Nodular regenerative hyperplasia in X-linked agammaglobulinemia: An underestimated and severe complication - 05/01/22

Doi : 10.1016/j.jaci.2021.05.028

Cristiane J. Nunes-Santos, MD ^a,^{∗
These authors contributed equally to this work.}, Christopher Koh, MD, MHSc ^b,^{∗
These authors contributed equally to this work.}, Anjali Rai, MD ^b,^{∗
These authors contributed equally to this work.}, Keith Sacco, MD ^c,^{∗
These authors contributed equally to this work.}, Beatriz E. Marciano, MD ^c, David E. Kleiner, MD, PhD ^d, Jamie Marko, MD ^e, Jenna R.E. Bergerson, MD, MPH ^c, Michael Stack, BSc ^c, Maria M. Rivera, MD ^b, Gregory Constantine, MD ^f, Warren Strober, MD ^g, Gulbu Uzel, MD ^c, Ivan J. Fuss, MD ^g, Luigi D. Notarangelo, MD ^c,^{‡
These authors contributed equally to this work.}, Steven M. Holland, MD ^c,^{‡
These authors contributed equally to this work.}, Sergio D. Rosenzweig, MD, PhD ^a,^⁎,^{‡
These authors contributed equally to this work.} , Theo Heller, MD ^b,^⁎,^{‡
These authors contributed equally to this work.}
^a Immunology Service, Department of Laboratory Medicine, National Institutes of Health (NIH) Clinical Center, Bethesda, Md
^b Liver Diseases Branch, National Institute of Diabetes and Digestive & Kidney Diseases, NIH, Bethesda, Md
^c Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Md
^d Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Md
^e Department of Radiology and Imaging Sciences, National Institutes of Health (NIH) Clinical Center, Bethesda, Md
^f Allergy and Immunology Fellowship Program, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Md
^g Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Md

^∗Corresponding authors: Sergio D. Rosenzweig, MD, PhD, Immunology Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Building 10, Room 2C306, 10 Center Drive, Bethesda, MD 20892.Immunology ServiceDepartment of Laboratory MedicineNational Institutes of Health Clinical CenterBuilding 10Room 2C30610 Center DriveBethesdaMD20892^∗∗Theo Heller, MD, Translational Hepatology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive & Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892.Translational Hepatology SectionLiver Diseases BranchNational Institute of Diabetes and Digestive & Kidney DiseasesNational Institutes of Health10 Center DriveBethesdaMD20892

Abstract

Background

Late-onset complications in X-linked agammaglobulinemia (XLA) are increasingly recognized. Nodular regenerative hyperplasia (NRH) has been reported in primary immunodeficiency but data in XLA are limited.

Objectives

This study sought to describe NRH prevalence, associated features, and impact in patients with XLA.

Methods

Medical records of all patients with XLA referred to the National Institutes of Health between October 1994 and June 2019 were reviewed. Liver biopsies were performed when clinically indicated. Patients were stratified into NRH+ or NRH− groups, according to their NRH biopsy status. Fisher exact test and Mann-Whitney test were used for statistical comparisons.

Results

Records of 21 patients with XLA were reviewed, with a cumulative follow-up of 129 patient-years. Eight patients underwent ≥1 liver biopsy of whom 6 (29% of the National Institutes of Health XLA cohort) were NRH+. The median age at NRH diagnosis was 20 years (range, 17-31). Among patients who had liver biopsies, alkaline phosphatase levels were only increased in patients who were NRH+ (P = .04). Persistently low platelet count (<100,000 per μL for >6 months), mildly to highly elevated hepatic venous pressure gradient and either hepatomegaly and/or splenomegaly were present in all patients who were NRH+. In opposition, persistently low platelet counts were not seen in patients who were NRH−, and hepatosplenomegaly was observed in only 1 patient who was NRH−. Hepatic venous pressure gradient was normal in the only patient tested who was NRH−. All-cause mortality was higher among patients who were NRH+ (5 of 6, 83%) than in the rest of the cohort (1 of 15, 7% among patients who were NRH− and who were classified as unknown; P = .002). Conclusions: NRH is an underreported, frequent, and severe complication in XLA, which is associated with increased morbidity and mortality.

Le texte complet de cet article est disponible en PDF.

Graphical abstract

Le texte complet de cet article est disponible en PDF.

Key words : Primary immunodeficiency, inborn errors of immunity, liver disease, thrombocytopenia, splenomegaly, hepatomegaly, alkaline phosphatase, portal hypertension, CVID, HSCT

Abbreviations used : CVID, IEI, NIH, NRH, PID, XLA

Plan

Liver biochemistry tests

Platelet count

Endoscopic and imaging findings

Clinical outcome

Discussion

	This work was supported by the Intramural Research Program at the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Institute of Diabetes and Digestion and Kidney Diseases.
	Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

Export

Vol 149 - N° 1

P. 400 - janvier 2022 Retour au numéro

Article précédent

Rubella vaccine–induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity
Miriam Groß, Carsten Speckmann, Annette May, Tania Gajardo-Carrasco, Katharina Wustrau, Sarah Lena Maier, Marcus Panning, Daniela Huzly, Abbas Agaimy, Yenan T. Bryceson, Sharon Choo, C.W. Chow, Gregor Dückers, Anders Fasth, Sylvie Fraitag, Katja Gräwe, Sabine Haxelmans, Dirk Holzinger, Ole Hudowenz, Judith M. Hübschen, Claudia Khurana, Korbinian Kienle, Roman Klifa, Klaus Korn, Heinz Kutzner, Tim Lämmermann, Svea Ledig, Dan Lipsker, Marie Meeths, Nora Naumann-Bartsch, Jelena Rascon, Anne Schänzer, Maximilian Seidl, Bianca Tesi, Christelle Vauloup-Fellous, Beate Vollmer-Kary, Klaus Warnatz, Claudia Wehr, Bénédicte Neven, Pablo Vargas, Fernando E. Sepulveda, Kai Lehmberg, Annette Schmitt-Graeff, Stephan Ehl

| Article suivant

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome
Dimana Dimitrova, Zohreh Nademi, Maria Elena Maccari, Stephan Ehl, Gulbu Uzel, Takahiro Tomoda, Tsubasa Okano, Kohsuke Imai, Benjamin Carpenter, Winnie Ip, Kanchan Rao, Austen J.J. Worth, Alexandra Laberko, Anna Mukhina, Bénédicte Néven, Despina Moshous, Carsten Speckmann, Klaus Warnatz, Claudia Wehr, Hassan Abolhassani, Asghar Aghamohammadi, Jacob J. Bleesing, Jasmeen Dara, Christopher C. Dvorak, Sujal Ghosh, Hyoung Jin Kang, Gašper Markelj, Arunkumar Modi, Diana K. Bayer, Luigi D. Notarangelo, Ansgar Schulz, Marina Garcia-Prat, Pere Soler-Palacín, Musa Karakükcü, Ebru Yilmaz, Eleonora Gambineri, Mariacristina Menconi, Tania N. Masmas, Mette Holm, Carmem Bonfim, Carolina Prando, Stephen Hughes, Stephen Jolles, Emma C. Morris, Neena Kapoor, Sylwia Koltan, Shankara Paneesha, Colin Steward, Robert Wynn, Ulrich Duffner, Andrew R. Gennery, Arjan C. Lankester, Mary Slatter, Jennifer A. Kanakry

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

Nodular regenerative hyperplasia in X-linked agammaglobulinemia: An underestimated and severe complication - 05/01/22

Abstract

Background

Objectives

Methods

Results

Graphical abstract

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL