Symptômes cliniques ou biologiques devant amener à rechercher une amylose

The amyloidoses are a large group of postsecretory protein misfolding and deposition diseases. There are over 20 secreted human proteins whose misfolding and misassembly outside the cell is linked to amyloidosis. In this paper, we described epidemiological and clinical aspects of non-hereditary systemic amyloidosis, including senile systemic amyloidosis (SSA) and systemic AL amyloidosis. SSA, induced by wild-type transthyretin (TTR) deposition, is a prevalent aging-related disorder, as about 25% of people over age 80 have TTR deposition in the heart, but it is usually detected by microscopic examination at autopsy. Although SSA is usually associated with cardiac disease, TTR deposition is not limited to the heart and is found in systemic organs. Carpal tunnel syndrome is one of the most common clinical manifestations of SSA and often precedes cardiac symptoms. Systemic AL amyloidosis is the most common non-hereditary systemic amyloidosis induced by immunoglobulin light chain deposition. Involvement of visceral organs usually dominates the clinical picture of systemic AL amyloidosis, but some patients suffer from serious peripheral neuropathy, including polyneuropathy, carpal tunnel syndrome, and autonomic dysfunction. High-dose melphalan with stem cell transplantation improves prognosis of systemic AL amyloidosis including neurological symptoms.

Systemic lupus erythematosus in a 15-year-old with graft-versus-host disease following liver transplant and unexpected full hematopoietic engraftment

To describe a patient with a long disease history who was finally diagnosed with neurosarcoidosis and to discuss the reasons behind the delayed diagnosis. A 58-year-old man with sick sinus syndrome and bradycardia, which was treated with a pacemaker, developed first right and then left facial palsy. Subsequently, multiple cranial nerve palsies developed and later spontaneously resolved. Neurosarcoidosis was suspected at that stage, but excluded because the patient had no typical sarcoid lung changes, his serum and cerebrospinal fluid angiotensin converting enzyme activity levels were normal and a computed tomography scan disclosed no central nervous system changes. During follow-up, the patient developed extremely dry eyes and mouth, suggesting Sjögren's syndrome. Rheumatology consultation did not reveal any autoimmune or visceral features typical of Sjögren's syndrome and autoantibodies were negative. However, both labial salivary gland and conjunctival biopsies revealed non-caseating granulomas, and neurosarcoidosis was diagnosed. Neurosarcoidosis is a relatively rare disease with a somewhat poor longterm prognosis in one-third of cases, although the neurological manifestations often diminish or disappear in response to glucocorticoid treatment. Diagnosis is often a clinical challenge, especially in the absence of pulmonary changes or other features typical of sarcoidosis. The labial salivary gland and conjunctiva provide helpful biopsy sites for histopathological confirmation of the diagnosis.

Two cases of familial Mediterranean fever associated with sarcoidosis (<scp>L</scp>ofgren's syndrome) and rheumatoid arthritis

Mucopolysaccharidosis type I is a rare metabolic disorder characterized by the accumulation of glycosaminoglycans, leading to musculoskeletal disorders such as carpal tunnel syndrome. This retrospective cohort study was performed to determine the prevalence and timing of the development of carpal tunnel syndrome, assess the efficacy of surgery on recurrence and the effect of haematopoietic stem cell transplantation in resolving accumulated degradation products. Thirty-three mucopolysaccharidosis type I patients, born between 2001 and 2023, were included in this study. They received annual screening and treatment at our specialist hospital. Patient demographics, clinical symptoms of carpal tunnel syndrome pre- and post-carpal tunnel release and histopathological sections of the flexor retinaculum were collected. Regression analyses were conducted to assess cumulative risks and determine hazard ratios and survival curves were plotted. Twenty-seven of 33 mucopolysaccharidosis type I patients, with a median age at the latest follow-up of 13 years (IQR 7.7 to 18.3), were diagnosed with carpal tunnel syndrome on electrophysiological tests or ultrasound at a median age of 3.6 years (IQR 2.8 to 5.2). Only a few patients exhibited clinical symptoms. Twenty-one patients underwent carpal tunnel release and 13 patients experienced recurrence. The highest risk of developing carpal tunnel syndrome was within the first 6 years of life. Eight of the 11 patients accumulated degradation products within lysosomes despite successful haematopoietic stem cell transplantation. In this study, 27 mucopolysaccharidosis type I patients were diagnosed with carpal tunnel syndrome, showing a high-risk window from 0 to 6 years of age. Recurrence of carpal tunnel syndrome after carpal tunnel release surgery was common, occurring in 61.9% of patients. III.

Neurologic and other systemic manifestations in FMF: Published and own experience

Early vs late diagnosis in infectious encephalitis: a population-based cohort study.

Identification of HLA-Matched Related Donors for Hematopoietic Stem Cell Transplant in Adult Sickle Cell Patients: Experience from an Adult Referral Center in France

Amyloses multisystémiques: Étude clinique de 39 patients au Liban

Purpose: Patients with sickle cell disease (SCD) are prone to dys- or autoimmune disorders, such as autoimmune hepatitis (AIH), sclerosing cholangitis, or ulcerative colitis. Sclerosing cholangitis can develop in young children with an unusually severe course due to associated vaso-occlusion and ischemia. Liver transplantation may be indicated early but is a challenging procedure in SCD, with uncertain outcomes (Hurtova Liver Transpl 2011, Duvoux [abstract] JFHOD 2021). Hematopoietic stem cell transplantation (HSCT) can cure SCD, although conditioning may induce hepatic complications. Herein we report a series of 6 children with SCD and autoimmune disorders, 3 for whom liver or digestive symptoms resolved after successful HSCT, and 3 for whom cirrhosis precluded HSCT conditioning. Materials and methods: Of the 6 children (5 girls), 5 were HbSS and 1 was HbSC. Dysimmune symptoms appeared at a median age of 4.5 (3-12) years and were colitis (n=2), cerebral vasculitis (n=1), and AIH (n=3). In 4/6 patients, liver disease was an overlap AIH-sclerosing cholangitis, while 2/6 patients had either isolated AIH or sclerosing cholangitis. Liver biopsy showed cirrhosis in 3 patients. Median age at last follow-up (FU) was 13.5 (8-17) years. Results: The 3 patients without cirrhosis, including 2 with sclerosing cholangitis and dilated bile ducts, underwent HSCT with a geno-identical donor, at 6, 11.5 and 16 years old. Autoimmune disease was controlled with steroids, azathioprine, infliximab or cyclophosphamide with plasma exchanges and rituximab. Conditioning included hepatotoxic drugs busulfan (n=2) and treosulfan (n=1), with antilymphocyte globulins, fludarabine (n=3) and thiotepa (n=1). Transient hepatitis developed in 1 patient and moderate graft-vs-host disease (GVHD) in 2, which resolved after adapting immunosuppression treatment. HSCT was uneventful in the third patient. With a FU of 1 to 2.5 years, all 3 patients had no digestive or liver symptoms, normal or mildly elevated liver enzymes and unchanged liver imaging. The 3 patients with cirrhosis upon first visit, at ages 7, 8.5, 13 years old, were on regular exchange transfusions at last FU. One patient developed recurrent infectious cholangitis and received a liver transplant at age 10, with many complications; at 7 years of FU, sclerosing cholangitis relapsed and re-transplantation was discussed. Another had moderate portal hypertension, bilirubin levels of 100-200 µM, and prothrombin time 60%, on steroids. The third patient was on tacrolimus, had presented 2 episodes of reversible liver failure, bilirubin levels of 100 µM and prothrombin time 45% at last FU and had developed myasthenia. Conclusion: Autoimmune liver disease in children with SCD may rapidly lead to end-stage liver disease. Upon diagnosis, these disorders should be considered as severe complications of SCD and prompt early discussion of HSCT. HSCT should be performed before conditioning with hepatotoxic drugs is not feasible. If a geno-identical donor is not available, alternative donors could be considered (haplo-identical, unrelated). If the liver disease is not stabilized after HSCT, liver transplantation could be performed with a standard risk, in a patient rid of SCD. If liver transplantation must be performed before HSCT, HSCT could be discussed rapidly afterwards to avoid possible relapse of SCD-related liver disease and dysimmune liver disease. The authors do not declare any conflict of interest

Hereditary transthyretin amyloidosis (hATTR) is associated with significant morbidity and mortality. Early diagnosis and treatment are essential to improve patient's outcome. Carpal tunnel syndrome (CTS) is a common complication of hATTR amyloidosis. However, because CTS is also common in the general population, we wanted to assess whether CTS, when associated with systemic manifestations, could help direct physicians to screen for TTR gene mutation and early diagnosis. We reviewed the charts and interviewed the patients with hATTR seen between 2017 and 2018. We noted the details of CTS diagnosis, treatment, and other systemic features of the disease. Seventeen of the 23 patients studied had CTS. CTS was the first manifestation of the disease in 10 of 17 patients. On average, CTS symptoms occurred 10.4 years before their diagnosis of hATTR amyloidosis. In 6 of 10 patients with CTS, the following systemic symptoms were present as the first manifestation: erectile dysfunction, dysautonomia, polyneuropathy, exercise intolerance, and gastrointestinal and ocular symptoms. CTS occurs in most patients with hATTR amyloidosis and frequently precedes the hATTR diagnosis. Most patients with CTS preceding hATTR diagnosis have systemic features. Recognizing systemic features at the time of CTS presentation may help in early diagnosis of hATTR amyloidosis.

Transthyretin familial amyloid polyneuropathy (TTR‐FAP) is a rare, progressive, life‐threatening, hereditary disorder caused by mutations in the transthyretin gene and characterized by extracellular deposition of transthyretin‐derived amyloid fibrils in peripheral and autonomic nerves, heart, and other organs. TTR‐FAP is frequently diagnosed late because the disease is difficult to recognize due to phenotypic heterogeneity. Based on published literature and expert opinion, symptom clusters suggesting TTR‐FAP are reviewed, and practical guidance to facilitate earlier diagnosis is provided. TTR‐FAP should be suspected if progressive peripheral sensory‐motor neuropathy is observed in combination with one or more of the following: family history of a neuropathy, autonomic dysfunction, cardiac hypertrophy, gastrointestinal problems, inexplicable weight loss, carpal tunnel syndrome, renal impairment, or ocular involvement. If TTR‐FAP is suspected, transthyretin genotyping, confirmation of amyloid in tissue biopsy, large‐ and small‐fiber assessment by nerve conduction studies and autonomic system evaluations, and cardiac testing should be performed.

Erythropoietic protoporphyria in an adult with sequential liver and hematopoietic stem cell transplantation: A case report.

THU0558 Increased frequency of febrile seizures in two periodic fever syndromes: familial mediterranean fever and pfapa syndrome

Dialysis-related amyloidosis is a serious complication in patients on long-term dialysis. Amyloid fibrils, that major component is beta(2)-microglobulin (beta(2)-m) , deposit mainly in osteoarticular joint tissues and cause various complications such as carpal tunnel syndrome, destructive spondyloarthropathy, bone cysts, and various organ dysfunction. The retention of beta(2)-m in chronic kidney disease (CKD) induces the amyloid fibril formation according to a nucleation-dependent polymerization model. Specific molecules such as glycosaminoglycans and proteoglycans that affect the conformation and stability of beta(2)-m and amyloid fibrils are considered to have significant effects on the formation and deposition of amyloid fibrils.