X-linked Agammaglobulinemia in Community-acquired Pneumonia Cases Revealed by Immunoglobulin Level Screening at Hospital Admission

Z. Vancikova; T. Freiberger; W. Vach; M. Trojanek; M. Rizzi; A. Janda

doi:10.1055/s-0033-1354415

Klin Padiatr 2013; 225(06): 339-342
DOI: 10.1055/s-0033-1354415

Original Article

X-linked Agammaglobulinemia in Community-acquired Pneumonia Cases Revealed by Immunoglobulin Level Screening at Hospital Admission

X-gekoppelte Agammaglobulinämie in Patienten mit ambulant erworbener Pneumonie, entdeckt durch Immunglobulinbestimmung bei der Krankenhausaufnahme

Z. Vancikova

¹Department of Pediatrics, 1st Medical Faculty and Thomayer’s University Hospital, Charles University in Prague, Czech Republic

,

T. Freiberger

²Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, and Department of Clinical Immunology and Allergology, Masaryk University, Brno, Czech Republic

,

W. Vach

³Clinical Epidemiology, Institute of Medical Biometry and Medical Informatics, University Medical Centre, University of Freiburg, Germany

,

M. Trojanek

⁴1st Department of Infectious Diseases, 2nd Medical Faculty, Charles University in Prague, Czech Republic

,

M. Rizzi

⁵Centre of Chronic Immunodeficiency (CCI), University Medical Centre, University of Freiburg, Germany

,

A. Janda

⁵Centre of Chronic Immunodeficiency (CCI), University Medical Centre, University of Freiburg, Germany

› Institutsangaben

Abstract

In children with primary immunodeficiencies, the onset of symptoms precedes the diagnosis and the initiation of appropriate treatment by months or years. This delay in diagnosis is due to the fact that while these disorders are rare, some of the infections seen in immunodeficient patients are common. Defective antibody production represents the largest group among these disorders, with otitis, sinusitis and pneumonia as the most frequent initial manifestation. We performed a prospective study of humoral immunity in children hospitalized due to community-acquired pneumonia in tertiary care hospital. Out of 254 patients (131 boys, 123 girls, median age 4.5 years) recruited over 3 years, we found 2 boys (age 11 and 21 months) lacking serum immunoglobulins and circulating B cells. Subsequent genetic analysis confirmed diagnosis of X-linked agammaglobulinemia. Despite their immunodeficiency, the pneumonia was uncomplicated in both patients and did not call for immunological evaluation. However, the immunoglobulin screening at admission allowed for an early diagnosis of the immunodeficiency and timely initiation of immunoglobulin substitution, the key prerequisite for a favorable course of the disease.

Conclusions:

Simple and inexpensive immunoglobulin measurement during the management of hospitalized children with community-acquired pneumonia may help in early identification of patients with compromised humoral immunity and prevent serious complications.

Zusammenfassung

Bei Kindern mit primärer Immundefizienz kann die Latenz zwischen klinischer Erstmanifestation und der definitiven Diagnosestellung Monate oder sogar Jahre betragen. Diese Verzögerung in der Diagnosestellung ist u. a. der Tatsache geschuldet, dass angeborene Immundefekte seltene Erkrankungen sind, während einige der Infektionen, zu denen primäre Immundefekte prädisponieren, häufig auftreten. Eine der größten Gruppen innerhalb dieser Erkrankungen stellen Defekte in der Antikörperproduktion dar, die in vielen Fällen als Otitis, Sinusitis und Pneumonie manifest werden. Wir stellen die Ergebnisse einer prospektiven Studie zur humoralen Immunität bei Kindern vor, die mit ambulant erworbener Pneumonie in einem Krankenhaus der maximalen Versorgungsstufe hospitalisiert wurden. Unter 254 Patienten (131 Jungen, 123 Mädchen, Durchschnittsalter 4,5 Jahre), die über einen Zeitraum von 3 Jahren rekrutiert wurden, waren 2 Jungen (11 bzw. 21 Monate alt) mit einem Mangel an Serumimmunglobulinen und erniedrigten B-Lymphozyten. In der genetischen Analyse konnte bei beiden Patienten eine X-chromosomal-vermittelte Agammaglobulinämie diagnostiziert werden. Die Bestimmung der Immunoglobuline bei stationärer Aufnahme erlaubte frühe Diagnosestellung des Immundefekts und einen zeitnahen Beginn der Immunglobulinsubstitution. Beides sind wesentliche Voraussetzung für einen günstigen Krankheitsverlauf.

Schlussfolgerung:

Die einfache und kostengünstige Bestimmung von Serumimmunglobulinen während der stationären Behandlung von Kindern mit ambulant erworbenen Pneumonien kann dabei helfen, Patienten mit Defekten der humoralen Immunität frühzeitig zu identifizieren, und schwere Komplikationen verhindern.

Key words:

X-linked agammaglobulinemia - immunodeficiency - humoral immunity - community-acquired pneumonia - childhood

Schlüsselwörter

X-gekoppelte Agammaglobulinämie - Immundefizienz - humorale Immunität - ambulant erworbene Pneumonie - Kindesalter

Volltext

Referenzen

References
1 Bradley JS, Byington CL, Shah SS et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis 2011; 53: e25-e76
2 Conley ME, Howard V. Clinical findings leading to the diagnosis of X-linked agammaglobulinemia. J Pediatr 2002; 141: 566-571
3 Farmand S, Baumann U, von Bernuth H et al. [Interdisciplinary AWMF guideline for the diagnostics of primary immunodeficiency]. Klin Padiatr 2011; 223: 378-385
4 Gathmann B, Binder N, Ehl S et al. The European internet-based patient and research database for primary immunodeficiencies: update 2011. Clin Exp Immunol 2012; 167: 479-491
5 Harris M, Clark J, Coote N et al. British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011. Thorax 2011; 66 ((suppl 2)) ii1-23
6 Krudewig J, Baumann U, Bernuth von H et al. Interdisciplinary AWMF guideline for the treatment of primary antibody deficiencies. Klin Padiatr 2012; 224: 404-415
7 Ochs HD, Smith CI. X-linked agammaglobulinemia. A clinical and molecular analysis. Medicine (Baltimore) 1996; 75: 287-299
8 Rudan I, Boschi-Pinto C, Biloglav Z et al. Epidemiology and etiology of childhood pneumonia. Bulletin of the World Health Organization 2008; 86: 408-416
9 Stein RT, Marostica PJ. Community-acquired pneumonia: a review and recent advances. Pediatr Pulmonol 2007; 42: 1095-1103
10 Subbarayan A, Colarusso G, Hughes SM et al. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics 2011; 127: 810-816
11 Toth B, Volokha A, Mihas A et al. Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe: a cohort study. Molecular immunology 2009; 46: 2140-2146
12 Weigl JA, Bader HM, Everding A et al. Population-based burden of pneumonia before school entry in Schleswig-Holstein, Germany. Eur J Pediatr 2003; 162: 309-316
13 Winkelstein JA, Marino MC, Lederman HM et al. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine (Baltimore) 2006; 85: 193-202