Snapshot A 22-year-old female with a history of celiac disease comes to the office for chronic watery diarrhea. She recently returned from a vacation in Mexico. On further chart review, she has had multiple episodes of sinus infections, pneumonia, and otitis media throughout her childhood. After her last pregnancy, she received a blood transfusion following severe post-partum hemorrhage and experienced an anaphylactic reaction. Physical exam reveals chronic eczema on the flexural surface of the arms. Stool analysis is positive for Giardia. Introduction Primary immunodeficiency with decreased levels of IgA Epidemiology Most common primary immunodeficiency May be inherited (recessive and dominant forms identified) May be drug-induced Most common in individuals of European descent Prevalence 1 in 500 persons ETIOLOGY Pathogenesis cause is unknown B-cells fail to differentiate into IgA producing plasma cells impairs mucosal immunity, leading to sinopulmonary infections Associated conditions increased incidence of autoimmune diseases celiac disease atopy allergies atopic dermatitis asthma Presentation Symptoms most = asymptomatic sinus and lung infections usually Streptococcus pneumoniae and other encapsulated bacteria GI infections especially giardiasis severe allergies atopic dermatitis anaphylaxis with exposure to blood products containing IgA IMAGING Radiography to identify infections secondary to low IgA STUDIES Serology ↓ IgA (< 7 mg/dL) normal IgG and IgM false positive β-hCG Differential Diagnosis Common variable immunodeficiency IgG deficiency Ataxia-telangiectasia (↓ IgA, IgG, and IgE) Hyper-IgM syndrome (↓ IgA, IgG, IgE, and ↑ IgM) normal B and T cell by flow cytometry may have deficient expression of CD40L on activated T-helper cells presents with severe pyogenic infections early in life chronic diarrhea opportunistic infections, such as recurrent pneumonia increased risk for hyperviscosity syndrome due to elevated levels of IgM malignancies (HCC and carcinoid tumor) DIAGNOSIS Diagnosis based on clinical history Treatment Prevention avoid blood transfusions unless treated with saline wash or from IgA deficient individual Usually no specific treatment Antibiotics as needed for infections Immunizations Blood transfusions wash RBCs with saline or obtain blood from IgA-deficient donor Complications Recurrent sinopulmonary infections Diarrhea from Giardiasis Fatal anaphylaxis Prognosis Typically very good Some patients spontaneously develop normal IgA levels