James M. Quinn

The natural history of exposure to the imported fire ant (Solenopsis invicta).

BACKGROUND Imported fire ants (IFA) are a common cause of insect venom hypersensitivity in the southeastern United States. The purpose of this study was to determine the sting attack rate and development of specific IgE in an unsensitized population. METHODS Study participants consisted of 137 medical students with limited exposure to IFA-endemic areas who were temporarily training in San Antonio, Tex. Subjects were surveyed for prior IFA exposure with a questionnaire, and IFA-specific IgE was evaluated with RAST and intradermal skin testing. Evaluations were performed on arrival and reported at departure from the endemic area 3 weeks later. RESULTS One hundred seven subjects completed the study. Field stings were reported in 55 subjects, resulting in a sting attack rate of 51%. In these 55 subjects 53 (96%) reported a pustule or a small local reaction at the sting site, one (2%) reported an isolated large local reaction, and none reported a systemic reaction. At the 3-week follow-up skin test and RAST conversions occurred in seven subjects (13%) and in one subject (1.8%), respectively. CONCLUSIONS Even brief exposures to IFA-endemic areas result in significant sting rates and concurrent rapid development of IFA-specific IgE in 16% of stung subjects.

Subcutaneous immunoglobulin replacement therapy for primary antibody deficiency: advancements into the 21st century

OBJECTIVES To provide a review of the world literature and discuss the clinical role of subcutaneous immunoglobulin (SCIG) therapy for primary antibody deficiency. DATA SOURCES English-language publications on SCIG therapy were identified through MEDLINE and through the reference list of the initially identified publications. STUDY SELECTION Articles pertaining to SCIG for the treatment of immunodeficiency, particularly primary antibody deficiency, were selected. RESULTS SCIG therapy has been shown to be effective and safe for the treatment of primary immunodeficiency. The risk of systemic reactions during infusion is generally reported to be less than 1%. Many patients prefer SCIG over conventional intravenous immunoglobulin therapy because of increased convenience and independence associated with SCIG therapy. Publications show SCIG therapy to be advantageous in selected patient populations, such as children, pregnant women, and patients with poor intravenous access. CONCLUSION SCIG therapy has been widely used in some European countries for a number of years, but a Food and Drug Administration-approved product was only recently introduced into the United States in 2006. SCIG therapy offers unique advantages that are applicable to many patients receiving immunoglobulin therapy for primary immunodeficiency.

Determination of the incidence of sensitization after penicillin skin testing

BACKGROUND Concerns for sensitization after penicillin skin testing are a factor in limiting the timing and population for whom this testing is offered. The sensitizing potential of the penicillin skin test has never been studied directly. METHODS A total of 329 volunteers underwent prick and intradermal skin testing with penicillin G, benzylpenicilloyl-polylysine, and a minor determinant mixture. Those with negative skin testing had repeat testing 4 weeks later. Medical history and antibiotic use were determined by interview, questionnaire, and electronic pharmacy records. RESULTS Seventy-two of the 329 subjects (22%) reported a history of previous beta-lactam reaction, of which 10 (14%) had a positive initial skin test. Overall, the initial skin test was positive in 23 of 329 (7%). Of the subjects with a negative initial skin test, 239 completed the second test 4 weeks later. Of these, 6 subjects (2.5%, 95% confidence interval 0.5% to 4.5%) converted to a positive skin test. None had taken a beta-lactam antibiotic between the two tests, and none had any previous history of beta-lactam reaction. One subject reported having never taken a beta-lactam antibiotic before. In comparison to the 233 subjects who did not convert their skin test, the statistically significant factors favoring sensitization were: female sex (odds ratio [OR] 6.53, P = 0.05), atopy (OR 5.31, P = 0.04), and history of food allergy (OR 6.35, P = 0.02). There was a trend toward more recent penicillin use in the newly sensitized subjects, but this was not statistically significant.. CONCLUSION Penicillin skin testing may sensitize a small number of individuals to penicillin.

Inpatient consultation of allergy/immunology in a tertiary care setting

BACKGROUND Few studies examine the referral patterns for allergy/immunology (A/I) inpatient consultation. OBJECTIVE The purpose of this study was to examine the primary reason and trends for A/I inpatient consultation to improve fellowship training. METHODS We performed a retrospective chart review of all inpatient A/I consults from July 1, 1987 to June 30, 2001 to determine the primary reason for consultation. We also reviewed trends in the total admissions and the average daily patient load compared with A/I consultation. RESULTS A total of 1,284 A/I inpatient consults were reviewed. Thirty-six percent (460 of 1,284) of inpatient consults were for evaluation of adverse drug reactions, 21% (270 of 1,284) asthma, 21% (272 of 1,284) miscellaneous reasons, 8% (109 of 1,284) possible immunodeficiency, 7% (93 of 1,284) angioedema/urticaria, and 6% (80 of 1,284) anaphylaxis. Our results demonstrated a fall in inpatient consults that correlated with a similar fall in total hospital admissions. The ratio of A/I inpatient consults to total admissions remained constant. Additionally, the ratio of A/I consults to average daily patient load increased over the study period. There was a decrease in asthma and adverse drug reaction consults, whereas immunodeficiency and anaphylaxis referrals remained stable. CONCLUSIONS Identifying the most common reasons for inpatient consultation provides a guide for the education of A/I fellows and primary care residents. Inpatient consultation continues to play a crucial role in A/I training as it provides unique opportunities to evaluate serious life threatening diseases. An unchanged trend of consultation for immunodeficiency and anaphylaxis reaffirms the importance of the allergist/immunologist as a valuable resource for inpatient consultation.

Imported fire ant field reaction and immunotherapy safety characteristics: The IFACS study

BACKGROUND Imported fire ants (IFAs) are endemic in the southeastern United States, including Texas; can sting multiple times; and are a well-known cause of anaphylaxis. There are few data available on how many stings typically lead to systemic reactions (SRs). Likewise, there are no reports currently in the literature that characterize the safety of IFA subcutaneous immunotherapy (SCIT). OBJECTIVE We sought to analyze a case-cohort sample of patients for IFA SCIT risk factors and to characterize the index field reactions of these patients. METHODS A case-cohort study based on a 3-year retrospective chart review (2005-2008) at a single institution was performed for patients receiving IFA SCIT. Field reactions leading to initiation of IFA SCIT were also reviewed. RESULTS Seventy-seven patients (40 female patients; mean age, 34 years) received 1,887 injections, and 7 patients experienced 8 SRs, for a rate of 0.4% per injection and 9.1% per patient. SRs were mild. Having an SR to skin testing was associated with increased odds of having an SR to IFA SCIT (odds ratio, 4.75; 95% CI, 1.13-20.0), as were large local reactions (odds ratio, 34.5; 95% CI, 6.52-182). No other risk factors were identified. Of the index field reactions leading to IFA SCIT, 59% were the result of 1 sting, and 87% of subjects experienced only 1 SR before initiation of IFA SCIT. Two of 4 patients who experienced loss of consciousness during the index field reaction required an increased maintenance dose for optimal response. CONCLUSIONS IFA SCIT is safe; however, having an SR to skin testing or the presence of large local reactions increases the odds of having an SR to IFA SCIT. The majority of SRs to IFA field stings resulted from 1 sting.

Reasons for outpatient consultation in allergy/immunology.

There is little data in the literature regarding outpatient consultation in allergy/immunology (A/I). The purpose of this study was to determine the relative frequency of different reasons for A/I outpatient consultation to help guide graduate medical education (GME) and assist with A/I practice management. We retrospectively reviewed the electronic medical records of all outpatient A/I consultations from January 1, 2006 to December 31, 2006. The study was performed at our tertiary care referral center which is a GME training site. There were 1412 A/I consults requested during the 1-year period. The consults per month ranged from a low of 69 to a high of 157. The referrals consisted of 35% pediatric and 65% adult patients. There were 52.8% female and 47.2% male patients. We received 74.3% of referrals from primary care, 19.8% from specialty care, and 5.9% from the emergency department. The most common reasons for consultation included 808 (57.2%) patients for chronic rhinitis, 288 (20.4%) for asthma, 196 (13.9%) for food allergy, 89 (6.3%) for venom allergy, 68 (4.8%) for atopic dermatitis, 66 (4.7%) for drug allergy, 62 (4.4%) for chronic urticaria, 45 (3.2%) for acute urticaria, 34 (2.4%) for immunodeficiency, 31 (2.2%) for anaphylaxis, and 162 (11.5%) for other reasons. More than one reason was given for 27.1% of consults, and there was an average of 1.3 reasons for consultation per patient. Although the allergist/immunologist is consulted for a variety of reasons, the top three reasons make up a majority of outpatient consults, and consults are often requested to address more than one diagnosis.

The environment, the airway, and the athlete

OBJECTIVE To review the interaction of environmental factors with host conditions, including atopy, the potential resulting impaired upper and lower airway function, and diagnostic and therapeutic considerations in the athlete. DATA SOURCES OVID, MEDLINE, and PubMed searches were performed cross-referencing the keywords asthma, athlete, atopy, bronchospasm, exercise, pollution, and rhinitis. STUDY SELECTION Articles were selected based on relevance to the subject matter. RESULTS Recent studies have yielded significant advances in our understanding of how intrinsic and extrinsic factors can potentially result in impaired function of the airways of athletes. Extrinsic factors include environmental exposure to temperature, humidity, aeroallergens, irritants, and pollution. Intrinsic factors include atopy, allergic rhinitis, asthma, and anatomical variants. These intrinsic and extrinsic factors can affect both the athletes quality of life and athletic performance. However, uncertainty remains regarding relative contributions of these factors in explaining the high degree of bronchospasm seen in various populations of athletes with and without asthma, and no consensus exists regarding the most appropriate diagnostic and therapeutic modalities. CONCLUSIONS Great variability exists in the presentation, laboratory findings, diagnostic maneuvers, and response to therapeutic measures among populations of athletes in different sports and among individuals. An improved understanding of the unique exposures faced by athletes in different disciplines, of the available tests for pursuing the appropriate diagnosis, and of the available therapies will allow the allergist to provide clinical improvement and allow the athlete to find relief and achieve his/her full potential.

Adherence to imported fire ant subcutaneous immunotherapy

BACKGROUND Imported fire ant (IFA) subcutaneous immunotherapy (SCIT) is safe and effective. For optimal protection, SCIT is given monthly for 3 to 5 years. Successful outcomes require patient adherence. OBJECTIVE To evaluate SCIT adherence in IFA allergic patients in an endemic area. METHODS Patients with systemic reactions to an IFA sting, with detectable specific IgE, who received a recommendation to start IFA SCIT were included. Initial reaction severity and demographic data were collected. Patients were contacted at 1 year regarding interval reactions to stings, SCIT adherence, and reason for nonadherence. Adherence rates were analyzed for association with age, sex, and severity of initial reaction. RESULTS Seventy-six patients were enrolled, and 71% adhered to the recommendation to start IFA SCIT. Subgroup analysis did not find significant differences. At 1 year, 97% completed follow-up for analysis, and only 35% remained adherent. Subgroup analysis did not find significant differences. Inconvenience and fear were reported as reasons for not following the recommendation to start or continue with IFA SCIT. CONCLUSION IFA SCIT is a life-saving therapy that is safe and effective. Despite this, only 71% followed the recommendation to start, and at 1 year only 35% remained adherent. Adherence was not statistically related to age, sex, or severity of initial reaction. Logistical constraints and fear were significant impediments.

Frequency of imported fire ant stings in patients receiving immunotherapy.

BACKGROUND Imported fire ant (IFA) stings are an important cause of stinging insect hypersensitivity in endemic areas. IFA stings are difficult to avoid, and many studies have shown high field sting rates. No studies report the natural IFA sting rate that patients experience while receiving IFA immunotherapy. OBJECTIVE To determine the frequency of IFA stings in patients receiving IFA immunotherapy compared with an aeroallergen immunotherapy control group. METHODS Patients were surveyed by telephone to characterize the frequency of stings, reactions, and attitudes toward IFA avoidance. RESULTS A total of 23 of 28 patients reported IFA stings during their IFA immunotherapy compared with 16 of 28 patients during their aeroallergen immunotherapy. More of the IFA immunotherapy-treated patients were stung than the aeroallergen immunotherapy patients, which is inconsistent with our hypothesis (chi2 = 4.139, P < .042). The annualized sting rates between the IFA immunotherapy and aeroallergen immunotherapy groups were similar (1.82 vs 1.72 stings per year, P < .55). The IFA immunotherapy patients were more likely to report any kind of reaction (chi2 = 9.124, P < .003) compared with the control group. Most patients reported feeling careful to avoid stings. CONCLUSIONS Patients with IFA hypersensitivity treated with IFA immunotherapy do not experience a decreased frequency of stings resulting from attention to sting avoidance. IFA stings are frequent and difficult to avoid. Rush IFA immunotherapy is a good option for many patients to achieve protection quickly.

EXERCISE-INDUCED HYPERVENTILATION

Exercise-induced respiratory symptoms are present in up to 80% of patients with asthma.1,2 Herein, we explore the differential diagnosis of a patient with exercise-induced dyspnea referred for an asthma evaluation. A 42-year-old man was evaluated for dyspnea with activity. He predominantly had trouble “catching his breath” during exertive activity for several years, and he also had episodes of dyspnea at night, awaking him on occasion. Treatment with a short-acting -agonist and a trial of an inhaled corticosteroid with a long-acting -agonist had incompletely improved his symptoms. On physical examination his vital signs were as follows: blood pressure, 132/83 mm Hg; heart rate, 68 beats/min; respiratory rate, 16/min; and oxygen saturation by pulse oximeter, 99% while breathing room air. His body mass index (calculated as weight in kilograms divided by height in meters squared) was 23.5. His physical examination on presentation was notable for edematous nasal mucosa and posterior pharyngeal cobblestoning. His lungs were clear, without evidence of wheezing. His examination was otherwise unremarkable. Spirometry and lung volumes revealed the following values: forced vital capacity (FVC), 4.26 L (81%); forced expiratory volume in 1 second (FEV1), 3.32 L (80%); FEV1/FVC ratio, 0.78; total lung capacity, 5.69 L (80%); residual volume, 1.81 L (88%); and diffusion capacity of carbon monoxide, 32.98 mL/min/mm Hg (110%). There was no response to bronchodilator therapy. Results of routine laboratory testing, including a complete metabolic panel, thyroid-stimulating hormone level, and a complete blood cell count, were within the respective reference ranges. Results of methacholine challenge testing were negative (tested to 8 mg/mL of methacholine), with a decline in FEV1 of 2.1%. The patient then underwent outpatient Holter monitoring, echocardiography, and treadmill stress testing, all of which revealed no cardiac etiology for his symptoms. Findings from high-resolution chest computed tomography were normal. Exercise testing was then performed and provoked symptoms; however, his FEV1 did not change substantially after exercise. Rhinoscopy was performed while the patient was symptomatic, revealing normal vocal cord abduction and adduction and normal phonation. It was observed that he seemed to hyperventilate during exercise when his symptoms were present. To perform testing for exercise-induced hyperventilation, a portable carbon dioxide (CO2) monitor was used (Ohmeda 5250 CO2 Monitor; Datex-Ohmeda, Madison, Wisconsin) to monitor the patient’s end tidal CO2 level during an exercise challenge. A control patient with stable mild asthma was also tested using the same equipment. The results are shown in Figure 1. The patient reported his index symptoms when his CO2 level dropped to less than 30 mm Hg within 6 to 8 minutes of exercise. He was monitored after the challenge for 1 hour, and his CO2 level gradually returned to normal. After testing, the patient was educated about the coincidence of his symptoms with his CO2 level during exercise. He was instructed on techniques to slow his breathing and to pay attention to his symptoms and respiratory rate during exercise. He was also directed to cease using asthma medication, which he did successfully. He reports improvement in his quality of life after his workup and diagnosis and currently has minimal respiratory symptoms with exercise. On revisiting his history of nighttime episodes of dyspnea, he reported that his spouse noted snoring, gagging, and choking in the patient during sleep. A sleep study demonstrated moderate obstructive sleep apnea (apnea to hypopnea index of 18), and the patient was referred to the pulmonary department for titration of continuous positive airway pressure, which ameliorated his nighttime symptoms. The hyperventilation syndrome is characterized by ventilation in excess of metabolic needs.3 There is no gold standard for the diagnosis of hyperventilation syndrome. Methods of diagnosis have included the hyperventilation provocation test,4 cardiopulmonary exercise testing,5 CO2 monitoring,6 and a symptom questionnaire.7 Monitoring of CO2 levels, whether end tidal or transcutaneous, during activities that provoke symptoms can help make the connection between symptoms and CO2 levels. In 32 patients with atypical symptoms of exercise-induced asthma, symptomatic patients were found to have a decrease in CO2 levels on average of 23.2% compared with 9.8% in controls.6 The present patient had a decrease of 34% (from 39 to 26 mm Hg), which accompanied his symptoms. He also had delayed recovery of his CO2 level compared with the control (Fig 1). Hyperventilation syndrome should be considered during the workup of a patient with unexplained respiratory symptoms, particularly during exercise. In this patient, persistence in pursuing the differential diagnosis for his symptoms led to correct identification of the cause, avoidance of unnecessary pharmacotherapy, and improvement of symptoms. Additional research is needed to further define and standardize the diagnosis of hyperventilation syndrome. The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the US Department of the US Air Force, the Department of Defense, or the US Government. Disclosures: Authors have nothing to disclose. Figure 1. Carbon dioxide (CO2) monitoring during exercise challenge and recovery (after the arrow) in the patient and the control. Asterisk indicates the patient’s onset of symptoms during the challenge test.