Anti-SMN autoantibodies in mixed connective tissue disease are associated with a severe systemic sclerosis phenotype.

OBJECTIVES: The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis patients. The aim of this study was to compare phenotypic features of anti-U1RNP+ mixed connective tissue disease (MCTD) patients with and without anti-SMN aAbs. METHODS: A retrospective MCTD cohort was studied. Addressable laser bead immunoassay was used to detect specific anti-SMN aAbs with <300 mean fluorescence intensity (MFI) as normal reference range, 300-999 MFI as low-titre and ≥1000 MFI as high-titre positivity. Comparison of clinical features between anti-SMN+ and anti-SMN- subgroups used two-tailed Fisher's exact test, and logistic regression analyses. RESULTS: Sixty-six patients were included. Median age at MCTD diagnosis was 40.6 years, and duration of follow-up was 12 years. Based on the highest available titre, 39 (59%) were anti-SMN+: 10 (26%) had low titre and 29 (74%) had high titre. Anti-SMN+ patients had a higher frequency of fingertip pitting scars (anti-SMN+ 23% vs anti-SMN- 4%, p=0.04), lower gastrointestinal (GI) involvement (26% vs 4%, p=0.04), and myocarditis (16% vs 0%, p=0.04). The combined outcome of pitting scars and/or lower GI involvement and/or myositis and/or myocarditis was highest among high-titre anti-SMN+ patients: adjusted OR 7.79 (2.33 to 30.45, p=0.002). CONCLUSIONS: Anti-SMN aAbs were present in 59% of our MCTD cohort. Their presence, especially at high-titres, was associated with a severe systemic sclerosis (scleroderma) phenotype including myositis, myocarditis and lower GI involvement.

Myositis with prominent B cell aggregates may meet classification criteria for sporadic inclusion body myositis.

The objective of this study was to report the clinical, serological and pathological features of patients with autoimmune myositis other than dermatomyositis, who displayed both muscle weakness on physical examination and prominent B cell aggregates on muscle pathology, defined as ≥ 30 CD20+ cells/aggregate. Specifically, the presence of a brachio-cervical inflammatory myopathies or a sporadic inclusion body myositis (sIBM) phenotype was recorded. Over a three-year period, eight patients were identified from two university neuropathology referral centers. Seven of 8 (88%) patients had an associated connective tissue disease (CTD): rheumatoid arthritis (n=3), systemic sclerosis (n=2), Sjögren's syndrome (n=1) and systemic lupus erythematosus (n=1), while one patient died on initial presentation without a complete serological and cancer investigation. A brachio-cervical phenotype, i.e. neck weakness, proximal weakness more than distal and shoulder abduction weakness greater than hip flexors, was seen in two patients (25%), while one patient had both proximal and diaphragmatic weakness. In contrast, an IBM-like clinical phenotype was seen in the last five patients (63%), who either had finger flexor weakness and/or quadriceps weakness ≤ 4 on the manual muscle testing MRC-5 scale. Although these 5 patients met at least one set of classification criteria for sIBM, an integrated clinico-sero-pathological approach argued against a diagnosis of sIBM. In summary, in a weak patient with myositis plus an associated CTD and lymphoid aggregates at muscle pathology, B cell predominant aggregates may represent a morphological biomarker against a diagnosis of sIBM.

Capillary pathology with prominent basement membrane reduplication is the hallmark histopathological feature of scleromyositis.

AIMS: We aim to perform ultrastructural and histopathological analysis of muscle biopsies from a large group of systemic sclerosis (SSc) patients, including some with early/mild SSc features, and examine whether capillary pathology differentiates 'scleromyositis' (SM) from other auto-immune myositis (AIM) subsets. METHODS: Muscle biopsies from a total of 60 SM patients and 43 AIM controls from two independent cohorts were examined by electron microscopy, collagen-4 immunofluorescence (Col4IF) and routine light microscopy. RESULTS: Ultrastructural examination revealed prominent capillary basement membrane (BM) reduplication (4+ layers in >50% of capillaries) in 65% of SM vs 0% of AIM controls (p < 0.001). In SM cases without prominent BM reduplication, capillary dilation was the most distinctive feature, present in 8% of capillaries in SM vs 2% in controls (p = 0.001). Accumulation of ensheathed pericyte processes was another characteristic feature of SM and closely correlated with the degree of BM reduplication (r = 0.833, p < 0.001). On light microscopy, BM marker Col4IF revealed more frequent capillary enlargement in SM than in controls (84% vs 21%, p < 0.001). SM cases were classified as non-inflammatory myopathy (36%), non-specific myositis (33%) or immune-mediated necrotizing myopathy (31%), but despite this histopathological heterogeneity, prominent BM reduplication remained a constant finding. In the 16 SM patients with early/mild SSc features, 63% showed prominent BM reduplication. CONCLUSIONS: These results show that capillary pathology, and in particular prominent capillary BM reduplication, is the hallmark histopathological feature of SM even in patients with early/mild SSc and support the concept of SM as an organ manifestation of SSc and a distinct subset of AIM.

Myositis with prominent B-cell aggregates causing shrinking lung syndrome in systemic lupus erythematosus: a case report.

BACKGROUND: Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE) characterized by decreased lung volumes and diaphragmatic weakness in a dyspneic patient. Chest wall dysfunction secondary to pleuritis is the most commonly proposed cause. In this case report, we highlight a new potential mechanism of SLS in SLE, namely diaphragmatic weakness associated with myositis with CD20 positive B-cell aggregates. CASE PRESENTATION: A 51-year-old Caucasian woman was diagnosed with SLE and secondary Sjögren's syndrome based on a history of pleuritis, constrictive pericarditis, polyarthritis, photosensitivity, alopecia, oral ulcers, xerophthalmia and xerostomia. Serologies were significant for positive antinuclear antibodies, anti-SSA, lupus anticoagulant and anti-cardiolopin. Blood work revealed a low C3 and C4, lymphopenia and thrombocytopenia. She was treated with with low-dose prednisone and remained in remission with oral hydroxychloroquine. Seven years later, she developed mild proximal muscle weakness and exertional dyspnea. Pulmonary function testing revealed a restrictive pattern with small lung volumes. Pulmonary imaging showed elevation of the right hemidiaphragm without evidence of interstitial lung disease. Diaphragmatic ultrasound was suggestive of profound diaphragmatic weakness and dysfunction. Based on these findings, a diagnosis of SLS was made. Her proximal muscle weakness was investigated, and creatine kinase (CK) levels were normal. Electromyography revealed fibrillation potentials in the biceps, iliopsoas, cervical and thoracic paraspinal muscles, and complex repetitive discharges in cervical paraspinal muscles. Biceps muscle biopsy revealed dense endomysial lymphocytic aggregates rich in CD20 positive B cells, perimysial fragmentation with plasma cell-rich perivascular infiltrates, diffuse sarcolemmal upregulation of class I MHC, perifascicular upregulation of class II MHC, and focal sarcolemmal deposition of C5b-9. Treatment with prednisone 15 mg/day and oral mycophenolate mofetil 2 g/day was initiated. Shortness of breath and proximal muscle weakness improved significantly. CONCLUSION: Diaphragmatic weakness was the inaugural manifestation of myositis in this patient with SLE. The spectrum of myologic manifestations of myositis with prominent CD20 positive B-cell aggregates in SLE now includes normal CK levels and diaphragmatic involvement, in association with SLS.

Risk of rheumatic disease in breast implant users: a qualitative systematic review.

BACKGROUND: Recent studies on the risk of rheumatic disease among breast implant users have reported conflicting results. The primary objective of this study was to provide a systematic and critical review of the literature on the association between breast implants and the risk of rheumatic disease. METHODS: A qualitative systematic review was conducted in PubMed, MEDLINE, EMBASE, EBM-Reviews and CINAHL Complete from database inception to June 23rd, 2021. Eligible papers were full-length articles in English or French reporting original data on the incident risk of rheumatic disease among individuals with and without breast implants. Data were extracted from published reports and appraised using the Newcastle-Ottawa scale. The main outcome was incident risk of systemic sclerosis (SSc), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), fibromyalgia and other rheumatic disorders and symptoms. RESULTS: Out of 3,425 identified citations, 86 met inclusion criteria. Two cohort studies suggested a two-fold increase in risk of SSc, whereas three case-control studies showed no increase in risk. Three cohort studies did not find an increased risk of incident and confirmed SS among breast implant users, however symptoms of sicca, myalgia and fatigue were reported more frequently. A meta-analysis of heterogenous studies reported a less than two-fold increase in risk of RA. Studies did not support an association with SLE. Insufficient evidence was available for autoimmune myositis and other rheumatic diseases. Implant rupture detected on imaging was not clearly associated with incident rheumatic disease, although no studies specifically examined the risk associated with acute/traumatic rupture. Little data was available on the safety of saline breast implants. Explantation often led to temporary improvement. CONCLUSIONS: Based on a small number of high-quality and methodologically robust studies, an association between breast implants and a small increase in risk of SSc and RA could not be excluded. Symptoms of sicca, myalgia and fatigue were reported more frequently among breast implant users. Overall, there remains much uncertainty in regard to the association between breast implants and the risk of incident rheumatic diseases. Individuals considering the placement of breast implants should be informed of this uncertainty. TRIAL REGISTRATION: This study was registered in the PROSPERO database (#CRD42019133616).

Does hydroxychloroquine improve patient reported outcomes in patients with lupus?

BACKGROUND: Hydroxychloroquine (HCQ) use is associated with less disease activity, flares, damage and improved survival in Systemic Lupus Erythematosus (SLE). However, its effect on patient reported health outcomes (PROs) such as quality of life (QOL) is not known. METHODS: International data from Study on Outcomes of Lupus (SOUL) from 2,161 SLE patients were compared by HCQ use. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC-ACR/SDI. QOL was evaluated using LupusPRO and Lupus Impact Tracker (LIT). Linear regression analyses were performed with LupusPRO summary scores health related HRQOL, non-health related NHRQOL and LIT as dependent and HCQ use as independent variable. Analyses were undertaken to test mediation of effects of HCQ use on QOL through disease activity. RESULTS: Mean age was 40.5 ± 12.8 years, 93% were women. Sixty-three (1363/2161) percent were on HCQ. On univariate analysis, HCQ use was associated with (a) better QOL (LupusPRO-HRQOL: ß 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: ß 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: ß -9.37, 95% CI -12.24, -6.50, P ≤ 0.001). On multivariate and mediational analyses, the effects of HCQ on QOL were indirectly and completely mediated through disease activity. CONCLUSIONS: HCQ use in SLE is associated with better patient reported health outcomes (LupusPRO-HRQOL and NHRQOL and impact on daily life), and the effects are mediated through disease activity. This information can facilitate patients and physician's communication with decision-making regarding the use of HCQ for SLE management.

Development and validation of the RACER (Readiness for Adult Care in Rheumatology) transition instrument in youth with juvenile idiopathic arthritis.

BACKGROUND: Current evidence suggests that many adolescents with juvenile idiopathic arthritis (JIA) do not successfully transfer to adult care, which can result in adverse health outcomes. Although a growing number of clinical programs have been designed to support healthcare transition, there is a lack of psychometrically sound instruments to evaluate their impact on development of transition-related knowledge and skills in youth with JIA. The purpose of this study was to develop and validate RACER (Readiness for Adult Care in Rheumatology), a self-administered instrument designed to measure stages of readiness for key transition-related skills in adolescents with JIA. METHODS: A phased approach was used to develop and evaluate the validity and reliability of RACER. Phase 1 A was a consensus conference with 19 key stakeholders to inform instrument domains and items. Phase 1B determined initial content validity using a sample of 30 adolescents with JIA and 15 clinical and research experts. Finally, Phase 2 was a prospective cohort study with repeated measures to evaluate the internal consistency, test-retest reliability, construct validity and responsiveness of the instrument within a sample of adolescents with JIA. RESULTS: In Phase 1 A, initial item generation yielded a total of 242 items across six domains from the consensus conference, which was subsequently reduced to a 32-item instrument. Phase 1B established the content validity of the instrument in adolescents with JIA. In the Phase 2 study, with a sample of 96 adolescents, the RACER instrument exhibited good internal consistency in five of its six subscales (Cronbach's α > 0.7), and strong test-retest reliability between the first two administrations (ICC = 0.83). It also showed robust convergent validity by highly correlating with measures of self-management (SMSAG, rho = 0.73) and transition (TRANSITION-Q, rho = 0.76). The RACER was not correlated with unrelated measures (discriminant validity; PedsQL, rho = 0.14). The RACER scores increased significantly over time as expected, supporting measure responsiveness. CONCLUSIONS: The RACER is a reliable and valid instrument which is sensitive to change for assessing transition readiness in adolescents with JIA.

Histopathological features of systemic sclerosis-associated myopathy: A scoping review.

BACKGROUND: Scleromyositis (SM) is an emerging subset of myositis associated with features of systemic sclerosis (SSc) but it is currently not recognized as a distinct histopathological subset by the European NeuroMuscular Center (ENMC). Our aim was to review studies reporting muscle biopsies from SSc patients with myositis and to identify unique histopathological features of SM. METHODS: A scoping review was conducted and included all studies reporting histopathological findings in SSc patients with myositis searching the following databases: PubMed, MEDLINE, EMBASE, CINAHL and EBM-Reviews. Clinical, serological, and histopathological data were extracted using a standardized protocol. RESULTS: Out of 371 citations, 77 studies that included 559 muscle biopsies were extracted. Fifty-seven percent (n = 227/400) had inflammatory infiltrates, predominantly T cells, which were endomysial (49%), perimysial (42%) and perivascular (41%). Few studies (18%, n = 8/44) evaluated the presence of B-cells. Myofiber atrophy was present in 48% (n = 104/218) of biopsies, and was predominantly perifascicular in 19% (n = 6/31), with necrosis reported in 56% (n = 162/290) of cases. Sarcolemmal MHC-I upregulation was found in 72% (n = 64/89) of biopsies. Non-specified C5b-9 deposition was described in 39% of muscle biopsies (n = 28/72). Neurogenic features were present in 23% (n = 44/191); endomysial fibrosis was reported in 35% (n = 120/340); and rimmed vacuoles were observed in 32% (n = 11/34) of biopsies. Capillaropathy, such as capillary dropout and/or ultrastructural endothelial abnormalities, was reported in 33% (n = 43/129) of cases. Reported ENMC categories were mainly polymyositis (21%), non-specific myositis (19%), immune-mediated necrotizing myopathy (16%), and dermatomyositis (8%). Histopathological features were analyzed according to serological subtypes in 28 studies, including anti-PM-Scl (n = 48), -Ku (n = 23) and -U1RNP (n = 90). Most of these biopsies demonstrated inflammatory infiltrates (range 49-85%) as well as MHC-I expression (range 63-81%). Necrosis was associated with anti-Ku (85%) and anti-U1RNP (73%), while anti-Ku was also associated with neurogenic features and rimmed vacuoles in 57% and 25% of cases, respectively. CONCLUSION: Our review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets.

Recognising the spectrum of scleromyositis: HEp-2 ANA patterns allow identification of a novel clinical subset with anti-SMN autoantibodies.

OBJECTIVE: To describe systemic sclerosis (SSc) with myopathy in patients without classic SSc-specific and SSc-overlap autoantibodies (aAbs), referred to as seronegative scleromyositis. METHODS: Twenty patients with seronegative scleromyositis diagnosed by expert opinion were analysed retrospectively for SSc features at myositis diagnosis and follow-up, and stratified based on HEp-2 nuclear patterns by indirect immunofluorescence (IIF) according to International Consensus of Autoantibody Patterns. Specificities were analysed by protein A-assisted immunoprecipitation. Myopathy was considered an organ involvement of SSc. RESULTS: SSc sine scleroderma was a frequent presentation (45%) at myositis diagnosis. Myositis was the most common first non-Raynaud manifestation of SSc (55%). Lower oesophagal dysmotility was present in 10 of 11 (91%) investigated patients. At follow-up, 80% of the patients met the American College of Rheumatology/EULAR SSc classification criteria. Two-thirds of patients had a positive HEp-2 IIF nuclear pattern (all with titers ≥1/320), defining three novel scleromyositis subsets. First, antinuclear antibody (ANA)-negative scleromyositis was associated with interstitial lung disease (ILD) and renal crisis. Second, a speckled pattern uncovered multiple rare SSc-specific aAbs. Third, the nuclear dots pattern was associated with aAbs to survival of motor neuron (SMN) complex and a novel scleromyositis subset characteriszed by calcinosis but infrequent ILD and renal crisis. CONCLUSIONS: SSc skin involvement is often absent in early seronegative scleromyositis. ANA positivity, Raynaud phenomenon, SSc-type capillaroscopy and/or lower oesophagal dysmotility may be clues for scleromyositis. Using HEp-2 IIF patterns, three novel clinicoserological subsets of scleromyositis emerged, notably (1) ANA-negative, (2) ANA-positive with a speckled pattern and (3) ANA-positive with nuclear dots and anti-SMN aAbs.

Eslicarbazepine for focal epilepsy and acute intermittent porphyria.

Porphyrias are rare genetic disorders which cause a deficiency in the enzymes involved in the biosynthesis of heme. The treatment of epilepsy in patients with acute intermittent porphyria can be difficult since many anticonvulsants can increase heme synthesis and trigger porphyric attacks. We report a patient with focal epilepsy successfully treated with eslicarbazepine without exacerbation of porphyria.

Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients.

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

Statin-associated anti-HMGCR immune-mediated necrotizing myopathy with dermatomyositis-like features: A case report.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) immune-mediated necrotizing myopathy is a subtype of idiopathic inflammatory myopathy which may be associated with statin exposure. It presents with severe proximal muscle weakness, high creatine kinase levels and muscle fiber necrosis. Treatment with intravenous immunoglobulins and immunosuppressants is often necessary. This entity is not commonly known among dermatologists as there are usually no extramuscular manifestations. We report a rare case of statin-associated anti-HMGCR immune-mediated necrotizing myopathy with dermatomyositis-like cutaneous features. The possibility of anti-HMGCR immune-mediated necrotizing myopathy should be considered in patients with cutaneous dermatomyositis-like features associated with severe proximal muscle weakness, highly elevated creatine kinase levels and possible statin exposure. This indicates the importance of muscle biopsy and specific autoantibody testing for accurate diagnosis, as well as significant therapeutic implications.

Drivers of Satisfaction With Care for Patients With Lupus.

OBJECTIVE: Quality of life (QOL) and quality of care (QOC) in systemic lupus erythematosus (SLE) remains poor. Satisfaction with care (SC), a QOC surrogate, correlates with health behaviors and outcomes. This study aimed to determine correlates of SC in SLE. METHODS: A total of 1262 patients with SLE were recruited from various countries. Demographics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index for the Safety of Estrogens in Lupus Erythematosus: National Assessment trial [SELENA-SLEDAI]), and QOL (LupusPRO version 1.7) were collected. SC was collected using LupusPRO version 1.7. Regression analyses were conducted using demographic, disease (duration, disease activity, damage, and medications), geographic (eg, China vs United States), and QOL factors as independent predictors. RESULTS: The mean (SD) age was 41.7 (13.5) years; 93% of patients were women. On the univariate analysis, age, ethnicity, current steroid use, disease activity, and QOL (social support, coping) were associated with SC. On the multivariate analysis, Asian participants had worse SC, whereas African American and Hispanic patients had better SC. Greater disease activity, better coping, and social support remained independent correlates of better SC. Compared with US patients, patients from China and Canada had worse SC on the univariate analysis. In the multivariate models, Asian ethnicity remained independently associated with worse SC, even after we adjusted for geographic background (China). No associations between African American or Hispanic ethnicity and SC were retained when geographic location (Canada) was added to the multivariate model. Canadian patients had worse SC when compared with US patients. Higher disease activity, better social support, and coping remained associated with better SC. CONCLUSION: Greater social support, coping, and, paradoxically, SLE disease activity are associated with better SC. Social support and coping are modifiable factors that should be addressed by the provider, especially in the Asian population. Therefore, evaluation of a patient's external and internal resources using a biopsychosocial model is recommended. Higher disease activity correlated with better SC, suggesting that the latter may not be a good surrogate for QOC or health outcomes.

Sex Differences in Quality of Life in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) predominantly affects women. Clinical phenotype and outcomes in SLE may vary by sex and are further complicated by unique concerns that are dependent upon sex-defined roles. We aimed to describe sex differences in disease-specific quality of life (QoL) assessment scores using the Lupus Patient-Reported Outcome (LupusPRO) tool in a large international study. METHODS: Cross-sectional data from 1,803 patients with SLE on demographics, self-identified sex status, LupusPRO, and disease activity were analyzed. The LupusPRO tool has 2 constructs: health-related QoL (HRQoL) and non-HRQoL. Disease activity and damage were evaluated using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, respectively. Nonparametric tests were used to compare QoL and disease activity by sex. RESULTS: A total of 122 men and 1,681 women with SLE participated. The mean age was similar by sex, but the damage scores were greater among men. Men fared worse on the non-HRQoL social support domain than women (P = 0.02). When comparing disease and QoL among men and women ages ≤45 years, men were found to have greater damage and worse social support than women. However, women fared significantly worse on lupus symptoms, cognition, and procreation domains with trends for worse functioning on physical health and pain-vitality domains. CONCLUSION: In the largest study of a diverse group of SLE patients, utilizing a disease-specific QoL tool, sex differences in QoL were observed on both HRQoL and non-HRQoL constructs. Although men performed worse in the social support domain, women (especially those in the reproductive age group) fared worse in other domains. These observations may assist physicians in appropriately addressing QoL issues in a sex-focused manner.

Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus.

OBJECTIVE: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada. METHODS: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online. RESULTS: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination. CONCLUSION: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

Monitoring of Osteonecrosis in Systemic Lupus Erythematosus: A Systematic Review and Metaanalysis.

OBJECTIVE: Nontraumatic osteonecrosis (ON) is a well-recognized complication causing disability and affecting quality of life in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify the risk factors for ON, and to identify the minimal investigation(s) needed to optimally monitor the risk of ON in patients with SLE. METHODS: A systematic review was conducted using MEDLINE and EMBASE. These databases were searched up to January 2016 using the Medical Subject Heading (MeSH) terms "Osteonecrosis," "Systemic lupus erythematosus," and synonymous text words. Randomized controlled trials, case control, cohort, and cross-sectional studies were included. Risk factors for ON in patients with SLE were compiled. The quality of each study was assessed using the Newcastle-Ottawa scale for nonrandomized studies. The quality of evidence of each risk factor was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method. RESULTS: Of the 545 references yielded, 50 met inclusion criteria. Corticosteroid (CS) use may be strongly associated with ON in patients with SLE. Other clinical variables were moderately associated, including hypertension, serositis, renal disease, vasculitis, arthritis, and central nervous system disease. However, the evidence was low to very low in quality. CONCLUSION: Based on the best evidence available, CS use may be strongly associated with ON in patients with SLE. Results of this review were considered in the development of recommendations for the diagnosis and monitoring of patients with SLE in Canada and will guide clinicians in their assessment of these patients.

Atorvastatin-induced necrotizing autoimmune myositis: An emerging dominant entity in patients with autoimmune myositis presenting with a pure polymyositis phenotype.

The general aim of this study was to evaluate the disease spectrum in patients presenting with a pure polymyositis (pPM) phenotype. Specific objectives were to characterize clinical features, autoantibodies (aAbs), and membrane attack complex (MAC) in muscle biopsies of patients with treatment-responsive, statin-exposed necrotizing autoimmune myositis (NAM). Patients from the Centre hospitalier de l'Université de Montréal autoimmune myositis (AIM) Cohort with a pPM phenotype, response to immunosuppression, and follow-up ≥3 years were included. Of 17 consecutive patients with pPM, 14 patients had a NAM, of whom 12 were previously exposed to atorvastatin (mean 38.8 months). These 12 patients were therefore suspected of atorvastatin-induced AIM (atorAIM) and selected for study. All had aAbs to 3-hydroxy-3-methylglutaryl coenzyme A reductase, and none had overlap aAbs, aAbs to signal recognition particle, or cancer. Three stages of myopathy were recognized: stage 1 (isolated serum creatine kinase [CK] elevation), stage 2 (CK elevation, normal strength, and abnormal electromyogram [EMG]), and stage 3 (CK elevation, proximal weakness, and abnormal EMG). At diagnosis, 10/12 (83%) patients had stage 3 myopathy (mean CK elevation: 7247 U/L). The presenting mode was stage 1 in 6 patients (50%) (mean CK elevation: 1540 U/L), all of whom progressed to stage 3 (mean delay: 37 months) despite atorvastatin discontinuation. MAC deposition was observed in all muscle biopsies (isolated sarcolemmal deposition on non-necrotic fibers, isolated granular deposition on endomysial capillaries, or mixed pattern). Oral corticosteroids alone failed to normalize CKs and induce remission. Ten patients (83%) received intravenous immune globulin (IVIG) as part of an induction regimen. Of 10 patients with ≥1 year remission on stable maintenance therapy, IVIG was needed in 50%, either with methotrexate (MTX) monotherapy or combination immunosuppression. In the remaining patients, MTX monotherapy or combination therapy maintained remission without IVIG. AtorAIM emerged as the dominant entity in patients with a pPM phenotype and treatment-responsive myopathy. Isolated CK elevation was the mode of presentation of atorAIM. The new onset of isolated CK elevation on atorvastatin and persistent CK elevation on statin discontinuation should raise early suspicion for atorAIM. Statin-induced AIM should be included in the differential diagnosis of asymptomatic hyperCKemia. Three patterns of MAC deposition, while nonpathognomonic, were pathological clues to atorAIM. AtorAIM was uniformly corticosteroid resistant but responsive to IVIG as induction and maintenance therapy.

Hereditary Heterozygous C2 Deficiency: Variable Clinical and Serological Manifestations Among Three Sisters.

The causal link between inherited complement deficiencies and systemic lupus erythematosus (SLE) has been well established, although it remains a rare cause of the disease. We present the case of three biological sisters with hereditary heterozygous C2 deficiency, but who differ widely in their clinical and serological manifestations. Patient 1 is 25 years old and was diagnosed with SLE at the age of 12. Further testing revealed positive ANA and anti-dsDNA, antiphospholipid syndrome (APS) and decreased C2, C3 and C4 levels. Patients 2 and 3 are 21-year-old dizygotic twins. Both have positive ANA and antiphospholipid (APL) antibodies, and decreased C2 and C4 levels. We present a case of familial heterozygous C2 deficiency with different disease phenotypes. The presence of positive APL antibodies in all 3 patients is significant, as this association has been rarely described. The variable clinical and serological manifestations among our patients further reflect the complex and multifactorial nature of SLE.