Absence Of Systemic Lupus Erythematosus Research Articles

Trends in and outcomes of delivery hospitalizations with lupus and antiphospholipid syndrome.

To assess trends and outcomes associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) during US delivery hospitalizations. The National Inpatient Sample from 2000 to 2019 was used for this repeated cross-sectional analysis. We identified delivery hospitalizations with and without SLE. Temporal trends in SLE during delivery hospitalizations were determined using joinpoint regression. Adjusted logistic regression models accounting for demographic, clinical, and hospital factors were used to determine adjusted odds ratios (aORs) for adverse outcomes based on the presence or absence of SLE. Of an estimated 76 698 775 delivery hospitalizations identified in the NIS, 79386 (0.10%) had an associated diagnosis of SLE. Over the study period, SLE increased from 6.7 to 14.6 cases per 10 000 delivery hospitalizations (average annual percent change 4.5%, 95% CI 4.0-5.1). Deliveries with SLE had greater odds of non-transfusion severe morbidity (aOR 2.21, 95% CI 2.00, 2.44) and underwent a larger absolute increase in morbidity risk over the study period. SLE was associated with a range of other adverse outcomes including preterm delivery, eclampsia, cesarean delivery, and blood transfusion. The proportion of deliveries to women with SLE has increased over time in the US, and SLE and APS are associated with a broad range of adverse outcomes.

Machine Learning Approach for Predicting Systemic Lupus Erythematosus in an Oman-Based Cohort.

This study aimed to design a machine learning-based prediction framework to predict the presence or absence of systemic lupus erythematosus (SLE) in a cohort of Omani patients. Data of 219 patients from 2006 to 2019 were extracted from Sultan Qaboos University Hospital's electronic records. Among these, 138 patients had SLE, while the remaining 81 had other rheumatologic diseases. Clinical and demographic features were analysed to focus on the early stages of the disease. Recursive feature selection was implemented to choose the most informative features. The CatBoost classification algorithm was utilised to predict SLE, and the SHAP explainer algorithm was applied on top of the CatBoost model to provide individual prediction reasoning, which was then validated by rheumatologists. CatBoost achieved an area under the receiver operating characteristic curve score of 0.95 and a sensitivity of 92%. The SHAP algorithm identified four clinical features (alopecia, renal disorders, acute cutaneous lupus and haemolytic anaemia) and the patient's age as having the greatest contribution to the prediction. An explainable framework to predict SLE in patients and provide reasoning for its prediction was designed and validated. This framework enables clinicians to implement early interventions that will lead to positive healthcare outcomes.

The appearance of C1q deposition in transplanted kidney allografts and its clinical and histopathologic features.

BackgroundC1q nephropathy is an uncommon type of glomerulonephritis characterized by extensive and dominant C1q mesangial deposition in the absence of systemic lupus erythematosus. However, there are limited studies about C1q deposition in renal allografts. This study aimed to report the prevalence of C1q deposition in transplanted kidney allograft biopsies and describe its clinical and histopathologic features.MethodsBetween January 2005 and December 2018, a total of 1,742 kidney transplantations were performed at Seoul National University Hospital. All renal allograft biopsies (n=10,217) of these patients were retrospectively screened for C1q deposition. C1q deposition was detected in the renal allograft biopsies of 104 patients (6.0%). Only 28 cases (1.6%) had intense (≥2+) C1q dominance and were reviewed in this study.ResultsAmong the 28 cases, only four (14.3%) had accompanying proliferative glomerulonephritis. Most did not have any other glomerular changes on light microscopy. No patients had nephrotic-range proteinuria at the time of biopsy. A follow-up biopsy was undertaken in 15 of the cases (53.6%). In these follow-up biopsies, C1q deposition either completely disappeared (n=13, 86.7%) or showed diminished staining (n=2, 13.3%).ConclusionsThe prevalence of dominant or codominant C1q deposition in transplanted renal allograft biopsies was 1.6%. Most cases did not have any other accompanying glomerular changes. The follow-up biopsies of these allografts showed spontaneous disappearance or diminished staining of C1q deposition. These findings suggest that C1q deposition found in renal allografts is most likely clinically benign, although this possibility should be confirmed in further large-scale studies.

Racial Disparities in the Incidence of Primary Chronic Cutaneous Lupus Erythematosus in the Southeastern US: The Georgia Lupus Registry.

Relative to studies of systemic lupus erythematosus (SLE), epidemiologic studies of chronic cutaneous lupus erythematosus (CCLE) are rare and are limited to populations with no racial diversity. We sought to provide minimum estimates of the incidence of primary CCLE (CCLE in the absence of SLE) in a population comprised predominantly of white individuals and black individuals in the southeastern region of the US. The Georgia Lupus Registry allowed for the use of multiple sources for case-finding, including dermatology and rheumatology practices, multispecialty health care facilities, and dermatopathology reports. Cases with a clinical or clinical/histologic diagnosis of CCLE were classified as definite. Cases ascertained exclusively from dermatopathology reports were categorized as probable. Age-standardized incidence rates stratified by sex and race were calculated for discoid lupus erythematosus (DLE) in particular and for CCLE in general. The overall age-adjusted estimates for combined (definite and probable) CCLE were 3.9 per 100,000 person-years (95% confidence interval [95% CI] 3.4-4.5). The overall age-adjusted incidences of definite and combined DLE were 2.9 (95% CI 2.4-3.4) and 3.7 (95% CI 3.2-4.3) per 100,000 person-years, respectively. When capture-recapture methods were used, the age-adjusted incidence of definite DLE increased to 4.0 (95% CI 3.2-4.3). The black:white and female:male incidence ratios for definite DLE were 5.4 and 3.1, respectively. Our findings underscore the striking racial disparities in susceptibility to primary CCLE, with black individuals having a 3-fold to 5-fold increased incidence of CCLE in general, and DLE in particular, compared with white individuals. The observed sex differences were consistent with those reported previously, with a 3 times higher risk of DLE in women compared with men.

Acute glomerulonephritis with large confluent IgA-dominant deposits associated with liver cirrhosis.

BackgroundSmall glomerular IgA deposits have been reported in patients with liver cirrhosis, mainly as an incidental finding in autopsy studies. We recently encountered nine cirrhotic patients who presented with acute proliferative glomerulonephritis with unusually large, exuberant glomerular immune complex deposits, in the absence of systemic lupus erythematosus (SLE) or monoclonal gammopathy-related kidney disease. Deposits were typically IgA dominant/codominant. Our aim was to further elucidate the etiology, diagnostic pitfalls, and clinical outcomes.MethodsWe present clinical features and kidney biopsy findings of nine cirrhotic patients with an unusual acute immune complex glomerulonephritis. We also identified native kidney biopsies from all patients with liver cirrhosis at our institution over a 13-year period (January 2004 to December 2016) to evaluate presence of glomerular IgA deposits in them (n = 118).ResultsSix of nine cirrhotic patients with the large immune deposits had a recent/concurrent acute bacterial infection, prompting a diagnosis of infection-associated glomerulonephritis and treatment with antibiotics. In the remaining three patients, no infection was identified and corticosteroids were initiated. Three of nine patients recovered kidney function (one recovered kidney function after liver transplant); three patients developed chronic kidney disease but remained off dialysis; two patients became dialysis-dependent and one patient developed sepsis and expired shortly after biopsy. Within the total cohort of 118 patients with cirrhosis, 67 others also showed IgA deposits, albeit small; and 42 patients had no IgA deposits.ConclusionsThese cases provide support to the theory that liver dysfunction may compromise clearance of circulating immune complexes, enabling deposition in the kidney. At least in a subset of cirrhotic patients, a superimposed bacterial infection may serve as a “second-hit” and lead to acute glomerulonephritis with exuberant immune complex deposits. Therefore, a trial of antibiotics is recommended and caution is advised before immunosuppressive treatment is offered. Unfortunately, most of these patients have advanced liver failure; therefore both diagnosis and management remain a challenge.

The existential experience of everyday life with systemic lupus erythematosus.

To explore from the perspective of women the nature of basic existential conditions while living with systemic lupus erythematosus. Systemic lupus erythematosus has an unpredictable disease course and is documented to cause an existential rearrangement of life. The significance of changes in existential conditions and related experiences are unclear in the context of nursing and women with systemic lupus erythematosus. A qualitative design guided by Van Manen's hermeneutic-phenomenological methodology. Individual in-depth interviews with 15 women diagnosed with systemic lupus erythematosus and of various ages, disease durations and severities were undertaken from September 2013 - October 2015. Data were analysed following van Manen's phenomenological approach and using drawing as an interpretive tool. The main existential experience was interpreted as a person "moving with the waves of systemic lupus erythematosus" constituted by the themes "oscillating between presence and absence of systemic lupus erythematosus," "recognizing space and bodily possibilities and limitations" and "being enriched through relationships and activities." When systemic lupus erythematosus was flaring, well-being was threatened and a laborious time to escape the feeling of a setback-in-life persisted long after the disease was medically under control. Daily life with systemic lupus erythematosus is conditioned by a prominent need to be in existential motion, related to the absence and presence of systemic lupus erythematosus. The experience of a setback-in-life by illness might challenge well-being and indicates that periods of disease flares or disturbing symptoms are critical time points to provide support.

Proliferative lupus nephritis in the absence of overt systemic lupus erythematosus: A historical study of 12 adult patients.

Severe lupus nephritis in the absence of systemic lupus erythematosus (SLE) is a rare condition with an unclear clinical presentation and outcome.We conducted a historical observational study of 12 adult (age >18 years) patients with biopsy-proven severe lupus nephritis or lupus-like nephritis without SLE immunological markers at diagnosis or during follow-up. Excluded were patients with chronic infections with HIV or hepatitis B or C; patients with a bacterial infectious disease; and patients with pure membranous nephropathy. Electron microscopy was retrospectively performed when the material was available. End points were the proportion of patients with a complete response (urine protein to creatinine ratio <0.5 g/day and a normal or near-normal eGFR), partial response (≥50% reduction in proteinuria to subnephrotic levels and a normal or near-normal eGFR), or nonresponse at 12 months or later after the initiation of the treatment.The study included 12 patients (66% female) with a median age of 36.5 years. At diagnosis, median creatinine and proteinuria levels were 1.21 mg/dL (range 0.5–11.6) and 7.5 g/day (1.4–26.7), respectively. Six patients had nephrotic syndrome and acute kidney injury. Renal biopsy examinations revealed class III or class IV A/C lupus nephritis in all cases. Electron microscopy was performed on samples from 5 patients. The results showed mesangial and subendothelial dense deposits consistent with LN in 4 cases, and a retrospective diagnosis of pseudo-amyloid fibrillary glomerulonephritis was made in 1 patient.Patients received immunosuppressive therapy consisting of induction therapy followed by maintenance therapy, similar to treatment for severe lupus nephritis. Remission was recorded in 10 patients at 12 months after the initiation of treatment. One patient reached end-stage renal disease. After a median follow-up of 24 months, 2 patients relapsed.Lupus nephritis in the absence of overt SLE is a nosological entity requiring careful etiological investigation, including systematic electron microscopy examination of renal biopsies to rule out fibrillary glomerulonephritis. In this series, most patients presented with severe glomerulonephritis, which was highly similar to lupus nephritis at presentation and in terms of response to immunosuppressive therapy.

Immune Complex Disease With a Lupus-like Pattern of Deposition in an Antinuclear Antibody–Negative Patient

Immune complex-mediated glomerulonephritis can be caused by a multitude of disease processes and may manifest in a variety of histologic patterns. Lupus nephritis is an immune complex disease, the diagnosis of which requires that the affected patient have systemic lupus erythematosus (SLE). In the absence of SLE, the finding of glomerulonephritis with certain patterns of immune complex deposition characteristic of lupus nephritis has been referred to as lupus-like glomerulonephritis. Immunoglobulin G (IgG), IgA, IgM, complement C3, and C1q deposition in glomerular immune deposits is one such pattern. We report a case of immune complex disease in a primarily membranous distribution with mesangial, subendothelial, and tubular basement membrane deposits with IgG, IgA, IgM, C3, and C1q deposition in a patient with proteinuria, photosensitive dermatitis, and a positive lupus anticoagulant test. The patient had 3 of the clinical criteria for SLE, thus failing to meet the diagnosis based on the American College of Rheumatology definition. In this case, a diagnosis of lupus-like glomerulonephritis was made after other causes of membranous glomerulopathy were excluded. This teaching case highlights the broad differential diagnosis of this pattern of injury and reviews similar cases in the literature.

Primary Antiphospholipid Antibody Syndrome and Libmann-Sachs Endocarditis

Primary antiphospholipid antibody syndrome is defined by the presence of anticardiolipin antibodies in the absence of systemic lupus erythematosus. Thrombotic phenomena, stroke, and rarely chorea are components of this syndrome. Libmann-Sachs endocarditis is present in 35% to 50% of these patients, with a potential for systemic embolization. A 27-year-old patient presented with chorea, headache, and visual disturbances. Retinoscopy demonstrated a cotton wool spot (A, black circle), suggesting occlusion of the retinal artery branch. Three-dimensional echocardiography depicted vegetation (1.5 × 0.7 cm) (B, blue arrow) in the midportion of the anterior mitral leaflet (B, white arrows) with severe mitral regurgitation. Intraoperative photography confirmed this (blue arrow, C) and a smaller vegetation on the posterior mitral leaflet (C, orange arrow). Figure D shows the repaired mitral valve with resuspension of the anterior mitral leaflet with neo-chordae (*) with suture annuloplasty (D, white arrows).

Retinitis preceding systemic lupus erythematosus in absence of anti-phospholipid antibodies

Retinitis preceding systemic lupus erythematosus in absence of anti-phospholipid antibodies

Elevated Serum Type I Interferon Activity and Type I Interferon Peripheral Blood Gene Signature In a Subset of Patients with Acquired ADAMTS13-Deficient Thrombotic Thrombocytopenic Purpura.

AbstractAbstract 3694 Background:Current treatments for Thrombotic Thrombocytopenic Purpura (TTP) fail to successfully control this life-threatening syndrome in up to 20% of patients, and of those patients who survive the first episode, a substantial fraction experience at least one relapse. Genetic mutation or autoantibody inhibition of the ultra-large von-Willebrand factor protease, A Disintegrin And Metalloproteinase with a Thrombospondin Type 1 Motif (ADAMTS13), reduces its enzymatic activity and is an important factor that promotes TTP development. Case reports of acute TTP episodes following infections or Type I interferon (IFN) treatment, a phenomenon also observed in systemic lupus erythematosus (SLE), suggest that inflammatory dysregulation could be important in this disease. SLE patients have elevated serum Type I IFN activity and a peripheral blood Type I IFN gene signature, which are associated with the presence of autoantibodies specific for RNA-binding nuclear antigens. Purpose:This study was undertaken to determine whether, in the absence of SLE, Type I IFN is elevated in acquired TTP patients, and/or is associated with autoantibodies to RNA-binding proteins. Study Participants:We obtained blood and serum samples from patients with acquired ADAMTS13-deficient TTP and matched healthy controls. Patient Inclusion Criteria: 1) ADAMTS13 activity <10% during either the initial episode or during a relapse, 2) at least six months follow-up after an initial or relapse episode; Exclusion criteria: 1) institutionalized or not alive at the time of study 2) previous diagnosis of an autoimmune disorder. Methods and Results:Blood samples were collected from 38 eligible TTP subjects during remission and from 38 age- (±5 years), race- and sex-matched healthy controls. While anti-nuclear autoantibody prevalence (titer ≥1:120) did not significantly differ between TTP patients and controls, specific autoantibodies against one or more of the following RNA-binding antigens: Ro, La, Sm or nRNP, were more frequent in TTP patients (31.6%) compared to controls (5.3%) (McNemar c2 p=0.0063). Using previously-banked serum samples from acute phase(s) of the disease obtained from the same patients, we observed no differences in the prevalence of these autoantibodies among TTP subjects in the acute phase of disease compared to remission. Serum Type I IFN activity was measured by the capacity of serum samples to induce expression of Type I IFN genes in the WISH epithelial cell line and was significantly increased in remission TTP samples compared to controls (McNemar c2 p=0.0313). Finally, global gene expression was examined (Illumina WG6 version 3 chips) in globin RNA-cleared total RNA taken from whole blood samples of the TTP patients in remission and controls. In initial analysis, 17 genes were found to be ≥ 1.5× differentially expressed in the peripheral blood of TTP patients compared to controls. Among the 7 genes exhibiting the greatest expression difference, 6 are recognized interferon-regulated genes. The relative expression of IFI44 effectively partitioned 13 of the TTP samples (34.2%) into a subset bearing a Type I interferon gene signature similar to that observed in SLE, compared to occurrence of a Type I interferon gene signature observed in 3 of the healthy controls (7.9%) (McNemar c2 p=0.0020). The Type I IFN gene signature was significantly associated with autoantibodies against specific RNA-binding nuclear antigens, defined as the presence of detectable IgG antibodies to one or more of the Ro, La, Sm, or nRNP antigens (Fisher p=0.0086) and correlated with serum Type I interferon activity in the WISH assay (r=.47, p=.0031). However, the Type I interferon gene signature did not associate with tendency of a patient to relapse after a first episode. Conclusion:From these studies, we propose a new subset of acquired, ADAMTS13–deficient TTP patients characterized by elevated serum Type I interferon activity, Type I interferon gene signature and IgG antibodies directed to RNA-binding proteins. Disclosures:Merrill:MedImmune: Consultancy, Honoraria; Genentech: Consultancy, Honoraria.

C1q deposition in the renal allograft: a report of 24 cases

C1q nephropathy is an uncommon glomerular disease characterized by dominant or codominant mesangial staining for C1q in the absence of systemic lupus erythematosus. There are no series in the literature addressing the significance of C1q deposition in the renal allograft. We retrospectively analyzed 24 patients, most of whom were white (83%) and male (63%), with a mean age at transplant of 31 years. None of the patients were diagnosed with C1q nephropathy in the native kidney or had any features of systemic lupus erythematosus. The mean time from transplant to detection of mesangial C1q deposits was 37 months (>12 months in 71% of cases). Half of the patients had a preceding infection. The indication for biopsy was surveillance (63%) or graft dysfunction (37%). At biopsy, 52% had proteinuria (>1g/day in only 17%). The mean creatinine was 1.8 mg per 100 ml. Only 9% developed hematuria and none had hypoalbuminemia. The glomerular pattern on light microscopy was mesangial hypercellularity (46%), focal segmental glomerulosclerosis (21%), or no lesions (33%). All cases showed intense (≥2+) dominant (67%) or codominant (33%) mesangial staining for C1q on immunofluorescence. Mesangial electron-dense deposits were seen in 82% of cases. On follow-up (mean 1 year) of the 10 patients without rejection, most had stable creatinine with no or stable proteinuria, and none lost their graft. We conclude that C1q-dominant mesangial deposition in the renal allograft is a morphological pattern with no apparent clinical significance in the majority of patients. It is usually detected after the first year. The rate of preceding infection and the prevalence of proteinuria seem to be similar to the renal transplant recipients in general. Most cases show mesangial hypercellularity or no glomerular changes on light microscopy.

Traumatic Intracerebral Venous Thrombosis Associated With an Abnormal Golf Swing

To describe the occurrence of cerebral venous thrombosis in a 40-year-old man whose cerebral event was induced by a poor golf swing, to review the literature on possible mechanisms producing venous thrombosis, and to compare this case with the literature. Headache is the most frequent symptom in patients with cerebral venous thrombosis. However, patients presenting with a headache due to cerebral venous thrombosis are uncommon. The known risk factors for thrombosis include both acquired and genetic factors. When the interaction of these two groups occurs, the magnitude of this interaction is thought to produce a dynamic state that can favor thrombosis. Our case report illustrates that moderate levels of anticardiolipin antibodies together with the mild trauma of a golf swing can induce a cerebral venous thrombosis. This case also suggests that although headache is rarely due to cerebral venous thrombosis, it should be excluded by good medical acumen and testing. Minor trauma induced by a poor golf swing was chronologically related to the development of a progressive cerebral venous thrombosis. The patient had none of the risk factors associated with a predisposition to venous thrombosis: hypercoagulable state, concurrent infection, pregnancy/puerperium, collagen vascular disorder, malignancy, migraine, false-positive VDRL, previous deep vein thrombosis, renal disease, factor V Leiden, or a hematological disorder. There was no anatomical abnormality that would predispose the patient to a cerebral venous thrombosis. The only laboratory abnormality was a moderate anticardiolipin antibody level (25 GPL). The patient was placed on warfarin sodium therapy and is currently without clinical sequela from the venous thrombotic event. Under certain circumstances, minor trauma can induce cerebral venous thrombosis. A review of the literature indicates that cerebral venous thrombosis in the presence of anticardiolipin antibodies and in the absence of systemic lupus erythematosus is a rare event. Previously, only major traumatic events have been reported to be associated with cerebral venous thromboses. The chronological development of cerebral venous thrombosis after a faulty golf swing strongly indicates that given a background of moderate levels of anticardiolipin antibodies, even minor trauma can induce a venous thrombotic event.

Ultrastructural Localization of Monoclonal Antiphospholipid Antibody Binding to Rat Brain

Antiphospholipid antibodies (aPL), in the presence or absence of systemic lupus erythematosus, are associated with a number of neurologic complications. However, the role aPL play in pathology is unclear. A thrombotic etiology seems likely for many associated disorders, but not for others. Here we describe aPL-reactive sites in the central nervous system (CNS). Previously, using light microscopy, we showed direct binding of two monoclonal phosphatidylserine-reactive antibodies (aPS) to ependyma and myelin of fixed cat brain. In this study we determined the ultrastructural localization of their binding sites in rat CNS using immunogold electron microscopy techniques. Both monoclonal antibodies reacted strongly with myelin, preferentially with the major dense line formed by the cytoplasmic apposition of the oligodendrocyte plasma membrane. Both monoclonal antibodies also reacted with an antigen that appears associated with the axoneme in cilia of ependymal and choroid plexus epithelium. One monoclonal aPS also showed some reactivity with brain vascular endothelium and reacted slightly with mitochondria, while the other aPS did not react with these structures. While the etiology of aPL-associated neurologic disorders remains unclear, our data suggest possible target sites within the CNS with which aPL can react.

Systemic Lupus Erythematosus Associated with Moyamoya Disease Case Report and Review of the Literature

Moyamoya disease is a rare chronic cerebrovascular occlusive disease diagnosed by angiogram with primary features consisting of bilateral occlusion of the internal carotid arteries and of the vessels forming the circle of Willis, and subsequent development of small collateral vessels. These collateral vessels may rupture, leading to the clinical presentation of transient ischemic attacks and intracerebral hemorrhage. We describe a young Korean woman with known moyamoya disease presenting with her second major vascular event who was also found to have active, undiagnosed systemic lupus erythematosus (SLE). SLE, with or without anti-cardioli-pin, or anti-cardiolipin antibody syndrome, can be associated with "pseudo-moyamoya" (unilateral central nervous system disease). SLE, anti-cardiolipin antibody syndrome, pseudo-moyamoya, or moyamoya disease can all present in young women with intracerebral events, making diagnosis difficult.Our patient presented with fatigue, anemia, leukopenia, and a positive anti-nuclear antibody. Her physicians initially entertained a diagnosis of SLE, but when she developed a thalamic infarct, this diagnosis was abandoned, because a cerebral angiogram revealed a bilateral "cigarette smoke" appearance of blood vessels characteristic of moyamoya disease rather than the similar unilateral findings more typical of pseudo-moyamoya. Subsequently, it became clear that our patient had full-blown SLE and moyamoya disease. The clinician should be aware of the diagnosis of moyamoya because patients with this disease may present with intracerebral events associated with features of autoimmune disease, even in the absence of SLE. The concurrent development of SLE may confound the diagnosis even further.

Manifestations neurologiques associées aux anticorps antiphospholipides. Ou que restetil du neurolupus ?

Antiphospholipid antibody is associated with a clinical syndrome of vascular thrombosis, thrombocytopenia, recurrent fetal loss and livedo reticularis, whether or not a clinical diagnosis of systemic lupus erythematosus (SLE) coexists. Central nervous system involvement in SLE is multifactorial, thrombotic events, antineuronal antibodies, hypertension, infection, side effects of drugs etc. Antiphospholipid antibodies may play a role in focal neurological manifestations in SLE. In the absence of SLE, different neurological symptoms are well associated with antiphospholipid antibodies including stroke, seizures, dementia, migraine, ocular ischemia, chorea, transverse myelopathy, cerebral phlebitis. Other association are more controversal like Guillain Barré syndrome, motor neuron disease, communicating hydrocephalus. In all patients with antiphospholipid antibodies with neurological involvement, cerebral MRI may be performed with an echocardiographic study because a possible association with Libman and Sacks endocarditis, valve dysfunction or cardiac thrombus source of cerebral ischemia.

Antinuclear Antibodies in Pleural Fluid

Systemic lupus erythematosus (SLE) frequently involves the pleura with resultant pleural effusion. Previous studies have reported that detection of antinuclear antibodies (ANA) in pleural fluid using animal tissue as substrate was a sensitive and specific method for distinguishing SLE pleural effusions from other etiologies. The HEp-2 ANA, which uses a human cell line as substrate, is now the preferred ANA test; however, to our knowledge, no studies on pleural fluid using this assay have been reported. To determine its sensitivity and specificity, when measured in pleural fluid, HEp-2 ANA levels were determined in pleural effusion samples associated with a variety of different etiologies, including SLE, malignancy, congestive heart failure, pneumonia, tuberculosis, and a miscellaneous group of diseases. Pleural fluid ANA results were positive in 14 of 82 samples. Six of the eight (75 percent) pleural fluid samples collected from patients with SLE were ANA positive, and all but one had high titers (> 1:160) with a homogenous staining pattern. The remaining two patients with SLE with negative pleural fluid ANA had recurrent pulmonary emboli and congestive heart failure, rather than lupus pleuritis. Eight of 74 patients (10.8 percent) without clinical evidence of SLE had a positive pleural fluid ANA, with the majority having a speckled pattern. High titers were noted in three. These results indicate that a negative or low titer ANA and a speckled staining pattern in pleural fluid from a patient suspected of lupus pleuritis suggest an alternative diagnosis. High pleural fluid titers (up to 1:640) were seen occasionally in patients with inflammatory pleural effusions in the absence of SLE.

Comparison of the primary and secondary antiphospholipid syndrome: A European multicenter study of 114 patients

purpose: To determine whether the features of the antiphospholipid syndrome (APS) are in any way influenced by the presence or absence of systemic lupus erythematosus (SLE). We followed up patients with ‘primary’ APS (PAPS) and APS secondary to SLE (APS plus SLE) with the objective of comparing laboratory and clinical events and of determining whether patients with PAPS would have evolution to SLE. patients and methods: A total of 114 patients from 3 European referral centers were included in this study. Fifty-six had APS plus SLE and 58 had PAPS. Laboratory and clinical data were collected during an average 2-year period. results: Patients with PAPS and patients with APS plus SLE had similar clinical and laboratory profiles, with the exceptions of autoimmune hemolytic anemia, endocardial valve disease, neutropenia, and low C4 levels, all of which occurred more frequently in patients with APS plus SLE (p values: <0.05, <0.005, <0.01, and <0.001, respectively). On follow-up, 10 thrombotic episodes occurred in 10 patients, 8 of whom were receiving anticoagulant therapy. No patient with PAPS had either anti-DNA or anti-extractable nuclear antigen antibodies, and these patients had a significantly lower prevalence of antinuclear antibodies (41%) than patients with APS plus SLE (89%). conclusions: Patients with APS plus SLE and PAPS have similar clinical profiles, although heart valve disease, hemolytic anemia, low C4 levels, and neutropenia seem to be more common in patients with APS plus SLE. Patients with APS may develop further thrombotic events despite anticoagulation therapy.

Retinal migraine, chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome

We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome.

Cerebrovascular and neurologic disease associated with antiphospholipid antibodies

Lupus anticoagulants and anticardiolipin antibodies are antiphospholipid antibodies (APLAb) with related antigenic specificities and are newly recognized markers for an increased risk of thrombosis. We studied 48 patients who presented with cerebral or visual dysfunction associated with APLAb to help clarify the diagnostic, clinical, laboratory, radiologic, and pathologic features in these patients. Most patients presented with transient cerebral ischemia or cerebral infarction. Recurrent and stereotypic events were frequent. Visual disturbances resulted from amaurosis fugax, retinal arterial or venous occlusion, occipital ischemia, diplopia, and migraine-like disturbances. Three patients presented with severe atypical classic migraine. Recurrent infarcts of brain and eye were significantly associated with the presence of cigarette smoking, hyperlipidemia, and a positive antinuclear antibody. During 44.4 patient-years of prospective follow-up, the combined stroke and systemic thrombotic event rate was 0.27 events per patient-year and was 0.54 events per patient-year if TIA and death were included. Forty (83%) of the patients did not have systemic lupus erythematosus (SLE). Thrombocytopenia was present in 15 (31%) and a false-positive VDRL in 11 (23%) of the patients. Cerebral angiography was normal or revealed large-vessel occlusion or stenosis without changes suggestive of vasculitis. Patients with only transient dysfunction generally had normal radiologic studies, including angiography. Organs and arterial vessels studied pathologically revealed thrombotic occlusive disease without vasculitis. APLAb are strongly associated with an immune-mediated thrombotic tendency, generally in the absence of SLE. Other stroke risk factors may add to the risk of recurrent ischemic events in patients with APLAb.