Removing penicillin allergy label in a hospitalized adolescent with a remote penicillin and recent cephalosporin allergy.

Background: ß-Lactam antibiotics are widely used with increased utilization in hospitalized patients. Of this population, as high as 10-20% report an allergy to ß-lactam antibiotics but <5% are at risk of developing clinically significant immunoglobulin E- or T-lymphocyte-mediated reactions. Most of the time, these reported allergies are present during an illness with no previous inquiry of their validity, which makes investigation and possible removal of this allergy label a challenge. Methods: We report a 16-year-old boy who presented with 1 week of night sweats, chills, headaches, and fatigue, followed by 1 day of fever and right knee swelling and who was diagnosed with septic bursitis. Due to concern of a penicillin allergy label, the patient was started on a cefepime infusion. Five minutes into the infusion, the patient reported puffy eyes and itchy throat, followed by a witnessed cascading flat nonpruritic erythematous rash from head to shoulders. This rash went away in 3 minutes after stopping the infusion and the patient being given 50 mg of intravenous diphenhydramine and 10 mg of oral dexamethasone. He was subsequently diagnosed with a cefepime allergy. Results: Allergy/immunology was the speciality consulted, and, by using a screening questionnaire, the patient's reported penicillin allergy was determined to be low risk. Subsequent 1-step oral challenge was the key to providing the patient with the necessary antibiotic course to resolve his infection. Conclusion: Multiple reported antibiotic allergies lead to poor antibiotic stewardship that causes impactful health and financial burden on the patient and health-care system. It is thus important to have an evidence-based systematic approach to de-label penicillin antibiotic allergy labels to reduce these potential harms.

Pearls and pitfalls: Cold-induced urticaria.

Background: Cold-induced urticaria can take place either due to direct cold exposure, cryoglobulinemia, or genetic component (such as cryopyrin-associated periodic syndrome), which leads to the rapid onset of urticaria and/or angioedema. It is more common in younger patients and more likely to affect females compared with males. Objective: To increase awareness of such systemic reactions of anaphylaxis and provide a focused review of the differential diagnosis, underlying mechanisms, broad workup, and management of this disease process for allergy/immunology fellows, residents, general physicians, and general practitioners. Methods: Pertinent information was included from the patient's clinical course. Also, a review of the available literature to include additional references that were obtained by using the works cited in the most up-to-date reviews was completed. Results: A case of a patient with cold-induced urticaria with common sequela was presented, followed by a discussion of the pathophysiology, diagnosis and its differential diagnosis, workup, and management. Conclusion: Cold-induced urticaria is a complex disease with several different catalysts. Providers should be aware of the different forms of cold-induced urticaria and recognize the risk for anaphylaxis in this patient population. Pearls and pitfalls of the diagnosis and management are provided.

Evaluating Penicillin Allergies Without Skin Testing.

PURPOSE OF REVIEW: An unconfirmed penicillin allergy is known to confer significant risk to patients. Only a small minority of patients labeled with penicillin allergy will be confirmed to be hypersensitive with the current reference standard test, an oral amoxicillin therapeutic dose challenge. Skin testing has been recommended prior to oral challenges to reduce the risk of severe acute challenge reactions. The rate of severe acute anaphylactic reactions with oral amoxicillin is currently extremely low. Unfortunately, penicillin skin testing, as commonly performed, has a high rate of false positive results. RECENT FINDINGS: Encouraging skin testing in all individuals with an unconfirmed penicillin allergy, prior to a confirmatory oral challenge, would be technically difficult, make testing all individuals with an unconfirmed penicillin allergy very unlikely, and ultimately increase the risk to patients because of suboptimal antibiotic use. Most patients, who are appropriate candidates for a direct oral amoxicillin challenge, to confirm current penicillin tolerance, can be safely identified by their clinical histories. Higher risk individuals, those with a history of anaphylaxis or other acute onset potentially IgE-mediated reaction such as hives within 6 h of the first dose of the last course of a penicillin, may benefit from properly performed puncture and intradermal skin testing, using commercially available penicilloyl-polylysine, prior to an oral challenge, if skin test negative. Direct oral amoxicillin challenges in low-risk individuals are well accepted by patients and a safe and effective part of penicillin allergy delabeling.

Environmental Exposures and Asthma in Active Duty Service Members.

PURPOSE OF REVIEW: Reports of respiratory symptoms, including asthma and hyper-reactive airway disease, have been more numerous in the media and medical literature since active duty service members (SM) began to support campaigns in South West Asia (SWA). Numerous environmental exposures have been reported and this review assesses the available evidence surrounding exposures, confounding conditions, and attempts to develop screening mechanisms. RECENT FINDINGS: While particulate matter exposures and particularly exposure to burn pits have garnered much attention, a 2010 Armed Forces Health Surveillance Center report and 2011 Institute of Medicine publication did not identify a link between exposure to particulate matter with SM respiratory disease. The "Study of Active Duty Military for Pulmonary Disease related to Environmental Deployment Exposure," (STAMPEDE) and STAMPEDE II have not identified effective forms of routine screening and these and other sources point to the importance of other factors in SM respiratory disease. These include higher than anticipated rates of tobacco use in deployed settings, impacts of obesity, recurrence of childhood asthma, and of confounding conditions such as Paradoxical Vocal Fold Motion. As with the general population, a complex set of clinical inputs and environmental exposures surround asthma and similar respiratory processes in SM. Concrete relationships and mechanisms for assessment continue to be assessed and refined, but clear associations and pathways have remained elusive.

Pearls and pitfalls: Autoimmune lymphoproliferative syndrome and autoimmune lymphoproliferative syndrome-like disease.

A case of autoimmune lymphoproliferative syndrome (ALPS) was presented, followed by a discussion of the clinical characteristics, pathophysiology, diagnosis, and management of this disease. Clinical pearls and pitfalls are emphasized for the use of the practicing allergist and the fellow in-training. The diagnosis of ALPS was guided by published criteria. A careful history and workup were needed to exclude other possible etiologies for the patient's symptoms and physical findings. ALPS often carries significant morbidity and is best managed through a multidisciplinary approach.

Allergy-immunology practice parameters and strength of recommendation data: an evolutionary perspective.

BACKGROUND: The practice parameters for allergy and immunology (A/I) are a valuable tool guiding practitioners' clinical practice. The A/I practice parameters have evolved over time in the context of evidence-based medicine milestones. OBJECTIVES: To identify evolutionary trends in the character, scope, and evidence underlying recommendations in the A/I practice parameters. METHODS: Practice parameters that have guided A/I from 1995 through 2014 were analyzed. Statements and recommendations with strength of recommendation categories A and B were considered to have a basis in evidence from controlled trials. RESULTS: Forty-three publications and updates covering 25 unique topics were identified. There was great variability in the number of recommendations made and the proportion of statements with controlled trial evidence. The mean number of recommendations made per practice parameter has decreased significantly, from 95.8 to a mean of 38.3. There also is a trend toward an increased proportion of recommendations based on controlled trial evidence in practice parameters with fewer recommendations, with a mean of 30.7% in practice parameters with at least 100 recommendations based on controlled trial evidence compared with 48.3% in practice parameters with 30 to 100 recommendations and 51.0% in those with fewer than 30 recommendations. CONCLUSION: The A/I practice parameters have evolved significantly over time. Encouragingly, greater controlled trial evidence is associated with updated practice parameters and a recent trend of more narrowly focused topics. These findings should only bolster and inspire confidence in the utility of the A/I practice parameters in assisting practitioners to navigate through the uncertainty that is intrinsic to medicine in making informed decisions with patients.

Drug reaction with eosinophilia and systemic symptoms syndrome.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening adverse drug reaction. OBJECTIVE: To increase awareness of the potential for recurrence in patients with a history of DRESS syndrome and provide a brief review of the clinical characteristics, diagnosis, and management of this disease process. METHODS: The authors selected and reviewed salient articles on the topic and incorporated pertinent information from the patient's clinical course. RESULTS: A case of recurrent DRESS triggered by a structurally unrelated drug is presented, followed by discussion of the clinical characteristics, diagnosis, and management. Clinical pearls and pitfalls are emphasized for the practicing allergist, clinical immunologist, and fellow-in-training. CONCLUSIONS: The most important steps in the treatment of this condition are the identification and removal of the offending agent. Providers should be aware of the potential for recurrent DRESS and recognize the importance of prompt management.

Practice parameters and strength of recommendation data: a variable compass.

BACKGROUND: Practice parameters and guidelines shape and influence the method and manner in which medicine is practiced. With more than 121 scales and methods of assessing and rating evidence, a comparison of practice parameters can appear daunting. An evaluation of the evidence engenders a sense of the evolution of a specialty and a roadmap for the future. OBJECTIVE: To assess the level of evidence underlying recommendations in allergy-immunology (AI) practice parameters. METHODS: We analyzed the practice parameters that guide AI (n = 15), otolaryngology (n = 8), pediatrics (n = 13), and internal medicine (n = 10) as they appeared on August 30, 2012. Strength of recommendation data was compared after making adjustments for differences in rating scales. RESULTS: The strength of recommendation calculated from strong to weak for the AI practice parameters using a standardized format yielded the following grades: A in 195 (13.9%), B in 342 (24.4%), C in 606 (43.2%), D in 231 (16.4%), and E in 29 (2.1%). Controlled trial-based evidence (A and B) demonstrated considerable variability among individual AI practice parameters (range, 1.3%-100%). Evidence from controlled trials was lower in the subspecialty fields (38.3% in AI and 38.2% in otolaryngology) compared with the primary care fields (55.6% in pediatrics and 86.1% in internal medicine). CONCLUSION: Considerable variability exists in the strength of recommendations within the AI practice parameters. The guidelines created by the primary care fields rest on a larger base of evidence collected from controlled trials. These findings likely reflect the adopted approach of making recommendations for less well-studied conditions and practices in AI to assist practitioners and patients and at the same time highlight the myriad opportunities for future research.

Silver clusters as both chromophoric reporters and DNA ligands.

Molecular silver clusters conjugated with DNA act as analyte sensors. Our studies evaluate a type of cluster-laden DNA strand whose structure and silver stoichiometry change with hybridization. The sensor strand integrates two functions: the 3' region binds target DNA strands through base recognition while the 5' sequence C(3)AC(3)AC(3)TC(3)A favors formation of a near-infrared absorbing and emitting cluster. This precursor form exclusively harbors an ∼11 silver atom cluster that absorbs at 400 nm and that condenses its single-stranded host. The 3' recognition site associates with a complementary target strand, thereby effecting a 330 nm red-shift in cluster absorption and a background-limited recovery of cluster emission at 790 nm. One factor underlying these changes is sensor unfolding and aggregation. Variations in salt and oligonucleotide concentrations control cluster development by influencing DNA association. Structural studies using fluorescence anisotropy, fluorescence correlation spectroscopy, and size exclusion chromatography show that the sensor-cluster conjugate opens and subsequently dimerizes with hybridization. A second factor contributing to the spectral and photophysical changes is cluster transformation. Empirical silver stoichiometries are preserved through hybridization, so hybridized, dimeric near-infrared conjugates host twice the amount of silver in relation to their violet absorbing predecessors. These DNA structure and net silver stoichiometry alterations provide insight into how DNA-silver conjugates recognize analytes.

Atrophic rhinitis.

A case of atrophic rhinitis complicated by nasal septum perforation is presented, followed by a discussion of the clinical characteristics, pathophysiology, diagnosis, and management of this disease process. Clinical pearls and pitfalls are emphasized for the use of the practicing allergist and fellow in-training. The diagnosis of atrophic rhinitis is guided by a careful clinical history and evaluation to exclude other possible etiologies for the patient's symptoms and physical findings. Because atrophic rhinitis is a poorly understood process, it is surrounded by considerable contention in the literature and its management is not well defined. Atrophic rhinitis often carries significant morbidity and is best addressed by a multidisciplinary approach.

Cross-reactivity and masqueraders in seafood reactions.

Confounding variables play a significant role in many adverse seafood reactions and a clear understanding of these factors is important in properly characterizing reactions associated with potential masqueraders and mimics. Although the medical literature is replete with reviews of seafood hypersensitivity and reports of cross-reactive and newly characterized allergens, there has not been a recent effort to provide an updated overview of the several processes that may lead clinicians to draw incorrect conclusions in evaluating reported reactions to seafood. Ranging from seafood intoxications to other nonallergic or complex seafood reactions, these events can easily be misconstrued as representing a seafood IgE-mediated allergy. Among these are the more familiar topics of cross-reactivity and scombroid intoxication, and those with a still evolving understanding such as ciguatera fish poisoning and Anisakis reactions. This article seeks to provide an accessible but comprehensive summary of the relevant information surrounding these confounders in assessing adverse reactions to seafood. Such knowledge may be instrumental in unraveling complex or otherwise unclear presentations and aid clinicians in accurately evaluating and managing patients with reported seafood reactions.

A Case of Refractory Eosinophilic Gastrointestinal Disease Successfully Treated With Dupilumab.

Eosinophilic infiltration of the gastrointestinal (GI) tract beyond the esophagus is a rare condition in adults with limited data on treatment. Current treatments with steroids and diet modifications have shown benefit, but when these treatments fall short, there is little research-driven guidance for further recommendations. We present a case of eosinophilic GI disease with extensive involvement of the GI tract successfully treated with dupilumab after failure of traditional treatment occurred.

Allergen Immunotherapy Extract Shortages and Their Effects on Clinical Care: A Work Group Report of the AAAAI Immunotherapy, Allergen Standardization, and Allergy Diagnostics Committee.

Allergen immunotherapy (AIT) is the only disease-modifying therapy indicated for treatment of allergic asthma, rhinitis, conjunctivitis, and Hymenoptera hypersensitivity. Manufacturing of the extracts used in AIT involve multistep complex processes as well as regulatory oversight. Furthermore, some source materials are vulnerable to unexpected events of nature. Given these circumstances, allergen extract supply can be disrupted with a potential to adversely impact patient care. A group of members from the American Academy of Allergy, Asthma, and Immunology (AAAAI) Immunotherapy, Allergy Standardization and Allergy Diagnostic Committee formed a workgroup to assess the frequency and effects of allergen extract shortages and associated factors. This workgroup developed a survey that was distributed to a random 20% of the AAAAI membership. In addition, the group also performed a review of the scientific literature on allergen extract supply and shortage. Based on the findings of the survey study and literature review, the workgroup reports frequency and extent of shortages, potential ways to improve communication with suppliers, and need for further guidance in patient care during times of shortage.

The use of dried blood spot cards to assess serologic responses of individuals vaccinated against measles, hepatitis A, tetanus, influenza and varicella zoster.

Traditional blood sampling by venipuncture is cumbersome and relatively expensive. Dried blood spot (DBS) sampling is desirable because of its ease of sample collection, transportation and storage. It has been used in clinical diagnosis but not been thoroughly studied for the potential use to assess the immune status of individuals following natural infection or preventive vaccination. The goal of this study was to compare DBS to traditional blood samplings in detection of antibodies in individuals vaccinated against measles, hepatitis A, tetanus, influenza and varicella zoster. Enzyme linked immunosorbent assay (ELISA) was used to test DBS eluates and serum samples for antibodies against measles, varicella, tetanus and hepatitis A. Sensitivities, specificities, and correlation coefficients were evaluated to compare optical density (OD) values of paired serum and DBS samples. The long-term stability of DBS samples at different temperatures was assessed using simulated immune measles blood. DBS OD was highly correlated with serum OD for antibodies to measles (r = 0.93), varicella (r = 0.82), and tetanus (r = 0.91). Sensitivities of DBS OD ranged from 86-99% and specificities ranged from 96-100% using cut-offs established by each assay. By contrast, the hepatitis A data showed a low sensitivity (31%) and weak correlation (r = 0.14) between DBS and serum samples. Antibody titers in serum samples for anti-influenza A (H1N1 and H3N1) failed to correlate in DBS eluates in HAI and MN assays. DBS samples were stable for 4 weeks when stored at room temperature and for 6 months at 4°C. DBS sampling was sensitive, specific, and highly correlated with traditional venipuncture sampling in detection of antibodies against measles, tetanus and varicella zoster, but not hepatitis A and influenza. Thus, the success of using DBS sampling to assess the antibody levels in immunized individuals may be dependent on the pathogens and the development of the assay used.

Multisite evaluation of fire ant venom immunotherapy safety and efficacy.

Background: Imported fire ant (IFA) venom immunotherapy (VIT) is the only disease-modifying treatment reported to be effective at decreasing the risk of systemic reactions (SRs) to IFA stings. Objective: Our aims were to determine the baseline rates of IFA sensitization in subjects, describe IFA VIT prescribing patterns across the military health system (MHS), and retrospectively evaluate the safety and efficacy of IFA VIT. Methods: We prospectively compared IFA sensitization in participants with and without an SR to flying Hymenoptera venom. Separately, IFA VIT prescription records were extracted from a centralized repository, and rates were described across the MHS. Additionally, we retrospectively reviewed the clinical course of patients being treated with IFA VIT at 11 military treatment facilities. Results: The in vitro IFA sensitization rates in our prospective cohort ranged from 19.1% to 24.1%. Sensitization rates did not differ statistically between the subjects with or without an SR to flying Hymenoptera venom. We found that 60.9% of all MHS IFA VIT prescriptions (491 of 806) were from the 11 facilities in this study. We retrospectively identified 137 subjects actively undergoing IFA VIT. Among the subjects actively undergoing IFA VIT, 28 reported an SR to IFA venom and repeat stings by IFAs after reaching VIT maintenance, and 85.7% (24 of 28) of the subjects noted symptoms no worse than a large swelling reaction after a repeat IFA sting. Notably, only 2.9% of the subjects (4 of 137) had an SR due to VIT. Conclusion: This study's results align with those of prior IFA sensitization reports. A substantial proportion of patients undergoing IFA VIT experienced protection against anaphylaxis with reexposure, with relatively few adverse events.