Immunodeficiency and Down Syndrome

We are all familiar with the major features of Down Syndrome (partially because they are distinctive and partially because tests love to have questions about them), but one that is commonly undervalued is the relative immunodeficiency that exists concurrently with Down Syndrome.  When we weigh our decisions about treatment of patients with infections, we need to know the patient’s risk factors for the infection getting out of control.  Remember to place Down Syndrome on your list of conditions that may place the patient at greater risk.

Down Syndrome is the most common chromosomal anomaly among live-born infants in the United States (1:600 to 1:900).  Unfortunately, people with Down Syndrome are more likely to have increased morbidity from recurrent infections, of which the majority are respiratory infections.  Furthermore, patients with Down Syndrome suffer from prolonged courses of infections (2 to 3 times long duration of infection versus non-Down Syndrome patients). This places them at greater risk for complications of simple infections, like ARDS and Sepsis.

Some commonly considered associated conditions (abridged)

• Dysmorphic features
• Mental disability
• Heart disease (ASD, VSD, PDA, AV Canal, Tetralogy of Fallot)
• GI issues (Small Bowel Obstruction, Imperforate anus, Annular pancrease, Hirschprung’s Disease, GERD, Malabsorption)
• Hematologic issues – Acute Lymphoblastic Leukemia, Acute Megakaryoblastic Leukemia
• AtlantoAxial Instability (Remember this if you need to intubate!!)
• Autoimmune (Hypothyroidism, Celiac Disease)

Factors that place patient with Down Syndrome at great risk for infection

• Adaptive Immunity
  • T and B cell subsets are decreased below the 10th percentile in almost 90% of Down Syndrome children.
  • Thymus size is reported to be smaller with decreased T cell expansion in infancy.
  • Decreased T Cell receptors
  • Mild to moderate Lymphopenia.
  • IgA deficiency in saliva
  • Decreased antibody response to immunizations
  • Decreased neutrophil chemotaxis
• Nutritional Deficiencies
  • Malabsorption can lead to zinc deficiency
• Anatomic abnormalities
  • Airway anomalies can impair clearance of secretions
  • Relatively large adenoids and tonsils and tongue with hypotonia also impair secretion clearance
  • External ear canal stenosis and small Eustachian Tubes increase risk for middle ear infections.
• GERD and hypotonia
  • places child at risk for aspiration

So, while you are managing patients with Down Syndrome, realize that they will have more frequent infections, are at risk for having a prolonged course with those infections, and are also at risk for increased morbidity because of those infections.  Naturally, Down Syndrome demonstrates a vast range of disease, so consider the patient’s personal history with prior infections when you determine your management strategy.