A 14-month-old boy is admitted to the hospital for treatment of pneumonia. The patient has a fever, cough, and labored breathing. He has had 3 episodes of bronchiolitis during infancy and an episode of pneumococcal pneumonia 2 months ago that required intubation and hospitalization in the intensive care unit. The patient also has a history of recurrent otitis media. He takes no medications, and vaccinations are up to date. Weight is 7 kg (15 lb 7 oz,

Question

A 14-month-old boy is admitted to the hospital for treatment of pneumonia.  The patient has a fever, cough, and labored breathing.  He has had 3 episodes of bronchiolitis during infancy and an episode of pneumococcal pneumonia 2 months ago that required intubation and hospitalization in the intensive care unit.  The patient also has a history of recurrent otitis media.  He takes no medications, and vaccinations are up to date.  Weight is 7 kg (15 lb 7 oz, <3rd percentile).  Temperature is 39.6 C (103.3 F), blood pressure is 90/50 mm Hg, pulse is 128/min, and respirations are 38/min.  On examination, the patient appears listless and is in mild respiratory distress.  Bilateral ear canals contain purulent drainage.  Crackles are heard in the left lung base.  Laboratory results are as follows:  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec25c8_d626_b355_bc81_9d952b986008_MD0003_00 Although frequent, mild respiratory infections are common in childhood, this patient has severe, recurrent sinopulmonary infections, leading to intubation, tympanic membrane perforation (ie, purulent otorrhea), and poor growth. These findings are concerning for a primary immunodeficiency. In the setting of low IgA and IgG and markedly elevated IgM, the most likely cause is hyper-IgM syndrome. Hyper-IgM syndrome is an X-linked recessive defect in the CD40 ligand, which is normally present on T cells and binds to CD40 on B cells. This interaction induces immunoglobulin class switching, in which immature B cells that normally express only IgM isotypes can produce other isotypes (ie, IgG, IgA, IgE). Deficiency of CD40 ligand in hyper-IgM syndrome prevents class switching, leading to elevated IgM levels and a deficiency of all other immunoglobulin types. Although they are dysfunctional, B- and T-cell concentrations are normal. Lymphocytosis can occur during active infection, and neutropenia, as seen in this patient, is common. immunoglobulin class switching Hyper-IgM syndrome generally presents in infancy with recurrent sinopulmonary infections (eg, acute otitis media, pneumonia, sinusitis) caused by encapsulated bacteria (due to lack of opsonizing IgG). Patients also have frequent viral infections and an increased risk of opportunistic infections (eg, Pneumocystis jiroveci pneumonia), reflecting impaired T-cell interaction with antigen-presenting cells. Growth impairment can result from a high energy expenditure and poor intake during illness. Treatment includes antibiotic prophylaxis and intravenous immunoglobulin. (Choice A) X-linked (Bruton) agammaglobulinemia presents in infancy with recurrent sinopulmonary infections but is characterized by low levels of IgG, IgM, and IgA, as well as low or absent B lymphocytes. (Choice B) Common variable immunodeficiency is characterized by a normal B-lymphocyte count and low levels of IgG, IgM, and IgA. It most commonly presents in adolescents or young adults. (Choice C) HIV classically presents with severe opportunistic infections, diarrhea, and failure to thrive. However, leukopenia is expected, and the CD4/CD8 ratio would be low. Because of chronic inflammation, IgG and IgA may be elevated, but IgM is typically low. (Choice E) IgA deficiency is often asymptomatic but can cause recurrent respiratory, gastrointestinal, and/or urogenital infections. Serum IgA is low, whereas IgM and IgG are normal. (Choice F) Wiskott-Aldrich syndrome is characterized by bleeding due to microthrombocytopenia, recurrent infections, and eczema. This patient's normal platelet count excludes this diagnosis. Educational objective: Hyper-IgM syndrome is a primary humoral immunodeficiency due to CD40 ligand deficiency. Patients have recurrent sinopulmonary infections, and their immunoglobulin profile shows high IgM levels and low IgG and IgA. References: The hyper IgM syndromes: epidemiology, pathogenesis, clinical manifestations, diagnosis and management. (http://www.ncbi.nlm.nih.gov/pubmed/30439505) CD40 ligand deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/31831191)

A 14-Month-Old Boy Is Admitted to the Hospital for Treatment