Immunodeficiency Red Flags: Recurrent Infections and What Doctors Look For

When a child keeps getting sick-ear infections, pneumonia, sinus infections-it’s easy to blame daycare, bad luck, or a weak immune system. But when infections keep coming back, don’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 aren’t diagnosed until years after symptoms start. The key isn’t just how often someone gets sick-it’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 something’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 don’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 aren’t vague suggestions-they’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 didn’t help, it’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, that’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 don’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, it’s not a coincidence-it’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/μL suggests a T-cell problem. In infants under 1 year, anything below 3,000 cells/μL is concerning.

Next, immunoglobulin levels: IgG, IgA, and IgM. But here’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 “normal” on a generic lab range, but it’s dangerously low for their age. That’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/μL in a child over 2 is abnormal and needs urgent follow-up.

Testing Antibody Function-The Gold Standard

Measuring IgG levels alone isn’t enough. A person can have normal IgG but still can’t make antibodies when they need them. That’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 ≥0.1 IU/mL. For polysaccharide antigens like pneumococcal vaccines, they wait 4-8 weeks and look for ≥1.3 μg/mL. If the body doesn’t respond, it’s not just low antibodies-it’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 “normal” 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 won’t fix the root problem-and could mask a cancer or autoimmune disorder.

The American College of Physicians warns: don’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.

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-it’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. That’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 Foundation’s 10 Warning Signs, that’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.

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