恶性抗磷脂综合征7例临床分析并文献复习

目的：探讨恶性抗磷脂综合征（CAPS）的临床特点及预后，以期提高临床医生对该病的认识及诊治水平。方法：回顾性分析我院风湿科收治的7例恶性抗磷脂综合征患者临床表现、实验室检查及预后等资料并复习相关文献。结果：7例CAPS患者中，1例为原发APS，6例为SLE继发APS。静脉血栓发生5例次，主要是下肢深静脉血栓、眼中央静脉栓塞；动脉血栓13例次，以脑梗死为主（6例次）。6例抗心磷脂抗体阳性，3例抗β2-GPⅠ抗体阳性，3例狼疮抗凝物阳性。5例患者在1周内相继出现心、肺、肾等多器官功能衰竭而导致死亡。结论：CAPS患者短时间内发生大量微血栓形成，可导致多器官功能衰竭。本病的预后差，及早诊断、及时治疗是改善患者预后的关键。     

Autoimmune polyendocrine syndrome type 2 associated with autoimmune hypophysitis and coeliac disease

Autoimmune polyendocrine syndromes (APS) are organ-specific autoimmune disorders affecting multiple endocrine glands; these are gradually destroyed by action of autoantibodies. Similarly to other autoimmune diseases, the presence of certain genetic predisposition is an essential prerequisite to the disease development; polymorphism of the main histocompatible system (HLA in humans) appears to play the most important role. APS are categorized into four types, based on what combination of endocrine glands is affected. APS type 1, characterised by hypoparathyreosis, mucocutaneous candidiasis and Addison's disease, is frequently seen in childhood. For a more common APS type 2 to be diagnosed, Addison's disease together with autoimmune thyroiditis (Schmidt's syndrome) and/or together with diabetes mellitus type I (Carpenter's syndrome) must be present. The third type of autoimmune polyendocrine syndromes (APS type 3) involves the same disorder of endocrine glands as type 2 but usually without any defect of adrenal cortex. If the autoimmune endocrine gland disorder does not fulfil the criteria of APS 1-3, the disease may be categorized as autoimmune polyendocrine syndrome type 4. The authors present a case of 33 years old APS type 2 patient who, over 20 years, developed a wide range of autoimmune endocrinopathies, including endocrinopathies that are less common, such as adenohypophysitis, and are associated with other organ-specific diseases (coeliac disease). The case is presented to demonstrate the fact that APS represent a dynamic process and that it is always important to keep in mind that, over time, a patient may develop other autoimmune diseases. To conclude, the authors emphasise the recommendation to test patients with monoglandular endocrinopathy for the presence of any secondary endocrine disorders.     

自身免疫性多内分泌腺病综合征的临床进展

自身免疫性多内分泌腺病综合征(APS)是指由自身免疫引起的多内分泌腺功能受损为主要表现的系列综合征,可分为APS Ⅰ型和APSⅡ型.二者的疾病组成成分和发病机制有显著区别.APS Ⅰ型是由位于21号染色体上的自身免疫调节基因(AIRE)的突变导致,所以用基因检测的.方法 即可确诊,而APSⅡ型为多基因遗传病,遗传性状表...     

Atypical Hemolytic‐Uremic Syndrome: An Update on Pathophysiology,Diagnosis, and Treatment

Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic microangiopathy, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The condition is associated with poor clinical outcomes with high morbidity and mortality. Atypical HUS predominantly affects the kidneys but has the potential to cause multi‐organ system dysfunction. This uncommon disorder is caused by a genetic abnormality in the complement alternative pathway resulting in over‐activation of the complement system and formation of microvascular thrombi. Abnormalities of the complement pathway may be in the form of mutations in key complement genes or autoantibodies against specific complement factors. We discuss the pathophysiology, clinical manifestations, diagnosis, complications, and management of aHUS. We also review the efficacy and safety of the novel therapeutic agent, eculizumab, in aHUS, pregnancy‐associated aHUS, and aHUS in renal transplant patients.     

ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity

A very rare syndrome of rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) has been recently described as causing morbidity due to hypothalamic dysfunction and respiratory arrest. Its prognosis is poor and often cardiac arrest occurs due to alveolar hypoventilation. This disorder can mimic genetic obesity syndromes and several endocrine disorders. We present a 13-year-old female patient who was reported to be healthy until the age of 3 years. She was admitted to our emergency department, presenting with respiratory distress. Features matching ROHHAD syndrome such as rapid-onset obesity, alveolar hypoventilation, central hypothyroidism, hyperprolactinemia, Raynaud phenomenon and hypothalamic hypernatremia were detected in the patient. In addition to these features, the patient was found to have hypergonadotropic hypogonadism and megaloblastic anemia. Because of its high mortality and morbidity, the possibility of ROHHAD syndrome needs to be considered in all pediatric cases of early- and rapid-onset obesity associated with hypothalamic-pituitary endocrine dysfunction.     

Haemolytic uraemic syndrome

Haemolytic uraemic syndrome (HUS) is defined by the simultaneous occurrence of nonimmune haemolytic anaemia, thrombocytopenia and acute renal failure. This leads to the pathological lesion termed thrombotic microangiopathy, which mainly affects the kidney, as well as other organs. HUS is associated with endothelial cell injury and platelet activation, although the underlying cause may differ. Most cases of HUS are associated with gastrointestinal infection with Shiga toxin‐producing enterohaemorrhagic Escherichia coli (EHEC) strains. Atypical HUS (aHUS) is associated with complement dysregulation due to mutations or autoantibodies. In this review, we will describe the causes of HUS. In addition, we will review the clinical, pathological, haematological and biochemical features, epidemiology and pathogenetic mechanisms as well as the biochemical, microbiological, immunological and genetic investigations leading to diagnosis. Understanding the underlying mechanisms of the different subtypes of HUS enables tailoring of appropriate treatment and management. To date, there is no specific treatment for EHEC‐associated HUS but patients benefit from supportive care, whereas patients with aHUS are effectively treated with anti‐C5 antibody to prevent recurrences, both before and after renal transplantation.     

Antibodies and clinical features of the antiphospholipid syndrome as criteria for systemic lupus erythematosus

The antiphospholipid syndrome (APS) can occur as a primary diagnosis or as a prominent feature of other diseases, predominantly systemic lupus erythematosus (SLE). The 1982 revised criteria for SLE were published prior to many of the studies which have illuminated current understanding of the antiphospholipid syndrome and several current clinical criteria for SLE, when arising from thrombotic damage to different organ systems, could be attributed to APS, leading to some confusion about where the diagnoses of these two disorders should begin and end. Additionally, APS is a significant generalized risk factor for irreversible organ damage and overall mortality in SLE patients and genetic linkages to HLA in APS hold up whether the disorder is primary or linked to SLE. It is increasingly recognized that APS itself is a complex, heterogenous disorder, involving a spectrum of autoantibodies to phospholipid-binding proteins, many of which have known coagulation-regulating functions. Although the combination of more than one antiphospholipid-related antibody might indicate a more severe phenotype, it is not suggested here that additive criteria for the diagnosis of SLE be accumulated with more than one of these pathologically related autoantibodies. Patients with multiple criteria for APS should be considered to have severe APS but it would be recommended to restrict APS-attributed criteria for SLE to a maximal of two: one immunologic and one clinical. Thus people meeting the Sapporo criteria for APS could gain only a maximum of two criteria for SLE, regardless of how many autoantibodies were detected or how severe the clinical syndrome might be. This would allow manifestations of fullblown APS an appropriate impact towards the diagnosis of SLE without leading to a premature diagnosis of SLE for people who might better be considered to have moderate to severe primary APS.     

连续性血液净化治疗多脏器功能障碍综合征疗效观察

目的:观察连续性血液净化(CBP)对多器官功能障碍综合征(MODS)的疗效及血液动力学影响.方法:回顾性分析83例经CBP治疗的MODS患者的临床资料.结果:CBP清除了患者的尿毒症毒素,较快纠正水、电解质、酸碱平衡失调,使血压、平均动脉压回升,中心静脉压、心率下降.83例患者总病死率37.35%,病死率与脏器衰竭数目相关,4个或4个以上器官衰竭病死率近100%.结论:CBP能明显改善MODS患者的血液动力学及血液生化指标,降低2～3个器官衰竭患者的病死率,宜广泛应用于临床.     

Idiopathic Atypical Hemolytic Uremic Syndrome (aHUS) with Trilineage Myelodysplasia

Atypical hemolytic uremic syndrome (HUS) is a heterogeneous group of disorders, with an unexplained pathogenesis. We report here with an interesting case of a 6 years old male child presenting with atypical feature of HUS and bone marrow trilineage myelodysplasia.     

The Characteristics of Bronchoalveolar Lavage from a Patient with Antiphospholipid Syndrome who Developed Acute Respiratory Distress Syndrome

The purpose of this study was to investigate the biochemical characteristics as well as the occurrence and specificity of antiphospholipid antibodies in the bronchoalveolar lavage (BAL) fluid from a patient with both antiphospholipid antibodies syndrome (APS) and acute respiratory distress syndrome (ARDS). Proteins, lipids, cells and autoantibodies were determined. Immunoglobulins were purified with affinity chromatography. Autoantibody identification was assessed with enzyme-linked immunosorbent assay (ELISA) and with electrophoresis, followed by immunoblotting and revelation with antihuman IgG–peroxidase conjugate. Antiphospholipid antibodies were found to be present in the BAL fluid as well as in the serum from a patient with APS. Specifically, antiphosphatidylserine and antiphosphatidic acid IgG antibodies in the BAL fluid and antiphosphatidylcholine and anticardiolipin IgG antibodies in the serum were detected at high levels. BAL fluid protein and the percentage of neutrophils were found to be increased. A quantitative as well as qualitative deficiency of surfactant phospholipids was also observed. Antibodies directed against surfactant phospholipids could cause surfactant abnormalities and an inflammatory reaction. These disorders may be one of the causes of the ARDS or a factor in the perpetuation of the inflammation. Received: 16 February 2000 / Accepted: 6 September 2000     

Thrombotic microangiopathy with liver, gut, and bone infarction (catastrophic antiphospholipid syndrome) associated with HELLP syndrome

Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is a thrombotic microangiopathy complicating pregnancy and shares many clinical and biological features with thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Thrombotic microangiopathy is also a pathological feature of catastrophic antiphospholipid syndrome (CAPS). An association between refractory HELLP syndrome and antiphospholipid syndrome (APS) has been reported in a few cases. We describe a 19-year-old woman with APS and multiorgan failure conforming to a diagnosis of CAPS who developed refractory HELLP syndrome.     

Syndrome des anticorps antiphospholipides et nécrose hypophysaire

Antiphospholipid syndrome (APS) is an acquired thrombotic disorder. It mainly occurs with systemic disease or as a primary disorder. All organs may be involved by thrombosis, but to date the most common endocrine manifestation is chronic adrenal insufficiency. Very few cases of hypopituitarism with primary APS have been reported. We report the case of a 27-year-old woman, victim of a stroke leading to double vision and intracranial hypertension. Magnetic resonance imaging showed a macro-adenoma with hemorrhage of a suprasellar lesion. Hormone assessment showed hyper prolactinemia with positive anticardiolipin antibody. Our case is the second reported associating APS with apoplexy. We discuss the clinical, biological and radiological features observed in our case. We conclude that APS should be searched for whenever a history of adenoma with apoplexy is found associated with recurrent thrombosis.     

Prothrombotic mechanisms based on the impairment of fibrinolysis in the antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterised by thrombosis, venous or arterial, and recurrent pregnancy morbidity in association with the persistence of antiphospholipid antibodies (aPL). The clinical variety of aPL ranges from asymptomatic individuals to those with multiple organ thromboses and failure developing over a short period, also known as catastrophic APS. An increasing number of phospholipid-binding proteins with crucial functions in the regulation of blood coagulation and fibrinolysis are targeted by APS-related autoantibodies. Disruption of fibrinolysis is one of the proposed pathophysiological mechanisms for the APS. There are some experimental data for an association between impaired overall fibrinolytic activity and autoimmune aPL; however, evidence is still inconclusive and more studies are needed in this area. In this article, we review the evidence by which aPL may disturb fibrinolysis.     

Syndrome de renutrition inappropriée

Refeeding syndrome (RS) is a rare but severe condition that is poorly understood, often under-diagnosed and can lead to death. It occurs within 5 days after refeeding in patients after prolonged fasting or in a context of undernutrition. As a consequence of the abrupt transition from catabolism to anabolism, RS is defined as a decrease in plasma levels of phosphorus, potassium and/or magnesium, whether or not associated with organ dysfunction resulting from a decrease in one of the electrolytes or a thiamine deficiency, after refeeding. The clinical symptoms are varied and non-specific and are related to hydro electrolyte disorders, sodium-hydroxide retention or failure of one or more organs. Patient management should be appropriate with regular clinical examination and careful biological monitoring, including hydro electrolyte monitoring. The correction of hydroelectrolytic disorders and systematic thiamine supplementation are essential during refeeding, that must be done carefully and very progressively, whatever its form (oral, enteral or parenteral). The severity of the refeeding syndrome indicates that its prevention and screening are the corners of its management in at-risk patients.     

产后溶血尿毒症综合征1例报告及文献复习

目的：探讨产后溶血尿毒症综合征(PHUS)的临床特征、诊断治疗及预后情况。方法：报告1例PHUS患者，并复习有关文献就PHUS的临床特征、诊断治疗及预后等情况进行讨论。结果：该患者于正常分娩后第4天出现微血管病性溶血性贫血，血小板减少，肾功能急剧恶化，经血浆置换及血液透析等治疗无效，于发病后第14天死于多器官功能衰竭。结论：正常妊娠及分娩后发生微血管病性溶血性贫血、急性肾功能衰竭、血小板减少为PHUS的临床特征。早期诊断、及时正确治疗，对于降低PHUS患者死亡率至关重要。     

Hemolytic-uremic syndrome associated with pancreatitis in an HIV-positive patient

Summary Hemolytic-uremic syndrome (HUS) is a newly recognized hematologic manifestation of HIV infection that may be triggered by local or systemic infections as well as by immunological disorders. We report the case of a 36-year-old HIV-positive man, an intravenous drug abuser who developed HUS during an episode of acute pancreatitis. Hematologic and clinical improvement occurred following 2 weeks of nonaggressive therapy including vitamin E and fresh-frozen plasma.     

Catastrophic exacerbation of antiphospholipid syndrome after lung adenocarcinoma biopsy

We describe a 60-year-old man with nephrotic syndrome due to a glomerular thrombotic microangiopathy caused by the antiphospholipid syndrome (APS) associated with a lung adenocarcinoma. Although no significant aggravation of APS was noted following renal biopsy, catastrophic exacerbation of APS occurred 3 days after a lung adenocarcinoma biopsy while warfarin and prednisolone were being administered. The patient died of multiple organ failure 37 days after the lung adenocarcinoma biopsy. This case emphasizes the need for great caution for catastrophic exacerbation of malignancy associated APS following biopsy of the underlying malignancy.     

Chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is defined by symptoms and diagnosed without any objective diagnostic tests. Risk factors for developing CFS may include infection, psychiatric disorders, and allergies. Modest dysfunction of multiple organ systems, including the immune, central nervous, endocrine, and muscular systems, have been identified in cases of CFS. Symptoms of various organic, psychiatric, and poorly understood disorders overlap those of CFS. There is no known cure for CFS; however, exercise, counseling, and medications may provide symptomatic relief.     

Liver transplantation in a patient with primary antiphospholipid syndrome and Budd-Chiari syndrome

The antiphospholipid syndrome (APS) is an acquired thrombophilic disorder in which autoantibodies are produced to a variety of phospholipids determinants of cell membranes or phospholipid binding proteins. There are few reports about association between antiphospholipid antibodies and development of Budd-Chiari syndrome (BCS). We report the case of BCS development in young Russian male with primary APS. The patient underwent orthotopic liver transplantation on August 26, 2012. At present time his state is good, the blood flow in the liver restored and its function is not impaired. We report about the first time the successful use of dabigatran etexilate for prolonged anticoagulation therapy in APS patient with BCS. In addition patient is managed with immunosuppressive drugs.     

The VWF/ADAMTS13 axis in the antiphospholipid syndrome: ADAMTS13 antibodies and ADAMTS13 dysfunction

Autoantibodies to ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I motif, member 13) play an important role in the development of microthrombosis in thrombotic thrombocytopenic purpura (TTP). In severe cases of antiphospholipid syndrome (APS), microthrombosis can occur similar to that seen in TTP, suggesting possible mutual pathogenic factors. However, the role of ADAMTS13 in APS is unknown. We hypothesised that aberrations in ADAMTS13 may occur in APS and evaluated ADAMTS13 and von Willebrand factor (VWF) in 68 patients with antiphospholipid antibodies (aPA) including 52 with APS. Thirty-three (49%) had IgG anti-ADAMTS13 with 12 of these patients having reduced ADAMTS13 activity, suggesting neutralising antibodies. Low ADAMTS13 activity (median 34%) was demonstrated in 22/68 (33%), all with normal ADAMTS13 antigen levels consistent with dysfunctional ADAMTS13. Reduced ADAMTS13 activity was not secondary to elevated von Willebrand factor (VWF), or increased VWF secretion (normal VWF propeptide), although a reduced VWF clearance was noted in APS. Analysis found no associations between the ADAMTS13 abnormalities and any aPA profile or thrombotic/obstetric complications, although this study was not adequately powered to address clinical associations. Nevertheless, these findings highlight that ADAMTS13 autoantibodies and ADAMTS13 dysfunction can occur in APS, and although the clinical significance remains undetermined, ADAMTS13 dysfunction may be contributory to thrombogenesis in autoimmune conditions other than TTP.