Immunodeficiency Red Flags: Recognizing Recurrent Infections and When to Test

Most kids get sick. A cold here, an ear infection there - it’s normal. But when infections keep coming back, no matter how many antibiotics you try, something deeper might be going on. Recurrent infections aren’t just bad luck. They could be the first sign of a hidden immune system problem - one that, if caught early, can change a child’s life.

When Is a Recurrent Infection a Red Flag?

Healthy children can have up to 12 respiratory infections a year, especially if they’re in daycare or school. That’s normal. But if your child has four or more ear infections in a year, two or more serious sinus infections, or two or more pneumonias, it’s time to look beyond typical viruses. These aren’t just colds - they’re signals.

Other warning signs include:

• Deep skin or organ abscesses that won’t heal
• Oral thrush (white patches in the mouth) that lasts past age 1
• Infections that don’t improve after two months of antibiotics
• Needing IV antibiotics just to clear a simple infection
• Two or more deep-seated infections like septicemia or meningitis
• Failure to gain weight or grow normally
• A family history of early deaths from infections or known immune disorders

One of the most telling signs? Infections caused by organisms that rarely affect healthy people - like Pneumocystis jirovecii pneumonia or persistent candida in the lungs. These are called opportunistic infections. If they show up, it’s not a coincidence. It’s a red flag.

What Does the Body Show Beyond Infections?

Physical clues matter just as much as infection patterns. During a check-up, a doctor might notice:

• Absent tonsils or lymph nodes - seen in nearly 80% of severe combined immunodeficiency (SCID) cases
• Spider-like blood vessels on the skin (telangiectasias) - a hallmark of ataxia-telangiectasia
• Chronic diarrhea with poor weight gain - often tied to antibody deficiencies
• Autoimmune conditions like low platelets or anemia - which can accompany immune disorders like CVID

These signs don’t always show up together. Sometimes, the only clue is a child who’s always sick but doesn’t look obviously ill. That’s why doctors need to connect the dots - not just treat each infection as it comes.

Basic Blood Tests: The First Step

If red flags are present, the workup starts with simple blood tests. A complete blood count (CBC) with manual differential is the first step. In children over one year, a lymphocyte count below 1,500 cells/μL raises concern. In babies under one, anything below 3,000 cells/μL needs attention.

Next come immunoglobulin levels: IgG, IgA, and IgM. But here’s the catch - these numbers change with age. A 3-month-old with an IgG of 243 mg/dL is normal. An 8-year-old with the same level is severely deficient. Many pediatricians miss this. I’ve seen cases where a child’s IgG was 420 mg/dL - just above the “normal” cutoff - but way below what’s expected for their age. That child had Common Variable Immunodeficiency (CVID), but it was missed for over a year.

Normal IgG levels rise with age:

• 3 months: ~243 mg/dL
• 6 months: ~558 mg/dL
• By age 5: adult range - 700 to 1,600 mg/dL

Low IgG alone isn’t enough. You need to see if the body can make antibodies when challenged. That’s where vaccine testing comes in.

Testing Antibody Function: The Gold Standard

A low IgG level doesn’t always mean the immune system is broken. Maybe it’s just slow to mature. The real test is whether the body can respond to vaccines.

After giving a tetanus or diphtheria shot, doctors wait 4 to 6 weeks and check IgG levels. A protective level is at least 0.1 IU/mL. For pneumococcal vaccines (which use polysaccharides), the target is 1.3 μg/mL or higher. If the response is weak or absent, it’s not just low antibodies - it’s faulty function.

This step is often skipped. Too many patients get IV immunoglobulin (IVIG) without ever proving they can’t make their own antibodies. That’s risky and unnecessary. Studies show 22% of people on IVIG don’t actually need it.

Looking Deeper: Flow Cytometry and Genetic Testing

If basic tests suggest a problem, the next step is flow cytometry. This test counts different types of immune cells - T cells (CD3, CD4, CD8), B cells (CD19), and natural killer cells (CD56). A CD3+ T-cell count below 1,000 cells/μL in a child over two years is abnormal. It points to T-cell deficiencies like SCID or DiGeorge syndrome.

Now, genetic testing is changing the game. In 2023, the FDA approved next-generation panels that scan 484 immune-related genes. These tests find the exact genetic cause in 35% of suspected cases - nearly double the rate of older methods. For kids with SCID, finding the mutation early means faster treatment and a 94% survival rate if treated before 3.5 months of age. Delay diagnosis, and survival drops to 69%.

But these tests aren’t always easy to get. In many places, access is limited. That’s why experts stress starting with the basics - CBC, immunoglobulins, vaccine response - before jumping to expensive genetic panels.

Ruling Out Other Causes First

Not every recurrent infection is due to immunodeficiency. In fact, nearly half the time, something else is going on. Anatomical problems like a deviated septum, cystic fibrosis, or chronic sinus blockages can mimic immune disorders. Inhaled foreign bodies - like a small toy part - cause recurrent pneumonia in 18% of cases.

And then there are secondary causes. Up to 30% of adults diagnosed with CVID actually have another condition: lupus, lymphoma, or medications like long-term steroids or chemotherapy. Treating the immune system when the real problem is cancer? That’s dangerous.

That’s why the diagnostic process isn’t linear. You don’t just test for immunodeficiency. You rule out everything else first. A chest X-ray. A sweat test for cystic fibrosis. A CT scan of the sinuses. You don’t skip these steps.

What Happens After Diagnosis?

Once a diagnosis is confirmed, treatment is targeted. For antibody deficiencies like CVID or X-linked agammaglobulinemia, regular IVIG or subcutaneous infusions replace missing antibodies. For T-cell defects, bone marrow transplants can be curative - especially in infants.

But prevention matters just as much. Patients need live vaccines avoided (like MMR or varicella) until their immune status is confirmed. They need pneumococcal and flu shots every year. And they need to avoid environments with high infection risk - until they’re protected.

Early diagnosis doesn’t just prevent infections. It prevents lung damage, liver disease, and even cancer. People with untreated CVID have a 25% lifetime risk of developing lymphoma. Catch it early, and that risk drops dramatically.

Why So Many Cases Are Still Missed

Despite all the guidelines, most patients wait years for a diagnosis. The average delay? Nine years. That’s nine years of missed school, hospital visits, and antibiotics that don’t work.

Why? Because many doctors don’t know the red flags. Or they think, “It’s just a kid - they get sick.” Or they misread lab values. One study found 41% of pediatricians started IVIG for transient hypogammaglobulinemia of infancy - a harmless, temporary condition that resolves on its own.

Tools like the Jeffrey Modell Foundation’s “10 Warning Signs” campaign have helped. Since 2015, PID diagnoses have risen 37% in the U.S. because more parents and doctors are asking the right questions.

But the gap remains. In low-income countries, basic immunoglobulin testing isn’t available. In the U.S., access to functional antibody testing is still limited in rural areas. That’s why every primary care provider needs to know: if a child has recurrent infections and doesn’t respond to standard care - don’t wait. Refer early.

What Parents Should Do

If your child has multiple infections and isn’t improving:

1. Keep a detailed log: type of infection, how often, how long it lasted, what treatments were tried
2. Ask your doctor: “Could this be an immune problem?”
3. Request a CBC, immunoglobulin levels, and vaccine response testing
4. If the answer is no - ask for a referral to an immunologist
5. Don’t accept “it’s just growing up” if the pattern is severe

There’s no shame in asking. You’re not overreacting. You’re protecting your child’s future.

What’s Next for Immunodeficiency Diagnosis?

The future is faster. The NIH is launching a 5,000-patient study to build AI tools that predict immune disorders from routine blood work - with 92% accuracy in early trials. Whole exome sequencing may become the first test within five years, cutting diagnosis time from years to weeks.

But until then, the tools we have work - if we use them right. The science is clear. The signs are known. What’s missing isn’t knowledge. It’s action.