Candice Fabre1, Caroline Thumerelle2, Morgane Dervaux1, Rola Abou-Taam3, Tiphaine Bihouee4, Jacques Brouard5, Annick Clement6, Christophe Delacourt3, Céline Delestrain7, Ralph Epaud7, Sofiane Ghdifan8, Alice Hadchouel3, Véronique Houdouin9, Géraldine Labouret10, Caroline Perisson11, Philippe Reix12,13, Marie-Catherine Renoux14, Françoise Troussier15, Laurence Weiss16, Julie Mazenq1, Nadia Nathan6, Jean-Christophe Dubus17,18,19. 1. Pediatric Pulmonology Department, University Timone Hospital for Children, AP-HM, Marseille, France. 2. Pediatric Pulmonology and Allergy Department, Jeanne de Flandre Hospital, CHU Lille, Univ. Lille, Pole Enfant, Lille, France. 3. AP-HP, Pediatric Pulmonology Department, Reference Center for Rare Lung Diseases, University Hospital of Necker-Enfants Malades, Paris, France. 4. Chronic Childhood Diseases Unit, Pediatric Department, Nantes University Hospital, Nantes, France. 5. Service de Pédiatrie Médicale, CHU Caen, Caen, et UMR1311 DYNAMICURE, Normandie Université, UNICAEN, UNIROUEN, Rouen, France. 6. AP-HP, Pediatric Pulmonology Department and Reference Center for Rare Lung Diseases (RespiRare), Sorbonne University, Inserm UMR S-933 Childhood Genetic Disorders, Armand Trousseau Hospital, Paris, France. 7. Center for Rare Lung Diseases (RespiRare), Centre Hospitalier Intercommunal of Créteil, University Paris Est Créteil, INSERM, IMRB, Créteil, France. 8. Pediatric Unit, Grenoble-Alpes University Hospital, Grenoble, France. 9. AP-HP, Pediatric Pulmonology Department, UMR S 976 INSERM Human Immunology, Paris University, Robert Debre Hospital, Paris, France. 10. Pediatric Pulmonology Department, University Hospital for Children, Toulouse, France. 11. Pediatric Unit, University Hospital Sud Reunion, Saint-Pierre, France. 12. Pediatric Pulmonology, Allergology, Cystic Fibrosis Department, Hospices Civils of Lyon, Hôpital Femme Mère Enfant, Bron, France. 13. UMR 5558, Equipe EMET, CNRS, University Claude Bernard Lyon 1, Lyon, France. 14. Paediatric Cardiology and Pulmonology Department, Montpellier University Hospital, Montpellier, France. 15. Pediatric Department, University Hospital, Angers, France. 16. Specialized Pediatric Department, University Hospital of Strasbourg, Strasbourg, France. 17. Pediatric Pulmonology Department, University Timone Hospital for Children, AP-HM, Marseille, France. jean-christophe.dubus@ap-hm.fr. 18. IRD, Aix Marseille University, MEPHI, IHU Méditerranée Infection, Marseille, France. jean-christophe.dubus@ap-hm.fr. 19. Unité de Pneumopédiatrie, CHU Timone-Enfants, 13385, Cedex 5/0491386816, Marseille, France. jean-christophe.dubus@ap-hm.fr.
Abstract
Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current practice, a clinical and radiological approach is more and more preferred (NEHI syndrome). This national study aimed to address diagnosis and initial management of patients followed up for a NEHI pattern in pediatric centers for rare lung diseases (RespiRare, France). Data on neonatal and familial events, symptoms at diagnosis, explorations performed and results, and therapeutic management were collected by questionnaire. Fifty-four children were included (boys 63%). The mean onset of symptoms was 3.8 ± 2.6 months. The most frequent symptoms at diagnosis were tachypnea (100%), retraction (79.6%), crackles (66.7%), and hypoxemia (59.3%). The mean NEHI clinical score, evocative when ≥ 7/10, was 7.9 ± 1.4 (76% with a score ≥ 7). All chest CT-scans showed ground glass opacities evolving at least the middle lobe and the lingula. Lung biopsy was performed in 38.9% of the cases and was typical of NEHI in only 52.4%, even when the clinical presentation was typical. Initial treatments were oxygen (83.6%) and more curiously intravenous pulses of steroids (83.3%) and azithromycin (70.2%). CONCLUSION: This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs. WHAT IS KNOWN: •Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy. WHAT IS NEW: •In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively. •Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI.
Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current practice, a clinical and radiological approach is more and more preferred (NEHI syndrome). This national study aimed to address diagnosis and initial management of patients followed up for a NEHI pattern in pediatric centers for rare lung diseases (RespiRare, France). Data on neonatal and familial events, symptoms at diagnosis, explorations performed and results, and therapeutic management were collected by questionnaire. Fifty-four children were included (boys 63%). The mean onset of symptoms was 3.8 ± 2.6 months. The most frequent symptoms at diagnosis were tachypnea (100%), retraction (79.6%), crackles (66.7%), and hypoxemia (59.3%). The mean NEHI clinical score, evocative when ≥ 7/10, was 7.9 ± 1.4 (76% with a score ≥ 7). All chest CT-scans showed ground glass opacities evolving at least the middle lobe and the lingula. Lung biopsy was performed in 38.9% of the cases and was typical of NEHI in only 52.4%, even when the clinical presentation was typical. Initial treatments were oxygen (83.6%) and more curiously intravenous pulses of steroids (83.3%) and azithromycin (70.2%). CONCLUSION: This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs. WHAT IS KNOWN: •Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy. WHAT IS NEW: •In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively. •Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI.