the extracellular deposition of insoluble fibrillar proteins in organs and tissues. Cardiovascular amyloidosis can be primary, a part of systemic amyloidosis, or a result of chronic systemic diseases elsewhere in the body. The most common presentations are congestive heart failure-mainly a restrictive infiltrative pattern--and conduction system disturbances. Recent developments in imaging techniques and extracardiac tissue sampling have minimized the need for invasive endomyocardial biopsy for amyloidosis. Despite advances in treatment, the prognosis for patients with amyloidosis is still poor and depends on the underlying disease type. Herein, we present new insights and recent advances in cardiovascular amyloidosis.

Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL).

Light chain-associated amyloidosis (AL) is a plasma cell dyscrasia in which the secreted monoclonal immunoglobulin (Ig) light chains form amyloid fibrils. There is considerable heterogeneity in clinical presentation, and prognosis of the disease relates to the severity of organ dysfunction induced by amyloid deposits. The mechanisms by which the amyloid fibrils are deposited as well as the predilection for specific organ sites have not been clearly elucidated. This study characterizes the repertoire of immunoglobulin light chain variable genes used by the clonal B cell in AL amyloid patients, and the association of light chain variable region (VL) genes with clinical presentation and outcome is assessed in 58 (32 lambda and 26 kappa) patients. A preferential use of VL germ-line genes was noted for both AL kappa and lambda patients. There was a significant correlation between the use of the Vlambda VI germ-line donor, 6a, and renal involvement as well as the Vlambda III gene, 3r, with soft-tissue AL. The use of a biased VL gene repertoire also correlated with clinical outcome, revealing important trends for predicting prognosis. The use of Vlambda II germ-line genes was associated with cardiac amyloidosis and affected survival adversely. The presence of multiple myeloma also correlated with a poor prognosis. The presence of renal disease, on the other hand, was associated with improved survival. Therefore, identification of the clonal VL gene in AL has important implications in determining clinical outcome.