Light chain deposition disease

The aim of the study is to put forward the recent knowledge about a relatively rare clinical condition caused by the deposition of immunoglobulin light chains κ or λ into the parenchyme of kidneys and other vital organs, leading to a progressive loss of their function with terminal organ failure. The paper focuses on the etiopathogenesis of light chain deposition disease, and the differentiation of idiopatic form of the disease from multiple myeloma associated conditions and other B lymphoproliferative disorders. We concentrate on the issue of clinical manifestation, contemporary diagnostic possibilities and differential diagnosis of the disease. Finally, we summarize recent therapeutic approaches using chemo-immunotherapy (bortezomib) and high-dosed chemotherapy with support of autologous peripheral stem cell transplantation that lead to a substantial improvement of the prognosis of this prognostically unfavorable disorder.     

Mu-heavy chain disease associated with systemic amyloidosis

mu-heavy chain disease (HCD) is very rare, with only 30 cases reported in the literature. We report a patient with mu-HCD associated with systemic amyloidosis. The diagnosis of mu-HCD was based on findings of mu-heavy chain fragments in the serum, Bence Jones proteinuria and vacuolated plasma cells in the bone marrow. To our knowledge, this is the third case in which systemic amyloidosis led to the patient's death.     

华氏巨球蛋白血症相关的轻链沉积病

中年男性,贫血、高黏血症、肾功能不全、尿检阴性,免疫球蛋白lgM升高、k型lgM单克隆免疫球蛋白条带,骨髓活检提示华氏巨球蛋白血症.肾脏病理组织学见弥漫肾小管萎缩,小管基膜增厚明显;间质嗜酸性细胞浸润;肾小球病变较轻.免疫荧光染色免疫球蛋白和补体染色阴性.轻链染色显示肾小球毛细血管袢、肾小管基膜、血管壁κ轻链染色阳性.电镜下见肾小球毛细血管袢基膜内侧缘、包曼囊壁、肾小管基膜外侧缘、血管壁见泥沙样电子致密物沉积.结台临床及病理,最终诊断华氏巨球蛋白血症相关的K型轻链沉积病伴急性间质性肾炎.     

肾脏轻-重链沉积病

中年男性,病程3年,临床表现为中等量蛋白尿、少量镜下血尿、高血压、肾功能不全,伴贫血、白细胞减低,血清免疫固定电泳见λ型IgA单克隆免疫球蛋白条带,骨髓细胞学检查浆细胞比例5%。组织学改变为肾小球结节样病变,免疫荧光染色IgA及单一λ轻链均呈线状沉积于肾小球毛细血管袢及肾小管基膜,超微结构见肾小球基膜内侧缘及肾小管基膜外侧缘细沙状、高电子密度的致密物沉积。最终诊断为轻-重链沉积病(IgA-λ型)。     

Hepatic amyloidosis with light chain deposition disease. A rare association

Monoclonal immunoglobulin deposition diseases are due to pathological protein deposition in various tissues and organs. Protein deposits may be found in a single tissue or systemically and the organs most frequently involved are kidney, heart, peripheral nerves and the liver. Depending on the pattern of the deposits and the type of immunoglobulin, these diseases are distinguished as primary amyloidosis, light chain deposition disease. Differential diagnosis is made in tissue specimens: microscopically by the identification of positive Congo red staining of the deposits, by immunohistochemical demonstration of proteins reacting with light chain (λ or k) antisera or by recognition of fibrillar structures on electron microscopy. We report an unusual case of light chain deposition disease associated with amyloidosis, where hepatomegaly was the presenting manifestation and liver failure the cause of death, without any kidney involvement.     

Human ehrlichiosis: a rickettsial disease associated with severe cholestasis and multisystemic disease

We report an unusual case of a typically canine rickettsial disease, ehrlichiosis, in a 56-year-old man. Although only occasionally affecting humans with a mild illness, exposure to a tick bite in our patient led to severe multisystemic disease with intense cholestasis. Coma, acute renal failure and respiratory failure requiring mechanical ventilation ensued. Imaging procedures showed no biliary obstruction. A liver biopsy demonstrated bile stasis and sinusoidal lymphoid infiltrates. The diagnosis was confirmed serologically. Only partial improvement occurred with tetracycline therapy, but total resolution of all abnormalities eventually followed therapy with chloramphenicol.     

Hepatic amyloidosis as cause of severe intrahepatic cholestasis

The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.     

Graves' disease presenting with severe cholestasis

BACKGROUND: Hyperthyroidism has been associated with liver function abnormalities; however, cholestasis as the presenting feature of adolescent Graves' disease has not been previously reported. PATIENT SUMMARY: The patient was a 17-year-old girl who presented with severe cholestasis and was found to have Graves' disease. She also had a positive hepatitis A immunoglobulin M antibody but her clinical course, the liver histopathology, and her mildly elevated transaminases indicated that the acute hepatitis A infection was not dominant at the time of presentation with severe cholestasis. Other causes of cholestasis, including congestive heart failure, autoimmune hepatitis, and viral infection, were excluded. Treatment with methimazole resolved the hyperthyroidism, and the cholestasis improved, as well. CONCLUSION: Severe cholestasis is a rare presenting feature of Graves' disease. With careful monitoring, methimazole can be used to treat the hyperthyroidism in the setting of cholestasis.     

Light chain deposition disease. Experience in our environment

The Light chain deposition disease (LCDD) is a strange entity characterised by the deposition of only one type of light chain in the renal tubular basement membranes. It can be associated to a plasma cell dyscrasia, however, it can occur in the absence of any detectable hematological disorder and it is called idiopathic LCDD. The clinical manifestation is renal insufficiency and nephrotic proteinuria, it does not have a clearly fixed treatment and has a severe prognosis. The aim of this work is to analyse the characteristics of the LCDD cases diagnosed within our environment. Six cases were identified, all of them between 1999 and 2005, from a total amount of 640 renal biopsies performed during this period, 4 women and 2 men, average age of 57. Multiple myeloma in 3 patients were detected (50%). The acute renal failure or rapidly progressive renal insufficiency was the most frequent clinical presentation (66%) together with nephrotic proteinuria (66%). All the biopsies showed tubular basement membranes thickening and kappa chains with a linear distribution within the same. The most frequent glomerular pathological finding was the nodular sclerosing glomerulopathy (83%). In one of the cases the affectation was exclusively tubular interstitial with tubular casts. 3 patients were treated, 2 with multiple myeloma. 5 patients needed dialysis: 3 with idiopathic LCDD within an average time of 7 days from the diagnosis to its reception and 2 with myeloma, who started needing dialysis in an average of 46 days. 4 patients died, 2 of them with myeloma. The monitoring time until the death was 13 weeks for the patients with myeloma and 110 weeks for the rest. CONCLUSION: The LCDD seems to be more frequent than what has been published and it is associated to the myeloma in half of the cases. It appears together with severe renal insufficiency and the patient's and renal prognosis is poor.     

A case of localized AL-type amyloidosis of the stomach]

A 78-year-old woman was admitted to our hospital for treatment of liver cirrhosis and an esophageal varix. Endoscopy revealed a protruding nodular lesion with a transparent smooth surface proximal to the pylorus, which was accompanied by a partly yellow-whitish spot. A depressed lesion with an even edge was found. Histologically, the protruding lesion and depressed lesion showed amyloid deposits, mainly in the mucosal layer. The lesions were found to correspond to AL type amyloidosis by immunochemical analysis. General examination showed no other amyloid deposits. Thus, we diagnosed localized amyloidosis of the stomach.     

Spontaneous rupture of the liver associated with amyloidosis

Fatal spontaneous rupture of the liver is described in a 46-year-old women with hepatic amyloidosis diagnosed premortem by liver biopsy. An autopsy revealed systemic amyloidosis, with no evidence of an underlying chronic inflammatory condition, infection, or immunocyte dyscrasia. By computerized search, this is only the third reported case of spontaneous rupture of the liver complicating amyloidosis.     

Light chain deposition disease: novel biological insights and treatment advances

Light chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of immunoglobulin light chains in various organs. Most cases present with renal dysfunction, a ubiquitous feature of this disease, and in some instances, it may progress to end-stage renal disease. Unfortunately, until now, no standard treatment has been established. The use of alkylating agents and steroids has been extensively reported. However, conventional chemotherapy response is generally limited with minor effects on kidney function. The use of novel agents such as bortezomib has shown a more rapid response with a dramatically important reduction of light chains in serum and/or urine in small series of cases. Furthermore, autologous stem cell transplantation has been reported as a feasible strategy in LCDD, able to prolong the dialysis-free survival. Nonetheless, toxicity from these therapies should be considered carefully because most of patients might present with kidney dysfunction that could limit the use of some agents.     

Charge differences between in vivo deposits in immunoglobulin light chain amyloidosis and non-amyloid light chain deposition disease

Immunoglobulin light chain amyloidosis (AL) and non-amyloid light chain deposition disease (NALCDD) are different forms of protein aggregation disorders that may occur in plasma cell dyscrasias with dysproteinemia. In systemic AL, the deposits are fibrillar and patchy in distribution, within and amongst different organs, whereas in NALCDD, the deposits are granular and diffusely distributed in systemic basement membranes, suggesting different mechanisms of aggregation and deposition. Previous evidence, that charge differences between the light chains in AL and NALCDD might account for their different phenotypes, prompted the present study, which compared the isoelectric points (pIs) of AL and NALCDD protein deposits extracted from human tissues. The pI profiles (5.2-8.8) of polypeptides in AL deposits were heterogenous in four cases, with a spread of both anionic and cationic isoforms; in contrast, in three of NALCDD the pI profiles (8.2-8.8) were homogeneous and restricted in the cationic range. These in vivo findings in human disease, together with other reported in vitro and in vivo experimental data, suggest that the fibrillar deposits in AL may form by electrostatic interaction between oppositely charged polypeptides, whereas the granular deposits in NALCDD form by the binding of cationic polypeptides to anionic proteoglycans sites in basement membranes.     

肝淀粉样变性合并重度淤胆及角膜K-F环1例报告并文献复习

1病历资料患者女,54岁。因"腹胀2年伴进行性身目黄染1个月",于2010年11月入住中山大学附属第一医院消化内科。患者近2年体重下降平均4.5 kg/年,无神经精神症状,否认嗜酒等其他可能引起肝病的危险因素。体格检查示巩膜重度黄染,肝右锁骨     

Granulomatous liver disease and cholestasis

Development of hepatic granulomas, especially those located within portal tracts, is associated with injury to septal and interlobular bile ducts. Dysfunction of the bile ducts in turn leads to cholestasis,and ongoing damage by the granulomatous inflammation eventually results in ductopenia. A multitude of causes of hepatic granulomas have been described over the last few decades. Diligent and prioritized search for cause of hepatic granulomas should proceed within the environmental and epidemiologic context of a given patient. The therapeutic approaches, including amelioration of the cholestatic syndrome, are often determined by successful identification of specific etiologic factors causing the granulomas in the liver.     

Primary amyloidosis with spontaneous splenic rupture, cholestasis, and liver failure treated with emergency liver transplantation

A 61-yr-old man with cholestatic jaundice soon after presentation had an emergency operation because of spontaneous rupture of the spleen. This was found to be caused by primary systemic amyloidosis. After the splenectomy, the patient deteriorated with liver failure and was successfully treated with liver transplantation. Osteopenic fractures of the thoracic columna developed after transplantation. Except for this, the patient is well 18 months after transplantation.