The records of 52 active CVID patients from the Immunology Division of seven different reference centres in Mexico were studied. CVID was diagnosed according to the diagnostic criteria of the European Society for Immunodeficiency Diseases (ESID). Information from each CVID subject was collected by means of a structured questionnaire applied by a single physician: demographics, age at onset of symptoms, age at diagnosis, pedigree, clinical manifestations, current infections, autoimmunity, lymphoproliferative disease, allergy and malignancies, lymphocyte subsets and immunoglobulin levels at the first clinical visit, and route and dosage of immunoglobulin.

The protocol was reviewed and approved by the appropriate local Ethics and Research Committees in accordance with the guidelines of the International Conference on Harmonization Good Clinical Practice and the Declaration of Helsinki, to access details of clinical records, and on the publication of patient data on their manuscript for research and divulgation purposes for the scientific community.

Results are shown as mean±sd (if the variable is normally distributed) and median (interquartile range) for continuous variables. Dichotomous and nominal variables were expressed as frequencies and percentages. All two-sided P-values <0.05 were considered to be statistically significant. Data were analysed using the Statistical Package for Social Science (SPSS) for Windows (version 12.00, SPSS Inc., Chicago, IL, USA).

Diagnosis was confirmed for 43 patients; 23 (53.5%) were males, and 20 (46.5%) were females; two patients were sisters. The median age at the onset of disease was 13.7 years (9.37–18.0), and the median age at diagnosis was 19 years (14.5–23.5), thus indicating that the average delay in diagnosis was 12.5 (10.7–26.8) years. The mean follow-up time was 24.5 years (±15) (Table 1).

The median total serum levels of IgG, IgM, and IgA at diagnosis were 175 (160–253), 18.0 (20.8–57.5), and 17.8 (13.1–23.8)mg/dL, respectively (Table 1). Lymphocyte subset distribution was also assessed. The median expression for CD3 was 77% (67–80), 34% (29–45) for CD4, and 37% (35–47) for CD8. The median CD19+ B cells was 8.15% (6.7–13.2).

Infections were the most common clinical manifestation. All the patients had recurrent infections as the initial manifestation, except for two patients having autoimmunity. Among infections, the four most frequent were sinusitis (36, 83%), pneumonia (36, 83%), gastrointestinal infection (30, 70%), and acute otitis media (21, 49%). The less frequent were urinary tract infections (7, 16%), meningitis (6, 14%), mastoiditis (3, 7%), and vulvovaginitis (3, 7%). Culture-proven sepsis, stomatitis, osteomyelitis, cellulitis, and perianal abscess were each found in two patients (5%). Septic arthritis, brain abscess, mucocutaneous herpes simplex virus, peritonitis, fasciitis, and endocarditis were each found in one patient (2%).

Organisms most commonly isolated from the respiratory tract were Streptococcus pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus viridans. Giardia lamblia and Salmonella enterica were the most frequent causes of gastrointestinal infections. The remaining infectious agents were diverse and included gram-negative bacteria, mycobacteria, and fungus (Table 2).

Clinical and serological viral infections were positive for Epstein Barr virus (n=5), varicella-zoster virus (n=3), and cytomegalovirus (n=1).

Ninety-five percent of the patients were hospitalised at least once due to infection. The median number of hospitalisations per patient was 3.1 (3.0–7.14), and the overall median length of hospitalisation was 50 days (37.3–80.9) per patient.

Bronchiectasis, detected through high-resolution computed tomography, was found in 22 (51%) patients at the time of evaluation for this study. Of the patients who suffered from pneumonia, 61% developed bronchiectasis (Table 1).

Nineteen (44%) patients showed non-infectious chronic diarrhoea, and 15 out of 19 (79%) patients experienced weight loss. Biopsies performed in two patients with chronic diarrhoea revealed eosinophilic infiltration in one patient, and eosinophilic infiltration and lymphoid hyperplasia in the other (Tables 1 and 3).

Two patients showed autoimmunity as first manifestation; both suffered from autoimmune thrombocytopenic purpura (ATP), and one additionally suffered from autoimmune haemolytic anaemia.

A family history of autoimmunity was present in three patients: systemic lupus erythematous in one, and idiopathic thrombocytopenic purpura in two. Autoimmunity occurred in 10 (23.2%) patients, including seven females and three males. This finding was evident from eight different diseases: haemolytic anaemia (1), vitiligo (2), thyroiditis (2), arthritis (1), vasculitis (1), Behcet's disease (1), and idiopathic pulmonary fibrosis (1). One patient had haemolytic anaemia and autoimmune thrombocytopenic purpura. The median age at autoimmune disease onset was 12.5 (10.7–26.7) years, and the median age at diagnosis was 14 (11.2–27). Two out of four patients with splenomegaly had autoimmune cytopenia (Table 1).

Allergy was present in 13 (30.2%) patients. Manifestations were allergic rhinitis and asthma (6), rhinitis (2), atopic dermatitis (1), asthma and atopic dermatitis (1), and drug allergy (3). Median IgE level was 8 (5.8–20.9)μI/mL (Table 1).

One patient suffered from myeloid metaplasia with liver and spleen infiltration, and cutaneous T-cell lymphoma.

Tonsils were present in 34 (79.1%) patients, absent in three patients, and undocumented in two patients. Lymph nodes, liver, and spleen had increased size in 29, 4, and 4 patients, respectively.

All the patients started with intravenous immunoglobulin (IVIG) at diagnosis, and the mean dose was 408mg/kg (±130), and received prophylactic antibiotic with azithromycin.

The authors declare that no experiments were performed on humans or animals for this investigation.

The authors declare that they have followed the protocols of their health center to access details of clinical records, and on the publication of patient data on their manuscript for research and divulgation purposes for the scientific community.

Being a retrospective study, there is no informed consent of patients referred in this study. However, it has been authorized by the Ethics and Research Committees of the National Institute of Pediatrics.