Combined immunodeficiency and atopy caused by a dominant negative mutation in caspase activation and recruitment domain family member 11 (CARD11).

BACKGROUND: Combined immunodeficiency (CID) is a T-cell defect frequently presenting with recurrent infections, as well as associated immune dysregulation manifesting as autoimmunity or allergic inflammation. OBJECTIVE: We sought to identify the genetic aberration in 4 related patients with CID, early-onset asthma, eczema, and food allergies, as well as autoimmunity. METHODS: We performed whole-exome sequencing, followed by Sanger confirmation, assessment of the genetic variant effect on cell signaling, and evaluation of the resultant immune function. RESULTS: A heterozygous novel c.C88T 1-bp substitution resulting in amino acid change R30W in caspase activation and recruitment domain family member 11 (CARD11) was identified by using whole-exome sequencing and segregated perfectly to family members with severe atopy only but was not found in healthy subjects. We demonstrate that the R30W mutation results in loss of function while also exerting a dominant negative effect on wild-type CARD11. The CARD11 defect altered the classical nuclear factor κB pathway, resulting in poor in vitro T-cell responses to mitogens and antigens caused by reduced secretion of IFN-γ and IL-2. CONCLUSION: Unlike patients with biallelic mutations in CARD11 causing severe CID, the R30W defect results in a less profound yet prominent susceptibility to infections, as well as multiorgan atopy and autoimmunity.

Pediatric Wells syndrome (eosinophilic cellulitis) after vaccination: A case report and review of the literature.

A 4-year-old boy presented with erythematous vesicular plaques, ulceration, edema, and pruritus on the left foot and ankle 10 days after receiving the tetanus, diphtheria, pertussis, and polio; measles, mumps, rubella, and varicella; and hepatitis A/B vaccines. Biopsy showed eosinophilic infiltrates and flame figures, suggesting Wells syndrome. Patch testing showed a 1+ reaction to neomycin and aluminum hydroxide, with a recall reaction of Wells syndrome of the feet bilaterally. We report a rare case of pediatric Wells syndrome triggered by nonthimerosal vaccine components confirmed by patch testing.

Evaluation of immediate allergic reactions to cephalosporins in non-penicillin-allergic patients.

BACKGROUND: Cephalosporins can induce severe or life-threatening IgE-mediated reactions in some individuals. In this study, we wish to describe a group of non-penicillin-allergic patients who were evaluated for immediate allergic reactions to cephalosporins. METHODS: The patients were assessed by skin tests with the culprit cephalosporin as well as with other cephalosporins and penicillins. If indicated, oral challenge testing was performed. RESULTS: Six patients were assessed. A total of 42 skin tests and 20 oral challenges were performed. In 4 patients, skin tests included the causative drug; in 2 patients, the diagnosis of a cephalosporin allergy was made by skin test; in 4 patients, the diagnosis of a cephalosporin hypersensitivity was made by oral challenge. In 96.9% of the oral challenges, which were done using medications with no structural side chain similarities to the culprit drug, no adverse reaction occurred. CONCLUSION: A positive skin test to cephalosporin implies the presence of drug-specific IgE antibodies. Cephalosporins without side chain similarities are suggested to patients with cephalosporin reactions and no beta-lactam reactivity.

Vaccine-strain varicella zoster virus causing recurrent herpes zoster in an immunocompetent 2-year-old.

Varivax III is a live attenuated vaccine against varicella zoster virus (VZV). We report a case of recurrent vaccine-strain herpes zoster in an immunocompetent 2-year-old child. Vaccine-strain VZV was identified through polymerase chain reaction. This report aims to alert physicians that recurrent vaccine-strain herpes zoster can be a rare complication of VZV vaccination in apparently immunocompetent hosts.

Prospective evaluation of testing with baked milk to predict safe ingestion of baked milk in unheated milk-allergic children.

BACKGROUND: Cow's milk allergy is one of the most common food allergies affecting young children. A subset of milk-allergic individuals can eat baked milk without allergic symptoms which is beneficial in terms of prognostication and liberalization of the diet. A retrospective study suggested that skin prick testing (SPT) with a baked milk (muffin) slurry may provide a sensitive means of predicting the outcome of a medically supervised baked milk oral food challenge. We evaluated the predictive value of SPT with baked milk to identify unheated milk-allergic children who are able to safely eat baked milk. METHODS: Children aged 2-16 years with a prior history of reaction to milk and a milk extract SPT of 8-14 mm were recruited. Investigator-blinded SPT to muffin slurry and powdered milk in triplicate and specific IgE (sIgE) to casein and milk were performed. Graded oral challenge to egg-free baked milk muffins (total 2.6 gm milk protein) was performed in the hospital. Reliability of tests was analyzed for intraclass correlation. Statistical significance for clinical characteristics of population and muffin testing versus baked milk reactivity was calculated with Fisher exact test for dichotomous and t-test for continuous variables. Wilcoxon rank sum test was used to compare immunological characteristics between individuals who tolerated or reacted to baked milk. Fitted predicted probability curves and ROC curves were generated. RESULTS: Thirty-eight children were consented and 30 met study criteria. The muffin SPT and casein sIgE were significantly different in those who passed versus failed baked milk challenge. Negative (<3 mm) baked milk tests were found in 8/30 children (27 %) and were associated with non-reactivity to baked milk (p = 0.01) with a sensitivity of 1 (0.70-1.00). All children with negative SPT for baked milk passed the oral challenge. Specificity was 0.41 (0.19-0.67). The optimal decision point for the muffin SPT was 4 mm and the casein sIgE was 6 kU/L. The powdered milk test was not helpful. CONCLUSIONS: Skin prick testing with a baked milk (muffin) slurry may have a role in clinical practice to identify baked milk tolerance in milk-allergic patients.