The criteria for antiphospholipid syndrome (APS) include severe preeclampsia and/or placental insufficiency leading to preterm delivery before 34 weeks of gestation, but this APS manifestation has ...been rarely studied. Thus, we report a series of severe preeclampsia occurred in patients with APS.
We retrospectively analysed data of women with APS (Sydney criteria) who experienced severe preeclampsia with delivery before 34 weeks' gestation between 2000 and 2017 at five French internal medicine departments and one Italian rheumatology unit.
The 40 women had a mean age of 30.5 ± 4.6 years at their first episode of preeclampsia; 21 were nulligravid (52.5%), 12 (30%) had already been diagnosed with APS, and 21 (52.5%) had a triple-positive antiphospholipid (aPL) antibody test. Preeclampsia occurred at a median gestational age of 25.5 weeks (IQR 23-29). It was associated with HELLP in 18 cases (45%), eclampsia in 6 (15%), placental abruption in 3 (7.5%), catastrophic APS in 3 (7.5%), and foetal and neonatal death in 11 and 15 cases. Overall, 14 (35%) children survived, born at a median gestational age of 31 weeks. Among other APS criteria, 16 women (40%) experienced at least one thrombosis, 17 (42.5%) an intrauterine foetal death, and 19 (47.5%) at least one episode of HELLP during follow-up (median 5 years, IQR = 2-8). None had three or more consecutive miscarriages. Notably, 12 women (30%) had systemic lupus erythematosus.
Severe preeclampsia led to high mortality in the offspring. Almost half of these women experienced other APS features, but not three consecutive miscarriages.
Glucocorticoids (GCs) plus rituximab (RTX) represent the first-line treatment of nonviral mixed cryoglobulinemia vasculitis (CryoVas). However, data on therapeutic management and outcome of patients ...refractory to RTX are lacking.
We conducted a European collaborative retrospective multicenter study of patients with nonviral mixed CryoVas refractory to RTX and performed a literature review.
Twenty-six original cases and 7 additional patients from the literature were included. All patients but one had type 2 cryoglobulinemia, and causes were autoimmune disease (51%), malignant hemopathy (12%) or essential CryoVas (42%). CryoVas was primary refractory to RTX in 42%, while 58% had an initial response to RTX before immune escape. After RTX failure, patients received a median of 1 (IQR, 1–3) line of treatment, representing 65 treatment periods during follow-up. Main treatments used were GCs in 92%, alkylating agents in 43%, RTX in combination with other treatments in 46%, and belimumab in 17%. Combination of anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents provided the highest rates of clinical response in 100% 82% and 73%, respectively, but showed poor immunological response, in 50%, 30% and 38%, respectively. Rates of severe infection were 57%, 9% and 0% in patients receiving anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents, respectively.
In patients with nonviral mixed CryoVas refractory to RTX, anti-CD20 plus belimumab, and alkylating agents associated or not with anti-CD20, provide the highest rates of clinical response. However, anti-CD20 plus belimumab was frequently associated with severe infections.
•In rare cases, patients with nonviral mixed cryoglobulinemia vasculitis may be refractory to rituximab plus glucocorticoids.•In a European study combined with literature review, we found 33 refractory patients, amongst them 42% were primary refractory to rituximab.•Anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents provided the highest rates of clinical response.•Anti-CD20 plus belimumab was frequently associated with severe infections.
Although one of the three obstetric manifestations of antiphospholipid syndrome (APS) is intrauterine fetal death (IUFD), little is known about it in this context. We report the first large series of ...patients with APS and IUFD.
We retrospectively analyzed the history and clinical data of women at four French hospitals. All had (1) APS diagnosis (Sydney criteria) and (2) IUFD at or after 10 weeks of gestation (weeks) between 2000 and 2016.
The study included 65 women. Their median age at the index IUFD was 29 years (IQR 26-33); 38 (58%) were primigravidas. The index IUFD was the first APS clinical manifestation in 48 women (74%). Overall, 35% had a triple-positive antibody profile. IUFD occurred at a median gestational age of 24 weeks (IQR 18-27) and was associated with maternal obstetric complications in 16 women (25%), namely, preeclampsia (n = 12), hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP) (n = 6), and/or placental abruption (n = 5). Half of the 50 women with available data had a small-for-gestational-age fetus. Overall, including during the follow-up period of 4 years (IQR 2-9), 28 women (43%) had at least one thrombosis, and 29% were diagnosed with systemic lupus erythematosus (SLE). Ultimately, 54 women (83%) had at least one live birth. Only one woman had three consecutive early miscarriages.
IUFD was most often the inaugural sign of APS. Of the APS classification criteria, IUFD, preeclampsia, and thromboses were common in this cohort, while the "3 consecutive early miscarriages" criterion was met only once. With treatment, most of the women successfully had at least one live birth.
ObjectiveAlthough airway disease associated with Sjögren’s disease (Sjo-AD) is common, it is poorly studied compared with interstitial lung disease (ILD). In this study, we aimed to assess factors ...associated with Sjo-AD, the characteristics and prognosis of this manifestation.MethodsWe performed a retrospective multicentric study involving nine centres. We included Sjo-AD patients confirmed by at least one clinician and one CT scan report. Clinical and biological data, pulmonary function test (PFT), and CT scans were collected. A single radiologist specialist in thoracic diseases reviewed CT scans. Sjo-AD patients were compared with Sjo controls without pulmonary involvement, randomly selected after matching for age and disease duration.ResultsWe included 31 Sjo-AD and 62 Sjo controls without pulmonary history. Sjo-AD had a higher disease activity (ESSDAI) compared with controls, even when excluding the pulmonary domain of the score (7 vs 3.8, p<0.05), mainly due to the biological activity. Sjo-AD was multilobar (72%) and associated with signs of both bronchiectasis and bronchiolitis (60%). Obstructive lung disease occurred in 32% at the time of Sjo-AD diagnosis. Overall, PFT was stable after 8.7±7 years follow-up but repeated CT scans showed extended lesions in 41% of cases within 6±3.2 years. No patient developed Sjo-ILD. Sjo-AD progression was independent of the global disease activity.ConclusionsSjo-AD preferentially affects Sjo patients with higher biological activity. It is often characterised as a diffuse disease, affecting both proximal and distal airways, with a slow evolution over time and no progression to Sjo-ILD.
Objective
Even though systemic vasculitides (SVs) affect primarily patients over 50 years of age, they can occur among women of childbearing age. Preterm birth (PTB) and hypertensive disorders are ...frequent complications of pregnancy in SVs. This study aims to evaluate the risk of hypertensive disorders and PTB among pregnant women with SVs, and to identify associated risk factors.
Method
Using the French health insurance data warehouse, we conducted a nationwide cohort study including all pregnancies between 2013 and 2018 in women with SVs. Theses pregnancies were matched to pregnancies among women without SVs. We estimated risk of hypertensive disorders and PTB risk during pregnancy among women with SVs and investigated associated risk factors using a nested case‐control design.
Results
Among 3,155,723 pregnancies, we identified 646 pregnancies in women with SVs, matched to 3,230 controls. SVs were significantly associated with hypertensive disorders (odds ratio OR 1.7, 95% confidence interval 95% CI 1.3–2.2) and PTB (OR 1.8, 95% CI 1.4–2.3). Chronic renal failure before pregnancy, history of or treated arterial hypertension, the occurrence of vasculitides flare during pregnancy, and the subgroup of SVs were independently associated with the occurrence of hypertensive disorders. Maternal age at delivery, chronic renal failure before conception, and the occurrence of vasculitides flare during pregnancy were independently associated with the occurrence of PTB.
Conclusion
About one of seven pregnancies in women with SVs is associated with hypertensive disorders or preterm birth. The occurrence of vasculitides flare was associated with these complications. Our findings support the importance of prepregnancy counseling to ensure disease stability.
ObjectiveG1 and G2 polymorphisms of APOL1 gene, exclusively found among patients of African ancestry, have been associated with chronic kidney disease (CKD) and collapsing glomerulopathy. We ...investigated their impact on lupus nephritis (LN).MethodsWe included patients from 6 hospitals in Paris and Marseille in France, between January 2017 and March 2020, with biopsy-proven LN, African ancestry and age >18 years at the time of inclusion. We excluded those with HIV infection. The data were retrospectively collected at LN diagnosis, 1 year after diagnosis and at last follow-up. APOL1 genotyping was performed and we divided patients in 2 groups: the high-risk genotype (HRG) group with 2 risk alleles and the low-risk genotype (LRG) group with 1 or 0 risk allele. All patients signed a consent form for the genetic analysis and protocol approval was obtained from the ethic committee CERAPHP (Comité d’Ethique de la Recherche AP-HP Centre), registration number 00011928.ResultsNinety-nine patients were included, 13 in the HRG group and 86 in the LRG group. At LN diagnosis, clinical and biological characteristics were similar except for kidney function that was more impaired in the HRG group compared to the LRG group with a median serum creatinine of 131μmol/L 73–641 versus 66μmol/L 53–128 (p=0.01). Patients in the HRG group were more likely to have a serum creatinine above 200μmol/L compared to the LRG group (46% versus 11%, p=0.01, OR 7.11.8–28.6), and required acute haemodialysis more frequently (31% versus 1% respectively, p = 0.001, OR 34.73.5–345.1). Collapsing glomerulopathy was more frequent in the HRG group (46% of patients, versus 5%, OR 17.53.3–91.9, p=0.001). Patients in the HRG group were more likely to develop CKD at 1 year follow-up (33% versus 5%, OR 9.62.0–46.1) (table 1). Survival without kidney failure was poorer in the HRG group with a hazard ratio (HR) of 4.6 1.5–14.2, p=0.006, even after adjusting with the kidney response at 12 months (adjusted HR 6.241.8–21.6, p=0.004) (figure 1).Conclusion APOL1 high risk genotype was associated to a worse kidney function at diagnosis, development of collapsing glomerulopathy and higher risk of subsequent kidney failure.Abstract O24 Table 1Data at Lupus nephritis diagnosis, at 1 year follow-up and at last follow-up Variables HRG N=13 LRG N=86 OR CI95% P value Data at LN diagnosis Age at LN diagnosis, median IQR 26 21–32 25 20–34 - 0.9 Inaugural LN, N (%) 7/13 (54) 38/86 (44) 1.5 0.5–4.8 0.6 Serum creatinine (μmol/L), median IQR 131 73–641 66 53–128 - 0.01 eGFR, median IQR 44 8–103 107 52–126 - 0.006 Serum creatinine > 200μmol/L, N (%) 5/11 (46) 8/76 (11) 7.1 1.8 - 28.6 0.01 Need for haemodialysis, N (%) 4/13 (31) 1/79 (1) 34.7 3.5 - 345.1 0.001 Proteinuria (g/g), median IQR 3.7 1.6–5.9 4.4 2.0–7.1 - 0.5 Nephrotic syndrome, N (%) 7/12 (58) 47/74 (64) 0.8 0.2–2.8 0.8 Type ISN/RPS I or II, N (%) 1/13 (8) 11/83 (13) 0.6 0.1–4.6 0.9 Type ISN/RPS III or IV (± V), N (%) 11/13 (85) 48/83 (58) 4.0 0.8–19.3 0.08 Isolated Type ISN/RPS V, N (%) 0/13 (0) 24/83 (29) 0.09 0.0 - 1.6 0.03 Type ISN/RPS VI, N (%) 1/13 (8) 0/83 (0) 20.0 0.8–520.0 0.1 Glomerulosclerosis, N (%)* 4/12 (33) 5/67 (7) 6.2 1.4 - 28.0 0.03 Interstitial fibrosis, N (%)** 5/11 (46) 14/68 (21) 3.2 0.9–12.1 0.1 FSGS, N (%) 7/11 (64) 22/69 (31) 3.7 1.0–14.1 0.09 CG, N (%) 5/11 (46) 3/66 (5) 17.5 3.3 - 91.9 0.001 MCTD, N (%) 3/10 (33) 5/67 (8) 5.3 1.0–27.2 0.06 Outcomes at 1 year follow-up RAASi treatment, N (%) 5/10 (50) 43/58 (74) 0.35 0.1–1.4 0.2 eGFR, median IQR 99 63–106 116 92–126 - 0.02 Proteinuria g/g, median IQR 1.8 0.3–3.8 0.6 0.1–2.6 - 0.2 Overall kidney response, N (%)* 7/12 (58) 62/81 (77) 0.43 0.1–1.5 0.3 CKD III-V, N (%) 4/12 (33) 4/81 (5) 9.6 2.0 - 46.1 0.009 Kidney failure, N (%) 1/12 (1) 0/84 (0) 22.0 0.9–574.3 0.1 Outcomes at last follow-up Years of follow-up, median IQR*** 7.9 2.7–18.1 7.7 3.3–13.8 - 0.7 eGFR, median IQR 22 10–98 99 54–118 - 0.02 HR CI95% Kidney failure at last follow-up, N (%) 5/12 (42) 7/86 (8) 4.6 1.5–14.2 0.006 Legends N: Number of patients; IQR: Interquartile range; LN: Lupus nephritis; eGFR: estimated Glomerular Filtration Rate; ISN/RPS: International Society of Nephrology/Renal Pathology Society; FSGS: Focal and Segmental Glomerular Sclerosis; CG: Collapsing glomerulopathy; MCTD: microcystic tubular dilatation; RAASi : Renin-angiotensin-aldosterone system inhibitors ; HRG: High-risk genotype; LRG: Low-risk genotype; OR CI95%: Odds ratio with 95% interval of confidence ; HR CI95%: Hazard ratio with 95% interval of confidence *Glomerulosclerosis is considered if above or equal 10% of the glomeruli **Interstitial fibrosis is considered if above or equal to 10% of the kidney parenchyma *** Number of years between lupus nephritis diagnosis and last follow-up (end of study, loss of sight or end stage kidney disease) *** Related to duration of follow-up in yearsAbstract O24 Figure 1Patient survival without end-stage kidney disease. Legends: Data were censored at 15 years after LN diagnosis. Kaplan Meyer curve was analyzed with the log rank test. ESKD: End stage kidney disease; HRG: High risk genotype; LRG: Low risk genotype; HR: Hazard Ratio. *Hazard ratio was calculated based on the Cox regression, and was adjusted with the kidney response at 12 months (overall response versus none).
Although combining corticosteroids and cyclophosphamide has greatly improved the prognoses of severe necrotizing vasculitides, some patients continue to have fulminating disease and die within the ...first year of diagnosis. To evaluate the characteristics of these patients, we retrospectively studied the files of 60 patients who died within the first year (20 patients with hepatitis B virus-associated polyarteritis nodosa HBV-PAN, 18 with non-HBV PAN, 13 with microscopic polyangiitis MPA, and 9 with Churg-Strauss syndrome CSS) and 535 first-year survivors (89 patients with HBV-PAN, 182 with non-HBV PAN, 140 with MPA, and 124 with CSS), 85 of whom died during a mean follow-up of 6.4 years. The 2 groups were compared for prognostic factors defined by the five-factor score (FFS) and Birmingham Vasculitis Activity Score at baseline, clinical signs, treatment, outcome, and causes of death. For first-year nonsurvivors, the clinical signs predictive of death were as follows: renal involvement (hazard ratio HR, 1.6; 95% confidence intervals CI, 1.09-2.3) or central nervous system involvement (HR, 2.3; 95% CI, 1.5-3.7), and a trend toward cardiomyopathy (HR, 1.4; 95% CI, 1.000-2.115). Older patients died earlier (HR, 1.04; 95% CI, 1.023-1.051). Gastrointestinal symptoms were most frequently associated with early death from HBV-PAN, while 83% of CSS patients died of cardiac involvement. Treatment had no significant impact on early death, except for patients with FFS > or = 2, for whom steroids alone were associated (p < 0.05). The major cause of early death was uncontrolled vasculitis (58%), followed by infection (26%). Cyclophosphamide-induced cytopenia and infection were responsible for 2 deaths. Despite these iatrogenic complications, early deaths were more frequently the consequence of insufficient or inappropriate therapy.
IntroductionPregnancies in patients with systemic lupus erythematosus (SLE) are associated with an increased risk of adverse maternal (including flares) and fetal outcomes. Hydroxychloroquine (HCQ) ...decreases disease activity and the occurrence of flares, but little is known about the usefulness of monitoring HCQ blood levels during pregnancy. The aim of this study was to evaluate the correlation between HCQ blood levels in the first trimester of pregnancy, and the maternal and fetal outcomes in these patients.MethodsWe included pregnant SLE patients enrolled in the French prospective ‘Groupe de recherche sur la Grossesse et les Maladies Rares’ (GR2) study, with at least one available first-trimester whole-blood HCQ level. We evaluated several cut-offs: 500 ng/ml, 750, and 1000 ng/ml, as a therapeutic target, and a threshold of 200 ng/ml for assessing severe non-adherence. The primary outcomes were maternal flares (mild/moderate or severe, identified by SLEDAI Flare Index) during the 2nd and 3rd trimesters of pregnancy, and any adverse pregnancy outcomes (APOs), which included fetal/neonatal death, placental insufficiency resulting in preterm delivery, and/or small-for-gestational-age neonates.ResultsWe included 174 patients (median age 32.1 years -IQR 28.8–35.2-). Thirty (17.2%) patients had flares, 4 (2.3%) of these were severe. APOs occurred in 28 patients (16.1%). There were no significant differences in APOs according to HCQ levels, neither between those with infra-therapeutic HCQ levels ≤500 ng/ml vs >500 ng/ml (23.5% vs 14.3%, p=0.19), nor between those with non-adherent HCQ levels ≤200 ng/ml vs >200 ng/ml (20.0% vs 15.7%, p=0.67). There were no significant differences in maternal flares based on varying HCQ cut-offs. However, there was a significant increase in severe flares among patients with infra-therapeutic (HCQ ≤500 ng/ml) (8.8% vs 0.7%, p=0.005), and non-adherent (≤ 200 ng/ml) HCQ levels (13.3% vs 1.3%, p=0.003).ConclusionFirst-trimester HCQ blood levels did not predict APOs, but infra-therapeutic (≤500 ng/ml) and non-adherent HCQ levels (≤200 ng/ml) were associated with severe maternal flares during pregnancy. Therefore, this study supports the assessment of HCQ blood level monitoring in pregnant women with SLE, as an indicator of severe non-adherence, and a predictor of severe maternal disease activity during pregnancy.
Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration (HCQ) varies widely between patients and is a marker and predictor of SLE ...flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target HCQ ≥1000 ng/ml to reduce SLE flares.
HCQ was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with HCQ from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target HCQ (group 2). The primary end point was the number of patients with flares during 7 months of follow-up.
Overall, mean HCQ was 918±451 ng/ml. Active SLE was less prevalent in patients with higher HCQ. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in HCQ in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low HCQ (20.5% vs 35.1%, p=0.12).
Although low HCQ is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.
Objective
The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus ...erythematosus (SLE) flares, damage, and mortality rates over five years of follow‐up.
Methods
The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index SDI increase ≥1 point) and mortality with separate Cox proportional hazard models.
Results
Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244–566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval CI 1.80–6.42) and an increase in the SDI within each of the first three years (hazard ratio HR 1.92 at three years; 95% CI 1.05–3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43–20.39).
Conclusion
Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five‐year mortality.
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