Objective
No simple or standardized assay is available to quantify interferon‐α (IFNα) in routine clinical practice. Single‐molecule array (Simoa) digital enzyme‐linked immunosorbent assay (ELISA) ...technology enables direct IFNα quantification at attomolar (femtogram per milliliter fg/ml) concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity.
Methods
IFNα concentrations in serum samples from 150 consecutive SLE patients in a cross‐sectional study were determined with digital ELISA and a functional biologic activity assay (bioassay). According to their Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) flare composite scores, patients were divided into groups with inactive SLE (SLEDAI score of <4 or clinical SLEDAI score of 0) or active SLE (SLEDAI score of ≥4 or clinical SLEDAI score of >0), and into groups with no flare or mild/moderate flare or severe flare.
Results
Based on serum samples from healthy blood donors, the abnormal serum IFNα level threshold value was 136 fg/ml. Next, using receiver operating characteristic curves for an SLE patient series that was widely heterogeneous in terms of disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/ml. The digital ELISA–assessed serum IFNα level was a better biomarker of disease activity than the Farr assay because its specificity, likelihood ratio for positive results, and positive predictive value better discerned active SLE or flare from inactive disease. The digital ELISA was more sensitive than the bioassay for detecting low‐abnormal serum IFNα concentrations and identifying patients with low disease activity.
Conclusion
Direct serum IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti‐IFNα treatment.
The vasculitis of Behçet disease (BD) is distinctive because of involvement of both arteries and veins of all sizes. The concept of vasculo-Behçet disease has been adopted for cases in which vascular ...manifestations are present and often dominate the clinical features. While venous manifestations are frequent and have been reported in many publications, data regarding arterial lesions in patients with BD are rare and often isolated. In this study, we report the main characteristics, treatment, and long-term outcome of 101 patients with arterial lesions among a cohort of 820 (12.3%) BD patients. Factors that affect prognosis were assessed by multivariate analysis. There were 93 (91.2%) male patients; the median (Q1-Q3) age at diagnosis of BD was 33 (27-41) years. Arterial lesions included aneurysms (47.3%), occlusions (36.5%), stenosis (13.5%), and aortitis (2.7%). Lesions mainly involved the aorta (n = 25) and femoral (n = 23) and pulmonary (n = 21) arteries. Patients with arterial lesions were more frequently male (91.2% vs. 62.4%, respectively; p = 0.017) and had higher rates of venous involvement (80.4% vs. 29.8%, respectively; p < 0.001) compared to patients without arterial manifestations. Thirty-nine (38.6%) patients achieved complete remission. In multivariate analysis, the presence of venous involvement (odds ratio OR, 0.29; 95% confidence interval CI, 0.08-1.11) and arterial occlusive lesions (OR, 0.13; 95% CI, 0.01-1.25) were negatively associated with complete remission. The use of immunosuppressants (OR, 3.38; 95% CI, 0.87-13.23) was associated with the occurrence of complete remission. The 20-year survival rate was significantly lower in BD patients with arterial involvement than in those without arterial lesions (73% vs. 89%, respectively; p < 0.0001). In conclusion, the long-term outcome of arterial lesions in BD is poor, especially in the case of occlusive lesions and associated venous involvement. The use of immunosuppressants improved the prognosis.
Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have ...found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). Conclusions We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.
Hydroxychloroquine-induced pigmentation is not a rare adverse effect. Our data support the hypothesis that hydroxychloroquine-induced pigmentation is secondary to ecchymosis or bruising.
To describe ...the clinical features and outcome of hydroxychloroquine (HCQ)-induced pigmentation in patients with systemic lupus erythematosus (SLE).
In a case-control study conducted at a French referral center for SLE and antiphospholipid syndrome, 24 patients with SLE, with a diagnosis of HCQ-induced pigmentation, were compared with 517 SLE controls treated with HCQ.
The primary outcome was the clinical features of HCQ-induced pigmentation. Skin biopsies were performed on 5 patients, both in healthy skin and in the pigmented lesions. The statistical associations of HCQ-induced pigmentation with several variables were calculated using univariate and multivariate analyses.
Among the 24 patients, skin pigmentation appeared after a median HCQ treatment duration of 6.1 years (range, 3 months-22 years). Twenty-two patients (92%) reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or brown pigmentation that persisted. Twenty-three patients (96%) had at least 1 condition predisposing them to easy bruising. Results from skin biopsies performed on 5 patients showed that the median concentration of iron was significantly higher in biopsy specimens of pigmented lesions compared with normal skin (4115 vs 413 nmol/g; P < .001). Using multivariate logistic regression, we found that HCQ-induced pigmentation was independently associated with previous treatment with oral anticoagulants and/or antiplatelet agents and with higher blood HCQ concentration.
Hydroxychloroquine-induced pigmentation is not a rare adverse effect of HCQ. Our data support the hypothesis that HCQ-induced pigmentation is secondary to ecchymosis or bruising.
To compile and assess data about complication and success rates for
fertilization (IVF) of women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). To date, such data are ...sparse.
This retrospective study described women with SLE and/or APS who have had at least 1 IVF cycle.
Thirty-seven women with SLE (n = 23, including 8 with antiphospholipid antibodies), SLE with APS (n = 4), or primary APS (n = 10) underwent 97 IVF procedures. For 43% of cases, the infertility was female in origin, for 19% male, 14% mixed, and 24% unexplained. No women had premature ovarian insufficiency because of cyclophosphamide. Median age at IVF was 34 years (range 26-46). The median number of IVF cycles was 2.6 (1-8). Patients were treated with hydroxychloroquine (72%), steroids (70%), azathioprine (3%), aspirin (92%), and/or low molecular weight heparin (62%). There were 27 (28%) pregnancies, 23 live births among 26 neonates (3 twin pregnancies), 2 miscarriages, and 2 terminations for trisomy 13 and 21. Six spontaneous pregnancies occurred during the followup. Finally, 26 women (70%) delivered at least 1 healthy child. Complications occurred in or after 8 IVF cycles (8%): SLE flares in 4 (polyarthritis in 3 and lupus enteritis in 1) and thromboembolic events in 4 others. One SLE flare was the first sign of previously undiagnosed SLE. Poor treatment adherence was obvious in 2 other flares and 2 thromboses. No ovarian hyperstimulation syndrome was reported.
These preliminary results confirm that IVF can be safely and successfully performed in women with SLE and/or APS.
Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening disease caused by the onset of rapidly progressive and widespread small-vessel thromboses in the presence of aPLs. The aim of this ...study was to examine pregnancy-related CAPS.
Retrospective series of 13 patients with pregnancy-related CAPS with special focus on the follow-up. RESULTS; Eleven patients had known APS and had been treated with low-molecular-weight heparin (n = 10), aspirin (n = 8), oral anticoagulants (n = 1), HCQ (n = 3) and/or steroids (n = 1) during pregnancy. The most frequent manifestations of CAPS were cutaneous (n = 11), hepatic (n = 11), renal (n = 10), cardiac (n = 8) and neurological (n = 5). CAPS usually followed haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome (n = 12), which was associated with pre-eclampsia (n = 6) or with eclampsia (n = 3). No maternal death was observed. The perinatal mortality of 54% was related to prematurity with a mean gestational age of 26.6 weeks at onset of CAPS or HELLP syndrome. During a mean follow-up of 4.8 years (range 2-8 years), seven new pregnancies occurred in five patients and led to one miscarriage, four successful pregnancies and two HELLP syndrome with pre-eclampsia or eclampsia that occurred at 28 weeks gestation in both cases despite optimal treatment. No relapse of CAPS was observed. Two mothers suddenly died 2.5 and 6 years after CAPS.
The occurrence of HELLP syndrome in a patient with APS should raise the suspicion of CAPS in the following days, and anticoagulation should be maintained post-partum or post-abortum. Subsequent pregnancies are at very high risk.
To report the long-term outcome of neurologic involvement in patients with Behçet's disease (BD).
We performed a retrospective analysis of 115 patients who fulfilled the international criteria for BD ...(57% male; median age 37 years interquartile range (IQR) 30-46 years) and had neuro-BD (NBD) after exclusion of cerebral venous thrombosis. Factors associated with relapse of NBD, inability to perform activities of daily living, and mortality were assessed.
Seventy-eight patients (68%) presented with acute NBD and 37 (32%) presented with a progressive course. The HLA-B51 allele was carried by 49% of the patients. Overall, 46 of 115 patients (40%) had severe disability at baseline, represented by a Rankin score of ≥3. The 5- and 7-year event-free survival rates were 65% and 53%, respectively. In multivariate analysis, a positive HLA-B51 status was independently associated with the risk of NBD relapse, with an odds ratio (OR) of 3.6 (95% confidence interval 95% CI 1.5-9.1). After a median followup of 73 months (IQR 59-102 months), 29 patients (25.2%) became dependent (were unable to perform activities of daily living) or died. Factors independently associated with poor outcome were paresis at onset (OR 6.47 95% CI 1.73-24.23) and location of inflammatory lesions at the brainstem on magnetic resonance imaging (OR 8.41 1.03-68.43). All 115 patients were treated with corticosteroids; 53 (46.1%) also took cyclophosphamide and 40 (34.8%) also took azathioprine. A trend toward longer event-free survival was observed in patients with severe NBD (i.e., with a Rankin score of ≥3 at onset) receiving intravenous cyclophosphamide compared with those receiving azathioprine (P = 0.06).
Our findings indicate that NBD is a severe condition in which patients with the HLA-B51 allele appear to experience a worse prognosis.
The aim of this study was to determine the characteristics, treatment, and outcome according to each etiology of pachymeningitis.We conducted a retrospective multicenter French nationwide study ...between 2000 and 2016 to describe the characteristics, outcome, and treatment of pachymeningitis.We included 60 patients (median age 55.5 years; interquartile range IQR 30-80, female/male ratio 0.43). Neurologic signs were present in 59 patients (98%) and consisted of headache in 43 (72%), cranial nerve palsy in 33 (55%), confusion in 10 (17%), seizures in 7 (12%), and focal neurologic signs in 9 (15%). Fever and weight loss were present in 8 (13%) and 13 cases (22%), respectively. Cerebral venous thrombosis was present in 8 cases (13%). Analysis of cerebrospinal fluid showed moderate hyperproteinorachia (median 0.68 g/L; IQR 0.46-3.2) with or without pleiocytosis. Diagnosis included idiopathic pachymeningitis (n = 18; 30%); granulomatosis with polyangiitis (n = 13; 17%); Erdheim-Chester disease (n = 10; 17%); IgG4-related disease and tuberculosis (n = 3; 5% each); Rosai-Dofman disease, microscopic polyangiitis, and sarcoidosis (n = 2, 3% each); cryptococcal meningitis, Lyme disease, ear-nose-throat infection, postlumbar puncture, low spinal-fluid pressure syndrome, and lymphoma (n = 1 each). We found no difference in demographics and neurologic presentation among idiopathic pachymeningitis, Erdheim-Chester disease, and granulomatosis with polyangiitis. In contrast, frequencies were lower with idiopathic pachymeningitis than Erdheim-Chester disease for general signs (6% and 40%, respectively, P = .041) and complete neurologic response (0% vs 39%, P = .045).The detection of extraneurologic signs and routine screening are needed to classify the pachymeningitis origin. Prospective studies are warranted to determine the best treatment in each case.
Objective Arterial aneurysms are characteristic of medium-size vessel vasculitis but are a very unusual feature of Wegener’s granulomatosis (WG). We describe a typical WG case, complicated by ...arterial aneurysms and review previously reported cases. Methods Medline database search of cases published between January 1978 and July 2006, in English, reporting arterial aneurysms complicating WG. Results Five years after diagnosis, a 29-year-old man with typical WG developed macro- and microaneurysms located on branches of the hepatic and renal arteries during a disease relapse. The main symptoms were abdominal pain, vomiting, and altered general status. He was successfully treated by coil embolization in combination with prednisone, intravenous mycophenolate mofetil, and high-dose immunoglobulins. Twelve additional cases of WG complicated by arterial aneurysms are reported in the English literature. This represents a life-threatening complication since rupture occurred in half of the patients. Conclusions Although small-vessel injury predominates in WG, inflammation of medium-size arteries may occur and lead to aneurysm formation. Abdominal angiography should be recommended when unexplained abdominal pain occurs during a WG flare.
Objective
To retrospectively study the incidence of chronic cutaneous lupus erythematosus (CCLE) in French Guiana (FG), South America, during the period 1995–1999.
Methods
Private and public ...physicians specializing in dermatology, rheumatology, and internal medicine were asked during the year 2000 about lupus cases. We reviewed hospitals' files in data‐processing departments.
Results
Twenty new cases of CCLE, mostly discoid form, were identified during this 5‐year period in this population of predominantly African descent. The average annual incidence of the disease was 2.59 per 100,000 inhabitants (95% confidence interval 1.5–4). However, our methodology could introduce underestimation of the incidence of the disease.
Conclusion
The average annual incidence of CCLE in FG appears to be low in this retrospective study, but is very similar to the only previously published data in the US.
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