Benralizumab for eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series. METHODS: We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day. RESULTS: Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004). CONCLUSIONS: Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab.

Extreme gonococcal susceptibility associated with acquired complement deficiency secondary to hypocomplementemic urticarial vasculitis and systemic lupus erythematosus.

Gonococcal infection is rarely associated with septic shock. We describe a recurrent case of septic shock related to disseminated gonococcemia in a patient with systemic lupus erythematosus and hypocomplementemic urticarial vasculitis, and discuss the implication of profound acquired complement deficiency secondary to these auto-immune diseases. This case raises the question of systematic antibioprophylaxis in patients with acquired complement deficiency.

Massive vulvar edema revealing idiopathic systemic capillary leak syndrome.

Idiopathic systemic capillary leak syndrome is a rare disease characterized by recurrent episodes of hypotension, hypoalbuminemia and peripheral edema caused by capillary hyperpermeability with approximately 350 documented cases worldwide. We report herein the case of a 22-year-old primiparous patient with an unusual compartment syndrome represented with spontaneous massive vulvar edema. Treatment consisted of volume replacement and intravenous polyvalent immunoglobulins perfusions. Vulvar edema was treated surgically by incision and drainage with favorable outcome. The pregnancy follow-up did not show any fetal abnormalities. The childbirth at 35 weeks was natural and the newborn was healthy.

Trimethoprim-sulfamethoxazole as de-escalation in ventilator-associated pneumonia: a cohort study subanalysis.

PURPOSE: This is a subanalysis of a previous study which compared the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) with all other regimens for treatment of ventilator-associated pneumonia (VAP). Aim of the current study was to focus on the effectiveness of a strategy based on TMP-SMX as de-escalation from ß-lactam including regimens. METHODS: Retrospective cohort study including patients who were hospitalized for VAP from 2011 to 2019. Patients were distributed in two groups: NO SWITCH TO TMP-SMX group, including patients who received ß-lactams for all treatment duration, and SWITCH TO TMP-SMX group, which included patients who switched to TMP-SMX from a ß-lactam including regimen after microbiology diagnosis. Three clinical outcomes were analyzed: mortality at 30 days from the start of the antibiotic treatment (T30), mortality at the end of treatment (EoT), and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. RESULTS: Overall, 70 patients were included in the current study, 32/70 (45.7%) in NO SWITCH TO TMP-SMX group and 38/70 (54.3%) in SWITCH TO TMP-SMX group, 37/70 (52.8%) had been already included in the previous study. No significant differences in clinical outcomes and patient's characteristics were found when the two groups were compared. CONCLUSIONS: De-escalation to TMP-SMX for VAP treatment was not associated with higher mortality at EoT and T30 than standard treatment with ß-lactam. Monotherapy with TMP-SMX as de-escalation from broad-spectrum empirical regimens is a ß-lactam sparing strategy worthy to be further investigated in either multicenter cohort studies or randomized clinical trials.

Successful benralizumab for eosinophilic myocarditis in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterised by many features, including asthma, allergic rhinitis, peripheral and tissue eosinophilia, and vasculitis. Its pathophysiology is still unclear and we suggest that there are different phenotypes of EGPA, which may respond differently to available treatments. Within the most promising targeting biotherapy, benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has proved both highly effective and safe. We report herewith a case of EGPA presenting a myocarditis relapse successfully treated with benralizumab.

Primary Sjögren's syndrome: central and peripheral nervous system involvements.

Primary Sjögren's syndrome (pSS) is a common systemic autoimmune disease characterised by exocrinopathy resulting in dryness of the mouth and eyes, unexplained fatigue and diffuse pain. Neurological involvement is uncommon in pSS, involving the central nervous system in 2-5% of cases and more frequently the peripheral nervous system in 5-15% of cases. The diagnosis of pSS is to be considered when confronted with symptoms such as mouth and eye dryness, fatigue and pain, the most frequent of pSS symptoms. Objective measures of oral and eye dryness may help assert the diagnosis of pSS, as well as ACR/EULAR criteria. Differential diagnoses have to be excluded in patients exhibiting neurological symptoms, such as cryoglobulinaemic vasculitis or multiple sclerosis, before considering a neurological involvement specific to pSS. The treatment of these neurological manifestations takes into account different parameters, such as the presence of cryoglobulinaemic vasculitis, the severity of the symptoms, a rapidly progressing evolution and the failure of previous symptomatic treatments.

A Retrospective Study on Amoxicillin Susceptibility in Severe Haemophilus influenzae Pneumonia.

INTRODUCTION: Treatment of Haemophilus influenzae (Hi) pneumonia is on concern because resistance to amoxicillin is largely diffused. This study describes the evolution of resistance to amoxicillin and amoxicillin/clavulanic acid (AMC) in Hi isolates and characteristics of patients with Hi severe pneumonia. METHODS: A monocentric retrospective observational study including patients from 2008 to 2017 with severe pneumonia hospitalized in ICU. Evolution of amoxicillin and AMC susceptibility was showed. Characteristics of patients with Hi pneumonia were compared to characteristics of patients with Streptococcus pneumoniae (Sp) pneumonia, as reference. Risk factors for amoxicillin resistance in Hi were investigated. RESULTS: Overall, 113 patients with Hi and 132 with Sp pneumonia were included. The percentages of AMC resistance among Hi strains decreased over the years (from 10% in 2008-2009 to 0% in 2016-2017) while resistance to amoxicillin remained stable at 20%. Also, percentages of Sp resistant strains for amoxicillin decreased over years (from 25% to 3%). Patients with Hi pneumonia experienced higher prevalence of bronchitis (18% vs. 8%, p=0.02, chronic obstructive pulmonary disease (43% vs. 30% p=0.03), HAP (18% vs. 7%, p=0.01, ventilator-associated pneumonia (27% vs. 17%, p=0.04, and longer duration of mechanical ventilation (8 days vs. 6 days, p=0.04) than patients with Sp pneumonia. Patients with Sp pneumonia had more frequently local complications than patients with Hi pneumonia (17% vs. 7%, p=0.03). De-escalation of antibiotics was more frequent in patients with Sp than in patients with Hi (67% vs. 53%, p=0.03). No risk factors were associated with amoxicillin resistance among patients with Hi pneumonia. CONCLUSIONS: Amoxicillin resistance was stable over time, but no risk factors were detected. AMC resistance was extremely low, suggesting that AMC could be used for empiric treatment of Hi pneumonia, as well as other molecules, namely, cephalosporins. Patients with Hi pneumonia had more pulmonary comorbidities and severe diseases than patients with Sp pneumonia.

Evolution of haemostatic parameters and risk of bleeding during treatment with cefazolin.

In 2017, five cases of severe haemorrhages during treatment with cefazolin occurred in France. The aim of this study was to assess the risk of haemorrhage related to treatment with cefazolin by evaluating haemostatic parameters and bleeding events. A retrospective study was conducted from January 2016 to December 2017. Two populations were analysed: (i) overall population, which included all patients treated with cefazolin during this period and (ii) coagulation study population, which included all patients treated with cefazolin with available coagulation parameters (activated partial thromboplastin time (aPTT) and international normalised ratio (INR) at baseline and at the end of treatment or EoT). Values of either aPTT or INR at baseline and at EoT were compared. Cases of severe haemorrhages were reported and correlated with values of aPTT and INR. Overall, 132 patients received cefazolin and 59/132 (45%) were included in the coagulation study group. A significant increase of median aPTT was observed from baseline to EoT (39.5 and 44.3 sec; p = 0.004, respectively). Overall, severe haemorrhage occurred in 7/132 (5%) patients. Coagulation parameters were available in three of them, and no correlation was observed between bleeding events and aPTT increase. This study showed that bleeding is probably more frequent than ever reported before during cefazolin treatment. The significant increase of aPTT observed during cefazolin treatment was not correlated with risk of haemorrhage. Further studies are needed to explore the possible physio-pathological pathways behind the modification of haemostatic parameters and risk of haemorrhage.

Neuro-Behçet's disease: A review.

Behcet disease (BD) is a systemic vasculitis which can involve many different organ systems. Neurological involvement (NBD) occurs in 5.3% to 59% of BD patients. The diagnosis is challenging especially in case of inaugural neurological presentation, and is based on a constellation of clinical, laboratory, and neuroimaging findings. NBD can be subdivided into parenchymal NBD through an immune mediated meningoencephalitis with a predilection to the brainstem, basal ganglia, thalamus, cranial nerves, and spinal cord involvement, and extraparenchymal NBD encompassing cerebral veinous thrombosis and intracranial arterial involvement. Brain magnetic resonance shows ill-defined areas of oedema with high signal intensity on T2-FLAIR images, isointense or hypointense in T1-weighted images in the basal ganglia area or in the brainstem, which may extend to the diencephalic structures. Swelling might be noticed. Hemorrhages can be seen, such as contrast enhancement (blood brain barrier disruption). Magnetic resonance venography and computerized tomographic angiography can be used to diagnose extraparenchymal NBD. Treatment of parenchymatous forms is based on glucocorticoids associated with oral immunosuppressants (azathioprine, mycophenolate mofetil or methotrexate) in mild forms, and intravenous cyclophosphamide or infliximab in severe forms. The management of cerebral thrombosis consists of steroids course associated with an oral anticoagulation. An early recognition of this condition is mandatory to initiate adequate therapies in order to improve outcomes and limit the risk of sequelae, relapses, or death. The aim of this review is to summarize a comprehensive review on the various neurological presentations of BD with emphasizes on diagnostic tools, prognosis, and therapeutic issues.

Chlamydia psittaci-related pleuro-myocarditis.

Chlamydia psittaci ‒ related community-acquired pneumonia associated to acute myocarditis was diagnosed in a young man with no medical history, and a professional exposition to birds. The diagnosis was confirmed with positive specific polymerase chain reaction in bronchoalveolar lavage. The patient was treated with spiramycin for two weeks with anti-inflammatory treatment for myocarditis for three months. Clinical and biological improvement was rapidly observed followed by normalization of electrocardiogram and chest CT scan. No relapse was reported for over a two-year follow-up.

Annular Leukocytoclastic Vasculitis: A New Feature of IgA Vasculitis.

Background: Annular erythema is a rare manifestation of leukocytoclastic vasculitis. It may be associated with various drugs, infections, malignancies, or systemic diseases. Case description: A 36-year-old woman with no personal medical history presented with annular erythema with target lesions and petechial purpura. The patient had fever and joint arthralgia. A skin biopsy showed leukocytoclastic vasculitis with IgA deposits on direct immunofluorescence. The diagnosis of immunoglobulin A vasculitis with annular leukocytoclastic vasculitis was made. The patient showed global improvement with topical steroids without relapse. Conclusion: An annular variant of leukocytoclastic vasculitis is a rare manifestation of immunoglobulin A vasculitis. LEARNING POINTS: Annular erythema may reveal an IgA vasculitis.Annular leukocytoclastic vasculitis is a rare manifestation of IgA vasculitis.This presentation is treated with topical steroids.

Successful Introduction of Benralizumab for Eosinophilic Ascites.

Eosinophilic ascites is a rare disorder, reported in both adult and pediatric patients, characterized by high eosinophil counts in the peritoneal fluid. Eosinophilic ascites appears as a manifestation of various diseases such as parasitic and fungal infections, malignancy, and hypereosinophilic syndrome. It also represents an uncommon manifestation of eosinophilic gastroenteritis, usually treated with corticosteroids. We present the case of a 16-year-old woman with abdominal distention related to abundant ascites. Further work-up concluded that it was eosinophilic gastroenteritis complicated with eosinophilic ascites. The patient was on oral steroids for three weeks, but various abdominal relapses were observed, leading to the introduction of benralizumab, as a steroid-sparing therapy with a favorable outcome.

State of the Art of Cardiac Amyloidosis.

Cardiac amyloidosis is defined by extracellular deposition of misfolded proteins in the heart. The most frequent cases of cardiac amyloidosis are caused by transthyretin and light chain amyloidosis. This condition is underdiagnosed, and its incidence has been continuously rising in recent studies because of the aging of the population and the development of noninvasive multimodal diagnostic tools. Amyloid infiltration affects all cardiac tunics and causes heart failure with preserved ejection fraction, aortic stenosis, arrythmia, and conductive disorder. Innovative, specific therapeutic approaches have demonstrated an improvement in affected organs and the global survival of patients. This condition is no longer considered rare and incurable. Thus, better knowledge of the disease is mandatory. This review will provide a digest of the clinical signs and symptoms of cardiac amyloidosis, the diagnostic tools used to confirm the diagnosis, and current symptomatic and etiopathogenic management considerations according to guidelines and recommendations.

Lactobacillus rhamnosus a cause of Gram-positive rods bacteremia after prophylactic probiotic consumption.

•Lactobacillus rhamnosus bacteremia was diagnosed in a patient with radiation enteritis after prophylactic probiotic consumption.•L. rhamnosus was identified by culture and MALDI-TOF-MS.•L. rhamnosus may have high MIC values for amoxicillin.•In case of L. rhamnosus bacteremia, bowel diseases should be considered as a possible source of infections.

Atrial Septal Defect Associated With Right Bundle Branch Block Masking Brugada Syndrome.

A type 1 Brugada electrocardiogram pattern may be masked by typical right bundle branch block aspect. We present 2 cases (male patients, aged 18 and 22 years) of associated ostium secundum atrial septal defect with a right bundle branch block aspect and symptomatic confirmed Brugada syndrome. Both patients underwent cardiac defibrillator implantation. (Level of Difficulty: Advanced.).

Pulmonary cavitary disease due to Mycobacterium xenopi.

Non-tuberculous mycobacteria are a significant cause of pulmonary infections worldwide and can be clinically challenging. Mycobacterium xenopi (M. xenopi) has a low pathogenicity and usually requires immunosuppression or lung diseases. We describe herein a scarce case of pulmonary cavitary disease attributed to M. xenopi in a 57-year-old Caucasian patient with underlying structural lung disease successfully treated with rifampicin, ethambutol, clarithromycin, and amikacin.

Atypical miller-fisher syndrome after COVID-19 and sleeve gastrectomy: Contribution of neurochemical markers to early diagnosis.

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in late 2019. More recently, there have been sporadic case reports on development of Miller-Fisher Syndrome , a rare variant of Guillain-Barré Syndrome in COVID-19 patients. Case report: We reported herein the case of a French young women presenting with ophtalmoplegia, cerebellar ataxia, and universal areflexia following a bariatric surgery (sleeve gastrectomy). A concomitant COVID-19 diagnosis was retained based on microbiological testing. The patient was successfully treated after high-dose intravenous thiamine, but areflexia persisted. Underlying COVID-19 related Miller-Fisher Syndrome was established on physical examination and confirmed by pathologic neurophysiological findings and elevated level of phosphorylated neurofilament heavy chain protein in cerebrospinal fluid analysis. Conclusions: Guillain-Barré Syndrome and its variants after SARS-CoV-2 infection are extremely rare. The measurement of phosphorylated neurofilament heavy chain protein should be considered as an easy tool to detect an early affection of the peripheral nervous system.

Recurrent obstructive prostatitis revealing granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA) associated; vasculitis affecting small vessels and mainly cause upper and lower respiratory tract and renal involvement. Urogenital involvement is extremely rare and poorly described in the literature. We report herein a case of a 46-year old immunocompetent patient presenting with recurrent urinary tract infections and bladder retention with incidental findings of sinusitis, and pulmonary mass revealing GPA.

Cardiovascular Magnetic Resonance Imaging Pattern in Campylobacter jejuni-related Myocarditis.

BACKGROUND: Campylobacter jejuni (C. jejuni) is a common cause of mostly self-limiting enterocolitis. Although rare, myocarditis has been increasingly documented as a complication following campylobacteriosis. Such cases have occurred predominantly in younger males and involved a single causative species, namely C. jejuni. CASE REPORT: We report herein a case of myocarditis complicating gastroenteritis in a 23-year-old immunocompetent patient, caused by this bacterium with a favorable outcome. Cardiac magnetic resonance imagining was useful in establishing an early diagnosis. CONCLUSIONS: Myocarditis should be considered in younger patients presenting with chest pain and plasmatic troponin elevations. The occurrence of myocarditis complicating C. jejuni is reviewed.

Consecutive Severe Orofacial Complications in Intensive Care Unit Patients: Quincke's Disease and Macroglossia due to Prolonged Prone Positioning for Management of Acute Respiratory Distress Syndrome.

Critically ill patients admitted into the intensive care units are susceptible to a wide array of complications that can be life-threatening, or lead to long-term complications. Some complications are inherent to the patient's condition and others are related to therapeutics or care procedure. The prolonged prone positioning and mechanical ventilation devices are the first risk factors for orofacial complications. We report the case of a 47-year-old male patient, with a history of sleep apnoea syndrome, morbid obesity (body mass index of 43 kg/m2), and gastroesophageal reflux disease, presented to the emergency department with recent otorhinolaryngological symptoms of dysphonia and exertional dyspnoea lasting two days, and complicated with Quincke's disease. First-line treatment consisted of a compilation of intravenous antihistamines and corticosteroids. The patient's condition worsened. He developed an acute respiratory distress syndrome secondary to ventilator-acquired pneumonia with prone positioning ventilation, complicated by severe macroglossia. Soaked gauze dressings were placed around his tongue. Progressively, the size of his tongue reduced. LEARNING POINTS: Intensive care unit (ICU) patients are susceptible to a wide array of life-threatening complications that can be linked.Oral severe acquired Quincke's disease is an isolated form of angioneurotic oedema that is induced by several factors including gastroesophageal reflux disease, sleep apnoea, inhalation exposure, or drug reactions. Macroglossia is rare life-threatening complication due to prolonged prone positioning of unknown pathogenesis. An experienced critical care staff with standardised protocol is needed to prevent such a complication.Because of possible consecutive severe orofacial complications, prolonged prone positioning for management of acute respiratory distress syndrome (ARDS) is not recommended in patients with inaugural oral angioedema.