Systemic Light Chain Deposition Disease Research Articles

A Case of Light Chain Deposition Disease Leading to Acute Liver Failure and Review of Literature

Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease characterized by light chain deposition in soft tissues and viscera, causing systemic organ dysfunction with an underlying lymphoproliferative disorder. While the kidney is the most affected organ, cardiac and hepatic involvement is also seen with LCDD. Hepatic manifestation can range from mild hepatic injury to fulminant liver failure. Herein, we are presenting a case of an 83-year-old woman with a monoclonal gammopathy of undetermined significance (MGUS), who presented to our institution with acute liver failure progressing to circulatory shock and multiorgan failure. After an extensive workup, a diagnosis of hepatic LCDD was determined. In conjunction with the hematology and oncology department, chemotherapy options were discussed, but given her poor prognosis, the family decided to pursue a palliative route. Though establishing a prompt diagnosis is important for any acute condition, the rarity of this condition, along with paucity of data, makes timely diagnosis and treatment challenging. The available literature shows variable rates of success with chemotherapy for systemic LCDD. Despite chemotherapeutic advances, liver failure in LCDD indicates a dismal prognosis, where further clinical trials are difficult owing to the low prevalence of the condition. In our article, we will also be reviewing previous case reports on this disease.

S3089 Monoclonal Immunoglobulin Deposition Disease: A Rare Case of Acute Liver Failure

Introduction: Light chain deposition disease (LCDD) is a characterized by deposition of immunoglobulin light chain in extracellular tissue. Classically it involves the kidneys, however, can rarely affect other organs such as liver. Its manifestation is mostly non-specific and presents as mild cholestatic liver injury and, acute liver failure is extremely rare. Case Description/Methods: An 83-year-old female with Monoclonal Gammopathy of Undetermined Significance (MGUS) was admitted to the hospital for dyspnea and anasarca. Her initial labs were remarkable for mild, predominantly cholestatic, pattern of liver injury. Additional workup was negative for common etiologies of liver injury, with normal appearance of liver and new-onset diastolic cardiac dysfunction. Initial diagnosis was acute liver injury in the setting of recent heart failure and treatment with aggressive diuresis was commenced. However, she progressed to acute liver dysfunction and multi-organ failure manifesting as encephalopathy, jaundice (T.Bili 16.25) and coagulopathy (INR 1.3). Her Alk-Phos was 1116 and AST, ALT were 289 and 95, respectively. Liver biopsy revealed deposition of pink hyaline material expanding the sinusoids. This was initially suspected to be amyloid, until a positive PAS and negative Congo-Red stain established the diagnosis of LCDD. SPEP revealed a M-protein light chain with elevated κ/λ ratio of 16.6. Chemotherapy was rejected considering poor prognosis and patient was discharged on hospice care. Discussion: LCDD results from excessive production and deposition of monoclonal light chains into various organs including liver. Concurrent plasma cell dyscrasias and multiple myeloma are often seen in these patients. High suspicion of disease and biopsy without delay is imperative for diagnosis, which typically show granular, κ LC predominant deposits in the perisinusoidal basement membrane which unlike amyloid, appear unorganized and stain positive with PAS and negative with Congo-Red. At present, there is no consensus on LCDD treatment, however, autologous stem cell transplant following bone marrow conditioning with high dose melphalan and bortezomib based induction chemotherapy with or without systemic glucocorticoids have been reported to treat hepatic and systemic LCDD with some success.

Epidemiological and clinical characteristics and outcome of monoclonal gammopathy of renal significance-related lesions in Latin America.

Monoclonal gammopathy of renal significance (MGRS)-related lesions are infrequent entities. There are no publications on these disorders in Latin America (LA). The aim of this study was to describe epidemiological and clinical characteristics of these patients in LA. We performed a multicentre retrospective study. Patients with diagnosis of MGRS between 2012 and 2018 were included. Epidemiological and clinical data were collected from clinical records. Twenty-seven patients from Chile, Argentina, Ecuador and Uruguay were included. Half debuted with a nephrotic syndrome, and 32% required dialysis. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits was found in 33%, amyloidosis in 26% and monoclonal immunoglobulin deposition disease also in 26%. The immunoglobulin most frequently found in renal biopsies was IgG kappa. In 67% a paraprotein was found. Twenty patients received an anti-plasma cell regimen, and 3 a rituximab-based regimen (IgM-MGRS). Renal response (RR) was achieved in 56%. Early treatment (≤3 months) was associated with higher RR (75% vs 43%). Three patients relapsed within 21.5 months, and 3 progressed: 1 to multiple myeloma, 1 to systemic amyloidosis and another to systemic light-chain deposition disease. Two patients died, both due to infection during induction treatment. There was a higher than expected frequency of patients requiring dialysis. The most common MGRS-related lesion was PGNMD. Early treatment was associated with better response. As a rare disease, increasing awareness and promoting early diagnosis are necessary in LA to improve outcomes. SUMMARY AT A GLANCE A collection of 27 cases of MGRS from Latin America with information on epidemiology, clinical characteristics, treatment and outcome of patients diagnosed of MGRS-related renal lesions.

Epidemiological and Clinical Characteristics of Monoclonal Gammopathy of Renal Significance (MGRS) in South America

▪BackgroundMonoclonal gammopathy of renal significance (MGRS) is a recently defined entity. It is a group of renal diseases due to paraprotein deposition from a small B lymphocyte or plasma cell clon, not meeting the criteria for an overt gammopathy-associated neoplasm. Despite this feature, the secondary kidney damage may be severe and irreversible; therefore, its early recognition and treatment are crucial. There are few studies on MGRS in the international literature, and no reported data from Latin America (LA).AimsTo describe epidemiological and clinical characteristics of patients diagnosed with MGRS in LA.To evaluate patients outcomes.Material and methodsThis is an international multicentric retrospective case series study.All members of GELAMM (Grupo de estudio latinoamericano de Mieloma Múltiple) were invited to participate.Patients with diagnosis of MGRS according to the IMWG definition were included. All cases had pathological diagnosis provided by a renal biopsy.Epidemiological and clinical data were collected from clinical records in a standardized report form.Renal response was arbitrarily defined as the partial or total recovery of renal failure or renal symtoms at the end of treatment.Statistical analysis was performed by descriptive statistics using STATA 12.ResultsWe received data from 18 patients, from centers in Chile, Argentina and Uruguay. Median follow up was 22,5 months.The patients characteristics are shown in table 1. The median age was 58 years (36 to 78 years). Male to female ratio was 1:1,25. Twelve had history of hypertension and one patient of renal transplantation. Anemia was present in 78% of cases (mean 10,7g/dL +/-2,3), hypoalbuminemia in 72% (mean 2,8g/dL +/-0,7), renal failure in 83% (mean creatinine of 4,6mg/dL +/- 4,8) with 47% of these (7 patients) requiring renal replacement therapy (RRT). Proteinuria was measured in 16 patients. Its average was 4,4gr (range 0,12 - 11,5gr/24hrs). LDH and calcemia were normal in all cases.Half of the patients presented as a nephrotic syndrome. Regarding histological subtypes, the most frequently diagnosed was the proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). The paraprotein most frequently found was Kappa, and in the renal biopsy was IgG Kappa deposition (table 1).Serum protein electrophoresis (sPEP) was performed in all cases. Only 8 out 18 patients underwent urine protein electrophoresis (uPEP) and 14 had urine and serum immunofixation (IFX) done. Serum free light chain (sFLC) were performed in 94% of the patients. The paraprotein identification according to each of this exams is shown in figure 1.Seventeen patients received treatment; 13 received an anti-plasma cell drug, 7 a thalidomide based regimen and 6 a bortezomib based regimen. The patient with IgM MGRS was treated with a rituximab based regimen. Regarding renal responses, there were no data in 5 patients. Nine out 13 of the patients achieved renal response: 3 achieved partial recovery and 9 complete recovery. Three patients become RRT independent. There was no mortality in our cohort. No patient relapsed, but 3 progressed: 1 to multiple myeloma (MM), 1 to systemic amyloidosis and another to systemic light chain deposition disease (LCDD).DiscussionOnly 18 cases from 3 South American countries were collected. The lack of hematologists in some countries, difficulties in achieving a renal biopsy, non-availability of immunofluorescence in the histological studies and few experienced pathologists could be some of the problems in our region.Our cohort is of rather young patients, which is probably related to the fact that these patients are mostly undergoing renal biopsy. We believe, however, that the incidence of MGRS (similar to what happens with MGUS), increases with age, which could mean a problem of underdiagnoses.As expected, nephropathies frequently associated with MM were found: AL amyloidosis and LCDD. However, the most common renal pathology was PGNMID, a rare entity. This data must be corroborated with a larger study.The high sensitivity of sFLC to identify the paraprotein was corroborated and highlighted the importance of this test in the follow up.Half of patients achieved a renal response, which reinforces the fact that they must be promptly treated.ConclusionAccording to our knowledge, this is the larger cases series study in LA, and we hope it will be a contribution to the knowledge of this pathology. DisclosuresNo relevant conflicts of interest to declare.

Serous retinal detachments associated with light chain deposition disease.

To report the clinical, fluorescein angiography, spectral-domain optical coherence tomography, and fundus autofluorescence (AF) findings of a 64-year-old woman with systemic light chain deposition disease. Clinical examination, fundus photographs, fundus AF, spectral-domain optical coherence tomography, and fluorescein angiography before and after renal transplantation in a patient with light chain deposition disease. The patient presented with decreased visual acuity in her right eye. Fundus examination showed bilateral drusenoid subretinal deposits associated with subretinal fluid. Fluorescein angiography showed staining of the lesions seen on clinical examination. Spectral-domain optical coherence tomography showed hyperreflective material below the neurosensory retina associated with subretinal fluid. Fundus AF showed areas of increased AF corresponding to the lesions. The lesions showed improvement after renal transplantation and initiation of immunosuppressive agents. Patients with light chain deposition disease may present with subretinal deposits that can be seen clinically and demonstrated on fluorescein angiography, AF, and optical coherence tomography. They may also present with localized serious retinal detachments. Both these deposits and serous retinal detachments may improve with renal transplantation or immunosuppressive therapy.

A Case of Isolated Light Chain Deposition Disease in the Duodenum

Light chain deposition disease (LCDD) is a rare disorder associated with a clonal proliferation of plasma cells, which synthesize abnormal monoclonal immunoglobulin light chains. LCDD is characterized by systemic deposition of light chains in various organs, with the kidneys being most commonly affected. There have been few reports of isolated LCDD. We report a rare case of LCDD limited to a duodenal polyp. A 63-yr-old man visited our hospital for health screening without symptoms in 2009. On gastrofiberscopy, a duodenal polyp was observed. The biopsy showed diffuse infiltration by atypical plasma cells, which were positive for kappa-type light chains by immunohistochemistry. While the patient refused further management, we could find no evidence of recurrence until 2 yr after the initial diagnosis. It has been reported that isolated LCDD has relatively good prognosis compared to systemic LCDD. However, treatment for this disease has not been established yet.

Case report: A case of light chain deposition disease involving liver and stomach with chronic hepatitis C virus infection and hepatocellular carcinoma

Light chain deposition disease (LCDD) is a rare, plasma cell proliferative disorder characterized by mainly abnormal light chain deposition in various organs. Hepatitis C virus (HCV) is a hepatotrophic and lymphotrophic virus and significantly related to B-cell proliferation. This is a case report of systemic LCDD involving liver, stomach, bone marrow, and probably kidney, in a patient with HCV-related hepatocellular carcinoma (HCC). A 62-year-old man with chronic HCV infection who presented with a small HCC in segment 8 of the liver and nephrotic syndrome showed kappa typed immunoglobulin light chain depositions in biopsy specimens of bone marrow, stomach, and non-tumorous liver parenchyma. After treatment of the HCC with transarterial chemoembolization, antiviral therapy for chronic hepatitis C was started. The patient showed early virologic response at 12 weeks of treatment; however, antiviral therapy was discontinued due to adverse effects and he was lost to follow-up. This is the first case of LCDD involving the liver and stomach in a patient with chronic HCV infection and HCC, which may represent LCDD as a rare HCV-associated B cell proliferative disease.

Amyloid-like Pulmonary Nodules, Including Localized Light-Chain Deposition

Amyloid-like pulmonary nodules have been described in patients with systemic light-chain deposition disease, but their significance in other clinical contexts is unknown. We examined biopsy specimens of amyloid-like pulmonary nodules from 3 women without systemic light-chain deposition disease. Patient 1 (aged 62 years) had multiple pulmonary nodules and underwent 2 separate lung biopsies, the first showing nodules composed of κ light-chain deposits accompanied by low-grade lymphoplasmacytic lymphoma limited to the lung and the second, obtained after chemotherapy 9 months later, showing only residual nodules without persistent lymphoma. Patients 2 (aged 65 years) and 3 (aged 69 years) had asymptomatic solitary pulmonary nodules. In all cases, electron microscopic examination showed dense granular extracellular deposits without the fibrillary characteristics of amyloid. Amyloid-like nodules should be distinguished from nodular amyloidosis and, in some patients, might represent a localized form of light-chain deposition.

Tumoral non‐amyloidotic monoclonal immunoglobulin light chain deposits (‘aggregoma’): presenting feature of B‐cell dyscrasia in three cases with immunohistochemical and biochemical analyses

Tumoral monoclonal immunoglobulin (Ig) light chain non-fibrillar deposits ('aggregomas'), which can be considered analogous to solitary light chain amyloidomas, are a rare presenting feature of B-cell dyscrasias. It is not certain if they are truly localized or if in reality they represent an initial expression of a silent systemic non-amyloid light chain deposition disease (LCDD). This report describes three patients, two of whom presented with cervical masses and the third with a solitary lung nodule, each comprising granular aggregates of monoclonal kappa light chain. Extracted deposits from the lymph node of one patient were shown by N-terminal amino acid sequence analysis to belong to the variable-region kappa I (Vkappa I) light chain subgroup, the first reported kappa-LCDD protein encoded by the L9 gene and the first report of an expressed protein related to this gene. Extracted deposits from the lung nodule of the second patient belonged to the Vkappa IV light chain subgroup encoded by the B3 germ line gene. The N-terminal amino acid sequences of the light chains from the aggregomas were compared with the related germ line sequences and to the N-terminal amino acid sequences of the nine other known kappa-LCDD light chains reported thus far from patients with systemic LCDD.

Ocular manifestations of immunologic and rheumatologic inflammatory disorders

New manifestations of immunologically mediated ocular disease continue to be recognized while knowledge of the mechanisms involved gradually expands. Optic atrophy associated with antiphos-pholipid antibodies has been described. Ocular manifestations of linear scleroderma, including levator and extraocular muscle atrophy, have been recognized, as has orbital fat atrophy in systemic scleroderma. The role of eosinophil degranulation in histiocystosis X, orbital pseudotumor, and Wegener's granulomatosis has been investigated. Further characterization of immunopathologic conjunctival changes in ocular cicatricial pemphigoid and Sjogren's syndrome clarifies our understanding of these disorders. Unusual manifestations of rheumatoid arthritis, systemic light chain deposition disease, and Raynaud's disease have been noted, and new developments in Behçet's disease and Vogt-Koyanagi-Harada syndrome have been reported.

RETINAL VASCULOPATHY ASSOCIATED WITH SYSTEMIC LIGHT CHAIN DEPOSITION DISEASE

A 35-year-old black male with the abrupt onset of blurred vision and decreased visual acuity was found to have severe retinal vasculopathy associated with systemic light chain deposition disease. While ocular manifestations are frequently reported in other plasma cell dyscrasias; ophthalmologic symptoms have not been previously reported in systemic light chain deposition disease alone. A possible mechanism of light chain deposition and damage to the retinal vasculature is proposed.