Definite Systemic Lupus Erythematosus Research Articles

Excellent response to treatment with hydroxychloroquine in pediatric patients with SLE-related immune thrombocytopenia.

Pediatric immune thrombocytopenia (ITP) may precede systemic autoimmune disorders. In adolescent patients with ITP, routine screening for systemic lupus erythematosus (SLE) may be performed by testing for antinuclear antibody (ANA) titer. Hydroxychloroquine (HCQ) is a safe and effective immunomodulatory drug in patients with SLE but rarely used in ITP. We analyzed the platelet count response and safety of HCQ in treating pediatric patients with SLE-related ITP. A retrospective study including pediatric patients with ITP and definite or incomplete SLE, who were treated with HCQ during 2010-2021. SLE was defined by ANA titer≥1:160 as measured by immunofluorescence and ≥10 points according to the 2019 EULAR/ACR 2019 classification criteria, while patients with incomplete SLE achieved a score<10. Complete response (CR) of the platelet count was defined as platelet count>100 × 109/L; partial response (PR) as platelet count 30-100 × 109/L and exceeding≥twice baseline counts. Of the 17 patients included (median age 15.5 years; IQR 3.6), 15 (88.2%) were female, 13 had definite SLE, and four had incomplete SLE. HCQ was initiated at a median of 17 months after ITP diagnosis with a median platelet count of 38 × 109/L (IQR 28). At 8weeks, 8 (47.1%) patients responded, including 6 (35.3%) achieving CR. After one year, the overall response was 82.4%, with the remaining patients having stable platelet counts requiring no additional ITP therapy. The response was maintained at a median follow-up of 42 months. No adverse effects to HCQ were noted. Pediatric patients with SLE-related ITP may benefit from treatment with HCQ.

Differentiating between UCTD and early-stage SLE: from definitions to clinical approach.

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations that can potentially affect every organ and system. SLE is usually identified on the basis of clinical or serological manifestations; however, some individuals can present with signs and symptoms that are consistent with SLE but are not sufficient for a definite diagnosis. Disease in these individuals can either progress over time to definite SLE or remain stable, in which case their disease is often described as intermediate, possible or probable SLE. Alternatively, such individuals might have undifferentiated connective tissue disease (UCTD). Being able to differentiate between those with stable UCTD and those with SLE at an early stage is important to avoid irreversible target-organ damage from occurring. This Review provides insight into existing and evolving perceptions of the early stages of SLE, including clinical and mechanistic considerations, as well as potential paths towards early identification and intervention. Further research into the earliest phases of SLE will be important for the development of targeted diagnostic approaches and biomarkers for the identification of individuals with early disease who are likely to progress to definite SLE.

Neutropenia Following Intravenous Immunoglobulin Therapy in Adult Patients with Immune Thrombocytopenic Purpura

BackgroundImmune thrombocytopenic purpura (ITP) is an autoimmune disease in which anti-platelet antibodies accelerate the destruction of platelets. Traditional therapies such as steroid therapy, intravenous immunoglobulin (IVIG) therapy, and splenectomy generally reduce the peripheral destruction of platelets. However, they may cause significant side effects. In particular, it has been recently reported that neutropenia sometimes develops in children as an adverse effect after IVIG administration. On the other hand, there is no previous report on neutropenia developing as a complication of IVIG therapy in adult patients with ITP. The aim of this study was to further investigate the incidence and course of neutropenia following IVIG therapy in adults with ITP.MethodsWe performed a retrospective chart review of 88 ITP patients who had received IVIG to manage severe thrombocytopenia between January 2006 and March 2016 at Pusan National University Hospital in Korea. Inclusion criteria were the following: age ≥ 18 years, ITP diagnosis according to the American Society of Hematology guidelines (platelet count of less than 100 × 109/L in the absence of other causes or disorders that may be associated with thrombocytopenia). Exclusion criteria included other diseases known to be associated with ITP, such as human immunodeficiency virus or hepatitis C virus infection, lympho-proliferative disorders, thyroid or liver disease, and definite systemic lupus erythematosus. Patients included in this study had a complete and differential blood count performed before and after the IVIG treatment. Patients were treated according to a standard protocol, consisting of IVIG administration (1 g/kg per day for two days).ResultsThe baseline characteristics of patients are shown in Table 1. Among 88 patients, 24 (27.3%) were male, and 64 (72.7%) were female. The median ages were 45 years in the group that developed neutropenia and 41 years in the group that did not develop neutropenia. The groups were comparable in age, sex distribution, initial white blood cell (WBC) count, and absolute neutrophil count (ANC). Neutropenia developed in 43 patients (48.9%) after IVIG treatment. In patients with a decrease in WBC count and ANC compared to baseline, median WBC count decreased from 6,280/μL to 4,530/μL after IVIG therapy, and median ANC decreased from 3,840/μL to 2,840/μL after IVIG therapy. Only two patients in this study developed a post-treatment ANC of less than 1,000/μL, and only one patient developed neutropenic fever, which subsided soon without any treatment. The neutropenia induced by IVIG had resolved spontaneously after several days, and the mean recovery time was 8.72 days after the completion of the IVIG treatment (Table 1, Figure 1 and 2). Including the present case, we identified previous reports of neutropenia developing as a complication of IVIG therapy in the English literature (Table 2). The majority of reports of neutropenia following IVIG therapy are pediatric patients with ITP. There were two reports on the incidence of neutropenia induced IVIG in adults except for pediatric patients with ITP. Matsuda M et al. reported neutropenia induced by high-dose IVIG in adult patients with neuro-immunologic disorders. And Lemos S et al. reported acute neutropenia in patients with primary antibody-deficiencies, after receiving IVIG. However, as mentioned earlier, there has been no reports of neutropenia following IVIG therapy in adult patients with ITP. Therefore, this study is the first report of neutropenia after IVIG therapy in adult patients with ITP. Although further studies are required in order to clarify the precise mechanism of neutropenia following IVIG treatment, this would be the important report of neutropenia following IVIG therapy in adult patients with ITP.ConclusionsThe results of this study suggest that IVIG may cause neutropenia commonly in adults with ITP, and it seems to be transient and self-limited. This study is meaningful as the first report that not only pediatric ITP patients may develop neutropenia post IVIG administration, but also adult patients suffering ITP. Therefore, an awareness of this common association of neutropenia following IVIG treatment in adult patients with ITP is likely to aid physicians in caring for these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

What Is the Role of Sphingosine-1-Phosphate Receptors in Pain?

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations that can occur over a long period of time. Electronic health record (EHR) data presents a rich source of information that can be used to understand the varied presentation of SLE. We examined three clinical classification criteria for SLE to assess whether they could be a foundation for phenotype-based detection of patients with SLE in EHR data. <h3>Methods</h3> We assessed algorithm performance over 600 medical records from the Northwestern Medicine Electronic Data Warehouse, 472 of which had definite SLE and 128 which did not, based on chart review. We developed algorithms, based on the American College of Rheumatology (ACR), Systemic Lupus International Collaborating Clinics (SLICC) and the proposed European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria using only structured data elements (diagnosis codes (ICD9/ICD10) and lab results) to determine whether patients met the classification criteria for definite SLE. <h3>Results</h3> As shown in table 1, the overall identification rate of SLE ranged from 58% to 78% across the three algorithms. All three criteria-based algorithms had greater than 95% specificity and greater than 98% positive predictive value (PPV). Sensitivity of the algorithms ranged from 52% to 69% and negative predictive value (NPV) from 35% to 55%. The SLICC-based algorithm had the overall highest performance, detecting 78% of the patients with definite SLE as determined by chart review, with 99% PPV, 69% sensitivity, 98% specificity and 55% NPV. <h3>Conclusions</h3> The ACR-, SLICC- and proposed EULAR/ACR- based EHR algorithms all detect a significant proportion of patients that were classified as having definite SLE by chart review, with high PPV and specificity. Low NPV of all three algorithms likely reflects undetected cases of SLE resulting from low detection of clinical and laboratory criteria (such as arthralgia and ANA tests) that are not consistently documented in structured data in the medical record. Use of structured data improves portability of the algorithms to other EHR datasets, but may have reduced the ability of the algorithms to detect important/highly weighted classification criteria that are documented primarily in free text notes. All three algorithms may improve through use of natural language processing (NLP) of physician notes for criteria that were difficult to detect using only diagnosis codes and labs, but may reduce portability as a result of the customization required for NLP to be effective. <h3>Funding Source(s):</h3> National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21 AR072263) and NHGRI U01HG006388

Clinical and laboratory relationships in patients with different variants of the course of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by a variability in clinical manifestations and laboratory abnormalities, which creates objective diagnostic difficulties.Objective: to investigate clinical and laboratory parameters in patients with definite and probable SLE.Patients and methods. The investigation enrolled 94 patients, 38 of whom were diagnosed with probable SLE. All the patients underwent immunological examination and unaffected skin biopsies, followed by an immunohistochemical study, the so-called lupus strip test (LST).Results and discussion. The group of patients with definite SLE showed a direct correlation between positive LST and disease activity (r=0.6), acute skin lesion (r=0.42), and elevated anti-double-stranded DNA antibody concentrations (r=0.37), and their inverse correlation with dry syndrome (r=-0.44). In patients with probable SLE, deposition of immunoreactants in the unaffected skin was detected in almost half of the cases, despite lower disease activity and specific antibody deficiency. Thus, LST that is quite easy to use and interpret its results can be used as an additional criterion for the differential diagnosis of SLE, especially in its early stages.

The Role of Hydroxychloroquine as a Steroid-sparing Agent in the Treatment of Immune Thrombocytopenia: A Review of the Literature.

Immune Thrombocytopenia (ITP) is an autoimmune disease in which platelet destruction causes thrombocytopenia. Due to the known steroid toxicities, alternative agents have been evaluated for the treatment of these patients. We aimed to review the literature and find evidences regarding the potential benefits of hydroxychloroquine (HCQ) as a steroid-sparing agent in the treatment of ITP. We searched English language articles within Web of Science, PubMed, and Scopus. Cohorts, clinical trials, case reports, conference papers, and letters were included. We excluded papers which either focused on administration of HCQ for non-ITP conditions or studies on other treatment modalities for ITP. In total, 54 ITP cases with either primary or systemic lupus erythematosus (SLE)-associated ITP were included in four studies (SLE-associated ITP; n = 23). All patients have received corticosteroids previously and >90% received other agents with HCQ concomitantly. Overall response was achieved in more than 60% of patients. Sustained response in 18 (33.3%) patients was associated with no treatment or HCQ alone. One of the studies reported a significantly better response in patients with definite SLE compared to those with positive antinuclear antibody and no definite SLE. Similarly, another study found a nonsignificant trend toward better long-term response in patients with definite SLE compared to incomplete SLE. The included articles reported the efficacy of the HCQ with acceptable safety. Available data regarding the use of HCQ for this indication are spare and more studies are needed in ITP with different severity. It seems that HCQ can be considered as an option in the treatment of SLE-associated ITP, and although promising, currently, the place of HCQ in the treatment of ITP continues to evolve.

Clinical association between Kikuchi׳s disease and systemic lupus erythematosus: A systematic literature review.

To perform a systematic review of all cases of the association between Kikuchi's disease (KD) and systemic lupus erythematosus (SLE), and to ascertain the clinical and laboratory characteristics of this association (KD-SLE). We conducted a systematic search of the scientific literature until 31 January 2016. For study purposes, only patients aged >14 years, with histologically proven KD, definite SLE and adequate clinical data were included. To compare KD-SLE against isolated KD and SLE, we selected 2 large series of patients with KD and 4 series of SLE patients. The search found 158 adults with proven KD-SLE. Of these, 113 with sufficient clinical information were included; 86 were women (female:male ratio = 5.0); mean age at diagnosis was 34 years (range: 14-56 years); and an ethnic distribution of 50.5% Asian, 34% Caucasian, and 15% other. KD-SLE patients differed significantly from patients with isolated KD, presenting with a higher frequency of high fever (90%), severe KD (88%), and extranodal manifestations. When compared to patients with SLE, those with KD-SLE presented with a higher frequency of fever and systemic symptoms and a lower frequency of lupus nephritis (22%). SLE had been diagnosed before KD in 18% of cases, simultaneously in 51%, and after KD in 31%. No significant differences were found in terms of time of diagnosis. While KD-SLE patients share many clinical and laboratory manifestations with SLE, they differ in a lower frequency of lupus nephritis. The relative time of diagnosis of each disease did not affect the clinical expression of KD-SLE.

The Risk of Systemic Lupus Erythematosus Associated With Vaccines: An International Case‐Control Study

Studies have suggested that systemic lupus erythematosus (SLE) may be triggered by vaccinations. We undertook this study to investigate the relationship between vaccination and onset of SLE. This international case-control study was conducted between April 2008 and June 2012 in 36 specialist referral centers (34 in France and 2 in Quebec, Canada) and recruited patients ≤60 years old recently diagnosed as having either definite SLE (meeting ≥4 American College of Rheumatology [ACR] criteria including at least 1 immunologic criterion) or probable SLE (meeting 3 ACR criteria including at least 1 immunologic criterion). Controls were recruited from general practice settings through a closely monitored protocol and matched to patients by age, sex, region of residence, and date of recruitment. Vaccinations and other potential risk factors for SLE were assessed using a standardized telephone interview. We compared proportions of patients and controls who were vaccinated 12 and 24 months before the index date (date of first clinical symptom presented by the patient) using odds ratios (ORs) from conditional logistic regression. We assessed 105 patients (89 with definite SLE and 16 with probable SLE) and 712 controls. Twenty-two of the 105 patients (21.0%) and 181 of the 712 controls (25.4%) had received at least 1 vaccination within 24 months before the index date (adjusted OR 0.9 [95% confidence interval 0.5-1.5]). The proportions of patients and controls vaccinated within the previous 12 months were also similar. Our study showed no association between exposure to vaccination and risk of developing SLE.

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

To identify factors associated with development of systemic lupus erythematosus (SLE) among patients evaluated at a tertiary care Lupus Center for potential SLE. 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. 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. 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.

AB0626 Dynamic study of B-cells using highly sensitive flow cytometry (HSFC) in systemic lupus erythematosus patients’ receiving anti-B-cell therapy

ObjectivesDynamic study of B-cell using HSFC in systemic lupus erythematosus (SLE) patients’(pts) receiving anti-B-cell therapy with Rituximab (RTM) and definition of correlation with clinical and laboratory disease activity on the...

THU0383 Kikuchi’s disease and systemic lupus erythematous: A systematic literature review

BackgroundKikuchi disease (KD) and systemic lupus erythematosus (SLE) share many clinical and histological features. The association of both entities has been reinforced over time with the publication of numerous case...

Cognitive Impairment in Systemic Lupus Erythematosus: Prevalence and Clinical Importance

Neurologists are often called to evaluate central nervous system [CNS] manifestations in patients with suspected or definite systemic lupus erythematosus [SLE]. The manifestations are highly diverse and often have major prognostic consequences. The major difficulties are to determine if the given manifestation is primarily due to SLE activity in the brain, or a consequence of metabolic disturbances, infection, or corticosteroid use. The true incidence of CNS manifestations attributable to SLE is not entirely clear, but several studies show prevalence rate between 15-75%, depending on criteria adopted. For cognitive impairment, the prevalence ranges from 17-59%. Cognitive impairment may be attributed to emotional distress, corticosteroid use, active systemic disease or primary CNS dysfunction. These manifestations may occur even in the absence of other neuropsychiatric [NP] manifestations clearly attributable to SLE. The etiology of cognitive impairment may be related to autoimmune mechanisms, such as brain-specific autoantibodies. Despite several studies using computer tomography [CT] and magnetic resonance imaging [MRI], brain structural abnormalities could not be associated with cognitive findings in SLE patients. Functional neuroimaging methods may be more sensitive for detecting subclinical brain involvement related to cognitive dysfunction in SLE. Despite the fact that cognitive impairment may be residual in patients with previous CNS involvement, it also may be an early marker of CNS involvement in previous asymptomatic patients. This article will review clinical assessment, pathogenic mechanism, and the role of neuroimaging methods in the evaluating of SLE patients with cognitive impairment.

Neuropsychiatric Syndromes in Systemic Lupus Erythematosus: A Meta-Analysis

To assess the prevalence of the 19 neuropsychiatric (NP) syndromes in systemic lupus erythematosus (SLE) patients, as defined by the American College of Rheumatology (ACR) in 1999, and better understand the reasons for interstudy variability of prevalence estimates, by performing a meta-analysis of relevant publications. A literature search from April 1999 to May 2008 was performed to identify studies investigating NP syndromes in patients with definite SLE, applying the 1999 ACR case definitions and having a sample size of at least 30 patients. Excluded were studies that did not relate to all 19 NPSLE syndromes, presented duplicate data, or were irrelevant. Seventeen of 112 identified studies matched the inclusion criteria, reporting on a total of 5057 SLE patients, including 1439 NPSLE patients, with 2709 NPSLE syndromes. In a subanalysis of the 10 higher quality prospective and elicited studies (2049 patients) using the random-effects model, the prevalence of NP syndromes in SLE patients was estimated to be 56.3% (95% CI 42.5%-74.7%), and the most frequent NP syndromes were headache 28.3% (18.2%-44.1%), mood disorders 20.7% (11.5%-37.4%), cognitive dysfunction 19.7% (10.7%-36%), seizures 9.9% (4.8%-20.5%), and cerebrovascular disease 8.0% (4.5%-14.3%), although significant between-study heterogeneity was present (P < 0.05). Autonomic disorder and Guillain-Barré syndrome carried a prevalence of less than 0.1%. No case of plexopathy was reported. NP syndromes were estimated to exist in more than half of SLE patients. The most prevalent manifestations were headache, mood disorders, and cognitive dysfunction. A major limitation of the study was the significant heterogeneity of prevalence estimates between studies.

Increased level of tumor necrosis factor-α in patients with antiphospholipid syndrome: marker not only of inflammation but also of the prothrombotic state

Connections between inflammation and thrombosis are intriguing, especially in a condition such as an antiphospholipid syndrome (APS), a disease characterized by immune-mediated thrombosis. Tumor necrosis factor alpha (TNF-α) is a cytokine which shares proinflammatory and prothrombotic actions, while a soluble form of interlukin-2 receptor (sIL-2R) is considered a typical marker of (auto)immune inflammation with not known direct links to thrombosis. The differences in the pathogenesis of APS as compared to other autoimmune diseases might be connected with different serum levels of both mediators. To answer this question, we studied 147 patients with systemic lupus erythematosus (SLE), 21 with SLE-like syndrome (SLE-LS), 20 with isolated APS (primary antiphospholipid syndrome, PAPS), and 32 healthy controls. Thirty-six patients from the SLE group fulfilled the updated APS criteria (secondary APS, SAPS). In comparison to healthy subjects, TNF-α concentration was increased in all patients, while sIL-2R rose significantly in the SLE group only. APS (both SAPS and PAPS) was characterized by the highest levels of TNF-α. Moreover, patients with lupus anticoagulant or elevated levels of IgG anticardiolipin or IgG anti-β(2)-glycoprotein I antibodies had higher TNF-α levels than patients without the presence of any type of antiphospholipid antibodies (aPL). In conclusion, the presence of aPL is associated with higher TNF-α level, whereas increased level of sIL-2R is rather connected with definite SLE where inflammatory processes prevail. It might be hypothesized that TNF-α plays a major role in pathogenesis of APS thrombotic phenomena.

SLE disease patterns in a Danish population-based lupus cohort: an 8-year prospective study

In 1995 all systemic lupus erythematosus (SLE) patients in the county of Funen were retrieved from four separate and independent sources as part of an 8-year prospective study to determine the pattern of disease activity and damage accumulation in a community based lupus cohort of predominantly Scandinavian ancestry. Incident cases were subsequently identified by surveillance of these sources. Established and new cases underwent annual, structured interviews, clinical examination and blood sampling. The Systemic Lupus Erythematosus Diseases Activity Index SLEDAI and Systemic Lupus International Collaborating Clinics SLICC scores were calculated. Flares were defined as modified - SLEDAI >or= 4. The annual flare rate in definite SLE (D-SLE) was 0.21 (95%CI 0.18-0.24) versus 0.03 (95%CI 0.01-0.07) in incomplete SLE (I-SLE). Forty-three per cent of the entire study population had no disease exacerbations. Infections requiring hospital admission and thrombocytopenia were significantly more frequent among patients with relapsing disease (p < 0.04-0.01). Patients with flares had slightly shorter disease duration and were younger at disease onset than patients with a quiescent course. The most recently diagnosed patients had the lowest annual rate of damage accrual. According to flare rate, two major subsets of almost equal size were identified - one having a long quiescent course, the other exhibiting relapses alternating with remissions. An increased risk of flares was associated with short disease duration and younger age at disease onset, infections requiring hospital admission and thrombocytopenia. Temporal damage increment was the lowest in the most recently diagnosed patients.

Hydroxychloroquine for the Treatment of Immune Thrombocytopenia Associated with Antinuclear Antibody in Patients Refractory to First-Line treatments .

Abstract 2414Poster Board II-391 Background and objective:Although, corticosteroids (CS) are commonly used as the first-line treatment for lupus-associated immune thrombocytopenia (ITP), few patients fail to respond to CS and a majority of the responders relapse when CS are withdrawn. Hydroxychloroquine (HCQ) is commonly used in both cutaneous and systemic lupus due to its immunomodulatory properties. In a previous report on lupus-associated immune thrombocytopenia (ITP), it has been suggested that HCQ could have an effect on the platelet count in this setting (Arnal C et al. J Rheumatol 2002). The objective of the study was to better assess the efficacy of HCQ as a treatment of ITP associated with positive antnuclear antibody (ANA) in patients who failed to achieve a durable response after a first-line treatment. Patients and Methods:This single centre retrospective study was conducted at the French national referral center for adult's immune cytopenias. To be included in the study, all patients had to fulfil the following criteria: 1) Definite diagnosis of ITP with a platelet count < 50 × 109/l at diagnosis 2) Positive ANA at a significant titer (i.e ≥ 1/160 on Hep2 cells), with or without a definite diagnosis of systemic lupus erythematosus (SLE) according to the ACR-revised criteria and 3) No response or incomplete response to at least one previous treatment-line. Response to HCQ was considered when the platelet count was persistently (at least for 3 consecutive months) maintained above 150×109/l (complete response: CR), and when the platelet count increased and persisted above 30 × 109/l with at least a doubling of the baseline count (partial response: PR). Results:The data from 40 patients (32 F, 8 M) with a median age of 35 yrs (range: 15-75) were analyzed. The median platelet count at ITP diagnosis was 13×109/l (range: 1-46). Twelve (30%) patients had a SLE-associated ITP (4 or more SLE ACR-criteria) whereas 28 patients (70%) had positive ANA without definite SLE. The median HCQ dose was 200 mg bid (200 to 600 mg/d) and the median time between ANA-associated-ITP diagnosis and HCQ first administration was 4 months (range: 1-120). HCQ was given after failure of a median of 2 treatment-lines [1 to 5 including oral prednisone (n=39), IVIg (n=15), danazol (n=5), dapsone (n=2), splenectomy (n=2), anti-D (n=1) and immunosuppressive agents (n=2)]. HCQ was given in combination with other treatments in 36 patients (90%) including oral prednisone (n=36) (median initial dose: 50 mg/day, range: 30 to 65 mg/day), dapsone (n=8), danazol (n=5). The median duration of HCQ treatment was 5 years (range: 0.4 to 12 yrs).The overall response rate for was 60% (24/40), with 18 CR and 6 PR. All the responses were sustained with a median follow-up of 64 months (range: 6 to 146 mths). At the end of the follow-up period, all concomitant therapies could be either stopped (n = 29 patients) or tapered [n = 7 patient left on low dose of prednisone (less than 10 mg/d)].The response rate was significantly higher in the SLE group (83%; 10/12) when compared to the ANA-positive group (50%; 14/28) (p <0.05). The overall safety of HCQ was good and none of the patients stopped the treatment because of a side-effect. Blood HCQ concentration was checked in 2 non-responding patients and was found below therapeutic range in both cases. Conclusion:This retrospective study strongly suggests that HCQ is a safe, and effective treatment for ITP patients with high titer of ANA who failed to achieve a lasting response after a first-line treatment and mainly after CS. HCQ appears particularly attractive in the subgroup of patients who fulfil the SLE ACR-revised criteria. This costless treatment should therefore be systematically considered in this setting regardless SLE-activity. Moreover, it is likely that HCQ may also be helpful as a corticosteroid-sparing strategy in patients with chronic ITP and positive ANA but this observation needs further confirmation throughout a prospective analysis. Disclosures:No relevant conflicts of interest to declare.

Relationship of T regulatory cells content, activity and serum autoantibodies level in patients with systemic lupus erythematosus receiving rituximab

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Occurrence of systemic lupus erythematosus in a Danish community: an 8‐year prospective study

Objectives: To determine the prevalence and annual incidence of definite systemic lupus erythematosus (D‐SLE) and incomplete SLE (I‐SLE) in a community‐based lupus cohort of predominantly Nordic ancestry in an 8‐year prospective study from 1995 to 2003, and also to calculate the annual transition rate of I‐SLE to D‐SLE.Methods: In 1995 all SLE patients in the county of Funen were retrieved from four separate and independent sources. Incident cases were subsequently identified by surveillance of these sources.Results: During the 8‐year study period the median annual incidence of D‐SLE (1.04 per 100 000) and I‐SLE (0.36 per 100 000) remained almost constant. The point prevalence (PP) of D‐SLE increased from 21.9 to 28.3 per 100 000, and from 6.19 to 7.53 per 100 000 for I‐SLE. During follow‐up, seven I‐SLE patients transformed into D‐SLE at a progression rate of 3.64 per 100 person‐years at risk [95% confidence interval (CI) 1.44–7.55].Conclusions: Denmark is a low‐incidence lupus area but lupus prevalence is increasing slowly. I‐SLE is a disease variant that may eventually convert into D‐SLE.

Genetic Variation in C-Reactive Protein (CRP) Gene May Be Associated with Risk of Systemic Lupus Erythematosus and CRP Concentrations

The gene coding for C-reactive protein (CRP) is located on chromosome 1q23.2, which falls within a linkage region thought to harbor a systemic lupus erythematosus (SLE) susceptibility gene. Recently, 2 single-nucleotide polymorphisms (SNP) in the CRP gene (+838, +2043) have been shown to be associated with CRP concentrations and/or SLE risk in a British family-based cohort. Our study was done to confirm the reported association in an independent population-based case-control cohort, and also to investigate the influence of 3 additional CRP tagSNP (-861, -390, +90) on SLE risk and serum CRP concentrations. DNA from 337 Caucasian women who met the American College of Rheumatology criteria for definite (n = 324) or probable (n = 13) SLE and 448 Caucasian healthy female controls was genotyped for 5 CRP tagSNP (-861, -390, +90, +838, +2043). Genotyping was performed using restriction fragment length polymorphism-polymerase chain reaction, pyrosequencing, or TaqMan assays. Serum CRP levels were measured using ELISA. Association studies were performed using the chi-squared distribution, Z-test, Fisher's exact test, and analysis of variance. Haplotype analysis was performed using EH software and the haplo.stats package in R 2.1.2. While none of the SNP were found to be associated with SLE risk individually, there was an association with the 5 SNP haplotypes (p < 0.001). Three SNP (-861, -390, +90) were found to significantly influence serum CRP level in SLE cases, both independently and as haplotypes. Our data suggest that unique haplotype combinations in the CRP gene may modify the risk of developing SLE and influence circulating CRP levels.

Characteristics and Outcome of Connective Tissue Diseases in Patients with Sickle-Cell Disease: Report of 30 Cases

To analyze the main characteristics of adults with sickle cell disease (SCD) and concurrent connective tissue disease (CTD). A retrospective investigational study was performed. CTD was diagnosed according to standard international criteria. Severity of SCD was assessed by a clinical severity score. Thirty patients, 23 women (76%) and 7 men, with hemoglobin S/S (n = 25) or S/C (n = 5) SCD were included. The subtypes of CTD were rheumatoid arthritis (RA) (n = 15), definite systemic lupus erythematosus or "incomplete lupus" requiring treatment (n = 13), primary Sjögren's syndrome with central nervous system involvement (n = 1), and systemic sclerosis (n = 1). Twenty-five of the 30 patients (83%) received steroid treatment, and 15 (50%) received at least 1 immunosuppressive agent (methotrexate in 14 cases) to control CTD. Four RA patients were given antitumor necrosis factor (TNF)alpha and 1 was treated with rituximab without SCD exacerbation. After a median follow-up of 4.5 years [range: 6 months to 30 years] from CTD diagnosis, 11 of the 25 (44%) patients receiving steroids had at least 1 episode of severe infection (mostly due to Staphylococcus aureus or Escherichia coli). SCD exacerbated in 13 of the 30 (43%) patients after CTD onset; 12 of these patients were receiving prednisone and/or methotrexate. Six patients (20%) had died from sepsis (n = 2), stroke (n = 2), or acute chest syndrome (n = 2). CTD-related clinical manifestations and outcome were not particularly severe in patients with SCD. However, those with active CTD and undergoing steroid +/- methotrexate treatment had more serious SCD-related manifestations, a higher rate of severe infections, and an overall patient mortality rate of 20%. Thus, the management of patients with CTD and underlying SCD should consider the risk/benefit ratio of each treatment and steroid-sparing strategies should be implemented.