Objectives:
Women with Rheumatoid Arthritis (RA) can experience flares during pregnancy that might influence pregnancy outcomes. We aimed at assessing the disease course during pregnancy and ...identifying risk factors for flares.
Methods:
Data about prospectively-followed pregnancies in RA were retrospectively collected before conception, during each trimester and in the post-partum period. Clinical characteristics, disease activity (DAS28-CRP3), medication use, and pregnancy outcomes were analysed with regard to disease flares.
Results:
Among 73 women who had a live birth, 64 (88%) were in remission/low disease activity before conception. During pregnancy, a flare occurred in 27 (37%) patients, mainly during first and second trimester. Flares during pregnancy were associated with the discontinuation of bDMARDs at positive pregnancy test (55% of patients with flare vs
.
30% of patients with no flare,
p
0.034, OR 2.857, 95% CI 1.112–8.323) and a previous use of >1 bDMARDs (33% of patients with flare vs
.
10% of patients with no flare,
p
0.019, OR 4.1, 95%CI 1.204–13.966). Preterm pregnancies were characterised by higher values of CRP 10 mg/L (5–11) vs
.
3 mg/L (2.5–5),
p
0.01 and DAS28-CRP3 4.2 (1.9–4.5) vs
.
1.9 (1.7–2.6),
p
0.01 during the first trimester as compared with pregnancies at term. Preterm delivery was associated with the occurrence of flare during pregnancy (flare 27% vs
.
no-flare 7%,
p
0.034, OR 4.625, 95%CI 1.027–20.829).
Conclusion:
Preterm delivery in RA patients was associated with flares during pregnancy. Flares occurred more frequently after the discontinuation of bDMARDs at positive pregnancy test. Women with aggressive RA on treatment with bDMARDs should be considered as candidates for continuing bDMARDs during pregnancy in order to reduce the risk of flare and adverse pregnancy outcomes.
Sjögren’s syndrome (SS) is a complex autoimmune rheumatic disease that specifically targets salivary and lachrymal glands. As such, patients typically had ocular and oral dryness and salivary gland ...swelling. Moreover, skin, nasal and vaginal dryness are frequently present. In addition to dryness, musculoskeletal pain and fatigue are the hallmarks of this disease and constitute the classic symptom triad presented by the vast majority of patients. Up to 30% to 50 % of patients with SS may present systemic disease; moreover, there is an increased risk for the development of non-Hodgkin’s lymphoma that occurs in a minority of patients. The present work was developed in the framework of the European Reference Network (ERN) dedicated to Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET). In line with its goals of aiming to improve early diagnosis, treatment and care of rare connective and musculoskeletal diseases, ERN-ReCONNET set to review the current state of clinical practice guidelines (CPGs) in the rare and complex connective tissue diseases of interest of the network. Therefore, the present work was aimed at providing a state of the art of CPGs for SS.
Despite the widely recognized practical importance of anticardiolipin (aCL) ELISA, the reliability of this test has been recently discussed. In order to investigate this area on European scale, we ...sent to 30 experienced centers a questionnaire focusing on the diagnostic procedures applied to patients with antiphospholipid syndrome (APS) and on the detailed protocols used to perform aCL. Anticardiolipin ELISA was found to be the most frequently performed test in patients with suspected APS, but significant difference was shown among the various protocols. The cross-laboratory multiple examination of ten serum samples evaluated independently by the 24 centers pointed out the difficulty in getting comparable results. Therefore a "consensus" protocol was derived from the aCL methods giving the best performance. The materials and reagents necessary to perform the "consensus" method, including, as putative standards, one IgG and one IgM monoclonal antibody (HCAL and EY2C9) were distributed to 19 Centers. The results of one IgG and one IgM aCL high positive sera measured in serial dilutions were compared. A progressive decrease in the variability of the values obtained for a given sample appeared evident when all the laboratories used the same standard, in their own in-house ELISA and even more in the "consensus" ELISA. Our data show that aCL ELISA standardization is necessary in order to obtain comparable results in different laboratories.
A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia.
A prospective series of 100 consecutive patients ...admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response.
The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24–72 h and 10 days after tocilizumab administration.
Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 IQR 0–2), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died.
All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10.
In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.
The aim of the study was to evaluate predictors of disease flares during pregnancy and obstetric and fetal complications in a cohort of systemic lupus erythematosus (SLE) patients. One hundred and ...thirty-two pregnancies in 96 SLE patients were prospectively followed by monthly clinical and laboratory evaluations. Predictors of lupus flares, fetal and obstetric complications during pregnancy were identified performing stepwise logistic regression analysis. Maternal lupus flares occurred in 57 % of pregnancies and were being best predicted by the number of flares before conception. Manifestations during flares were best predicted by the same features occurred before conception: dermatological flares by skin rash, renal flares by nephritis, and hematological flares by hematological abnormalities. There were 110 live births and 22 fetal losses. Among live newborns, 22 % were premature. Fetal loss was best predicted by hypertension at conception; miscarriages by the amount of steroids taken during the last year before conception; stillbirth by the number of flares during the last year before conception; preterm birth by the coexistence of anti-phospholipid antibody syndrome and anti-double-stranded DNA antibody levels before conception; premature rupture of membranes by high ECLAM score during the 6 months before conception, small for gestation age by hypertension at conception; and preeclampsia by positive lupus anticoagulant. Some independent predictors of lupus flares and fetal and obstetric complications were identified, which can help the risk assessment of pregnancy in SLE patients.
To evaluate in vivo changes after therapy using autologous serum (AS) eye drops in Sjögren's syndrome (SS)-related dry eyes by confocal microscopy.
In this study, 24 patients with SS-related dry eyes ...12 in AS eye drop therapy and 12 in artificial tear (AT) therapy and 24 healthy volunteers were recruited. Ocular Surface Disease Index (OSDI), central corneal thickness, tear film, break-up time, corneal and conjunctival staining, Schirmer's test and corneal confocal microscopy were investigated.
Tear production, tear stability, corneal staining, inflammation, and central corneal thickness, Langherans cells, activated keratocytes, intermediate epithelial cell density, nerve tortuosity, number of sub-basal nerve branches, and number of bead-like formations differed between patients and controls (p<0.0001). The AT and AS groups differed in the OSDI, number of branches, and number of beadings (p<0.0001).
AS eye drops improve symptoms and confocal microscopy findings in SS-related dry eyes.
Objective. To analyse risk factors and comorbidities potentially associated with CNS involvement in a large cohort of Italian patients affected by SLE.
Methods. A number of generic (not strictly SLE ...related) and specific (disease related) risk factors to which all patients have been exposed in the span of 5 years before the first neuropsychiatric (NP) event or before the last available observation were checked for and their distribution was analysed in 959 SLE patients with and without NP involvement; all the first NP events that occurred in a time frame of 10 years were recorded and categorized as SLE related or SLE unrelated.
Results. Three hundred and twenty-six SLE patients with and 633 SLE patients without NP manifestations were included in the study. A total of 469 NP events were recorded. Headache (26.1%), cerebrovascular events (22.7%), mood disorders (8.9%), seizures (14.4%) and cognitive dysfunctions (9.5%) were the most frequent SLE-related NP events. More risk factors mean 4.52 (2.44) vs 3.73 (2.01); P < 0.0001 were observed in patients with than without NP involvement. Overall, aPLs, LA and APS were factors more strongly associated with NP involvement.
Conclusions. In SLE, NP involvement and aPLs were confirmed as closely related. Furthermore, other modifiable generic risk factors, such as hypertension, carotid vasculopathy and dyslipidaemia, appeared to be related to the occurrence of cerebral vascular accident (CVA) and cognitive dysfunctions, suggesting the need for a more intensive preventive strategy to optimize the management of NP lupus.
To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective ...observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery.
Key Points
•
In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy.
•
Flares were observed only in PLA and OLA-E patients.
•
Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.
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