Immunodeficiency Red Flags: Recurrent Infections and What Doctors Look For
Stuart Moore 13 November 2025 12

When a child keeps getting sick-ear infections, pneumonia, sinus infections-itā€™s easy to blame daycare, bad luck, or a weak immune system. But when infections keep coming back, donā€™t just wait it out. Recurrent infections can be the earliest and most telling sign of an underlying immune disorder. In fact, up to 1 in 1,200 people in the U.S. have a primary immunodeficiency (PID), and many arenā€™t diagnosed until years after symptoms start. The key isnā€™t just how often someone gets sick-itā€™s what kind of infections, how severe they are, and whether standard treatments fail.

When Is a Recurrent Infection a Red Flag?

Not every cold or ear infection means somethingā€™s wrong. Healthy kids can have 6 to 12 respiratory infections a year, especially before age 5. But there are clear patterns that go beyond normal. The American Academy of Allergy, Asthma & Immunology and the European Society for Immunodeficiencies agree on these red flags:

  • Four or more ear infections in one year
  • Two or more serious sinus infections in one year
  • Two or more pneumonias within 12 months
  • Persistent oral thrush after age 1
  • Deep skin or organ abscesses that keep coming back
  • Infections that donā€™t clear up after two months of antibiotics
  • Need for intravenous antibiotics to treat infections
  • Two or more deep-seated infections like septicemia or meningitis
  • Failure to gain weight or grow normally
  • A family history of immune problems

These arenā€™t vague suggestions-theyā€™re clinical thresholds backed by data. For example, oral thrush after age 1 has an 89% specificity for antibody deficiency. That means if a child still has white patches in the mouth after turning one, and antibiotics didnā€™t help, itā€™s far more likely to be an immune issue than a simple yeast overgrowth.

What Doctors Look For During the Exam

A physical exam can give early clues. Some immune disorders have visible signs. If a child has no tonsils or lymph nodes, thatā€™s a major red flag-78% of children with severe combined immunodeficiency (SCID) show this. Skin changes matter too. Telangiectasias (tiny red blood vessels on the skin) are seen in 95% of cases of ataxia-telangiectasia. Poor growth is another signal: 63% of children with PIDs fall below the 5th percentile for height and weight.

Doctors donā€™t just count infections-they look for patterns in the bugs causing them. Infections with unusual organisms like Pneumocystis jirovecii, Cryptosporidium, or persistent Candida are absolute red flags. These are opportunistic pathogens that rarely harm healthy people. If a child gets one of these, itā€™s not a coincidence-itā€™s a warning.

Basic Lab Tests to Start the Workup

The first step in evaluating recurrent infections is simple blood work. A complete blood count (CBC) with manual differential is the starting point. In children over 1 year, a lymphocyte count under 1,500 cells/Ī¼L suggests a T-cell problem. In infants under 1 year, anything below 3,000 cells/Ī¼L is concerning.

Next, immunoglobulin levels: IgG, IgA, and IgM. But hereā€™s where most providers get tripped up-these numbers change with age. At 3 months, a normal IgG level is around 243 mg/dL. By age 5, it should be 700-1,600 mg/dL, just like adults. If an 8-year-old has an IgG of 420 mg/dL, it might look ā€œnormalā€ on a generic lab range, but itā€™s dangerously low for their age. Thatā€™s how some cases of Common Variable Immunodeficiency (CVID) get missed.

Flow cytometry for lymphocyte subsets (CD3, CD4, CD8, CD19, CD56) tells you if the body is making enough T cells, B cells, or natural killer cells. A CD3+ T-cell count below 1,000 cells/Ī¼L in a child over 2 is abnormal and needs urgent follow-up.

A bone family tree with immune disorders and vaccine light beams, pathogens as skeleton creatures in vibrant colors.

Testing Antibody Function-The Gold Standard

Measuring IgG levels alone isnā€™t enough. A person can have normal IgG but still canā€™t make antibodies when they need them. Thatā€™s why vaccine challenge testing is critical.

Doctors check antibody responses to vaccines given in the past few months. For protein antigens like tetanus or diphtheria, they measure IgG levels 4-6 weeks after vaccination. Protective levels are ā‰„0.1 IU/mL. For polysaccharide antigens like pneumococcal vaccines, they wait 4-8 weeks and look for ā‰„1.3 Ī¼g/mL. If the body doesnā€™t respond, itā€™s not just low antibodies-itā€™s a functional failure.

CVID diagnosis requires three things: IgG under 400 mg/dL, low IgA or IgM, and a poor response to vaccines. Many patients are misdiagnosed as having chronic bronchitis or asthma because their IgG is just above the ā€œnormalā€ cutoff-but still far too low for their age.

What Else Could It Be? Ruling Out Mimics

Before jumping to a diagnosis of immunodeficiency, doctors have to rule out other causes. About 43% of children with recurrent infections have anatomical problems, not immune ones. Cystic fibrosis accounts for 12% of cases. Chronic sinusitis from blocked nasal passages makes up another 31%. Inhaled foreign bodies-like a small toy part or peanut-cause 18% of recurrent pneumonias in kids.

Even more surprising: up to 30% of patients labeled with CVID actually have a secondary cause. Autoimmune diseases like lupus, certain cancers, or medications like steroids or biologics can suppress antibody production. Giving IVIG to someone with a drug-induced low IgG wonā€™t fix the root problem-and could mask a cancer or autoimmune disorder.

The American College of Physicians warns: donā€™t start immunoglobulin replacement without proof of functional antibody failure. One study found 22% of patients received IVIG unnecessarily-costing thousands and exposing them to avoidable risks.

An hourglass draining into a childā€™s chest as immune cells crumble, with medical reports as butterflies in Day of the Dead style.

Testing Logistics and Common Mistakes

Timing matters. If a child got a live vaccine (like MMR or varicella) in the last 4 weeks, antibody tests could be falsely high. Inactivated vaccines (like DTaP or flu shots) need at least 8 weeks before testing. Polysaccharide and conjugate pneumococcal vaccines must be spaced at least 6 months apart.

One of the biggest mistakes? Mistaking transient hypogammaglobulinemia of infancy (THI) for CVID. THI happens in 2-5% of babies-itā€™s temporary. IgG levels dip around 6 months and recover by age 2-3. But 41% of pediatricians in one survey started IVIG for these kids anyway. Thatā€™s unnecessary, expensive, and potentially harmful.

New Tools and Faster Diagnosis

In 2023, the FDA approved next-generation genetic panels like StrataID Immune, which tests 484 immune-related genes. These panels find the genetic cause in 35% of suspected PID cases-double the rate of older tests. Newborn screening for SCID is now mandatory in 38 U.S. states, up from 26 in 2018. Babies diagnosed before 3.5 months have a 94% survival rate. Those diagnosed later? Only 69% survive.

AI tools are coming fast. The NIH is testing algorithms that predict specific immunodeficiencies using routine lab results-with 92% accuracy in early trials. Within five years, whole exome sequencing may become the first test for suspected PIDs, cutting diagnostic delays from years to weeks.

Why This Matters

The average time to diagnose a PID used to be 9.2 years. Thanks to awareness campaigns like the Jeffrey Modell Foundationā€™s 10 Warning Signs, thatā€™s dropped to 2.1 years in centers following standardized protocols. Early diagnosis means fewer hospital stays, less lung damage from repeated pneumonia, and better long-term outcomes.

Itā€™s not about being overly cautious. Itā€™s about recognizing patterns others miss. A child who gets pneumonia twice in a year isnā€™t just unlucky. A toddler with thrush after age 1 isnā€™t just having a yeast flare-up. These arenā€™t normal. Theyā€™re signals. And when you listen to them, you can change a life.

How many ear infections are too many for a child?

Four or more ear infections in one year is a red flag for possible immunodeficiency. Healthy children may have up to 6-8 infections annually, especially under age 5, but recurring infections that require antibiotics or lead to hearing loss should prompt evaluation. The key is not just frequency, but severity and response to treatment.

Can adults have primary immunodeficiency too?

Yes. Many people are diagnosed in adulthood, especially with Common Variable Immunodeficiency (CVID), which often shows up between ages 20 and 40. Adults with recurrent sinusitis, pneumonia, or gastrointestinal infections from unusual pathogens should be tested. CVID accounts for 68% of antibody deficiencies diagnosed in adults.

Is IVIG always the answer for recurrent infections?

No. Intravenous immunoglobulin (IVIG) is only recommended after confirming a functional antibody deficiency through vaccine response testing. Giving IVIG without this evidence can mask underlying conditions like cancer or autoimmune disease. Studies show 22% of patients receive IVIG unnecessarily.

What does failure to thrive mean in this context?

Failure to thrive means a childā€™s weight and height fall below the 5th percentile for their age and sex, and they arenā€™t growing normally despite adequate nutrition. In immunodeficiency, chronic infections and gut inflammation from pathogens like Giardia or Cryptosporidium can impair nutrient absorption. This is seen in 63% of pediatric PID cases.

Can a normal CBC rule out immunodeficiency?

No. A normal CBC doesnā€™t rule out immunodeficiency. Many patients with antibody deficiencies like CVID have normal white blood cell counts. The problem isnā€™t the number of cells-itā€™s whether they work. Immunoglobulin levels and vaccine response tests are needed to detect functional problems.

Whatā€™s the difference between primary and secondary immunodeficiency?

Primary immunodeficiency is inherited and caused by genetic defects in immune cells. Secondary immunodeficiency is acquired-caused by things like HIV, chemotherapy, malnutrition, or long-term steroid use. Treatment differs: primary PIDs may need lifelong IVIG or stem cell transplant; secondary causes require treating the underlying condition.

Should I get my child tested if a sibling has immunodeficiency?

Yes. Family history is one of the top red flags. Many PIDs are inherited, especially X-linked disorders like X-linked agammaglobulinemia, which affects 85% of pediatric antibody deficiency cases. If one child has a PID, siblings should be evaluated-even if they seem healthy-because early detection saves lives.

How long does it take to get a diagnosis?

With a structured workup following AAAAI guidelines, diagnosis takes about 112 days on average. Without a clear plan, it can take over a year-and sometimes up to 9 years. Early testing, proper lab interpretation, and avoiding misdiagnosis are the biggest factors in reducing delays.