1
Introduction Allergic rhinitis (AR) is a common chronic disease which is diagnosed by a variety of clinical parameters. There is currently no widely accepted screening test for AR. Measurement of total serum IgE has not been recommended for use as a screening test due to prior limitations. However, this is a low cost test that may in fact have value in screening selected populations for AR. The aim of this study is to determine the utility of total serum IgE in the diagnosis of AR. Methods The charts of 1073 patients undergoing laboratory testing for the workup of allergic rhinitis were retrospectively reviewed. Data on patient demographics, clinical parameters, and results of serum specific IgE levels were recorded. Multivariate logistic regression was performed to ascertain the influence of various factors on the likelihood of a positive in vitro tests. The predictive values of total serum IgE in forecasting a positive or negative in vitro specific allergy test was determined. Results Total serum IgE demonstrated an incremental statistically and clinically significant positive and negative predictive values for identifying positive in vitro allergy tests. Differences in age, gender, ethnicity, clinical diagnosis, use of medications, month in which testing was performed, and the presence of co-morbid conditions were not statistically significant. Conclusions Total IgE levels offer clinical utility as a low- cost screening measure for patients with suspected AR. Total IgE level is independent of multiple demographic, seasonal, and clinical factors. Significance of Serum Total IgE in the Diagnosis of Allergic Rhinitis Daniel Chung MA 1 , KT Park MD 2 , Bharat Yarlagadda MD 1 , Elizabeth Mahoney MD 1 , Michael Platt MD 1 1 Department of Otolaryngology Head & Neck Surgery, Boston University School of Medicine, Boston, MA 2 Division of Gastroenterology, Lucille Packard Children’s Hospital, Stanford University, Palo Alto, CA INTRODUCTION RESULTS CONCLUSIONS DISCUSSION METHODS ABSTRACT CONTACT n % Odds Ratio (CI) P value Gender Male 431 40.2 Female 642 59.8 Age Mean 36.9 Range 1-91 Ethnicity White 296 27.6 1.7 (0.37 8.28) 0.48 Black 330 30.8 0.9 (0.19 3.92) 0.84 Hispanic 245 22.8 1.1 (0.23 5.35) 0.90 Asian 72 6.7 2.0 (0.27 15.4) 0.50 Other 79 7.4 0.8 (0.11 6.00) 0.83 Uncertain 51 4.8 Primary Rhinitis 70.2 Diagnosis Laryngitis 2.5 Otitis 1.4 Rash 0.2 Angioedema 1.5 Chronic Sinusitis 18.9 Other 5.3 Total IgE < 10 148 13.8 N/A (IU/ml) 10 50 303 28.3 8.2 (2.21 30.3) 0.002 51 100 170 15.9 41.3 (9.31 182.6) < 0.001 101 150 90 8.4 99.8 (13.5 741.0) < 0.001 > 150 362 33.8 76.0 (17.0 340.0) < 0.001 Associated Nasal Polyps 119 11.1 0.1 (0.15 0.67) 0.02 Diseases Asthma 264 24.6 1.7 (0.71 4.0) 0.23 Anaphylaxis 39 0.04 2.3 (0.15 34.9) 0.54 Allergic rhinitis (AR) is a common chronic disease which has significant impact on quality of life, loss of productivity, and financial expenditure 1,2 . Diagnosis of AR is performed by clinical parameters as well as measurement of specific IgE reactivity through in vitro or in vivo methods. There is currently no accepted screening test for differentiating AR from diseases with similar symptoms. The measurement of total serum IgE level is a low-cost test that is used in diagnosis of AR , however, current guidelines do not endorse its use in clinical practice 3,4 . The aim of this study is to identify the clinical usefulness of total serum IgE in the diagnosis of AR. A retrospective chart review was performed for patients being evaluated for AR at an academic otolaryngic allergy clinic over a 5 year period. Charts were reviewed for demographic data, clinical diagnoses, and total and specific IgE results. STATA Software was used to construct a multivariate logistic regression model to determine the likelihood of patients having a positive specific in vitro test for at least one antigen (>0.35 IU/ml), given clinically relevant covariates (Table 1). The positive and negative predictive value total IgE level in the diagnosis of AR, as defined by clinical manifestations and a positive specific IgE in vitro test, were calculated. Table 1. Demographics of the sample population and odds ratio of a positive in vitro test after multivariate logistic regression of the influence of pre-test variables. Figure 1. Positive predictive value and odds ratio of total serum IgE (IU/ml) in identifying a positive specific IgE by in vitro methods. 13 40.9 65.3 77.8 89.6 1 8.19 41.3 99.8 76 0 20 40 60 80 100 < 10 10 - 50 51 - 100 101 - 150 > 150 PPV Odds Ratio Signs and symptoms of allergic rhinitis overlap with other clinical syndromes that display similar findings. Due to increased costs and possible risks of allergy testing, a simple and low-cost screening test would be an important tool for identifying patients with AR. Total serum IgE demonstrated favorable positive and negative predictive values for patients with allergy symptoms. The most clinically useful values are found at the extremes of these tests. Total serum IgE level was not affected by primary clinical diagnosis, patient demographics, medications (other than oral steroids), associated conditions (asthma or anaphylaxis), or seasonal variation. Nasal polyps demonstrated a negative association which may be due to the screening of these patients without classical allergy symptoms. REFERENCES 1 Fajraoui, et al. Contribution of serum total immunoglobulin E measurement in the diagnosis of respiratory allergic disease. Tuni Med. Jan;86(1):32-7. 2008. 2 Meltzer, et al. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy Asthma Immunol 106, S12-16. 2011. 3 Wallace, et al. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. Aug;122(2 Suppl):S1-84. 2008. 4 Kerkhof, et al. Role and interpretation of total serum IgE measurements in the diagnosis of allergic airway disease in adults. Allergy. Sep;58(9):905-11. 2003. Elevated total IgE has a high positive predictive value for identification of in vitro specific IgE in the diagnosis of allergic rhinitis Total IgE level has a high negative predictive value at the lower range, suggesting that specific IgE testing may not be warranted in those patients with low total IgE (< 10 IU/ml). Further analysis is needed to determine the effect of specific allergy sub-classes on total IgE test statistics. There were a total of 1,232 patients identified who had both serum total IgE level and specific IgE reactivity by in vitro testing. One hundred and fifty nine patients were excluded due to incomplete total IgE result (5), insufficient clinical information (39), use of oral steroids (22) and insufficient allergens tested on specific IgE panels (93). Total serum IgE demonstrated an incremental statistically and clinically significant positive predictive value for identifying positive in vitro allergy tests. (Figure 1). Differences in age, gender, ethnicity, clinical diagnosis, use of medications, month in which testing was performed, and the presence of co-morbid conditions were not statistically significant (Table 1). The presence of nasal polyps revealed a negative association with positive allergy testing. The negative predictive value ranged from 86.9 to 60.6 depending on total IgE cutoff level for diagnosis of a “negative” test. Figure 2. Negative predictive value of total serum IgE (IU/ml) in identifying a negative specific IgE by in vitro methods. 86.9 69.2 66.3 60.6 0 20 40 60 80 100 < 10 10 - 50 51 - 100 101 - 150 NPV Michael Platt, MD Boston University School of Medicine Dept. of Otolaryngology Head & Neck Surgery Email: [email protected] Phone: 617-638-8000 Website: bu-ent.com

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Page 1: Significance of Serum Total IgE in the Diagnosis of ...(IU/ml) in identifying a positive specific IgE by in vitro methods. 13 40.9 65.3 77.8 89.6 1 8.19 41.3 99.8 76 0 20 40 60 80

Introduction

Allergic rhinitis (AR) is a common chronic

disease which is diagnosed by a variety of

clinical parameters. There is currently no

widely accepted screening test for AR.

Measurement of total serum IgE has not

been recommended for use as a screening

test due to prior limitations. However, this is

a low cost test that may in fact have value in

screening selected populations for AR. The

aim of this study is to determine the utility of

total serum IgE in the diagnosis of AR.

Methods

The charts of 1073 patients undergoing

laboratory testing for the workup of allergic

rhinitis were retrospectively reviewed. Data

on patient demographics, clinical

parameters, and results of serum specific

IgE levels were recorded. Multivariate

logistic regression was performed to

ascertain the influence of various factors on

the likelihood of a positive in vitro tests. The

predictive values of total serum IgE in

forecasting a positive or negative in vitro

specific allergy test was determined.

Results

Total serum IgE demonstrated an

incremental statistically and clinically

significant positive and negative predictive

values for identifying positive in vitro allergy

tests. Differences in age, gender, ethnicity,

clinical diagnosis, use of medications, month

in which testing was performed, and the

presence of co-morbid conditions were not

statistically significant.

Conclusions

Total IgE levels offer clinical utility as a low-

cost screening measure for patients with

suspected AR. Total IgE level is

independent of multiple demographic,

seasonal, and clinical factors.

Significance of Serum Total IgE in the Diagnosis of Allergic Rhinitis

Daniel Chung MA 1, KT Park MD 2, Bharat Yarlagadda MD 1, Elizabeth Mahoney MD 1, Michael Platt MD 1

1 Department of Otolaryngology – Head & Neck Surgery, Boston University School of Medicine, Boston, MA 2 Division of Gastroenterology, Lucille Packard Children’s Hospital, Stanford University, Palo Alto, CA

INTRODUCTION RESULTS

CONCLUSIONS

DISCUSSION

METHODS

ABSTRACT

CONTACT

n % Odds Ratio (CI) P value

Gender Male 431 40.2

Female 642 59.8

Age Mean 36.9

Range 1-91

Ethnicity White 296 27.6 1.7 (0.37 – 8.28) 0.48

Black 330 30.8 0.9 (0.19 – 3.92) 0.84

Hispanic 245 22.8 1.1 (0.23 – 5.35) 0.90

Asian 72 6.7 2.0 (0.27 – 15.4) 0.50

Other 79 7.4 0.8 (0.11 – 6.00) 0.83

Uncertain 51 4.8

Primary Rhinitis 70.2

Diagnosis Laryngitis 2.5

Otitis 1.4

Rash 0.2

Angioedema 1.5

Chronic

Sinusitis 18.9

Other 5.3

Total IgE < 10 148 13.8 N/A

(IU/ml) 10 – 50 303 28.3 8.2 (2.21 – 30.3) 0.002

51 – 100 170 15.9 41.3 (9.31 – 182.6) < 0.001

101 – 150 90 8.4 99.8 (13.5 – 741.0) < 0.001

> 150 362 33.8 76.0 (17.0 – 340.0) < 0.001

Associated Nasal Polyps 119 11.1 0.1 (0.15 – 0.67) 0.02

Diseases Asthma 264 24.6 1.7 (0.71 – 4.0) 0.23

Anaphylaxis 39 0.04 2.3 (0.15 – 34.9) 0.54

Allergic rhinitis (AR) is a common chronic disease which has

significant impact on quality of life, loss of productivity, and

financial expenditure1,2. Diagnosis of AR is performed by clinical

parameters as well as measurement of specific IgE reactivity

through in vitro or in vivo methods. There is currently no

accepted screening test for differentiating AR from diseases with

similar symptoms. The measurement of total serum IgE level is

a low-cost test that is used in diagnosis of AR , however, current

guidelines do not endorse its use in clinical practice3,4. The aim

of this study is to identify the clinical usefulness of total serum

IgE in the diagnosis of AR.

A retrospective chart review was performed for patients being

evaluated for AR at an academic otolaryngic allergy clinic over

a 5 year period. Charts were reviewed for demographic data,

clinical diagnoses, and total and specific IgE results. STATA

Software was used to construct a multivariate logistic

regression model to determine the likelihood of patients having

a positive specific in vitro test for at least one antigen (>0.35

IU/ml), given clinically relevant covariates (Table 1). The

positive and negative predictive value total IgE level in the

diagnosis of AR, as defined by clinical manifestations and a

positive specific IgE in vitro test, were calculated.

Table 1. Demographics of the sample population and odds ratio of a

positive in vitro test after multivariate logistic regression of the

influence of pre-test variables.

Figure 1. Positive predictive value and odds ratio of total serum IgE

(IU/ml) in identifying a positive specific IgE by in vitro methods.

13

40.9

65.3

77.8

89.6

1 8.19

41.3

99.8

76

0

20

40

60

80

100

< 10 10 - 50 51 - 100 101 - 150 > 150PPV Odds Ratio

Signs and symptoms of allergic rhinitis overlap

with other clinical syndromes that display

similar findings. Due to increased costs and

possible risks of allergy testing, a simple and

low-cost screening test would be an important

tool for identifying patients with AR.

Total serum IgE demonstrated favorable

positive and negative predictive values for

patients with allergy symptoms. The most

clinically useful values are found at the

extremes of these tests.

Total serum IgE level was not affected by

primary clinical diagnosis, patient

demographics, medications (other than oral

steroids), associated conditions (asthma or

anaphylaxis), or seasonal variation.

Nasal polyps demonstrated a negative

association which may be due to the screening

of these patients without classical allergy

symptoms.

REFERENCES 1Fajraoui, et al. Contribution of serum total immunoglobulin E

measurement in the diagnosis of respiratory allergic disease. Tuni

Med. Jan;86(1):32-7. 2008.

2Meltzer, et al. The economic impact of allergic rhinitis and current

guidelines for treatment. Ann Allergy Asthma Immunol 106, S12-16.

2011.

3Wallace, et al. The diagnosis and management of rhinitis: an updated

practice parameter. J Allergy Clin Immunol. Aug;122(2 Suppl):S1-84.

2008.

4Kerkhof, et al. Role and interpretation of total serum IgE

measurements in the diagnosis of allergic airway disease in adults.

Allergy. Sep;58(9):905-11. 2003.

Elevated total IgE has a high positive predictive

value for identification of in vitro specific IgE in

the diagnosis of allergic rhinitis

Total IgE level has a high negative predictive

value at the lower range, suggesting that specific

IgE testing may not be warranted in those

patients with low total IgE (< 10 IU/ml).

Further analysis is needed to determine the

effect of specific allergy sub-classes on total IgE

test statistics.

There were a total of 1,232 patients identified who had both

serum total IgE level and specific IgE reactivity by in vitro testing.

One hundred and fifty nine patients were excluded due to

incomplete total IgE result (5), insufficient clinical information

(39), use of oral steroids (22) and insufficient allergens tested on

specific IgE panels (93).

Total serum IgE demonstrated an incremental statistically and

clinically significant positive predictive value for identifying

positive in vitro allergy tests. (Figure 1). Differences in age,

gender, ethnicity, clinical diagnosis, use of medications, month in

which testing was performed, and the presence of co-morbid

conditions were not statistically significant (Table 1). The

presence of nasal polyps revealed a negative association with

positive allergy testing. The negative predictive value ranged

from 86.9 to 60.6 depending on total IgE cutoff level for

diagnosis of a “negative” test.

Figure 2. Negative predictive value of total serum IgE (IU/ml) in

identifying a negative specific IgE by in vitro methods.

86.9

69.2 66.3 60.6

0

20

40

60

80

100

< 10 10 - 50 51 - 100 101 - 150

NPV

Michael Platt, MD

Boston University School of Medicine

Dept. of Otolaryngology –

Head & Neck Surgery

Email: [email protected]

Phone: 617-638-8000

Website: bu-ent.com