Incidence and variables associated with short and long-term mortality in patients with systemic lupus erythematosus and sepsis admitted in intensive care units.

Background Infections are common among patients with systemic lupus erythematosus (SLE), and are associated with increased morbidity and mortality. Objectives To determine whether SLE is an independent risk factor for short- and long-term mortality in patients admitted to an intensive care unit (ICU) with sepsis, and to identify the characteristics of SLE patients admitted to an ICU with sepsis. Methods A retrospective age- and sex-matched cohort study, based on data of the SEPSIS-ISR (Sepsis Israel) Registry, an ongoing study that collects data on all patients admitted with sepsis to the ICUs. The primary outcome was to determine whether SLE is an independent risk factor for 30-day and 3-year mortality. Secondary outcomes were 30-day and 3-year survival rates, and the identification of variables associated with mortality within the group of patients with SLE. Results In total, 29 SLE and 87 non-SLE patients (median age 55 years; 79.3% females) were included. The primary sites of infection as well as pathogen distributions were similar between the two groups. The most common infections among the SLE and non-SLE patients were pneumonia (48.3 vs. 31%, p = 0.09), urinary tract infection (20.7 vs. 14.9%, p = 0.56) and peritonitis (13.8 vs. 16.1%, p = 0.77). Severe sepsis and septic shock were diagnosed in 79.3 versus 80.5% ( p = 0.89) and 55.2 versus 33.3% ( p = 0.04) of the SLE and non-SLE patients, respectively. The 30-day and 3-year survival rates did not differ between SLE and non-SLE patients, and were 69 versus 67.8% ( p = 0.79) and 41.4 versus 47.1% ( p = 0.69), respectively. In multivariate Cox regression analysis, age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) 1.00-1.05) and cardiovascular involvement during sepsis (HR = 3.32; 95% CI 1.4-7.86) were significant independent risk factors for 30-day mortality. Multiorgan dysfunction during sepsis admission was associated with increased 3-year mortality (HR = 1.37; 95% CI 1.07-1.75). Conclusions SLE is not an independent risk factor for 30-day or 3-year mortality following ICU admission with sepsis. Increased late mortality was associated with congestive heart failure within the SLE patients alone. None of the SLE-related variables were statistically different between the living and deceased SLE patients.

Safety of vaccination of patients with systemic lupus erythematosus.

Live vaccines are not safe for immuno-compromised patients and should not be given to patients with systemic lupus erythematosus. In addition, all vaccines are not recommended for systemic lupus erythematosus patients when their disease is very active and mainly for patients with very active lupus nephritis. Systemic lupus erythematosus patients with quiescent or mildly active disease should be encouraged to receive vaccination according the recommendations given by the Immunization Practices Advisory Committee. Among this group of systemic lupus erythematosus patients, vaccines are safe and they do not affect the clinical manifestations of systemic lupus erythematosus including renal features, disease activity, or the requirement for steroids or cytotoxic drugs. However, vaccines may trigger the generation of autoantibodies which is usually short term and has no clinical significance. In individual cases vaccines exacerbate systemic lupus erythematosus; however, no specific clinical or laboratory variables have been identified to be associated with flare of systemic lupus erythematosus following vaccination.

Antiphospholipid antibody syndrome: the flow cytometric annexin A5 competition assay as a diagnostic tool.

The mechanism underlying hypercoagulability in antiphospholipid antibody syndrome (APS) is uncertain. Here, we present a flow-cytometric assay (FCA) based on the hypothesis that anti-platelet-anionic-phospholipid autoantibodies (aPL) interfere with the activity of the natural anticoagulant protein annexin A5, thereby accelerating platelet procoagulant activity. This study assessed the clinical utility of the feasible FCA, which demonstrates the competition of the patient's aPL with the binding of annexin A5 to the platelet-anionic-phospholipids, in the diagnosis of APS. Sixty-two (94%) of 66 APS patients, 20 (51%) of 39 patients with systemic lupus erythematosus and two (4%) of 49 healthy individuals were positive by FCA. Compared with the anticardiolipin (aCL) assay, the relative sensitivity was 82% and the specificity 73.3%. However, 19 (25%) aCL-negative patients were positive by FCA; 12 were positive for lupus-anticoagulant (LA). Compared with LA assay, the relative sensitivity was 85% and the specificity 72.2%. However, 21 (26%) LA-negative patients were FCA-positive, 12 were positive for aCL. The FCA was particularly sensitive for APS patients with arterial (97.0%) and gestational vascular complications (100%) with overall sensitivity of 95% and specificity of 97%. Our findings suggest that the FCA is practical, sensitive and specific for the detection of clinically relevant aPL in the diagnosis of APS.

Pleural effusion associated with rheumatoid arthritis: what cell predominance to anticipate?

Pleural involvement is the most frequent manifestation of rheumatoid arthritis (RA) in the chest. We report here two patients who presented with large exudative pleural effusions and subsequently developed sero-positive RA. In both cases, the differential cell count of the pleural effusion suggested empyema. A literature review identified that RA-associated pleural effusion afflicts more men than women and 95% of the patients have high titers of rheumatoid factor (RF). In 46% of cases, RA-associated pleural effusion is diagnosed in close temporal relationship with the diagnosis of RA. The effusion is an exudate and is characterized by low pH and glucose level, and high lactic dehydrogenase (LDH) and cell count. At diagnosis there is a tendency for predominant neutrophils to occur consistent with an empyema and 7-11 days later, the cells in the pleural effusion are replaced by lymphocytes. Pleural effusion with predominant eosinophilia is rare. RA patients with acidic effusion and low glucose content with neutrophils predominance should be treated with thoracic drainage and antibiotics until an infection is ruled out. The histo-pathologic findings in pleural fluid of tadpole cells and multinucleated giant cells and the replacement of the mesothelial cells on the parietal pleural surface with a palisade of macrophage derived cells are described as pathogonomic for RA. Treatment with systemic steroids and intra-pleural steroids are effective in most cases.

Sense of coherence and its impact on quality of life of patients with systemic lupus erythematosus.

The sense of coherence (SOC) construct refers to a global orientation, which significantly determines the link between stressors, coping with disease and health. The aim of this work was to assess possible associations between SOC and quality of life (QOL) scores among women with SLE. Sixty consecutive SLE women and 88 healthy women were included in the study. QOL was assessed using the SF-36 and the WHO QOL-Bref scales. The SOC has three main sub-scales: comprehensibility, manageability and meaningfulness. Regression analyses were used to study associations between various parameters of SF-36, WHO QOL-Bref, SOC, SLEDAI, indices of end organ damage (SDI), and demographic variables. Mean SLEDAI and SDI scores were 4.5 (SD = 5.6) and 1.29 (SD=2). SLE patients had significantly lower scores for all individual and summary sub-scales in the two QOL questionnaires compared with controls. SLE patients had significantly lower scores for the general, comprehensibility and meaningfulness sub-scales of SOC. No significant correlation was seen between SOC scores and measures of disease activity or end-organ damage. A strong linear correlation was seen between the scores of SOC, general WHO QOL-Bref, and the mental and physical component summary (MCS & PCS) scores of SF36. Age, SOC and SDI significantly affected the PCS score. SOC was the only variable independently associated with MCS. Education and SOC were significantly associated with the general WHO QOL-Bref. Age, education, SDI and SOC were independently associated with QOL of women with SLE.

Dobutamine stress echocardiography in women with systemic lupus erythematosus: increased occurrence of left ventricular outflow gradient.

Dobutamine stress echocardiography (DSE) is an accurate noninvasive test used for the diagnosis and evaluation of patients with known or suspected coronary artery disease (CAD). The aim of this study was to determine the rate of positive findings in DSE, to define the echocardiographic and clinical characteristics of women with systemic lupus erythematosus (SLE) and to evaluate the safety of DSE in SLE patients. Thirty consecutive SLE patients were enrolled in the study and underwent DSE study. The mean age of patients was 44 years (range 20-76). Mean duration of SLE was 8.1 years and mean SLEDAI was 5.5. None of the DSE tests performed were positive for myocardial ischaemia. A left ventricular outflow gradient (LVOG) was found in 15/28 (54%) patients who completed the test, a result higher than the reported 20% prevalence of this finding in the literature. There were no significant differences in baseline characteristics between patients who developed a gradient and patients in whom a gradient was not found. There were no significant adverse effects during the study. In the general population, LVOG has been reported to be associated with an increased rate of chest discomfort and with a significantly lower prevalence of CAD. Whether this is true for SLE patients requires further study.

Influenza virus vaccination of patients with SLE: effects on generation of autoantibodies.

The sera of 24 women with SLE who received influenza vaccine were tested by ELISA for anti-DNA, anticardiolipin, anti-Sm, anti-Sm/RNP, anti-Ro and anti-La. Blood samples were withdrawn at the time of vaccination and 6 and 12 weeks after vaccination. The mean age at enrolment into the study was 46.1 years. The mean disease duration was 9.1 years. SLEDAI scores were 6.6 at vaccination, 4.9 at 6 weeks and 5.1 at week 12. The vaccine was not associated with the generation of anti-DNA. At time of vaccination a single patient had anti-Sm, four patients had anti-Sm/RNP antibodies, none of the patients had anti-La antibody and six had anti-Ro antibodies. Six weeks after vaccination four, eight, nine and three patients had autoantibodies reacting with Sm, Sm/RNP, Ro and La, respectively. Twelve weeks after vaccination none of the patients had anti-Sm, three had anti-Sm/RNP, five had anti-Ro and two had anti-La antibodies. Following vaccination six and three patients developed IgG and IgM anticardiolipin antibodies, respectively. In summary, although the influenza virus vaccine is clinically safe for patients with SLE it may trigger the generation of autoantibodies. This effect is usually short term and has no clinical significance.

Immunization of naive BALB/c mice with human beta2-glycoprotein I breaks tolerance to the murine molecule.

OBJECTIVE: Immunization of naive mice with beta2-glycoprotein I (beta2GPI) leads to the generation of pathogenic anticardiolipin antibodies associated with clinical manifestations of the antiphospholipid syndrome (APS). The aim of this study was to determine whether immunization of naive mice with human beta2GPI, which shares homology with mouse beta2GPI molecules, breaks tolerance to murine beta2GPI and leads to the generation of anti-mouse beta2GPI. METHODS: Twenty-four female BALB/c mice were immunized in the footpads with 10 microg of human beta2GPI. Twelve age- and sex-matched BALB/c mice were immunized in the same manner with Freund's complete adjuvant and served as controls. The reactivity of whole sera, polyclonal IgG, and affinity-purified anti-beta2GPI IgG antibodies against human, bovine, and mouse beta2GPI was evaluated by enzyme-linked immunosorbent assay. RESULTS: High titers of anti-human beta2GPI IgG antibodies were detected 1 month after immunization. Progressively increasing titers against murine and bovine beta2GPI were recorded 1-4 months after injection. CONCLUSION: Immunization of mice with human beta2GPI resulted in the generation of antibodies reacting with human, bovine, and murine beta2GPI. The loss of tolerance to mouse beta2GPI is attributable to the high interspecies homology of beta2GPI. These results may point to molecular mimicry as a possible cause of APS.

Systemic lupus erythematosus and cancer: associated or not?

The frequency of cancer in patients with SLE is between 2.5 and 13.8%. A literature review has identified nine full-length studies that estimated the overall risk of cancer in SLE patients compared with the general population. Five of them have not noted an increased risk for the development of overall cancers among SLE patients compared with the general population. One study identified a 30% increased risk (SIR or 1.3) for occurrence of cancer among 1585 SLE patients followed over 10,807 patient-years. Taken together, it is controversial whether the risk of all cancers is increased in SLE patients compared with the general population. Increased risk of lymphatic malignancies has been shown in multiple large series of SLE patients, but SLE is not associated with an increased risk for the development of most of the solid tumors. Pathogenic mechanisms involved with the development of lymphoproliferative malignancies in association with SLE include a common etiologic agent for both diseases, environmental factors as the use of cytotoxic or immunosuppressive agents, genetic variables, and immunologic factors as immunoregulatory disturbances of the immune system.

The prevalence of musculoskeletal pain and fibromyalgia in patients hospitalized on internal medicine wards.

OBJECTIVES: To estimate the prevalence of nonarticular pain complaints (chronic widespread pain, chronic localized pain, transient pain) and fibromyalgia in hospitalized patients and to study utilization patterns of health services associated with pain related problems. METHODS: Five hundred twenty-two patients hospitalized on internal medicine wards were enrolled. Data were collected with a questionnaire covering demographic background, information on pain and other symptoms, utilization of health services, and drug consumption. All subjects were classified into four pain groups: those with no pain, transient pain, chronic regional pain, and chronic widespread pain. Tenderness was assessed by thumb palpation, and patients were diagnosed as having fibromyalgia if they met the 1990 American College of Rheumatology criteria. RESULTS: Sixty-two percent of the patients reported pain; 36% reported chronic regional pain, 21% reported chronic widespread pain, and 5% reported transient pain. Fifteen percent of all patients had fibromyalgia, most of whom (91%) were women. The prevalence of chronic widespread pain and of fibromyalgia in women increased with age. Sleep problems, headache, and fatigue were highly prevalent, especially among those with chronic widespread pain. Patients with chronic widespread pain reported more visits to family physicians (6.2 visits per year) and more frequent use of drugs. They also were more frequently referred to rheumatologists, and they reported more hospitalizations. CONCLUSIONS: Pain syndromes and related symptoms are prevalent among hospitalized patients on the medicine wards. The internist taking care of these patients should be aware of the presence of these syndromes and realize that some of the reported symptoms are partly related to these (undiagnosed) pain syndromes rather than to the cause of hospitalization.

Balneotherapy at the Dead Sea area for patients with psoriatic arthritis and concomitant fibromyalgia.

BACKGROUND: Balneotherapy has been successfully used to treat various rheumatic diseases, but has only recently been evaluated for the treatment of fibromyalgia. Since no effective treatment exists for this common rheumatic disease, complementary methods of treatment have been attempted. OBJECTIVES: To assess the effectiveness of balneotherapy at the Dead Sea area in the treatment of patients suffering from both fibromyalgia and psoriatic arthritis. METHODS: Twenty-eight patients with psoriatic arthritis and fibromyalgia were treated with various modalities of balneotherapy at the Dead Sea area. Clinical indices assessed were duration of morning stiffness, number of active joints, a point count of 18 fibrositic tender points, and determination of the threshold of tenderness in nine fibrositic and in four control points using a dolorimeter. RESULTS: The number of active joints was reduced from 18.4 +/- 10.9 to 9 +/- 8.2 (P < 0.001). The number of tender points was reduced from 12.6 +/- 2 to 7.1 +/- 5 in men (P < 0.003) and from 13.1 +/- 2 to 7.5 +/- 3.7 in women (P < 0.001). A significant improvement was found in dolorimetric threshold readings after the treatment period in women (P < 0.001). No correlation was observed between the reduction in the number of active joints and the reduction in the number of tender points in the same patients (r = 0.2). CONCLUSIONS: Balneotherapy at the Dead Sea area appears to produce a statistically significant substantial improvement in the number of active joints and tender points in both male and female patients with fibromyalgia and psoriatic arthritis. Further research is needed to elucidate the distinction between the benefits of staying at the Dead Sea area without balneotherapy and the effects of balneotherapy in the study population.

Balneotherapy for fibromyalgia at the Dead Sea.

The aim of this study was to evaluate the effectiveness of balneotherapy on patients with fibromyalgia (FM) at the Dead Sea. Forty-eight patients with FM were randomly assigned to a treatment group receiving sulfur baths and a control group. All participants stayed for 10 days at a Dead Sea spa. Physical functioning, FM-related symptoms, and tenderness measurements (point count and dolorimetry) were assessed at four time points: prior to arrival at the Dead Sea, after 10 days of treatment, and 1 and 3 months after leaving the spa. Physical functioning and tenderness moderately improved in both groups. With the exception of tenderness threshold, the improvement was especially notable in the treatment group and it persisted even after 3 months. Relief in the severity of FM-related symptoms (pain, fatigue, stiffness, and anxiety) and reduced frequency of symptoms (headache, sleep problems, and subjective joint swelling) were reported in both groups but lasted longer in the treatment group. In conclusion, treatment of FM at the Dead Sea is effective and safe and may become an additional therapeutic modality in FM. Future studies should address the outcome and possible mechanisms of this treatment in FM patients.

Azathioprine therapy for patients with systemic lupus erythematosus.

Azathioprine is the only purine analog that is widely used for the management of systemic lupus erythematosus (SLE). For SLE patients without renal involvement, it is given to those patients who require a maintenance dose of 15 mg or higher of prednisone and for those who experience recurrent flares. Azathioprine in combination with steroids may be given to a large number of patients with lupus nephritis. It is also effective for patients with skin lesions, pneumonitis, thrombocytopenia or hemolytic anemia. Azathioprine may be used during pregnancy but not during lactation. It has not been shown to increase the risk for the development of malignancies among patients with SLE.

Abnormal sympathovagal balance in men with fibromyalgia.

OBJECTIVE: It is possible that there are differences in clinical manifestations between men and women with fibromyalgia syndrome (FM), especially in autonomic dysfunction; we assessed the interaction between the sympathetic and parasympathetic systems in postural change in men with FM using power spectral analysis (PSA) of heart rate variability (HRV), and investigated the pathogenesis of the orthostatic intolerance. METHODS: We studied 19 men with FM and 19 controls matched for age and sex. A high resolution electrocardiogram was obtained in supine and standing postures during complete rest. Spectral analysis of R-R intervals was done by the fast Fourier transform algorithm. RESULTS: PSA of HRV revealed that men with FM at rest are characterized by sympathetic hyperactivity and concomitantly reduced parasympathetic activity. During postural changes, male patients demonstrated an abnormal sympathovagal response. These results provide the physiological basis for the orthostatic intolerance in men with FM. CONCLUSION: This report of autonomic dysfunction in men with FM revealed an abnormal autonomic response to orthostatic stress. This abnormality may have implications regarding the symptoms of FM.

Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies.

OBJECTIVES: To review the autoimmune and rheumatic manifestations of patients with malignancy. METHODS: A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes. RESULTS: Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (a) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). (b) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. (c) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy. CONCLUSION: Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.

The effect of balneotherapy at the Dead Sea on the quality of life of patients with fibromyalgia syndrome.

Fibromyalgia (FS) is an idiopathic chronic pain syndrome defined by widespread non-articular musculoskeletal pain and generalised tender points. As there is no effective treatment, patients with this condition have impaired quality of life (QoL). The aim of this study was to assess the possible effect of balneotherapy at the Dead Sea area on the QoL of patients with FS. Forty-eight subjects participated in the study; half of them received balneotherapy, and half did not. Their QoL (using SF-36), psychological well-being and FS-related symptoms were assessed prior to arrival at the spa hotel in the Dead Sea area, at the end of the 10-day stay, and 1 and 3 months later. A significant improvement was reported on most subscales of the SF-36 and on most symptoms. The improvement in physical aspects of QoL lasted usually 3 months, but on psychological measures the improvement was shorter. Subjects in the balneotherapy group reported higher and longer-lasting improvement than subjects in the control group. In conclusion, staying at the Dead Sea spa, in addition to balneotherapy, can transiently improve the QoL of patients with FS. Other studies with longer follow-up are needed to support our findings.

The dual association between lymphoma and autoimmunity.

Autoimmune rheumatic diseases and lymphocytic malignancies are related and this association is bidirectional. Lymphomas occur more frequently in the course of autoimmune disease and autoimmune rheumatic manifestations occur in the course of lymphocytic malignancies. An increased incidence of malignant lymphocytic diseases is present in patients with rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and autoimmune thyroid disease. Descriptions of lymphocytic malignancies among other autoimmune rheumatic disease have been published. In some patients, the malignant disease is diagnosed months or years before the appearance of the rheumatic disease.