Specific systemic lupus erythematosus disease manifestations in the six months prior to conception are associated with similar disease manifestations during pregnancy.

Past studies have focused on aggregate lupus disease activity during pregnancy and have produced conflicting results. Our study evaluated lupus activity based on involvement of five specific organ systems during the six months prior to conception and during pregnancy. We assessed 147 pregnancies among 113 women followed at Brigham and Women's Lupus Center, 1990-2013. Organ-specific activity included hematologic disorder, nephritis, skin disease, arthritis, and serositis. We hypothesized that the presence of organ-specific activity six months prior to conception would increase the risk for that same type of activity during pregnancy. Our study population was 68% white; 100% had a positive ANA and 30% had a history of nephritis. Among women with organ-specific lupus activity during the six months before conception, the crude odds for the same type of activity during pregnancy was 7.7- to 32.5-fold higher compared to women without that type of activity immediately before conception. An adjusted logistic regression model also indicated significantly higher odds of organ-specific activity during pregnancy if that type of activity were present six months before conception. Approaching lupus based on specific organ systems may be a useful way for women and their physicians to consider the potential risk for disease activity during pregnancy.

Development of SLE among "potential SLE" patients seen in consultation: long-term follow-up.

OBJECTIVE: To identify factors associated with development of systemic lupus erythematosus (SLE) among patients evaluated at a tertiary care Lupus Center for potential SLE. METHODS: We identified patients first seen at the Brigham and Women's Hospital Lupus Center between 1 January 1992 and 31 December 2012 and thought to have potential SLE by a board-certified rheumatologist. All had 1-3 SLE ACR criteria at initial visit and > 2 follow-up visits ≥ 3 months apart. We reviewed medical records through 15 May 2013 for: SLE signs and symptoms, autoimmune serologies, prescriptions and diagnoses by board-certified rheumatologists. Bivariable analyses and multivariable logistic regression models were used to identify independent predictors of developing SLE. RESULTS: Two hundred and sixty four patients met inclusion criteria. At initial visit, mean age was 39.2 (SD 12.4) years, 94% were female and 67% white. Mean number of SLE ACR criteria was 2.7 (SD 1.0) and 88% were antinuclear antibody (ANA) positive at initial consultation. Mean follow-up time was 6.3 (SD 4.3) years and 67% were prescribed hydroxychloroquine in follow-up. At most recent visit, 56 (21%) had been diagnosed with SLE; 47 (18%) were thought not to have SLE and 161 (61%) were still considered to have potential SLE. In multivariable regression models, oral ulcers (OR 2.40, 95% CI 1.03-5.58), anti-dsDNA (OR 2.59, 95% CI 1.25-5.35) and baseline proteinuria or cellular casts (OR 16.20, 95% CI 1.63-161.02) were independent predictors of developing SLE. The most common other final diagnoses included fibromyalgia, Sjögren's syndrome, mixed connective tissue disease and cutaneous lupus. CONCLUSION: Among patients with potential SLE at initial consultation, 21% were diagnosed with definite SLE within 6.3 years. Oral ulcers, anti-dsDNA and proteinuria or cellular casts were independent predictors of developing definite SLE. A better means of accurately identifying those who will develop SLE among those presenting with potential disease is necessary.

Clinical manifestations and survival among adults with (SLE) according to age at diagnosis.

OBJECTIVES: The objective of this paper is to determine the effect of clinical and laboratory manifestations, and medication prescribing, on survival according to patient age at diagnosis in a large academic systemic lupus erythematosus (SLE) cohort. METHODS: We identified SLE patients with a diagnosis at age ≥18, seen between 1970 through 2011, and with more than two visits to our lupus center. Data collection included SLE manifestations, serologies, other laboratory tests, medications, dates, and causes of death. We examined characteristics of those diagnosed before age 50 (adult onset) compared to those diagnosed at or after age 50 (late onset) using descriptive statistics. We used Kaplan-Meier curves with log rank tests to estimate five- and 10-year survival in age-stratified cohorts. Predictors of 10-year survival were assessed using Cox regression models, adjusted for calendar year, race/ethnicity, sex, lupus nephritis, and medication use. RESULTS: Of 928 SLE patients, the mean age at diagnosis was 35. Among the adult-onset group, there was significantly higher prevalence of malar rashes and lupus nephritis. Glucocorticoids, azathioprine, mycophenolate, and cyclophosphamide use were also more frequent in the adult-onset group compared to the late-onset group. Five-year survival rates were 99.5% and 94.9% and 10-year survival rates were 97.8% and 89.5%, among those diagnosed before and at or after age 50. In the entire cohort, increasing age at diagnosis, male sex, and black race were statistically significant predictors of reduced 10-year survival. Compared to those diagnosed before age 50, the late-onset group had a multivariable-adjusted hazard ratio for 10-year risk of death of 4.96 (95% CI 1.75-14.08). The most frequent cause of known death was a lupus manifestation, followed by cardiovascular disease and infection. CONCLUSIONS: In our cohort, several demographic features, SLE manifestations, and medication prescribing differed between those with adult-onset and late-onset SLE. Ten-year survival rates were high for both groups, but relatively lower among late-onset patients. A lupus manifestation as the cause of death was more common among adult-onset compared with late-onset patients.

Designing an intervention for women with systemic lupus erythematosus from medically underserved areas to improve care: a qualitative study.

OBJECTIVE: Systemic lupus erythematosus (lupus) disproportionately affects women, racial/ethnic minorities and low-income populations. We held focus groups for women from medically underserved communities to discuss interventions to improve care. METHODS: From our Lupus Registry, we invited 282 women, ≥18 years, residing in urban, medically underserved areas. Hospital-based clinics and support groups also recruited participants. Women were randomly assigned to three focus groups. Seventy-five-minute sessions were recorded, transcribed and coded thematically using interpretative phenomenologic analysis and single counting methods. We categorized interventions by benefits, limitations, target populations and implementation questions. RESULTS: Twenty-nine women with lupus participated in three focus groups, (n = 9, 9, 11). 80% were African American and 83% were from medically underserved zip codes. Themes included the desire for lupus education, isolation at the time of diagnosis, emotional and physical barriers to care, and the need for assistance navigating the healthcare system. Twenty of 29 participants (69%) favored a peer support intervention; 17 (59%) also supported a lupus health passport. Newly diagnosed women were optimal intervention targets. Improvements in quality of life and mental health were proposed outcome measures. CONCLUSION: Women with lupus from medically underserved areas have unique needs best addressed with an intervention designed through collaboration between community members and researchers.

Identification and validation of lupus nephritis cases using administrative data.

Large administrative databases such as Medicaid billing databases could be used to study care and outcomes of lupus nephritis if these patients could be correctly identified from claims data. We aimed to develop and validate an algorithm for the correct identification of cases of lupus nephritis using ICD-9 billing codes. We used the Research Patient Data Resource query tool at our institution to identify patients with potential lupus nephritis. We compared four ICD-9 code based strategies, identifying patients seen between 2000 and 2007 with Medicaid medical insurance with greater than two claims for a diagnosis of SLE (ICD-9 code 710.0) and a combination of greater than two nephrologist visits and/or renal ICD-9 codes. We assessed performance using the positive predictive value. Two hundred and thirty four subjects were identified and medical records reviewed. Our third strategy, based on a combination of lupus and renal ICD-9 codes and nephrologist encounter claims, had the highest positive predictive value (88%) for the identification of patients with lupus nephritis. This strategy may offer a sound method of identifying patients with lupus nephritis for health services research in addition to serving as a model for using claims data as a way to better understand rare diseases such as lupus.

Cost-effectiveness of abatacept in patients with moderately to severely active rheumatoid arthritis and inadequate response to methotrexate.

OBJECTIVE: To assess cost-effectiveness of abatacept in patients with moderately to severely active RA and inadequate response to MTX. METHODS: We developed a simulation model to depict progression of disability [in terms of the HAQ Disability Index (HAQ-DI)] in women aged 55-64 yrs with moderately to severely active RA and inadequate response to MTX. At model entry, patients were assumed to receive either only MTX or MTX plus abatacept. Patients were then tracked from model entry until death. Future health-state utilities and medical-care costs (except study therapy) were estimated based on predicted values of the HAQ-DI. The model was estimated using data from a Phase III clinical trial of abatacept plus various secondary sources. Cost-effectiveness was expressed in terms of incremental cost (2006 US$) per quality-adjusted life-year (QALY) gained over alternatively 10 yrs and a lifetime. Costs and health effects were both discounted at 3% annually. RESULTS: Over 10 yrs, abatacept would yield 1.2 additional QALYs (undiscounted) per patient (4.6 vs 3.4 for MTX) at an incremental (discounted) cost of $51,426 ($103,601 vs $52,175, respectively); over a lifetime, corresponding figures were 2.0 QALYS (6.8 vs 4.8) and $67,757 ($147,853 vs $80,096). Cost-effectiveness was [mean (95% CI)] $47,910 ($44,641, $52,136) per QALY gained over 10 yrs and $43,041 ($39,070, $46,725) per QALY gained over a lifetime. Findings were robust in sensitivity analyses. CONCLUSION: Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to MTX.

High sensitivity, specificity and predictive value of the Connective Tissue Disease Screening Questionnaire among urban African-American women.

The Connective Tissue Disease Screening Questionnaire (CSQ), developed to screen populations for SLE and other CTDs, has been validated in a predominantly Caucasian population with hospital-based controls. We aimed to test the performance characteristics of the CSQ in an urban, predominantly African-American population. The CSQ was administered by interview to women recruited for a study of environmental risk factors and SLE, including 99 cases with SLE validated by medical record review and 202 healthy controls recruited from the community. Overall, 88% of subjects had African heritage, 6% were Hispanic and 4% were non-Hispanic Caucasian. Controls were more likely to report African heritage than cases (91% versus 82%, P = 0.001). Sensitivity for detecting SLE was 88% and specificity was 91%. In this study, where the prevalence of SLE was 33%, predictive value of a positive CSQ was 82% and predictive value of a negative CSQ was 94%. The CSQ has slightly lower sensitivity but greater specificity for SLE in an urban, predominantly African-American population with community-based controls compared with a Caucasian population with hospital-based controls. These results suggest that the CSQ has adequate sensitivity and specificity and could be used in population studies to screen African-American women for SLE.

The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status.

We have recently described the association between rheumatoid arthritis and a coding single-nucleotide polymorphism in the intracellular protein tyrosine phosphatase, PTPN22. The disease-associated polymorphism, 1858 C/T (rs2476601), encodes an amino-acid change (R620W) in one of four SH3 domain binding sites in the PTPN22 molecule. We have now extended our initial studies to address three questions: (1) Is the association with rheumatoid arthritis limited to rheumatoid factor (RF) positive disease? (2) Does homozygosity for PTPN22 R620W substantially increase disease susceptibility? (3) Is there an interaction between PTPN22 and the rheumatoid arthritis (RA)-associated HLA-DRB1 shared epitope alleles? A total of 1413 Caucasian rheumatoid arthritis patients and 1401 Caucasian controls were genotyped. The results support the view that PTPN22 was strongly and preferentially associated with RF positive disease (OR=1.75, 95% CI 1.46-2.10, P=1.3 x 10(-9)). The PTPN22 risk allele was not significantly associated with RF negative disease (OR=1.19, 95% CI 0.92-1.53, P=0.18), although a very weak association cannot be completely excluded. There was a strong dose effect on disease risk; two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA (OR=4.57, 95% CI 2.35-8.89). There was no evidence of a genetic association between PTPN22 and HLA susceptibility alleles.

Medical aspects of rheumatoid arthritis. Diagnosis and treatment.

Rheumatoid arthritis commonly affects the hand and wrist. The differential diagnosis of inflammatory conditions affecting the hand is broad. A proper diagnostic approach necessitates a thoughtful interpretation of the presenting clinical features, laboratory tests, synovial fluid analysis, and radiographic data. Early, aggressive medical therapy with a combination of antiinflammatory and remittive agents may reduce mortality in selected patients and prevent the consequences of uncontrolled synovial proliferation. Despite proper medical therapy, joint destruction often results and surgical treatment of the joint deformities may be required for restoration of function.

Chronic inflammatory arthritis after treatment with high-dose interleukin-2 for malignancy.

Interleukin-2 (IL-2) immunotherapy resulted in the development of inflammatory arthritis in three male patients with metastatic cancer. Two patients developed a clinical picture consistent with rheumatoid arthritis. A third patient with a remote history of Reiter's syndrome developed a recrudescence of an inflammatory arthritis after treatment with IL-2. The clinical, laboratory, and histologic data on the patients and the potential pathophysiologic mechanisms are discussed.

Treatment of early Lyme disease.

PURPOSE: To compare the safety and efficacy of azithromycin, amoxicillin/probenecid, and doxycycline for the treatment of early Lyme disease, to identify risk factors for treatment failure, and to describe the serologic response in treated patients. PATIENTS AND METHODS: Fifty-five patients with erythema migrans and two patients with flu-like symptoms alone and fourfold changes in antibody titers to Borrelia burgdorferi were randomized to receive (1) oral azithromycin, 500 mg on the first day followed by 250 mg once a day for 4 days; (2) oral amoxicillin 500 mg and probenecid 500 mg, three times a day for each for 10 days; or (3) doxcycline, 100 mg twice a day for 10 days. If symptoms were still present at 10 days, treatment was extended with amoxicillin/probenecid or doxycycline for 10 more days. Evaluations were done at study entry and 10, 30, and 180 days later. RESULTS: Three of the patients who initially had symptoms suggestive of spread of the spirochete to the nervous system, one from each antibiotic treatment group, subsequently developed neurologic abnormalities, but symptoms in the other 54 patients resolved within 3 to 30 days after study entry. Six of the 19 patients (32%) (95% confidence interval, 13% to 57%) given amoxicillin/probenecid developed a drug eruption, whereas none of the patients given azithromycin or doxycycline had this complication. The presence of dysesthesias at study entry was the only risk factor significantly associated with treatment failure (p less than 0.001). By convalescence, 72% of the patients were seropositive, and 56% still had detectable IgM responses to the spirochete 6 months later. CONCLUSIONS: The three antibiotic regimens tested in this study were generally effective for the treatment of early Lyme disease, but the regimens differ in the frequency of side effects and in ease of administration.

Septic arthritis due to Listeria monocytogenes: report and review of the literature.

Septic arthritis due to Listeria monocytogenes is an uncommon infection amenable to antibiotic therapy along with open or closed drainage. We report successful antibiotic treatment of a prosthetic joint infection in a man with seropositive rheumatoid arthritis and present a review of the literature describing this specific infection.