The goal of the present study was to estimate the risk ratio of herpes zoster among systemic lupus erythematosus patients after disease onset compared with a cohort of patients without systemic lupus erythematosus over a three-year period.
A nationwide population-based cohort study using the National Health Insurance Research Database identified 10,337 new cases of systemic lupus erythematosus as the study cohort. In addition, 62,022 patients without systemic lupus erythematosus, who were matched for age, gender, and date of systemic lupus erythematosus diagnosis, were used as the comparison cohort. These cohorts were followed-up for three years. A Cox proportional hazard regression was performed to estimate the risk ratio of herpes zoster, with adjustments for age, gender, level of insurance, urbanization level, geographic region, comorbid medical conditions, average daily dosage of corticosteroids, and the use of immune-modulation agents.
Compared to patients without systemic lupus erythematosus, the crude risk ratio and adjusted risk ratio of herpes zoster among systemic lupus erythematosus patients were 7.37 (95% confidence interval 6.75-8.04) and 2.45 (95% confidence interval 1.77-3.40), respectively. Stratified by gender, the adjusted risk ratio of herpes zoster was 2.10 (95% confidence interval 1.45-2.99) in women and 7.51 (95% confidence interval 2.89-19.52) in men. Stratified by age, the adjusted risk ratio peaked in systemic lupus erythematosus patients who were aged 18 to 24 years (risk ratio 8.78, 95% confidence interval 3.08-24.97).
Based on nationwide population-based data, there is an increased risk of herpes zoster in systemic lupus erythematosus patients compared with non-systemic lupus erythematosus patients, particularly among males and patients aged 18 to 24 years. Further research on the associated risk factors for herpes zoster in systemic lupus erythematosus patients is needed.
Herpes Zoster; Risk; Systemic Lupus Erythematosus; Population-Based Cohort Study; Database
Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial
etiology. Although clinical manifestations are varied, the skin is an important
target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17
new criteria for the diagnosis of the disease, according to the Systemic Lupus
International Collaborating Clinics. The cutaneous manifestations of lupus are
pleomorphic. Depending on their clinical characteristics, they can be classified into
Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic
Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus.
Treatment is based on preventive measures, reversal of inflammation, prevention of
damage to target organs and relief of adverse events due to pharmacological therapy.
The most commonly used treatment options are topical, systemic and surgical
treatment, as well as phototherapy. The correct handling of the cases depends on a
careful evaluation of the morphology of the lesions and the patient's general status,
always taking into consideration not only the benefits but also the side effects of
each therapeutic proposal.
Lupus erythematosus, cutaneous; Phototherapy; Skin; Smoking
The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice.
Cancer and infections are leading causes of mortality in systemic lupus erythematosus (SLE) after diseases of the circulatory system, and therefore preventing these complications is important. In this study, we examined two categories of preventive services in SLE: cancer surveillance (cervical, breast, and colon) and immunizations (influenza and pneumococcal). We compared the receipt of these services in SLE to the general population, and identified subgroups of patients who were less likely to receive these services.
We compared preventive services reported by insured women with SLE enrolled in the University of California, San Francisco Lupus Outcomes Study (n = 685) to two representative samples derived from a statewide health interview survey, a general population sample (n = 18,013) and a sample with non-rheumatic chronic conditions (n = 4,515). In addition, using data from the cohort in both men and women (n = 742), we applied multivariate regression analyses to determine whether characteristics of individuals (for example, sociodemographic and disease factors), health systems (for example, number of visits, involvement of generalists or rheumatologists in care, type of health insurance) or neighborhoods (neighborhood poverty) influenced the receipt of services.
The receipt of preventive care in SLE was similar to both comparison samples. For cancer surveillance, 70% of eligible respondents reported receipt of cervical cancer screening and mammography, and 62% reported colon cancer screening. For immunizations, 59% of eligible respondents reported influenza immunization, and 60% reported pneumococcal immunization. In multivariate regression analyses, several factors were associated with a lower likelihood of receiving preventive services, including younger age and lower educational attainment. We did not observe any effects by neighborhood poverty. A higher number of physician visits and involvement of generalist providers in care was associated with a higher likelihood of receiving most services.
Although receipt of cancer screening procedures and immunizations in our cohort was comparable to the general population, we observed significant variability by sociodemographic factors such as age and educational attainment. Further research is needed to identify the physician, patient or health system factors contributing to this observed variation in order to develop effective quality improvement interventions.
To evaluate treatment with the peptide-based agent, Lupuzor, in a double-blind, randomised, placebo-controlled study of patients with systemic lupus erythematosus.
Patients who met ≥4 of the American College of Rheumatology criteria, had a score of ≥6 on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and did not have an A score on the British Isles Lupus Assessment Group (BILAG)-2004 scale were eligible. 149 intention-to-treat (ITT) patients were randomly assigned to receive Lupuzor (200 μg) subcutaneously every 4 weeks (n=49; group 1) or every 2 weeks (n=51; group 2) or placebo (n=49; group 3) in addition to standard of care (SOC). A target population (136 ITT patients) consisting of patients having a clinical SLEDAI score ≥6 at week 0 was considered. The clinical SLEDAI score is the SLEDAI-2K score obtained by omitting low complement and increased DNA binding components.
In the ITT overall population, 53.1% in group 1 (p=0.048), 45.1% in group 2 (p=0.18) and 36.2% in the placebo group achieved an SLE Responder Index (SRI) response at week 12. In the target population, the results were more impressive: 61.9% in group 1 (p=0.016), 48.0% in group 2 (p=0.18) and 38.6% in the placebo group achieved an SRI response at week 12. An interim analysis including 114 patients from the target population demonstrated an even better efficacy (according to SLEDAI score) in group 1 compared with placebo (67.6% vs 41.5% (p<0.025) at week 12 and 84.2% vs 45.8% (p<0.025) at week 24). The most common adverse event was a mild injection-site erythema.
Lupuzor/200 µg given three times at 4-week intervals during 12 weeks in addition to SOC is efficacious and generally well tolerated.
Systemic Lupus Erythematosus; Treatment; T Cells
BACKGROUND: The association of allergic diseases, drug adverse reactions and elevated total immunoglobulin E (IgE) concentration in systemic lupus erythematosus patients remains controversial. The aim of the study was to investigate the prevalence of those features in active and inactive systemic lupus erythematosus patients, and in the control group as well. METHODS: Total IgE concentration was evaluated by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSIONS: The results of our study revealed that concomitant allergic diseases were not more frequent in systemic lupus erythematosus patients than in the general population. Total IgE concentration was significantly higher during the active stage of the disease. Drug reactions were very frequent but not connected with IgE elevation. Our results indicate that IgE may play a role in lupus pathogenesis, especially in the active phase of the disease.
Patients with systemic lupus erythematosus may develop premature atherosclerosis, notably coronary artery disease. A group of 10 patients with peripheral vascular disease presenting with intermittent claudication or gangrene were studied from a group of 563 patients followed prospectively at the Wellesley Hospital Lupus Clinic. These 10 patients were compared with the next lupus clinic patient matched for age and sex, with respect to demographic characteristics and risk factors. The patients and controls did not differ significantly in lupus activity criteria count, partial thromboplastin time, the number with antibody to cardiolipin, number receiving steroids or mean steroid dose, family history of atherosclerosis, hyperlipidaemia, smoking, hypertension or use of oral contraceptives. The risk factors for developing peripheral vascular disease were a longer duration of systemic lupus erythematosus and a longer duration of use of steroids. Eight of the 10 patients had coexistent coronary artery disease or transient ischaemic attack.
To study ethnic differences in mortality from systemic lupus erythematosus (lupus) in two large, population‐based datasets.
We analysed the national death data (1979–98) from the National Center for Health Statistics (Hyattsville, Maryland, USA) and hospitalisation data (1993–2002) from the Nationwide Inpatient Sample (NIS), the largest hospitalisation database in the US.
The overall, unadjusted, lupus mortality in the National Center for Health Statistics data was 4.6 per million, whereas the proportion of in‐hospital mortality from the NIS was 2.9%. African‐Americans had disproportionately higher mortality risk than Caucasians (all‐cause mortality relative risk adjusted for age = 1.24 (women), 1.36 (men); lupus mortality relative risk = 3.91 (women), 2.40 (men)). Excess risk was found among in‐hospital deaths (odds ratio adjusted for age = 1.4 (women), 1.3 (men)). Lupus death rates increased overall from 1979 to 98 (p<0.001). The proportional increase was greatest among African‐Americans. Among Caucasian men, death rates declined significantly (p<0.001), but rates did not change substantially for African‐American men. The African‐American:Caucasian mortality ratio rose with time among men, but there was little change among women. In analyses of the NIS data adjusted for age, the in‐hospital mortality risk decreased with time among Caucasian women (p<0.001).
African‐Americans with lupus have 2–3‐fold higher lupus mortality risk than Caucasians. The magnitude of the risk disparity is disproportionately higher than the disparity in all‐cause mortality. A lupus‐specific biological factor, as opposed to socioeconomic and access‐to‐care factors, may be responsible for this phenomenon.
OBJECTIVE--To examine the relations among tissue plasminogen activator antigen, plasminogen activator inhibitor, the lupus anticoagulant, and anticardiolipin antibodies in patients with systemic lupus erythematosus. DESIGN--Prospective study of blood samples (a) from selected patients with systemic lupus erythematosus whose disease was and was not complicated by a history of thrombosis or recurrent abortions, or both, and (b) from a series of healthy controls with a similar age and sex distribution. SETTING--University based medical clinic. SUBJECTS--23 Patients with definite systemic lupus erythematosus (American Rheumatism Association criteria), of whom 11 (eight women) aged 26-51 had a history of thrombosis or recurrent abortions, or both, and 12 (10 women) aged 23-53 had no such history. 15 Healthy subjects (10 women) aged 25-58 served as controls. MAIN OUTCOME MEASURES--Tissue plasminogen activator concentrations, plasminogen activator inhibitor activities, detection of the lupus anticoagulant, and values of anticardiolipin antibodies in the two groups of patients and in the patients with a history of thrombosis or abortions compared with controls. Other measurements included concentrations of proteins that are known to change during the acute phase of systemic lupus erythematosus--namely, fibrinogen, C3 and C4, and C reactive protein. RESULTS--Patients with a history of thrombosis or abortions, or both, had significantly higher values of tissue plasminogen activator and plasminogen activator inhibitor than patients with no such history. A significant correlation between tissue plasminogen activator and plasminogen activator inhibitor (r = 0.80) was found only in the patients with a history of complications of their disease. The lupus anticoagulant was detected in six of the 11 patients with a history of thrombosis or abortions when tested by measuring the activated partial thromboplastin time but was found in all 11 patients when tested by measuring the diluted activated partial thromboplastin time. Nine of these 11 patients had raised values of anticardiolipin antibodies. The findings showed no relation to the activity of the disease. CONCLUSIONS--A significant correlation between tissue plasminogen activator concentrations and plasminogen activator inhibitor activities was found only in patients whose systemic lupus erythematosus was complicated by a history of thrombosis or recurrent abortions. The findings show that these patients have raised plasminogen activator inhibitor activities, and the frequent association between these raised activities and the presence of the lupus anticoagulant suggests that the two may be linked.
The diagnostic significance of anti-double-stranded deoxyribonucleic acid (anti-dsDNA) determination was evaluated in a prospective manner from 1974 to 1982 in a group of 441 patients without systemic lupus erythematosus whose sera were found to contain antibodies to dsDNA on routine screening (Farr assay). Within one year 69% (304) of these patients fulfilled the preliminary American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). Eighty-two of the remaining 137 patients were followed up for several years. At the end of the study 52% of these patients had also developed systemic lupus erythematosus. Patients who developed systemic lupus erythematosus were characterised by the occurrence of relatively high avidity anti-dsDNA in the circulation compared with patients who did not develop systemic lupus erythematosus. It can be concluded that about 85% of patients without systemic lupus erythematosus with anti-dsDNA in the circulation will develop SLE within a few years. Taking into account the relative avidity of anti-dsDNA, as determined by calculation of Farr/polyethylene glycol (PEG) ratios, we conclude that patients with relatively high avidity anti-dsDNA are more prone to develop systemic lupus erythematosus than patients with relatively low avidity anti-dsDNA.
Human immunodeficiency virus (HIV)-associated lupus-like glomerulonephritis (GN) is a chronic immune complex disease occurring in HIV-infected patients. Although the light, immunofluorescence, and electron microscopy findings indicate features of lupus nephritis, no evidence of systemic lupus erythematosus (SLE) is observed in the affected patients. We present the case of a 45-year-old Caucasian woman with HIV infection who was admitted to the hospital with a nephrotic syndrome 10 years after the HIV diagnosis. A renal biopsy revealed HIV-associated lupus-like GN and necrotizing arteritis affecting two interlobular arteries. Necrotizing arteritis is a type of renal vasculopathy associated with SLE, but has not been reported previously in HIV-associated lupus-like GN. In this case, necrotizing arteritis was found to be a histological feature common to both HIV-associated lupus-like GN and SLE. This histological finding reinforces the resemblance between HIV-associated lupus-like GN and nephritis caused by lupus.
HIV; glomerulonephritis; necrotizing arteritis
Blood rheology is one of the determinants of perfusion and might therefore have an impact on the thromboembolic complications of lupus erythematosus. This study aimed at defining the flow properties of blood in patients with various types of lupus erythematosus. Results for 51 patients were compared with those for 20 controls matched for sex. The patients were divided into subgroups--chronic discoid, subacute cutaneous, and systemic lupus erythematosus--according to their clinical or laboratory characteristics. Blood and plasma viscosity, packed cell volume, red cell aggregation, and red cell deformability were used as parameters of blood rheology. Blood and plasma viscosity and red cell aggregation were significantly different in patients compared with controls, indicating reduced blood fluidity in lupus erythematosus. There were no marked sex differences. The rheological effects were greater in those with systemic lupus erythematosus than in those with chronic discoid or subacute cutaneous lupus erythematosus. The presence of a positive antinuclear antibody titre or methods of treatment (systemic steroids or retinoids) had no apparent effect on the parameters tested. It is suggested that a complex haemorheological deficit exists in lupus patients.
Tumid lupus erythematosus is a rare variant of chronic cutaneous lupus erythematosus that is characterized clinically by smooth, nonscarring, pink to violaceous papules or plaques without evidence of surface change. Histopathologic features include superficial and deep lymphocytic infiltration in a perivascular and periadnexal distribution, with dermal interstitial mucin deposition and focal or absent dermoepidermal junction involvement. These clinical and histopathologic features can be challenging to differentiate from other cutaneous diseases. This is particularly true because patients with tumid lupus erythematosus usually do not have other manifestations of systemic lupus erythematosus or cutaneous lupus erythematosus. We present two cases of tumid lupus erythematosus, one associated with concomitant systemic lupus erythematosus and the other occurring concurrently with discoid lupus erythematosus. Furthermore, we demonstrate the rare occurrence of a patient with tumid LE occurring below the waist at a photoprotected site.
tumid lupus erythematosus; systemic lupus erythematosus; discoid lupus erythematosus; chronic cutaneous lupus erythematosus
The number of CD27++ plasma cells (PCs) in peripheral blood may be a valuable biomarker for systemic lupus erythematosus (SLE) disease management. More insights into the behavior of the PC population are, however, required to validate CD27 as a reliable biomarker. In the current study, we have monitored the PC compartment of patients with acute bacterial infections and patients with SLE and, in addition, examined the relationship between the presence of serum antinuclear antibodies (ANAs) and the number of peripheral PCs. Kinetic analyses in patients with bacterial infection revealed a 10–60-fold expansion of the CD27++ PC compartment that peaked at day 2–5 and returned toward normal values at day 7–9 after hospital admission. The transient expansion of the PC population appeared to be a late phenomenon in the process of recovering from a bacterial infection. SLE subjects had significantly increased frequencies of PCs compared with patients suspected of a connective tissue disease and healthy controls. In patients suspected of a connective tissue disease, no relationship was found between the presence of serum ANAs and the number of CD27++ PCs. Additionally, the presence of serum ANAs was not associated with abnormalities in other peripheral B-cell subsets. It remains to be established at which stage of SLE development the expansion of the PC compartment is initiated.
Antinuclear antibodies; CD27; Infection; Plasma cells; SLE
Systemic lupus involves different body organs including lungs. However, there is limited information on the systemic lupus without respiratory symptoms. The aim of this study was to investigate the diffusing capacity of the lung for carbon monoxide in women with disseminated lupus erythematosus and to compare it with a control group.
This prospective study was conducted during 2005 in the Rheumatology Clinic of Alzahra Hospital, Isfahan, Iran. The diffusing capacity of the lung for carbon monoxide and pulmonary parameters were measured using the unrelated samples in 76 female patients with systemic lupus.
Mean diffusing capacity of the lung for carbon monoxide in patients with lupus was lower than the control group (P ≤ 0.001). The amount of corrected volumetric capacity of carbon monoxide in lungs of patients was significantly different from the control group (P ≤ 0.001). Residual volume and total capacity of lungs in the female patients with lupus were higher than the control group (P ≤ 0.001).
Decreased diffusing capacity for carbon monoxide in lungs of females with systemic lupus without respiratory symptoms is prevalent. It indicates alveolar capillary membrane involvement in these patients. Increased residual volume and total capacity of lungs in these patients can be caused by bronchiolitis.
Lupus Erythematosus; Transfer Capacity; Carbon Monoxide in Lungs; Total Capacity of Lungs
Patients with systemic lupus erythematosus (SLE) have an increased risk of acute myocardial infarction (AMI). We examined if nephritis or other clinical manifestations of SLE identified patients at increased risk.
In this population-based case-control study, we identified patients with SLE hospitalized with an AMI in California in 1996–2000. We compared the frequency of six manifestations of SLE (nephritis, pleuritis, hemolytic anemia, thrombocytopenia, psychosis/major depression, seizures) and of venous thrombosis/pulmonary embolism, in this group (n=535) to the frequency of these manifestations in two control groups: patients with SLE hospitalised for pulmonary disease (n=529), and patients with SLE hospitalised for gastrointestinal bleeding (n=349).
Nephritis was present in 23.7% of patients with AMI, 11.0% of patients with pulmonary disease and 25.2% of patients with gastrointestinal bleeding. In adjusted analyses, nephritis was more common in the AMI group (odds ratio (OR) 2.85, 95% confidence interval (CI) 1.97–4.14; p<.0001) than in the pulmonary disease control group. Among women, nephritis was more common in the AMI group (OR 2.83; 95% CI 1.33–6.01; p=0.007) than in the gastrointestinal bleeding control group. Psychosis/major depression was less common among patients with AMI.
Among patients with SLE, nephritis was associated with 2.8-fold increased risk of AMI.
Systemic lupus erythematosus; myocardial infarction; cardiovascular disease; lupus nephritis
The prevalence of autoimmune diseases, including systemic lupus erythematosus, is increased in failure of certain host defence mechanisms. Systemic lupus erythematosus, however, has not been recorded as a late complication of the Staphylococcus aureus hyperimmunoglobulinaemia E (hyper-IgE) syndrome. Such a case was investigated in a man suffering from a classic example of the syndrome. Antinuclear antibodies were analysed on a molecular basis. The emergence of immunological and clinical features of systemic lupus erythematosus in patients with defective host defence mechanisms against staphylococcal infections is unlikely to be fortuitous and may help elucidate the pathogenesis of systemic lupus erythematosus. The observations will also aid the long term management of patients with S aureus hyper-IgE syndrome.
It has been observed that patients with systemic lupus erythematosus and discoid
lesions have a milder systemic disease.
To compare the clinical, demographic and autoantibody profile of systemic lupus
erythematosus patients with and without discoid lesions.
We carried out a retrospective study involving 288 systemic lupus erythematosus
patients who met at least four classification criteria of the American College of
Rheumatology for systemic lupus erythematosus, comparing the clinical, serological
and demographic factors between patients with and without discoid manifestations.
Of the 288 patients, 13.8% had discoid lesions. Univariate analysis found no
differences in the prevalence of malar rash, photosensitivity, arthritis,
serositis, leukopenia, lymphopenia and hemolytic anemia or anemia of the central
nervous system (p = ns). Renal lesions were more common in those without discoid
lesions (p =0.016), and hemolysis (p<0.0001) was more common in those with
discoid lesions. Regarding the profile of autoantibodies, only the anti-RNP
antibody was more common in those with discoid events (p =0.04). In a logistic
regression study, only the renal lesions and anti-RNP maintained their
associations with discoid manifestations.
Patients with lesions of systemic lupus erythematosus and discoid lesions have
lower prevalence of renal involvement and a greater presence of anti RNP.
Glomerulonephritis; Lupus erythematosus, cutaneous; Lupus erythematosus, discoid; Lupus erythematosus, systemic
Paroxysmal nocturnal hemoglobinuria is an acquired disorder of hemopoiesis and is characterized by recurrent episodes of intravascular hemolysis due to an increased sensitivity to complement-mediated hemolysis. Systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. We report a case of paroxysmal nocturnal hemoglobinuria that developed in a patient with systemic lupus erythematosus and lupus nephritis.
A 29-year-old Mongolian woman had systemic lupus erythematosus, which manifested only as skin lesions when she was 12 years old. She had leg edema and proteinuria when she was 23 years old, and a renal biopsy revealed lupus nephritis (World Health Organization type IV). She had been treated with steroids and immunosuppressant therapy. At 29, she had headaches, nausea, general fatigue, and severe pancytopenia and was admitted to our hospital. A laboratory evaluation showed hemolytic anemia. Further examination showed a neutrophil alkaline phosphatase score of 46 points, a CD55 value of 18%, and a CD59 value of 78.6%. The results of Ham test and sugar water tests were positive. The constellation of symptoms throughout the clinical course and the laboratory findings suggested paroxysmal nocturnal hemoglobinuria.
To the best of our knowledge, systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. Clinicians should be aware of the association between autoimmune and hematological diseases.
Sera from groups of patient with systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, and progressive systemic sclerosis and normal controls were compared, using different antinuclear antibody assays. Hep-II cells, used as a substrate for the detection of antinuclear antibodies, appeared to be more sensitive than rat liver substrate. In addition, the fluorescent patterns were easier to identify on Hep-II cells. All systemic lupus erythematosus sera with antibodies reactive with kinetoplasts of Crithidia luciliae had binding greater than 43% for single-stranded DNA. Based on the high sensitivity of the Hep-II substrate and the relative specificity of high (greater than 43%) binding for single stranded DNA by sera from patients with systemic lupus erythematosus, it appears that these two tests are most useful in differential diagnosis and for the detection of systemic lupus erythematosus.
Regulatory/suppressor T cells (Tregs) maintain immunologic homeo-stasis and prevent autoimmunity. In this article, past studies and recent studies of Tregs in mouse models for lupus and of human systemic lupus erythematosus are reviewed concentrating on CD4+CD25+Foxp3+ Tregs. These cells consist of thymus-derived, natural Tregs and peripherally induced Tregs that are similar phenotypically and functionally. These Tregs are decreased in young lupus-prone mice, but are present in normal numbers in mice with established disease. In humans, most workers report CD4+Tregs are decreased in subjects with active systemic lupus erythematosus, but the cells increase with treatment and clinical improvement. The role of immunogenic and tolerogenic dendritic cells in controlling Tregs is discussed, along with new strategies to normalize Treg function in systemic lupus erythematosus.
B cells play important roles in autoimmune diseases ranging from multiple sclerosis to rheumatoid arthritis. B cells have long been considered central players in systemic lupus erythematosus. However, anti-CD20 mediated B cell depletion was not effective in two clinical lupus studies, while anti-BLyS, which inhibits B cell survival, was effective. Others and we previously found that anti-CD20 based depletion was surprisingly ineffective in tissues of lupus-prone mice, but that persistent high doses eventually led to depletion and ameliorated lupus. Lupus patients might also have incomplete depletion, as suggested in several studies, and which could have led to therapeutic failure. Here we investigated the mechanism of resistance to Ab-mediated cellular depletion in murine lupus. B cells from lupus-prone mice were easily depleted when transferred into normal environments or in lupus-prone mice that lacked serum Ig. Serum from lupus-prone mice transferred depletion resistance, with the active component being IgG. Because depletion is FcγR-dependent, we assayed macrophages and neutrophils exposed to lupus mouse serum, showing they are impaired in IgG-mediated phagocytosis. We conclude that depletion resistance is an acquired, reversible phagocytic defect depending on exposure to lupus serum IgG. These results have implications for optimizing and monitoring cellular depletion therapy.
The association of systemic lupus erythematosus with malignancies is an uncommon occurrence. We present the case of an osteosarcoma of the urinary bladder developing in a patient with a prolonged history of active systemic lupus erythematosus. This is a previously unreported association. Primary osteosarcoma is an extremely rare disease in the urinary bladder.
A 24-year-old Caucasian woman with a 13-year history of systemic lupus erythematosus, who had been treated with high dose immunosuppressive agents, presented with pain and hematuria. A deeply invasive high-grade tumor was detected in the urinary bladder and the patient underwent radical surgery. A diagnosis of osteosarcoma was made based on the characteristic histology.
Predisposing factors for primary sarcomas in the urinary bladder are mostly unknown; however, in our case, long-term administration of immunosuppressive agents, as well as long standing systemic lupus erythematosus, may both be of significance.
The relative prevalence and clinical pattern of the major rheumatic diseases in the patient population of a teaching hospital in Jamaica were studied over the 3-year period 1974--7. The prevalence of systemic lupus erythematosus approached that of rheumatoid arthritis (RA). All grades of severity of RA were seen, and there was an unusually high proportion of females with RA. Rheumatic fever and exacerbations were relatively common, and in the absence of carditis differentiation from infective polyarthritis, especially gonococcal, was occasionally difficult.
Background: Infections are one of the main causes of morbidity and mortality in patients with systemic lupus erythematosus.
Objective: To analyse urinary tract infection (UTI) risk factors in lupus patients; the influence of these factors on disease activity, organ damage, and disease development; the type and prevalence of UTI; and the micro-organisms involved.
Method: 86 control subjects and 81 lupus patients were studied prospectively over a 12 month period and examined on five occasions. Epidemiological data and information on urinary symptoms, disease activity (SLEDAI), and organ damage (SLICC/ACR) data were collected. Autoantibodies, complement levels, urine culture, and antibiogram were determined; urological studies were also carried out. SPPS 10.0 and STATA 6.0. were used for statistical analysis.
Results: The prevalence of UTI in lupus patients was 36%. Lupus influences the onset of UTI (p = 0.001), regardless of other variables. UTI risk factors in lupus patients were age (p = 0.002), previous cases of UTI (p = 0.0001), antinuclear antibodies (ANA) >1/80 IU/ml (p = 0.022), thrombocytopenia (p = 0.02), and admission to hospital due to UTI (p = 0.002). Leucopenia (p = 0.09) and the weekly administration of methotrexate (p = 0.06) had a bearing on the onset of UTI; disease development (p = 0.99), lupus activity (p = 0.32), and organ damage (p = 0.36) do not. The uropathogen most frequently isolated was E coli (60%).
Conclusions: Lupus patients are likely to have UTI, usually manifesting in the lower tract. They are community acquired, basically caused by E coli, and favoured by age, previous UTI, admissions to hospital due to UTI, thrombopenia, ANA, leucopenia, and methotrexate treatments.