Immunodeficiency Red Flags: Recurrent Infections and When to Suspect It

Recurrent infections aren’t always just bad luck

If your child gets ear infections every few months, or you keep ending up in the hospital with pneumonia, it’s easy to blame it on stress, school germs, or a weak immune system. But sometimes, repeated infections aren’t normal-they’re a warning sign. Immunodeficiency might be the real culprit. Unlike occasional colds or flu, true immune disorders don’t just cause more sickness-they cause the wrong kind of sickness, at the wrong times, and they don’t respond the way they should.

Most healthy kids get 6 to 12 respiratory infections a year. That’s normal. But if your child has four ear infections in one year, two pneumonias, or thrush that won’t go away after age one, it’s not just bad timing. It’s a signal. The same goes for adults: if you need IV antibiotics just to clear a sinus infection, or if you get fungal infections in your lungs or skin that don’t respond to standard treatment, something deeper is going on.

What counts as a red flag?

Doctors don’t guess when to suspect immunodeficiency. They follow clear, evidence-based criteria. The most widely accepted red flags come from the Immune Deficiency Foundation and the American Academy of Allergy, Asthma & Immunology. Here’s what to watch for:

• Four or more ear infections in one year
• Two or more serious sinus infections in one year
• Two or more pneumonias within a year
• Persistent oral thrush after age one
• Deep skin or organ abscesses that keep coming back
• Infections that don’t improve after two months of antibiotics
• Need for intravenous antibiotics to treat common infections
• Failure to gain weight or grow normally
• Family history of immunodeficiency
• Infections caused by unusual organisms-like Pneumocystis jirovecii or Candida in the lungs

These aren’t vague suggestions. They’re thresholds backed by data. For example, oral thrush after age one has an 89% specificity for antibody deficiency. That means if a child still has white patches in the mouth past their first birthday, and no other cause is found, there’s a very high chance their immune system isn’t making the right antibodies.

Physical signs that tell the story

Beyond infections, your body gives other clues. A doctor checking for immunodeficiency doesn’t just ask about symptoms-they look. They feel for lymph nodes. They check the tonsils. They examine the skin.

Absent or tiny tonsils and lymph nodes? That’s common in severe combined immunodeficiency (SCID). In fact, 78% of SCID cases show this finding. Skin changes matter too. Telangiectasias-tiny red spider veins on the face or eyes-are seen in 95% of people with ataxia-telangiectasia, a rare but serious immune disorder. A child with chronic diarrhea, poor growth, and these skin changes? That’s not just a digestive issue. It’s a red flag for an underlying genetic immune problem.

And growth isn’t just about height. If a child is below the 5th percentile for weight or height, and they’ve had multiple infections, that’s a major clue. Sixty-three percent of children with primary immunodeficiency show signs of failure to thrive by the time they’re diagnosed.

How do you test for it?

Testing doesn’t start with fancy gene panels. It starts with the basics-and they’re simple, cheap, and widely available.

First: a complete blood count (CBC) with manual differential. In kids over one year, a lymphocyte count below 1,500 cells/μL raises concern. In babies under one, it’s below 3,000. Low lymphocytes mean your body isn’t making enough immune cells.

Next: immunoglobulin levels. IgG, IgA, IgM. These are the antibodies your body uses to fight infection. But here’s the catch-they change with age. A 3-month-old’s normal IgG is around 243 mg/dL. By age 5, it should be 700-1,600 mg/dL. If your 8-year-old has an IgG of 420 mg/dL, it might look “normal” on a general lab report. But for their age? It’s dangerously low. That’s how some cases of Common Variable Immunodeficiency (CVID) get missed.

Then comes flow cytometry. This test looks at the types of white blood cells-T cells, B cells, NK cells. A CD3+ T-cell count below 1,000 cells/μL in a child over two is abnormal. It points to T-cell deficiency, which can be life-threatening if not caught early.

The gold standard? Vaccine response testing. You give a vaccine-like tetanus or pneumococcal-and then check antibody levels four to six weeks later. If your body doesn’t make a protective response, you have an antibody deficiency. For tetanus, a level below 0.1 IU/mL means no protection. For pneumococcus, below 1.3 μg/mL is a failure. Many doctors skip this step. But without it, you can’t confirm the diagnosis.

What’s not immunodeficiency?

Not every recurrent infection is due to a broken immune system. In fact, up to 43% of cases in children are caused by something else.

Cystic fibrosis is a big one. It causes thick mucus that traps bacteria in the lungs, leading to repeated pneumonia. Structural problems in the sinuses-like a deviated septum or polyps-can cause chronic sinus infections that mimic immune deficiency. Inhaled foreign bodies, like a small toy part or peanut, can cause one-sided pneumonia and get missed for months.

And then there’s secondary causes. Up to 30% of patients diagnosed with CVID actually have something else: an autoimmune disease like lupus, a cancer like lymphoma, or even a medication like long-term steroids or chemotherapy. These can lower antibody levels without being a true genetic immune disorder.

That’s why you don’t jump straight to IV immunoglobulin therapy. The American College of Physicians found that 22% of patients got IVIG without proof of antibody failure. That’s expensive, unnecessary, and potentially risky. Treatment should follow diagnosis-not the other way around.

What happens if you wait too long?

Delay isn’t just inconvenient-it’s dangerous. The earlier you catch severe combined immunodeficiency (SCID), the better the outcome. If diagnosed before 3.5 months of age, survival is 94%. If diagnosed after that? It drops to 69%. Why? Because infections cause irreversible damage. Lung scarring, liver damage, chronic sinusitis-all of it can become permanent.

And the diagnostic delay is real. Historically, people waited an average of 9.2 years to get diagnosed with CVID. That’s nearly a decade of unnecessary infections, missed school, hospital visits, and antibiotics that didn’t work. But when doctors use the 10-warning-sign criteria, that delay drops to 2.1 years. That’s a massive difference in quality of life.

New tools, faster answers

Testing is getting faster. In 2023, the FDA approved next-generation gene panels that screen for 484 immune-related genes. These tests find the genetic cause in 35% of suspected cases-nearly double the rate of older methods. In some centers, whole exome sequencing is becoming the first test, not the last.

Newborn screening for SCID is now mandatory in 38 U.S. states. That means babies are being caught before they even get sick. The result? Fewer deaths, fewer complications, and better long-term outcomes.

But access isn’t equal. In low- and middle-income countries, 78% of people can’t even get basic immunoglobulin testing. That’s a global crisis. For now, in places with access, the path is clear: recognize the signs, test the basics, confirm with function, and don’t treat without proof.

What to do next

If you’re seeing the red flags-repeated infections, poor growth, unusual organisms, or family history-don’t wait. Ask your doctor for a referral to an immunologist. Bring a list of infections: type, frequency, treatments tried, and response. Record your child’s growth over time. If you’ve had multiple courses of IV antibiotics, note them.

Don’t let a normal lab result fool you. Age matters. Context matters. And sometimes, the most important test is the one your doctor hasn’t ordered yet.