scholarly journals An Unusual Case of Cholestatic Hepatitis due to Light-Chain Deposition Disease

2020 ◽  
Vol 13 (3) ◽  
pp. 1343-1348
Author(s):  
Alessandro Grembiale ◽  
Elena Garlatti ◽  
Anna Ermacora ◽  
Silvia Grazioli ◽  
Massimiliano Balbi ◽  
...  
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Clinical State ◽  
Fibrillar Structure ◽  
Kappa Light Chain ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Monoclonal Immunoglobulins ◽  
Intestine Mucosa ◽  
Light Chain Deposition

Light-chain deposition disease (LCDD) is a rare paraproteinaemia characterized by the deposition of monoclonal immunoglobulins with a non-fibrillar structure and hence Congo red negative deposits. Kidney disease is the more frequent manifestation, but other organs may also be involved. A 70-year-old man with hypertension and mild chronic renal failure showed a hepatomegaly without splenomegaly. His renal and liver test rapidly got worse. A serum electrophoresis and immunofixation isolated monoclonal kappa light-chain gammopathy, with serum free kappa light chain excess. The bone marrow biopsy showed the presence of interstitial infiltration of plasma cells like multiple myeloma type at initial phase. Periumbilical fat biopsy was negative. Echocardiography demonstrated an infiltrative cardiac disease. The biopsies of the duodenum small intestine mucosa showed flaps with eosinophil material (Masson’s staining) with atrophic crypts and chronic inflammation at chorion level. Amyloid substance was negative. There was a strong positivity for light chains kappa compatible with LCDD. A liver biopsy confirmed this finding. Therapy with dexamethasone and bortezomib improved clinical state and hepatic and renal laboratory tests. Chemotherapy based on novel anti-myeloma agents should be rapidly considered in LCDD patients with severe organ involvement.

Light-chain deposition disease

2018 ◽  
Author(s):  
Dirk R. J. Kuypers ◽  
Morie A. Gertz
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Renal Involvement ◽  
Bone Marrow Examination ◽  
Therapeutic Monitoring ◽  
Light Chains ◽  
Monoclonal Immunoglobulin ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

Light-chain deposition disease (LCDD) is characterized by extracellular tissue deposition of non-amyloid monoclonal immunoglobulin light chains (predominantly kappa light chains) in various organs including kidneys, heart, and liver. It is a rare cause of renal insufficiency. In two-thirds of cases it is associated with multiple myeloma, while in the remainder their monoclonal B cell proliferation does not meet the criteria for that diagnosis.Renal involvement occurs almost invariably and dominates the clinical course of the disease: greater than 90% of patients with LCDD have renal functional impairment; acute or rapidly progressive kidney failure usually develops over a period of months. Nephrotic-range proteinuria is present in 40–50% of patients while approximately 20% of patients develop nephrotic syndrome. Arterial hypertension and microscopic haematuria can be present. Extrarenal symptoms are related to affected organs with cardiomyopathy, cachexia, haemorrhages, infections, and MM progression as main causes of death.The diagnosis of LCDD is often delayed and whilst bone marrow examination will often identify associated MM, renal biopsy frequently provides the final diagnostic proof. Abnormal light chains can be detected and quantified by serum or urine protein electrophoresis and immunofixation. Quantification of urine and serum free kappa/lambda light chains has proven a useful screening tool and might also plays a role in therapeutic monitoring.Treatment consists of chemotherapy directed against the monoclonal immunoglobulin-producing plasma cells.

scholarly journals Glomerulosclerosis and kidney failure in a mouse model of monoclonal immunoglobulin light-chain deposition disease

2019 ◽  
Author(s):  
Sébastien Bender ◽  
Maria Victoria Ayala ◽  
Amélie Bonaud ◽  
Vincent Javaugue ◽  
Claire Carrion ◽  
...  
Keyword(s):  
Mouse Model ◽  
Light Chain ◽  
Kidney Failure ◽  
Plasma Cells ◽  
Kidney Diseases ◽  
Variable Domain ◽  
Monoclonal Immunoglobulin ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

AbstractLight chain deposition disease (LCDD) is a rare disorder characterized by glomerular and peritubular amorphous deposits of a monoclonal immunoglobulin (Ig) light chain (LC), leading to nodular glomerulosclerosis and nephrotic syndrome. We developed a transgenic model using site-directed insertion of the variable domain of a pathogenic human LC gene into the mouse Ig kappa locus, ensuring its production by all plasma cells. High free LC levels were achieved after backcrossing with mice presenting increased plasma cell differentiation and no Ig heavy chain (HC) production. Our mouse model recapitulates the characteristic features of LCDD, including progressive glomerulosclerosis, nephrotic-range proteinuria and finally, kidney failure. The variable domain of the LC bears alone the structural properties involved in its pathogenicity. RNA sequencing conducted on plasma cells demonstrated that LCDD LC induces endoplasmic reticulum stress, likely accounting for the high efficiency of proteasome inhibitor-based therapy. Accordingly, reduction of circulating pathogenic LC was efficiently achieved and not only preserved renal function, but partially reversed kidney lesions. Finally, transcriptome analysis of pre-sclerotic glomeruli revealed that proliferation and extracellular matrix remodelling represented the first steps of glomerulosclerosis, paving the way for future therapeutic strategies in LCDD and other kidney diseases featuring diffuse glomerulosclerosis, particularly diabetic nephropathy.

Primary CNS Nonamyloidogenic Light Chain Deposition Disease: Case Report and Brief Review

2017 ◽  
Vol 25 (8) ◽  
pp. 755-760 ◽  
Author(s):  
Juan Jose Mercado ◽  
James M. Markert ◽  
William Meador ◽  
Philip Chapman ◽  
Arie Perry ◽  
...  
Keyword(s):  
Light Chain ◽  
Congo Red ◽  
Plasma Cells ◽  
Stereotactic Brain Biopsy ◽  
Light Chain Deposition Disease ◽  
True Incidence ◽  
Brain White Matter ◽  
Deposition Disease ◽  
Disease Case ◽  
Light Chain Deposition

The true incidence of light chain deposition disease (LCDD) restricted to the central nervous system (CNS) is unknown. To our knowledge only 7 cases of LCDD restricted to the brain have been previously reported. We herein describe an unusual example. A 44-year-old man presented with a history of ischemic retinopathy in 2004 and left lower extremity hypoesthesia in 2007 that progressed gradually to left-sided weakness and numbness in the 2 years prior to his hospitalization in 2015. A stereotactic brain biopsy was performed, displaying nonspecific hyaline deposits of amorphous “amyloid-like” material involving deep brain white matter and vessels. These were Congo red negative and were accompanied by a sparse lymphoplasmacytic infiltrate. Plasma cells demonstrated kappa light chain class restriction by chromogenic in situ hybridization (CISH). There was patchy reactivity with kappa immunohistochemistry in the amorphous deposits. A diagnosis of light chain deposition disease was made. Subsequent systemic myeloma and lymphoma workups were negative. Previously reported cases have included men and women, spanning the ages of 19 and 72 years, often presenting with hemiparesis, hypoesthesia, or seizures. Deposits have been reported in the cerebrum and cerebellum. T2/FLAIR (fluid attenuation inversion recovery) changes are usual, but lesions may or may not produce contrast enhancement. The light chain deposition may be of kappa or lambda class. Most lesions have been accompanied by local lymphoid and/or plasma cell infiltrates exhibiting light chain restriction of the same class as the deposits. In summary, LCDD limited to the CNS is a rare lesion consisting of deposition of amyloid-like, but Congo red–negative monotypic light chain usually produced by local lymphoplasmacytic infiltrates.

Recovery from LCDD-associated Severe Liver Cholestasis: a Case Report and Literature Review

2016 ◽  
Vol 25 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Benoit Brilland ◽  
Johnny Sayegh ◽  
Anne Croue ◽  
Frank Bridoux ◽  
Jean-François Subra ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Intrahepatic Cholestasis ◽  
Relevant Literature ◽  
Gamma Glutamyl Transferase ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Uncommon Presentation ◽  
Light Chain Deposition ◽  
Glutamyl Transferase

Light chain deposition disease (LCDD) is a rare multisystemic disorder associated with plasma cell proliferation. It mainly affects the kidney, but liver and heart involvement may occur, sometimes mimicking the picture of systemic amyloidosis. Liver disease in LCDD is usually asymptomatic and exceptionally manifests with severe cholestatic hepatitis. We report the case of a 66-year-old female with κ-LCDD and cast nephropathy in the setting of symptomatic multiple myeloma who, after a first cycle of bortezomib-dexamethasone chemotherapy, developed severe and rapidly worsening intrahepatic cholestasis secondary to liver κ-light chain deposition. Intrahepatic cholestasis was attributed to LCDD on the basis of the liver histology and exclusion of possible diagnoses. Chemotherapy was maintained and resulted in progressive resolution of cholestasis. We report here an uncommon presentation of LCDD, with prominent liver involvement that fully recovered with bortezomib-based chemotherapy, and briefly review the relevant literature. Abbreviations: AKI: Acute kidney injury; ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CMV: Cytomegalovirus; EBV: Epstein–Barr virus; GGT: gamma-glutamyl transferase; HSV: Herpes simplex virus; LC: light chain; LCDD: Light chain deposition disease; MIDD: Monoclonal immunoglobulin deposition disease; MM: Multiple myeloma.

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