Sex: F
Vaccine: PPV
Symptoms: Blood immunoglobulin A normal, Blood immunoglobulin G normal, Blood immunoglobulin M normal, Computerised tomogram abnormal, Condition aggravated
Clinical narrative: Pneumococcal serotype-specific IgG levels were undetectable to 20 of 23 serotypes tested at baseline, and only 4 were considered protective post-vaccination;   This literature marketed report has been received from authors of a published article, titled as above, regarding a 31 years old female patient.  The patient presented with asthma, atopic dermatitis, allergic rhinitis, and a history of episodic fatigue and sinusitis for several years. Episodic fatigue occurred every 2-3 weeks and was described as not feeling rested even after 12 h of sleep. Chronic sinusitis was treated with 4-5 prolonged antibiotic courses per year. Nasal cultures grew methicillinsensitive and methicillin-resistant Staphylococcus aureus and Haemophilus irifluenzae. Three separate sinus surgeries over the prior few years moderately reduced her sinus symptoms. Other relevant history was significant for recurrent urinary tract infections with E. coli and Klebsiella, recurrent otitis media as a child, and a diagnosis of transient hypogammaglobulinemia of infancy that resolved at 4 years of age.  Review of systems revealed intermittent axillary lymphadenopathy, longstanding eczema that responded to topical tacrolimus, multiple environmental allergies, and recently diagnosed asthma that improved with inhaled budesonide (+) formoterol. As a teenager, she received allergen immunotherapy (AIT) for a few years but stopped due to frequent adverse reactions. Family history revealed that her mother received AIT for seasonal allergies, and her father died from infection associated with chemotherapy for non-Hodgkin's lymphoma. Physical exam at the initial evaluation was only remarkable for nasal turbinate hypertrophy.  Laboratory evaluation demonstrated normal immunoglobulin G (IgG) 886 mg/dL, immunoglobulin M (IgM) 139 mg/dL, immunoglobulin A (IgA) 156 mg/dL, elevated immunoglobulin E (IgE) 373 kU/L, normal T and natural killer (NK) cell enumeration, slightly decreased total B cells (180 cells/microliter, 5.6% of lymphocytes), and normal B cell subsets (CD19+CD27-IgM+ 67%, CD19+ CD27+IgM+17%, CD19+IgM-CD27+ 13%). Tetanus antibody titer was protective (0.27 IU/mL), but haemophilus influenzae type B (Hib) antibody titer was undetectable at less than 0.15 IU/mL and not protective after vaccination (0.53 IU/mL). Pneumococcal serotype-specific lgG levels were undetectable to 20 of 23 serotypes tested at baseline, and only 4 were considered protective post-vaccination with pneumococcal vaccine, polyvalent (23-valent) (PNEUMOVAX23) (antibody test negative). QuantiFERON gold assays consistently showed interferon (IFN)-gamma release more than 10.00 IU/mL in response to "PHA" (positive control), demonstrating T cell responsiveness to this mitogen. Due to poor antibody response and continued sinus infections, she was started on IgG replacement for the diagnosis of specific antibody deficiency. Her fatigue and sinus symptoms improved moderately, but she continued to require antibiotics. Sinus computed tomography (CT) scans continued to demonstrate significant disease. An in-house focused exome panel showed only a novel heterozygous caspase recruitment domain family member 11 (CARD11) variant (c.215G more than T, p.R72L). Specific antibody deficiency as observed in the patient was commonly seen in CARD11-associated atopy with dominant interference of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling (CADINS). The outcome of the event antibody test negative was unknown.  The causality between the event and pneumococcal vaccine, polyvalent (23-valent) (PNEUMOVAX23) was assessed as related.  A copy of the published article is attached as further documentation of the patient's experience.