What Are Common Presentations of Primary Immunodeficiencies?

Patient Presentation
A 4-year-old male with known X-linked agammaglobulinaemia (XLA) came to clinic with persistent diarrhea for the past 2 days. The stools were initially looser but now had a watery consistency and were increasing in frequency. There was no blood or mucous in the stools but they were noxious smelling. His last antibiotic treatment was one month ago for otitis media. The younger sibling attended daycare and rotavirus was occurring in the toddler rooms, but the sibling was asymptomatic. He was able to drink and was urinating 3-4 times/day.

The past medical history showed the diagnosis of XLA at 9-10 months of age after several episodes of otitis media, diarrheal infections and a complicated pneumonia. He also had poor weight gain. The pertinent physical exam showed a tired appearing male with normal vital signs. He was thin appearing with weight at the 10% and height at the 15%. HEENT showed multiple scars of his tympanic membranes. Mucous membranes were wet. His lungs were clear. His abdominal examination showed increased bowel sounds without organomegaly. Genitourinary examination was normal. The diagnosis of probable viral diarrhea in an immunocompromised child was made. After discussion with his immunologist, the patient was sent home with instructions for increasing fluids, home monitoring and close telephone contact. The laboratory evaluation of a stool culture was eventually positive for rotavirus, and he slowly improved over the next week.

Discussion
Of the various primary immunodeficiencies (PIDs), primary antibody deficiencies are the most common. B-cell deficiencies that occur early in the maturational process (i.e. Bruton’s or X-linked agammaglobulinaemia) tend to be more severe than those that occur later (selective IgA and IgG subclass deficiencies.)

X-linked agammaglobulinaemia (XLA) was first described by Bruton in 1952 and is caused by the gene BTK, a protein tyrosine kinase that blocks B-cell maturation resulting in severely decreased B-cells and all classes of antibodies. Female carriers are asymptomatic generally and males have clinical manifestations with problems occurring after 3-4 months of age (because of circulating maternal antibodies) but before 1 year. Recurrent respiratory tract infections are frequent presentations (60-80%) especially otitis media, sinusitis, and pneumonia. Diarrhea also occurs (25%). Common pathogens include S. pneumonia, H. influenzae, Staphlococcus sp., Pseudomonas sp., and Giardia sp.. Long term, patients may have malignancies and chronic pulmonary damage.

Children with immunodeficiencies often have other logical reasons for the problems they are having. Thus, their immunodeficiency is not diagnosed or is diagnosed later.
There is no absolute indicator as to when a child should be evaluated for a potential immune problem but the following can be considered:

  • Systemic bacterial infections, 2 or more, e.g. sepsis, meningitis, deep abscess
  • Bacterial infections, 3 or more, e.g. draining otitis media
  • Upper respiratory infections, > 6-8 in one year
  • Recurrent infection of same organism, e.g. meningococcemia
  • Need for surgical treatment, e.g. drainage of abscess, lobectomy for chronic pneumonia
  • Failure to thrive, weight loss or growth retardation
  • Unusual infections, i.e. Pseudomonas carinii in a presumably normal child

For a listing of common immunological tests to consider see When Should I Order an Immune Workup?

Learning Point
Common suspected primary immunodeficiencies with common mimics include:

  • Recurrent infections of the airway and head and neck
    • Antibody deficiency – normal recurrent infections
    • Complement deficiency – cystic fibrosis, primary ciliary dyskinesia, congenital anomaly
    • HIV – adenoid hypertrophy
    • Phagocyte deficiency – hyperreactivity including asthma, allergy
    • Wiskott Aldrich syndrome – inhaled foreign body
  • Recurrent infection with same pathogen
    • Encapsulated bacteria (= antibody deficiency) – recurrent exposure
    • Meningococci (= complement deficiency) – primary infection inadequately treated
    • Candida (= T-lymphocyte deficiency) – anatomical defects
    • Mycobacteria (= macrophage) – T-cell interaction problem
  • Recurrent pyogenic infections
    • Congenital granulocyte defects - neutropenia (drug-related or autoimmune), hematological malignancy, skin problems (i.e. burn, eczema), Staphlococcus aureus carriage of virulent strain
  • Unusual infections
    • HIV – chronic disease, malignancy, malnutrition, immunosuppressive therapy
    • Inate immunity defects
    • T-cell deficiencies including severe combined immunodeficiency and HIV – secondary immunodeficiency
    • Wiskott Aldrich
  • Failure to thrive
    • T-cell deficiencies including severe combined immunodeficiency and HIV – multiple causes

Questions for Further Discussion
1. Describe the laboratory findings for common variable immunodeficiency?
2. List common T-cell defects?
3. What vaccines are contraindicated in children with various immunodeficiencies?
4. How effective are the vaccines that can be given?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Diarrhea and Immune System and Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Yong PF, Chee R, Grimbacher B. Hypogammaglobulinaemia. Immunol Allergy Clin North Am. 2008 Nov;28(4):691-713, vii.

de Vries E, Driessen G. Educational paper: Primary immunodeficiencies in children: a diagnostic challenge. Eur J Pediatr. 2011 Feb;170(2):169-77.

Driessen G, van der Burg M. Educational paper: primary antibody deficiencies. Eur J Pediatr. 2011 Jun;170(6):693-702.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    Date
    December 17, 2012