Objective
Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on this disease remain scarce. This study ...was undertaken to describe patient characteristics and disease evolution, identify prognostic factors, and define different clinical phenotypes of RP.
Methods
We performed a retrospective study of 142 patients with RP who were seen between 2000 and 2012 in a single center.
Results
Of the 142 patients, 86 (61%) were women. The mean ± SD age at first symptoms was 43.5 ± 15 years. Patients had the following chondritis types: auricular (89%; n = 127), nasal (63%; n = 89), laryngeal (43%; n = 61), tracheobronchial (22%; n = 32), and/orcostochondritis (40%; n = 57). The main other manifestations were articular (69%; n = 98), ophthalmologic (56%; n = 80), audiovestibular (34%; n = 48), cardiac (27%; n = 38), and cutaneous (28%; n = 40). At a mean ± SD followup of 13 ± 9 years, the 5‐ and 10‐year survival rates were 95 ± 2% and 91 ± 3%, respectively. Factors associated with death on multivariable analysis were male sex (P = 0.01), cardiac abnormalities (P = 0.03), and concomitant myelodysplastic syndrome (MDS) (P = 0.004) or another hematologic malignancy (P = 0.01). Cluster analysis revealed that separating patients into 3 groups was clinically relevant, thereby separating patients with associated MDS, those with tracheobronchial involvement, and those without the 2 features in terms of clinical characteristics, therapeutic management, and prognosis.
Conclusion
This large series of patients with definite RP revealed an improvement in survival as compared with previous studies. Factors associated with death were male sex, cardiac involvement, and concomitant hematologic malignancy. We identified 3 distinct phenotypes.
Objective
To report the long‐term outcome of neurologic involvement in patients with Behçet's disease (BD).
Methods
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.
Results
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).
Conclusion
Our findings indicate that NBD is a severe condition in which patients with the HLA–B51 allele appear to experience a worse prognosis.
Summary
Catastrophic antiphospholipid syndrome is the most severe complication of antiphospholipid syndrome. Vitamin K antagonists are the reference treatment for preventing relapsing thrombotic ...complications in patients with antiphospholipid syndrome. Direct oral anticoagulants are nonetheless sometimes used in this setting. We report two cases of women who were triple-positive for antiphospholipid antibodies and developed catastrophic antiphospholipid syndrome in the week after the introduction of rivaroxaban. The first patient, who had had a previous thrombotic event, had multiorgan failure 3 days after vitamin K antagonists was replaced by rivaroxaban, and the second developed a similar clinical presentation 7 days after introduction of the same treatment. Both catastrophic antiphospholipid syndrome episodes were successfully treated with heparin followed by vitamin K antagonists, corticosteroids, and plasmapheresis. These two cases highlight for the inefficacy of rivaroxaban preventing severe thrombotic events such as catastrophic antiphospholipid syndrome and thus provide further support for recommendations that vitamin K antagonists must remain the reference anticoagulant in patients with triple-positive antiphospholipid antibodies.
Cardiac involvement during systemic lupus erythematosus (SLE) may include the pericardium, myocardium, valvular tissue, and coronary arteries. The aim of this study was to describe the clinical, ...biological, and radiological presentation of lupus myocarditis (LM) as well as the treatment response and longterm outcomes.
We conducted a multicentric retrospective study of LM from January 2000 to May 2014.
Twenty-nine patients (3 men and 26 women) fulfilled the inclusion criteria (median age at the diagnosis of SLE: 30 yrs, range 16-57). Myocarditis was the first sign of SLE in 17/29 cases (58.6%). Troponin was elevated in 20/25 cases. Electrocardiogram results were abnormal in 25/28 cases. Echocardiography revealed low (≤ 45%) left ventricular ejection fraction (LVEF; 19/29, 66%) and pericardium effusion (20/29, 69%). Cardiac magnetic resonance imaging revealed delayed gadolinium enhancement in 9/13 patients (69%). Patients were treated with corticosteroids (n = 28), cyclophosphamide (CYC; n = 16), intravenous immunoglobulins (n = 8), and/or mycophenolate mofetil (n = 2). The median followup was 37 months. One month after the beginning of the treatment, 10/23 patients (43%) who had undergone echocardiography had an LVEF ≥ 55%. At the end of followup, 21/26 patients (81%) exhibited an LVEF ≥ 55%. Three patients died during followup, and 2 died from LM.
LM is a severe manifestation of SLE. It can be the first manifestation of the disease or it can occur during followup, in particular in untreated patients. However, the longterm prognosis is typically positive. Patients with less severe disease exhibited good LVEF recovery without CYC.
Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half‐life and can be quantified by ...high‐performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ < 200 ng/ml or undetectable desethylchloroquine), and self‐administered questionnaires (MASRI < 80%). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 23.4% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self‐administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.)
A recent case-control study suggested a benefit of hydroxychloroquine (HCQ) in lowering the risk of cardiac manifestations of neonatal lupus (cardiac-NL) in pregnancies of anti-SSA/Ro-positive ...patients with systemic lupus erythematosus. A historical cohort assembled from 3 international databases was used to evaluate whether HCQ reduces the nearly 10-fold increase in risk of recurrence of cardiac-NL independently of maternal health status.
Two hundred fifty-seven pregnancies of anti-SSA/Ro-positive mothers (40 exposed and 217 unexposed to HCQ) subsequent to the birth of a child with cardiac-NL were identified from 3 databases (United States, England, and France). Exposure was defined as the sustained use of HCQ throughout pregnancy with initiation before 10 weeks of gestation. The recurrence rate of cardiac-NL in fetuses exposed to HCQ was 7.5% (3 of 40) compared with 21.2% (46 of 217) in the unexposed group (P=0.050). Although there were no deaths in the exposed group, the overall case fatality rate of the cardiac-NL fetuses in the unexposed group was 21.7%. In a multivariable analysis that adjusted for database source, maternal race/ethnicity, and anti-SSB/La status, HCQ use remained significantly associated with a decreased risk of cardiac-NL (odds ratio, 0.23; 95% confidence interval, 0.06-0.92; P=0.037). Similar results were obtained with propensity score analysis, an alternative approach to adjust for possible confounding by indication.
Aggregate data from a multinational effort show that in mothers at high risk of having a child with cardiac-NL, the use of HCQ may protect against recurrence of disease in a subsequent pregnancy.
To assess the efficacy and the safety of biologics in a cohort of patients with relapsing polychondritis (RP).
We conducted a French multicentre retrospective cohort study including patients treated ...with biologics for RP. Efficacy outcomes were clinical response (partial or complete) and complete response during the first 6 months of exposure, plus daily corticosteroid dose at 6 months. Other outcomes were adverse drug reactions (ADRs), persistence of biologics and factors associated with a response.
This study included 41 patients exposed to 105 biologics (tumour-necrosis factor (TNF) inhibitors, n=60; tocilizumab, n=17; anakinra, n=15; rituximab, n=7; abatacept, n=6). Overall response rate during the first 6 months of exposure was 62.9%. Complete response rate was 19.0%. Reduced corticosteroid doses were highly variable among patients. ADRs were mostly infections (n=42). Reasons for biologic withdrawal (73.3%) were insufficient efficacy (34.3%; ranging from 23.5% for tocilizumab to 72.7% for etanercept), loss of efficacy (18.1%) and ADRs (20.9%; mostly for anakinra: 46.7%). Persistence was comparable among biologic classes. Among TNF inhibitors, the highest persistence was observed with adalimumab. Differences in clinical response rates were observed depending on biologics and organ involvement. There were trends towards a lower response rate in cases with associated myelodysplastic syndrome and for a higher response rate for nasal/auricular chondritis, sternal chondritis and concomitant exposure to non-biologic disease-modifying antirheumatic drugs.
This study describes the efficacy of biologics for refractory RP. However, the number of complete responses was low and there were concerns about the risk of ADRs, particularly infections.
Abstract Since the association between antiphospholipid antibodies (aPL) and syphilis was first described, many other viral, bacterial and parasitic infections have been shown to induce ...antiphospholipid antibodies, notably anticardiolipin antibodies (aCL). A review of the literature shows that while aCL occur frequently in viral infections, particularly in HIV (49.75%), HBV (24%) and HCV (20%), it is very rarely associated with anti-β2 glycoprotein I antibodies (anti-β2GPI) and is not correlated with thrombosis risk or hematological manifestations of the antiphospholipid syndrome (APS). Concerning bacterial infections, aCL is often present in leprosy (42.7%), where it is frequently associated with the presence of anti-β2GPI (44.8%), and in syphilis infections (8 to 67%), though without correlation with thrombotic events. Though few individual patients with unequivocal infection-induced aPL satisfy criteria for APS, the lack of statistical association with thrombotic events strongly argues against the identification of a true APS subset in this context. However, physicians should keep in mind the fact that an infection, generally bacterial, in patients with confirmed APS, may lead to catastrophic antiphospholipid syndrome with a possible fatal outcome.
From 1979 to 2004, 22 patients were seen with leiomyosarcomas of the inferior vena cava (IVC). Twenty were treated surgically. Involvement of the IVC included the infrarenal segment in 3 cases, the ...suprarenal and/or retrohepatic segment in 13, and the suprahepatic segment in 4. Nineteen patients underwent wide tumor resection followed by ligation of the IVC in 5 cases, replacement with a PTFE prosthesis in 13, and cavoplasty in 1. An intracardiac tumor extension was resected during hypothermic circulatory arrest in 1 patient. Vascular exclusion of the liver was used in 5 cases and simple clamping of the IVC in 13 cases. There were 1 intraoperative death due to cardiac failure and 3 postoperative deaths due to multiple organ failure, liver failure, and duodenal fistula after treatment of a bleeding ulcer. Fifteen of the 16 surviving patients underwent adjuvant chemotherapy associated with radiation therapy in 4 cases. One patient was lost from follow-up at 10 months. Four patients including one with metastasis are still alive with a mean follow-up of 18.3 months. Eleven patients died after a mean follow-up period of 43.7 months due to local recurrence and/or distant metastasis in 9 cases and complications of chemotherapy in 2. The 3- and 5-year mean actuarial survival rates in patients who underwent resection were 52.0% and 34.8%, respectively. Leiomyosarcoma of the IVC is a serious disease. Although surgical resection combined with chemotherapy is usually not curative, it can achieve reasonably long-term survival. We recommend aggressive operative management using the latest vascular surgery and oncology techniques.
PDF
