Comparison of incidence, causes and prognosis of adult and pediatric epidermal necrolysis: a population-based study in France.

BACKGROUND: Epidermal necrolysis (EN), comprising Stevens Johnson syndrome and toxic epidermal necrolysis is a rare and severe blistering reaction, mainly induced by drugs. Differences have been discussed between pediatric and adult patients regarding incidence, causes, and outcomes, but only based on a limited number of patients, in small case-series. OBJECTIVES: To directly compare incidence, causes and prognosis between adult and pediatric EN patients. METHODS: We used the French Health System Database from January 1st 2013 to December 31st 2022. We included adult and pediatric patients hospitalized for EN using the international classification of diseases, 10th revision codes combined with validated algorithms. The outcomes were incidence of EN; presence of a suspected drug before EN onset, defined by a new drug dispensation from 5 to 56 days before hospitalization; and in-hospital mortality. To estimate the association between pediatric EN and the presence of a suspected drug, we computed a multivariable logistic regression with odd ratios (OR). To estimate the association with mortality, we computed a multivariable Cox proportional hazard ratio (HR) model. RESULTS: A total of 1440 EN patients were included, with 799 (55.5%) females, comprising 219 children and 1221 adults. Among children, EN incidence was 1.5 cases (95%CI: 1.3-1.7) per million people year compared with 2.6 cases (95%CI: 2.5-2.7) in adults. Moreover, children had less chances to have a culprit drug before EN onset (93/219 (42.5%) versus 829/1221 (67.9%)), with an adjusted OR of 0.43 (95%CI: 0.32-0.59), p < 0.0001, together with a better prognosis, with death rates of 1.4% (95%CI: 0.4%-3.7%) in pediatric patients compared with 19.4% (95%CI: 17.3%-21.7%) in adult patients, and an adjusted HR of 0.12 (95%CI: 0.04-0.38), p = 0.0003 for in-hospital mortality. CONCLUSION: Pediatric EN seems to be rarer, with less chances to be caused by drugs, together with a better prognosis than adult EN. These results suggest the existence of different underlying pathophysiological mechanisms and clinical particularities between adult and pediatric patients.

Drugs associated with epidermal necrolysis in children: A World Health Organization pharmacovigilance database analysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening mucocutaneous reactions most often induced by drugs. To date, no large pharmacovigilance study has been conducted in the paediatric population. OBJECTIVES: To describe the spectrum of drugs associated with SJS-TEN in children through the analysis of cases reported in the WHO pharmacovigilance database (VigiBase). METHODS: Disproportionality study using data from VigiBase. All paediatric (age under 18 years) cases reported between January 1, 1967, and July 6, 2022, were included. For each molecule, a case-non-case study was performed to assess a potential pharmacovigilance signal by computing the lower end of the 95% credibility interval for the information component (IC025). We performed sensitivity analyses, (i) taking into account only cases reported by physicians and (ii) taking into account only cases reported in the last 10 years. RESULTS: Among 31,376,783 adverse drug reactions reported in VigiBase, 2,248,727 were paediatric cases and 7342 were encoded as paediatric SJS-TEN. Significant statistical pharmacovigilance signals were observed for 165 drugs. The two most represented drug classes were antiepileptics and anti-infectious drugs. The five drugs with the highest IC025 were lamotrigine (IC025 4.99), carbamazepine (IC025 4.88), phenobarbital (IC025 4.67), phenytoin (IC025 4.52) and nimesulide (IC025 4.23). Acetaminophen was significantly associated with paediatric SJS-TEN (IC025 2.85) and we also described various new suspected drugs. Vaccines had no significant pharmacovigilance signal. These results were confirmed with the sensitivity analyses. CONCLUSIONS: This study updates the spectrum of drugs potentially associated with paediatric SJS-TEN.

Proton Pump Inhibitors Associated With Drug-Induced Lupus Erythematosus.

This descriptive case series investigates the potential association between the use of proton pump inhibitors and drug-induced lupus erythematosus in cases reported in 2 large pharmacovigilance databases.

Paradoxical reactions and biologic agents: a French cohort study of 9303 patients.

BACKGROUND: Paradoxical reactions (PRs) are defined as the occurrence during biologic therapy of a pathological condition that usually responds to these drugs. OBJECTIVES: To estimate the incidence of PRs and identify risk factors. METHODS: Multicentre study of the database for the Greater Paris University Hospitals, including biologic-naive patients receiving anti-tumour necrosis factor-α, anti-interleukin-12/23, anti-interleukin-17 or anti-α4ß7-integrin agents for psoriasis, inflammatory rheumatism or inflammatory bowel disease (IBD). We used natural language processing algorithms to extract data. A cohort and a case-control study nested in the cohort with controls selected by incidence density sampling was used to identify risk factors. RESULTS: Most of the 9303 included patients (median age 43·0, 53·8% women) presented an IBD (3773, 40·6%) or a chronic inflammatory rheumatic disease (3708, 39·9%), and 8489 (91·3%) received anti-TNF-α agents. A total of 297 (3·2%) had a PR. The global incidence rate was 7·6 per 1000 person-years [95% confidence interval (CI) 6·8-8·5]. The likelihood of PR was associated with IBD [adjusted odds ratio (aOR) 1·9, 95% CI 1·1-3·2, P = 0·021] and a combination of at least two inflammatory diseases (aOR 6·1, 95% CI 3·6-10·6, P < 0·001) and was reduced with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and corticosteroids (aOR 0·6, 95% CI 0·4-0·8, P = 0·002; and OR 0·4, 95% CI 0·2-0·6, P = 0·002, respectively). CONCLUSIONS: The likelihood of PRs was associated with IBD or a combination of a least two inflammatory diseases. More studies are needed to assess the benefit of systematically adding csDMARDs for such high-risk patients. What is already known about this topic? Most published studies about paradoxical reactions concern paradoxical psoriasis in patients receiving anti-tumour necrosis factor-α agents. Few data are available for other paradoxical reactions and the most recent biologics. What does this study add? Risk of paradoxical reactions was increased with inflammatory bowel disease and a combination of at least two inflammatory diseases. Risk of paradoxical reactions was reduced with conventional synthetic disease-modifying antirheumatic drugs or corticosteroid therapy, which could be added for high-risk patients.

Performance of the Kleihauer Betke test in the prediction of neonatal anemia.

OBJECTIVES: The aim of this study was to correlate antenatal Kleihauer (KT) test results with fetal hemoglobin at birth to find a threshold for predicting severe fetal anemia. The secondary objectives were to assess the impact of KT on obstetric management and to study the correlation between the middle cerebral artery peack systolic velocity and fetal anemia. RESULTS: One thousand forty-six KT were positive over the 10-year period, but only 147 were included from 88 patients, of which 17 fetuses were anemic. Demographic and obstetric characteristics were similar between anemic and non-anemic groups. As regards new-born, there was a higher risk of prematurity among anemic as long as a lower birth rate in accordance. While a negative correlation was observed between KT and hemoglobin at birth, no KT upper threshold could be found that was both sensitive and specific. In addition, there was no case of fetal anemia when KT was repeated, even though it increased. KT showed little usefulness in obstetrics management to help improving neonatal care for anemia. Conversely, the MCA PSV demonstrated good performance in this matter and the ROC curve area was 0.91 (figure). DISCUSSION: Feto-maternal hemorrhage is a rare but grave pathology which could lead to anemia. The most common clinical sign is reduced fetal movement and it was the main indication to perform a KT. Cardiotocography patterns suggestive of anemia are sinusoidal, micro-oscillatory and non-reactive monitoring. Ultrasound features were polyhydramnios, hydrop fetalis and increased MCA peack systolic velocity. KT was correlated with MCA PSV and with hemoglobin level at birth. However, the latter showed a better diagnostic performance. MCA PSV measurement is a powerful test to screen for fetal anemia, and should be part of the regular training of obstetricians. Indeed, this technic gives immediate and reliable results, while those of KT are delayed. CONCLUSION: The KT should not be used as a tool to screen for fetal anemia but rather as a test to explain a fetal anemia. However, the MCA PSV is reliable in this matter and give immediate result, thus obstetrician should be trained to routinely perform it.