Rare Classroom: Primary Immunodeficiency

Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Primary Immunodeficiency

What is Primary Immunodeficiency?

  • Primary immunodeficiency diseases (PI) are a group of more than 200 rare, chronic disorders in which part of the body’s immune system is missing or functions improperly
  • The diseases share one common feature: each results from a defect in one of the functions of the body’s normal immune system
  • Patients with PI commonly have an increased susceptibility to infection​
  • People with PI live their entire lives more susceptible to infections–enduring recurrent health problems and often developing serious and debilitating illnesses
  • PI has no unique or specific symptoms.  It shares symptoms with many other conditions.  It is often mistaken for ordinary infections, such as infections of the ears, gastrointestinal tract, sinuses, and/or lungs
  • Types of Primary Immunodeficiency
  • Antibody Deficiencies
    • Agammaglobulinemia: X-Linked and Autosomal Recessive​
    • Common Variable Immune Deficiency​
    • IgG Subclass Deficiency​
    • Selective IgA Deficiency​
    • Specific Antibody Deficiency​
    • Transient Hypogammaglobulinemia of Infancy​
    • Other Antibody Deficiency Disorders​​​
  • Cellular Immunodeficiencies
    • Severe Combined Immune Deficiency and Combined Immune Deficiency​
    • Wiskott-Aldrich Syndrome​
    • Hyper IgM Syndromes​
    • Ataxia Telangiectasia​
    • DiGeorge Syndrome​
    • Other Primary Cellular Immunodeficiencies​
  • Innate Immune Disorders
    • Chronic Granulomatous Disease and Other Phagocytic Cell Disorders​
    • Hyper IgE Syndrome​
    • Complement Deficiencies​
    • Innate Immune Defects​
    • NEMO Deficiency Syndrome​

How Do You Get It?

  • The basic cause of all PI diseases are genetic mutations​
    • Many of these genetic mutations are inherited​
    • The inherited conditions cause a lack or dysfunction of white blood cells which have an important role in fighting infections​
  • Once thought to be rare, but now considered more common​
  • An estimated 500,000 Americans are afflicted with PI’s​
  • 5,000 to 10,000 are severely affected​
  • There are approximately 50,000 cases diagnosed each year​
  • A 2007 survey of 10,000 households by the Immune Deficiency Foundation (IDF) showed the prevalence of PI to be 1 in 1200, or 83 per 100,000 people in the U.S. ​

What Are The Symptoms?

  • There are 10 recognized warning signs of PI diseases, if someone is affected by 2 or more, they should consult a physician regarding the presence of a PI disease
    • Four or more new ear infections within one year (two or more for adults)​
    • Two or more serious sinus infections within one year (in absence of allergy for adults)​
    • Two or more months on antibiotics with little effect​
    • Two or more pneumonias within one year (one or more for adults)​
    • Failure of an infant to gain weight or grow normally​
    • Recurrent deep abscesses of the skin or internal organs​
    • Recurrent need for intravenous antibiotics to clear infections​
    • Persistent thrush or fungal infections​
    • Two or more deep-seated infections including septicemia (not noted in adult criteria)​
    • A family history of PIDD​
  • As there are many different types of primary immunodeficiency, the signs, symptoms, and other characteristics tend to vary between them. Here are some of the more prevalent types and their symptoms:
    • Common variable immunodeficiency
      • Most people with CVID have frequent bacterial infections of the ears, sinuses, and lungs 
      • More common in families with immunoglobulin A (IgA) deficiency
      • Have low levels of immunoglobulin and an increased risk for infection​
    • X-linked agammaglobulinemia (XLA)
      • An inability to produce B cells or immunoglobulin
      • Infants with XLA develop frequent infections of the ears, throat, lungs, and sinuses
    • Wiskott-Aldrich syndrome (WAS)
      • Difficulties with B cells, T cells, and platelets
      • Reduced platelet counts that lead to small bruises or bleeding in the skin, bowels, and gums or prolonged nose bleeds.  Also common to have upper and lower respiratory tract infections and eczema
      • Due to different gene variations, can be milder or more severe
    • Severe Combined Immunodeficiency
      • Complete absence of B and T-cell function
      • Symptoms occur in infancy and include serious or life-threatening infections, especially viral infections, which result in pneumonia and chronic diarrhea

How Is It Treated?

  • The overall goal in treating primary immunodeficiency (PI) is to restore a person’s immune system, allowing them to maintain a normal life and live longer
  • Note that treatment will depend on the specific PI disease that a patient has.  Not all patients receive every treatment.
  • Treatment
    • Manage all infections caused by PI with medications like antibiotics.  This can include oral or IV antibiotics. Some may need to be taken long term​.
    • Treat the underlying cause of the PI to minimize or prevent severe and frequent infections and associated complications with therapies that “boost the immune system.”
  • Three common immune system “boosters” include:
    • Immunoglobulin therapy (also called gamma globulin therapy)
      • “Immunoglobulin” refers to the fraction of blood plasma that contains immunoglobulins or antibodies
      • These immunoglobulins (Ig) in the serum or plasma are IgG, IgM, IgA, IgD, and IgE
      • Individuals who are unable to produce adequate amounts of Ig or antibodies, such as patients with XLA, CVID, Hyper-IgM Syndromes, Wiskott Aldrich syndrome, or other forms of hypogammaglobulinemia, may benefit from replacement therapy with Ig
      • Only the IgG is purified from the plasma to produce commercial Ig products, so Ig used for treatment contains very little of any of the other Ig types
      • Ig treatment partly replaces what the body should be making, but does not stimulate the patient’s own immune system to make more Ig.​
      • Ig only provides temporary protection.  Most antibodies are metabolized and must be replenished.​
      • Approximately half of the infused antibodies are metabolized over three to four weeks, so repeat doses of Ig are required at regular intervals.​
      • Ig replacement is usually necessary for the patient’s lifetime.​
      • Depending on the route of administration, this may be done by giving small infusions under the skin (subcutaneous immunoglobulin -SCIG) weekly or as often as every one to three days, or by giving larger intravenous immunoglobulin (IVIG) infusions once every three or four weeks.​
      • Route of administration is decided based on a number of factors including the clinical characteristics of each patient including side effects, the patient’s preferences for therapy, site of care (home, hospital, infusion center), and sometimes, even insurance coverage​
    • Gamma interferon therapy
      • Used to treat chronic granulomatous disease, given as an injection in the thigh or arm three times a week
    • Growth factors
      • Used when immune deficiency is caused by a lack of certain white blood cells
    • Gene therapy may be a future treatment option
  • Prevention
    • Avoid further infections through proper hygiene, healthy diet, and avoiding exposure
  • Cure
    • Hematopoietic stem cell transplantation (HSCT)​
    • Gene Therapy – Currently in clinical trials​
    • Not all those with PI are candidates for these therapies.​

Where Can I Learn More???

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