Diagnosing and Treating Primary Immunodeficiency (PI)
- What is PI?
- Diagnostic delay
- Underdiagnosis causes
- Identifying PI
- Diagnostic process
- Evaluating results
What is PI?
PI is an umbrella term for more than 400 disorders in which genetic or congenital defects in the immune system cause an increased susceptibility to infections. PI can affect anyone, regardless of age or gender. Although some types of PI are diagnosed at birth or soon after, other types are often not recognized and diagnosed until later in life.1
US population prevalence per 100,000 people2-4
Despite having similar prevalence to better-known genetic disorders, PI often goes unrecognized.
Diagnostic delay for patients with PI
People with PI may live many years with recurrent infections before they are accurately diagnosed.5
Average time from symptom onset to PI diagnosis*
In addition to clinical complications, patients with undiagnosed PI tend to have a poorer quality of life. In the years before their diagnosis, these patients may experience one or more of the following6,7†:
- Acute and severe infections
- Days with chronic infections
- Visits to physicians and/or emergency departments
- Days spent in the hospital
- Days of school and/or work missed
- End organ damage
*According to the 2013 Immune Deficiency Foundation (IDF) national survey among 1,437 people with PI, the average time from symptom onset to diagnosis is 15 years.
†According to a US Jeffrey Modell Centers survey (n=10,192).
What may cause underdiagnosis?
There are as many as 500,000 undiagnosed cases of PI in the US alone. However, awareness of PI is low among both physicians and the general public, and many patients are left undiagnosed.6 Reasons for this may include:
- A lack of awareness of PIs and/or their management6
- The masking of symptoms due to frequent antibiotic use7
- Symptoms may present differently to different specialists over a number of years7
- The lengthy process of confirmation, which includes many tests and consultations8
Supporting patients with PI
Patients may live many years with PI before they are accurately diagnosed.6 Once patients have a diagnosis, they may benefit from information about their type of PI and how to find additional support for living with PI.
View PI resources
Identifying PI1,9
PI can hide among other conditions. Despite its complex presentations, physicians may be able to identify PI using the “SPUR” criteria for patients who present with an infection that is:
S
(requiring hospitalization or intravenous antibiotics)P
(clearing up slowly or not at all)U
(resulting from an uncommon organism)R
(continually resurfacing)10 Warning signs of PI
PI may be suspected in adults who present with 2 or more of the following warning signs10:
- Two or more new ear infections within 1 year
- Two or more serious sinus infections within 1 year, in the absence of allergy
- One pneumonia per year for more than 1 year
- Chronic diarrhea with weight loss
- Recurrent viral infections (cold, herpes, warts, condyloma)
- Recurrent need for intravenous antibiotics to clear infections
- Recurrent, deep abscesses of the skin or internal organs
- Persistent thrush or fungal infection on skin or elsewhere
- Infection with normally harmless tuberculosis-like bacteria
- A family history of PI
What is the diagnostic process?
If you have a patient you suspect may have PI, the AAAAI and ACAAI guidelines recommend that you consider11:
- An immunological evaluation, beginning with a thorough medical history and physical exam including family history
- A complete blood count (CBC) with manual differential
- Total immunoglobulin levels (IgG, IgM, IgA)
- Antibody response to protein or polysaccharide vaccines provides important diagnostic information
AAAAI=American Academy of Allergy, Asthma & Immunology
ACAAI=American College of Allergy, Asthma and Immunology
How are results evaluated?
Quantitative measurement determines the concentration of IgG, IgM, and IgA in serum.
- Levels below the normal range for a patient raise the index of suspicion for an antibody deficiency8
- However, a patient may present with normal levels and still have an antibody deficiency12
Qualitative measurement determines the antibody response to the antigenic challenge of vaccines.13
- Protein (eg, diphtheria and tetanus): T-dependent antigens that require T-cell and B-cell cooperation
- Polysaccharide (pneumococcal): T-independent antigens. This measurement serves 2 purposes: it determines patient capability of mounting protective antibody responses and determines the magnitude of the response
Some people diagnosed with PI can have normal IG levels, such as patients with SAD.13 Because of this, vaccine response testing is needed to confirm a diagnosis.8
Laboratory findings in common types of PI8
| Diagnosis | IgG | IgA | Vaccine response |
B cells |
|---|---|---|---|---|
|
Specific antibody deficiency (SAD) |
Normal | Normal | Low | Normal |
| Common variable immunodeficiency (CVID) | Low | Low | Low | Normal or Low |
| Hypogammaglobulinemia | Low | Normal or Low | Normal | Normal or Low |
Explore GAMMAGARD LIQUID for patients with PI
Once a patient is diagnosed with PI, GAMMAGARD LIQUID offers options for intravenous immune globulin (IVIG) or subcutaneous IG (SCIG) administration. Review the efficacy data from the clinical trials.
Clinical trial data
