2023 ACR/EULAR classification criteria in existing research cohorts: an international study.

OBJECTIVE: Assessing the impact of the updated ACR/EULAR APS classification criteria to our research cohort. METHODS: Consecutive patients who tested persistently positive for at least one aPL in the last three years were enrolled. The first APS Sydney index event was considered and computed for the comparison between Sydney and 2023 APS criteria. When computing the 2023 APS criteria, additional manifestations were also considered. RESULTS: The cohort comprised 249 patients (185 with APS and 64 aPL carriers according to Sydney criteria). The 185 patients had as first index event VT in 55 cases (29.8%) AT in 63 (34%) and PM in 67 (36.2%). When applying the updated criteria, 90 subjects (48.7%) failed to reach the composite score of the new criteria. The percentage of thrombotic APS per Sydney criteria decreased from 47.3% to 34.9% because of high cardiovascular risk in 23 cases, IgM aPL profile in 6 cases and in 2 patients for both reasons. Patients with PM decreased from 26.9-3.2% (39 cases of recurrent early pregnancy loss and 20 of fetal losses). Consequently, the percentage of aPL carriers increased from 26% to 61%. When looking at the disease evolution at follow-up, 32 additional patients out of 90 (35.6%) fulfilled the new APS criteria, after developing additional clinical manifestation following index event. CONCLUSION: When applying the new APS criteria to our research cohort, not negligible differences exist in patients' classification. A multidisciplinary approach will be mandatory to assess the impact into research and, ultimately, patient's care of new criteria.

Clinical manifestations in patients with antiphospholipid antibodies: Beyond thrombosis and pregnancy loss.

The clinical spectrum of the antiphospholipid syndrome (APS) encompasses additional manifestations other than thrombosis and pregnancy morbidity, which may potentially affect every organ and system. The pathophysiology of APS indeed cannot be explained exclusively by a prothrombotic state and the "extra-criteria" manifestations of the syndrome should be attributed to other mechanisms, such as inflammation, complement and platelet activation. In this case-series, we report patients with uncommon clinical APS presentations, to highlight relevant peculiarities of the syndrome, potentially paving the way for a further update of clinical as well as laboratory manifestations of this complex immunological condition.

Impact of the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus in a Multicenter Cohort Study of 133 Women With Undifferentiated Connective Tissue Disease.

OBJECTIVE: We aimed to investigate the impact of applying the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) in a previously described cohort of women with undifferentiated connective tissue disease (UCTD). METHODS: This study included 133 women with UCTD. At the time of inclusion into the study, none of the patients met any classification criteria for other defined systemic connective tissue disease. RESULTS: When applying the 2019 EULAR/ACR classification criteria to the cohort, 22 patients (17%) fulfilled the classification criteria for SLE. Patients classified as having SLE had significantly higher frequencies of mucocutaneous manifestations (23% versus 5%; P = 0.007), arthritis (59% versus 17%; P < 0.001), isolated urine abnormalities (18% versus 1%; P < 0.001), and highly specific antibodies (50% versus 15%; P < 0.001) compared to the other patients with UCTD. At follow-up, these patients were statistically significantly more likely to also meet the 1997 ACR revised SLE criteria and the Systemic Lupus International Collaborating Clinics (SLICC) criteria (18.2% versus 1.8%; P < 0.001) compared to the other UCTD patients. Patients who were diagnosed as having SLE according to the ACR 1997 update of the SLE revised criteria and the SLICC criteria during the follow-up scored higher on outcome measures when classified as having SLE according to the new 2019 EULAR/ACR classification criteria when compared to the other patients with UCTD (mean ± SD score 8.3 ± 3.7 versus 4.5 ± 4; P < 0.05). CONCLUSION: When applying the 2019 EULAR/ACR criteria for SLE in a cohort of patients with UCTD, we observed that in up to 17% of cases the original classification could be challenged. New implementation will help to identify earlier patients at higher risk of developing more severe CTD manifestations.

The prevalence of antiphospholipid antibodies in women with late pregnancy complications and low-risk for chromosomal abnormalities.

BACKGROUND: Antiphospholipid antibodies (aPL) are known to increase the risk of obstetrical complications. However, aPL significance and prevalence in women with late-onset pregnancy complications (LO-PC) need further clarification. OBJECTIVES: To investigate the prevalence of aPL in a cohort of women who experienced LO-PC and to compare it with a cohort of uneventful pregnancies. METHODS: One hundred pregnant women who experienced LO-PC, had a low risk for chromosomal abnormalities, and absence of fetal abnormalities were recruited from August 2018 to August 2019. One hundred women with uneventful pregnancy were included as controls. aPL testing was performed on serum samples derived from prenatal screening test and included both criteria and "extra criteria" aPL. RESULTS: Patients with LO-PC had significantly higher aPL prevalence when compared with controls (31/100 [31%] vs 10/100 [10%]; P < .001). More in detail, up to 26% of women with LO-PC were positive for one aPL, with an overall prevalence significantly higher than controls (26% vs 9%; P < .05). Among single aPL positivity, patients had significantly higher rate of positivity and titers of anticardiolipin IgG (10% vs 2%; mean ± standard deviation 11 ± 13 vs 4 ± 9.6 chemoluminescent unit; P < .05) and phosphatidylserine-prothrombin antibodies (aPS/PT) IgM (15% vs 6%; mean ± standard deviation 10.2 ± 21.7 vs 3.7 ± 13.7 U; P < .05). Testing for aPS/PT (IgM/IgG) alone allowed the identification of 17 patients negative for criteria aPL. aPL-positive patients had a significantly higher risk of preterm birth (34-36 + 6 weeks; 10% vs 8%; P < .012). CONCLUSIONS: We report a high prevalence of aPL in our cohort. Testing for both criteria and "extra criteria" aPL in women with previous LO-PC could improve the diagnostic accuracy identifying women at higher risk for recurrent pregnancy complications.

Antiphosphatidylserine/Prothrombin Antibodies: An Update on Their Association with Clinical Manifestations of Antiphospholipid Syndrome.

OBJECTIVE: The aim of the study is to perform a systematic review on the recent available evidence on antiphosphatidylserine/prothrombin (aPS/PT) antibodies and their association with clinical manifestations of the antiphospholipid syndrome (APS). METHODS: A detailed literature search was applied a priori to Ovid MEDLINE, In-Process and Other Non-Indexed Citation 2012 to present and to abstract from EULAR and ACR/ARHP Annual Meetings (2012-2019). RESULTS: Data from 2,901 patients, 587 diseases controls and 559 healthy controls included in 15 retrieved studies was analyzed. The patient population included 1,219 patients classified as APS according to the Sidney criteria, 285 patients with isolated persistently positive antiphospholipid antibodies (aPL) and 1,397 patients with a clinical suspicion of APS. Twelve studies, including 1,888 patients, analyzed the association between aPS/PT antibodies and thrombosis. We observed a statistically significant association between aPS/PT IgG/IgM positivity and thrombotic events (mean odds ratio [OR]: 6.8 [95% CI: 3.18-16.4], p < 0.05), confirmed when analyzing aPS/PT IgG (mean OR: 6.7 [95% CI: 3.04-21.6], p < 0.05) and aPS/PT IgM (mean OR: 4.35 [95% CI: 1.54-17.77], p < 0.05) separately. Seven studies, including 1,388 patients, evaluated the association between aPS/PT antibodies and PM. When pooled together, we found a statistically significant association between any PM and aPS/PT IgG/IgM positivity (mean OR: 10.6 [95% CI: 3.54-35.38], p < 0.05), particularly aPS/PT IgG positivity (mean OR: 6.7 [95% CI: 3.04-21.6], p < 0.05). CONCLUSION: Our results highlight the strong association between aPS/PT and the clinical manifestations of APS. With the available level of evidence, aPS/PT testing can be considered as a robust test applicable in the investigation of patients suspected for APS, also beyond the research settings.

A multicentre study of 244 pregnancies in undifferentiated connective tissue disease: maternal/fetal outcomes and disease evolution.

OBJECTIVES: To investigate fetal/perinatal and maternal outcomes from a large multicentre cohort of women diagnosed with UCTD. METHODS: This multicentre retrospective cohort study describes the outcomes of 224 pregnancies in 133 consecutive women with a diagnosis of UCTD, positive for ANA and aged <45 years old at study inclusion. RESULTS: Of the 224 pregnancies analysed, 177 (79%) resulted in live births, 45 (20.1%) in miscarriages (defined as pregnancy loss before 12 weeks' gestation), 2 (0.9%) in stillbirths (pregnancy loss after 20 weeks' gestation) and 6 (2.7%) cases showed intrauterine growth restriction. Miscarriages and stillbirths were strongly associated with the presence of aPL and ENA antibodies (P < 0.05). Maternal pregnancy complications were as follows: 5 (2.2%) cases developed pre-eclampsia, 11 (4.9%) cases gestational hypertension and 12 (5.4%) cases gestational diabetes. Joint involvement represented the most frequent clinical manifestation of the cohort (57.9%), followed by RP (40.6%), photosensitivity (32.3%) and haematological manifestations (27.1%). The rate of disease evolution of our cohort from a diagnosis of UCTD to a diagnosis of definite CTD was 12% within a mean time of 5.3 ± 2.8 years. With a total follow-up after first pregnancy of 1417 patient-years, we observed the evolution to a defined CTD in one out of every 88 patient- years. CONCLUSION: In our multicentre cohort, women with UCTD had a live birth rate of 79%. Women with UCTD should be referred to specialist follow-up when planning a pregnancy. ENA profiling and aPL testing should be mandatory in this setting, and further therapeutic approaches and management should be planned accordingly.