[PAGID] Puzzling case of hypergammaglobulinemia with absence of antibody responses

[Howard M Lederman]

I am evaluating a 20 month old girl with a perplexing combination of findings, and could use some help:She was a full-term infant who began having recurrent otitis media at 10 months of age. For unclear reasons, she was treated with 5 days of prednisone + antibiotics for each OM.  At age 12 months, she stopped standing, putting weight on her legs, and cruising.  She had normal brain MRI, EMG, and nerve conduction velocity tests.  Shortly after, she was treated with Decadron on 3 occasions within 2 wks for croup.  The following week, she developed stridor, and was intubated with findings of laryngeal and subglottic swelling.  She was treated with pressors, blood transfusion, and GM-CSF.  During her hospitalization, a trachea culture was positive for Pseudomonas and Enterobacter.  Blood cultures were negative.  She developed candidal esophagitis and C. difficile diarrhea. During her hospitalization, she was found to have hepatosplenomegaly, still of unknown etiology. She was found to have a drenal insufficiency, presumed to be secondary to steroid use, and was started on replacement therapy.

While hospitalized in 05/2008, she was evaluated for immunodeficiency. She had normal immunoglobulin levels (IgA 291 mg/dL, IgG 1270 mg/dL, and IgM 372 mg/dL).  She had normal adenosine deaminase (67.3 nmol/h/mg) and purine nucleoside phosphorylase (1730 nmol/h/mg) levels.  She had diminished lymphoproliferative responses to PHA (33% normal control), concanavalin A (6% normal control), and pokeweed mitogen (58% normal control).  She had low percentages and numbers of CD3 (31%; 294/cu mm), CD4 (24%; 223/cu mm) and CD8 (7%, 65/cu mm) T-lymphocytes.

When I first saw her last month, she had normal responses to T-cell mitogens (unstimulated 318 cpm, Phytohemagglutinin A 77,979 cpm, Concanavalin A 29,606 cpm), and negative FISH for 22q11 deletions.  She had a borderline low white blood count (5850/cu mm) with 63% lymphocytes (3710/cu mm).  She had low percentages of CD3 (35%), CD4 (29%; 998/cu mm) and CD8 (5%) T lymphocytes.  Despite the high levels of IgG (and IgA), she had no detectable IgG Ab to previously administered vaccines, nor to a subsequent booster dose of Prevnar.   PCR tests for HIV, CMV and EBV were negative.  Ferritin normal (17 ng/mL), trigylcerides slightly high (169 mg/dL).  Her IgG and IgA levels have increased.  IFE shows multiple bands of restricted electrophoretic mibility in IgG, IgA, kappa and lamda lanes
I am anxious for ideas to explain all of this.
Howard
Howard M. Lederman, M.D., Ph.D. 
Professor of Pediatrics, Medicine and Pathology 
Division of Pediatric Allergy and Immunology 
Johns Hopkins Hospital - CMSC 1102 
600 N. Wolfe Street 
Baltimore, MD 21287-3923 
Phone: 410-955-5883 
Fax: 410-955-0229 
Email: Hlederm1 at jhem.jhmi.edu 

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