Recurrent Infections: Normal, Allergic, or Immunodeficiency?

The human immune system is a complex defence system, consisting of cells and proteins that act together; to fight infections caused by bacteria, viruses, and parasites. We are constantly exposed to infectious agents, and everyone gets an infection once in a while. However, some people get recurrent infections. There are several reasons for these individuals to have an increased susceptibility to infections.

In assessing the child with recurrent infections one need's to remember the rarity of true immunodefeciency and the high prevalence of allergy (atopy), exposure to cigarette smoke, attendance to day care (with high level exposure to bugs), and anatomic variations as predisposing factors for infections.

The Immune System

The major function of the immune system is to recognise foreign substances and react to them. An immune system that is functioning adequately should defend the body from infectious organisms (bacteria, viruses, fungi, and parasites) and protect the body from development of cancers. The major organs of the immune system include the bone marrow, liver, thymus, tonsils, lymph nodes, the spleen, and blood. These organs manufacture, process and store the major components of the immune system, which include:

  • T- Lymphocytes or T-cells – White blood cells important in regulating the immune system and helping fighting viral infections.
  • B- Lymphocytes or B-cells – Cells that make specific proteins called antibodies to protect from bacteria that cause ear infections, sinusitis and pneumonia, etc. The chemical name for antibody proteins is immunoglobulins or gammaglobulins. There are four major classes of antibodies or immunoglobulins:
    • Immunoglobulin G (IgG)
    • Immunoglobulin A (IgA)
    • Immunoglobulin M (IgM)
    • Immunoglobulin E (IgE)

Each immunoglobulin class has special chemical characteristics that provide it with specific advantages. For example, antibodies in the IgG fraction are formed in large quantities, last for over a month and travel from the blood stream to the tissues easily. The IgG antibodies are the only immunoglobulins that cross the placenta and pass immunity from the mother to the newborn. Because our immune system can't make the most important antibody, IgG, in sufficient quantity until about six months of age, IgG antibodies passed on by a mother before birth, protects the baby. If the baby's own immune system does not "turn on" at the right time, the child may get recurrent infections. This is called "Transient hypogammaglobulinemia (low immunoglobulin) of infancy", transient because the child will outgrow it by the age of 2 or 3 years, as the immune system matures.

IgA antibodies are produced near mucous membranes and find their way into secretions such as tears, saliva, and mucus, where they protect against infection in the respiratory tract and intestines.

IgM antibodies are the first antibodies to be formed in response to infection. Therefore, they are important in the early days of an infection.

IgE antibodies are responsible for allergic reactions and parasitic infections.

  • Phagocytes – Cells that ingest foreign bodies and bacteria to kill them.
  • Complement – Proteins that may kill bacteria that may cause infection.

A Primary Immunodeficiency occurs when the abnormality to the immune system develops from an inborn defect in the cells. It is a disorder in immune function that is not a result of infection (eg. AIDS) or extrinsic manipulation. The cells that are affected include T-cells, B-cells, phagocytic cells, or the complement system. Most primary immune deficiencies are inherited diseases. The disease is not always evident at birth . There are about 95 known primary immunedeficiency diseases. Some examples of Primary Immunodeficiencies include:

  • Selective IgA deficiency – relatively common, about 1/333 – 1/1000 in USA
  • Severe common immunodefeciency (SCID)
  • Common variable immunodefeciency (CVID)
  • X-linked Agammaglobulinemia (XLA)

While primary immune deficiencies are uncommon it is essential they be diagnosed promptly to prevent damage to organs such as the lungs and ears, and also to prevent life threatening infections. A careful history, physical examination, and sometimes a simple blood test are often all that is required to rule out an underlying immune deficiency.

Secondary Immune deficiencies occur when damage is caused by an environmental factor. Radiation, chemotherapy, burns, and infections contribute to the many causes of secondary immune deficiencies. Acquired Immune Deficiency is a secondary immune deficiency caused by the Human Immunedeficiency Virus (HIV). In Leukemia, Lymphomas, and metastatic cancer, abnormal cancerous cells crowd out normal stem cells of the bone marrow. These abnormal cells reduce the number of B cells and lead to hypogammaglobulinemia or secondary immune deficiency.

10 Warning signs of Primary Immunodeficiency

(Compiled by the Medical Advisory Board of Jeffery Modell Foundation)

  • 8 or more ear infections within 1 year
  • 2 or more serious sinus infections within 1 year
  • 2 or more months on antibiotics with little effect
  • 2 or more pneumonia within 1 year
  • Failure of an infant to gain weight or grow normally
  • Frequent deep skin or organ abscesses
  • Need for intravenous antibiotics to clear infections
  • Persistent thrush in the mouth or elsewhere on the skin after 12 months of age
  • 2 or more deep seeded infections such as meningitis, osteomyelitis, cellulitis, or sepsis.
  • Family history of Primary Immunodeficiency

Common Infections caused by increased exposure to bugs seen in normal

A study in the USA in the 80's showed that recurring middle-ear infections among preschoolers rose sharply between 1981 and 1988, in part because more children were in day care centres than before.

The most common infections are viral respiratory tract infections (the common cold). The average young child may get up to 12 colds a year. Typically, cold symptoms last 5-10 days. These frequent colds are usually not a cause for concern, as colds are a result of the close contact of young children with a relatively immature immune system.

Allergies and recurrent infections

In people with allergies, there is an over-reaction and loss of control, where the immune system launches attack against a perfectly harmless substance, such as grass pollen, cat dander or peanut or penicillin. The harmful end results of these attacks are called immediate hypersensitivity or allergy.

The first line of defence against infection is located where the body has contact with the rest of the world. In atopic eczema, where the skin barrier is often broken from scratching, it is easy for organisms to enter the skin and cause infection. Similarly, inflammation (irritation, swelling and injury) to the mucous membranes lining the nose, sinuses, and lungs provide a fertile ground for secondary infections. In patients who have year-round allergies to house dust mites, pollen and moulds, there will be some injury to the mucus membranes, which increases their susceptibility to infections.

Nasal blockage due to allergic rhinitis is also thought to lead to secretions and eustachian tube blockages that promote ear infections.

Many people confuse persistent (perennial) allergic rhinitis due to house dust mites or cat allergy with a prolonged cold or sinus infection, since the symptoms of nasal stuffiness, nasal itch, and runny nose are common to both. It is therefore important for all patients with "prolonged cold symptoms or sinusitis" to have a skin prick test for inhalant allergens.

There is also good evidence to suggest that atopic (allergic) individuals have an inherited defective (abnormal) B and T cell functioning, which contributes to their increased risk (and prolongation) of infections.

Structural (Anatomical) changes causing recurrent Infections

Structural changes in the sinuses or Eustachian tubes (connecting tubes in each ear) are a cause of repeated infections in childhood. The term "structural changes" refers to differences in the bony parts of the skull, the sinuses, and ears. These differences are often inherited. These differences in body structure makes it easier for that person to get infections because the normal drainage of the (Eustachian tubes (in the ear) or sinuses (in the nose) is blocked. Another common anatomical variation (abnormality) is a deviated nasal septum (the cartilage, usually midline, which separates right and left nostrils. This predisposes to improper drainage of the sinuses on the narrower side, especially when there is also nasal blockage from any cause, but commonly from allergic rhinitis.

Conclusions

  • Recurrent infections in early childhood are usually normal, and relate to a relatively immature immune system.
  • Allergies can present as recurrent infections, or be a predisposing factor for recurrent infections, therefore all kids with recurrent infections should be considered for skin prick testing.
  • Primary Immunodeficiency is rare but should be considered in anyone with recurrent infections, especially if the infections are severe, difficult to treat or caused by unusual bugs.
  • While primary immune deficiencies are uncommon it is essential they be diagnosed promptly to prevent organ damage and life-threatening infections.
  • A careful history, physical examination, and sometimes a simple blood test are often all that is required to rule out an underlying immune deficiency.

ACKNOWLEDGMENT

I thank Dr Jan P. Sinclair, Allergist and Paediatrician, for her contribution to this article.

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