Safety of Live Viral Vaccines in Patients With Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome)

The package inserts of live viral vaccines include immunodeficiency as a contraindication. Nevertheless, patients with mild forms of immunodeficiency may benefit from vaccination. No published guidelines exist for the administration of these vaccines specifically to patients with chromosome 22q11.2 deletion syndrome. This syndrome is also sometimes called DiGeorge syndrome and is associated with thymic hypoplasia and diminished T-cell numbers and has a wide spectrum of phenotypic features that include cardiac anomalies, dysmorphic facial features, and hypocalcemia. Patients generally exhibit a mild to moderate decrement in T-cell numbers with preservation of T-cell function. The aims of this study were to investigate the incidence of side effects after live viral vaccine administration in a population with chromosome 22q11.2 deletion syndrome. The high frequency of this syndrome in the population (1: 3000 children) mandates a greater understanding of the risks and benefits related to live viral vaccine administration. A retrospective analysis of vaccine adverse events was performed. The data acquisition form evaluated the frequency of live vaccine administration and the consequences of both vaccination and withholding the vaccine. Flow cytometric enumeration of T cells was performed as part of an immunologic evaluation. Thirty-two of 59 responders were vaccinated with the varicella vaccine. Only 9% of patients reported adverse events. However, 63% of unvaccinated children developed chickenpox. Comparison of patients who tolerated the vaccine with those who reported adverse events showed no statistically significant differences in current age (7 vs 5.7 years), age at vaccination (3 vs 2.5 years), or T-cell subset counts: CD3 (1951 vs 2083 cells/ L), CD4 (1283 vs 1463 cells/ L), and CD8 (530 vs 502 cells/ L). Fifty-two of 59 responders were vaccinated with measles-mumps-rubella (MMR). Twelve (23%) of 52 reported mild side effects, including fever, rash, and constitutional symptoms. No severe adverse reactions were reported. No patient reported natural disease with measles, mumps, or rubella. There were no statistically significant differences between the T-cell counts in the vaccinated group reporting side effects versus the vaccinated group without side effects (mean CD3 counts: 1928 vs 1736 cells/ L; CD4 counts: 1250 vs 1127 cells/ L; and CD8 counts: 528 vs 483 cells/ L). In our study, patients with chromosome 22q11.2 deletion syndrome had a similar incidence of adverse effects with varicella and MMR vaccines compared with that reported in the general population. All side effects were mild. However, in patients who did not receive the varicella vaccine, an overwhelming 63% contracted the disease. Patients who were not vaccinated against MMR did not develop natural disease. The data suggest that this is a cohort of patients with 22q11.2 deletion syndrome who have tolerated live viral vaccinations without evidence of significant side effects. A prospective study could address whether there are T-cell thresholds below which vaccination is unsafe; however, the information that we present suggests that vaccinating children with chromosome 22q11.2 deletion with live viral vaccines does not carry a significantly higher risk of adverse reactions compared with the general population, provided that they have no evidence of severe immunocompromise. Pediatrics 2003;112:e325–e327. URL: http://www.pediatrics.org/cgi/content/full/112/4/e325; immunodeficiency, T lymphocytes, adverse events, varicella, MMR. ABBREVIATION. MMR, measles-mumps-rubella. Live attenuated viral vaccines are a part of routine childhood immunizations and over the years have proved their safety and efficacy in the general population. Mild adverse effects of measles-mumps-rubella (MMR) vaccination include fever, rash, and lymphadenopathy and occur in approximately 5% to 15% of vaccine recipients.1,2 Similarly, side effects of the varicella vaccine include injection site reactions, fever, and rash, which occur in 5% to 30% of individuals.3–5 Severe side effects are exceedingly rare with both vaccinations.5,6 The package inserts for both the varicella and MMR vaccines warn against use in patients with any form of cellular or humoral immunodeficiency. However, the most recent Advisory Committee on Immunization Practices allows the use of varicella vaccine in patients with a humoral immunodeficiency as well as in patients with human immunodeficiency virus with age-specific CD4 count 25%.4 No published guidelines exist for the administration of these vaccines to patients with chromosome 22q11.2 deletion syndrome.7 This syndrome is associated with thymic hypoplasia and diminished T-cell numbers and has a wide spectrum of phenotypic features that include cardiac anomalies, dysmorphic facial features, and hypocalcemia.8,9 Patients generFrom the *Division of Allergy and Immunology and the ‡Division of Clinical Genetics at Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and the §Division of Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Received for publication Apr 16, 2003; accepted Jun 13, 2003. Address correspondence to Kathleen E. Sullivan, MD, PhD, Division of Allergy and Immunology, Children’s Hospital of Philadelphia, 3400 Civic Center Blvd, Philadelphia, PA 19104. E-mail: [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 2003 by the American Academy of Pediatrics. http://www.pediatrics.org/cgi/content/full/112/4/e325 PEDIATRICS Vol. 112 No. 4 October 2003 e325 by guest on September 23, 2017 http://pediatrics.aappublications.org/ Downloaded from ally exhibit a mild to moderate decrement in T-cell numbers with preservation of T-cell function.10 Thus, patients with chromosome 22q11.2 deletion syndrome are at risk for disease from attenuated vaccine-strain virus and from wild-type viral infection. The aims of this study were to investigate the incidence of side effects after live viral vaccine administration in a population with chromosome 22q11.2 deletion syndrome. The high frequency of this syndrome in the population (1:3000 children) mandates a greater understanding of the risks and benefits related to live viral vaccine administration in this population.11