[Cardiac amyloidosis]. / Les amyloses cardiaques.

Different types of amyloid deposits involve the heart. Transthyretin and light chain amyloidosis are the most frequent. Diagnostic performance, typing and treatments have improved in the last decade, and prognosis of cardiac amyloidosis is now significantly better thanks to targeted therapies. In this article, we will describe the clinical manifestations of cardiac amyloidosis, the diagnostic approach and detail the characteristics and specific treatments of the most frequent types of cardiac amyloidosis. We will focus on the histopathological aspects, especially on the importance of amyloid typing.

[Interest of daratumumab in refractory AL amyloidosis in a 96-year-old patient]. / Intérêt du daratumumab dans l'amylose AL réfractaire chez une patiente de 96ans.

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+plasma cells, resulting in organ dysfunction. Cardiac involvement has a major prognostic value. Antiplasma cell chemotherapy reduces the synthesis of immunoglobulin light chains (precursors of amyloid deposits). We describe a case of AL amyloidosis in a 95-year-old patient. Our patient responded poorly to treatment with rituximab, cyclophosphamide-bortezomib-dexamethasone, and rituximab-bendamustine. Finally, the anti-CD38 antibody daratumumab was associated with the best hematologic responsiveness without significant adverse effects. In conclusion, our case suggests that daratumumab is an effective and well-tolerated alternative to chemotherapy in the treatment af AL amyloidosis in very elderly patients.

[A rare cause of pulmonary arterial hypertension: Thoracic amyloidosis]. / Une cause rare d'hypertension artérielle pulmonaire : l'amylose thoracique.

Isolated thoracic involvement in amyloidosis is a rare and serious condition. Its association with pulmonary arterial hypertension (PAH) usually weakens the prognosis. We report the case of a 40-year-old man with a smoking history, hospitalized for chest pain, abdominal pain and acute respiratory distress. The cardiac ultrasound revealed a circumferential pericardial effusion as well as a pulmonary artery systolic pressure (PAPS) at 80mmHg. Chest imaging (computed tomography scan and magnetic resonance imaging) showed a tissue process developed in the pericardial sheath (60×45mm) sheathing the ascending aorta and infiltrating the trunk of the pulmonary artery and its right branch. Anatomopathological and immunohistochemical study of the process revealed AL amyloidosis. Note that the patient had no signs of extrathoracic amyloidosis. Blood and urine electrophoresis and immunoelectrophoresis as well as bone marrow mylogram and biopsy were normal. The patient was put on oral anticoagulant as he presented with PAH. A therapeutic protocol with thalidomide and dexamethasone has been initiated. The course of the disease was marked by total regression of the clinical signs, a marked decrease in the amyloid process on imaging and a normalization of the PAPS; our follow-up being three years.

[A systemic disease mimicking a rheumatoid arthritis]. / Une maladie systémique mimant une polyarthrite rhumatoïde.

INTRODUCTION: Rare systemic diseases such as amyloidosis can mimic inflammatory rheumatic diseases. Because of their poor prognosis, physicians should rule them out at the onset of inflammatory rheumatism. We report a case of AL amyloidosis misdiagnosed as rheumatoid arthritis. CASE REPORT: A 71-year-old woman was referred for seronegative rheumatoid arthritis, resistant to three biologic therapies. She had an IgA lambda monoclonal gammopathy of undetermined significance (MGUS). The patient subsequently developed glomerular proteinuria. Abdominal fat and accessory salivary glands biopsies revealed amyloid light-chain (AL) amyloidosis. Treatment with bortezomib-cyclophosphamide-dexamethasone, led to complete hematologic, renal and rheumatologic remission. Ten months after treatment interruption, the patient had an articular and hematologic relapse. CONCLUSION: Amyloid light-chain amyloidosis arthropathy is probably underdiagnosed. A review of amyloid arthropathy associated with multiple myeloma found that 33% of patients had been misdiagnosed with rheumatoid arthritis.

Treatment of AL amyloidosis / Traitement de l'amylose AL.

AL amyloidosis is caused by the conversion of monoclonal immunoglobulin light chains into amyloid fibrillar aggregates that deposit in tissue and lead to organ dysfunction. Diagnosis is histological and relies primarily on non-invasive biopsies, showing Congo red-positive amorphous deposits containing immunoglobulin light chains, most commonly of lambda isotype. The clinical presentation is extremely polymorphous, due to the large number of organs that can be affected by the disease. The kidneys and the heart are most frequently involved organs, in about two thirds of patients each, responsible for nephrotic syndrome and restrictive cardiomyopathy. Treatment is based on chemotherapy aimed at eliminating the medullary clone producing the pathogenic monoclonal light chains. It is guided by risk assessment, based on the serum levels of cardiac biomarkers. Its effectiveness must be regularly assessed by the serum free light chain assay. Current reference regimens combine an alkylating agent, with high doses of dexamethasone and most often a proteasome inhibitor. They are effective in the majority of patients. The overall prognosis depends on the importance of the initial severity of organ involvement, particularly the heart, and is strongly influenced by the haematological response. The treatment must be rapidly modified in non-responders, especially in those with severe cardiac disease, with the introduction of immunomodulatory drugs and antibodies targeting plasma cells. However, effective therapies for patients with the more severe amyloid cardiopathy are an unmet need. Strategies directly accelerating the removal of amyloid deposits, despite disappointing preliminary results, could further improve the prognosis of this disease.

[Clinical, radiological, pathological features, treatment and follow-up of periocular and/or orbital amyloidosis: Report of 6 cases and literature review]. / Caractéristiques cliniques, radiologiques, anatomopathologiques, thérapeutiques et évolutives de l'amylose périoculaire et/ou intraorbitaire : à propos de 6 cas et revue de la littérature.

PURPOSE: To assess demographic, clinical, radiological, pathological features, treatment and follow-up of periocular or/and orbital amyloidosis. PATIENTS AND METHODS: We conducted an observational retrospective monocentric study from January 2004 to April 2017 in patients diagnosed with histologically proven periocular or/and orbital amyloidosis. RESULTS: Six patients were included (2 females, 4 males). Mean age was 76.8 years (range 66-88 years). Mean time between first ophthalmological symptoms and diagnosis was 27 months (range 11-36 months). The main symptoms were subconjunctival infiltration (6 patients; 100%), periocular pain or discomfort (4 patients; 66.6%) and subconjunctival hemorrhage (1 patient; 16.6%). Clinical findings included ptosis (4 patients; 66.6%), keratitis (3 patients; 50%) leading to corneal perforation in one patient, and proptosis (3 patients; 50%). One-half of the patients showed bilateral involvement. AL amyloidosis was identified on immunohistochemistry in 5 patients (83.3%). One case of B cell marginal zone orbital lymphoma was diagnosed. Systemic work-up was negative for all patients. Treatment consisted of simple monitoring (1 patient; 16.6%), surgical debulking (3 patients; 50%), ptosis surgery (1 patient; 16.6%), eyelid or eyelash malposition surgery (2 patients; 33.3%) and orbital radiation beam therapy (2 patients; 33.3%). Mean follow-up was 14.6 months (range 6-36 months), and no progression nor recurrence were noted. CONCLUSION: Periocular or/and orbital amyloidosis is rarely encountered. Diagnosis is based on pathological examination, and immunohistochemistry analysis should always be performed to guide systemic work-up. Orbital lymphoma and multiple myeloma should be ruled out if AL amyloidosis is diagnosed. Progression is slow, and surgery is the mainstay of treatment in symptomatic patients. Long-term multidisciplinary follow-up is advocated.

[Classification and therapeutic management of monoclonal gammopathies of renal significance]. / Classification et prise en charge thérapeutique des gammapathies monoclonales de signification rénale.

Two categories of renal disorders associated with monoclonal gammopathies are to be distinguished, according to the characteristics of the underlying B-cell clone. The first group of renal diseases always occurs in the setting of high tumor mass with production of large amounts of monoclonal immunoglobulins. The main complication is the so-called myeloma cast nephropathy, which almost invariably complicates high tumor mass myeloma. The second group includes all renal disorders caused by a monoclonal immunoglobulin secreted by a nonmalignant B-cell clone, and currently referred as a "monoclonal gammopathy of renal significance (MGRS)". This term was introduced to distinguish monoclonal gammopathies that are responsible for the development of kidney damage from those that are truly benign. The spectrum of renal diseases in MGRS is wide and its classification relies on the localization of renal lesions, either glomerular or tubular, and on the pattern of ultrastructural organization of immunoglobulin deposits. Physicochemical characteristics of the pathogenic monoclonal immunoglobulin are probably involved in their propensity to deposit or precipitate in the kidney, as illustrated by the high rate of recurrence of each specific type after kidney transplantation. Early diagnosis and efficient chemotherapy targeting the causal B-cell clone are mandatory to improve renal prognosis and patient survival.

[Chronic lymphoid leukemia and renal complication: Report on 10 cases from Marseille over 16 years]. / Néphropathies au cours de la leucémie lymphoïde chronique : à propos d'une étude monocentrique de 10 cas.

INTRODUCTION: Chronic lymphoid leukemia (CLL) is a hematological malignant disease, associated with a clonal B cell proliferation. The incidence is 4400 new cases per year in France. The prevalence increases with age with a median age at diagnostic of 65 years. Renal involvement is rare and estimated at 1.2% of patients with CLL. Renal pathological diagnoses associated with CLL are variable and are not always related to the hematological disease. We report here on cases of patients with CLL who underwent a renal biopsy over the past 16 years in Marseille. METHODS: All cases of renal biopsies performed in patients with CLL between2000 and 2016 in Marseille were included. Pathological analysis was performed by the same experimented pathologist. Data were collected at the time of biopsy and after treatment. RESULTS: Ten patients were included in this study. The reason for renal biopsy was acute kidney injury or the onset of nephrotic syndrome. We report on 4 cases of membranous nephropathy, 1 minimal change disease, 1 cryglobulinemia-related membrano-proliferative glomerulonephritis, 1 light chain amyloidosis, 1 fibrillary glomerulonephritis, 1 interstitial monoclonal infiltration and one case of non-specific tubular lesions. Only one patient was treated before the biopsy, 7 patients received a specific hematological treatment of CLL because of its renal involvement. Renal and hematological responses were variable. CONCLUSION: Renal involvement of CLL is rare and is not mentioned in the Binet classification. Yet, it can be severe, with acute kidney injury or nephrotic syndrome, and can lead to the initiation of a specific treatment. The most frequent presentation this series was secondary MN, which differs from previous series.

[AL amyloidosis]. / Amylose AL.

AL amyloidosis belongs to the group of conformational diseases. It is the most common type of amyloidosis with an estimated 500 new cases per year in France. It is due to a small and usually indolent plasma cell clone which synthesizes an unstable, misfolded monoclonal immunoglobulin light chain that is prone to aggregate and form amyloid fibrils. Non-invasive biopsy such as abdominal fat aspiration or minor salivary gland biopsy should be performed to confirm the diagnosis and if negative, involved tissues have to be examined. Clinical presentation is very diverse, as AL amyloidosis can affect almost any organ or tissue in the body, other than the brain. The kidney is the most frequent organ involved, whereas heart disease characterized by restrictive cardiomyopathy is the most severe. Early diagnosis, before advanced cardiomyopathy, is essential for improving outcome. The association of alkylating agent and high-dose dexamethasone is effective in almost two-thirds of patients. Combinations of proteasome inhibitors, dexamethasone, and alkylating agents achieve high response rates. Close monitoring of clonal and organ response is mandatory to guide therapy changes and duration. New treatments designed to eliminate amyloid deposits are under development.