Systemic lupus erythematosus with a protein-losing enteropathy

Anasarca with pronounced hypoalbuminemia developed in a young woman 15 months after the onset of a mild, arthralgic type of systemic lupus erythematosus (SLE) without evidence of active nephritis. Investigation indicated a gastrointestinal rather than a renal site for protein loss. A full clinical remission was achieved with low-dose corticosteroid therapy.     

Human substance P receptor expressed in Chinese hamster ovary cells directly activates G(alpha q/11), G(alpha s), G(alpha o)

BACKGROUND: Abdominal pain is a common finding in patients with systemic lupus erythematosus (SLE), occurring in as many as half of all SLE patients in the course of their disease. The rheumatology and gastroenterology literature emphasizes etiologies of abdominal pain in patients with SLE such as peritonitis from polyserositis, dyspepsia from reflux, nausea and vomiting from bowel edema, ascites, mesenteric ischemia, pancreatitis, pneumatosis intestinalis from necrotizing enterocolitis, and hepatobiliary abnormalities. But in clinical practice, caring for SLE patients in a community teaching hospital, these seem to be rare entities. PATIENTS AND METHODS: A chart review study was performed of all patients with SLE with the diagnosis of abdominal pain admitted to a community teaching hospital between 1980 and 1995. RESULTS: Of 13 patients who presented with abdominal pain, 9 required surgical intervention for cholecystitis, perforated ulcer, colonic perforation, diverticulitis, and adhesions. There were no negative laparotomies for polyserositis or bowel edema, or cases of mesenteric infarction or ascites. CONCLUSION: Despite some unusual diagnostic possibilities in abdominal pain in SLE such as polyserositis and mesenteric infarction, and despite the superimposed problems of steroid therapy in most of the patients in this study, the majority of lupus patients with abdominal pain presenting at community hospitals have relatively conventional illnesses.     

Systemic lupus erythematosus with membranous glomerulonephritis and transverse myelitis associated with anabolic steroid use

This report describes a 29-year-old bodybuilder taking anabolic steroids who presented with urinary retention, arthralgias, and peripheral edema, subsequently developed acute lower-extremity paralysis, and was diagnosed as having transverse myelitis and membranous glomerulonephritis secondary to systemic lupus erythematosus (SLE). The association of anabolic steroid use and hyperprolactinemia, and their possible link to the development of SLE, are reviewed.     

Protection of side-branches in coronary lesions with a new stent design

Although the association between transverse myelitis (TM) and systemic lupus erythematosus (SLE) has been reported previously, it remains a rare clinical condition. Our experience treating three women with lupus TM within a few months is presented. In each patient, spinal cord dysfunction was accompanied by laboratory or clinical evidence of SLE. Further neurologic manifestations, such as optic neuritis, developed in all patients, suggesting other diagnoses, including multiple sclerosis (MS), Devic's syndrome, and lupoid sclerosis. The outcomes for these three women were severe disability, death, and moderate disability, respectively. The severity of outcome did not seem to correlate with the timing or intensity of treatment. Physiatrists should be aware of the potential for neurologic progression in lupus TM, because patients with this condition invariably require rehabilitation.     

Down syndrome associated with systemic lupus erythematosus: a mere coincidence or a significant association?

An 8-year-old male, who had Down syndrome associated with systemic lupus erythematosus (SLE), is described. He also had a partial complement 4 deficiency. This case is a reminder that the physician should be aware of the possibility of an immune defect in a male presenting with SLE at a young age. The question of whether the association of Down syndrome with SLE is coincidental or whether there is a predilection for autoimmune disorders in Down syndrome is discussed.     

Epidemiology and socioeconomic impact of skin disease in lupus erythematosus

The prevalence rates of systemic lupus erythematosus (SLE) may vary within 17-48/100,000 population worldwide. Although population-based epidemiological studies are still missing, the cutaneous variants of lupus erythematosus (LE) are 2-3 times more frequent than SLE itself. The most common age of onset is 20-40 y. Overall, cutaneous LE is regarded as a variant with less severe course and better prognosis. However, CDLE and SCLE last for many years and may lead, like SLE, to severe disability for work and limited life quality; also, a small proportion of patients with cutaneous LE develops SLE during the course of their disease. This implies considerable amount of medical management and costs for the community. Early recognition of cutaneous LE patients at risk to develop SLE and preventive measures against disease triggering factors are important tasks for physicians attending with cutaneous LE patients. It seems that signs of nephropathy, elevated ANA-titers and arthralgias may serve as prognostic predictors for transition into SLE. Characteristic features of cutaneous LE are photosensitivity and female predominance. UV light is a major environmental triggering factor in cutaneous LE. Skin lesions may be induced or preexistent lesions may exacerbate due to UV light in up to 80-90% of all patients. Therefore, socioeconomic counseling of the young patients, for example choice of occupation and sun protection, are essentials in compliant patients. Also, since females are 3-6 times more frequently affected than males, the possibility of hormonal influences including pregnancy and estrogen-containing drugs should be discussed. Risk considerations for females wishing to become pregnant are required, and avoidance of estrogen-containing contraceptives should be recommended.     

Genetic analysis of interleukin-10 promoter region in patients with systemic lupus erythematosus in Taiwan

Overproduction of interleukin-10 (IL-10) may play an important role in the development of systemic lupus erythematosus (SLE) or lupus nephritis. There is also a polymorphic dinucleotide repeat in the human IL-10 promoter region (IL-10PR). Our aim was to study whether or not the IL-10PR alleles contributed to the susceptibility to SLE or lupus nephritis. One hundred SLE patients and 103 healthy controls were studied for IL-10PR by PCR and electrophoretic analysis. The distribution of IL-10PR alleles, genotypes and the sum of both alleles (SBA) from different groups or subgroups were analyzed. SLE patients showed no difference in the distribution of IL-10PR alleles, genotypes and SBA, as compared to healthy controls. Lupus nephritis patients (N = 49) also showed no difference in IL-10PR alleles, genotypes and SBA, as compared to SLE patients without nephritis (N = 51). Of 49 lupus nephritis patients, ten developed end-stage renal disease (ESRD) and four of them were found to suffer from rapid progressive renal failure (RPRF). Patients with RPRF presented much smaller SBA than other ESRD patients (p = 0.005). Lupus nephritis patients carrying small SBA (< 18) suffered from a higher prevalence of RPRF than lupus nephritis patients without small SBA (50% V.S. 0%, p < 0.001, relative risk 82). Our data provide the first evidence of a strong association between IL-10PR and severe progression of lupus nephritis in human patients. In the future, a prospective genetic analysis of IL-10PR for patients with lupus nephritis is recommended. It might be helpful for physicians to identify the lupus nephritis subgroup with a high risk of developing RPRF early, because this might lead to a better therapy and prognosis for these patients.     

Familial clustering of end-stage renal disease in blacks with lupus nephritis

The factors that determine a patient's susceptibility to specific target organ involvement in systemic lupus erythematosus (SLE) remain unknown. Lupus nephritis can be a particularly devastating complication, with an increased mortality and the risk of progressive renal damage resulting in end-stage renal disease (ESRD). This analysis was performed to determine whether renal disease aggregated in select families or was a sporadic complication in patients with SLE. We compared the family history of ESRD in 50 patients with SLE complicated by lupus nephritis with 37 controls who had SLE but lacked nephritis after a mean follow-up duration of more than 11 years. The frequency of relatives with ESRD in the lupus nephritis cases was compared with that in controls using Fisher's exact test (significance at P < or = 0.05). Fifty percent (25) of the 50 lupus nephritis patients were black and 50% (25) white, in contrast to 35% (13) and 65% (24) of the 37 lupus non-nephropathy controls, respectively. A first-, second-, or third-degree relative with ESRD was present in 16% (eight) of the 50 lupus nephritis cases and in 0% of the 37 SLE non-nephropathy controls (P = 0.019, Fisher's exact test, two-tail). Twenty-eight percent (seven) of the 25 black patients with lupus nephritis had relatives with ESRD compared with 0% of the 13 black lupus non-nephritis controls (P = 0.07). Only one of the eight relatives with ESRD had SLE or a collagen vascular disease. Lupus nephritis patients and the non-nephritis controls had similar ages (mean +/- SD: 38.5 +/- 10.0 years v 46.6 +/- 11.8 years; P = 0.28), family sizes (6.27 +/- 2.61 first-degree relatives v 6.35 +/- 3.25 first-degree relatives; P = 0.16), and duration of SLE (9.26 +/- 5.94 years v 11.35 +/- 6.43 years; P = 0.60). Familial clustering of ESRD was observed in black patients with SLE who had nephritis. This was unlikely to be related to differences in patient age, family size, or duration of SLE. This data, coupled with the known familial aggregation of ESRD in blacks with hypertensive and diabetic ESRD, supports the contention that genetic factors contribute to the familial clustering. The presence of relatives with etiologies of ESRD other than SLE suggests that there is an inherited susceptibility to progressive renal failure, independent of the etiology of ESRD.     

Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus

OBJECTIVE: To compare the role of antibodies against the ribosomal P protein (anti-P) with that of antibodies against neuronal cells (anti-N) in the pathogenesis of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS: Sera from 87 SLE patients (27 with non-CNS SLE, 34 with lupus psychosis, and 26 with nonpsychotic CNS lupus) and from 20 control patients with neurologic manifestations without SLE and cerebrospinal fluid (CSF) from 41 patients with CNS lupus and from the 20 control patients were assayed for IgG anti-P and anti-N by an enzyme-linked immunosorbent assay (ELISA) using ribosomal P synthetic peptides and by a cell ELISA using paraformaldehyde-fixed SK-N-MC neuroblastoma cell lines, respectively. RESULTS: Serum anti-P levels were significantly elevated in patients with lupus psychosis compared with those with non-CNS SLE or those with nonpsychotic CNS lupus, whereas there were no significant differences in serum anti-N levels among these 3 groups. In contrast, CSF anti-N levels were significantly elevated in patients with lupus psychosis compared with those with nonpsychotic CNS lupus and compared with non-SLE controls, whereas CSF anti-P were not detected in most of the patients. CONCLUSION: The results indicate that anti-P in the systemic circulation and anti-N in the CSF are involved in the development of lupus psychosis.     

Highly cationic anti-DNA antibodies in patients with lupus nephritis analyzed by two-dimensional electrophoresis and immunoblotting

The relationship between chemical properties of anti-DNA antibodies (Abs) and lupus nephritis was investigated. The anti-DNA Abs in sera from systemic lupus erythematosus (SLE) patients were separated by two-dimensional electrophoresis (2-DE) and immunoblotting with goat anti-human IgG Abs. Highly cationic anti-DNA Abs were detected in deoxyribonuclease I (DNase I)-treated sera from patients with lupus nephritis (in 8 of 9 cases) but not in the sera from SLE patients without nephritis (in 0 of 9 cases), normal subjects, or patients with other renal diseases (in 0 of 7 cases). The mean titers of anti-dsDNA Abs in patients with lupus nephritis were not significantly different from those in SLE patients without nephritis. The highly cationic anti-DNA Abs in the sera disappeared after incubation with heparin-Sepharose. These results suggest that highly cationic anti-DNA Abs are specific for lupus nephritis and may be involved in development of lupus nephritis via the binding to glycosaminoglycans on the endothelial cell surface.     

Risk factors for avascular bone necrosis in systemic lupus erythematosus

OBJECTIVE: To study the predictive factors for avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE). METHOD: The records of 38 SLE patients who developed clinically apparent AVN during the course of their disease were reviewed. Information on clinical presentation, corticosteroid usage and autoantibody profiles was obtained, and comparison was made between these patients and 143 consecutive control SLE patients who did not have AVN. RESULTS: The point prevalence of AVN in our SLE population was 12%. Patients with AVN, when compared with controls, had a significantly higher incidence of neurological disease (39% vs 14%; P < 0.001) and Cushingoid body habitus after steroid treatment (79% vs 53%; P = 0.004). The highest cumulative prednisolone dose in 1 and 4 months was significantly higher in the AVN group than the controls (1.8 vs 1.1 and 4.5 vs 2.8 g, respectively; P < 0.01 in both) and showed a linear trend with the incidence of AVN (chi2 test for trend, P < 0.01 in both). Lupus anticoagulant was associated with AVN (P = 0.02, odds ratio 2.88 [1.14-7.28]). Logistic regression analysis revealed that the highest cumulative prednisolone dose administered in 4 months, the maximum and mean daily prednisolone dosage, and the lupus anticoagulant were independent risk factors for AVN. CONCLUSIONS: Corticosteroid remains the major predisposing factor for AVN in SLE. Patients who require an initial high-dose steroid for disease control are at risk of AVN, especially if they are positive for the lupus anticoagulant or develop Cushingoid habitus after steroid treatment. High-risk patients should be closely monitored so that early AVN can be diagnosed by sensitive techniques such as magnetic resonance imaging and radioisotope bone scanning.     

Association of an insertion polymorphism of angiotensin-converting enzyme gene with the activity of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) shows various clinical manifestations, which are characterized by inflammation in many different organ systems. The cause of SLE is still unclear; however, the immunological abnormalities are considered to be responsible for the pathogenesis of SLE. As angiotensin I-converting enzyme (ACE) has been reported to be associated with various immunological phenomena, we investigated the correlation between insertion (I)/deletion (D) polymorphism of the ACE gene and the disease activity of SLE. Ninety-three patients with newly diagnosed SLE were enrolled in this study. ACE genotype was determined by the polymerase chain reaction (PCR). We measured serum levels of anti-double-stranded (ds) DNA antibody (Ab) and serum levels of total complements (CH50) as the parameter for lupus activity. Moreover, we evaluated the clinical disease activity by calculating SLE disease activity index (SLEDAI). Individuals with II genotype showed a significant increase in SLE activity. Patients with the ACE II genotype showed a higher serum level of anti-dsDNA Ab (14.3 IU/ml (5.475, 74.6, median (25th centile, 75th centile)) than those with the DD genotype (4.65IU/ml (4.05, 6.8)) (P<0.01). Moreover, patients with the 11 genotype also showed lower levels of serum CH50 than those with the DD genotype (P < 0.01). Patients with the II1 or DI genotype had significantly higher SLEDAI score than those with the DD genotype (P < 0.01). These results suggest that the ACE genotype could be associated with the disease activity of SLE. ACE insertion polymorphism might be used as one of predictive factors for the activity of lupus.     

The specificity of behavioral fever in the cricket Acheta domesticus

A 38-year-old male was admitted to our hospital because of high grade fever, erythema of face and extremities and oral ulcer. The laboratory examination showed leukopenia, high titer (320 dil.) of antinuclear antibody, a positive reaction of anti-Sm antibody. Especially histopathology of hand erythema showed hydrophilic degeneration consist with chilblain lupus. Because his symptoms were consistent with the criteria of American College of Rheumatology (1982), he was diagnosed as systemic lupus erythematosus (SLE). After administration of 60 mg prednisolone daily, the symptoms gradually improved. Any recrudescence of serological abnormalities or clinical symptoms was not observed until now, although chilblain lupus still persisted. Originally SLE is frequent in young female and often attended with renal disease, central nerve disease and serositis. We reported a case of middle-aged male who developed SLE with chilblain lupus which was rare skin lesion of SLE without severe organic lesion and discussed the relation among chilblain lupus, discoid lupus erythematosus (DLE) and SLE.     

Systemic lupus erythematosus: perinatal and neonatal implications

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect almost all organ systems in the body. It is most common in women of childbearing age and may cause multiple peripartum complications. This article reviews the pathophysiology of SLE and the effects of SLE on fertility and pregnancy. The complexities of managing a pregnant patient with SLE are reviewed, and the importance of interdisciplinary collaboration discussed, as well as the effects of SLE on the fetus and a review of neonatal lupus erythematosus. Finally, a case report of a pregnant patient with SLE with challenging clinical management issues is presented.     

Appraisal and implications of predictive testing for insulin-dependent diabetes mellitus

A patient with systemic lupus erythematosus (SLE) developed reactive hemophagocytosis. This case did not show any underlying diseases such as infection or malignancy other than SLE itself. The mechanisms inducing hemophagocytosis in SLE seem to be heterogeneous and remain to be elucidated. Although an immune complex-mediated mechanism in cases with acute lupus hemophagocytic syndrome has been proposed, we suggest the possible involvement of IL-1beta as the pathogenesis of our case.     

Depressive symptoms in patients with systemic lupus erythematosus: association with central nervous system lupus and Sj?gren's syndrome

OBJECTIVE: To determine if patients with systemic lupus erythematosus (SLE) with depressive symptoms differ in regard to organ involvement and serological activity from other patients with SLE. METHODS: Disease manifestations were compared between 71 patients with SLE with a history of depressive symptoms and 278 patients without a history of depressive symptoms by univariate analysis and multiple logistic regression. RESULTS: Both univariate and logistic regression analysis revealed an association of depressive symptoms with neuropsychiatric lupus and secondary Sj?gren's syndrome (SS). Patients with neuropsychiatric lupus had an adjusted odds ratio of 3.43 (95% CI 2.55, 4.63; p = 0.00005), and patients with secondary SS had an adjusted odds ratio of 2.97 (95% CI 2.08, 4.25; p = 0.0006) for depressive symptoms. No other organ involvement or serological abnormality was associated with depressed mood. CONCLUSION: These discrete associations of depressive symptoms with neuropsychiatric lupus and secondary SS suggest that depression does not occur purely as a response to social stresses, and may be a manifestation of autoimmune disease in some patients.     

Immunology in medical practice. II. Antiphospholipid antibodies in pregnancy

Antibodies against phospholipids are a risk factor for thrombotic disorders, but also for foetal death, pre-eclampsia, foetal distress and dysmaturity. This group of antibodies (aPLab) includes lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL). These antibodies are encountered in patients with systemic lupus erythematosus (SLE), but also in patients with lupus-like disease and in women with (a history of) symptoms compatible with the antiphospholipid syndrome. Screening for a aPLab is advisable in these patients when they want to conceive and in women with recurrent foetal death after the 12th week of pregnancy. It is not clear if the antibodies exert a direct noxious action or are an accompanying phenomenon. Secondary prevention is possible with acetylsalicylic acid (80 mg/day), if desired in combination with subcutaneous heparin (5000-12,000 units twice daily). The thrombosis prophylaxis should be continued for 6 weeks after delivery.     

Two cases of systemic lupus erythematosus associated with fatty liver and Basedow's disease

We present two cases of systemic lupus erythematosus (SLE) associated with both Basedow's disease and fatty liver. The first case is a 46-year-old Japanese female who was admitted because of high fever and general fatigue. She had been diagnosed as having Basedow's disease and treated with thiamazole for over 4 years. Since thiamazole-induced lupus was unlikely because of high titer anti-nuclear antibody and anti-DNA antibody and low levels of complements, a diagnosis of SLE was made. The upper abdominal ultrasound study and the specimen obtained by liver biopsy performed before initiating steroid therapy demonstrated marked fatty liver. SLE itself is considered as an etiology of fatty liver in this case. The second case was a 25-year-old Japanese female with SLE. She had been treated with prednisolone for 13 years and was complicated with Basedow's disease 10 years later. Fatty liver was also demonstrated in this patient on ultrasonography, and was thought to be resulted from long-term steroid hormone administration.     

Lupus cardiomyopathy: cardiac mechanics, hemodynamics, and coronary blood flow in uncomplicated systemic lupus erythematosus

Right and left heart pressures, left ventricular volumes, indices of contractility, myocardial wall stiffness, and coronary blood flow were determined in five young women with systemic lupus erythematosus (SLE) during diagnostic right and left heart catheterization. Examinations revealed (1) increases of right and left ventricular enddiastolic pressures; (2) decreases of cardiac output, stroke volume, ejection fraction, contractility indices, diastolic left ventricular volume inflow; (3) decreases of pharmacologically induced coronary vasodilation in SLE. The results demonstrate impaired pump function, reduced contractility, increased myocardial wall stiffness, and decreased coronary vascular reserve in SLE. It is concluded that lupus cardiomyopathy associated with an impairment of left ventricular function may be apparent in young women with SLE who have no clinical signs of cardiac dysfunction.     

Arterial disease in lupus and secondary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies but not with antibodies against oxidized low-density lipoprotein

The prevalence and clinical significance of antibodies against beta2-glycoprotein I (anti-beta2GPI) and antibodies against oxidized low-density lipoprotein (anti-ox-LDL) were evaluated as potential indicators of arterial disease in patients with systemic lupus erythematosus (SLE) and SLE with secondary antiphospholipid syndrome (APS). IgG anti-beta2GPI and IgG anti-ox-LDL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 118 patients with SLE, including 40 with secondary APS. IgG anti-beta2GPI were positive in 17% (20/118) of SLE patients. The presence and titres of IgG anti-beta2GPI were strongly associated with a history of arterial thrombosis. Haemolytic anaemia was also significantly associated with the presence of IgG anti-beta2GPI. The prevalence of IgG anti-ox-LDL was 53% (63/118), but there was no association with arterial thrombosis. No correlation between the values of anti-ox-LDL and those of anti-beta2GPI was found. These results suggest that IgG anti-beta2GPI could be a marker for arterial thrombosis in SLE patients, while IgG anti-ox-LDL were not associated with arterial disease in this group of lupus patients.