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INTRODUCTION The distinction between epidermal necrolysis [EN; including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. MATERIALS AND METHODS This French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow-up. RESULTS We included 62 children [43 boys, median age 10 years (range 3-18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P

Objectives To describe the cumulative incidences of adverse drug reactions (ADRs) associated with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients from real-world data (RWD), using the DREAM-RA registry, and to compare these with incidence frequencies mentioned in the Summary of Product Characteristics (SmPC). Methods All ADRs in patients with recorded use of adalimumab, etanercept, hydroxychloroquine, leflunomide, oral and subcutaneous methotrexate, and sulfasalazine from a single center participating in the DREAM-RA registry (n = 1,098 patients) that were directly sent to the Netherlands Pharmacovigilance Center Lareb were assessed. Cumulative incidences were calculated, described and compared to the most recently revised SmPCs. Results In total, 14 ADRs (>= 5 case reports) associated with the use of one of the included DMARDs were reported with a higher estimated cumulative incidence compared to the SmPC. For hydroxychloroquine and sulfasalazine, 5 ADRs (>= 5 case reports) mentioned with an 'unknown' incidence in the SmPC were reported as 'common' in this study. Conclusions Although ADR data in the DREAM-RA registry were partly comparable with data in the SmPCs, RWD from this patient registry provided an added value to the currently available information on the incidences of ADRs associated with DMARDs in RA patients as described in SmPCs.

The antipsychotic drug clozapine is associated with weight gain. The proposed mechanisms include blocking of serotonin (5-HT2a/2c ), dopamine (D2 ) and histamine (H1 ) receptors. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2) to norclozapine, a metabolite with more 5-HT2c -receptor and less H1 blocking capacity. We hypothesized that norclozapine serum levels correlate with body mass index (BMI), waist circumference and other parameters of the metabolic syndrome. We performed a retrospective cross-sectional study in 39 patients (female n = 8 (20.5%), smokers n = 18 (46.2%), average age 45.8 ± 9.9 years) of a clozapine outpatient clinic in the Netherlands between 1 January 2017 and 1 July 2020. Norclozapine concentrations correlated with waist circumference (r = 0.354, P = .03) and hemoglobin A1c (HbA1c) (r = 0.34, P = .03). In smokers (smoking induces CYP1A2), norclozapine concentrations correlated with waist circumference (r = 0.723, P = .001), HbA1c (r = 0.49, P = .04) and BMI (r = 0.63, P = .004). Elucidating the relationship between norclozapine and adverse effects of clozapine use offers perspectives for interventions and treatment options.

The diagnosis of exercise-induced laryngeal obstruction (EILO) should be suspected when exercise triggers inspiratory stridor. EILO is common in adolescent populations and has a significant impact on sports. Identification of laryngeal obstruction during continuous laryngoscopy during exercise (CLE) is the gold standard diagnostic tool for this disorder, which is not widely known in France. The challenge faced by otolaryngologists is to identify, among patients referred by pulmonologists or sports physicians, those with exercise-induced inspiratory symptoms or poorly controlled exercise-induced asthma, in whom a diagnosis of EILO is strongly suspected. Laryngoscopy at rest may reveal a laryngeal, glottic or supraglottic abnormality predictive of obstruction at increased inspiratory airflow. When pulmonary function tests are normal or in the case of failure of treatment of exercise-induced asthma, the otolaryngologist must complete the examination by a CLE test to confirm the diagnosis of EILO and identify the site of obstruction. This examination is well tolerated, minimally invasive and allows identification of the site of airflow obstruction, allowing specific conservative or surgical treatment. This technical note describes in detail clinical examination and CLE testing in patients with suspected EILO.

Introduction Inflammatory bowel disease (IBD) frequently requires chronic immunosuppressive treatment and active involvement from patients during treatment decision making. Information about the risk of developing adverse drug reactions (ADRs) to IBD therapies is required in this process. Objective The aim of this study was to describe the ADRs reported in IBD patients from real-world data, using the Dutch nationwide IBDREAM registry, and compare the occurrence and cumulative incidences with the Summary of Product Characteristics (SmPC) of the associated drugs. Methods In this retrospective multicentre study, ADRs related to IBD medication were assessed. Only reports associated with the use of drugs used for the maintenance treatment of IBD were included. All ADRs were verified by healthcare professionals and coded by trained pharmacovigilance assessors. Results In total, 3080 ADRs were reported in 1179 patients. Twenty-three new drug–ADR associations related to the use of azathioprine, mercaptopurine, infliximab, oral mesalamine and thioguanine were reported in the IBDREAM registry that were not mentioned in the corresponding SmPCs. The most frequently reported new association was pyrexia for azathioprine (3.1%) and mercaptopurine (4.9%). In addition, there were seven ADRs with a higher cumulative incidence in IBDREAM compared with the SmPC, and included, among others, arthralgia during mercaptopurine use (2.5%), and diarrhoea (1.4%), alopecia (1.2%) and infections (1.6%) during azathioprine use. Conclusions Based on real-world data, ADR reporting demonstrated new ADRs and higher incidences of ADRs to IBD therapies. This information will contribute to drug safety by updating the SmPCs, allowing better risk assessment and communication towards patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01045-3.

Propylthiouracil (PTU) is a synthetic antithyroid drug that can induce ANCA-associated vasculitis.A 27-year-old woman diagnosed with Graves' disease was on PTU for the past 10 years. She developed purpuric lesions of the legs and on the tip of the nose diagnosed as vasculitis. ANCAs were positive, with anti-MPO and anti-PR3 on blood ELISA. After discontinuation of PTU, she was able to fully recover.All synthetic antithyroid drugs can induce ANCA-associated vasculitis, more often PTU. In most cases, antibodies are directed against MPO. Dual anti-MPO and anti-PR3 positivity is possible, but rare. The mechanism could be through an accumulation of PTU in neutrophils, altering the structure of MPO and making it immunogenic. PTU can also induce ANCA-free or lupus vasculitis, maculopapular rashes or urticaria. Many other drugs can induce ANCA-associated vasculitis.

Caudal vena cava (CVC) diameter and collapsibility index (CVCThis retrospective study included 79 dogs with DMVD presented to the cardiology department between January 2017 and 2019. Subxiphoid views were used to obtain CVC cineloops. By visual inspection, CVC was subjectively scored as flat, normal or fat. Maximal and minimal CVCSubjective assessment was associated with American College of Veterinary Internal Medicine (ACVIM) stages (P 0.001). The proportion of fat CVC was greater in stages C and D. In stage D, CVCIn dogs with DMVD without clinically important right heart disease, CVC variables differ across ACVIM stage. Subjective and objective CVC variables may be used to predict hypervolemia.

Thanks to the progress made in the past few years in pediatric intensive care as well as the increased survival of preterm infants, the consequences of premature birth are increasingly well documented. With regard to ophthalmologic complications, retinopathy of prematurity is well described, but the optic nerve may also be affected. The goal of this study is to compare the optic nerves of preterm infants as a function of their gestational period with a control group of the same age.We conducted a case-control study pairing a full-term infant with each preterm infant. Inclusion criteria were: any child from 5- to 10-years-old, separated into three sub-groups according to their degree of prematurity. Variables were: cup/disc ratio, ocular biometry, intraocular pressure and RNFL thickness.Thirty-seven preterm infants and 37 controls were included in the study. The mean age at the time of inclusion was 7.05 years for the preterm group and 7.19 years for the control group. No significant difference was observed in axial length or spherical equivalent (P=0.31 and P=0.98, respectively). No significant difference was observed in pachymetry or intraocular pressure (P=0.28 and P=0.22, respectively). We observed a significant increase of 0.1 in the cup/disc ratio of the preterm group compared to the control group (P0.05). The preterm group cup/disc ratio was 0.36 versus 0.27 for the control group. No significant difference was observed in the 7 quadrants of RNFL between the two groups. However, when comparing infants born before 28 weeks gestation with the control group, we observed a mean decrease of 14.5 microns in the superior temporal sector (P=0.04), a 9 micron decrease in the global thickness G (P=0.03) and a 12.7 micron decrease in the nasal sector (P=0.01).In the case of the studied children (aged 5 to 10), the reduced RNFL fiber thickness is a phenomenon dependent essentially on the stage of prematurity. It would be useful to follow these preterm populations over the long term and to compare them to a matched control group to be able to obtain functional results.

Several previous functional imaging experiments have demonstrated that auditory presentation of speech, relative to tones or scrambled speech, activate the superior temporal sulci (STS) bilaterally. In this study, we attempted to segregate the neural responses to phonological, lexical, and semantic input by contrasting activation elicited by heard words, meaningless syllables, and environmental sounds. Inevitable differences between the duration and amplitude of each stimulus type were controlled with auditory noise bursts matched to each activation stimulus. Half the subjects were instructed to say “okay” in response to presentation of all stimuli. The other half repeated back the words and syllables, named the source of the sounds, and said “okay” to the control stimuli (noise bursts). We looked for stimulus effects that were consistent across task. The results revealed that central regions in the STS were equally responsive to speech (words and syllables) and familiar sounds, whereas the posterior and anterior regions of the left superior temporal gyrus were more active for speech. The effect of semantic input was small but revealed more activation in the inferior temporal cortex for words and familiar sounds than syllables and noise. In addition, words (relative to syllables, sounds, and noise) enhanced activation in the temporo-parietal areas that have previously been linked to modality independent semantic processing. Thus, in cognitive terms, we dissociate phono-logical (speech) and semantic responses and propose that word specificity arises from functional integration among shared phonological and semantic areas.