Denis Vital-Durand

Disseminated aseptic abscesses associated with Crohn's disease : A new entity?

Our purpose is to describe seven cases ofdisseminated aseptic abscesses with regard to clinical,biological, radiological, and histological information,treatment, and outcome. Data were collected on seven Caucasian patients who had proven sterile deepabscesses diagnosed in French university hospitals. Theonset of the disease related to abscesses began at timesfrom June 1988 to August 1994. Follow-up periods were 1 year, 7 months to 8 years, 2 months. Theage of the patients ranged from 15 to 26 years old. Atonset, all had fever and six had abdominal pain.Abscesses involved spleen and abdominal lymph nodes in six cases; liver in three; pancreas, brain,and chest in one. All had polymorphonuclearleukocytosis. Pathological examination showedgranulomatous abscesses. Direct and indirectinvestigations failed to identify any causal microorganism. On sixoccasions, Crohns disease was revealed 1 to 41 monthslater and in one case, it preceded the onset ofabscesses. One subsequently developed Sweets syndrome. Various antibiotic regimes were inefficient.Steroids, associated in three cases withimmunosuppressive agents, resulted in a rapidimprovement in six patients. In one case, splenectomyfollowed by 5-ASA therapy was used successfully. The dramaticeffectiveness of steroids and immunosuppressive agentsas well as follow-up suggest that disseminated asepticabscesses might be an extraintestinal manifestation of Crohns disease. Although the pathogenesisof this condition remains unknown, this entity may berelated to neutrophilic dermatosis in which sterile deepabscesses have been reported.

Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies.

OBJECTIVEnThis study aims to evaluate the response to rituximab (RTX) treatment in auto-immune hemolytic anemia (AIHA) patients.nnnMETHODSnStudies were selected from MEDLINE up to March 2014. Two investigators independently extracted data on study design, patient characteristics, clinical features (AIHA type, disease duration, previous treatments), dose-schedule of rituximab, duration of treatment follow-up, and toxicities. Pooled overall response rate (ORR) and complete response (CR) rates were evaluated to determine RTX efficacy and toxicity by calculating the weighted mean proportion with fixed or random-effects models in case of heterogeneity (p<0.1 or I(2)>50%).nnnRESULTSnTwenty-one studies encompassing 409 patients were included in the meta-analysis. The characteristics of the entire analyzed cohort reported were as follows: mean male proportion: 43%, mean age: 50 years, splenectomized patients range: 0-50%. Warm AIHA, primary AIHA and adults were mostly represented. With the random-effect model, the overall response rate (ORR) was 73% (95% CI 64-81%, 20 studies encompassing 402 patients). CR rate was 37% (95% CI 26-49%, 20 studies including 397 patients). The ORRs were close to 70% for warm AIHA (79%, 95% CI 60-90%, 11 studies, 154 patients), primary AIHA (67%, 95% CI 49-81%, 10 studies, 161 patients), and secondary AIHA (72%, 95% CI 60-82%, 8 studies, 66 patients). The ORR was 57% (95% CI 47-66%, 6 studies, 109 patients) for cold agglutinin disease (CAD). The CR rate was 42% (95% CI 27-58%, 11 studies, 154 patients) for warm AHAI, 32% (95% CI 17-51%, 11 studies, 176 patients) for primary AIHA, 46% (95% CI 30-62%, 9 studies, 87 patients) for secondary AIHA and only 21% (95% CI 6-51%, 7 studies, 118 patients) for CAD. Definitive response rates were evaluated during follow-up. CR rate was the highest within 2 to 4 months after RTX (13 studies, 203 patients, CR=70% [57-80%]). As for toxicities, 38 adverse events in 364 patients were noted (14% (95% CI 9-21%)). Sixteen events were infusion-linked side effects, mostly chills and fever, whereas twenty-two were severe. Only one opportunistic Pneumocystis jiroveci pneumonia was reported. Seventeen patients out of 364 (4.6%) died during follow-up. In univariate mixed-effect meta-regressions, ORR and CR were significantly associated with warm AIHA (p=0.002) and mean age (p<0.001), and marginally associated with disease type (p=0.06 and 0.005, respectively).nnnCONCLUSIONSnRituximab seems to be a safe and effective therapy for AIHA in this meta-analysis of observational studies. The authors suggest that it could be used at an earlier point in therapy, before more toxic immunosuppressive drugs, or in place of splenectomy in some cases.

Influence of age at disease onset in the outcome of paediatric systemic lupus erythematosus

OBJECTIVESnThe aim of this study was to investigate the influence of age at disease onset in the outcome of paediatric SLE (pSLE).nnnMETHODSnFifty-six patients with pSLE, divided into three groups (pre-pubertal, peripubertal and post-pubertal onset), were studied. The SDI (SLICC/ACR Damage Index for SLE), patients characteristics, disease manifestations and treatments were compared using Fishers exact test and Kruskal-Wallis test. Kaplan-Meier curves were constructed to compare the risk of damage occurrence.nnnRESULTSnThe risk of damage (SDI >or=1) significantly decreased when age at disease onset increased (89% in pre-pubertal pSLE, 57% in peripubertal pSLE and 38% in post-pubertal pSLE). This excess of risk was found in all disease duration intervals studied (1-3, 3-5, 5-8, 8-10, >10 years) and at the end of follow-up. Kaplan-Meier curves indicated a higher and earlier risk of damage in younger patients. Young children showed higher frequency of autoimmune family history. The frequency of neuropsychiatric disorders and damages decreased with age at disease onset (P < 0.05). Cumulative duration of high-dose prednisone (> 0.5 mg/kg/day) and number of immunosuppressive drugs used that seem to contribute to damage significantly increased when age at disease onset decreased.nnnCONCLUSIONSnThe risk of damage is inversely correlated with age at disease onset in pSLE. The poorer outcome observed in younger children may be explained by a more severe disease expression, may be a higher infectious susceptibility, and a more aggressive therapy, particularly within the first 6 months of disease course.

Consistency of Safety and Efficacy of New Oral Anticoagulants across Subgroups of Patients with Atrial Fibrillation

Aims The well-known limitations of vitamin K antagonists (VKA) led to development of new oral anticoagulants (NOAC) in non-valvular atrial fibrillation (NVAF). The aim of this meta-analysis was to determine the consistency of treatment effects of NOAC irrespective of age, comorbidities, or prior VKA exposure. Methods and Results All randomized, controlled phase III trials comparing NOAC to VKA up to October 2012 were eligible provided their results (stroke/systemic embolism (SSE) and major bleeding (MB)) were reported according to age (≤ or >75 years), renal function, CHADS2 score, presence of diabetes mellitus or heart failure, prior VKA use or previous cerebrovascular events. Interactions were considered significant at p <0.05. Three studies (50,578 patients) were included, respectively evaluating apixaban, rivaroxaban, and dabigatran versus warfarin. A trend towards interaction with heart failure (pu200a=u200a0.08) was observed with respect to SSE reduction, this being greater in patients not presenting heart failure (RRu200a=u200a0.76 [0.67–0.86]) than in those with heart failure (RRu200a=u200a0.90 [0.78–1.04]); Significant interaction (pu200a=u200a0.01) with CHADS2 score was observed, NOAC achieving a greater reduction in bleeding risk in patients with a score of 0–1 (RR 0.67 CI 0.57–0.79) than in those with a score ≥2 (RR 0.85 CI 0.74–0.98). Comparison of MB in patients with (RR 0.97 CI 0.79–1.18) and without (RR 0.76 CI 0.65–0.88) diabetes mellitus showed a similar trend (pu200a=u200a0.06). No other interactions were found. All subgroups derived benefit from NOA in terms of SSE or MB reduction. Conclusions NOAC appeared to be more effective and safer than VKA in reducing SSE or MB irrespective of patient comorbidities. Thromboembolism risk, evaluated by CHADS2 score and, to a lesser extent, diabetes mellitus modified the treatment effects of NOAC without complete loss of benefit with respect to MB reduction.

Central Nervous System Involvement in Whipple Disease: Clinical Study of 18 Patients and Long-Term Follow-Up

AbstractWhipple disease (WD) is a rare multisystemic infection with a protean clinical presentation. The central nervous system (CNS) is involved in 3 situations: CNS involvement in classic WD, CNS relapse in previously treated WD, and isolated CNS infection. We retrospectively analyzed clinical features, diagnostic workup, brain imaging, cerebrospinal fluid (CSF) study, treatment, and follow-up data in 18 patients with WD and CNS infection.Ten men and 8 women were included with a median age at diagnosis of 47 years (range, 30–56 yr). The median follow-up duration was 6 years (range, 1–19 yr). As categorized in the 3 subgroups, 11 patients had classic WD with CNS involvement, 4 had an isolated CNS infection, and 3 had a neurologic relapse of previously treated WD. CNS involvement occurred during prolonged trimethoprim-sulfamethoxazole (TMP-SMX) treatment in 1 patient with classic WD.The neurologic symptoms were various and always intermingled, as follows: confusion or coma (17%) related to meningo-encephalitis or status epilepticus; delirium (17%); cognitive impairment (61%) including memory loss and attention defects or typical frontal lobe syndrome; hypersomnia (17%); abnormal movements (myoclonus, choreiform movements, oculomasticatory myorhythmia) (39%); cerebellar ataxia (11%); upper motor neuron (44%) or extrapyramidal symptoms (33%); and ophthalmoplegia (17%) in conjunction or not with progressive supranuclear palsy. No specific pattern was correlated with any subgroup.Brain magnetic resonance imaging (MRI) revealed a unique focal lesion (35%), mostly as a tumorlike brain lesion, or multifocal lesions (23%) involving the medial temporal lobe, midbrain, hypothalamus, and thalamus. Periventricular diffuse leukopathy (6%), diffuse cortical atrophy (18%), and pachymeningitis (12%) were observed. The spinal cord was involved in 2 cases. MRI showed ischemic sequelae at diagnosis or during follow-up in 4 patients. Brain MRI was normal despite neurologic symptoms in 3 cases. CSF cytology was normal in 62% of patients, whereas Tropheryma whipplei polymerase chain reaction (PCR) analysis was positive in 92% of cases with tested CSF. Periodic acid–Schiff (PAS)-positive cells were identified in cerebral biopsies of 4 patients.All patients were treated with antimicrobial therapy for a mean duration of 2 years (range, 1–7 yr) with either oral monotherapy (TMP-SMX, doxycycline, third-generation cephalosporins) or a combination of antibiotics that sometimes followed parenteral treatment with beta-lactams and aminoglycosides. Eight patients also received hydroxychloroquine.At the end of follow-up, the clinical outcome was favorable in 14 patients (78%), with mild to moderate sequelae in 9. Thirteen patients (72%) had stopped treatment for an average time of 4 years (range, 0.7–14 yr). Four patients had clinical worsening despite antimicrobial therapy; 2 of those died following diffuse encephalitis (n = 1) and lung infection (n = 1).In conclusion, the neurologic manifestations of WD are diverse and may mimic almost any neurologic condition. Brain involvement may occur during or after TMP-SMX treatment. CSF T. whipplei PCR analysis is a major tool for diagnosis and may be positive in the absence of meningitis. Immune reconstitution syndrome may occur in the early months of treatment. Late prognosis may be better than previously reported, as a consequence of earlier diagnosis and a better use of antimicrobial therapy, including hydroxychloroquine and doxycycline combination.

Abnormal hemoglobins with high oxygen affinity in the differential diagnosis of polycythemia

Hemoglobin variant with high oxygen affinity is an uncommon, often misdiagnosed, etiology of erythrocytosis. We report two cases of erythrocytosis. Their hemoglobin–oxygen dissociation curve showed a P50 value (the oxygen tension at which hemoglobin is 50% saturated) below the normal range. Globin chains electrophoresis and DNA analysis evidenced hemoglobin Olympia and hemoglobin Malmo, respectively. More than 200 variants of hemoglobin with increased oxygen affinity have been described, that are in about one-third responsible of secondary erythocytosis because of tissular hypoxia. Such abnormal haemoglobin identification should be routinely included in the diagnostic work-up of unexplained erythocytosis, particularly in young people.Hemoglobin variant with high oxygen affinity is an uncommon, often misdiagnosed, etiology of erythrocytosis. We report two cases of erythrocytosis. Their hemoglobin-oxygen dissociation curve showed a P50 value (the oxygen tension at which hemoglobin is 50% saturated) below the normal range. Globin chains electrophoresis and DNA analysis evidenced hemoglobin Olympia and hemoglobin Malmö, respectively. More than 200 variants of hemoglobin with increased oxygen affinity have been described, that are in about one-third responsible of secondary erythocytosis because of tissular hypoxia. Such abnormal haemoglobin identification should be routinely included in the diagnostic work-up of unexplained erythocytosis, particularly in young people.

Polyglobulies : penser aux hémoglobines hyperaffines pour l’oxygène

Hemoglobin variant with high oxygen affinity is an uncommon, often misdiagnosed, etiology of erythrocytosis. We report two cases of erythrocytosis. Their hemoglobin–oxygen dissociation curve showed a P50 value (the oxygen tension at which hemoglobin is 50% saturated) below the normal range. Globin chains electrophoresis and DNA analysis evidenced hemoglobin Olympia and hemoglobin Malmo, respectively. More than 200 variants of hemoglobin with increased oxygen affinity have been described, that are in about one-third responsible of secondary erythocytosis because of tissular hypoxia. Such abnormal haemoglobin identification should be routinely included in the diagnostic work-up of unexplained erythocytosis, particularly in young people.Hemoglobin variant with high oxygen affinity is an uncommon, often misdiagnosed, etiology of erythrocytosis. We report two cases of erythrocytosis. Their hemoglobin-oxygen dissociation curve showed a P50 value (the oxygen tension at which hemoglobin is 50% saturated) below the normal range. Globin chains electrophoresis and DNA analysis evidenced hemoglobin Olympia and hemoglobin Malmö, respectively. More than 200 variants of hemoglobin with increased oxygen affinity have been described, that are in about one-third responsible of secondary erythocytosis because of tissular hypoxia. Such abnormal haemoglobin identification should be routinely included in the diagnostic work-up of unexplained erythocytosis, particularly in young people.

Cas cliniquePolyglobulies : penser aux hémoglobines hyperaffines pour l’oxygèneAbnormal haemoglobins with high oxygen affinity in the differential diagnostics of polycythemia

Hemoglobin variant with high oxygen affinity is an uncommon, often misdiagnosed, etiology of erythrocytosis. We report two cases of erythrocytosis. Their hemoglobin–oxygen dissociation curve showed a P50 value (the oxygen tension at which hemoglobin is 50% saturated) below the normal range. Globin chains electrophoresis and DNA analysis evidenced hemoglobin Olympia and hemoglobin Malmo, respectively. More than 200 variants of hemoglobin with increased oxygen affinity have been described, that are in about one-third responsible of secondary erythocytosis because of tissular hypoxia. Such abnormal haemoglobin identification should be routinely included in the diagnostic work-up of unexplained erythocytosis, particularly in young people.Hemoglobin variant with high oxygen affinity is an uncommon, often misdiagnosed, etiology of erythrocytosis. We report two cases of erythrocytosis. Their hemoglobin-oxygen dissociation curve showed a P50 value (the oxygen tension at which hemoglobin is 50% saturated) below the normal range. Globin chains electrophoresis and DNA analysis evidenced hemoglobin Olympia and hemoglobin Malmö, respectively. More than 200 variants of hemoglobin with increased oxygen affinity have been described, that are in about one-third responsible of secondary erythocytosis because of tissular hypoxia. Such abnormal haemoglobin identification should be routinely included in the diagnostic work-up of unexplained erythocytosis, particularly in young people.