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

Perez, Elena E.; Bokszczanin, Aleksandra; McDonald‐McGinn, Donna M.; Zackai, Elaine H.; Sullivan, Kathleen E.

doi:10.1542/peds.112.4.e325

Cited by 89 publications

(75 citation statements)

References 6 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[13][14][15] Few serious events were temporally associated with live vaccination, and none were assessed to be causally associated with live vaccination. These data are consistent with earlier studies 10,11,16,17 and suggest that live vaccines may be given safely to some patients with DGS. The benefits of MMR and varicella vaccination, in particular, appear to outweigh the potential risks for patients with DGS with mild-tomoderate immunosuppression.…”

Section: Discussionsupporting

confidence: 91%

“…10 Another study reported higher rates of varicella illness among unvaccinated patients with DGS, which could reflect greater disease exposure, lower vaccine uptake, or less herd immunity. 11,33 In our study, the paucity of severely immunosuppressed subjects could explain why there were relatively few AEFLIs despite high vaccination coverage. In support of this, patients with an AE after varicella vaccination had lower preceding CD4% (24.8%) versus those who did not (35.5%).…”

Section: Discussionmentioning

confidence: 70%

“…Of the latter, nearly 40% received MMR and/or varicella vaccines by 18 months of age. Nonetheless, AEFLIs were typically minor, as shown in smaller studies of subjects with DGS 10,11,16,17 and the general population. [13][14][15] Few serious events were temporally associated with live vaccination, and none were assessed to be causally associated with live vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…5 Most patients with DGS have mild-to-moderate immunosuppression (ie, partial DGS); ∼1% have thymic aplasia with severe T-cell deficiency (ie, complete DGS) that may necessitate thymus or bone marrow transplantation. [6][7][8][9] Patients with DGS are at increased risk of recurrent and/or prolonged viral infections, including vaccine-preventable infections (eg, varicella), 10,11 and secondary bacterial infections. 7 Live vaccines are generally contraindicated in individuals with severe cellmediated immunodeficiency, such as complete DGS, yet may be considered in those with less-severe T-cell immunodeficiencies, such as partial DGS.…”

mentioning

confidence: 99%

“…12,13 Earlier small retrospective studies revealed that many patients with DGS received measlesmumps-rubella (MMR) and varicella vaccines. 10,11 No serious adverse events (AEs) were reported after vaccination, although power was limited; 9% to 23% experienced minor AEs, comparable to rates seen in the general population. [13][14][15] Two small prospective studies similarly demonstrated that 7% to 21% of patients with DGS experienced minor AEs after MMR vaccination.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Live Vaccine Use and Safety in DiGeorge Syndrome

et al. 2014

View full text Add to dashboard Cite

WHAT'S KNOWN ON THIS SUBJECT: Individuals with DiGeorge syndrome (DGS) have varying degrees of immunodeficiency. All are susceptible to vaccine-preventable infections with serious complications. Although live vaccines are generally contraindicated in this population, limited evidence suggests that they may be effective and safe for select individuals.WHAT THIS STUDY ADDS: Many individuals with DGS received live vaccines despite having a known diagnosis. Adverse events following live immunizations were typically minor and self-limited, suggesting that live vaccines may be considered for patients with DGS who exhibit mild-to-moderate immunosuppression. abstract OBJECTIVE: Live vaccines are generally contraindicated in patients with DiGeorge syndrome (DGS), a congenital disorder characterized by cellular immune deficiency. Vaccine utilization and safety in this population are not well described. This study examined vaccination patterns and adverse events following live immunization (AEFLI) in these individuals. METHODS:A multicenter retrospective cohort study was conducted in subjects with DGS confirmed by fluorescence in situ hybridization assay (chromosome 22q11.2 microdeletion). Live vaccine-preventable illnesses, vaccination coverage and timeliness, and AEFLIs in the 56-day window after live vaccination were examined. Bivariate and multivariable analyses assessed the impact of demographics medical history, timing of diagnostic confirmation, and preceding immune function on vaccination patterns and AEFLIs.RESULTS: Of 194 subjects, 77% and 75% received measles-mumps-rubella (MMR) and varicella vaccines, respectively; 58% completed recommended vaccinations by age 19 to 35 months. Adverse events occurred after 14% and 20% of MMR and varicella vaccine doses, respectively. Most events were minor, few were serious, and no deaths were reported in post-live vaccination windows. Although early diagnostic confirmation negatively affected live vaccination coverage and timeliness (P , .001), baseline CD4% did not differ between subjects who did or did not receive live vaccines by 12 to 18 months. Among varicella vaccine recipients, those with a subsequent adverse event had a lower preceding CD4% (24.8% 6 7.3%) than those without (35.5% 6 11.7%) (P , .05); no CD4% differences were observed with MMR vaccination. Fourteen unvaccinated subjects experienced live vaccine-preventable illnesses.CONCLUSIONS: Live vaccines were frequently given and generally welltolerated among patients with DGS with mild-to-moderate immunosuppression.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Live Vaccine Use and Safety in DiGeorge Syndrome

et al. 2014

View full text Add to dashboard Cite

show abstract

The immune deficiency of chromosome 22q11.2 deletion syndrome

Morsheimer

Whitehorn

Heimall

et al. 2017

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

The syndrome originally described by Dr. Angelo DiGeorge had immunodeficiency as a central component. When a 22q11.2 deletion was identified as the cause in the majority of patients with DiGeorge syndrome, the clinical features of 22q11.2 deletion syndrome became so expansive that the immunodeficiency became less prominent in our thinking about the syndrome. This review will focus on the immune system and the changes in our understanding over the past 50 years. Initially characterized as a pure defect in T cell development, we now appreciate that many of the clinical features related to the immunodeficiency are well downstream of the limitation imposed by a small thymus. Dysfunctional B cells presumed to be secondary to compromised T cell help, issues related to T cell exhaustion, and high rates of atopy and autoimmunity are aspects of management that require consideration for optimal clinical care and for designing a cogent monitoring approach. New data on atopy are presented to further demonstrate the association.

show abstract

22q and two: 22q11.2 deletion syndrome and coexisting conditions

Cohen

Crowley

McGinn

et al. 2018

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

22q11.2 deletion syndrome (DS) is the most frequent copy number variant (CNV) affecting ~1/1,000 fetuses and ~1/2,000–4,000 children, resulting in recognizable but variable findings across multiple organ systems. Patients with atypical features should prompt consideration of coexisting diagnoses due to additional genome-wide mutations, CNVs, or mutations/CNVs on the other allele, unmasking autosomal recessive conditions. Importantly, a dual diagnosis compounds symptoms and impacts management. We previously reported seven patients with 22q11.2DS and: SCID, Trisomy 8 mosaicism, Bernard-Soulier, and CEDNIK syndromes. Here we present six additional unreported patients with 22q11.2DS and concurrent diagnoses. Records on 1,422 patients with 22q11.2DS, identified via FISH, microarray, or MLPA, followed in our 22q and You Center at the Children’s Hospital of Philadelphia (CHOP) were reviewed to identify a dual diagnosis. In addition to our seven previously reported cases, we identified an additional six with 22q11.2DS and another coexisting condition identified via: molecular/cytogenetic studies, newborn screening, coagulation factor studies, or enzyme testing; these include CHARGE syndrome (CHD7 mutation), cystic fibrosis, a maternally inherited 17q12 deletion, G6PD deficiency, von Willebrand disease, and 1q21.1 deletion, resulting in an incidence of dual diagnoses at our center of 0.9%. The range of dual diagnoses identified in our cohort is notable, medically actionable, and may alter long-term outcome and recurrence risk counseling. Thus, our findings may support testing patients with 22q11.2DS using a combination of microarray, mutational analysis of the other allele/WES, to ensure appropriate personalized care, as formulating medical management decisions hinges on establishing the correct diagnoses in their entirety.

show abstract

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

Cited by 89 publications

References 6 publications

Live Vaccine Use and Safety in DiGeorge Syndrome

Live Vaccine Use and Safety in DiGeorge Syndrome

The immune deficiency of chromosome 22q11.2 deletion syndrome

22q and two: 22q11.2 deletion syndrome and coexisting conditions

Contact Info

Product

Resources

About