Development of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria, Phase III-D Report: Multicriteria Decision Analysis.

OBJECTIVE: The 2023 American College of Rheumatology/EULAR antiphospholipid syndrome (APS) classification criteria development, which aimed to identify patients with high likelihood of APS for research, employed a four-phase methodology. Phase I and II resulted in 27 proposed candidate criteria, which are organized into laboratory and clinical domains. Here, we summarize the last stage of phase III efforts, employing a consensus-based multicriteria decision analysis (MCDA) to weigh candidate criteria and identify an APS classification threshold score. METHODS: We evaluated 192 unique, international real-world patients referred for "suspected APS" with a wide range of APS manifestations. Using proposed candidate criteria, subcommittee members rank ordered 20 representative patients from highly unlikely to highly likely to have APS. During an in-person meeting, the subcommittee refined definitions and participated in an MCDA exercise to identify relative weights of candidate criteria. Using consensus decisions and pairwise criteria comparisons, 1000Minds software assigned criteria weights, and we rank ordered 192 patients by their additive scores. A consensus-based threshold score for APS classification was set. RESULTS: Premeeting evaluation of 20 representative patients demonstrated variability in APS assessment. MCDA resolved 81 pairwise decisions; relative weights identified domain item hierarchy. After assessing 192 patients by weights and additive scores, the Steering Committee reached consensus that APS classification should require separate clinical and laboratory scores, rather than a single-aggregate score, to ensure high specificity. CONCLUSION: Using MCDA, candidate criteria preliminary weights were determined. Unlike other disease classification systems using a single-aggregate threshold score, separate clinical and laboratory domain thresholds were incorporated into the new APS classification criteria.

French protocol for the diagnosis and management of systemic lupus erythematosus.

Because Systemic Lupus Erythematosus (SLE) is a rare disease, and due to the significant prognostic impact of early management, a diagnosis confirmed by a physician with experience in SLE is recommended, for example from an expert center. Once the diagnosis is confirmed, existing manifestations should be identified in particular, renal involvement by an assessment of proteinuria, disease activity and severity should be determined, potential complications anticipated, associated diseases searched for, and the patient's socioprofessional and family context noted. Therapeutic management of SLE includes patient education on recognizing symptoms, understanding disease progression as well as when they should seek medical advice. Patients are informed about routine checkups, treatment side effects, and the need for regular vaccinations, especially if they are receiving immunosuppressive treatment. They are also advised on lifestyle factors such as the risks of smoking, sun exposure, and dietary adjustments, especially when they are receiving corticosteroids. The importance of contraception, particularly when teratogenic medications are being used, and regular cancer screening are emphasized. Support networks can help relieve a patient's isolation. The first-line medical treatment of SLE is hydroxychloroquine (HCQ), possibly combined with an immunosuppressant and/or low-dose corticosteroid therapy. The treatment of flares depends on their severity, and typically involves HCQ and NSAIDs, but may be escalated to corticosteroid therapy with immunosuppressants or biologic therapies in moderate to severe cases. Because there is no curative treatment, the goals of therapy are patient comfort, preventing progression and flares, and preserving overall long-term health and fertility. The frequency of follow-up visits depends on disease severity and any new symptoms. Regular specialized assessments are necessary, especially when treatment changes, but a frequency of every 3 to 6 months is recommended during periods of remission and monthly during active or severe disease, especially in children. These assessments include both clinical and laboratory tests to monitor complications and disease activity, with specific attention to proteinuria.

Hydroxychloroquine and Cardiovascular Events in Patients With Systemic Lupus Erythematosus.

Importance: Systemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed. Objective: To evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE. Design, Setting, and Participants: This cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023. Exposures: Hydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days. Main Outcomes and Measures: Outcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable. Results: The SLE cohort included 52 883 patients (mean [SD] age, 44.23 [16.09] years; 45 255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16 892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days. Conclusions and Relevance: In this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.

Cluster analysis of clinical manifestations assigns systemic lupus erythematosus-phenotype subgroups: A multicentre study on 440 patients.

OBJECTIVE: Systemic lupus erythematous (SLE) is a heterogenous disease characterised by a large panel of autoantibodies and a wide spectrum of clinical signs and symptoms that engender different outcomes. We aimed to identify distinct, homogeneous SLE patients' phenotypes. METHODS: This retrospective study enrolled SLE patients meeting the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, enrolled in the French multicentre "APS (antiphospholipid syndrome) and SLE" Registry. Based on 29 variables selected to cover a broad range of clinical and laboratory (excluding autoantibodies) SLE manifestations, unsupervised multiple correspondence analysis followed by hierarchical ascendent-clustering analysis assigned different phenotypes. RESULTS: We included 440 patients, mostly women (94.3%). Median age at SLE diagnosis was 24 (IQR 19-32) years. Cluster analysis yielded three distinct subgroups based on cumulative clinical manifestations, not autoantibody pattern. Cluster 1 (n=91) comprised mostly Caucasian patients, with APS-associated clinical and biological manifestations, e.g., livedo, seizure, thrombocytopaenia and haemolytic anaemia. Cluster 2 (n=221), the largest, included patients with mild clinical manifestations, mainly articular, more frequently associated with Sjögren's syndrome and with less frequent autoantibody-positivity. Cluster 3 (n=128) consisted of patients with the largest panel of SLE-specific clinical manifestations (cutaneous, articular, proliferative nephritis, pleural, cardiac and haematological), the most frequent autoantibody-positivity, low complement levels, and more often of Asian and sub-Saharan African origin. CONCLUSION: This unsupervised clustering method distinguished three distinct SLE patient subgroups, highlighting SLE heterogeneity.

Hydroxychloroquine levels in pregnancy and materno-fetal outcomes in Systemic Lupus Erythematosus patients.

OBJECTIVES: Data about hydroxychloroquine (HCQ) levels during pregnancy are sparse. We assessed HCQ whole blood levels at first trimester of pregnancy as a potential predictor of maternal and obstetric/fetal outcomes in patients with systemic lupus erythematosus (SLE). METHODS: We included pregnant SLE patients enrolled in the prospective GR2 study receiving HCQ, with at least one available first-trimester whole-blood HCQ assay. We evaluated several cut-offs for HCQ whole blood levels, including ≤200 ng/ml for severe non-adherence. Primary outcomes were maternal flares during the second and third trimesters of pregnancy, and adverse pregnancy outcomes (APOs: fetal/neonatal death, placental insufficiency with preterm delivery, and small-for-gestational-age neonates). RESULTS: We included 174 patients (median age: 32.1 years, IQR 28.8-35.2). Thirty (17.2%) patients had flares, 4 (2.3%) being severe. APOs occurred in 28 patients (16.1%). There were no significant differences in APOs by HCQ level for either those with subtherapeutic HCQ levels (≤500 ng/ml vs >500 ng/ml: 23.5% vs 14.3%, p = 0.19) or those with non-adherent HCQ levels (≤200 ng/ml vs >200 ng/ml: 20.0% vs 15.7%, p = 0.71). Similarly, the overall rate of maternal flares did not differ significantly by HCQ level cut-off, but patients with subtherapeutic (HCQ ≤500 ng/ml: 8.8% vs 0.7%, p = 0.02) and non-adherent HCQ levels (≤200 ng/ml: 13.3% vs 1.3%, p = 0.04) had significantly more severe flares. CONCLUSION: In this large prospective study of pregnant SLE patients, first-trimester subtherapeutic (≤500 ng/ml) and severe non-adherent (≤200 ng/ml) HCQ levels were associated with severe maternal flares, but not with APOs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02450396.

Challenges of designing and conducting cohort studies and clinical trials in populations of pregnant people.

Rheumatic and musculoskeletal diseases often affect individuals of childbearing age. The incidence and prevalence of rheumatic and musculoskeletal diseases is rising. More pregnancies in patients with rheumatic and musculoskeletal diseases are anticipated and some rheumatic and musculoskeletal diseases are associated with pregnancy complications (eg, miscarriages, fetal deaths, preterm births, and hypertensive disorders in pregnancy). Despite the need to understand the use of drugs to treat rheumatic and musculoskeletal diseases in pregnancy, clinical trials in pregnancy are rare, therapeutics in pregnancy are understudied, and pregnant individuals are routinely excluded as premarketing trial participants. Data on the effectiveness and safety of disease-modifying antirheumatic drugs are most often based on post-marketing observational data. Observational studies assessing the bidirectional relationship between rheumatic and musculoskeletal diseases and pregnancy, as well as interventional studies of treatments during pregnancy, are scarce. Historical reluctance to perform studies in what was deemed an at-risk group persists in pharmaceutical companies, regulatory bodies, and ethics boards. Additionally, patients must be engaged partners, which requires trust that the research respects the needs and interests of the patient and complies with the rules intended to protect the pregnant person and the fetus from harm. In this Series paper, we share challenges we have encountered in conducting prospective cohort studies and interventional trials of postmarketing approved medications, assessing pregnancy specific outcomes in pregnant women with rheumatic and musculoskeletal diseases in the EU, the UK, and the USA. We discuss the changing landscape around trials in pregnancy and present possible solutions to our challenges.

Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. METHODS: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. FINDINGS: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. INTERPRETATION: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. FUNDING: None.

Relapsing polychondritis: clinical updates and new differential diagnoses.

Relapsing polychondritis is a rare inflammatory disease characterized by recurrent inflammation of cartilaginous structures, mainly of the ears, nose and respiratory tract, with a broad spectrum of accompanying systemic features. Despite its rarity, prompt recognition and accurate diagnosis of relapsing polychondritis is crucial for appropriate management and optimal outcomes. Our understanding of relapsing polychondritis has changed markedly in the past couple of years with the identification of three distinct patient clusters that have different clinical manifestations and prognostic outcomes. With the progress of pangenomic sequencing and the discovery of new somatic and monogenic autoinflammatory diseases, new differential diagnoses have emerged, notably the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, autoinflammatory diseases and immune checkpoint inhibitor-related adverse events. In this Review, we present a detailed update of the newly identified clusters and highlight red flags that should raise suspicion of these alternative diagnoses. The identification of these different clusters and mimickers has a direct impact on the management, follow-up and prognosis of patients with relapsing polychondritis and autoinflammatory syndromes.

Chronic interstitial lung disease associated with systemic lupus erythematosus: A multicentric study of 89 cases.

BACKGROUND AND OBJECTIVE: Chronic interstitial lung disease (ILD) occurs rarely with systemic lupus erythematosus (SLE) as compared with other connective tissue diseases. This multicentric retrospective study of patients with SLE-ILD from the OrphaLung and French SLE networks during 2005-2020 aimed to describe the characteristics of patients with SLE-ILD and analyse factors associated with prognosis. METHODS: We analysed data for 89 patients with SLE-ILD (82 women, 92.1%) (median age at SLE diagnosis: 35 years [interquartile range 27-47]). All patients met the 2019 EULAR/ACR criteria for the diagnosis of SLE. RESULTS: Forty two (47.2%) patients were positive for anti-ribonuclear protein antibodies and 45 (50.6%) for anti SSA/Ro antibodies. A total of 58 (65.2%) patients had another connective tissue disease: Sjögren's syndrome (n = 33, 37.1%), systemic sclerosis (n = 14, 15.7%), inflammatory myopathy (n = 6, 6.7%), or rheumatoid arthritis (n = 6, 6.7%). ILD was diagnosed along with SLE in 25 (28.1%) patients and at a median of 6 (0-14) years after the SLE diagnosis. The most frequent CT pattern was suggestive of non-specific interstitial pneumonia (n = 41, 46.0%) with or without superimposed organizing pneumonia. After a median follow-up of 86.5 [39.5-161.2] months, 18 (20.2%) patients had died and 6 (6.7%) underwent lung transplantation. The median 5-year and 10-year transplantation-free survival were 96% (92-100) and 87% (78-97). In total, 44 (49.4%) patients showed ILD progression. Cutaneous manifestations and Raynaud's phenomenon were associated with better survival. Only forced vital capacity was significantly associated with survival and ILD progression. CONCLUSION: ILD is a rare manifestation of SLE with good overall prognosis but with possible risk of ILD progression. Patients with SLE-ILD frequently have another connective tissue disease.

Issues with pregnancy in systemic lupus.

Systemic lupus erythematosus is a disease that affects a large number of young women of childbearing age. Today, pregnancy is considered safe in almost all women with lupus, especially when the disease is under control. However, pregnancies in this population have a higher risk of maternal complications than in the general population. It is therefore important to plan pregnancies as effectively as possible, using effective contraception and pre-pregnancy counselling. In fact, effective, well-tolerated contraception is essential for patients for whom pregnancy cannot be safely envisaged, particularly in the setting of teratogenic treatment or significant disease activity. Preconception counselling is essential and helps to anticipate several aspects of a future pregnancy. Several recent prospective studies have clearly identified risk factors for obstetric complications and disease flare. High level of lupus activity, low complement, primigravida and a history of lupus nephritis are predictive factors of disease flare when antiphospholipid syndrome or antiphospholipid antibodies (specifically for lupus anticoagulant), damage, activity of lupus are predictive for obstetric events. Appropriate therapeutic management is essential, based primarily on the continuation of hydroxychloroquine, although some recent warnings about its use in pregnancy have been discussed controversially. Corticosteroid therapy can be continued at the lowest possible dose, as can certain immunosuppressive drugs. In the case of a history of lupus nephritis, low-dose aspirin is also prescribed. Although still exceptional, the risk of neonatal lupus is also higher, in patients with anti-SSA and anti-SSB antibodies. The aim of this review is to summarise the risk factors for adverse obstetric outcomes and to improve medical and obstetric management in this population of pregnant women with lupus.

Comparison of patients with isolated cutaneous lupus erythematosus versus systemic lupus erythematosus with cutaneous lupus erythematosus as the sole clinical feature: A monocentric study of 149 patients.

BACKGROUND: Cutaneous lupus erythematosus (CLE) may present as an isolated entity or be classified as Systemic lupus erythematosus (SLE) by the presence of laboratory abnormalities, including cytopenia, low complement levels, and/or autoantibodies (CLE with laboratory SLE). OBJECTIVE: To compare isolated CLE and CLE with laboratory SLE and to validate an existing 3-item score with age < 25 years (1 point), phototypes V to VI (1 point), antinuclear antibodies ≥ 1:320 (5 points) to predict the risk of progression from CLE to severe SLE (sSLE). METHODS: Monocentric cohort study including consecutive patients with CLE. CLE with laboratory SLE was defined by 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for SLE score of ≥10 points at baseline with CLE as the sole clinical feature. RESULTS: Of the 149 patients with CLE, 20 had CLE with laboratory SLE. The median follow-up duration was 11.3 years (IQR: 5.1-20.5). Ten patients (7%) had sSLE developed. In survival analysis, the risk of progression to sSLE was higher among CLE with laboratory SLE (hazard ratio = 6.69; 95% CI: 1.93-23.14, P < .001) compared to isolated CLE. In both groups, none of the patients with a risk score ≤ 2 had sSLE developed. LIMITATIONS: Monocentric study with a limited number of patients. CONCLUSIONS: CLE with laboratory patients with SLE have a higher risk of progression to sSLE than isolated CLE.

ANCA-associated scleritis: impact of ANCA on presentation, response to therapy and outcome.

OBJECTIVES: To describe the characteristics, treatment and outcome of isolated ANCA-associated scleritis at diagnosis compared with idiopathic scleritis with negative ANCA tests. METHODS: This retrospective multicentre case-control study was performed within the French Vasculitis Study Group (FVSG) network and in three French tertiary ophthalmologic centres. Data from patients with scleritis without any systemic manifestation and with positive ANCA results were compared with those of a control group of patients with idiopathic scleritis with negative ANCA tests. RESULTS: A total of 120 patients, including 38 patients with ANCA-associated scleritis and 82 control patients, diagnosed between January 2007 and April 2022 were included. The median follow-up was 28 months (IQR 10-60). The median age at diagnosis was 48 years (IQR 33-60) and 75% were females. Scleromalacia was more frequent in ANCA-positive patients (P = 0.027) and 54% had associated ophthalmologic manifestations, without significant differences. ANCA-associated scleritis more frequently required systemic medications, including glucocorticoids (76% vs 34%; P < 0.001), and rituximab (P = 0.03) and had a lower remission rate after the first- and second-line treatment. Systemic ANCA-associated vasculitis (AAV) occurred in 30.7% of patients with PR3- or MPO-ANCA, after a median interval of 30 months (IQR 16.3-44). Increased CRP >5 mg/l at diagnosis was the only significant risk factor of progression to systemic AAV [adjusted hazard ratio 5.85 (95% CI 1.10, 31.01), P = 0.038]. CONCLUSION: Isolated ANCA-associated scleritis is mostly anterior scleritis with a higher risk of scleromalacia than ANCA-negative idiopathic scleritis and is more often difficult to treat. One-third of patients with PR3- or MPO-ANCA scleritis progressed to systemic AAV.

Clinical presentation, course, and prognosis of patients with mixed connective tissue disease: A multicenter retrospective cohort.

OBJECTIVES: The objective of this study is to better characterize the features and outcomes of a large population of patients with mixed connective tissue disease (MCTD). METHODS: We performed an observational retrospective multicenter cohort study in France. Patients who fulfilled at least one diagnostic criterion set for MCTD and none of the criteria for other differentiated CTD (dCTD) were included. RESULTS: Three hundred and thirty patients (88% females, median [interquartile range] age of 35 years [26-45]) were included. The diagnostic criteria of Sharp or Kasukawa were met by 97.3% and 93.3% of patients, respectively. None met other classification criteria without fulfilling Sharp or Kasukawa criteria. After a median follow-up of 8 (3-14) years, 149 (45.2%) patients achieved remission, 92 (27.9%) had interstitial lung disease, 25 (7.6%) had pulmonary hypertension, and 18 (5.6%) died. Eighty-five (25.8%) patients progressed to a dCTD, mainly systemic sclerosis (15.8%) or systemic lupus erythematosus (10.6%). Median duration between diagnosis and progression to a dCTD was 5 (2-11) years. The presence at MCTD diagnosis of an abnormal pattern on nailfold capillaroscopy (odds ratio [OR] = 2.44, 95% confidence interval [95%CI] [1.11-5.58]) and parotid swelling (OR = 3.86, 95%CI [1.31-11.4]) were statistically associated with progression to a dCTD. Patients who did not progress to a dCTD were more likely to achieve remission at the last follow-up (51.8% vs. 25.9%). CONCLUSIONS: This study shows that MCTD is a distinct entity that can be classified using either Kasukawa or Sharp criteria, and that only 25.8% of patients progress to a dCTD during follow-up.

EBV-Positive Inflammatory Follicular Dendritic Cell Sarcoma of the Spleen: Report of an Aggressive Form With Molecular Characterization.

EBV-positive inflammatory follicular dendritic cell sarcoma (EBV+ inflammatory FDCS) is a rare neoplasm almost exclusively located in the spleen or liver. It is characterized by a proliferation of EBV-positive spindle-shaped cells bearing follicular dendritic cell markers, associated with an abundant lymphoplasmacytic infiltrate. EBV+ inflammatory FDCS is often asymptomatic or responsible for mild symptoms. It usually displays an indolent course and its prognosis is excellent after tumor removal, although relapsing and metastatic forms exist. Herein, we describe an aggressive form of splenic EBV+ inflammatory FDCS in a 79-year-old woman presenting with abdominal pain, deterioration of general health status, major inflammatory syndrome, and symptomatic hypercalcemia. A splenectomy was performed leading to a rapid improvement in her clinical condition and normalization of laboratory abnormalities. Unfortunately, her symptoms and laboratory abnormalities reappeared 4 months later. Computed tomography showed a mass in the splenectomy site and multiple liver and peritoneal nodules. Further analyses were performed on tumor tissue and showed positive phospho-ERK staining of tumoral cells indicating activation of MAPK pathway. Inactivating mutations were found on CDKN2A and NF1 genes. Subsequently, the patient's condition deteriorated rapidly. Since interleukin-6 levels were dramatically increased, tocilizumab was used but only had a transient effect on the patient's symptoms and inflammatory syndrome. Antitumor agent gemcitabine was initiated but her clinical condition continued to deteriorate and the patient died 2 weeks later. The management of aggressive forms of EBV+ inflammatory FDCS remains challenging. However, since these tumors seem to display genetic alterations, better characterization could lead to molecular targeted therapies.

Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry.

OBJECTIVES: Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. METHODS: We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. RESULTS: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. CONCLUSIONS: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation.

The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria.

OBJECTIVE: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. METHODS: This international multidisciplinary initiative included 4 phases: 1) Phase I, criteria generation by surveys and literature review; 2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; 3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and 4) Phase IV, validation using independent adjudicators' consensus as the gold standard. RESULTS: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and 2 laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-ß2 -glycoprotein I antibodies). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria versus the 2006 revised Sapporo classification criteria had a specificity of 99% versus 86%, and a sensitivity of 84% versus 99%. CONCLUSION: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.