Common variable immunodeficiency

Background

Characterized by decreased IgG immunoglobulins, with or without decreases in IgA and IgM, and decreased response to vaccination
Must exclude other causes of hypogammaglobulinemia

Wide spectrum of manifestations
Most common presentation is recurrent sinopulmonary infections
- Especially Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma species
- Empyema, bacteremia, meningitis, and osteomyelitis
Can eventually develop chronic lung disease including obstruction, restriction, and bronchiectasis
Diarrhea is common (21 to 57%)
- Giardia lamblia is the most common cause of chronic diarrhea
- Others include Cryptosporidium parvum, CMV, Salmonella species, Clostridium difficile, and Campylobacter jejuni
Can also develop sarcoidosis (8 to 22%), with granulomatous changes occurring years before the hypogammaglobulinemia
- Mainly in lung, lymph nodes, or liver
- Portends a higher risk of immune-mediated thrombocytopenia and autoimmune hemolytic anemia
Autoimmune phenomena include immune-mediated thrombocytopenia, autoimmune hemolytic anemia, Evans syndrome, and autoimmune neutropenia
Higher rates of malignancies, primarily non-Hodgkin lymphoma and stomach cancer
- The latter may be related to infection with Helicobacter pylori

Serum IgG (mg/dL)	Recommendation
<150	repeat immunoglobulins to confirm
150-250	repeat immunoglobulins to confirm consider tetanus and diphtheria titres consider pneumococcal vaccine titres pre- and post-vaccination
250-450	repeat immunoglobulins to confirm check tetanus and diphtheria titres check pneumococcal vaccine titres pre- and post-vaccination
450-600	repeat immunoglobulins to confirm check tetanus, diphtheria, MMR, and VZV titres check pneumococcal vaccine titres pre- and post-vaccination

The mainstay of therapy if IVIg 400 to 600 mg/kg IV monthly, usually given every 3 to 4 weeks
- Can be given subcutaneously, divided every 1 to 2 weeks, if IV access is difficult
Target trough depends on baseline IgG level
- <100 mg/dL: target trough 600 mg/dL
- 300 mg/dl: target trough 900 mg/dL
Although many are IgA deficient, there are low rates of anti-IgA antibodies in CVID, so IVIg is generally safe

Patients	Assessment	Interval
all	History and physical	annually
	CBC, liver and renal panel, albumin	annually
	spirometry	annually
	serum trough IgG ± IgA and IgM	6-12 months
	chest x-ray	on referral
lung disease	high-resolution CT chest	3-4 years or after change of therapy
lung disease	lung function with DLCO	annually
GI complications	upper and/or lower endoscopy	as required
malabsorption or loss of height	bone density and micronutrient assessment	as required