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Evaluation of the Child With Frequent Infections

Immunodeficiencies can be divided into primary and secondary immune deficiencies. There are about 70 primary immunodeficiencies and they are mostly antibody defects frequent infections, immunodeficiencies, susceptible to infections. Overall incidence is about 1 in 10,000. They are really pretty uncommon, primary immunodeficiencies do not happen all that often. Pure antibody deficiencies are present in about 50%. You’ll see antibody deficiency and combined cellular deficiencies here in this green, and 20% cellular deficiencies are present in about 10%. Phagocytic disorders, 18% and complement is the rarest of all, which is 2%. Secondary immunodeficiencies are much more common.

What are manifestations of immunodeficiency? In a fair number of them you may see increased frequency of infections, and this is when you have to be cautious about because you have to know what the normal frequency of infection is. That on average about six upper respiratory infections, to eight upper respiratory infections a year is completely normal, is average. And you may see kids who are having more frequent infections.

Key historical questions; I’m not going to review these because these things really are not going to come up on the Boards. Not helpful for the Board exam. You can review them later if you want, on your own, but they are really pretty obvious in terms of what are the key historical questions.

There are four basic types of children who may come to see you with recurrent infections. The first one is probably the well-child. About 50%. I think in my practice it’s well over 90%. So you have parents who come in, if their kid has had a cold a month for the last three months, or has had three ear infections, they are convinced the child must be immunodeficient. Ways that you can suspect that a child is normal and does not have immunodeficiency is that growth and development are normal, they are usually perfectly well between these episodes of infection, the onset of infection is recent - it hasn’t been lifelong - and often there is a new environmental situation. So they are new to daycare, they are new to nursery school, or in your case, new to internship probably caused your current infection. Second, the allergic child; about 30% can look like they can get recurrent infections, recurrent symptoms. Growth and development are usually normal. Illness is non-febrile, responds poorly to antibiotics.

Then finally, fourth is actually the immunodeficient child. It’s probably only about 10% of children, and the clues to these are several. First of all, the child may fail to thrive. You may see unusual organisms that may be cultures. Very importantly is; lymph nodes or tonsils may be absent. If you are seeing a child with recurrent severe infections, particularly if they are having recurrent otitis media, recurrent sino-pulmonary infections.

Clinical findings that are usually present include recurrent upper respiratory infections. The respiratory tract is a common site of infection when you have immunodeficiency. You may see severe bacterial infections and you may see persistent infections with common organisms that have a poor response to therapy. Next, a whole bunch of symptoms that are often present in immunodeficiency; failure to thrive, we already said, infection with an unusual organism, a whole host or range of skin lesions. Important ones may be seborrheic dermatitis.

Hypogammaglobulinemia of infancy. This one is just a lag in synthesis, and the reason this one is important is what you have to try and do is differentiate this from X-linked agammaglobulinemia. Again, chief findings you may get is recurrent bacterial infections in kids over about 4-6 months of age as that lag in immunoglobulin occurs. Usually not life-threatening infections, however. A range of other clinical manifestations you see.

A third one is common-variable immunodeficiency, also known as acquired agammaglobulinemia. This one … in this situation, patients are born with normal immunity but then something happens and for some reason you lose the ability to make immunoglobulins normally. B-cells essentially just stop working. One of the keys here, in differentiating from the first two - X-linked and transient - is the age of onset.

Selective IgA deficiency; in this one the basic defect is not really known but the chief findings is that IgA is deficient in both serum and secretions. So if you get serum IgA levels, levels will be low and the treatment, the main thing … oh, I missed the different presentations. Twenty-five percent of these will be asymptomatic.

IgG subclass deficiencies; chief findings here are recurrent infections which are usually respiratory with totally normal IgG. So this is one, if you send your screening IgG, total IgG is going to come out normal, and what you need to look at in these kind of cases, if you suspect an antibody disorder, is to get IgG subclasses.

Severe combined immunodeficiency; this is a very important one. It is, unlike the other ones that we have been talking about, this is a B and T-cell defect. The chief findings that you will see here is severe.

Wiskott-Aldrich. This is an important one because it has a fairly classic pattern of presentation. Not real common in real life, but common on the Boards. I’ll go so far as to say it will show up on the Boards and if not, everybody gets a refund for this course. (No, I’m kidding. You can’t…) It’s a classic one because you see a kind of a triad, which is severe recurrent bacterial infections, eczema and bleeding with thrombocytopenia.

Ataxic telangiectasia; these are combined B and T-cell defects. They have a pretty classic triad. Not surprisingly they have ataxia, and they also have telangiectasias. The telangiectasias initially are present in the conjunctiva but then can develop skin telangiectasias. The ataxia is really pretty progressive and can progress to severe cerebellar involvement, severe disability, and really most often presents.

Mucocutaneous candidiasis; this one is an interesting one. This is a pure T-cell defect and the T-cells are unresponsive to Candida, but that’s the only defect that they have. Completely normal otherwise. And obviously, as you would see, not surprisingly chronic Candida infections of the nails, mouth, hair and skin. There is no susceptibility to systemic candidiasis or other pathogens.

Hyper IgE syndrome, which we are now on to phagocytic problems. Also known as Joe Buckley. It’s chief findings are recurrent, severe staphylococcal infection. Not surprisingly because it’s called hyper IgE levels, the key test to get is IgE and you get profoundly high IgE levels, maybe often above 4,000. The treatment is usually in things like anti-staph drugs and Bactrim continuously.

Chronic granulomatous disease; basic defect here is that you can’t form reactive oxygen intermediates. Chief findings are that you get recurrent infections of soft tissues, bones, lungs and skin; Granulomas, suppurative adenopathy. The chief organisms that you are going to get are staph aureus, Serratia and aspergillus. Other clinical findings as well. Labs here, as we said before, diminished reduction of NBT test is the key to diagnosis. Treatment of choice in this case is actually interferon gamma.

Leukocyte adhesion defect is an interesting one because of the key clinical finding. And this is the one that’s associated with delayed detachment of the umbilical cord. They also have periodontitis and early infections. What you see, the problem is that white cells can’t chemotax or move well. So they can’t move to the tissue and the way that umbilical cords fall off is that it’s an inflammatory reaction. So the white cells can’t get to the cord.

Late complement component defects; this is an autosomal recessive condition and the presentation here is with recurrent Neisseria infection, meningitis and gonorrhea. Onset is often delayed until teenage years. So if you see a teenager who develops meningococcal meningitis you may want to think about, or consider this diagnosis; complement deficiencies. Key lab is CH50 activity, which is absent. Treatment; you may consider prophylactic antibiotics and use polysaccharide vaccine. So that does it in terms of an overview. One thing, this is an area that I think is very important and is very hard to remember.