Upper airway obstruction assessment: Peak inspiratory flow and clinical COPD Questionnaire.

OBJECTIVES: Spirometric evaluation of upper airway obstruction (UAO) is not commonly performed by Otolaryngologists. In addition, functional evaluation of UAO by flow-volume loops (FVL) is not available in all clinical settings. More recently, peak inspiratory flow (PIF) has proven to be a useful tool to monitor UAO at the patient's bedside. The aim of this work is to assess the role of PIF measured with a simple flow metre (In-Check method) as a standardised, simple, non-invasive tool in quantifying chronic and subacute UAO in a routine clinical practice. In addition, a Clinical COPD Questionnaire (CCQ), previously validated to assess the psychophysical status in patients with laryngotracheal stenosis, was utilised to evaluate respiratory function in UAO. DESIGN: Prospective cohort study. SETTINGS: University teaching hospital. PARTICIPANTS: Seventy 2 subjects, an UAO group of 26 patients and a control group of 46 healthy subjects. MAIN OUTCOME MEASURES: The ability of PIF values to discriminate between the UAO group and the control group was assessed using a ROC curve. A Spearman rank correlation was used to test the relationship between PIF measurements and the global CCQ score. Additionally, an analysis of CCQ at domain and items levels was performed. RESULTS: Peak inspiratory flow values were accurate, with an area under the ROC curve (AUC) of 0.98 (P < .05) for differentiating the control group from the UAO group. A threshold PIF value of 170 L/min was found for diagnosing UAO. An inconclusive negative trend was found (r = -.19; P = .35) between PIF values and CCQ global score. Concerning CCQ, the symptoms domain was the most affected by UAO, higher than mental domains (P < .001) as well as functional domains (P < .01). Exertional dyspnoea and cough were the items that obtained the highest disturbed scores. CONCLUSIONS: Peak inspiratory flow is a non-invasive, quantitative parameter to evaluate the severity of UAO. Testing can be easily performed in a routine clinical setting, with a non-expensive hand-held device, and could help medical follow-up programmes and prevent emergency situations. However, FVL may be necessary for further assessment of UAO diseases. The CCQ confirms that exertional dyspnoea is the main symptom of UAO, but cough remains a common symptom.

The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients.

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-ß2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-ß2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

Anti-C1q antibodies in systemic lupus erythematosus.

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Differential cytokine expression and regulatory cells in patients with primary and secondary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands. The aim of the study was to characterize and compare the presence of diverse cytokines and regulatory T and B cells in lip minor salivary gland (MSG) biopsies from patients with primary Sjögren's syndrome (pSS), secondary SS (sSS), and patients with connective tissue disease (CTD) without (w/o) SS. We included samples of MSG from 15 pSS, 24 sSS (six scleroderma, nine rheumatoid arthritis and nine lupus patients) and 15 patients with CTD w/o SS. Tissues were examined by an indirect immunoperoxidase technique (goat polyclonal anti-human IL-19, goat polyclonal anti-human IL-22 or mouse monoclonal anti-human IL-24). To determine the subpopulation of CD4(+)/IL-17A(+)-, CD4(+)/IL-4(+)-, CD4(+)/IFN-É£(+)-expressing T cells, CD25(+)/Foxp3(+) Treg cells and CD20(+)/IL-10(+)-producing B cell subset, a double-staining procedure was performed. We estimated the mean percentage of positively staining cells in two fields per sample. CD4(+)/IFN-É£(+), CD4(+)/IL-4(+) and IL-22(+) cell percentages were elevated in both SS varieties; however, the cells were more prevalent in pSS. Patients with pSS had a high number of CD4(+)/IL-17A(+) and IL-19(+) T cells and a lower percentage of IL-24(+) cells (P < 0.05). The Treg and IL-10-producing B cells were increased in pSS (P < 0.05). Concluding, in our patients, a pro-inflammatory and regulatory balance coexists in SS, being both responses more intense in pSS. The explanation of these differences may be related to disease activity, disease duration and treatment.

SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus.

OBJECTIVE: To examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE). METHODS: An international study evaluated newly diagnosed SLE patients for neuropsychiatric events attributed to SLE and non-SLE causes. The outcome of events was determined by a physician-completed seven-point scale and compared with patient-completed Short Form 36 (SF-36) health survey questionnaires. Statistical analysis used linear mixed-effects regression models with patient-specific random effects. RESULTS: 274 patients (92% female; 68% Caucasian), from a cohort of 1400, had one or more neuropsychiatric event in which the interval between assessments was 12.3 ± 2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (p<0.0001) following adjustments for gender, ethnicity, centre and previous score. A consistent improvement in neuropsychiatric status (N=295) was associated with an increase in the mean (SD) adjusted MCS score of 3.66 (0.89) in SF-36 scores. Between paired visits when the neuropsychiatric status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00 (1.96). For the physical component summary scores the corresponding changes were +1.73 (0.71) and -0.62 (1.58) (p<0.05), respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of neuropsychiatric events did not substantially alter the results. CONCLUSION: Changes in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of neuropsychiatric events in SLE patients.

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus.

OBJECTIVE: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. METHODS: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti-ß(2) glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. RESULTS: Disease duration at enrolment was 5.4 ± 4.2 months, follow-up was 3.6 ± 2.6 years. Patients were 89.1% female with mean (±SD) age 35.2 ± 13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-ß(2) glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. CONCLUSION: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity.

Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials.

International consensus for a definition of disease flare in lupus.

The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: "A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment." The LFA proposes this definition for lupus flare on the basis of its high face validity.

Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus.

OBJECTIVES: To determine the frequency, accrual, attribution and outcome of neuropsychiatric (NP) events and impact on quality of life over 3 years in a large inception cohort of patients with systemic lupus erythematosus (SLE). METHODS: The study was conducted by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis. NP events were identified using the American College of Rheumatology case definitions, and decision rules were derived to determine the proportion of NP disease attributable to SLE. The outcome of NP events was recorded and patient-perceived impact determined by the SF-36. RESULTS: 1206 patients (89.6% female) with a mean (+/-SD) age of 34.5+/-13.2 years were included in the study. The mean disease duration at enrollment was 5.4+/-4.2 months. Over a mean follow-up of 1.9+/-1.2 years, 486/1206 (40.3%) patients had > or =1 NP events, which were attributed to SLE in 13.0-23.6% of patients using two a priori decision rules. The frequency of individual NP events varied from 47.1% (headache) to 0% (myasthenia gravis). The outcome was significantly better for those NP events attributed to SLE, especially if they occurred within 1.5 years of the diagnosis of SLE. Patients with NP events, regardless of attribution, had significantly lower summary scores for both mental and physical health over the study. CONCLUSIONS: NP events in patients with SLE are of variable frequency, most commonly present early in the disease course and adversely impact patients' quality of life over time. Events attributed to non-SLE causes are more common than those due to SLE, although the latter have a more favourable outcome.

Validation of the Spanish, Portuguese and French versions of the Lupus Damage Index questionnaire: data from North and South America, Spain and Portugal.

We have previously developed and validated a self-administered questionnaire, modelled after the Systemic Lupus International Collaborating Clinics Damage Index (SDI), the Lupus Damage Index Questionnaire (LDIQ), which may allow the ascertainment of this construct in systemic lupus erythematosus (SLE) patients followed in the community and thus expand observations made about damage. We have now translated, back-translated and adapted the LDIQ to Spanish, Portuguese and French and applied it to patients followed at academic and non-academic centres in North and South America, Portugal and Spain while their physicians scored the SDI. A total of 887 patients (659 Spanish-speaking, 140 Portuguese-speaking and 80 French-speaking patients) and 40 physicians participated. Overall, patients scored all LDIQ versions higher than their physicians (total score and all domains). Infrequent manifestations had less optimal clinimetric properties but overall agreement was more than 95% for the majority of items. Higher correlations were observed among the Spanish-speaking patients than the Portuguese-speaking and French-speaking patients; further adjustments may be needed before the Portuguese and French versions of the LDIQ are applied in community-based studies. The relationship between the LDIQ and other outcome parameters is currently being investigated in a different patient sample.

Peak inspiratory flow as predictor for tracheotomy.

OBJECTIVES: Quantitative evaluation of upper airway obstruction cannot be commonly performed under acute dyspnea, especially in head and neck cancer (HNC); the decision whether or not to perform airway control surgery may be difficult to reach. Peak inspiratory flow (PIF) has been previously demonstrated to be a useful tool to decide on decannulation after HNC surgery. The aim of the present study was to assess the role of PIF as a standardized non-invasive tool in quantifying severe inspiratory dyspnea requiring emergency tracheostomy. MATERIALS AND METHODS: A single-center prospective observational pilot study analyzed PIF measurements in 22 patients exhibiting acute dyspnea due to upper airway obstruction. MAIN OUTCOME MEASURES: The decision whether or not to perform tracheotomy was taken prior to PIF measurement. PIF was measured with a hand-held PIF meter (In-Check method), and laryngeal fiberoscopy was then performed. Obstruction severity was defined by PIF values. RESULTS: PIF could be measured prior to tracheotomy (imminent in 21 cases, postponed in 1) in all cases. PIF values below 53.1 L/min (i.e., 18.3% of theoretic value) correlated with necessity for emergency tracheotomy. This threshold is concordant with that previously found for the feasibility of decannulation (60L/min). CONCLUSIONS: PIF is a non-invasive quantitative parameter assessing severity of upper airway obstruction, that may be helpful in decision-making for tracheostomy. Testing is simple, quick and reproducible.

Study of Flare Assessment in Systemic Lupus Erythematosus Based on Paper Patients.

OBJECTIVE: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. METHODS: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. RESULTS: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features. CONCLUSION: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.

Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort.

OBJECTIVE: To describe the frequency of myocardial infarction (MI) prior to the diagnosis of systemic lupus erythematosus (SLE) and within the first 2 years of follow-up. METHODS: The systemic lupus international collaborating clinics (SLICC) atherosclerosis inception cohort enters patients within 15 months of SLE diagnosis. MIs were reported and attributed on a specialised vascular event form. MIs were confirmed by one or more of the following: abnormal ECG, typical or atypical symptoms with ECG abnormalities and elevated enzymes (≥2 times upper limit of normal), or abnormal stress test, echocardiogram, nuclear scan or angiogram. Descriptive statistics were used. RESULTS: 31 of 1848 patients who entered the cohort had an MI. Of those, 23 patients had an MI prior to SLE diagnosis or within the first 2 years of disease. Of the 23 patients studied, 60.9% were female, 78.3% were Caucasian, 8.7% black, 8.7% Hispanic and 4.3% other. The mean age at SLE diagnosis was 52.5±15.0 years. Of the 23 MIs that occurred, 16 MIs occurred at a mean of 6.1±7.0 years prior to diagnosis and 7 occurred within the first 2 years of follow-up. Risk factors associated with early MI in univariate analysis are male sex, Caucasian, older age at diagnosis, hypertension, hypercholesterolaemia, family history of MI and smoking. In multivariate analysis only age (OR=1.06 95% CI 1.03 to 1.09), hypertension (OR=5.01, 95% CI 1.38 to 18.23), hypercholesterolaemia (OR=4.43, 95% CI 1.51 to 12.99) and smoking (OR=7.50, 95% CI 2.38 to 23.57) remained significant risk factors. CONCLUSIONS: In some patients with lupus, MI may develop even before the diagnosis of SLE or shortly thereafter, suggesting that there may be a link between autoimmune inflammation and atherosclerosis.

Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients.

Five hundred consecutive patients with systemic lupus erythematosus (SLE) were entered into a prospective study of anticardiolipin antibodies (ACLA) in their 3 major immunoglobulin isotypes and followed thereafter with repeated testing for a mean period of nearly 8 months. Manifestations of SLE that were strongly associated with ACLA included venous thrombosis (particularly when recurrent), thrombocytopenia, hemolytic anemia, recurrent fetal loss, and leg ulcers. Other manifestations found to be associated with ACLA were arterial occlusions, transverse myelitis, and pulmonary hypertension. Conversely, we found no relationship between ACLA and migraine, convulsions, transient ischemic attacks, psychoses, or avascular necrosis of bone. No relationship was found between the presence of ACLA and that of anti-DNA antibodies studied in the same serum sample. Association with ACLA grew stronger and titers became higher in patients with several of the associated manifestations. Statistical analyses revealed the existence of a syndrome, the antiphospholipid syndrome, comprising 2 or more manifestations in conjunction with ACLA titers 5 standard deviations above the mean of normal control subjects, particularly if ACLA had been positive on at least 2 occasions. We propose that such criteria could be applied to the definition of the antiphospholipid syndrome. The presence and the titers of these antibodies related to disease activity and titer decreased by treatment, particularly when they were of the IgM isotype. Patients in whom a thrombotic episode occurred during the course of the study were observed to have a coincident decrease in ACLA titers, a finding that might indicate consumption of the antibody during the event. Treatment and the resulting inactivation of disease appear to have independent effects on ACLA titers. Physicians should therefore be cautious in prescribing high doses of corticosteroids or immunosuppressants to patients with SLE solely because they have high titers of ACLA.

Disease activity during the premenopausal and postmenopausal periods in women with systemic lupus erythematosus.

PURPOSE: Cyclophosphamide-induced ovarian failure has been reported to be protective against flares of systemic lupus erythematosus (SLE). We studied whether patients with SLE experience a decrease in disease activity after natural menopause. SUBJECTS AND METHODS: We studied 30 SLE patients with natural menopause who had been observed at least 2 years before and after menopause and who did not receive hormone replacement therapy or danazol. Menopause was defined as the date of the last self-reported menstrual period. Disease activity was assessed retrospectively by medical chart review using standard measures (the SLE disease activity index) during the immediate premenopausal and postmenopausal periods, and 2 (n = 30 patients), 3 (n = 19), and 4 (n = 13) years before and after menopause. We also compared the use of health services and medications. RESULTS: Patients were studied for a mean (+/- SD) of 6.4 +/- 1.7 years (premenopausal, 3.3 +/- 0.9 years; postmenopausal, 3.2 +/- 0.9 years). During the premenopausal periods, the mean disease activity score was 2.3 +/- 2.3 (range, 0 to 9 on a 0 to 105 scale), compared with 2.3 +/- 2.9 (range, 0 to 12; P = 0.37) after menopause. The maximum disease activity score was somewhat greater in the premenopausal period (7.9 +/- 6.0 [range, 0 to 22] vs. 5.8 +/- 5.1 [range, 0 to 22]; P = 0.04). The incidence rates of flares (0.56 per year vs. 0.43 per year, P = 0.20) and severe flares (0.17 per year vs. 0.12 per year, P = 0.33) were similar in the premenopausal and postmenopausal periods. Differences in disease activity scores (mean and maximum) and the number of visits to a rheumatologist's office were only significant when the fourth year before menopause was compared with the fourth year after menopause. CONCLUSIONS: Disease activity is mild during the premenopausal and postmenopausal periods in women with SLE. A modest decrease, especially in the maximum disease activity, is seen after natural menopause.

Association of silicone breast implants with immunologic abnormalities: a prospective study.

PURPOSE: To study the possible association of silicone-breast-implant exposure and immunologic abnormalities within the Nurses' Health Study, an ongoing prospective cohort study of women. SUBJECTS AND METHODS: From this cohort, we randomly selected 200 women who had been exposed to silicone breast implants and who had never reported connective tissue diseases during 14 years of follow-up, and 500 age-matched, nonexposed women, including 100 with definite connective tissue diseases validated by medical record review, 100 with at least one symptom of a connective tissue disease, 100 with diabetes, and 200 healthy controls. Assays for antinuclear antibodies (ANA), including anti-dsDNA, anti-ssDNA, anti-Sm/RNP/Ro/La, and anti-Scl-70, rheumatoid factor, immunoglobulins, serum complement, and C-reactive protein level, and anticardiolipin, antithyroglobulin, antithyroid microsomal, and antisilicone antibodies were performed by standard techniques in blood samples collected in 1989 or 1990 before collection of silicone-breast-implant exposure data in 1992. RESULTS: ANA was positive (> or = 1:40) in 14% of women with silicone breast implants compared with 20% of healthy women (P = 0.11). Rheumatoid factor was positive (> or = 1:40) in 5% of women with silicone breast implants and 2% of healthy women (P = 0.16). Women with silicone breast implants had a significantly higher frequency of anti-ssDNA antibodies than healthy women (41% and 29%, P = 0.012). Duration of implant was associated with a higher frequency of anti-ssDNA antibodies (P = 0.03) but not with ANA or rheumatoid factor. No other significant differences in the frequencies of autoantibodies were observed in silicone breast implant-exposed women. Antisilicone antibodies were not found in any sample. CONCLUSION: We found no increased frequency of any immunologic abnormalities in women exposed to silicone breast implants, except for anti-ssDNA, which has unknown clinical relevance.

A connective tissue disease screening questionnaire for population studies.

To develop a technique to screen populations for potential connective tissue disease (CTD), we mailed a 30-item questionnaire to 253 randomly selected patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease (MCTD), or Sjögren's syndrome and to 340 randomly selected control subjects. The response rate after four mailings was 71% for case subjects and 54% for control subjects. Test-retest reliability for detection of any CTD was 0.82. Sensitivity for specific CTDs was 83 to 96% and specificity was 83 to 93%. The positive predictive value for any CTD (assuming an overall prevalence of 1.3%) was 5.5%; negative predictive value was 99.7%. The CTD Screening Questionnaire has high sensitivity and specificity for screening large populations.

Some patients with primary antiphospholipid syndrome have increased circulating CD5+ B cells that correlate with levels of IgM antiphospholipid antibodies.

Antibodies against bromelain-treated erythrocytes occurring in normal mice are germline gene-encoded IgM natural autoantibodies that are secreted by CD5+ B cells, and react primarily with phosphatidylcholine (PTC), but may crossreact with cardiolipin (aCL). Some of the IgM antiphospholipid antibodies (aPL) present in patients with the recently described primary antiphospholipid syndrome (PAPS) also react with PTC and could thus be natural autoantibodies akin to those found in mice. Patients with PAPS (n = 20) were found to have increased total B cells, as well as CD5 + B cells, in their peripheral blood, but normal total lymphocytes, as well as CD4 and CD8 T lymphocytes, compared to normal controls. The 6 PAPS patients with increased CD5+ B cells were found to have increased levels of IgM aPL, including aPTC. In them we also found a correlation between the number of CD5+ B cells and the levels of IgM aCL. Our findings suggest that within the family of aPLs present in patients with PAPS there may be some that could be IgM natural autoantibodies secreted by CD5+ B cells.

Autoantibody testing in patients with silicone implants.

The preceding evidence suggests that only those women with SBI who develop definite CTD or CTD-like symptoms should be tested for autoantibodies. Women with SBI who develop nonautoimmune diseases or who are asymptomatic should not be tested. These recommendations also apply for subjects with other silicone implants. Until other information becomes available from carefully controlled studies, patients should be evaluated and managed for disease without considering whether he or she has silicone implants.