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Immunodeficiency Diseases

Weíll start with immunoglobulin and B-cell deficiencies, and the first one is X-linked or Brutonís agammaglobulinemia. This is X-linked, recessive and the basic defect is that you have absent B-cells due to a tyrosine kinase deficiency. Onset, the age of onset, is after six months for hypogammaglobulinemia, common-variable immunodeficiency, selective IgA deficiency, hyper IgM syndrome, severe combined immunodeficiency, Wiscott-Aldrich, ataxia telangiectasia, chronic granulomatous disease. And thatís because of the presence of maternal immunoglobulins. You donít need a lot of immunoglobulins until you are about six months of age. Generally you see pyogenic infections, a lot of bacterial infections, and you will also have absent tonsils and lymph nodes. A whole host of other symptoms and you can get vaccine-related problems if you give these kids oral polio.

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. And the key labs here are that immunoglobulins are low.

A third one is common-variable immunodeficiency, also known as acquired agammaglobulinemia. This one Ö 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. Most often the age of onset is after five years of age.

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 Ö oh, I missed the different presentations. Twenty-five percent of these will be asymptomatic, 25% will have respiratory infections - primarily recurrent bacterial infection - 25% will have allergies, particularly food allergies. Food allergies make sense if secretory IgA.

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. One thing to note is that IgG4 may be low in 20-30%.

Impaired polysaccharide responsiveness; clinical features here are recurrent sino-pulmonary infections and otitis media. In this one, what you see is the IgG subclasses are normal - IgG and subclasses are normal - but what you see is antibody.

Hyper IgM syndrome; itís usually an X-linked disorder. Clinical features are really pretty similar to X-linked agammaglobulinemia. Key labs here that you will see is elevated IgM and also low IgG and low IgA. The problem here with hyper IgM syndrome is that they can make IgM but they canít switch over to IgG and IgA.

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 and very early presentation of severe viral and bacterial infections. Onset may be as early as two to three months, which is earlier in general than X-linked agammaglobulinemia and may present a clue. There is failure to thrive, a progressive downhill course, a whole range of other clinical symptoms.

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. Iíll go so far as to say it will show up on the Boards and if not, everybody gets a refund for this course. (No, Iím kidding. You canítÖ) Itís 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 presentsÖ that ataxia presents actually in infancy. A range of other findings that you may see.

Mucocutaneous candidiasis; this one is an interesting one. This is a pure T-cell defect and the T-cells are unresponsive to Candida, but thatís 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. You may see endocrine abnormalities in one form of the disease. Genetics is usually sporadic.

Hyper IgE syndrome, which we are now on to phagocytic problems. Also known as Joe Buckley. Itís chief findings are recurrent, severe staphylococcal infection. Not surprisingly because itís 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 canít 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 thatís associated with delayed detachment of the umbilical cord. They also have periodontitis and early infections. What you see, the problem is that white cells canít chemotax or move well. So they canít move to the tissue and the way that umbilical cords fall off.

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.