AL amyloidosis

Akasheh MS, Chang CP, Vesole DH. Acute tumour lysis syndrome a case in AL amyloidosis. Br J Haematol 1999 107(2) 387. 

Kumar, K.S., Lefkowitch, J., Russo, M.W., Hesdorffer, C., Kinkhab-wala, M., Kapur, S., Emond, J.C., Brown, R.S. Successful sequential liver and stem cell transplantation for hepatic failure due to primary AL amyloidosis. Gastroenterology 2002 122 2026 - 2031... 

Zhou, H., Linke, R.R, Schaefer, H.E., Miibius, W., Pfeifer, U. Progressive liver failure in a patient with adult Niemann-Pick disease associated with generalized AL amyloidosis. Virchows Arch. 1995 426 635-639... 

AL amyloidosis is the most common form of these disorders. Bone marrow plasmacytosis and excess plasma cell production of antigenicaHy identical monoclonal light chains are common to primary amyloidosis and multiple myeloma. Thus a clear distinction between these two conditions is not possible chemically. They appear to differ only in the presence or absence of osteolytic lesions. AL deposits may occur in the tongue, heart, lymph nodes, spleen, joints, peripheral nerves, and skin. 

A, Cadiot D, et al. Prognostic factors for survival and response after high-dose therapy and autologous stem cell transplantation in systemic AL amyloidosis a report on 21 patients. Br J Hematol 1998 101 ... 

Amyloidosis is a term encompassing many diseases that share a common feature— the extracellular deposition of pathologic insoluble fibrillar proteins called amyloid in organs and tissues. In Amy Lloyd s disease, amyloidosis/AL, the amyloid is derived from immunoglobulin light chains (AL = amyloidosis, light-chain related). 

In AL amyloidosis, amyloid is formed from degradation products of the X or k light chains that deposit most frequently in the extracellular matrix of the kidney and the heart but also may deposit in the tongue. In other types of amyloidosis, the amyloid arises from other proteins and deposits in a characteristic organ. For example, the amyloid associated with chronic inflammatory conditions, such as tuberculosis or rheumatoid arthritis, is derived from an acute phase serum protein called serum amyloid Athat is produced by the liver in response to inflammation. It deposits most frequently in the kidney, and cardiac involvement is rare. 

Amy Lloyd. Amy Lloyd has AL amyloidosis, which is characterized by [ ) deposition of amyloid fibers derived principally from the variable region of... 

Mikhael JAR, Schuster SR, Jimenez-Zepeda VH, Bello N, Spong J, Reeder CB, Stewart AK, Bergsagel PF, Fonseca R. Cyclophosphamide-bortezomib-dexamethasone (CtBorD) produces rapid and complete hematological response in patients with AL amyloidosis. Blood. 2012 10 4391 3942034. 

The true incidence of AL amyloidosis, an orphan disease, remains unknown. Extrapolating a 30-year experience at the Mayo Clinic, Gertz et al. (6) estimated that 3200 new cases occur annually in the United States. The National Center for Health reported an incidence of 4.5 cases per 100,000 population in the United States—or nearly 13,500 cases per year (7). Between 1994 and 2002, we evaluated 701 patients with AL amyloidosis at Boston University Medical Center (8). 

Among the 29 case reports over the past 30 years (17-19), 19 cases provide sufficient data to establish the diagnosis of AL amyloidosis. Pleural biopsies documented amyloid deposits in 13 (68%) of these cases. Although 16 of 19 cases (84%) had concomitant congestive heart failure (CHF), 56% expressed exudative pleural fluid chemistries, suggesting disruption of pleural membrane mechanics. 

The physiology of amyloid pleural effusions is complex. AL amyloidosis can alter the function of several organs that could contribute to effusion formation including the heart (infiltrative cardiomyopathy—48% cases), kidneys (nephrotic syndrome—65% cases), and thyroid (hypothyroidism—4% cases) (20). 

Taken together, these data indicate that left ventricular dysfunction and elevated cardiac filling pressures, hypothyroidism, and nephrotic syndrome/ hypoalbuminemia may all contribute but are not sufficient for the formation and maintenance of large persistent pleural effusion in AL amyloidosis. The incidence of exudative chemistries and the presence of amyloid deposits on pleural biopsies suggest that amyloid infiltrates and disrupts pleural mechanics, inducing fluid secretion and impairing parietal membrane drainage from the pleural space. 

Large persistent pleural effusions are associated with limited survival in AL amyloidosis. Untreated patients with large effusions lived a median of 1.6 months (1-18.5 months, range) versus 6 months (0-29 months, range) in untreated effusion-free cardiomyopathy patients (p = 0.031) (21). 

Chylothorax is rarely reported (21-23). The low incidence of chylous effusions despite the frequent appearance of mediastinal and hilar adenopathy in AL amyloidosis raises the possibility that direct amyloid infiltration of pleural lymphatics causes chylous effusions, not lymph node compression of mediastinal lymphatics. 

The literature includes eight case reports of pulmonary hypertension in AL amyloidosis attributed to pulmonary vascular amyloid deposition (Table 2). Autopsies confirmed pulmonary artery amyloid deposits in four out of four cases. The prevalence of restrictive cardiomyopathy and diastolic dysfunction in AL patients predisposes them to secondary forms of pulmonary vascular disease. Direct measurements of pulmonary artery pressures (PAP) were obtained in five cases (3 pulmonary arteriograms, 2 right heart catheterizations) however, only two reports include direct measures of left atrial filling pressures. Echocardio-graphic estimates of elevated right ventricular systolic pressures and normal diastolic function were reported in all cases. 

An autopsy series of 15 individuals with AL amyloidosis or multiple myeloma/AL amyloid found mild-to-severe pulmonary vessel amyloid deposition in >90% of cases (13). The ubiquity of pulmonary vascular amyloid in AL patients is in stark contrast to the small number of clinically recognized cases of amyloid-mediated pulmonary hypertension. It appears, therefore, pulmonary vascular amyloid deposition is required, but not sufficient, for inducing pulmonary hypertension in AL patients. 

Approximately 1 % of patients with chronic inflammatory conditions (connective tissue disease, malignancy, infection, cystic fibrosis, Castleman s disease) express AA amyloid (34). The incidence of AA amyloid increases 5- to 10-fold in Europe due to larger number of patients with chronic inflammatory disease. In the Western world, AA amyloidosis occurs in 0.5% to 0.86% of autopsies (7). In contrast to AL amyloidosis, we evaluated only 31 patients with AA amyloidosis at Boston University Medical Center between 1994 and 2002. 

Skinner M, Sanchorawala V, Seldin DC, et al. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis an 8-year study. Ann Intern Med 2004 140(2) 85-93. 

Santiago RM, Scharnhorst D, Ratkin G, et al. Respiratory muscle weakness and ventilatory failure in AL amyloidosis with muscular pseudohypertrophy. Am J Med 1987 83(1) 175-178. 

Setoguchi M, Hoshii Y, Kawano H, et al. Analysis of plasma cell clonality in localized AL amyloidosis. Amyloid 2000 7(l) 41-45. 

Hui AN, Koss MN, Hochholzer L, et al. Amyloidosis presenting in the lower respiratory tract. Clinicopathologic, radiologic, immunohistochemical, and histo-chemical studies on 48 cases. Arch Pathol Lab Med 1986 110(3) 212-218. 

Langerhans cell histiocytosis (Dr. Vassallo et al.), lymphangioleiomyomatosis (Dr. McCormack), pulmonary alveolar proteinosis (Dr. Wang et al.), amyloidosis (Dr. Berk), and drug-induced pulmonary disorders (Drs. Maldonado and Limper). 

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