If you’re like most doctors, who doesn’t spend the winter months prescribing antibiotics and treating upper respiratory infections?  But when is it serious enough to pull the trigger on a detailed work-up for immunodeficiency?

As with everything in medicine, when symptoms are outside of the “norm,” it’s time to intervene and start your work-up.  Consider the following:

1.  Severe infections such as sepsis or recurrent pneumonia are a no-brainer.  Do the work-up!

2.  The average number of yearly upper respiratory infections in a toddler is 8 to 12, so monthly episodes of a snotty nose aren’t that unusual.  I would be suspicious if fluid accumulates behind the ears, or antibiotics are required with every upper respiratory infection.

3.  Parental or patient anxiety should be included in your evaluation.  Remember, checking for antibodies as a screen will go a long way in relieving that nagging question, “is my child normal?”

4.  Remember, our job as physicians is to screen for immunodeficiency, not order every test available after the first encounter.  Signs & symptoms of immunodeficiency evolve and change our outlook as to how much testing is appropriate. 

Some suggestions for your consideration:

Categorize immunodeficiency into 5 subsets.  The appropriate tests to order follow in a logical pattern thereafter. 

1.  Antibody deficiency.  Labs for this diagnosis should include not only IgG, IgA, and IgM, but also specific antibody titers to Strep Pneumoniae.  Most children now receive PCV-7 or PCV-13 and a subset of kids with chronic infections won’t demonstrate a vigorous antibody response to these immunizations.  Interestingly, many of these children will respond to the adult Pneumovax™ and a good diagnostic test for antibody deficiency is to challenge with Pneumovax™ and repeat titers in one month. Want more info? This pocket guide is the best!

Lymphocytes are the traffic cops of the immune system

2.  T and B cell deficiency.  Infections in this category are viral infections that cause sepsis or meningitis, not self-limited colds.  AIDS falls into this category, although there are many T & B cell deficiencies in addition to AIDS.  Most labs will now provide panels that count the T/B and NK cell populations without having to remember each individual test.  As you can imagine, this saves time and headaches.  Don’t forget to order mitogen and antigen stimulation…determines how well lymphocytes respond to infection. Often the absolute cell number fails to tell the entire story.

3.  Neutrophils.  The PacMan of the immune system.  Usually infections due to chronic granulomatous disease (CGD) involve recurrent cellulitis or persistent abscesses.  You can order screens that measure the oxidative burst when a neutrophil is confronted with bacteria! 

This is what happens when neutrophils don't work

There are several prototypes of CGD depending on the missing enzyme, but most of them can’t produce superoxide anions when needed to kill the invading bug.

4.  Complement deficiencies are rare, but easy to measure.  Recurrent infections with Neisseria should raise the red flag.  CH50, C4, and C3 will tell you if further investigation is needed.

Shock because of Neisseria–think complement deficiency

5.  Last but not least, is the INNATE arm of immunity.  When I was a fellow 20 years ago, I was not taught about innate immunity because we didn’t know it existed.  How else does your body recognize a “new” infection without having to wait 7-10 days to mount an antibody response first?  Toll-like receptors are found on most surveillance cells that recognize nucleic components (DNA, RNA & other repeating sequences) found only on foreign invaders like bacteria, viruses, and fungi.  Believe me, you don’t want to memorize the list of Toll-like receptors (TLRs), but it’s a great cure for insomnia.  Labs can measure Mannose-binding protein, but other TLRs will have to wait their turn. 

If you examine a patient (young or old) with chronic infections and at least think of immunodeficiency, that’s a great start and you’ve come a long way!  Have fun with it–you can give someone their life back with the correct treatment.  (Sounds like another post to me!)

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