Interleukin 6 and C-reactive protein levels in patients with acute allergic reactions: an emergency department-based study.

BACKGROUND: Elevations of interleukin 6 (IL-6) have been described in drug-induced anaphylaxis. Although IL-6 is well known to stimulate an acute phase response, profiling acute phase protein levels, such as C-reactive protein (CRP), has, to our knowledge, never been performed in patients with acute allergic reactions. OBJECTIVE: To examine the pattern of IL-6 and CRP levels in patients with acute allergic reactions and to relate these to relevant clinical and laboratory parameters. METHODS: Plasma CRP and serum IL-6 levels were determined in 85 adult emergency department patients. These patients had been previously studied with questionnaires, physical examinations, and histamine/tryptase levels. Clinical and historical features were related to CRP and IL-6 levels. CRP and IL-6 levels were also examined for relationships with histamine and tryptase levels. RESULTS: CRP and IL-6 levels were significantly correlated with one another in the study patients (Spearman p = 0.36, P = 0.0008). Similar to histamine levels, IL-6 levels were significantly correlated with the extent of erythema manifested by the study patients. The extent of erythema was independently predicted by both IL-6 and histamine levels. Histamine levels were negatively correlated with CRP levels (Spearman p = -0.32, P = 0.003). Unlike histamine levels, IL-6 and CRP did not show significant relationships with the extent or presence of urticaria/angioedema or the presence of wheezing. IL-6 levels were correlated with the duration of symptoms before serologic sampling. An inverse correlation was observed between IL-6 levels and mean arterial blood pressure. Multivariate modeling showed significant independent effects from mean arterial pressure, duration of symptoms, erythema extent, and age in predicting IL-6 levels. Tryptase levels were higher in patients whose IL-6 levels were >20 pg/mL. CONCLUSIONS: CRP and IL-6 levels are not simple surrogate markers for histamine or tryptase release by mast cells or basophils in acute allergic reactions. Increasing IL-6 levels relate to greater erythema extent, lower mean arterial blood pressure, and a longer duration of symptoms. It would be interesting to speculate that CRP and IL-6 increases characterize a late-phase response in immediate hypersensitivity reactions. In this perspective, the inverse relationship between CRP and histamine levels could be explained. As histamine levels are waning, CRP levels are increasing. Timed studies for histamine and CRP/IL-6 levels in allergic reactions are necessary to confirm this hypothesis.

Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists.

STUDY OBJECTIVE: Although the addition of H(2) blockers to H(1) antagonists has been promoted for use in anaphylaxis, there have been no large studies establishing the advantage of this approach in treating acute allergic syndromes. In this study we tested the hypothesis that combined H(1) and H(2) blockage results in improved outcomes in patients treated for acute allergic syndromes compared with treatment with H(1) blockade alone. METHODS: In a randomized, double-blind, placebo-controlled trial, 91 adult patients with acute allergic syndromes were treated with either 50 mg of diphenhydramine and saline solution (control group) or with 50 mg of diphenhydramine and 50 mg of ranitidine (active group). These patients were treated with parenteral administration. Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were resolution of urticaria, angioedema, or erythema at 2 hours after protocol treatment. Areas of cutaneous involvement, heart rates, blood pressures, respiratory findings, and symptom scores were also assessed at baseline, 1 hour, and 2 hours. RESULTS: There were significantly more patients without urticaria at 2 hours among the patients in the active group compared with those in the control group. Both groups had similar proportions of urticaria at baseline. Logistic regression models to predict resolution of urticaria, which accounted for baseline urticarial involvement, showed odds ratios in favor of the active group treatment. Similar findings were observed when the absence of both urticaria and angioedema was considered as the dependent variable. There was not a significant difference between the 2 groups with regard to the absence of erythema or angioedema (irrespective of the presence of urticaria) at 2 hours. Blood pressure and symptoms did not show differences between the 2 groups over time. Lower heart rates were observed 1 hour after treatment in the active treatment group (mean reduction 10 beats/min) compared with those found in the placebo group (mean reduction 6 beats/min). CONCLUSION: These data show that adding H(2) blockers to H(1) antagonists results in additional improvement of certain cutaneous outcomes for patients presenting with acute allergic syndromes. These findings favor the recommendation for using combined H(1) and H(2) antihistamines in acute allergic syndromes.

Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study.

BACKGROUND: Emergency department visits for acute allergic reactions are common. Although the diagnosis and classification of these allergic reactions is primarily empiric, it is not always clear whether certain signs and symptoms constitute systemic mediator release syndromes, such as anaphylaxis, and thus may warrant more aggressive therapy or follow-up. OBJECTIVE: We sought to determine associations between various clinical signs and symptoms with both plasma histamine levels and serum tryptase levels in adult patients presenting to an emergency department with acute allergic syndromes. The clinical correlates of raised beta-tryptase levels were also investigated. METHODS: Ninety-seven adult emergency department patients were prospectively studied by using a questionnaire, physical examination, and serum-plasma sampling. Plasma histamine and serum total and beta-tryptase levels were determined. Clinical groupings were compared for mediator levels by using simple and multivariate analysis. RESULTS: Elevated levels of plasma histamine (>10 nmol/L) and serum total tryptase (>15 ng/mL) were observed in 42 and 20 patients, respectively. Detectable beta-tryptase (>/=1 ng/mL) was observed in 23 patients, including 15 of the patients with elevated total tryptase levels. Suspected food allergy incidences and the duration of reaction were similar in patients with increased histamine levels and in patients with increased tryptase levels. Increased total tryptase levels, histamine levels, or both were observed in some patients who did not have airway, cardiovascular, or abdominal signs. Histamine levels correlated better with clinical signs than tryptase levels. Histamine elevations (>10 nmol/L) were observed more frequently in patients characterized by the following clinical signs in univariate analysis: the presence of urticaria, more extensive erythema, abnormal abdominal findings, and wheezing. Total tryptase increases were observed more frequently only in patients with urticaria. Histamine levels correlated with initial heart rates. In multivariate analysis the extent of urticaria was the best single predictor of plasma histamine levels and of either an elevated histamine or tryptase level. Detectable beta-tryptase levels were observed in some patients who had neither elevated total tryptase nor elevated histamine levels. Unlike patients without detectable beta-tryptase levels, patients who had detectable beta-tryptase levels had a significant correlation between total tryptase and histamine levels (P <.05). CONCLUSIONS: Raised histamine and, less commonly, raised tryptase levels are observed in almost 50% of patients presenting to emergency departments with acute allergic reactions. Some cases associated with systemic mediator release do not have classical features of severe anaphylaxis, such as hypotension or tachycardia. The lack of total tryptase elevations in many patients with elevated plasma histamine levels suggests basophil involvement. The clinical utility of beta-tryptase determinations in the evaluation of acute allergic reactions needs further study.

Rapid improvement of peak flow in asthmatic patients treated with parenteral methylprednisolone in the emergency department: A randomized controlled study.

STUDY OBJECTIVE: Corticosteroids are thought to exert their physiologic effects in asthma over the course of several hours. In this study we tested the hypothesis that intravenous methylprednisolone improves airflow in a shorter time frame (2 hours) in adults with acute asthma. METHODS: In a randomized, double-blind, placebo-controlled trial, 56 adult asthmatic patients with peak expiratory flow rates (PEFRs) less than 50% predicted after an initial albuterol aerosol treatment were studied. These patients were randomly assigned to treatment with either 125 mg of intravenous methylprednisolone or an equivalent volume of normal saline solution (placebo). Patients were also treated with identical schedules of nebulized ipratropium and albuterol. Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were changes in PEFR and in percent predicted PEFR over time. PEFRs were assessed at baseline and at 1 and 2 hours. Heart rate changes over time and the proportion of admissions in the 2 groups were also compared. RESULTS: The increases in PEFR and percent predicted PEFR over time were both significantly greater in the methylprednisolone treatment group (P =. 002 and P =.005, respectively). The increases in geometric mean peak flow at 60 and 120 minutes were 79 and 96 L/min for the methylprednisolone group and 54 and 68 L/min for the placebo group. There was also a significantly different change in heart rates with time between the methylprednisolone and placebo groups (P =.029), with the placebo group showing a moderate increase in heart rate over time. Although the proportion of patients admitted for status asthmaticus was less in the methylprednisolone treatment group (8/30) compared with the placebo group (10/26), this difference in proportions (-.118, 95% confidence interval -.363 to.127) was not significant. CONCLUSION: These data suggest that use of corticosteroids should be considered relatively early in the treatment of patients with acute asthma in whom initial bronchodilator therapy fails to produce an adequate response.

Superiority of ipratropium plus albuterol over albuterol alone in the emergency department management of adult asthma: a randomized clinical trial.

STUDY OBJECTIVE: The use of nebulized ipratropium in combination with beta-agonists for the treatment of acute asthma in adults is controversial. We wished to test the hypothesis that combined aerosol treatment results in a greater rate of airflow improvement and a lower proportion of hospital admission in adults with acute asthma. METHODS: In a randomized, double-blind, placebo-controlled trial, 55 adult asthmatic patients with peak expiratory flow rate (PEFR) less than 200 L/min were randomly assigned to nebulization treatment with albuterol alone (2.5 mg initial dose followed by 2 more doses at 20-min intervals.), or the same albuterol regimen plus ipratropium (.5 mg combined with the initial dose of albuterol only). Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were changes in PEFR and in percent predicted PEFR over time (ie, treatment by time effect). PEFRs were assessed at baseline and at 20-minute intervals for a 1-hour period. The proportion of admissions in the two groups were examined as secondary endpoints. RESULTS: The increases in PEFR and percent predicted PEFR over time were both significantly greater in the combined ipratropium plus albuterol treatment group (P < or = .001). In addition, the proportion admitted patients was less in this group (3/27) than the proportion in the albuterol-only group (10/28). The 95% confidence interval for the absolute difference of 25% in the proportion admitted was 3% to 46%, P = .03. Most of the baseline clinical and historical features in the two groups were similar. CONCLUSION: These data suggest that ipratropium should be combined with initial albuterol nebulization in the ED treatment of acute asthma in adults, especially those with PEFRs less than 200 L/min.

Early parenteral corticosteroid administration in acute asthma.

To test the hypothesis that early parenteral corticosteroid administration may be associated with a rapid improvement in airflow obstruction in adult asthmatic patients, a randomized, double-blind placebo-controlled study was carried out. Forty-five adult asthmatic patients, with initial peak expiratory flow rates (PEFRs) of < 200 L/sec received an intravenous bolus of either 125 mg methylprednisolone (MP) or normal saline before any other emergency department treatments. This was immediately followed by 3 aerosol treatments of 2.5 mg of albuterol separated by 20-minute intervals. PEFRs and heart rates were measured over a 1-hour time frame. There was not a significantly higher rate of increase of PEFR in the MP group compared with the saline group. Similarly, the rate of increase in percent PEFR showed a trend to being higher in the saline group (P = .061). There was no significant difference in the proportion of hospitalizations and side effects between the two groups. Adjustment for other variables did not result in a model showing an enhanced PEFR improvement with MP treatment. This study does not support the concept that corticosteroid treatment effects are beneficial within the first hour after administration. Further studies of rapid-acting modalities to enhance bronchodilation are needed in treating acute asthmatics.