Cardiac manifestations in the antiphospholipid syndrome

Experimental evidence reveals that aPL are not only markers of APS, but also may play a causative role in the development of vascular thrombosis and pregnancy morbidity. The pathogenic mechanisms of aPL seem to be heterogeneous, including endothelial cell activation, the direct inhibition of the activated protein C pathway, abnormalities in platelet function, and in complement activation. aPLs induce proadhesive, proinflammatory, and procoagulant molecules that provide a persuasive explanation for induction of thrombosis in APS. Cardiac manifestations in APS include valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. aPL may be associated with accelerated atherosclerosis in APS patients. Valve disease is the most important and most common cardiac manifestation of APS. The precise mechanism by which valves become deformed is not yet fully known.     

Two uncommon manifestations of leptospirosis: Sweet's syndrome and central nervous system vasculitis

To leptospirosis is the commonest spirocheatal infection in the tropical and temperate countries of Indian sub-continent and Africa and the most common zoonosis worldwide. The protean manifestation of this infectious disease is a challenge for practising clinicians across the world. In poor developing countries, at most clinical suspicion it is essential in the diagnosis of this disease. In this report, we are able to document two uncommon manifestations of leptospirosis, namely Sweet's syndrome and central nervous system vasculitis.     

Dengue infection with central nervous system manifestations

A prospective observational study was conducted over a seven years period to determine the clinical and laboratory findings of dengue patients with central nervous system manifestations. Thirty serologically confirmed dengue infected patients with central nervous system manifestations were seen at the Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok and at Songkhla Hospital, Songkhla, Thailand. The age ranged between 3 months and 14 years with a mean age of 6.2 years. Seventeen were boys and thirteen were girls. The central nervous system manifestations included alteration of consciousness 76.7%, seizures 63.3%, pyramidal tract signs 36.7%, meningeal signs 30% and headache 26.7%. Eleven patients had primary while 19 had secondary dengue infection. Cerebrospinal fluid examination showed lymphocytic pleocytosis in 6 out of 28 patients while presence of anti-dengue IgM antibodies was detected in 2 out of 19 specimens of cerebrospinal fluid tested. Two patients died, autopsy was done on one patient and examination of the brain was compatible with viral encephalitis.     

Valvular heart disease in the primary antiphospholipid syndrome.

OBJECTIVE: To determine the prevalence of cardiac valvular involvement in patients with the primary antiphospholipid syndrome. DESIGN: Cross-sectional study with evaluation of case patients and control patients by Doppler echocardiography. The mean follow-up for case patients was 22 months. SETTING: University-based tertiary medical center. PATIENTS: Twenty-eight consecutive patients who were diagnosed with the primary antiphospholipid syndrome during a 10-year period; 28 age- and sex-matched healthy controls. MEASUREMENTS AND MAIN RESULTS: Ten patients (36%; 95% Cl, 19% to 56%) with the primary antiphospholipid syndrome had cardiac valvular involvement: Four patients had mitral valve involvement; four patients, aortic valve involvement; and two patients, both mitral and aortic valvular involvement; no patients had tricuspid or pulmonary valve disease. Eight of 10 patients had a regurgitant murmur. None of the control patients had valvular disease. The mean mitral valve thickness in patients with mitral valve involvement was 7.0 +/- 1.6 mm, compared with 2.7 +/- 0.8 mm in patients with normal valves and 3.2 +/- 0.9 mm in the control group. The mean aortic valve thickness in patients with aortic valve involvement was 3.8 +/- 0.5 mm compared with 1.4 +/- 0.3 mm in patients with normal valves and 1.4 +/- 0.5 mm in the control group. Stenotic lesions were not found. Regurgitation was severe in two patients (one required surgery), moderate in three patients, and mild in three patients. CONCLUSIONS: Valvular involvement is frequently found in patients with the primary antiphospholipid syndrome. The lesions are left-sided, causing regurgitation that may be clinically important.     

Neurologic manifestations of the antiphospholipid syndrome

Antiphospholipid syndrome is an important cause of neurologic morbidity. The clinical criteria for antiphospholipid syndrome include only cerebrovascular arterial and venous thrombosis, but many other neurologic manifestations have been associated with antiphospholipid antibodies (aPL). This review discusses the role of aPL in cerebrovascular manifestations and in some of the other neurologic manifestations commonly associated with these antibodies, as well as data pertaining to the pathophysiology of aPL-associated neurologic manifestations and treatment issues.     

Dermatologic manifestations of the antiphospholipid syndrome

A wide variety of dermatologic manifestations has been described in the antiphospholipid syndrome (APS). The most frequent skin lesion is livedo reticularis, present not only on the limbs but also on the trunk, with a fine irregular pattern. It belongs to the arterial subset of APS. Circumscribed ulcerations, resembling livedoid vasculitis, may be the first manifestation of APS. Ulcerations may also occur as a late complication of recurrent venous thrombosis. Extensive skin necrosis is a classic manifestation of catastrophic APS. Pseudo-vasculitis lesions are misdiagnosed if a skin biopsy is not performed, especially in the context of systemic lupus erythematosus. In systemic lupus erythematosus, primary anetoderma is always associated with antiphospholipid antibodies.     

Neurologic manifestations of the antiphospholipid syndrome

Neurologic disorders are among the most prominent clinical manifestations associated with the antiphospholipid syndrome. Such neurologic disorders are predominantly related to focal central nervous system thrombo-occlusive events. This review summarizes the latest data regarding the clinical aspects of stroke and other neurologic manifestations associated with antiphospholipid antibodies.     

Endocrinologic manifestations of the antiphospholipid syndrome

Our objective was to study the endocrinologic manifestations of the antiphospholipid syndrome (APS). We reviewed the medical literature from 1968 until 2005 using MEDLINE and the key words: APS, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid antibodies, adrenal, thyroid, parathyroid, pituitary, diabetes, ovaries and testes. Adrenal insufficiency is the most common endocrinologic manifestation and can be the presenting symptom of APS. In patients with autoimmune thyroid disease circulating aPL have been detected. However, no clinical manifestations of APS have been described. A few cases of hypopituitarism have been reported, including a case of Sheehan's syndrome. aPL has been detected in the sera of diabetic patients, probably associated with some macroangiopathic complications. Finally only very few cases of ovarian and testicular involvement have been reported. The adrenals are the most commonly involved glands in the APS. Clinicians should keep a high index of suspicion for adrenal insufficiency in patients with APS.     

Renal manifestations of the antiphospholipid syndrome

The antiphospholipid syndrome is characterized by recurrent arterial and venous thromboses and pregnancy morbidity in association with antiphospholipid antibodies. Recurrent thrombotic events are associated with significant morbidity and mortality. Renal involvement encompasses the whole renal vasculature and may lead to proteinuria, renal impairment, hypertension, and end-stage renal failure. Renal involvement is especially difficult to distinguish from glomerulonephritis when the antiphospholipid syndrome develops in patients with systemic lupus erythematosus. This article reviews the diagnosis and treatment of the major features of this syndrome, with particular reference to the kidney.     

Central nervous system involvement in the antiphospholipid (Hughes) syndrome

The antiphospholipid (Hughes) syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disorder or secondary to a connective tissue disease, most frequently systemic lupus erythematosus. Central nervous system (CNS) involvement is one of the most prominent clinical manifestations of APS, and includes arterial and venous thrombotic events, psychiatric features and a variety of other non-thrombotic neurological syndromes. In this review we focus on the common and some of the less common CNS manifestations that have been reported in association with antiphospholipid antibodies.     

HIV-related Hodgkin's disease with central nervous system involvement and association with Epstein-Barr virus

Central nervous system (CNS) involvement is a rare occurrence in the course of human immunodeficiency virus (HIV)-related Hodgkin's disease (HD). We report the clinical course of a patient with HIV infection who developed systemic HD, mixed cellularity subtype, later complicated by leptomeningeal involvement. The patient died from his illness, and autopsy was performed. Examining the brain lesion, Epstein-Barr virus (EBV) presence was demonstrated in Reed-Sternberg cells by immunohistochemistry using an EBER probe for EBV RNA. This is the second case report in the English literature of HD involving the CNS in an HIV-positive individual, and the first demonstrating EBV presence. Extranodal presence of Hodgkin's disease in patients with HIV infection is probably related to immunosuppression, and physicians treating this illness should be alert to the potential of unusual sites of involvement.     

The abdominal manifestations of the antiphospholipid syndrome

OBJECTIVES: To study the abdominal manifestations of the antiphospholipid syndrome (APS). METHODS: We reviewed the medical literature from 1968 to 2006 using MEDLINE and the key words: APS, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid (aPL) antibodies, catastrophic antiphospholipid syndrome, liver, hepatic biliary, pancreas, spleen, gastrointestinal and abdominal. RESULTS: Liver involvement is the most frequent abdominal manifestation associated with APS. Various hepatic manifestations have been reported including Budd-Chiari syndrome, hepatic-veno-occlusive disease and occlusion of small hepatic veins, nodular regenerative hyperplasia, hepatic infarction, cirrhosis, portal hypertension, autoimmune hepatitis and biliary cirrhosis. Acute intestinal infarction, intestinal angina, and intestinal bleeding have also been reported in association with aPL in addition to few sporadic cases of splenic infarction and acute pancreatitis. CONCLUSION: A high index of suspicion for any signs of abdominal involvement should be considered in patients with APS. In addition screening for aPL should be carried out in patients who present with hepatic vein occlusion and unexplained signs of intestinal angina.     

Myeloma of the central nervous system: association with high-risk chromosomal abnormalities, plasmablastic morphology and extramedullary manifestations

Involvement of the central nervous system (CNS) by multiple myeloma, as defined by the detection of malignant plasma cells in the cerebrospinal fluid in the presence of suggestive symptoms, is considered extremely rare. We report on the characteristics of 18 such patients diagnosed and treated at the University of Arkansas over the last 10 years for an overall incidence of approximately 1%. Their evaluation revealed association of CNS involvement with unfavourable cytogenetic abnormalities (especially translocations and deletion of the chromosome 13), high tumour mass, plasmablastic morphology, additional extramedullary myeloma manifestations and circulating plasma cells. The presence of these features should alert clinicians to the possibility of CNS involvement. The outcome of these patients was extremely poor despite the use of aggressive local and systemic treatment including autologous stem cell transplants. Given this universally poor prognosis, the application of allogeneic transplants should be studied in this clinical setting.     

The hematologic manifestations of the antiphospholipid syndrome

Various hematological pathologies have been described in association with antiphospholipid syndrome (APS). Thrombocytopenia is frequently found in APS patients, its incidence has ranged from 22-42% in different series, it is usually moderate (>50x10(9)/L) without clinical manifestation and requires no intervention. A high percentage of patients with isolated idiopathic thrombocytopenic purpura have antiphospholipid antibodies, however the pathogenetic role and the clinical importance of these antibodies in this condition is still not clear. Other hematological manifestations reported in association with APS include: bone marrow necrosis, and various thrombotic microangiopathic syndromes such as: thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, and catastrophic APS. A high index of suspicion is needed for the early recognition and treatment of these conditions.     

Neuroradiologic manifestations of central nervous system tuberculosis in 122 adults

PURPOSE: Central nervous system (CNS) tuberculosis remains a public health problem, particularly in developing countries. The aim of this study is to characterize neuroradiologic findings of various intracranial lesions. METHODS: We retrospectively reviewed data of 122 patients with CNS tuberculosis, without immunosuppression. CT scan was performed in all patients, whereas 17 patients had CT scan and MRI. RESULTS: We included 74 women (61%) and 48 men (39%) with a mean age of 37 years (17 -88y). 18 patients (14,7%) had a history of tuberculosis. Tuberculous meningitis was the most frequent clinical presentation (119 cases). Mycobacterium tuberculosis was isolated in cerebrospinal fluid of 18 patients (15%). Several types of lesions were identified : hydrocephalus (35 cases), tuberculomas (29 cases), leptomeningitis (26 cases), infarction (15 cases), abcesses (2 cases). Hydrocephalus was associated to other lesions in 26 cases. Communication hydrocephalus was present in 28 cases. Multiple tuberculomas were seen in 23 cases (80%), with miliary aspects in some cases. In 3 cases, tuberculoma was present without meningitis. Patients with leptomeningitis showed thick meningeal contrast enhancement involving all basal cisterns. Infarction resulted from arterial englobement or embols, and involved the area of middle cerebral artery (12 cases). CONCLUSION: Central nervous system tuberculosis has different appearences, mostly hydrocephalus and tuberculomas. MR with contrast is necessary for diagnosis and for follow-up during treatment.