Download posure to injectable cephalosporins were selected for

posure to injectable cephalosporins were selected for
study. Reactions had occurred 1 to 48 months before evaluation. All 6 children had reacted to ceftriaxone, and 5/6
had suffered anaphylaxis.
Methods. All participants were skin tested with penicilloylpolylysine, minor determinant mixture, penicillin G,
ampicillin, and amoxicillin; also, cephalothin, cefuroxime,
ceftazidime, cefotaxime, and ceftriaxone. The various
cephalosporins were tested at 2 mg/mL, a concentration
previously shown to be a nonirritant in healthy control
subjects. Radioallergosorbent tests (RASTs) were also performed to benzylpenicilloyl-polylysine, amoxicilloyl-polylysine, ampicilloyl-polylysine, and to the various cephalosporins conjugated to polylysine.
Results. All 6 children had positive skin tests (1 prick,
5 intradermal) for the culprit drug, but none had positive
RASTs. No child reacted to any of the other cephalosporins
or to any penicillin reagents. Among the adults, all but 2
individuals had positive skin tests, and 9 had positive
RASTs to the culprit drugs. No one had positive RASTs
with negative skin tests. Two adults had a total of 3 completely negative test batteries, including agents that had
caused anaphylaxis 24, 40, and 45 months earlier. A total of
10 adults reacted to ⬎1 cephalosporin, and there was no
compelling pattern of cross-reactivity. Similarly, there was
no pattern apparent in the 4 patients who reacted to penicillin reagents.
Conclusions. Most patients with histories of allergic reactions to cephalosporins are sensitized to determinants
specific for the given drug, although some display crossreactivity to other cephalosporins. A few individuals display reactivity to penicillin determinants, but this is not
predicted by culprit drug or nature of reaction.
Reviewer’s Comments. This study focused on reactions
after parenterally administered cephalosporins and clearly
highlights the low but unpredictable incidence of crossreactivity among these agents and the penicillins. Pediatricians dealing with the quandary of a child with a history of
suspected reaction from an orally administered preparation in the outpatient setting should realize that other
cephalosporins might be tolerated just fine. Because there
are no reagents for in vivo or in vitro testing for these oral
cephalosporins, the only test is administration followed by
a couple hours of observation in the office. For the hospitalized child with a history of allergy to an injected cephalosporin and in need of such now, it makes sense to skin
test first with the agent(s) to be considered. If the history is
one of reacting to an orally administered cephalosporin, it
is probably even likelier that the parenteral agent would be
well-tolerated. However, because most severe reactions
follow injected drug at any age, it would be wise to skin
test with the desired injectable cephalosporin first. Finally,
the authors described 2 adults with histories of anaphylaxis but with currently negative tests, as mentioned above.
These cases represented some of the longest intervals from
time of reaction to evaluation date among all the patients
studied. Drug allergy often wanes over months and years,
and this can happen even when the initial reactions were
life-threatening.
James R. Banks, MD
Arnold, MD
LACK OF ALLERGIC CROSS-REACTIVITY TO
CEPHALOSPORINS AMONG PATIENTS ALLERGIC
TO PENICILLINS
Novalbos A, Sastre J, Cuesta J, et al. Clin Exp Allergy.
2001;31:438 – 443
440
ALLERGY AND IMMUNOLOGY
Purpose of the Study. To assess the safety of administering cephalosporins to penicillin-allergic patients.
Study Population. Forty-one patients (age 19 –72, 14
male/27 female) with confirmed penicillin allergy by history, skin testing and in some cases by penicillin or amoxicillin challenge.
Methods. All subjects underwent skin testing for penicilloyl-polylysine (PPL), minor determinant mixture
(MDM), benzylpenicillin (PG), and amoxicillin (AX). A
wheal 3 mm greater than the saline control was considered
positive. If the prick skin tests were negative, than intradermal (ID) tests were performed, where a wheal 5 mm
greater than the negative control was considered positive.
If the ID tests were negative, PG was administered intramuscularly beginning with 1000 U and increasing incrementally to as high as 1.2 million U. After completing this
challenge, the subjects returned in 20 days and was skin
tested again and challenged to PG in a similar fashion. In
the case of amoxicillin allergy, oral AX was administered
in progressively increasing doses from 25 mg up to 500 mg
every 45 mins, unless a reaction occurred. Once the diagnosis of penicillin (PCN) allergy was confirmed, cephalosporin testing was performed for cefazoline, cefuroxime,
and ceftriaxone at 25 mg/mL and 250 mg/mL by puncture
test and at 2.5 mg/mL and 25 mg/mL for ID testing. If the
cephalosporin skin testing was negative, doses of each was
injected intramuscularly beginning with 25 mg increasing
progressively to as much as 500 mg. The challenges occurred over as long as 2 days. All challenges were performed in a single-blinded manner.
Results. Thirty-four patients had AX or amoxicillin/
clavulanic acid allergy, 1 had AX and cloxacillin allergy, 3
had PG allergy and in 3 cases the drug was unknown.
Thirty-eight had a positive skin test to some PCN or AX
reagent. Fifteen (36.5%) had positive skin test to AX only
with negative skin test to remaining PCN determinants.
Ten (24.3%) had 1 or more positive skin tests to PCN
determinants and negative to AX. Thirteen (31.7%) had
positive skin test to PCN determinants and AX. In 3 subjects, the skin testing for PCN and AX was negative, but
they had a positive oral challenge to AX. Two of them who
were rechallenged with PCN had good tolerance to it. Four
(9.7%) had the diagnosis of PCN allergy made during the
rechallenge study 20 days after the initial study. One of
these subjects had a systemic reaction during the intradermal test. Skin tests to cephalosporins were negative in 39
patients, equivocal by ID technique in 2 and all 41 tolerated
3 cephalosporins by the intramuscular route.
Conclusion. This study indicates that penicillin-allergic
patients may receive cephalosporins with a low risk of
having an allergic reaction, as long as the cephalosporin
has a different side chain from the PCN causing the allergic
reaction and the drug is given under careful supervision.
Reviewer’s Comments. More than a third of patients
with positive skin testing to only AX had negative skin
testing to major and minor determinants, which supports
testing for AX in addition to standard PCN testing. About
10% of subjects with PCN allergy were diagnosed at rechallenge, which supports the need to include rechallenge
in the evaluation of PCN allergy. Previous studies of crossreactivity between PCNs and cephalosporins have noted as
much as a four-fold risk for reactions in PCN-sensitive
subjects versus controls. These studies were performed
with cephalosporins with similar side chains to PG. Others
report between 12% to 38% of PCN-allergic subjects reacted to cephalosporins with similar sidechains, but reactions to cephalosporins without similar side chains have
not been described. Therefore, when it comes to crossreactivity between PCNs and cephalosporins, they are not
all alike in the level of risk and those with dissimilar side
chains offer the lowest risk of cross-reactivity.
Mary Beth Bollinger, DO
Baltimore, MD
IMMUNOTHERAPY
PREVENTION OF NEW SENSITIZATIONS IN
ASTHMATIC CHILDREN MONOSENSITIZED TO
HOUSE DUST MITE BY SPECIFIC
IMMUNOTHERAPY: A 6-YEAR FOLLOW-UP STUDY
Pajno GB, Barberio G, De Luca FR, Morabito L, Parmiani
S. Clin Exp Allergy. 2001;31:1392–1397
Purpose of the Study. Prevalence of atopic diseases has
increased in westernized countries despite current prevention strategies. The objective of this study was to determine
whether specific immunotherapy (IT) can stop progression
of sensitization to additional environmental allergens in
children monosensitized to house dust mites.
Study Population. One hundred thirty-four children
ages 5 to 8 years, with intermittent asthma, with or without
rhinitis, sensitized to house dust mites.
Methods. Children were evaluated by prick skin testing
and measurement of serum allergen-specific immunoglobulin E (IgE). Parents of 75 children accepted IT and these
children were received IT with dust mite extract for 3
years. The remaining 63 children were treated with medication and were considered a control group. All children
were skin tested and had serum allergen-IgE measured
every year for 6 years.
Results. Both groups were comparable in regard to
age, sex, and presence of rhinitis. At the end of the 6-year
study period, 25% of patients in the IT group showed new
sensitization(s), compared with 66% in the control group
(P ⬍ .0002). The most frequent new sensitizations were
pollens, animal danders, and Alternaria mold. The IT was
well-tolerated.
Conclusion. Specific IT may prevent the development
of new sensitizations in children with asthma, with or
without rhinitis, monosensitized to house dust mites.
Reviewer’s Comments. This nonrandomized clinical
trial highlights the renewed interest in immunotherapy
because of its potential to modify the natural history of
atopic sensitization. If subsequent studies confirm the results of this trial, our standard of care may change to
include early introduction of IT in atopic children, as opposed to current symptomatic management with medication with the use of immunotherapy as a second- or thirdline treatment.
Anna Nowak-Wegrzyn, MD
New York, NY
THE UPPER AIRWAY
SUPERIORITY OF AN INTRANASAL
CORTICOSTEROID COMPARED WITH AN ORAL
ANTIHISTAMINE IN THE AS-NEEDED
TREATMENT OF SEASONAL ALLERGIC RHINITIS
Kaszuba SM, Baroody FM, deTineo M, Haney L, Blair C,
Naclerio RM. Arch Intern Med. 2001;161:2581–2587
Purpose. The daily use of either intranasal corticosteroids or histamine 1 (H1) receptor antagonists has proved
to be efficacious in the treatment of seasonal allergic rhinitis. Most patients, however, use these medications as
needed. Our objective was to compare the effectiveness of
as-needed use of H1 receptor antagonists with that of
intranasal corticosteroids in the treatment of seasonal allergic rhinitis.
Study Population and Methods. We performed a randomized, open-label, parallel-group study comparing the
as-needed use of an H1 receptor antagonist (loratadine)
that of an intranasal corticosteroid (fluticasone propionate)
in the management of fall seasonal allergic rhinitis in the
fall of 1999. Subjects kept a diary of their daily symptoms
and were examined at enrollment into the study and biweekly for 4 weeks during treatment. Outcome measures
were the Rhinoconjunctivitis Quality of Life Questionnaire
score, daily symptom diary scores, and the number of
eosinophils and the levels of eosinophilic cationic protein
in nasal lavage samples.
Results. Patients in the fluticasone-treated group reported significantly better scores in the activity, sleep,
practical, nasal, and overall domains (P ⬍ .05) of the Rhinoconjunctivitis Quality of Life Questionnaire. The median
total symptom score in the fluticasone-treated group was
significantly lower than that in the loratadine-treated
group (4.0 vs 7.0; P ⬍ .01). After treatment, the number of
eosinophils was significantly smaller in the fluticasonetreated group compared with the loratadine-treated group
(P ⫽ .001). Eosinophilic cationic protein levels followed the
same pattern, with a significant correlation between the
levels of eosinophilic cationic protein and the number of
eosinophils (Rs ⫽ 0.70; P ⬍ .01).
Conclusion. As-needed intranasal corticosteroids reduce allergic inflammation and are more effective than
as-needed H1 receptor antagonists in the treatment of seasonal allergic rhinitis.
Reviewer’s Comments. What would a study from this
group be without nasal wash data? Everybody knows that
most patients don’t use their allergy medicines just the
way we tell them to. The results of this study are reassuring that patients can do well just by using their nasal
corticosteroids as needed. I usually count on the fact that
by instructing daily use of medications, most folks will use
them every 2 or 3 days. If we suggest that patients use
medications less frequently than that, they may not use
them at all.
Allen Adinoff, MD
Aurora, CO
RISK OF ADENOID HYPERTROPHY IN CHILDREN
WITH ALLERGIC RHINITIS
Huang S, Giannoni C. Ann Allergy Asthma Immunol.
2001;87:350 –355
Purpose of the Study. To determine the risk factor of
adenoidal hypertrophy in patients with known allergic
rhinitis (AR).
Study Population. Three hundred fifteen consecutive
patients between the age of 1 and 18 years with a diagnosis
of AR who were also found to have adenoid hypertrophy
(AH). A control group of 315 similarly aged patients with
AR and no evidence of AH were randomly selected.
Methods. This was a retrospective study reviewing patients seen in the allergy clinic at a University Medical
Center in Florida over a 10-year period. AR was diagnosed
by history, physical findings, and positive skin test results.
AH was determined radiographically defined as a narrowing of the airway attributable to adenoid mass by as much
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