questions 4

Hyper IgM Syndrome

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Topic updated on 04/23/17 9:36pm

Snapshot
  • A 6-month-old baby boy presents with a past medical history of skin infections presents with difficulty breathing, high fever, and nonproductive cough. He is immediately started on broad-spectrum antibiotics. On further questioning, his family history includes a maternal uncle dying at age 20 from overwhelming pneumonia. Sputum is induced with hypertonic saline inhalation, and eventual staining shows Pneumocystis. He is immediately started on IVIG.
Introduction
 

  • Inherited primary combined B- and T-cell immunodeficiency characterized by increased levels of IgM
  • Genetics
    • X-linked recessive
    • mutation in gene that codes for CD40 ligand (CD40L)
  • Pathogenesis
    • CD40L is expressed on activated T-helper cells
    • defect in humoral immunity
      • CD40L is necessary to induce B-cells to undergo Ig class-switching 
        • from IgM to IgG, IgA, and IgE
        • see illustration above
    • defect cell-mediated immunity
      • CD40L also required for maturation of T-cells, dendritic cells, and macrophages
  • Symptoms onset by 1 year, often with Pneumocystis infections
    • most diagnosed before 4 years
Presentation
  • Symptoms
    • severe pyogenic infections early in life
    • chronic diarrhea
    • opportunistic infections
      • pneumonia
      • Pneumocystis
      • Cryptosporidium
      • CMV
      • echovirus encephalitis
    • pancytopenia common
      • fatigue
      • infection
      • pallor
      • bleeding
Evaluation
  • Ig levels
    • ↑ IgM
    • ↓ IgA, IgG, and IgE
    • due to defect in class-switching
  • Diagnosis confirmed with flow cytometry
    • deficient expression of CD40L on activated T-helper cells
    • normal T- and B-cells
  • CBC
    • neutropenia
    • thrombocytopenia possible
Differential Diagnosis
  • Bruton agammaglobulinemia
  • CVID
  • SCID
Treatment
  • Prophylaxis of Pneumocystis
  • Regular IVIG replacement
Prognosis, Prevention, and Complications
  • Prognosis
    • 20% survival rate past young adulthood
    • leading cause of death
      • pneumonia
      • encephalitis
      • malignancy
  • Complications
    • increased risk of autoimmunity
    • increased risk of malignancies
      • HCC
      • carcinoid tumor
    • infection
    • bronchiectasis


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Qbank (2 Questions)

TAG
(M1.IM.74) A 3-month-old is referred to a pediatric immunologist by his pediatrician for further workup of recurrent sinopulmonary infections which have not abated despite adequate treatment. During the workup flow cytometry demonstrates a decrease in normal CD40L cells. Based on these findings, the immunologist decides to pursue a further workup and obtains immunoglobulin levels. Which of the following immunoglobulin profiles is most likely to be observed in this patient? Topic Review Topic

1. Increased IgE; Decreased IgG, IgM
2. Decreased IgE, IgM, IgA, IgG
3. Increased IgE, IgA; Decreased IgM
4. Increased IgE
5. Increased IgM; Decreased IgG, IgA, IgE

PREFERRED RESPONSE ▶
TAG
(M1.IM.126) A 3-year-old boy presents to the pediatrics clinic for follow-up. He has a history of severe pyogenic infections since birth. Further workup revealed a condition caused by a defect in CD40 ligand expressed on helper T cells. This congenital immunodeficiency has resulted in an inability to class switch and a poor specific antibody response to immunizations. Which of the following best characterizes this patient's immunoglobulin profile? Topic Review Topic

1. Increased IgE
2. Decreased IgA
3. Decreased Interferon gamma
4. Increased IgE and IgA; and decreased IgM
5. Increased IgM; decreased IgG, IgA, and IgE

PREFERRED RESPONSE ▶
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