Tumour necrosis factor inhibitors and serious infections in reproductive-age women and their offspring: a narrative review.

Tumour necrosis factor inhibitors (TNFi) are commonly used to treat patients with chronic inflammatory diseases, and function by inhibiting the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α). Although beneficial in reducing disease activity, they are associated with an increased risk of serious infections. Data on the risk of serious infections associated with TNFi use during the reproductive years, particularly in pregnancy, are limited. For pregnant women, there is an additional risk of immunosuppression in the offspring as TNFi can be actively transported across the placenta, which increases in the second and third trimesters. Several studies have explored the risk of serious infections with TNFi exposure in non-pregnant and pregnant patients and offspring exposed in utero, indicating an increased risk in non-pregnant patients and a potentially increased risk in pregnant patients. The studies on TNFi-exposed offspring showed conflicting results between in utero TNFi exposure and serious infections during the offspring's first year. Further research is needed to understand differential risks based on TNFi subtypes. Guidelines conditionally recommend the rotavirus vaccine before 6 months of age for offspring exposed to TNFi in utero, but more data are needed to support these recommendations because of limited evidence. This narrative review provides an overview of the risk in non-pregnant patients and summarizes evidence on how pregnancy can increase vulnerability to certain infections and how TNFi may influence this susceptibility. This review focuses on the evidence regarding the risk of serious infections in pregnant patients exposed to TNFi and the risk of infections in their offspring.

Use of disease-modifying anti-rheumatic or anti-tumour necrosis factor drugs and risk of hospitalized infection in ankylosing spondylitis.

OBJECTIVE: To assess the risk of hospitalized infection among initiators of disease-modifying anti-rheumatic drugs (DMARDs) and/or anti-tumour necrosis factor (anti-TNF) agents in ankylosing spondylitis (AS). METHOD: We studied AS patients, new users of anti-TNF drugs and/or DMARDs between 1 January 2001 and 31 December 2011. Cohort entry was defined as the date of first prescription of any of these drugs. We used Cox regression with three time-varying drug exposures: current use of DMARDs without biologics, current use of anti-TNF agents alone or in combination with DMARDs (anti-TNF ± DMARDs), and current non-use. Models were adjusted for baseline patient sociodemographic characteristics, comorbidity, outpatient visits and procedures, previous infection, non-steroidal anti-inflammatory drugs, and corticosteroids. Hospitalized infection was defined on the basis of hospitalization discharge diagnoses (primary or non-primary) coding for infection. RESULTS: The cohort included 747 AS patients, with a mean age of 51.1 years (sd 14.6), and 466 (62.4%) were men. During the median follow-up of 1.98 years, 57 hospitalized infections occurred, for an incidence rate of 2.9/100 person-years. The adjusted hazard ratio of infection (relative to unexposed) was 1.00 [95% confidence interval (CI) 0.47-2.11] for the anti-TNF ± DMARDs group and 0.96 (95% CI 0.45-2.04) for DMARDs alone. Use of healthcare, corticosteroids, and previous hospitalized infections were associated with infection. CONCLUSION: We found no clear evidence that the risk of hospitalized infection was linked to DMARD and/or anti-TNF drug use. Because of scarce published literature on infection risk in AS patients, our results have important implications for clinicians.

Breast cancer in systemic lupus erythematosus (SLE): receptor status and treatment.

Objective There is a decreased risk of breast cancer in systemic lupus erythematosus (SLE) versus the general population; little is known regarding the receptor status of breast cancers in SLE, or treatment. Methods Breast cancer cases occurring after SLE diagnosis were ascertained through linkage with tumor registries. We determined breast cancer positivity for estrogen receptors (ER), progesterone receptors (PR), and/or Human Epidermal Growth Factor Receptor 2 (HER2), as well as cancer treatment. Results We obtained information on ER, PR, and/or HER2 status for 63 SLE patients with breast cancer. Fifty-three had information on ER and/or PR status; 36 of these (69%) were ER positive. Thirty-six of the 63 had information on HER2 status; of these, 26 had complete information on all three receptors. Twenty-one of these 26 (81%) were HER2 negative; seven of 26(27%) were triple negative. All but one patient underwent surgery; 11.5% received both non-tamoxifen chemotherapy and radiotherapy, 16.4% radiotherapy without non-tamoxifen chemotherapy, and 14.7% received non-tamoxifen chemotherapy without radiotherapy. Conclusion ER positivity was similar to historical general population figures, with a trend toward a higher proportion of triple-negative breast cancers in SLE (possibly reflecting the relatively young age of our SLE patients).

Disease characterization of systemic lupus erythematosus (SLE) patients in Quebec.

Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an array of organ manifestations that can appear during flares and disappear during remissions. The objectives of this study were: (i) to examine SLE manifestation groups longitudinally in an SLE cohort; and (ii) to assess the association between early antimalarial treatment and renal manifestations. Methods Seven SLE manifestation groups-cutaneous, hematologic, lung, musculoskeletal, neuropsychiatric, serositis, renal-were tracked using Kaplan-Meier survival curves in an incident SLE cohort from Quebec health administrative data ( n = 2010). A subgroup with provincial drug insurance coverage was followed over time to examine the association between early antimalarial treatment (within three months after SLE diagnosis) and renal manifestations using a Cox proportional hazards survival model. Results Cutaneous manifestations was the most common manifestation at SLE diagnosis (30.0%, 95% CI: 27.7-32.2%). About two-thirds (66.2%, 95% CI: 63.4-68.9%) of patients had evidence of at least one SLE manifestation at diagnosis, which increased to 87.2% (95% CI: 84.2-90.3%) by the end of follow-up. After adjusting for age, sex, early concomitant systemic steroid therapy, Charlson comorbidity index, primary care visits in the year prior and other SLE manifestations at baseline, no statistically significant association was established between antimalarial therapy and renal manifestations. Conclusion This study provides insight regarding organ manifestations within a population-based sample. Most patients identified with SLE had other diagnostic evidence that supports an underlying diagnosis of SLE. No protective effects for antimalarial agents against renal manifestations could be established in this population-based cohort.

Breast cancer in systemic lupus.

Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug exposures over time. In univariate and multivariate models, the principal factor associated with breast cancers was older age at cohort entry. Conclusions There was little evidence that breast cancer risk in this SLE sample was strongly driven by any of the clinical factors that we studied. Further search for factors that determine the lower risk of breast cancer in SLE may be warranted.

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.

What investigations are needed to optimally monitor for malignancies in SLE?

OBJECTIVE: The overall cancer incidence risk in systemic lupus erythematosus (SLE) is approximately 15%-20% more than in the general population. Nevertheless, to date, the optimal malignancy screening measures in SLE remain undefined. Our objective is to determine what investigations are needed to optimally monitor for malignancies in SLE in order to inform upcoming Canadian Rheumatology Association recommendations. METHODS: We conducted a systematic search looking at three scientific sources, Embase, Medline and Cochrane, in an attempt to identify cancer screening recommendations for patients with SLE. We used a filter for observational studies and included articles published in 2000 and onward. RESULTS: The initial search strategy led to 986 records. After removal of duplicates and articles unrelated to SLE, we were left with 497 titles. From those, 79 research articles on cancer incidence in SLE were isolated and reviewed. Of the 79 original research papers, 25 offered screening recommendations, 14 suggested additional cancer screening whereas 11 studies simply promoted adherence to general population screening measures. The suggestions for more rigorous screening included recommending human papilloma virus testing in addition to routine cervical screening, and/or that cervical screening should be performed annually and/or suggested urine cancer screening in SLE patients with a history of cyclophosphamide exposure. CONCLUSIONS: We found no original research studies directly comparing cancer screening strategies in SLE. Generally, authors recommend adherence to general population screening measures, particularly cervical screening. This, possibly with adding targeted screening in special cases (e.g. annual urine cytology in patients with prior cyclophosphamide exposure, and considering existing lung cancer screening guidelines for past heavy smokers), may be a reasonable approach for cancer screening in 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.

Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS).

UNLABELLED: We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors. INTRODUCTION: Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50 + . METHODS: We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture. RESULTS: Among 6,645 subjects, 192 (2.9%) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7%) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95% confidence intervals (CI), 1.48-2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32-2.14). CONCLUSIONS: Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.

Neurodevelopmental disorders in children born to mothers with systemic lupus erythematosus.

Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring.

The French-Canadian validation of a disease-specific, patient-reported outcome measure for lupus.

OBJECTIVES: The objective of this paper is to perform the cross-cultural validation of the French version of the LupusPRO, a disease-targeted patient-reported outcome measure, among systemic lupus erythematosus (SLE) patients in Canada. METHODS: The French version of the LupusPRO and the MOS SF-36 were administered; demographic, clinical and serological characteristics were obtained. Disease activity (SELENA-SLEDAI and the Lupus Foundation of America definition of flare) and damage (SLICC/ACR SDI) were assessed. Physician disease activity and damage assessments were ascertained using visual analog scales. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity, damage or health status) and known group validity were tested. RESULTS: A total of 99 French-Canadian SLE patients participated (97% women, mean (SD) age 45.2 (14.5) years). The median (IQR) SELENA-SLEDAI and SDI were 3.5 (6.0) and 1.0 (2.0), respectively. The ICR of the LupusPRO domains ranged from 0.81 to 0.93 (except for lupus symptoms, procreation and coping), while TRT ranged from 0.72 to 0.95. Convergent and discriminant validity, criterion validity and known group validity against disease activity, damage and health status measures were observed. Confirmatory factor analysis showed a good fit. CONCLUSION: The LupusPRO has fair psychometric properties among French-Canadian patients with SLE.

Health Canada advisory impacts on the prevalence of oral codeine use in the Pediatric Canadian population: comparative study across provinces.

Health Canada (HC) has, since 2013, issued safety alerts restricting the use of codeine-containing drugs among breastfeeding women and children/adolescents under 18 years of age. These products are linked to breathing problems among ultra-rapid CYP2D6 metabolizers and early use of opioid can lead to future opioid misuse. Using a multi-province population-based cohort study, we estimate the impact of federal safety alerts on annual rates of codeine use in the Canadian pediatric population. We analyzed data from 8,156,948 children/adolescents in five Canadian provinces between 1996 and 2021, using a common protocol. Children/adolescents were categorized as: ≤ 12 years (children) or > 12 years (adolescents). We defined codeine exposure by ≥ 1 prescription filled for codeine alone or combined with other medications. For both age categories, we obtained province-specific codeine prescription filling rates per calendar year by dividing the number of children/adolescents with ≥ 1 codeine prescription filled by the number of person-time. Annual rates of codeine use per 1000 persons vary by province from 3.0 (Quebec) to 10.1 (Manitoba) in children, and from 5.5 to 51.3 in adolescents. After the 2013 HC advisory, exposure decreased in all provinces (adjusted level change from - 0.6 to - 18.4%) in children and from - 2.1 to - 17.9% in adolescents after the 2016 advisory. Annual rates declined over time in all provinces, following HC safety alerts specific to each of the two age categories.

Biologic disease-modifying anti-rheumatic drugs and the risk of non-vertebral osteoporotic fractures in patients with rheumatoid arthritis aged 50 years and over.

UNLABELLED: Prevention of bone mineral density loss in rheumatoid arthritis (RA) has been associated with use of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, in this study, we could not demonstrate a reduction in the risk of non-vertebral fractures. Additional research is required to clarify the impact of biologic DMARDs on fracture risk in RA. INTRODUCTION: Small studies have suggested biologic DMARDs preserve bone mineral density at 6-12 months. Our objective was to determine the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures in RA subjects aged ≥50 years. METHODS: A nested case-control study was conducted using Quebec physician billing and hospital discharge data. RA subjects were identified from International Classification of Disease-9/10 codes in billing and hospitalisation data and followed from cohort entry until the earliest of non-vertebral osteoporotic fracture, death, or end of study period. Controls were matched to cases (4:1 ratio) on age, sex, and date of cohort entry. Biologic DMARD exposure was defined as being on treatment for ≥180 days pre-fracture (index). Conditional logistic regression was used, adjusting for indicators of RA severity, comorbidity, drugs influencing fracture risk, and measures of health care utilisation. RESULTS: Over the study period, 1,515 cases were identified (6,023 controls). The most frequent fracture site was hip/femur (42.3%). In total, 172 subjects (49 cases and 123 controls) were exposed to biologic DMARDs. The median duration of exposure was 735 (interquartile range (IQR), 564) and 645 (IQR, 903) days in cases and controls, respectively. We were unable to demonstrate an association between biologic DMARDs and fracture risk (odds ratio, 1.03; 95% confidence interval, 0.42-2.53). RA duration significantly increased the fracture risk. CONCLUSIONS: Despite the positive impact of biologic DMARDs on bone remodelling observed in small studies, we were unable to demonstrate a reduction in the risk of non-vertebral osteoporotic fractures in older adults with RA.

Breast cancer in systemic lupus erythematosus.

OBJECTIVE: Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries. METHODS: Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year. RESULTS: We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as 'carcinoma not otherwise specified'. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.14] and for the 'special' subtypes it was age (OR 1.06, 95% CI 1.01-1.10) and SLE duration (OR 1.05, 95% CI 1.00-1.11). CONCLUSIONS: Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.

The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort.

OBJECTIVES: Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). METHODS: Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. RESULTS: Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6-8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p < 0.05): juvenile-onset lupus (2.2 [1.1-4.7]), number of ACR SLE criteria (1.4 [1.1-1.7], baseline body mass index (BMI) (1.1 [1.0-1.1]), psychosis (3.4 [1.2-9.9]), aboriginal race (3.2 [1.5-6.7]), anti-Smith (2.6 [1.2-5.4]), erythrocyte sedimentation rate >25 mm/hr (1.9 [1.1-3.4]), proteinuria >0.5 g/d (4.2 [1.9-9.3], and SLAM-2 score (1.1 [1.0-1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. CONCLUSIONS: The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.

Decreased breast cancer risk in systemic lupus erythematosus: the search for a genetic basis continues.

PURPOSE: Recent work has demonstrated an important decrease in breast cancers for women with systemic lupus erythematosus (SLE). The reason behind this phenomenon is unknown. Our purpose was to explore whether the single nucleotide polymorphisms (SNPs) predisposing to SLE might be protective against breast cancer (in women in the general population). METHODS: We focused on loci relevant to 10 SNPs associated with SLE (with a p value of <10(-9)). We determined whether we could establish a decreased frequency of these SNPs in breast cancer cases versus controls, within the general population. To do this we used a large breast cancer genome-wide association study (GWAS) dataset, involving 3,659 breast cancer cases and 4,897 controls. These subjects were all primarily of European ancestry. RESULTS: The population-based GWAS breast cancer data we examined suggested little evidence for important associations between breast cancer and SLE-related SNPs. Within the general population GWAS data, a cytosine(C) nucleotide substitution at rs9888739 (on chromosome 16p11.2) showed a very weak inverse association with breast cancer. The odds ratio (OR) for the rs9888739-C allele was 0.907551 (p value 0.049899) in the GWAS breast cancer sample, compared to controls. There was a slightly stronger, positive, association with breast cancer for rs6445975-G (Guanine) on chromosome 3p14.3, with a breast cancer OR of 1.0911 (p value 0.0097). CONCLUSIONS: Within this large breast cancer dataset, we did not demonstrate important associations with 10 lupus-associated SNPs. If decreased breast cancer risk in SLE is influenced by genetic profiles, this may be due to complex interactions and/or epigenetic factors.

Something's missing here: a look at the quality of rheumatology referral letters.

A convincing body of evidence points to an early window of opportunity for the treatment of rheumatoid arthritis. However, data indicate that in many cases, this window of opportunity is missed. Once a patient does present to their primary care provider, important additional delays in rheumatology assessment can occur. To report the results of our study assessing referral letters to rheumatologists, we examined referral letters received over a one-year period by one full-time rheumatologist practicing at a tertiary-care center. We found only a small percentage of referral letters made mention of the pattern of joint involvement. Just 17% of consults indicated symptom duration. Only 2% mentioned any circadian rhythm of symptoms (such as morning stiffness), and only 6% provided information about functional status. Almost two-thirds (62%) of consults specified only 'joint pain' in the referral letter. We provide objective evidence that referral letters sent to rheumatologists are often lacking in key elements of the medical history. This lack of information means that appropriate triage of referrals by rheumatologists is very difficult. As a response to this, we have developed, with family physicians and rheumatologists, a standardized referral template which is being pilot-tested. Our ultimate goal is to improve wait times for patients with urgent conditions such as inflammatory arthritis.

Prostate cancer in systemic lupus erythematosus.

Our research objective was to estimate prostate cancer risk in systemic lupus erythematosus (SLE), relative to the age-matched general population. A progressive literature review was performed to identify SLE cohort studies with cancer registry linkage for cancer ascertainment. Data were pooled from four studies of large SLE cohorts who met these criteria. The total number of prostate cancers observed was derived by pooling the incident cases across all studies. The total expected number of prostate, derived from applying appropriate general population cancer incidence data to the observed number of patient-years of follow-up for each study, was similarly determined. The parameter of interest was the standardized incidence ratio (SIR), the ratio of observed to expected malignancies. The four studies together provided a pool of 6,068 male SLE patients observed for a total of 38,186 patient-years (mean 6.3 years). Within these subjects, 80 prostate cancers were observed. In each contributing study, the number of cancers expected far exceeded that observed. The pooled SIR estimate for prostate cancer risk in males with SLE, compared to the general population, was 0.72 (95% CI 0.57, 0.89). These data suggest a decreased risk of prostate cancer in SLE; more definite conclusions require additional data. As alterations in androgen pathways can potentially alter prostate risk, a lower risk of prostate cancer in SLE could possibly be due to low hypoadrenergic states which some believe may occur in men with SLE; underlying genetic factors could also be at play. Further study of these issues in large cohorts is needed.

Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis.

BACKGROUND: An increased lymphoma risk is well documented in systemic lupus (SLE). Less attention has been focused on women's cancers, even though SLE affects mostly females. Our objective was to estimate the risk of breast, ovarian, and endometrial cancers in SLE, relative to the general population. METHODS: Data were included from five recent studies of large SLE cohorts. The number of cancers observed was determined for each cancer type. The expected number of malignancies was ascertained from general population data. The parameter of interest was the standardised incidence ratio (SIR), the ratio of observed to expected malignancies. RESULTS: The five studies included 47,325 SLE patients (42,171 females) observed for 282,553 patient years. There were 376 breast cancers, 66 endometrial cancers, and 44 ovarian cancers. The total number of cancers observed was less than that expected, with SIRs of 0.76 (95% CI: 0.69, 0.85) for breast cancer, 0.71 (95% CI: 0.55, 0.91) for endometrial cancer, and 0.66 (95% CI: 0.49, 0.90) for ovarian cancer. CONCLUSIONS: Data strongly support a decreased risk of breast, ovarian, and endometrial cancers in SLE. This may be due to inherent differences in women in SLE (vs the general population) regarding endogenous oestrogen, other medications, and/or genetic make-up.

The influence of systemic glucocorticoid therapy upon the risk of non-serious infection in older patients with rheumatoid arthritis: a nested case-control study.

BACKGROUND: Glucocorticoid therapy is strongly associated with an elevated risk of serious infections in patients with rheumatoid arthritis (RA). The association between glucocorticoids and common non-serious infections (NSI) is not well studied. METHODS: A cohort of 16 207 patients with RA aged over 65 years was assembled using administrative data from Quebec. Glucocorticoid and disease-modifying antirheumatic drug (DMARD) therapy were identified from drug dispensing records. NSI cases were defined as first occurrence of a community physician billing code for infection or community-dispensed anti-infectives. A nested case-control analysis was performed considering drugs dispensed within 45 days of the index date, adjusting for age, sex, markers of disease severity, DMARD and comorbidity. RESULTS: For 13 634 subjects, a NSI occurred during 28 695 person-years of follow-up, generating an incidence rate of 47.5/100 person-years. The crude rate of NSI in glucocorticoid-exposed and unexposed person time was 52.4 and 38.8/100 person-years, respectively. Glucocorticoid therapy was associated with an adjusted RR of 1.20 (95% CI 1.15 to 1.25). A dose response was seen, the adjusted RR increasing from 1.10 (<5 mg prednisolone/day) to 1.85 for doses greater than 20 mg/day. All glucocorticoid risk estimates (including <5 mg/day) were higher than that seen for methotrexate (adjusted RR 1.00; 0.95 to 1.04). CONCLUSION: Glucocorticoid therapy is associated with an increased risk of NSI. The magnitude of risk increases with dose, and is higher than that seen with methotrexate, although residual confounding may exist. While the RR is low at 1.20, the absolute risk is high with one additional infection seen for every 13 patients treated with glucocorticoids for 1 year.