Miguel A. Park

Common variable immunodeficiency: a new look at an old disease

Primary immunodeficiencies comprise many diseases caused by genetic defects primarily affecting the immune system. About 150 such diseases have been identified with more than 120 associated genetic defects. Although primary immunodeficiencies are quite rare in incidence, the prevalence can range from one in 500 to one in 500 000 in the general population, depending on the diagnostic skills and medical resources available in different countries. Common variable immunodeficiency (CVID) is the primary immunodeficiency most commonly encountered in clinical practice, and appropriate diagnosis and management of patients will have a significant effect on morbidity and mortality as well as financial aspects of health care. Advances in diagnostic laboratory methods, including B-cell subset analysis and genetic testing, coupled with new insights into the molecular basis of immune dysfunction in some patients with CVID, have enabled advances in the clinical classification of this heterogeneous disease.

Allergen immunotherapy safety: Characterizing systemic reactions and identifying risk factors

Systemic reactions (SRs) pose a risk to those treated with subcutaneous allergen immunotherapy (AIT). The goals of the study were to calculate a rate of SRs to AIT, characterize the timing and treatment of these SRs, and analyze a case-control sample of patients for putative SR risk factors. A case-control study based on a retrospective chart review from 2004 to 2006 at a single institution was performed for patients receiving AIT. A control group received AIT over the same time period but did not have an SR. Three hundred thirty-eight patients had 10,497 AIT injection visits and 25 patients experienced 29 SRs for a rate of 0.28% per injection visit and 7.4% per patient. Gender, phase (build-up versus maintenance), asthma, angiotensin-converting enzyme inhibitors, beta-blockers, initial skin-prick test size, or allergen type did not increase the odds of an SR to AIT. Nearly one-half (48%) of the SRs occurred >30 minutes after the injection. All five patients with an abnormal physical exam or a >20% decrease in peak expiratory flow during their SRs occurred in patients presenting with their SRs >30 minutes after the injection (p = 0.02). This study found a low rate of SRs to AIT. However, a high percentage of SRs occurred >30 minutes after the injection, and many of these SRs required epinephrine. This study was unable to identify specific risk factors that predict SRs to AIT.

Preoperative evaluation of patients with history of allergy to penicillin: Comparison of 2 models of practice

OBJECTIVE To study whether allergy consultation and penicillin allergy skin testing affects the selection of antibacterial prophylaxis perioperatively in surgical patients with history of allergy to penicillin (HOAP). PATIENTS AND METHODS From January 1 through June 30, 2004, we compared 2 different models of practice at our institution. At the Preoperative Evaluation Clinic (POEC), all patients with HOAP are evaluated by an allergist and undergo skin testing for allergy to penicillin. At other (non-POEC) preoperative evaluation settings (OPES), patients with HOAP do not undergo allergy consultation and penicillin skin testing before surgery. Of the 4889 patients screened at the POEC during the study period, 412 consecutive patients with HOAP were included in the study. Of the 416 patients screened at OPES, 69 consecutive patients with HOAP were studied. Logistic regression was used to assess whether allergy consultation was associated with the choice of antibiotic for antibacterial prophylaxis perioperatively, after adjusting for age, sex, and type of surgery. RESULTS Perioperative cephalosporin use was greater among patients screened at POEC vs those screened at OPES (70% vs 39%, P<.001 unadjusted; P=.04 adjusted for age, sex, and type of surgery). Vancomycin use was lower for patients screened at POEC vs those screened at OPES (10% vs 28%, P<.001 unadjusted; P=.03 adjusted). CONCLUSION For patients with HOAP, evaluation at the POEC was associated with increased use of cephalosporin and decreased use of vancomycin.

Outcomes of Allergy/Immunology Follow-Up After an Emergency Department Evaluation for Anaphylaxis

BACKGROUND Anaphylaxis guidelines currently recommend referring patients with anaphylaxis seen in the emergency department (ED) to an allergist for follow up. OBJECTIVE The objective of our study was to evaluate outcomes of allergy/immunology follow-up after an ED visit for anaphylaxis. METHODS A retrospective health records review was conducted from April 2008 to August 2012. Charts were reviewed independently by 2 allergists to determine outcomes. Descriptive statistics with corresponding 95% CIs were calculated. RESULTS Among 573 patients seen in the ED who met anaphylaxis diagnostic criteria, 217 (38%) had a documented allergy/immunology follow-up. After allergy/immunology evaluation, 16 patients (7% [95% CI, 5%-12%]) had anaphylaxis ruled out. Among those with an unknown ED trigger (n = 74), 24 (32% [95% CI, 23%-44%]) had a trigger identified; and, among those who had a specific suspected ED trigger (n = 143), 9 (6% [95% CI, 3%-12%]) had a trigger identified in a category other than the one suspected in the ED, and 28 (20% [95% CI, 14%-27%]) had an unknown trigger. Thus, there were a total of 77 patients (35% [95% CI, 29%-42%]) who had an alteration in the diagnosis of anaphylaxis or trigger after allergy/immunology evaluation. Four patients (2% [95% CI, 0.7%-4.6%]) were diagnosed with a mast cell activation disorder, and 13 patients (6% [95% CI, 4%-10%]) underwent immunotherapy or desensitization. CONCLUSION Overall, 35% of the patients with suspected anaphylaxis in the ED had an alteration in the diagnosis or suspected trigger after allergy/immunology evaluation. These results underscore the importance of allergy/immunology follow-up after an ED visit for anaphylaxis.

Increased Adverse Drug Reactions to Cephalosporins in Penicillin Allergy Patients with Positive Penicillin Skin Test

Background: Cephalosporin administration in patients with a history of penicillin allergy is controversial. Studies looking at the safety of cephalosporin in patients with a history of penicillin allergy lacked a control group, had a small number of patients, and/or lacked confirmation of penicillin allergy by penicillin skin testing. The purpose of this study was to determine whether patients with penicillin allergy were at increased risk of adverse drug reactions when administered cephalosporin. Methods: A cohort study of patients with a history of penicillin allergy and a positive or negative penicillin skin test when administered cephalosporin was conducted. Charts were reviewed for adverse drug reactions to cephalosporin after penicillin skin testing. Results: Eighty-five patients with a history of penicillin allergy and positive penicillin skin test and 726 patients with a history of penicillin allergy and negative penicillin skin test were administered cephalosporin. Five (6%) of 85 cases had an adverse drug reaction to cephalosporin as compared to 5 (0.7%) of 726 of the referent population (p = 0.0019). The rate of presumed IgE-mediated adverse drug reactions to the cephalosporins amongst the cases was 2 (2%) of 85 compared to 1 (0.1%) of 726 amongst the referent population (p = 0.0304). Conclusion: A greater risk of an adverse drug reaction to cephalosporin exists in patients with penicillin allergy. We recommend penicillin skin testing if cephalosporin, especially a first-generation cephalosporin, is to be administered to patients with a history of penicillin allergy.

Collaboration between allergists and pharmacists increases β-lactam antibiotic prescriptions in patients with a history of penicillin allergy.

Background: Over 90% of patients with a history of penicillin allergy have negative penicillin skin tests. Pharmacists are trained to identify and resolve medication-related problems. We hypothesized that collaboration between allergists and pharmacists to identify and evaluate patients with a history of penicillin allergy would increase β-lactam antibiotic prescription. Methods: We conducted a prospective observational study in which patients with a history of penicillin allergy were identified and educated at the pharmacy about penicillin allergy and offered an allergist consultation with a penicillin skin test. All patients were followed up to determine which antibiotics were subsequently prescribed. Results: A total of 503 patients were enrolled, and 71 (14%) were evaluated by an allergist. Sixty-seven of these 71 patients (94%) had a negative penicillin skin test. Twenty-nine patients evaluated by an allergist and 205 patients not evaluated were prescribed antibiotics. Patients prescribed antibiotics and evaluated by an allergist were compared to those not evaluated by an allergist, with the following results: 19 of 29 patients (66%) were prescribed a β-lactam antibiotic compared to 54 of 205 (26%; p < 0.0001); 8 of 29 patients (28%) were prescribed penicillin compared to 7 of 205 (3%; p < 0.0001); 15 of 29 patients (52%) were prescribed a cephalosporin compared to 48 of 205 (23%; p < 0.01), and 10 of 29 patients (34%) were prescribed a non-β-lactam antibiotic compared with 177 of 205 (86%; p < 0.0001). Conclusion: A collaborative effort between allergists and pharmacists can increase β-lactam antibiotic prescriptions and decrease non-β-lactam prescriptions in patients with a history of penicillin allergy.

Acute Urticaria and Angioedema Diagnostic and Treatment Considerations

Urticaria is defined as wheals consisting of three features: (i) central swelling of various sizes, with or without surrounding erythema; (ii) pruritus or occasional burning sensations; and (iii) the skin returning to normal appearance, usually within 1–24 hours. Angioedema is defined as: (i) abrupt swelling of the lower dermis and subcutis; (ii) occasional pain instead of pruritus; (iii) commonly involving the mucous membranes; and (iv) skin returning to normal appearance, usually within 72 hours. Acute urticaria and angioedema is defined by its duration (<6 weeks) comparedwith chronic urticaria and angioedema. The most common causes are infections, medications, and foods. The best tools in the evaluation of these patients are a comprehensive history and physical examination. There are a variety of skin conditions that may mimic acute urticaria and angioedema and the various reaction patterns associated with different drugs. Oral antihistamines are first-line treatment. In the event of a life-threatening reaction involving urticaria with angioedema, epinephrine may be needed to stabilize the patient. This review focuses on the value of a comprehensive clinical evaluation at the onset of symptoms. It underscores the importance of coordination of care among physicians, and the development of an action plan for evidence-based investigations, diagnosis, and therapy.

Penicillin Skin Testing Is a Safe and Effective Tool for Evaluating Penicillin Allergy in the Pediatric Population

BACKGROUND Penicillin skin testing has been validated in the evaluation of adult patients with penicillin allergy. However, the commercially available benzylpenicilloyl polylysine (Pre-Pen) is not indicated in the pediatric population. Moreover, the safety and validity of penicillin skin testing in the pediatric population has not been well studied. OBJECTIVE We describe the safety and validity of penicillin skin testing in the evaluation of children with a history of penicillin allergy. METHODS Children (<18 years) with a history of penicillin allergy were evaluated with penicillin skin tests and were reviewed for basic demographics, penicillin skin test results, adverse drug reaction to penicillin after penicillin skin test, and adverse reaction to penicillin skin test. By using the χ(2) test, we compared the differences in the proportion of children and adults with a positive penicillin skin test. P value (<.05) was considered statistically significant. The institutional review board approved the study, and all the subjects signed written informed consents. RESULTS A total of 778 children underwent penicillin skin testing; 703 of 778 patients had a negative penicillin skin test (90.4%), 66 had a positive test (8.5%), and 9 had an equivocal test (1.1%). Children were more likely to have a positive penicillin skin test (P < .0001) compared with adults (64 of 1759 [3.6%]); 369 of 703 patients with negative penicillin skin test (52%) were challenged with penicillin, and 14 of 369 patients (3.8%) had an adverse drug reaction. No adverse reactions to penicillin skin testing were observed. CONCLUSION Penicillin skin testing was safe and effective in the evaluation of children with a history of penicillin allergy.

Phenotypic and clinical heterogeneity associated with monoallelic TNFRSF13B-A181E mutations in common variable immunodeficiency

Mutations in the TNFRSF13B (TACI) gene have been reported to be associated with Common Variable ImmunoDeficiency (CVID). Of 48 patients evaluated within the immunodeficiency clinic, 39 had CVID, 6 had symptomatic IgA deficiency (IgAD) with or without IgG2 and IgG4 subclass deficiency, while 3 had unclassified immune dysregulatory disorders. In all 48 patients TACI genetic testing was performed, and monoallelic mutations were observed in 4 of the 39 CVID patients (10.26%), an incidence comparable to other studies. Of the 6 IgAD patients, 1 had a heterozygous TACI mutation (16.67%), while of the 3 unclassified patients, 1 had a monoallelic TACI mutation (33.3%), but his sibling who also had the same mutation had CVID. The A181E mutation is one of the statistically significant, among the known TACI gene mutations. Here, 5 of the 6 patients were found to have the A181E mutation (10.42%), which is higher than previously observed. We also evaluated 114 controls and found the A181E mutation in only 1 individual (0.88%). We report in this study that the A181E mutation is associated with a very heterogeneous clinical presentation along with variability in B-cell numbers and amount of TACI protein on memory B cells.

Outcomes of stepping down asthma medications in a guideline-based pediatric asthma management program

BACKGROUND Little is known about outcomes after stepping down asthma medications within an asthma management program. OBJECTIVE To determine outcomes of stepping down asthma medications in a pediatric asthma management program. METHODS We performed a retrospective study of 5- to 18-year-old children with asthma in an integrated primary care practice in the United States. Data were included on participants from March 1, 2009, until December 31, 2011. We first determined whether a child was eligible for step down and next recorded whether a step-down attempt was made and if the attempt was successful. In addition to descriptive statistics for the sample demographics and the outcomes of stepping down, univariate and multivariate analyses were performed to determine predictors of successful asthma medication step-down attempts. RESULTS Of the 477 children sampled for this study, 264 (55.3%) had a guideline-eligible opportunity to step down asthma medications. An attempted step down occurred in only 89 (33.7%) of children who had guideline-eligible opportunities. A total of 166 children (34.8%) attempted a step down of asthma medication at least once (including those guideline ineligible to step down). Of children with follow-up, 96 (71.6%) of step-down attempts were successful. Time of year (any season except fall) when the step down was attempted predicted successful step down in univariate and multivariate analysis (odds ratio = 3.81; 95% confidence interval, 1.23-11.85; P = .02). Being guideline eligible for step down predicted successful step down in univariate analysis only (odds ratio = 2.51; 95% confidence interval, 1.16-5.43; P = .02). CONCLUSION Our findings from this sample of children participating in an asthma management program suggest that stepping down asthma medication based on National Asthma Education and Prevention Program 3 guidelines is frequently successful.