M. Lambert

Takayasu Arteritis and Pregnancy

To assess the relationship between Takayasu arteritis (TAK) and pregnancy outcome.

Long-Term Outcomes and Prognostic Factors of Complications in Takayasu Arteritis: A Multicenter Study of 318 Patients

Background: Because of the wide variation in the course of Takayasu arteritis (TA), predicting outcome is challenging. We assess long-term outcome and prognosis factors for vascular complications in patients with TA. Methods: A retrospective multicenter study of characteristics and outcomes of 318 patients with TA fulfilling American College of Rheumatology and Ishikawa criteria was analyzed. Factors associated with event-free survival, relapse-free survival, and incidences of vascular complications were assessed. Risk factors for vascular complications were identified in a multivariable model. Results: The median age at TA diagnosis was 36 [25–47] years, and 276 patients (86.8%) were women. After a median follow-up of 6.1 years, relapses were observed in 43%, vascular complications in 38%, and death in 5%. Progressive clinical course was observed in 45%, carotidodynia in 10%, and retinopathy in 4%. The 5- and 10-year event-free survival, relapse-free survival, and complication-free survival were 48.2% (42.2; 54.9) and 36.4% (30.3; 43.9), 58.6% (52.7; 65.1) and 47.7% (41.2; 55.1), and 69.9% (64.3; 76.0) and 53.7% (46.8; 61.7), respectively. Progressive disease course (P=0.018) and carotidynia (P=0.036) were independently associated with event-free survival. Male sex (P=0.048), elevated C-reactive protein (P=0.013), and carotidynia (P=0.003) were associated with relapse-free survival. Progressive disease course (P=0.017), thoracic aorta involvement (P=0.009), and retinopathy (P=0.002) were associated with complication-free survival. Conclusions: This nationwide study shows that 50% of patients with TA will relapse and experience a vascular complication ⩽10 years from diagnosis. We identified specific characteristics that identified those at highest risk for subsequent vascular complications.

Risk factors for severe bacterial infections in patients with systemic autoimmune diseases receiving rituximab

The risk of serious bacterial infectious events (SIEs) after an RTX course used in severe and refractory cases of systemic autoimmune diseases (SAID) is well known. Risk factors for SIEs merit investigation. For this case–control study, data were collected in a single centre of internal medicine and included all patients who received rituximab (RTX) for SAID between 2005 and 2011 (rheumatoid arthritis was excluded). Sixty-nine patients with SAID received a total of 87 RTX courses. Thirteen SIEs were reported in 12 patients leading to death in 5 patients. Patients with a history of SIE were significantly older (63.6u2009±u200918.8 vs 48.8u2009±u200916.7; pu2009=u20090.0091), suffered most frequently of diabetes mellitus (33.3xa0% vs 5.3xa0%, pu2009=u20090.015), had a lower CD19 count (1.0u2009±u20091.2/mm3 vs 3.9u2009±u20097.2/mm3) and had most frequently a prednisone dose >15xa0mg/day (91.7xa0% vs 47.7xa0%) at the start of the first RTX course. The SIE rate was 18.7 per 100 patient-years. At the initiation of the RTX course, risk factors for SIEs were lower IgG levels (ORu2009=u20090.87, 95%CIu2009=u20090.77–0.99, pu2009=u20090.03), lower CD19 count (ORu2009=u20090.85, 95%CIu2009=u20090.73–1.00) and creatinine clearanceu2009≤u200945xa0ml/min (ORu2009=u20097.78, 95%CIu2009=u20091.36–44.38, pu2009=u20090.002). Conversely history of pneumococcal vaccination significantly decreased the risk of SIEs (ORu2009=u20090.11, 95%CIu2009=u20090.03–0.41, pu2009=u20090.0009). Concomitant treatment with prednisone at a dose >15xa0mg/day significantly increased the SIE risk (ORu2009=u20098.07, 95%CIu2009=u20091.94–33.59, pu2009=u20090.0004). SIEs are frequent in SAID treated with RTX, particularly in patients receiving high-dose corticosteroids, in patients with renal insufficiency and in patients with low IgG levels or a low CD19 count.

Efficacy of Anti-TNFα in Severe and Refractory Neuro-Behcet Disease: An Observational Study.

AbstractTo report the safety and efficacy of anti-tumor necrosis factor &agr; (TNF&agr;) therapy in severe and refractory neuro-Behçet disease (NBD) patients.Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24–60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNF&agr; (infliximab 5u200amg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months.Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1–6). The median Rankin score was 2 (1–4) at the initiation of anti-TNF&agr; versus 1 (0–4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases.TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population.

Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review

BACKGROUNDnCogan syndrome is mainly treated with steroids. We aimed to determine the place of DMARDs and biologic-targeted treatments.nnnPATIENTS AND METHODSnWe conducted a French nationwide retrospective study of patients with Cogan syndrome (n=40) and a literature review of cases (n=22) and analyzed the efficacy of disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor α (TNF-α) antagonists.nnnRESULTSnWe included 62 patients (31 females) (median age 37years [range 2-76]. At diagnosis, 61 patients (98%) had vestibulo-auditory symptoms, particularly bilateral hearing loss in 41% and deafness in 31%. Ocular signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%). The first-line treatment consisted of steroids alone (n=43; 70%) or associated with other immunosuppressive drugs (n=18; 30%). Overall, 13/43 (30%) and 4/18 (22%) patients with steroids alone and with associated immunosuppressive drugs, respectively (p=0.8), showed vestibulo-auditory response; 32/39 (82%) and 15/19 (79%) ocular response; and 23/28 (82%) and 10/14 (71%) general response. Overall 61 patients had used a total of 126 lines of treatment, consisting of steroids alone (n=51 lines), steroids with DMARDs (n=65) and infliximab (n=10). Vestibulo-auditory response was significantly more frequent with infliximab than DMARDs or steroids alone (80% vs 39% and 35%, respectively), whereas ocular, systemic and acute-phase reactant response rates were similar. Infliximab was the only significant predictor of vestibulo-auditory improvement (odds ratio 20.7 [95% confidence interval 1.65; 260], p=0.019).nnnCONCLUSIONnInfliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome, but prospective studies are necessary.

Overall survival and mortality risk factors in Takayasu's arteritis: A multicenter study of 318 patients

OBJECTIVEnTo report the long term mortality in Takayasu arteritis (TA) and to identify prognosis factors.nnnMETHODSnWe analyzed the causes of death and the factors associated with mortality in a cohort of 318 patients [median age at diagnosis was 36 [25-47] years and 276 (86%) patients were women] fulfilling American College of Rheumatology and/or Ishikawa criteria of TA. A prognostic score for death and vascular complications was elaborated based on a multivariate model.nnnRESULTSnAmong 318u202fTA patients, 16 (5%) died after a median [IQR] follow-up of 6.1 [2.8-13.0] years. The median age at death was 38 [25-47] years with 88% of women. Main causes of death included mesenteric ischemia (nu202f=u202f4, 25%) and aortic aneurysm rupture (nu202f=u202f4, 25%). The mortality rate at 5 and 10 years was of 1.9% and 3.9%, respectively. Caucasians (pu202f=u202f0.049) and smokers (pu202f=u202f0.002) TA patients were more likely to die. There was an increased mortality in TA (SMR with 95% confidence interval, 2.73 [1.69-4.22]) as compared to age and sex matched healthy controls. We defined high risk patients for death and vascular complications according to the presence of two of the following factors (i.e a progressive clinical course, thoracic aorta involvement and/or retinopathy). In the high risk TA group, the 5-year incidence of death and vascular complication was 48.5% compared to 21.6% (pu202f=u202f0.001) in those with low risk.nnnCONCLUSIONnThe overall mortality in our Takayasu cohort was 5% after a median follow-up of 6.1 years. We identified specific characteristics that distinguish TA patients at highest risk for death and vascular complications.

Nonhemorrhagic joint disorders and vitamin K antagonists: an under-recognized adverse drug reaction?

Isolated arthralgia, without hemorrhagic side effect, exists and is considered as a very rare adverse drug reaction according to vitamin K antagonists’ (VKAs) summary of product characteristics. Up to now, there are no literature reports of isolated, nonhemorrhagic joint complications in patients receiving VKAs. Hence, the objective of this study was to describe cases of VKA‐related nonhemorrhagic joint disorders (fluindione, warfarin, and acenocoumarol) reported in the French Pharmacovigilance Database (FPVD). Sixty‐one reports (male : female ratio, 1.18; median [interquartile range (IQR)] age: 60 [49–72]) were found. Fluindione, warfarin, and acenocoumarol were respectively suspected in 42, 12, and 7 cases. Arthralgia was reported in 47 cases (77%), arthritis in nine cases (15%), capsulitis in three cases (5%), and bursitis in two cases (3%). Although the joint symptoms mainly concerned the lower limbs, all types of joints were affected. Arthralgia was associated with myalgia in 14 cases and with tendinitis in three cases. The median (IQR) time interval between VKA introduction and arthralgia onset was 26 (10–98) days (range: 1–6935). VKA was withdrawn in 44 cases, and a decrease in the intensity of joint symptoms was observed in 30 cases. In three cases, reintroduction of the same VKA led to the recurrence of symptoms. In view of the large prescription of this drug class worldwide, patients and clinicians (and especially primary care physicians and geriatricians) should be aware of this possible adverse drug reaction when confronted with joint disorders in patients of all ages taking VKAs.

Interactions pharmacovigilance – service de médecine interne : une aide précieuse au diagnostic

PURPOSEnPatients hospitalized in internal medicine often have unexplained clinical symptoms for which a drug origin can be considered. The prevalence of patients hospitalized for iatrogenic is estimated between 4-22%. We wanted to evaluate the diagnostic value of the regional center of pharmacovigilance to identify or confirm an iatrogenic disease in the department of internal medicine of Lille and characterize factors associated with drug-related side effect.nnnMETHODSnThis is a single-center prospective diagnostic study. We included all subsequent requests from the department of internal medicine with the Nord-Pas-de-Calais regional pharmacovigilance center between 2010 and 2012. The opinion of the regional pharmacovigilance centre was held on the record of the adverse drug reaction in the national pharmacovigilance database and analyzed according to the conclusion of iatrogenic used by clinicians in internal medicine (reference diagnosis) with a follow-up to June 2013. The variables relating to the patient, medication and adverse events were analyzed by binary logistic regression.nnnRESULTSnWe analyzed 160 contacts: 118 concordant cases, 38 false-positives (drug-related side effect retained by the regional pharmacovigilance center only), 4 false negatives. Registration in the national pharmacovigilance database had a sensitivity of 96% (95% CI [0.92 to 0.99]), a specificity of 46% (95% CI [0.38 to 0.53]), a value positive predictive of 69% (95% CI [0.62 to 0.76]), a negative predictive value of 89% (95% CI [0.84 to 0.94]) and a negative likelihood ratio of 0.1. False-positive had chronological and semiological accountabilities questionable (adjusted RR=2.1, 95% CI [1.2 to 2.8]).nnnCONCLUSIONnIn our study, the regional pharmacovigilance center confirms the clinicians suspicion of drug-related side effects and helps to exclude drug-induced with a high negative predictive value.

Pneumopathie interstitielle diffuse sous mésalazine : un effet indésirable sous diagnostiqué ?

We report the case of a woman treated with adalimumab and mesalazine for a Crohns disease who presented 9 years after the beginning of the treatments an interstitial lung disease (ILD) discovered by chance during a routine medical examination. Several hypotheses were evocated: progression of the Crohns disease with a pulmonary involvement then the role of adalimumab was finally suspected. Adalimumab treatment was stopped, but several months later, the pulmonary disease persisted. Six months after the initial medical consult, mesalazine treatment was suspected and stopped. The ILD improved and finally completely resolved with no recurrence after one year. Interstitial lung disease is a rare side effect of mesalazine probably underdiagnosed by physicians especially in patients treated with TNF alpha inhibitors.

Enfermedad de Takayasu

La enfermedad de Takayasu es una aortoarteritis inespecifica que provoca una estenosis progresiva de las arterias de calibre grande y mediano (aorta y sus ramas principales, arteria pulmonar). La lesion mas tipica es la estenosis de las arterias subclavias, que explica la desaparicion del pulso radial. La estenosis de las arterias renales puede complicarse con una hipertension arterial vasculorrenal y la estenosis de las arterias mesentericas, con una angina intestinal. Actualmente, los metodos de diagnostico por imagen no invasivos suelen establecer el diagnostico sin necesidad de una biopsia arterial. La piedra angular del tratamiento es la corticoterapia, que a veces se asocia con inmunosupresores. En algunos casos es necesario proceder a una revascularizacion quirurgica.