Review Question - QID 108432

This case is most consistent with a diagnosis of Wiskott-Aldrich syndrome, a disease characterized by the classic triad thrombocytopenia, eczema, and recurrent infections. The disease is caused by a mutation in an actin binding protein and serological findings include increased IgA and IgE with decreased IgM and IgG.

Frequent infections in a child usually signify a congenital or developmental immunodeficiency. Narrowing the possible differential then requires either recognition of the classic symptoms in a syndrome or identification of a characteristic group of microorganisms (such as Neisseria infections in complement deficiency). In this case no information is provided about specific organisms so the surrounding symptoms should be characterized. Bloody diarrhea and petechial lesions are both signs of platelet type bleeding and indicate thrombocytopenia (coagulation factors cause deep bleeding). Red, itchy lesions in the flexor compartments of extremities is the classic description of eczema or atopic dermatitis. Combining these findings with recurrent infections yields the classic triad of Wiskott-Aldrich syndrome. This diagnosis is supported by the family history of another male on the maternal side as this syndrome has an X-linked recessive type inheritance pattern. The disease is caused by a mutation of an actin binding protein and the classic serological findings include increased IgE and IgA with decreased IgM.

Incorrect Answers:
Answer 1: Globally decreased levels of immunoglobulins are commonly found in disorders of B-cell development or maturation. A classic example is Bruton’s Agammaglobulinemia, which is an X-linked disorder caused by mutation of Bruton’s tyrosine kinase. This mutation inhibits B-cell maturation and leads to early B-cell apoptosis.

Answer 2: Increased IgM with decreased levels of other immunoglobulins indicate a defect in class switching and is found in hyper-IgM syndrome. This disease presents with pyogenic infections early in life especially with pneumocystis and cryptosporidium.

Answer 3: Decreased levels of IgA with normal levels of other immunoglobulins is found in selective IgA deficiency. This disease is of unknown etiology but presents with atopy, autoimmune disease, airway infections, and anaphylaxis when transfused with IgA containing products.

Answer 5: Selective increase in IgE levels is found in Job syndrome, which presents with coarse facies, retained teeth, and eczema as well as recurrent infections. It is caused by a mutation in STAT3 transmitters leading to a failure of Th17 subtype signaling.

Bullet Summary:
The key points to remember are that primarily immunodeficiency syndromes should be evaluated in the context of an overall syndrome. Wiskott-Aldrich syndrome involves thrombocytopenia and eczema along with recurrent infections and exhibits the classic findings of increased IgE and IgA with decreased IgM.