Diagnosis Of Primary Antiphospholipid Syndrome Research Articles

Primary Antiphospholipid Syndrome Presenting with Cerebellar Stroke and Positive Titres of Anti-β2 Glycoprotein-1 Antibody Only: A Case Report (P9-5.026)

<h3>Objective:</h3> To describe a case of Primary Antiphospholipid Syndrome presenting with Cerebellar Stroke and positive titres of anti-β2 glycoprotein-1 antibody only. <h3>Background:</h3> Antiphospholipid syndrome (APS) is an autoimmune disease where the presence of antiphospholipid antibodies leads to the development of arterial and/or venous thromboses and obstetric complications. Amongst the myriad of presentations, APS can manifest in the form of cerebrovascular stroke. However, overlapping clinico-radiological findings and a lack of classic APS features can sometimes pose a diagnostic dilemma. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 31-year-old female presented with occipital headache and difficulty in walking. Neurological examination revealed ataxia, dysdiadochokinesia and intention tremor. Preliminary laboratory findings revealed raised ESR along with normal CRP, aPTT and PT levels. MRI brain showed an acute infarct in the right cerebellar hemisphere and right postero-lateral upper medulla. MRA Head &amp; Neck revealed an occluded intracranial right vertebral artery with an extracranial segment showing multifocal occlusions with aorta and its major branches unaffected. These features and the absence of fever, rash, joint pain or obstetric complications led to the consideration of stroke due to Takayasu Arteritis. Treatment was initiated with corticosteroids, anticoagulants and antiplatelet drugs. However, on review of other laboratory tests, notably the auto-immune profile showed the presence of anti-ß2 glycoprotein-I antibodies with negligible titres of lupus anticoagulant and anti-cardiolipin antibody. This pointed towards a diagnosis of Primary Antiphospholipid Syndrome, which was confirmed after 12 weeks when repeat laboratory tests indicated the presence of IgM anti-ß2 glycoprotein-I antibodies. The patient is now on lifelong Warfarin therapy and is leading a symptom-free life. <h3>Conclusions:</h3> This case illustrates the potential of anti-β2 glycoprotein-1 antibody to cause a cerebellar stroke in the absence of other commonly involved antibodies. It also highlights the value of a holistic stroke workup. Recognition of APS is imperative for the timely administration of treatment and to prevent a recurrence. <b>Disclosure:</b> Mr. Shah has nothing to disclose. Mr. Shah has nothing to disclose. Dr. Nagrani has nothing to disclose.

Demographic, Clinical, and Serological Characteristics of Antiphospholipid Syndrome Patients From the Anticoagulation Clinic of Hospital Universitario San Vicente Fundación, Medellín, Colombia.

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia, characterized by vascular thrombosis or obstetric compromise, associated with the presence of antiphospholipid antibodies. Large international studies have analyzed the clinical/serological behavior of the disease and in Colombia, there are few cohorts that have been evaluated. The main objective is to characterize the patients with APS followed in the anticoagulation clinic of a tertiary care hospital and to determine the clinical manifestations and serological findings at diagnosis. A retrospective descriptive study was carried out to evaluate patients with a presumptive and/or confirmed diagnosis of APS, according to modified Sapporo criteria, which fulfilled the inclusion and exclusion criteria established by the authors. The information was collected from the review of medical records. We included 103 patients, with the female sex being the most prevalent (86.6%). 54.3% of the patients (n = 56) had a diagnosis of primary APS. Venous thrombotic events occurred in 87.3% (n = 90) of the patients, 34.9% (n = 36) had arterial thrombosis (n = 36), and 3.9% (n = 4) had catastrophic APS (n = 4). 15 cases of Obstetric APS were documented. Lupus coagulation inhibitor (LA) positivity was the most prevalent marker in 84% (n = 68) of cases. The clinical behavior in this cohort of patients is like that found in large international and national studies. Most patients have a probable diagnosis of APS, so they could overestimate the real prevalence and condition of long-term anticoagulant treatment.

Intracranial Bleeding as Primary Manifestation of Antiphospholipid Syndrome: Case Report

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder usually resulting in an increased risk of blood clots in the arterial-, venous-, or microvascular system. Various antibodies have been identified causing the activation and aggregation of thrombocytes and endothelial dysfunction resulting in a wide range of symptoms. Frequent manifestation may be arterial or venous clots in extremities or internal organs, neurological manifestation or pregnancy morbidities. Rarely, APS can manifest in the form of hemorrhage. We discuss the case of a 40-year-old male presenting with a severe headache, fatigue and fever. Head CT confirmed a subdural hematoma. Laboratory findings showed anemia, thrombocytopenia and elongated coagulation times. Immunoserology found the strong presence of lupus anticoagulant, anti-cardiolipin-, and anti-β2glycoprotein-I IgG antibodies confirming the diagnosis of primary antiphospholipid syndrome, specifically LA - hypoprothrombinemia syndrome. Following the administration of high dose glucocorticoids, we chose to give intravenous immunoglobulin followed by rituximab. Although his symptoms regressed and there was no further hemorrhaging, we chose to perform plasmapheresis due to continuously high concentration of anti- phospholipid antibodies to lower the antibody titer, which proved to be effective. Antithrombotic treatment can be challenging in such cases due to the co-occurrence of hypoprothrombinemia and prothrombotic antibodies. We decided to administer low-dose aspirin, with which the patient has no bleeding or blood clots for over 6 years. We find the case worth presenting due to the rare occurance of bleeding as primary manifestation of APS and due to the challenging treatment.

Bilateral anterior ischemic optical neuropathy against the background of newly diagnosed antiphospholipid syndrome in a young patient

Introduction. Antiphospholipid syndrome (APS) is one of the leading causes of nonarteritic anterior ischemic opticoneuropathy (AION) in young patients. Ocular pathology, often being the earliest and the only manifestation of APS, explains possible difficulties in diagnosis of this thrombophilic condition. Objective – to present a clinical case of bilateral anterior ischemic opticoneuropathy against the background of newly diagnosed antiphospholipid syndrome in a young patient. Materials and Methods. At admission, the patient, born in 1988, was diagnosed with bilateral acute ischemic nonarteritic ION on the basis of visual acuity decrease to 0,7, narrowing of peripheral borders of visual fields concentrically by 10–15°, optic disc edema (ODE) of both eyes and macular edema of the right eye according to ophthalmoscopy and optical coherence tomography (OCT). Laboratory examination revealed thrombocytopenia, antibodies to DNA and cardiolipin in elevated titer, which allowed the diagnosis of primary antiphospholipid syndrome. Local anticoagulant and anticoagulant therapy, systemic administration of antioxidants, antiaggregants, vitamins, as well as preparations, improving microcirculation, were carried out. Results and Discussion. Against the background of treatment visual function restored to 1.0 in the right eye and 0.9 in the left eye, residual ODE edema was diagnosed in both eyes in the upper nasal sector. At follow-up in 2.5 months the morphological parameters of the retina and optic nerve were restored. Conclusion. Thromboocclusive lesions of retinal and optic nerve vessels are an early and sometimes the only manifestation of antiphospholipid syndrome. Their presence in young patients requires clinical and laboratory follow-up examination for timely diagnosis of concomitant thrombophilic condition. High risk of recurrent thrombosis of different localization makes it necessary to take antiplatelet agents for a long time.

Case of a Man with Hemichorea and Behavioral Changes: "A Red Herring".

Progressive supranuclear palsy (PSP)-pallido-nigro-luysian atrophy (PNLA) is a neuropathological entity thought to be a variant of classic PSP. Clinical features and pathologic hallmarks are the same in both conditions; however, age and order of symptom onset, disease duration and prognosis, and distribution and density of pathology differentiate the 2 entities. This study presents a PSP-PNLA case confirmed pathologically with a clinical presentation of hemichorea/ballism, spasticity, progressive hemiparesis, and a frontal behavioral syndrome with relative cognitive sparing early in the disease course. We describe the clinical progression in this unique case supplemented with video and imaging findings in the form of magnetic resonance imaging and brain single photon emission computed tomography. Final diagnosis is via pathological analysis at autopsy. We present an elderly gentleman who manifested a clinical syndrome consisting of subacute onset of chorea that at presentation was distinctly unilateral and a frontal behavioral syndrome in the setting of mild thrombocytopenia and elevated anticardiolipin antibodies. Positive antiphospholipid antibodies resulted in an initial antemortem diagnosis of primary antiphospholipid syndrome as a cause of his chorea. Longitudinal follow-up over 5 years demonstrated a progression of clinical features with hemi-motor impersistence/chorea, disinhibition and impulsivity, and eventually corticospinal distribution weakness on the initially affected side. He required nursing home care and falls necessitated wheelchair use. Postmortem neuropathological study revealed a diagnosis of frontotemporal lobar degeneration-tau, PSP-PNLA. This case broadens the phenotype of PSP-PNLA and to our knowledge is the only case presenting with unilateral chorea.

Anti-Phosholipid Syndrome Misdiagnosed As Multiple Sclerosis: A Case Report.

Multiple sclerosis (MS) and anti-phospholipid syndrome (APS) are chronic, immune-mediated, relapsing-remitting disorders affecting young adults. APS is characterized by thrombosis and pregnancy mortality associated with anti-phospholipid antibodies. The diagnosis of APS may be difficult, and it is not uncommon for patients with APS to be misdiagnosed with multiple sclerosis. In this case report, we describe a patient who was diagnosed as having multiple sclerosis for eleven-year. Initially, the patient had neurological deficits with relapsing-remitting courses, like MS but he had not classic magnetic resonance imaging appearance of MS and absence of oligoclonal bands in the cerebrospinal fluid. He did not meet the 'dissemination criteria in time and place' specified in the MS diagnostic criteria. Also, he had an acute myocardial infarction and ischemic stroke at different times. The diagnosis of primary APS was made after the patient had thrombotic attacks, seizure and was positive for anti-phospholipid antibodies (aPLs) twice. Our observations raise awareness about the importance of the early and correct diagnosis of APS. When assessing MS patients, clinicians should consider APS, if the MS has atypical features.

A case of primary antiphospholipid syndrome under the mask of systemic lupus erythematosus

A case of late diagnosis of primary antiphospholipid syndrome in a patient with recurrent miscarriage is presented. The pronounced immunological activity of the antiphospholipid syndrome with severe arthritis, fibrosing alveolitis mimicked systemic lupus erythematosus.

Antiphospholipid syndrome (APS): Clinical and immunoserological differences between primary and secondary APS in a Colombian cohort

IntroductionAntiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent thrombosis that can affect the arterial and venous circulation. ObjectivesTo analyze the immunological and pharmacological differences, as well as the clinical outcomes of a cohort of patients with primary antiphospholipid syndrome and secondary antiphospholipid syndrome. Materials and methodsA retrospective cohort study was conducted that included 352 records of patients diagnosed with APS and treated between 2014 and 2018. A description is presented of the sociodemographic, clinical, and immunological profile of the population. A bivariate analysis performed using the chi-squared test to determine differences between groups with primary APS and secondary APS, and finally a multivariate analysis to search for associations with thrombotic clinical outcomes in patients with APS. ResultsThe mean age was 42.4 ± 14 years, and 84.6% were females. Two-thirds (67.6%) of the patients had a diagnosis of primary APS, and 32.4% of secondary APS, of which 84% were associated with systemic lupus erythematosus (SLE). Among the thrombotic events, the most frequent were deep vein thrombosis (17.3%) and stroke (9.9%). Obstetric events were frequent, with a prevalence of 39.4% for miscarriages. No differences were found in the sociodemographic or immunoserological profile when comparing the group of primary vs. secondary APS. Thrombotic events were more frequent in the primary APS group, although only pulmonary embolism reached statistical significance. There were no differences between the two groups as regards obstetric events, such as miscarriages. Women were found to be 5 times more likely to have a stroke and 3 times more to have deep vein thrombosis. The anti-B2GPI type IgM increased the probability of presenting miscarriages about 3 times in women with APS. ConclusionThe study contains one of the largest Colombian cohorts with APS reported so far, and although it is both clinically and sociodemographically similar to other cohorts, there is a higher prevalence of primary APS. There was a lower frequency of thrombotic complications compared to other cohorts. Patients with primary APS had a tendency to develop thrombosis, as has already been reported in the literature.

Psychosocial burden in young patients with primary anti-phospholipid syndrome: an Italian nationwide survey (The AQUEOUS study).

The AQUEOUS (Anti-phospholipid syndrome: a QUEstionnaire for yOUng patientS) study aimed to assess how the diagnosis of primary anti-phospholipid syndrome (PAPS) affects the psychosocial status of young patients. Subjects with PAPS aged 18-45 years were invited to compile an ad hoc designed questionnaire and the Short Form-12 to assess quality of life (QoL). Ninety-two patients (83.7% females) were recruited in 10 Italian centres. Vascular and obstetric manifestations were equally represented. Nearly half of the patients perceived the need for psychological support, 89.2% when considering women after pregnancy complications. Social activities and working efficiency were reduced in APS patients, also intimacy was threatened. In all cases, fatigue appeared to be the main determinant. PAPS affected family planning, due to fears of treatment side-effects, disease hereditariness, inability to care for the newborn child. Fertility appeared to be conserved: the median time to pregnancy was 2 months; assisted reproduction techniques were pursued by 5 women. Our survey documented significantly lower rates of hospitalisation and learning disabilities in 51 children born after APS diagnosis as compared to 48 children born before. PAPS patients displayed lower QoL in physical and, to a greater extent, mental scores compared to the general Italian population. Both components were significantly lower in women and in patients with fatigue. The AQUEOUS study assessed for the first time the unmet needs of young PAPS patients, enabling the development of a future "youth-focused" strategy to reduce disease burden.

Clinical characteristics and risk factors of microvascular involvement in primary antiphospholipid syndrome: a longitudinal single-center study in China.

The objective of this study was to investigate risk factors of microvascular involvement and survival in Chinese patients with primary antiphospholipid syndrome. In this single-center, retrospective study, we enrolled 112 patients with a confirmed diagnosis of primary antiphospholipid syndrome who were admitted to Peking Union Medical College Hospital from January 2004 to December 2016. Demographic data, clinical characteristics, laboratory results, and follow-up records were collected. A total of 112 patients with primary antiphospholipid syndrome were studied. Microvascular involvement was identified in 21 patients (18.75%). Patients with microvascular involvement experienced fewer episodes of arterial or venous thrombosis (28.6% vs. 84.6%) and a higher incidence of thrombocytopenia (85.7% vs. 54.9%), respectively. Low complement and elevated high-sensitivity CRP levels were observed more frequently in the microvascular group compared with the non-microvascular group (complement 38.1% vs. 18.7%; high-sensitivity CRP 71.4% vs. 31.9%, respectively). Anti-β2-glycoprotein I antibodies were more prevalent in patients with microvascular involvement than in patients without (66.7% vs. 33.0%, respectively). Multivariate logistic regression analysis revealed that thrombocytopenia (odds ratio = 4.523, 95% confidence interval 1.139-17.962), elevated high-sensitivity CRP levels (odds ratio = 6.385, 95% confidence interval 1.969-20.704), and anti-β2-glycoprotein I antibody positivity (odds ratio = 5.042, 95% confidence interval 1.555-16.352) were independent risk factors for microvascular involvement. A Kaplan-Meier analysis revealed that survival was significantly poorer in patients with microvascular involvement compared with patients without (p = 0.0278). In addition to arterial and venous thrombosis, antiphospholipid syndrome can affect the microvasculature of select organs. It is thus important for clinicians to be aware that antiphospholipid syndrome-associated microvascular involvement has a unique pathogenesis and can be a life-threatening condition.

Gluteus Muscle Bleeding

Case Presentation: A 59-year-old man on anticoagulation therapy with warfarin complained of sudden, progressive and severe pain and tenderness around right gluteus muscles and all the way down to the calf muscles of right leg. Two days earlier he slipped and suffered a trauma to gluteal region and both lower limbs. Over the past couple of days, he complained of debilitating pain and wasn’t able to sit, sleep or move. His past history was unremarkable apart from the diagnosis of primary antiphospholipid syndrome. On physical examination, the patient was fully conscious with stable vital signs, and no abnormality was detected other than large ecchymosis and bruises all over right gluteal, quadriceps and calf muscles with similar but to a much lower extent on left side. Laboratory investigations showed elevated international normalized ratio (INR) of 4.8 (prescribed ratio 2-3), hemoglobin dropped from 14.5 gm/dl down to 11.3 gm/dl. Lumbar and Pelvic Magnetic Resonance Imaging (MRI) sections demonstrated a big right sided collection extending in between the gluteus maximus and gluteus medius measures 20 × 2.3 × 11 cm presented as low to iso signal in T1 sections and high signal in T2 sections, associated with completely abnormal high signal of the gluteus medius muscle in T2 sections with lobulated collection inside having fluid- level measures about 8 × 4.5 cm in keeping with intramuscular hematoma with extra muscular blood spillage (Figures 1-4).

Antibodies Directed Against the Domain 1 of Beta2-Glicoprotein 1 May be Associated with Secondary Antiphospholipid Syndrome

Background: The diagnosis of antiphospholipid syndrome (APS) is based on the persistent positivity of lupus anticoagulant (LA), IgM or IgG anticardiolipin (aCL) or IgG anti-β2 glicoprotein 1 (aβ2GP1) antibodies in patients plasma. Particularly, the role of antibodies directed against the domain 1 of β2GP1 (aβ2GP1-D1) has been described as relevant for the mechanism of immunopathogenesis in APS. However, the role of the aβ2GP1-D1 antibodies in clinical diagnosis and management of APS has not been established.Aim: The aim of this study was to evaluated the association of the presence of aβ2GP1-D1 antibodies with the clinical course of patients with thrombotic APS.Patients and methods: Patientspreviously diagnosed with thrombotic APS were consecutively selected for the study, from December 2013 to July 2014, in the Hemostasis Clinic of the Hematology and Hemotherapy Center of the University of Campinas. Demographic features and clinical conditions were recorded at the inclusion and during the follow-up. The clinical parameters analyzed were APS etiology (primary versus secondary to systemic autoimmune diseases), vascular bed of the thrombosis, history of multiple thrombosis, concomitant obstetrical morbidity, the presence of antinuclear antibodies (ANA) and the profile of the antiphospholipid antibodies. Anti-β2GP1-D1 antibodies were determined in patients plasma by chemiluminescence (BioFlash/AcuStar®, Barcelona, ES). Exact Fisher test and logistic regression were performed for statistical analysis. P < 0.05 were considered statistical significant.Results: Eight-five patients were included in the study, all patients presented venous or arterial thrombosis. The antibodies distribution among patients was: 80% LA positive, 50% aCL positive, 54% aβ2GP1 positive and 26% triple positive. Twenty-one patients (25%) tested positive for aβ2GP1-D1, 94% of them had positive aβ2GP1 antibody, previously detected at diagnosis. The presence of aβ2GP1-D1 was not associated with age or gender. Detected clinical conditions related to APS severity, such as thrombosis recurrence, concomitant obstetrical and vascular morbidity and triple positive antiphospholipid antibodies were evaluated. The positivity for aβ2GPI-DI antibodies was not associated with thrombosis recurrence (OR=1.0, 95%CI=0.37-2.71,P=1.0), concomitant obstetrical and vascular morbidity (OR=1.5, 95%CI=0.33-7.34, P=0.58), or triple positive antibodies (OR=2.79 , 95%CI=0.76 - 8.84, P=0.13). Anti-β2GP1-D1 antibodies were associated with the diagnosis of systemic autoimmune disease, in particular with lupus, (OR= 3.49 , 95%CI=1.25-9.76, P=0.01) and with positive ANA test (OR= 3.3, 95%CI=1.08-10.1, P=0.03).Conclusion: In this study, aβ2GPI-DI antibody was detected mainly in patients who had already tested positive for aβ2GP1 antibody, so it is possible that aβ2GP1-D1 assay may not provide additional sensibility to the diagnosis of APS. However, our results also suggested that the presence of aβ2GP1-D1 antibody might be associated to the diagnosis of secondary APS. The diagnosis of primary APS is based on the exclusion of systemic autoimmune diseases and there are no current laboratory parameters that discriminate between primary and secondary APS. Besides the laboratory criteria for lupus diagnosis, there may be overlapping of the antibodies and hematological features between APS and lupus. Furthermore, after the diagnosis of primary APS, it may take long time of follow-up to detect the underlying autoimmune disease. Therefore, if our findings are confirmed, aβ2GP1-D1 assays may play a role as a laboratory tool for the differential diagnosis between primary and secondary APS. DisclosuresNo relevant conflicts of interest to declare.

Patients with longstanding primary antiphospholipid syndrome: retrospective analysis of organ damage and mortality.

To assess the prevalence of disease- and therapy-related complications and of the organ damage after a follow-up of 15 years or more in patients with primary antiphospholipid syndrome (PAPS). Medical records of patients prospectively followed in our centre for at least 15 years were retrospectively reviewed. Thirty-five Caucasian patients (33 female, two male) with diagnosis of PAPS followed from 1984 to 2013 with a mean age at onset of 32 years (SD 8.17) and a median follow-up of 20.5 years (range 15-30) were included. The occurrence of systemic autoimmune disease was observed in 14% of patients. Haemorrhagic, infective and neoplastic events were recorded in 34%, 6% and 9% respectively. Organ damage was present in 20% of patients at the end of the follow-up (17% neurological and 3% renal) and was significantly associated with the occurrence of thrombotic events (p: 0.027), particularly arterial (p<0.001). A 48-year-old patient died from sepsis. During long-term follow-up of PAPS systemic autoimmunity is not unexpected. Organ damage progresses in a significant proportion of patients especially if they have suffered previous arterial events. Our study clearly shows the possible evolution of the disease and of organ damage, suggesting that optimal therapy and optimal prophylaxis of each PAPS patient should be carefully identified and strictly applied.

The spectrum between antiphospholipid syndrome and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS) are interconnected autoimmune diseases. APS was primarily described by Graham Hughes in a group of patients with SLE who suffered from obstetric morbidity and/or recurrent thromboses [1]. Along the years, it was noted that patients may exhibit APS manifestations with no characteristic of SLE classified as primary APS, whereas APS presenting concomitantly with SLE was termed secondary APS. Unlike SLE, APS was not considered to be a systemic disease. However, in the course of time, APS was found to be associated with damage to various organs and systems and to evolve into SLE in about 10 % of patients. Moreover, the expression lupus-like APS was coined to define APS patients displaying systemic “SLE features” although SLE criteria cannot be fulfilled [2, 3]. For years, clinicians and scientist have tried to better discriminate between these conditions. Certain manifestations of SLE such as the presence of antinuclear antibodies, complement activation, or immune mediated kidney disease were accepted as markers to distinguish this disease from primary APS. However, in the last decades, the presence of antinuclear antibodies, hypocomplementemia, non-thrombotic kidney disease, and renal failure were all documented in patients diagnosed with primary APS and the activation of complement was found to be related with APS in experimental models [2]. Last but not the least, the antiphospholipid antibodies serve as criteria for both syndromes and are present in 100 % of APS patients and in up to 40 % of SLE patients, of which many will eventually develop overt APS [2–4]. Hence, the great heterogeneity and overlap between these autoimmune diseases raised the debate: Are they a single condition with varied phenotypes, or different diseases with diverse pathogenic mechanisms sharing phenotypes? [5–7]. In the current issue, Freire PV et al. [8] retrospectively analyzed a cohort of 80 patients with primary APS of which 14 (17.5 %) progressed within 5.2±4 years to SLE-APS. The latter was significantly younger at diagnosis and their disease duration was longer. In addition, the presence of autoantibodies and particularly antinuclear ones were noted in 100 % of patients finally diagnosed with concomitant APSSLE compared to 51 % of patients that remained with the diagnosis of primary APS (P=0.0005). Moreover, specific autoantibodies (i.e., anti-dsDNA, anti-ribosomal P, anti-Ro/ SS-A, anti-La/SS-B, and anti-U1RNP) were exclusively found among patients ultimately diagnosed with concomitant SLE, supporting the notion that primary APS may differ from APS associated with SLE. The role of autoantibodies as markers and players in the mosaic of autoimmunity is well established [9, 10]. For instance, antinuclear antibodies alongside a wide array of related specific autoantibodies are key markers and servers as criteria for diagnoses of some autoimmune diseases [9]. Furthermore, several specific antibodies were linked with clinical manifestations of different diseases further supporting their plausible pathogenic role [11, 12]. But perhaps the most substantial evidence is a series of studies demonstrating that specific autoantibodies can be detected years before the development of an overt disease. Indeed, Arbuckle et al. [13] found that 88 % of SLE patients were antibody positive up to 30 years prior to diagnosis and a stepwise accumulation of these antibodies was a marker of the preclinical stage of SLE. Similarly, the presence of anti-mitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC), anti-Saccharomyces cerevisiae antibodies in Chron’s disease, and anti-neutrophil cytoplasmic antibodies (ANCA) both in ulcerative colitis and in ANCAN. Agmon-Levin :Y. Shoenfeld (*) Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer 52621, Israel e-mail: shoenfel@post.tau.ac.il

Nonarteritic anterior ischemic optic neuropathy as the presenting manifestation of primary antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis or pregnancy morbidity. Ocular involvement in APS includes a broad spectrum of manifestations involving anterior and posterior segment or the presence of neuroophthalmologic features. Nonarteritic anterior ischemic optic neuropathy (NAION) is a very rare finding, and in this report a case having NAION as the prevailing sign of APS is presented. A middle-aged women who presented with visual disturbances in her left eye (LE) and turned out to have the diagnosis of primary APS with the help of rheumatological investigations is discussed. She was treated with oral steroids for NAION in her LE. With systemic and rheumatological work-up, primary APS was diagnosed, and hydroxychloroquine, coumadin, and aspirin were started, after which she remained stable under control. Due to the important diagnostic and therapeutic implications of APS, it should be considered in the differential diagnosis of NAION, particularly when the etiology is uncertain.

Primary Antiphospholipid Syndrome and Necrotizing Pancreatitis

The objective of this study was to report an unusual case of primary antiphospholipid syndrome (APS)-associated severe necrotizing pancreatitis. Since the APS was first recognized in the 1980s, a number of manifestations of the disorder have been described. We report primary APS presenting as severe necrotizing pancreatitis. This is the first such case to date that fulfills the revised Sapporo classification criteria. A 38-year-old previously healthy woman presented with new-onset hypertensive emergency and acute kidney injury. She subsequently developed severe epigastric pain attributable to necrotizing pancreatitis and extensive splenic infarcts. Biopsies of both the pancreas and kidney revealed thrombotic microangiopathy. Her lupus anticoagulant was positive on both weeks 1 and 12 of her disease course. A diagnosis of primary APS was made. Despite 6 months of aggressive care, she died of sepsis.

Primary antiphospholipid syndrome progressing to systemic lupus erythematosus: a case report

Introduction: Primary antiphospholipid syndrome (APS) is a thrombophilic disease that should be suspected in the presence of thrombotic events associated with hematologic abnormalities such as thrombocytopenia and prolongation of the activated partial thromboplastin time. The diagnosis must be confirmed by the demonstration of autoantibodies directed against anionic phospholipids and/or phospholipid-binding proteins. The disease can cause arterial thrombosis in any vascular district, including those of the kidney and central nervous system. Case report: In 2006 a 29-year-old male presented with kidney and brain involvement that was attributed to primary APS. The clinical diagnosis was confirmed by the results of a renal biopsy, which excluded the presence of systemic lupus erythematosus (SLE). The patient remained stable through 32 months of follow-up and then developed a malar rash with deteriorating renal function, decreasing platelet count, and reduced complement levels. Serological studies revealed positivity for ANA (homogeneous pattern), dsDNA, ACA, and beta-2-glycoprotein-1 antibodies. The diagnosis was revised to APS secondary to SLE. Conclusions: A diagnosis of primary APS should not be considered permanent: progression to SLE can occur, in some cases years after the original diagnosis. This case highlights the importance of ongoing follow-up of patients diagnosed with primary APS to detect changes that herald the emergence of SLE.

Pathological gambling and primary antiphospholipid (Hughes) syndrome: a unique neuropsychiatric association

Neuropsychiatric conditions are common in patients with primary antiphospholipid syndrome (APS) with or without vascular thrombosis of the central nervous system. There are frequent descriptions of memory alterations, cognition and mood disorders, such as depression, anxiety, and even conditions of mania and psychosis preceding the diagnosis of primary APS. However, this study is the first to present primary or secondary APS associated with habit or impulse control disorders. The authors describe the case of a 53-year-old male patient who had been a pathological gambler since adulthood and who has had APS for more than 20 years. We describe the case and review its characteristics, criteria for diagnosis and treatment offered for patients with this specific subtype of impulse disorder.

Splenomegaly in Primary Antiphospholipid Syndrome without Accompanying Portal Hypertension or Comorbidity

Objective: To demonstrate the presence of splenomegaly in primary antiphospholipid syndrome (PAPS) patients without accompanying portal hypertension or comorbidity. Methods: Twelve patients (7 women) aged 23–65 years followed upon the diagnosis of PAPS were enrolled in the study. We documented the identified causes of splenomegaly in patients with PAPS, and searched for the potential causes of splenomegaly in patients with spleen enlargement. PAPS patients with or without splenomegaly were evaluated in terms of demographic and clinical findings. Results: Splenomegaly was present in 6 of the 12 patients. In these patients, there were no infections, hematological disorders, portal hypertension or malignancy that might lead to splenomegaly. The long axis of spleen was found to be in the range of 137–155 mm in patients with splenomegaly. Splenomegaly was more frequently determined in female PAPS patients. The splenomegaly group had a longer duration of disease (median 5.5 vs. 0.75 years) and a higher number of thrombotic events (median 3 vs. 1.5). The splenomegaly group was especially composed of patients who never received any anticoagulant and acetylsalicylic acid, or who used these agents irregularly for very short periods. Conclusion: Splenomegaly was observed in association with disease duration, frequency of thrombotic events and irregular antiaggregant or anticoagulant treatment in patients with PAPS, in the absence of comorbidity or portal hypertension.

Case report: Branch retinal vein occlusion and primary antiphospholipid syndrome

Background Branch retinal vein occlusion (BRVO) is commonly encountered in older patients with vascular disease. This report presents a case of BRVO in an atypically young patient that precipitated additional testing and a subsequent diagnosis of primary antiphospholipid syndrome. This illustrates a need for a thrombophilic evaluation in atypical patients. Case report A 33-year-old white man presented with a BRVO in the left eye. Laboratory studies found the presence of persistently elevated anticardiolipin immunoglobulin G and immunoglobulin M antibodies in the absence of causative systemic disease, conferring the diagnosis of primary antiphospholipid syndrome and supporting a thrombotic component of this BRVO. Conclusion The presentation of a BRVO in young patients with minimal observable retinal effects from classic BRVO risk factors may indicate the necessity of a hematologic evaluation to determine possible compounding causes. Here we show a methodical inspection of the cause of an atypical BRVO and, more specifically, consideration for hypercoagulable pathologies and their treatment in such patient encounters.