Immunotherapy Safety for the Primary Care ... - U.S. Coast Guard

J ALLERGY CLIN IMMUNOL
VOLUME 120, NUMBER 3
Cox et al S45
minutes after the injection, but treatment was initiated 20
minutes after the onset of symptoms. The timing of the
reaction was unknown in 4 of the fatal reactions.
In an earlier AAAAI survey, 17 fatalities associated
with allergen immunotherapy were reported for the years
1985-1989. 190 Onset of anaphylaxis occurred within 20
minutes in 11 patients, within 20 to 30 minutes in 1 patient,
and after more than 30 minutes in 1 patient. Four patients
did not wait after the injection, and the onset of their systemic
reaction symptoms is not known.
In a prospective study a total of 20,588 extract injections
were administered to 628 patients, resulting in 52
systemic reactions in 42 patients, with 38% of the systemic
reactions occurring from 30 minutes to 6 hours after the
allergy vaccine administration. 192 In another prospective
study 8% of systemic reactions occurred more than 2
hours after injection. 193
Most of the extract manufacturers’ package inserts
recommend a wait period of either 20 to 30 minutes or 30
minutes after administration of the immunotherapy injection.
The European Academy of Allergy and Clinical
Immunology’s recommended observation period after an
allergen immunotherapy injection is 30 minutes. 194
Because most reactions that resulted from allergen
immunotherapy occurred within 30 minutes after an
injection, patients should remain in the physician’s office
for at least 30 minutes after receiving an injection, but
longer waits are reasonable, as directed by the physician.
In addition, patients who are at increased risk of a systemic
reaction might need to carry injectable epinephrine. Such
patients might also need to remain in the physician’s office
more than 30 minutes after an injection. These patients
should be instructed in the use of epinephrine to treat a
systemic reaction that occurs after they have left the
physician’s office or other location where the injection
was given. The risks and benefits of continuing allergen
immunotherapy in patients who have had a severe systemic
reaction should be carefully considered.
b-Adrenergic blocking agents
Summary Statement 17: b-Adrenergic blocking agents
might make allergen immunotherapy–related systemic
reactions more difficult to treat and delay the recovery.
Therefore a cautious attitude should be adopted toward
the concomitant use of b-blocker agents and inhalant
allergen immunotherapy. However, immunotherapy is
indicated in patients with life-threatening stinging insect
hypersensitivity who also require b-blocker medications
because the risk of the stinging insect hypersensitivity is
greater than the risk of an immunotherapy-related systemic
reaction. C
b-Blockade enhances pulmonary, cardiovascular, and
dermatologic end-organ effects of mediators and increases
mortality associated with experimental anaphylaxis induced
by either immunologic or nonimmunologic mechanisms.
Patients who are receiving b-adrenergic blocking
medications might be at increased risk if they experience a
systemic reaction to an allergen immunotherapy injection
because the b-receptor blockade might attenuate the
response to epinephrine. 195-202 Patients who are receiving
b-blocking drugs were almost 9 times more likely to be
hospitalized after an anaphylactoid reaction from radiocontrast
media. 198 Although topical b-blockers have
markedly less systemic b-antagonist effects than oral
b-blockers, they still might exhibit some systemic
b-antagonist effects. Whether topical b-blockers pose
the same or a smaller risk than oral b-blockers in regard
to the treatment of allergen immunotherapy–related systemic
reactions is not known.
There have been very few studies that have examined
the effect of b-blocker medications on allergen immunotherapy.
A prospective 1-year study designed to determine
whether patients taking b-blocker drugs were at increased
risk of immunotherapy-induced systemic reactions found
that there were 166 systemic reactions out of 56,105
injection visits in 3178 patients (68 were receiving a
b-blocker). 203 The systemic reactions occurred in 144
(4.5%) patients, and only 1 of these patients was receiving
a b-blocker medication. The authors calculated that by
chance, 3.08 patients receiving the b-blocker medications
drugs were expected to have had an systemic reaction and
concluded that b-blocker medications did not increase the
frequency of allergen immunotherapy systemic reactions
(P >.95).
In another study of 1389 patients prescribed immunotherapy
for Hymenoptera venom hypersensitivity who
were followed for 34 months, there were 25 patients who
received concomitant b-blocker medications. 204 Three
(12%) of the 25 patients receiving b-blocker medications
experienced systemic reactions during immunotherapy
compared with 23 (16.7%) of 117 patients with cardiovascular
disease not receiving b-blockers. Systemic reactions
after a field sting or challenge occurred in 1 (14.3%) of 7
cardiovascular patients receiving b-blocker medications
compared with 4 (13.8%) of 29 cardiovascular patients
not receiving b-blocker medications. No severe reactions
to immunotherapy or sting re-exposure were observed in
patients receiving b-blockers medications.
Immunotherapy is indicated in patients with life-threatening
stinging insect hypersensitivity who also require
b-blocker medications because the risk of the stinging
insect hypersensitivity is greater than the risk of an
immunotherapy-related systemic reaction. In such cases,
intravenous glucagon, which might reverse the refractory
bronchospasm and hypotension by activating the adenyl
cyclase directing and bypassing the b-adrenergic receptor,
might be used if epinephrine has not been effective. 205,206
Prospective studies are necessary to clarify the magnitude
of the risk of systemic reactions to allergens in patients
who are receiving concomitant therapy with b-blockers,
and a cautious attitude should be adopted toward the concomitant
use of b-blocker agents and inhalant allergen
immunotherapy.
Contraindications
Summary Statement 18: Medical conditions that reduce
the patient’s ability to survive the systemic allergic reaction
or the resultant treatment are relative contraindications