Common variable immunodeficiency in children
Background. Common variable immunodeficiency (CVID) is a primary immunodeficiency that shows considerable heterogeneity. Despite increased knowledge of the genetics of primary immunodeficiencies, the etiology of CVID remains largely unknown. CVID is the second most common primary immunodeficiency disorder after selective IgA deficiency (sIgAD). The majority of the patients presents with symptoms in early adulthood, but a minority of the patients presents with symptoms during childhood.
Objective. To study the literature about CVID in children, focusing on clinical and immunological features and known genetic causes. This subgroup is considerably less elucidated in the literature than the adult CVID population.
Methods. The project is based on reviews in books and on original and review articles in medical journals. The primary search was performed in PubMed/Medline with the keyword "common variable immunodeficiency", with "pediatric", "children" etc. used as additional keywords. Also, MeSH terms were used to standardize the searches. Due to the limited amount of hits, the search could not be limited any further. The references were written into a Reference Manager database. The project is primarily depending on data obtained from six paediatric studies.
Results. The limited number of relevant studies and the low number of paediatric patients in these studies make conclusions somewhat difficult. The children received the CVID diagnosis around the age of 10 years, and the reported median diagnostic delay was a little less than 6 years. The paediatric studies showed no great difference between the sexes (58% males, 42% females, N=71). Only one gene mutation was reported in the studies, i.e. a ring chromosome 18. Developing CVID probably requires a combination of predisposing gene mutation and a trigger factor of unknown nature. The immunoglobulins varied considerably within and between the studies, although one study concluded that 29 of 32 children with CVID (91%) had significantly reduced serum levels of all immunoglobulin classes (IgG, IgA and IgM), and all 32 children had reduced serum IgG. All children with CVID had suffered from recurrent infections. Three studies (N=54) showed that 42 children (78%) had had pneumonia, 41 (76%) sinusitis and 37 (69%) otitis media. The frequency of allergies varied considerably between the studies, suggesting that different criteria have been used. One study showed that autoimmune diseases were present in 10 of 32 children with CVID (31%). The frequency of growth retardation also varied considerably between the studies (6-80%). All studies taken together showed growth retardation in 20 of 71 children (28%). Cancer is particularily reviewed in two studies. Lymphomas were dominating, and 8 of 42 children (19%) had malignancies. Bronchiectasis was altogether found in 30 of 87 children with CVID (34%), but the frequency varied from 12 to 90% between the studies. Several other disease associations were reported, but mostly as single cases. Splenomegaly was found in 20 of 42 children (48%) in two studies. One study (N=32) found enlarged lymph nodes (i.e. diameter >1 cm) locally in 15 children (47%) and diffusely in 10 children (31%). The same study found hepatomegaly in 9 children (28%). The treatment consists of immunoglobulin substitution therapy and antibiotic prophylaxis. The immunoglobulin substitution can be administered intravenously (IVIG) or subcutanously (SCIG). One study (N=32) showed that 27 children (84%) received IVIG, while 3 children (9%) received SCIG. However, SCIG is gaining popularity. The long-term survival is considerably reduced for CVID patients at all ages, compared to the normal population. The prognosis depends upon the clinical phenotype.
Conclusion. CVID has been considerably less studied in children than in adults. The relevant reports are few, the number of patients described are small, and much of the findings reported are difficult to compare. It would be of considerable interest to perform a retrospective study on Norwegian paediatric CVID patients.