Snapshot A 35-year-old man presents to the emergency room for watery diarrhea. He reports that he feels as though he is always sick with sinusitis, upper respiratory infections, or diarrhea. He cannot recall when in the past year he has been free of symptoms. On physical exam, he is clinically dehydrated with poor skin turgor, sunken eyes, and dry mucous membranes. Lung exam reveals crackles bilaterally, and his abdomen is soft and tender to palpation. Bowel sounds are hyperactive. After reviewing his 10+ visits to his primary care physician and emergency room, the physician decides to evaluate this patient's immunoglobulin levels. Both his IgG and IgA levels come back low. He is started on intravenous immunoglobulin therapy. Introduction Clinical definition immunodeficiency disorders characterized by a decrease in all immunoglobulins (Ig), especially IgG and IgM or IgA arises from B-cell dysfunction Epidemiology Demographics most commonly presents between 20-40 years of age ETIOLOGY Pathogenesis unknown except that etiology is heterogeneous usually a combined B-cell and T-cell defect defect in B-cell differentiation no clear pattern of inheritance Associated conditions at increased risk for autoimmune diseases alopecia areata granulomatous diseases at increased risk for lymphoma Presentation Symptoms recurrent pyogenic sinopulmonary and gastrointestinal infections permanent damage to the lungs bronchiectasis malignancies persistent diarrhea Giardia lamblia Physical exam generalized lymphadenopathy splenomegaly Studies Diagnostic testing studies labs ↓ B-cells that produce antibodies (plasma cells) ↓ all immunoglobulin classes, especially IgA and IgG d lymph node biopsy to exclude malignancy reactive follicular hyperplasia Differential X-linked agammaglobulinemia distinguishing factors found only in males and often presents in childhood after 6 months of age also, treat with IVIG Severe combined immunodeficiency (SCID) distinguishing factors much more severe and presents in childhood treatment with bone marrow or stem cell transplant and IVIG presents with chronic candidiasis, severe bacterial, and opportunistic infections DIAGNOSIS Diagnostic criteria age > 4 years low serum IgG and low serum IgA or IgM poor response to vaccines exclusion of other causes of low serum immunoglobulins Treatment Management approach treatment goals focus on preventing infections and treating specific complications of the disease First-line intravenous immunoglobulin (IVIG) replacement therapy may pre-medicate with antihistamines Second-line antibiotics Complications Lymphoma is a common cause of death in these patients ~20% develop autoimmune disease