2000 2001 Series: Update Sessions from ACPASIMs 2000 Annual Session
Margaret Ring Gillock, Editor/David A. Cramer, MD, Co-Editor/Paul T. Kefalides, MD, Co-Editor
Update in Allergy and Immunology
Anthony Montanaro, MD, and Stephen A. Tilles, MD
T he medical literature addressed many different topics
in the field of allergy and immunology in the past
year. For this Update, we focus on topics that are par-
ticularly relevant to internal medicine: latex allergy,
trimethoprimsulfamethoxazole (TMP-SMX) allergy,
environmental controls for persons with allergies, food
allergy, use of inhaled corticosteroids, use of monoclonal
anti-IgE antibody, asthma, and allergic rhinitis.
Latex Allergy
Although latex allergy has become an increasingly im-
portant allergic disorder in U.S. society, it presents a
difficult diagnostic problem in both primary and spe-
cialty care. One of the major difficulties in diagnosing
latex allergy has been the lack of a standardized skin
testing reagent.
Study Supports the Efficacy of Nonammoniated Latex Skin
Test Reagent for Confirmatory Puncture Skin Tests
Hamilton RG, Adkinson NF Jr. Diagnosis of natural rubber latex
allergy: multicenter latex skin testing efficacy study. Multicenter
Latex Skin Testing Study Task Force. J Allergy Clin Immunol. 1998;
102:482-90. [PMID: 0009768592]
In testing for latex allergy, allergists have relied on ex-
tracts of unknown potency or have performed skin tests
by directly puncturing uncharacterized powdered latex
gloves. Reliable in vitro testing is available for latex-
specific IgE, but the diagnostic sensitivity and specificity
of these assays are generally regarded as being lower than
those of puncture skin tests. To document the safety
and diagnostic sensitivity of a nonammoniated latex ex-
tract, Hamilton and colleagues studied 358 adults. The
study participants were divided into three groups on the
basis of their clinical history: those who reported no
history of allergy to latex (n 180), those who reported
an unequivocal allergy to latex (n 124), or those in
whom latex hypersensitivity had been restricted to con-
Ann Intern Med. 2001;134:291-297.
For author affiliations and current addresses, see end of text.
Update
tact dermatitis (n 54). The participants underwent se-
rologic testing for the presence of latex-specific IgE and
skin testing. The latter was performed by using a
nonammonium latex allergen preparation at an initial
concentration of 100 g/mL; this was increased to 1
mg/mL if results were negative at the lower concentra-
tion. Appropriate positive and negative controls were
undertaken with glycerinsaline and histamine. The
Pharmacia CAP system was used for serologic testing.
The rate of positive prick skin tests (diagnostic sen-
sitivity) in the latex allergy group was 95% at 100
g/mL and increased to 99% at 1 mg/mL. The rate of
negative prick skin tests (diagnostic specificity) in the
group without latex allergy was 100% at 100 g/mL
and decreased to 96% at 1 mg/mL. Skin testing was not
associated with significant episodes of systemic anaphy-
laxis. Of the participants in the latex allergy group, 16%
reported mild systemic reactions of pruritus, rash, rhini-
tis, ocular itch, or urticaria immediately after skin test-
ing. One person in this group had a peak flow rate that
transiently decreased by 28%.
These data demonstrate the diagnostic specificity
and sensitivity of the soon-to-be-available nonammoni-
ated latex skin test reagent. Mild local or systemic reac-
tions may occur in many patients undergoing skin test-
ing; no cases of severe systemic anaphylaxis were
reported in this study, although severe anaphylaxis re-
mains a possibility.
For internists and other primary care physicians, as
well as allergy specialists, latex allergy is an increasing
clinical problem. A suggestive clinical history of latex
allergy is necessary but not sufficient for a definitive
diagnosis of IgE-dependent latex allergy. Patients with
suspected latex allergy should have serologic testing or
skin testing. The skin testing should be done by some-
one who is expert in the administration of this test and
interpretation of the results and who has the necessary
emergency equipment available for treatment of any lo-
cal or systemic reactions. It is important to recognize
that there are rare cases of patients who present with a
highly suggestive clinical history, have negative results
on serologic and skin testing for latex, and require con-
trolled provocation testing to establish a reliable diagnosis.
2001 American College of PhysiciansAmerican Society of Internal Medicine 291
Update Update in Allergy and Immunology
TMP-SMX Desensitization in HIV-Infected Patients
For prophylaxis against Pneumocystis carinii pneumonia
in HIV-infected patients, TMP-SMX is the best avail-
able choice for therapy. However, hypersensitivity reac-
tions to TMP-SMX are more frequent in these patients
and often result in discontinuation of therapy.
A New Protocol for TMP-SMX Desensitization in
HIV-Infected Patients Is Safe and Effective
Demoly P, Messaad D, Sahla H, et al. Six-hour trimethoprim-sulfa-
methoxazole-graded challenge in HIV-infected patients. J Allergy
Clin Immunol. 1998;102:1033-6. [PMID: 0009847446]
Because TMP-SMX is clearly the most cost-effective
therapy available for P. carinii pneumonia prophylaxis,
it is preferable to other, more expensive and less effective
agents. Patients with HIV infection appear to have a rate
of hypersensitivity reactions to TMP-SMX approxi-
mately 10 to 50 times greater than the rate in the gen-
eral population, and previous studies have indicated the
usefulness of desensitization protocols that take up to 26
days. As a result, Demoly and colleagues studied a rapid
oral graded challenge.
The study evaluated 44 consecutive HIV-infected
patients from two AIDS units who were hypersensitive
to TMP-SMX. These persons underwent outpatient de-
sensitization that required ingestion of 12 doses of in-
creasing amounts of TMP-SMX at 30-minute intervals.
The challenge doses ranged from 0.2 g (TMP)/1 g
(SMX) to 60/300 mg. These challenges were under-
taken in an outpatient allergy department setting and
involved treating through the occurrence of nonbul-
lous cutaneous adverse reactions.
All 44 persons who undertook the challenge com-
pleted the challenge without any serious adverse reac-
tions. Eleven of the 44 patients experienced mild
hypersensitivity reactions on days 1 through 10. Most
reactions consisted of a pruritic macular papular drug
eruption that did not necessitate discontinuation of the
challenge. Forty participants could continue receiving
daily doses of TMP-SMX (80/400 mg) for 1 month, for
an overall success rate of 91%. Two of the four patients
who discontinued the desensitization process underwent
successful rechallenge later. After 10 months of follow-
up, 42 patients were actively taking TMP-SMX without
any adverse reactions, for an overall success rate of 95%.
292 20 February 2001 Annals of Internal Medicine Volume 134 Number 4
The researchers concluded that a 6-hour graded
challenge with 12 increasing doses of TMP-SMX ap-
pears to be safe and effective in HIV-infected persons.
From the internists point of view, it is extremely useful
to consider desensitization in patients who have previ-
ously experienced hypersensitivity reactions to TMP-
SMX. However, it is not clear that we can generalize
these results to persons without HIV infection. We rec-
ommended that desensitizations be undertaken in inpa-
tient or outpatient settings where the staff undertaking
the desensitization protocol are trained to recognize and
treat adverse reactions. Although no life-threatening
anaphylactic reactions were described in this study, ana-
phylaxis has been reported in previous studies of TMP-
SMX desensitization.
Environmental Controls
Maintaining an indoor relative humidity below 50% has
been shown to control dust mites in human dwellings;
this intervention has become an important part of envi-
ronmental control measures for persons allergic to dust
mites (1). Although internists have known this for some
time, it has now become apparent that dust mites may
be responsible not only for inducing but also for perpet-
uating allergic responses in the airway. The following
article reports on the advantage of controlling the dust
mite population in indoor environments.
Maintaining Average Daily Relative Humidity below 50%
Restricts the Growth of Dust Mite Populations
Arlian LG, Neal JS, Vyszenski-Moher DL. Reducing relative humidity
to control the house dust mite Dermatophagoides farinae. J Allergy
Clin Immunol. 1999;104:852-6. [PMID: 0010518832]
Arlian and colleagues sought to determine whether brief
daily periods of moist air alternating with long spells of
low ambient relative humidity can influence the survival
and growth of the common house dust mite. Population
growth for Dermatophagoides farinae was determined at
daily relative humidity regimens of 2, 4, 6, and 8 hours
at 75% or 85% relative humidity, alternating with 22,
20, 18, and 16 hours at 0% to 35% relative humidity.
Results supported findings from previous studies:
The D. farinae population declined with the use of daily
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regimens of 2 hours of 75% or 85% relative humidity
alternating with 22 hours of 0% to 35% relative humid-
ity. Daily regimens of 4, 6, and 8 hours of 75% relative
humidity alternating with 20, 18, and 16 hours of 35%
relative humidity provided sufficient moisture for small
growth in the size of mite population. Population
growth after 10 weeks was reduced by 97% to 98% for
daily regimens that involved 4, 6, and 8 hours of 75%
relative humidity and the remainder of the day at 35%.
In contrast, rapid rates of growth were seen with con-
tinuous exposure to 75% relative humidity.
The researchers concluded that maintaining mean
daily relative humidity below 50% even with inter-
mittent increases in relative humidity above 50% for 2
to 8 hours effectively restricts population growth for
dust mites and the subsequent production of dust mite
allergen. The researchers also noted that to completely
prevent population growth of D. farinae, relative hu-
midity must be maintained below 35% for at least 22
hours per day.
Environmental control measures for indoor aller-
gens are perhaps the most effective allergy treatment that
both primary care and specialists can advise for allergic
persons. In temperate climates, the size of the dust mite
population peaks when average indoor relative humidity
exceeds 50%. Previous studies have indicated that con-
sistently maintaining relative humidity below 50% is
associated not only with decreased mite population but
also with decreased rates of sensitization and symptoms
in sensitive asthmatic and rhinitic patients. This study
provides useful practical information for patients who
cannot maintain relative humidity at a constant level
below 50%. Relative humidity fluctuates at various
times in the day and may be associated with temperature
changes and use of air conditioning units. Practitioners
can advise patients that daily fluctuations in humidity
will not preclude the use of dehumidification as an im-
portant part of a comprehensive plan to control house
dust mites.
Allergies to Food and Food Additives
Food allergies pose an interesting challenge for physi-
cians. Both the diagnosis and treatment of these condi-
tions can be fraught with complications and questions.
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Update in Allergy and Immunology Update
The three food and food additive allergies examined
here are monosodium glutamate (MSG) sensitivity, egg
allergy and its potential cross-reaction with the influenza
vaccine, and peanut and tree nut allergies.
MSG Does Not Appear To Be an Allergen
Woessner KM, Simon RA, Stevenson DD. Monosodium glutamate
sensitivity in asthma. J Allergy Clin Immunol. 1999;104:305-10. [PMID:
0010452749]
Patients often report experiencing the so-called Asian
restaurant syndrome. Although MSG has been impli-
cated as a trigger for asthma in these circumstances, the
connection has been controversial and the literature on
the topic has been contradictory. To determine whether
MSG ingestion provokes asthma symptoms in patients
with asthma, Woessner and colleagues conducted a sin-
gle-blind, placebo-controlled, oral MSG challenge in 30
asthmatic patients who reported a history of asthma at-
tacks after MSG ingestion and 70 asthmatic patients
who had no MSG-related symptoms.
No patients experienced acute asthma symptoms or
reduction in FEV1 after ingestion of 2.5 g of MSG.
From these data, the researchers concluded that MSG-
induced asthma may not exist.
The existence of MSG-induced asthma has been
controversial; previous studies were poorly controlled
and yielded conflicting results. This study suggests that
internists should remain skeptical when patients at-
tribute asthma symptoms to MSG.
Patients Allergic to Eggs Can Be Safely Vaccinated by Using
a Two-Dose Protocol if the Egg Protein Content of the
Vaccine Is Less Than 1.2 g/mL
James JM, Zeiger RS, Lester MR, et al. Safe administration of
influenza vaccine to patients with egg allergy. J Pediatr. 1998;133:
624-8. [PMID: 0009821418]
Patients who are allergic to eggs have traditionally been
advised not to receive an influenza vaccine until they
have had appropriate skin testing with a diluted prepa-
ration of the vaccine. If the skin test response is positive,
the patient is advised against receiving the vaccination in
the usual manner. When vaccination is nonetheless im-
perative, multiple graded doses of the influenza vaccine
may be administered by trained personnel. These rec-
ommendations have caused confusion among both pa-
20 February 2001 Annals of Internal Medicine Volume 134 Number 4 293
Update Update in Allergy and Immunology
tients and health care providers. James and colleagues
evaluated the safety of a two-dose method of adminis-
tering influenza vaccine to 83 patients with egg allergy.
The participants had skin testing with influenza vac-
cine (1.2 g of egg protein per mL) and were then
vaccinated by using a two-step method: One tenth of
the total influenza vaccine dose was administered, fol-
lowed 30 minutes later by the remaining nine tenths of
the dose. Control patients, who did not have egg allergy
(n 124), were also vaccinated.
Four patients with egg allergy and one control pa-
tient had a positive skin test response to the vaccine. All
patients were successfully vaccinated, and none experi-
enced significant allergic reactions to the influenza vac-
cine. The researchers concluded that patients who are
allergic to eggs can be safely vaccinated by using a two-
dose protocol when the vaccine contains less than 1.2
g of egg protein per mL.
We agree with the researchers as far as the limita-
tions of the study will allow (that is, for the years studied
[1994 1997], these vaccines could be safely adminis-
tered to patients who are allergic to eggs without using
complicated skin testing and challenge protocols). Sub-
sequent vaccines could contain higher concentrations of
egg protein, however, and we therefore recommend that
the situation be analyzed anew each year.
Only about Half of Patients with Peanut or Tree Nut Allergy
Seek Medical Advice for This Potentially Life-Threatening
Condition
Sicherer SH, Munoz-Furlong A, Burks AW, et al. Prevalence of
peanut and tree nut allergy in the US determined by a random digit
dial telephone survey. J Allergy Clin Immunol. 1999;103:559-62.
[PMID: 0010200001]
Peanut and tree nut allergies are responsible for most
severe food-induced allergic reactions (2). Scherer and
colleagues sought to determine the prevalence of peanut
and tree nut allergy in the United States on the basis of
results of standardized questionnaires administered to
4374 persons using a nationwide, cross-sectional ran-
dom-digit-dial technique.
Peanut or tree nut allergy was self-reported in 1.4%
of participants (95% CI, 2.9% to 4.0%). The preva-
lence of peanut or tree nut allergy was 1.6% in adults
and 0.6% in children. Of note, only 53% of patients
allergic to peanuts or tree nuts had ever seen a physician
294 20 February 2001 Annals of Internal Medicine Volume 134 Number 4
for the problem, and injectable epinephrine had been
prescribed for only 7%. The researchers concluded that
peanut or tree nut allergy affects approximately 3 mil-
lion Americans and that nearly half of these do not seek
treatment.
From the internists perspective, the data indicate
that peanut and tree nut allergies are potentially life-
threatening conditions that require education regarding
avoidance and preparedness for accidental ingestion. Al-
though extensive educational resources are available,
alarmingly few patients seek medical advice about these
allergies. An awareness of these issues will help primary
providers identify these patients earlier, thereby avoiding
repeated ingestion of these allergens.
Inhaled Corticosteroid Therapy
The availability of topically active corticosteroids deliv-
ered directly to the airways by inhalation has changed
the anti-inflammatory treatment of asthma. The familiar
adverse effects associated with oral corticosteroid main-
tenance therapy are no longer an issue for patients using
low doses of inhaled corticosteroids, but high-dose,
long-term therapy with inhaled corticosteroids may be
associated with some systemic adverse effects.
Long-Term, High-Dose Corticosteroid Therapy May Be a
Risk Factor in Development of Adrenal Suppression,
Osteoporosis, and Posterior Subocular Cataracts
Lipworth BJ. Systemic adverse effects of inhaled corticosteroid ther-
apy: a systematic review and meta-analysis. Arch Intern Med. 1999;
159:941-55. [PMID: 0010326936]
To evaluate the available data on systemic adverse effects
of currently available inhaled corticosteroids, Lipworth
searched three medical literature databases (MEDLINE,
EMBASE, and BIDS) for reports published from Janu-
ary 1966 through July 1998. All reports on the systemic
effects of inhaled corticosteroids on adrenal function,
growth, bone, skin, and eye were reviewed. This meta-
analysis examined the degree of adrenal suppression re-
ported in 27 studies.
The results indicated that the potential for dose-
related adrenal suppression is much greater with flutica-
sone than with beclomethasone dipropionate, budes-
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onide, or triamcinolone. Significant adrenal suppression
was noted with high dosages of all inhaled corticoste-
roids, that is, dosages greater than 1.5 mg/d for be-
clomethasone dipropionate, budesonide, or triamcino-
lone or 0.75 mg/d for fluticasone. With dosages in this
range, bone density may also be significantly reduced.
Although studies have indicated that medium-term
growth may be suppressed by 400 g of beclomethasone
dipropionate per day, no evidence supported any signif-
icant effect on final adult height. Long-term, high-dose
inhaled corticosteroid exposure may increase the risk for
posterior subcapsular cataracts and, to a lesser degree, for
ocular hypertension and glaucoma. Skin bruising was
associated with high-dose exposure and correlated with
the degree of adrenal suppression. The risk for subcap-
sular cataracts in patients treated with inhaled cortico-
steroids is influenced by age, ethnicity, and previous oral
corticosteroid treatment. The reported incidence in the
reviewed studies varied from 0% to 54% (average,
10%).
These data indicate that systemic adverse effects
may be seen after long-term, high-dose inhaled cortico-
steroid use and that fluticasone should be considered a
high-potency inhaled corticosteroid whose power is ap-
proximately twice that of previously available prepara-
tions. When fluticasone is increased to a dosage exceed-
ing 0.8 mg/d, dose-dependent suppression of adrenal
function may occur, indicating that substantial amounts
of the inhaled steroid are absorbed. In many cases, stud-
ies evaluating the effects of inhaled corticosteroids on
bone mineralization and ocular side effects are compli-
cated by previous use of systemic steroids. Although
some studies have found a consistent effect of low-dose
inhaled steroids on increased development of posterior
subcapsular cataracts and on increased intraocular pres-
sure, other studies have not confirmed these observa-
tions. Most studies have shown no differences in bone
mineral density between steroid- and nonsteroid-treated
groups of adults receiving long-term inhaled cortico-
steroid therapy. Studies reporting changes in bone min-
eral density have found no association with increased
vertebral fracture. These results support the long-term
safety of low-dose inhaled corticosteroids. Lipworth
concluded, however, that long-term, high-dose inhaled
corticosteroid use should be considered a possible risk
factor for adrenal suppression, osteoporosis, and poste-
rior subcapsular cataracts.
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Update in Allergy and Immunology Update
The internist must realize that when caring for pa-
tients with chronic persistent asthma, inhaled corticoste-
roids remain the most effective form of anti-inflamma-
tory therapy, as described in the National Heart, Lung,
and Blood Institute and National Asthma Education
Program Guidelines. Because of the potential for sys-
temic adverse effects with high-dose inhaled corticoste-
roids, practitioners now attempt to use the lowest effec-
tive dose of inhaled corticosteroids. With the increasing
number of effective alternative nonsteroidal therapies
now available, including long-acting -agonists, the-
ophylline, and antileukotrienes, internists should con-
sider using add-on therapy when low-dose inhaled cor-
ticosteroids are inadequate rather than increasing the
dose of inhaled corticosteroids. We suggest that for the
small proportion of patients who require long-term,
high-dose inhaled steroid therapy, biannual checks for
systemic effects on the adrenal glands, bones, and eyes
seem reasonable. The bottom line is that it is prudent to
taper the inhaled corticosteroid dose to the lowest effec-
tive maintenance dose that will achieve long-term con-
trol of the underlying disease.
Monoclonal Anti-IgE Receptor Antibody
With the increasing recognition that most patients with
asthma have specific allergic triggers, treatment regimens
for asthma have increasingly targeted allergic mecha-
nisms.
Recombinant Humanized Monoclonal Antibody Directed
against the IgE Receptor Is Potentially Effective for
Treatment of Allergic Asthma
Milgrom H, Fick RB Jr, Su JQ, et al. Treatment of allergic asthma
with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group.
N Engl J Med. 1999;341:1966-73. [PMID: 0010607813]
Milgrom and colleagues conducted a multicenter study
to investigate the efficacy and safety of a recombinant
humanized monoclonal antibody directed against the
high-affinity IgE receptor (rhu-MAb-E 25). They stud-
ied 317 steroid-dependent patients with allergic asthma.
Patients ranged in age from 11 to 50 years and had
moderate to severe persistent asthma. They underwent
active treatment for 20 weeks after a 4-week run-in
20 February 2001 Annals of Internal Medicine Volume 134 Number 4 295
Update Update in Allergy and Immunology
period, during which time either high-dose (5.8 g per
kg of body weight per ng of IgE per mL) or low-dose
(2.5 g per kg of body weight per ng of IgE per mL)
antibody was administered intravenously every other
week for 20 weeks. Primary outcome measures were
asthma symptom scores. Secondary outcome measures
were use of rescue -agonists, reduction in oral or in-
haled corticosteroid doses, changes in FEV1 and peak
flows, and asthma-specific quality of life.
Symptom scores measured on a 7-point scale were
reduced from 4.0 at baseline to 2.8 in both treatment
groups. In the placebo group, scores decreased from 4.0
to 3.1. Peak flows increased approximately 20 to 30
L/min in the treatment groups, a change associated with
an increase in FEV1 of approximately 2% in both
groups. In both treatment groups, 50% of patients
could reduce their oral or inhaled corticosteroid dose by
50%. In the placebo group, 38% of patients could de-
crease their corticosteroid requirement by 50%. Asthma-
specific quality-of-life scores increased from 1.2 to 1.4,
respectively, in the treatment group and increased by 0.8
in the placebo group. Serum free IgE concentrations
decreased by more than 95% in both treatment groups.
The treatment was well tolerated, and no serious sys-
temic side effects occurred. Antitreatment antibodies did
not develop in either treatment group.
This study suggests that anti-IgE receptor antibody
treatment may be helpful in patients with steroid-depen-
dent asthma because the benefits of both high-dose and
low-dose treatment appear to be statistically significant.
On the other hand, the observed clinical benefit is only
marginal. It is unclear whether this new form of therapy
will achieve clinical utility as a single therapy for allergic
asthma. It is also likely that it may be used as adjunctive
therapy in the setting of rush desensitization (during
which patients could conceivably be desensitized in
weeks rather than the years required with the current
practice). Further study is needed.
Asthma Severity
Gauging the severity of asthma goes beyond observing
current symptoms. Because severe asthma can be very
well controlled at any particular moment in time, a full
296 20 February 2001 Annals of Internal Medicine Volume 134 Number 4
knowledge of the patients history should direct treat-
ment strategies.
Symptoms Alone Do Not Reflect the Severity of Asthma
Osborne ML, Vollmer WM, Pedula KL, et al. Lack of correlation of
symptoms with specialist-assessed long-term asthma severity. Chest.
1999;115:85-91. [PMID: 0009925066]
Osborne and colleagues conducted a cross-sectional
study to validate three indicators of asthma severity as
defined by the National Asthma Education Program
frequency of symptoms, degree of airflow obstruction,
and frequency of use of systemic corticosteroidsindi-
vidually and in combination. The study also compared
these observations with severity of asthma assessed by
pulmonary experts privy to the 24-month medical chart
data. A 2-year retrospective chart review and assessment
by an asthma specialist were compared with a cross-
sectional assessment of symptoms, spirometry, and med-
ications.
On the basis of the full chart review of 193 patients
with asthma, the researchers concluded that asthma was
mild in 45% of patients, moderate in 45%, and severe
in 9%. The severity scale is based on daytime and
nocturnal symptom frequency: Mild indicated symp-
toms occurring less than once a week; moderate,
symptoms occurring 2 to 6 times a week; and severe,
symptoms occurring daily. Retrospective asthma severity
assessments correlated with current spirometry and cor-
ticosteroid requirement but not with current asthma
symptoms.
These findings led the researchers to conclude that
underlying asthma severity is not predicted by current
symptoms. These findings serve to remind the internist
that proper asthma management requires both accurate
severity staging (based on past medication requirements,
hospitalizations, emergency department visits, and spi-
rometry) and objective monitoring over time. The pa-
tient with severe asthma is at higher risk for future
asthma morbidity and therefore requires more careful
follow-up (for example, environmental assessment, trig-
ger avoidance, and serial spirometry) than the patient
with mild asthma who is not receiving medication reg-
ularly.
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Allergic Rhinitis
Rhinitis Seems To Be an Independent Risk Factor
for Asthma
Leynaert B, Bousquet J, Neukirch C, et al. Perennial rhinitis: an
independent risk factor for asthma in nonatopic subjects: results
from the European Community Respiratory Health Survey. J Allergy
Clin Immunol. 1999;104:301-4. [PMID: 0010452748]
The correlation between allergic asthma and allergic rhi-
nitis has been recognized for some time, but Leynaert
and colleagues conducted this study to determine the
strength of the association between asthma and rhinitis
in nonallergic persons. This population-based study of
6610 persons 20 to 44 years of age was performed by
using data from a questionnaire, skin tests, serologic
measurement of IgE, and methacholine challenge.
The frequency of bronchial hyperresponsiveness was
11.6% in nonatopic participants with rhinitis and 6.6%
in nonatopic controls (P 0.001). The frequency of
bronchial hyperresponsiveness was 26.7% and 10%,
respectively (P 0.001). The probability of having
asthma was strongly associated with rhinitis, with an
odds ratio greater than 9. These associations were inde-
pendent of serum total IgE levels.
The researchers concluded that rhinitis may be an
independent risk factor for asthma. For the internist,
this study confirms that the association is not just due to
atopy and emphasizes that physicians need to be aware
of the risk for asthma in patients with chronic rhinitis.
Clinical Regression Induced by Immunotherapy Continues
after Injections Are Discontinued
Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy
of grass-pollen immunotherapy. N Engl J Med. 1999;341:468-75.
[PMID: 0010441602]
Pollen immunotherapy is effective in some patients with
IgE-mediated seasonal allergic rhinitis, but whether a
long-term benefit persists after discontinuation of treat-
ment has been a question. To determine whether the
efficacy of grass pollen immunotherapy continues when
injections are discontinued after 3 to 4 years of therapy,
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Update in Allergy and Immunology Update
Durham and colleagues conducted a randomized, dou-
ble-blind, placebo-controlled trial. Primary outcome
measures were symptom scores and medication use.
Other measures included skin testing, conjunctival chal-
lenge, and skin biopsy 24 hours after skin testing. The
investigators also studied a matched control group con-
sisting of patients with seasonal allergic rhinitis who had
not received immunotherapy.
Symptom scores and medication use did not differ
between patients who discontinued immunotherapy and
those who continued this therapy. However, symptom
scores and medication use were markedly lower in pa-
tients receiving immunotherapy than in matched con-
trols. Reduction of T-cell infiltration and expression of
interleukin-4 in skin biopsy specimens were unaffected
by the discontinuation of immunotherapy.
The researchers concluded that discontinuation of
grass pollen immunotherapy after 3 or 4 years of injec-
tions results in retained clinical efficacy and no loss of
suppression of markers of late-phase allergic reactivity.
For the internist, the important message is that the clin-
ical remission induced by immunotherapy can be main-
tained after discontinuation of injections. This suggests
that immunotherapy may be a cost-effective alternative
for many allergic patients.
From Oregon Health Sciences University, Portland, Oregon.
Requests for Single Reprints: Anthony Montanaro, MD, Division of
Allergy and Immunology, Oregon Health Sciences University, 3181 SW
Sam Jackson Park Road, Portland, OR 97201; e-mail, amontanaro
@ohsu.edu.
Current Author Addresses: Drs. Montanaro and Tilles: Division of
Allergy and Immunology, Oregon Health Sciences University, 3181 SW
Sam Jackson Park Road, Portland, OR 97201.
References
1. Guidelines for the Diagnosis and Management of Asthma. Expert Panel Re-
port 2. National Asthma Education and Prevention Program. Bethesda, MD:
National Institutes of Health; 1997. NIH publication no. 97-4051.
2. Yunginger JW, Sweeney KG, Sturner WQ, Giannandrea LA, Teigland JD,
Bray M, et al. Fatal food-induced anaphylaxis. JAMA. 1988;260:1450-2.
[PMID: 0003404604]
20 February 2001 Annals of Internal Medicine Volume 134 Number 4 297