Drug Allergy Mimics.

When approaching a case of apparent drug allergy, the consulting clinician should consider a broad differential diagnosis. This article presents a series of cases that could be commonly referred to an allergist for assessment as "drug allergy," however, a real diagnosis exists that mandates a different diagnostic and treatment strategy, including a case of inducible laryngeal obstruction, multiple drug intolerance syndrome, viral rash, seizure due to metastatic malignancy, and hemophagocytic lymphohistiocytosis initially diagnosed as drug reaction and eosinophilia with systemic symptoms. The initial misdiagnoses of these patients delayed or interfered with their medical care, emphasizing the importance of accurate diagnoses for the benefit of our patients.

Severe Multiple Drug Intolerance Syndrome in Fibromyalgia and Irritable Bowel Syndrome.

BACKGROUND: Multiple drug intolerance syndrome (MDIS) describes patients with multiple nonimmunologically mediated adverse reactions to medications. Patients with more than 10 medication intolerance labels are considered to have severe MDIS. There is overlap in the characteristics of patients with MDIS and fibromyalgia and irritable bowel syndrome (IBS). Severe MDIS can limit treatment options in this already complex patient group. OBJECTIVE: This study assessed the prevalence of severe MDIS in patients with fibromyalgia and IBS and its associated risk factors. METHODS: A retrospective chart review identified patients diagnosed with fibromyalgia or IBS who had been seen at a large academic center from August 2019 to July 2020. Exact birthdate- and sex-matched controls who had been seen within the same time frame were selected at random. Listed drug intolerance data and patient characteristics were then analyzed with logistic regression and χ2 testing. RESULTS: Patients with fibromyalgia and IBS were 12 and 3 times more likely to have severe MDIS compared with controls, respectively. Severe MDIS was associated with polypharmacy in both groups. Opiates were the most frequently reported drug intolerance across all participants. Although patients with IBS more often reported gastrointestinal symptoms as adverse reactions, individuals with fibromyalgia did not more frequently report pain or behavioral changes as adverse reactions. CONCLUSIONS: There was an increased rate of severe MDIS in patients diagnosed with fibromyalgia and IBS. Additional studies are needed to better understand the morbidity of MDIS and how it can best be managed in patients with fibromyalgia and IBS.

Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees.

Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.

A late preterm infant with lymphopenia.

The newborn screen for severe combined immunodeficiency (SCID) uses real-time quantitative polymerase chain reaction for T-cell receptor excision circles and is highly sensitive for SCID. However, T-cell lymphopenia from other primary and secondary causes, such as DiGeorge syndrome, prematurity, thymic involution from stress, and thymectomy during cardiac surgery, is also detected. We present a newborn girl with T-cell lymphopenia of unknown etiology detected via abnormal newborn screen.

Sulfonamide Hypersensitivity: Fact and Fiction.

Sulfonamide antimicrobials are commonly reported as causing drug allergy and have been implicated in a variety of hypersensitivity reactions including immediate IgE-mediated reactions, benign T-cell-mediated rashes, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Cross-reactivity is unlikely between sulfonamide antimicrobials and sulfonamide non-antimicrobials. In patients who develop reactions to a sulfonamide non-antimicrobial, there is no evidence to suggest that sulfonamide antimicrobials and other sulfonamide non-antimicrobials would cross-react. Although immediate skin testing can be performed in patients with histories of immediate reactions, they are infrequently positive and wane over time. Delayed skin testing including patch tests to sulfonamides is rarely positive. Drug challenges are a useful tool for patients with both immediate and delayed reactions to sulfonamides. The role of sulfamethoxazole desensitization is controversial as rates of hypersensitivity reactions are similar between desensitization and drug challenge.

Pediatric Drug Allergies: Updates on Beta-Lactam, Nonsteroidal Anti-Inflammatory Drug, and Chemotherapeutic Reactions.

Adverse drug reactions are frequently reported in pediatric patients. In this review article, the authors discuss pediatric drug allergies with emphasis on the most common culprits, beta-lactam antibiotics and non-steroidal anti-inflammatory drugs. The authors also discuss reactions to non-beta-lactam antibiotics and chemotherapeutics. Skin testing has not yet been validated for many drugs, although notable exceptions include penicillin and carboplatin. The gold standard for diagnosis in most cases remains drug challenge, and the need for penicillin skin testing prior to oral provocation challenge has been questioned in recent studies. Successful desensitizations have also been reported with several drugs.

The relationship between asthma and depression in a community-based sample.

OBJECTIVE: Asthma is an increasingly prevalent disease that is associated with substantial physical and financial burdens. Additionally, asthma is linked to psychiatric disorders. This study examines the relationship between asthma diagnosis, current depressive symptoms, and lifetime psychiatric disorder history in a large, community-based sample. METHODS: We analyzed data from 2168 participants in the Dallas Heart Study, a large, diverse, community-based sample of people designed to be representative of the Dallas County population. Logistic regressions analyzing the relationship between asthma diagnosis and history of a psychiatric disorder, as well as between asthma diagnosis and the Quick Inventory of Depressive Symptomatology (QIDS) scores were performed, controlling for demographic data. RESULTS: 13.4% of the sample had an asthma diagnosis. Asthma diagnosis was significantly associated with a history of nervous, emotional, or mental health disorder diagnosis [OR 1.810 (95% CI 1.280-2.559) p = 0.001], and with QIDS scores consistent with moderate or greater current depressive symptom severity [OR 1.586 (95%CI 1.106-2.274) p = 0.012]. The relationships were not moderated by age, gender, race, smoking status, or Body Mass Index. CONCLUSIONS: A diagnosis of asthma may be associated with current clinically significant levels of depressive symptoms and a lifetime psychiatric disorder. The current report adds to the existing literature in this area by assessing both current and lifetime symptoms and by using a large and diverse population. The findings highlight the clinical importance of considering the possibility of psychiatric illness in asthma patients and suggest further research in this area is needed.

A Proactive Approach to Penicillin Allergy Testing in Hospitalized Patients.

BACKGROUND: Penicillin allergy testing is underutilized in inpatients despite its potential to immediately impact antibiotic treatment. Although most tested patients are able to tolerate penicillin, limited availability and awareness of this tool leads to the use of costly and harmful substitutes. OBJECTIVE: We established an inpatient service at a large academic hospital to identify and test patients with a history of penicillin allergy with the goals of removing inaccurate diagnoses, reducing the use of beta-lactam alternatives, and educating patients and clinicians about the procedure. METHODS: Eligible inpatients were flagged daily through the electronic medical record and prioritized via a specialized algorithm. A trained clinical pharmacist performed penicillin skin tests and challenges preemptively or by provider request. Clinical characteristics and antibiotic use were analyzed in tested patients. RESULTS: A total of 1203 applicable charts were detected by our system leading to 252 direct evaluations over 18 months. Overall, 228 subjects (90.5%) had their penicillin allergy removed. Of these, 223 were cleared via testing and 5 by discovery of prior penicillin tolerance. Among patients testing negative, 85 (38%) subsequently received beta-lactams, preventing 504 inpatient days and 648 outpatient days on alternative agents. CONCLUSIONS: Penicillin allergy testing using a physician-pharmacist team model effectively removes reported allergies in hospitalized patients. The electronic medical record is a valuable asset for locating and stratifying individuals who benefit most from intervention. Proactive testing substantially reduces unnecessary inpatient and outpatient use of beta-lactam alternatives that may otherwise go unaddressed.

A 45-year-old man with shortness of breath and eosinophilia.

A 45-year-old man who presented with dyspnea and chest tightness was found to have obstructive lung disease and eosinophilia of 10,300 eosinophils/µL. The differential diagnosis encompassed causes of primary eosinophilia and secondary eosinophilia associated with pulmonary disease, including asthma, environmental allergic reaction, eosinophilic granulomatosis with polyangiitis, allergic bronchopulmonary aspergillosis, acute eosinophilic pneumonia, chronic eosinophilic pneumonia, parasitic infections, tuberculosis, fungal infection, sarcoidosis, mastocytosis, drug reaction with eosinophilia and systemic symptoms, lymphoproliferative hypereosinophilic syndrome, and myeloproliferative hypereosinophilic syndrome. Infectious workup, fiberoptic bronchoscopy with biopsy, and tests for myeloproliferative mutations help differentiate among these causes. Identifying the underlying cause of eosinophilia is imperative in guiding treatment.

An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. OBJECTIVE: We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. METHODS: Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. RESULTS: Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. CONCLUSION: Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day.

The relationship between asthma and self-reported anxiety in a predominantly healthy adult population.

BACKGROUND: Numerous studies involving patients with severe asthma have cited a relation between asthma and anxiety; this relation is responsible for decreased quality of life, increased morbidity, and higher health care usage. However, whether a link between milder asthma and anxiety exists remains unclear. OBJECTIVE: To determine whether asthma and anxiety share an association in a group of predominantly healthy adults. METHODS: Adults seen at the Cooper Clinic in Dallas, Texas from March 2000 through January 2013 for preventive medical examinations that included an extensive medical history, including a questionnaire regarding anxiety history, a physician-based physical examination, and laboratory and spirometric testing were used in the analysis. Multiple logistic regressions were used to determine the relation between asthma and anxiety. RESULTS: The sample consisted of 15,675 patients, of whom 1,403 (9%) had an asthma diagnosis. A sizeable majority of patients with asthma rated their health good or excellent, did not use an inhaler, and had a ratio of forced expiration volume in the first second to forced vital capacity greater than 70%. When controlling for covariates, milder asthma was significantly associated with anxiety (odds ratio 1.435, 95% confidence interval 1.238-1.663, P < .001). Smoking, a variable associated with asthma severity, was significantly associated with anxiety (odds ratio 1.432, 95% confidence interval 1.261-1.626, P < .001), although other variables, such as the ratio of forced expiration volume in the first second to forced vital capacity or use of an inhaled corticosteroid or combined inhaled corticosteroid and a long-acting ß agonist, were not significantly associated with anxiety. CONCLUSION: In this cohort of patients with predominantly mild asthma, there was a 43.5% increased risk of anxiety. All patients with asthma should be considered at a higher risk of anxiety and a target population for anxiety screening.

Drug allergy.

Drug allergy is one type of adverse reaction to drugs and encompasses a spectrum of hypersensitivity reactions with heterogeneous mechanisms and clinical presentations. A thorough history is essential to the management of drug allergy. Laboratory testing has a very limited role in the management of drug allergy. Graded dose challenges and procedures to induce drug tolerance might be required in patients with drug allergy when there is a definite need for a particular agent. Management of reactions to specific agents, including beta-lactam antibiotics, sulfonamides, local anesthetics, radiocontrast media, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, and biologic modifiers, will be discussed in further detail.

A 6-year-old boy with fever and eosinophilia.

Tissue and blood eosinophilia can be associated with a variety of infectious, allergic, and systemic diseases. Eosinophilia can range from mild and clinically inconsequential levels to high-grade eosinophilia with severe and potentially fatal consequences. Because of its ability to degranulate and produce cytotoxic mediators such as major basic protein and eosinophil peroxidase the eosinophil has the potential to cause considerable tissue damage, including potentially fatal conditions such as endomyocardial fibrosis. The most common infectious cause of eosinophilia worldwide is the parasitic helminth; fungal infection as a cause of eosinophilia is rarer, but must also be considered in the differential diagnosis. In this article we describe a unique case of reactive eosinophilia.

Antidepressant treatment of caregivers of children with asthma.

BACKGROUND: Depression is common in caregivers of children with asthma and is associated with increased emergency service utilization for the child's asthma. OBJECTIVE: This pilot study examined the impact of antidepressant treatment of depressed caregivers on the caregiver's depression and the child's asthma. METHOD: Eight depressed caregivers of children with asthma were given up to 6 months of algorithm-based antidepressant therapy. RESULTS: Caregiver depressive symptoms and the child's asthma symptoms improved significantly. CONCLUSION: Unscheduled clinic visits showed a trend toward significant decrease. Larger trials are needed to confirm these findings and identify mechanisms linking improvement in caregiver depression with improvement in their child's asthma.

Multiallergen nasal challenges in nonallergic rhinitis.

BACKGROUND: It has been proposed that some patients with nonallergic rhinitis may have "localized allergy" of the nasal mucosa. Nasal challenges with aeroallergens can help determine whether a patient is clinically allergic via an IgE-mediated pathway. OBJECTIVE: To determine the prevalence of localized allergy in patients with negative skin prick test results via nasal challenges with an array of allergens. METHODS: Twenty individuals with perennial rhinitis and negative epicutaneous test results to common perennial aeroallergens underwent nasal challenges to glycerin, Alternaria, cockroach, timothy grass, cat hair, and Dermatophagoides pteronyssinus. Total symptom scores, peak nasal inspiratory flow rates, and nasal eosinophil counts were determined. RESULTS: Of 20 patients with nonallergic rhinitis, 4 were hyperresponsive to glycerin and were not subsequently challenged. Eleven patients had negative nasal challenges. Five patients developed positive challenges (total symptom score > or = 5) to 7 allergens. These 5 patients returned for nasal provocation testing to their offending allergens, and these repeated challenges were negative. Three control subjects with allergic rhinitis developed positive challenges after nasal allergen challenge. CONCLUSIONS: Although some individuals with nonallergic rhinitis can have positive nasal allergen challenges, these results were not reproducible in the present patient population.