Felix Ackermann

Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study).

Introduction 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] ≥1000u2005ng/ml to reduce SLE flares. Patients and methods [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6u2005months. Patients with [HCQ] from 100 to 750u2005ng/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 7u2005months of follow-up. Results Overall, mean [HCQ] was 918±451u2005ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7u2005months. 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). Conclusions Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up. ClinicalTrials.gov NCT00413361

The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia: New Insights Based on a Survey of 44 Cases

AbstractImatinib is the treatment of choice for FIP1L1/PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P+ CEL), but its optimal dosing, duration, and possibility of discontinuation are still a matter of debate. A retrospective multicenter study was conducted with 44 F/P+ CEL patients identified in the French Eosinophil Network and treated with imatinib. The most frequently involved systems were skin (57%), spleen (52%), and lung (45%), and eosinophilic heart disease was observed in 15 patients (34%). Complete hematologic response (CHR) was obtained in all patients, and complete molecular response (CMR) in 95% of patients (average initial imatinib dose, 165 mg/d). For 29 patients the imatinib dose was tapered with a maintenance dose of 58 mg/d (±34 mg/d), allowing sustained CHR and CMR. None of the patients developed resistance during a median follow-up of 52.3 months (range, 1.4–97.4 mo). Imatinib was stopped in 11 patients; 6 of the patients subsequently relapsed, but 5 remained in persistent CHR or CMR (range, 9–88 mo). These results confirm that an initial low-dose regimen of imatinib (100 mg/d) followed by a lower maintenance dose can be efficient for obtaining long-term CHR and CMR. Our data also suggest that imatinib can be stopped in some patients without molecular relapse.

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

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 6u2005months (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±9.8u2005ng/mL. Deficiency (25(OH)D <10u2005ng/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.

Determinants of Hydroxychloroquine Blood Concentration Variations in Systemic Lupus Erythematosus

Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations.

Melioidosis in a European traveler without comorbidities: a case report and literature review

Melioidosis is an endemic disease in Southeast Asia and northern Australia. It habitually affects immune-depressed hosts and may have a wide range of clinical manifestations. The use of positron emission tomography-computed tomography (PET-CT) has not been described previously for this disease. We report the case of a European traveler without comorbidities who developed melioidosis with pulmonary and bone marrow involvement 1 year after exposure. Antibiotic treatment was managed by taking into account the evolution on PET-CT. We review the literature and suggest the use of PET-CT for the initial evaluation of melioidosis, especially to look for a bone location, and to manage the length of antibiotic therapy.

Renal mucormycosis complicating extracorporeal membrane oxygenation

Zygomycosis can manifest as severe infections, particularly in immunocompromised patients, which can be nosocomial in nature resulting from complications of invasive procedures. We report the case of a 65-year-old woman with a medical history of unclassified inflammatory rheumatism who underwent arteriovenous extracorporeal membrane oxygenation because of a myocardial failure following the drainage of a tuberculous tamponade. This procedure was complicated by a superinfection of the scarpa which revealed a disseminated zygomycosis with renal involvement. A favorable outcome was achieved after 15 months of antifungal therapy involving the use of liposomal amphotericin B followed with posaconazole which involved the close monitoring of the concentrations of this antifungal. Extracorporeal membrane oxygenation is a frequent procedure which could be complicated with severe fungal nosocomial infections such as zygomycosis. The outcome of such complication can be favorable with the utilization of new antifungal therapies.

Cytomegalovirus colitis complicating ulcerative colitis treated with adalimumab

TO THE EDITOR: Cytomegalovirus (CMV)associated colitis frequently occurs in immunocompromised patients, either those with HIV or those treated with immunosuppressive agents. CMV infections have been specifically described in patients with inflammatory bowel disease (IBD) [1], and may be associated with refractory disease [2]. Surprisingly, while anti-tumour necrosis factor (TNF)-a agents are a major therapeutic option in refractory IBD, only a few cases of CMV-associated colitis induced by antiTNF agents have been reported in patients with IBD. We report the case of a 39-year-old white woman with refractory ulcerative colitis (UC) who developed severe CMV-associated colitis 1 month after the initiation of adalimumab treatment. UC was diagnosed in July 2008. She was initially treated unsuccessfully with mesalazine, and further received topical betamethasone and azathioprin 200 mg/day. She relapsed and required prednisone 70 mg/day. After a transient remission, her condition worsened. A rectosigmoidoscopy showed extensive mucosal abrasion, without evidence of CMV on biopsies. Adalimumab was added (80 mg at Day 0, then 40 mg every 2 weeks) to steroids and azathioprin. The patient was admitted to hospital 1 month after the first injection of adalimumab because she remained febrile, with watery bowel movements. Her heart rate was 130 beats/min and she had no abdominal tenderness. Her laboratory examinations showed a white blood cell count of 7.93 G/l, haemoglobin 11 g/dl and C-reactive protein 125 mg/l. Serological testing was positive for CMV IgG and negative for IgM antibody. A quantitative CMV polymerase chain reaction exhibited a viral load of 1500 copies/ ml. Stool examination and cultures were negative for parasites and enteric pathogens. A rectosigmoidoscopy was performed and showed extensive mucosal abrasions and erythema. The biopsies demonstrated severely active colitis with involvement of CMV. Azathioprine and adalimumab were stopped and the dose of prednisone was lowered to 15 mg/day. The patient was administered intravenous ganciclovir 5 mg twice a day. Her condition improved dramatically and complete viral clearance was observed (CMV viral load < 500 copies/ml). Unfortunately, her condition worsened 1 week later and a total colectomy had to be performed. The operative specimen showed a preperforative colon with evidence of severe flare of UC and absence of CMV involvement. We have reported the first case of proven CMV colitis complicating IBD treated with adalimumab. Suspicion of the involvement of adalimumab in the appearance of CMV colitis was high because biopsies performed before the first injection did not demonstrate CMV involvement, unlike those performed 1 month later. Only two other cases of CMV colitis complicating anti-TNF-a therapy have been reported. The first was a patient who received a single dose of infliximab for a flare of Crohn’s disease and who experienced a disseminated CMV infection [3]. The second case occurred in a patient with Behçet’s syndrome receiving infliximab treatment [4]. CMV colitis can complicate the course of IBD [5] or cause severe flares of the disease. This is why

Life-threatening Hughes-Stovin syndrome: The Yin and Yang of anticoagulation therapy

Joint Bone Spine - In Press.Proof corrected by the author Available online since vendredi 20 novembre 2015

Encore un qu’aurait mieux fait de rester chez lui…

Un homme, âgé de 40 ans, sans antécédent, était hospitalisé n mars 2012 pour bilan d’une thrombocytopénie fébrile. Il vivait n concubinage dans le 16e arrondissement de Paris, était père e deux enfants et exerç ait le métier d’ingénieur en télécommuications. L’interrogatoire ne révélait pas de conduite sexuelle à isque, ni de voyage récent. Il n’avait pas d’animal domestique, de obby particulier ou d’allergie connue. La consommation d’alcool tait occasionnelle. L’histoire commenç ait trois jours avant son hositalisation où il notait l’apparition de frissons et d’une asthénie ssociés à une fièvre nocturne à 39 ◦C. Il était asymptomatique en ehors de vagues myalgies des membres inférieurs et il n’y avait as de notion de contage. La veille de son hospitalisation, il appelait OS médecin pour persistance de la fièvre. La biologie montrait une hrombocytopénie isolée à 67 000/mm3, un taux d’hémoglobine à 5,4 g/dL et des leucocytes à 5900/mm3 avec « des arguments pour ne infection urinaire ». Le patient prenait de l’ibuprofène et de ’ofloxacine (après prélèvements) et était adressé le jour même aux rgences.