Nature Reviews Disease Primers最新文献

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal dominant trait and caused by loss-of-function pathogenic variants in genes encoding proteins of the BMP signalling pathway. Up to 90% of disease-causal variants are observed in ENG and ACVRL1, with SMAD4 and GDF2 less frequently responsible for HHT. In adults, the most frequent HHT manifestations relate to iron deficiency and anaemia owing to recurrent epistaxis (nosebleeds) or bleeding from gastrointestinal telangiectases. Arteriovenous malformations (AVMs) in the lungs, liver and the central nervous system cause additional major complications and often complex symptoms, primarily due to vascular shunting, which is right-to-left through pulmonary AVMs (causing ischaemic stroke or cerebral abscess) and left-to-right through systemic AVMs (causing high cardiac output). Children usually experience isolated epistaxis; in rare cases, childhood complications occur from large AVMs in the lungs or central nervous system. Management goals encompass control of epistaxis and intestinal bleeding from telangiectases, screening for and treatment of iron deficiency (with or without anaemia) and AVMs, genetic counselling and evaluation of at-risk family members. Novel therapeutics, such as systemic antiangiogenic therapies, are actively being investigated. Although HHT is associated with increased morbidity, the appropriate screening and treatment of visceral AVMs, and the effective management of bleeding and anaemia, improves quality of life and overall survival.

Guillain-Barré syndrome (GBS) is a rare immune-mediated polyradiculoneuropathy. Patients typically develop rapidly progressive weakness and sensory deficits that can result in complete paralysis requiring mechanical ventilation. GBS is usually a monophasic disease in which an aberrant immune response to an infection or other trigger damages the peripheral nerves. For example, in patients with preceding Campylobacter jejuni infection, molecular mimicry causes a cross-reactive antibody response to nerve gangliosides. Diagnosis is based on clinical features, supported by cerebrospinal fluid analysis and nerve conduction studies. Effective treatments include plasma exchange and intravenous immunoglobulins. However, ~20% of patients who received treatment are unable to walk after 6 months and ~5% die as a consequence of GBS. Important knowledge gaps in GBS include its pathogenesis, especially after viral infections. In addition, there is a lack of specific biomarkers to improve the diagnosis, monitor the disease activity, and predict the clinical course and outcome of GBS. Major challenges for the future include finding more effective and personalized treatments, which are affordable in low-income and middle-income countries, and preparation for outbreaks of infections as potential triggers for GBS.

Ectopic pregnancy, defined as the implantation of a developing pregnancy outside of the endometrial cavity of the uterus, is the leading cause of early-pregnancy maternal mortality. The majority of ectopic pregnancies implant in a fallopian tube. Acute complications may include rupture of the fallopian tube or rupture of ectopic pregnancy, haemorrhage and hypovolaemic shock, or occur secondary to treatments such as emergency surgery or blood transfusions, and ultimately increase the risk of maternal death. After ectopic pregnancy, patients may experience ongoing morbidity, including chronic pain, infertility and psychological distress. Assessment of ectopic pregnancy should focus on prompt diagnosis based on clinical and investigative findings but should also reflect a patient-centred approach with acknowledgement of potential psychological distress associated with pregnancy loss and reduced future fertility. Over the last four decades, the foundations of non-invasive diagnosis have been transvaginal sonography and serum β-human chorionic gonadotropin, with diagnostic laparoscopy as a confirmatory test if surgical treatment is planned. Once diagnosed, ectopic pregnancy can be managed expectantly, treated medically with methotrexate or managed surgically. Future fertility is an important but often overlooked aspect in the management of ectopic pregnancy.

Body dysmorphic disorder (BDD) is an obsessive-compulsive disorder-related psychiatric condition characterized by an intense preoccupation with perceived physical flaws that are not observable by others. BDD affects ~2% of the adult population but is underdiagnosed, partly owing to limited clinician awareness, and undertreated, partly due to limited access to treatment. Research on the aetiology of BDD is scarce but likely involves an interplay between genetic and environmental factors. A few studies suggest functional and structural brain differences (compared with controls) in the regions involved in visual and emotional processing, although firm conclusions about the pathophysiology of the disorder cannot be made at this stage. Diagnosis requires the presence of repetitive behaviours or mental acts typically aimed at checking, correcting or concealing perceived flaws. The disorder typically has its onset before 18 years of age, with a female preponderance in youth but no major gender disparity in adults. Quality of life is markedly impaired across multiple domains and suicide risk is considerable. Evidence-based treatments include cognitive behavioural therapy and selective serotonin reuptake inhibitors. Future research should focus on understanding the biological and environmental factors that increase the risk of BDD, and on improving access to effective treatments, thereby addressing a critical gap in care for this often misunderstood and overlooked disorder.