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.
Abstract
Background
Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been ...compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients.
Methods
HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL.
Results
The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (
P
= 0.023), but not serum HCQ levels, were independently associated with active SLE.
From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76–0.94) and specificity of 0.89 (95% CI 0.72–0.98).
All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL).
Conclusions
These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.
Summary
Patients with common variable immunodeficiency (CVID) are at high risk of developing immune thrombocytopenia (ITP) and/or autoimmune haemolytic anaemia (AHA). Given their underlying ...immunodeficiency, immunosuppressive treatment of these manifestations may increase the risk of infection. To assess efficacy and safety of rituximab in patients with CVID‐associated ITP/AHA, a multicentre retrospective study was performed. Thirty‐three patients, 29 adults and four children, were included. Patients received an average of 2·6 treatments prior to rituximab including steroids, intravenous immunoglobulin and splenectomy (21%). The median ITP/AHA duration at time of first rituximab administration was 12 months range 1–324 and the indication for using rituximab was ITP (22 cases), AHA (n = 5) or both (n = 7); 1 patient was treated sequentially for ITP and then AHA. The overall initial response rate to rituximab was 85% including 74% complete responses. After a mean follow‐up of 39 ± 30 months after rituximab first administration, 10 of the initial responders relapsed and re‐treatment with rituximab was successful in 7/9. Severe infections occurred after rituximab in eight adults (24%), four of whom were not on immunoglobulin replacement therapy. In conclusion, rituximab appears to be highly effective and relatively safe for the management of CVID‐associated severe immune cytopenias.
Abstract The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French ...internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9 years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5 years (range: 1.6–35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36 months (range: 2–79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3–4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6 mg/d (range: 5–25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.
Objective
Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal ...complications and adverse outcomes were analysed.
Methods
All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015.
Results
The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (
n
= 15), 9% with pre-eclampsia (
n
= 4), 2% with HELLP syndrome (
n
= 1) and 14% with intrauterine growth restriction (IUGR,
n
= 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 27–42 weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 610–4310 grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (
n
= 25/43; 58%), azathioprine (
n
= 9/43; 21%) and infliximab (
n
= 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (
P
= 0.01 and
P
= 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study.
Conclusion
This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates
.
Pregnancy did not appear to influence TAK disease activity.
Key Points
•
We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high
.
Pregnancy did not appear to influence TA disease activity.
Abstract Objective Kawasaki disease (KD) is a vasculitis that mostly occurs in young children and rarely in adults. We analyzed the characteristics of adult-onset KD (AKD) in France. Methods We ...collected retrospective and prospective data for patients with a diagnosis of KD occurring after the age of 18 years. Cases were obtained via various French medical networks and identified from the international literature. Results We included 43 patients of AKD at 26 institution from 1992 to 2015, with mean (SD) age 30 (11) years (range 18–68) and sex ratio (M/F) 1.2; 34 patients met the American Heart Association criteria and 9 were incomplete AKD. The median time to diagnosis was 13 days (interquartile range 8–21). The main symptoms were fever (100%), exanthema (98%), changes in the extremities (91%), conjunctivitis (77%), oral cavity changes (89%), cervical adenitis (55%) and cardiac abnormalities (45%). Overall, 35% of patients showed large-vessel vasculitis: coronary vasculitis (26%) and coronary aneurysm (19%). Treatment was mostly intravenous immunoglobulins (79%) and aspirin (81%). Four patients showed myocardial infarction due to coronary vasculitis, but none were treated with IVIg because of late diagnosis. After a median follow-up of 5 months (range 1–117), persistent aneurysm was noted in 9% of cases. Damage was significantly lower with early treatment than late or no treatment (p = 0.01). Conclusion Given the high frequency of cardiac involvement and complications in this series of AKD, diagnosis and treatment should not be delayed, and early IVIg treatment seems to improve the outcome.
Cutaneous involvement in multiple myeloma with extramedullary disease is rare. We report the case of a refractory multiple myeloma patient who developed a cutaneous lesion. Histopathology revealed ...dermal immature plasma cell infiltrate with a lack of CD138 expression. This cutaneous location was associated with an aggressive clinical course and short survival.
Cutaneous infiltration is a rare manifestation of multiple myeloma. It generally occurs at a late stage of the disease and is an ominous clinical sign. Skin involvement is usually associated with poor prognosis and requires aggressive therapies.
Fluorodesoxyglucose Positron Emission Tomography (PET/CT) has never been compared to Chest-Abdomen-Pelvis CT (CAPCT) in patients with a fever of unknown origin (FUO), inflammation of unknown origin ...(IUO) and episodic fever of unknown origin (EFUO) through a prospective and multicentre study. In this study, we investigated the diagnostic value of PET/CT compared to CAPCT in these patients. The trial was performed between 1 May 2008 through 28 February 2013 with 7 French University Hospital centres. Patients who fulfilled the FUO, IUO or EFUO criteria were included. Diagnostic orientation (DO), diagnostic contribution (DC) and time for diagnosis of both imaging resources were evaluated. One hundred and three patients were included with 35 FUO, 35 IUO and 33 EFUO patients. PET/CT showed both a higher DO (28.2% vs. 7.8%,
< 0.001) and DC (19.4% vs. 5.8%,
< 0.001) than CAPCT and reduced the time for diagnosis in patients (3.8 vs. 17.6 months,
= 0.02). Arthralgia (OR 4.90,
= 0.0012), DO of PET/CT (OR 4.09,
= 0.016), CRP > 30 mg/L (OR 3.70,
= 0.033), and chills (OR 3.06,
= 0.0248) were associated with the achievement of a diagnosis (Se: 89.1%, Sp: 56.8%). PET/CT both orients and contributes to diagnoses at a higher rate than CAPCT, especially in patients with FUO and IUO, and reduces the time for diagnosis.
We report the case of an 80-year-old woman who presented one episode of cardiopulmonary arrest and two episodes of acute airway obstruction. We found in this patient the presence of tracheomalacia ...caused by megaesophagus compression secondary to achalasia probably responsible for episodes of acute airway obstruction and cardiopulmonary arrest.
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