ANAPHYLACTIC REACTIONS TO VACCINE IN PAEDIATRIC PATIENTS

- Kanmani.S

Department of Pharmacy Practice,

C L Baid Metha College Of Pharmacy.

DEFINITION

Anaphylaxis is a type of allergic reaction, in which the immune system responds to otherwise harmless substances from the environment.

Reaction may begin within minutes or even seconds of exposure, and rapidly progress to cause airway constriction, skin and intestinal irritation, and altered heart rhythms. In severe cases, it can result in complete airway obstruction, shock, and death.

The term is commonly used to denote the clinical reaction seen with system IgE-mediated hypersensitivity reaction

Angioedema of the face such that the boy cannot open his eyes. This reaction was caused by an allergen exposure

It typically causes more than one of the following: an itchy rash, throat or tongue swelling, shortness of breath, vomiting, light headedness, and low blood pressure. These symptoms typically come on over minutes to hours.

Anaphylaxis can occur in response to almost any foreign substance. Common triggers include : venom from insect bites or stings foods, and medications. Less common causes include: food additives such as monosodium glutamate and

food colors, and topical medications. Physical factors such as exercise (known as exercise-induced anaphylaxis) or temperature (either hot or cold) may also act as triggers through their direct effects on mast cells. Events caused by exercise are frequently associated with the ingestion of certain foods. During anesthesia, neuromuscular blocking agents, antibiotics, and latex are the most common causes. The cause remains unknown in 32–50% of cases, referred to as "idiopathic anaphylaxis”.

Six vaccines (MMR, varicella, influenza, hepatitis B, tetanus, meningococcal) are recognized as a cause for anaphylaxis, and HPV may cause anaphylaxis

Medications Any medication may potentially trigger anaphylaxis. The most common are β-lactam antibiotics (such as penicillin) followed by aspirin

and NSAIDs. Other relatively common causes include chemotherapy, vaccines, protamine and herbal preparations. Some medications (vancomycin, morphine, x-ray contrast among others) cause anaphylaxis by directly triggering mast cell degranulation.

Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in fewer than one in every 50,000 courses of treatment. Anaphylaxis to aspirin and NSAIDs occurs in about one in every 50,000 persons. If someone has a reaction to penicillins, his or her risk of a reaction to cephalosporins is greater but still less than one in 1,000

PATHOPHYSIOLOGY

Arise from the activation of mast cells and basophils through a mechanism generally understood to involve crosslinking of immunoglobulin (Ig) E and aggregation of the high-affinity receptors for IgE, FcRI.

Upon activation, mast cells and/or basophils quickly release preformed mediators from secretory granules that include histamine, tryptase, carboxypeptidase A, and proteoglycans. Downstream activation of phopholipase A2 (PLA2), followed by cyclooxygenases and lipoxygenases, produces arachidonic acid metabolites, including prostaglandins, leukotrienes, and platelet activating factor (PAF). The inflammatory cytokine, tumor necrosis factor-α (TNF-α) is released as a preformed mediator, and also as a late-phase mediator with other cytokines and chemokines.

Many of these mediators are believed responsible for the pathophysiology of anaphylaxis. Histamine stimulates vasodilation, and increases vascular permeability, heart rate, cardiac contraction, and glandular secretion. Prostaglandin D2 is a bronchoconstrictor, pulmonary and coronary vasoconstrictor, and a peripheral vasodilator. Leukotrienes produce bronchoconstriction, increase vascular permeability, and promote airway remodeling. PAF is also a potent bronchoconstrictor and increases vascular permeability. TNF-α activates neutrophils, recruits other effector cells, and enhances chemokine synthesis

These overlapping and synergistic physiological effects contribute to the overall pathophysiology of anaphylaxis that variably presents with generalized urticaria and angioedema, bronchospasm, and all related symptoms

SIGNS AND SYMPTOMS

CLASSIFICATION There are three main classifications of anaphylaxis: Anaphylactic shock is associated with systemic vasodilation that causes low blood pressure Biphasic anaphylaxis is the recurrence of symptoms within 1–72 hours with no further

exposure to the allergen.The recurrence typically occurs within 8 hours. It is managed in the same manner as anaphylaxis.

Pseudoanaphylaxis or anaphylactoid reactions are a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation Non-immune anaphylaxis is the current term used by the World Allergy Organization.

Probable anaphylactic reaction: reaction occurring within 4 hr of vaccination and S/S ≥ 1 systems Dermatologic,Respiratory,Cardiovascular,GI

Possible anaphylactic reaction S/S from only 1 system, S/S from ≥ 1 system but occurring > 4 hr after vaccination

CRITERIA

There are three diagnostic criteria, each reflecting a different clinical presentation of anaphylaxis.

Anaphylaxis is highly likely when any of the following criteria is fullfilled.

CRITERIA 1 Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal

tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)

AND AT LEAST ONE OF THE FOLLOWING: Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak

expiratory function [PEF], hypoxemia) Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction (eg,

hypotonia [collapse], syncope, incontinence) Because the majority of anaphylactic reactions (>80%) include skin symptoms, it was judged

that at least 80% of anaphylactic reactions should be identified by criterion 1 — even when the allergic status of the patient and potential cause of the reaction is unknown. However, cutaneous symptoms might be absent in up to 20% of anaphylactic reactions in children with food or insect sting allergy.

CRITERIA 2

Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):

1. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula)

2. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)

3. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)

4. Persistent GI symptoms (eg, cramping abdominal pain, vomiting).

In patients with a known allergic history and possible exposure, criterion 2 should provide ample evidence that an anaphylactic reaction is occurring.

CRITERIA 3

Reduced BP after exposure to known allergen for that patient (minutes to several hours):

1. Infants and children: low systolic BP* (age specific) or greater than 30% decrease in systolic BP

2. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline

Criterion 3 should identify the rare patients who experience an acute hypotensive episode after exposure to a known allergen.

DIAGNOSIS

When any one of the following three occurs within minutes or hours of exposure to an allergen there is a high likelihood of anaphylaxis:

1.Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure causing symptoms

2.Two or more of the following symptoms after a likely contact with an allergen: a. Involvement of the skin or mucosab. Respiratory difficultiesc. Low blood pressured. Gastrointestinal symptoms

3.Low blood pressure after exposure to a known allergen

Skin involvement may include:Hives, itchiness or a swollen tongue among others

Respiratory difficulties may include:Shortness of breath, stridor, or low oxygen levels among others.

Low blood pressure is defined as a greater than 30% decrease from a person's usual blood pressure. In adults a systolic blood pressure of less than 90 mmHg is often used.

During an attack, blood tests for tryptase or histamine (released from mast cells) might be useful in diagnosing anaphylaxis due to insect stings or medications. However these tests are of limited use if the cause is food or if the person has a normal blood pressure, and they are not specific for the diagnosis.

Classificationof

Vaccine Allergy

IgE-MEDIATED REACTION TO VACCINES

IgE- mediated reaction to vaccines are more often caused by additive or vaccine component, such as gelatin, rather than microbial immunizing agent itself.

GELATIN

Partially hydrolyzed collagen of bovine or porcine origin.

A stabilizer in many vaccines.

Responsible for many anaphylactic reactions to MMR, varicella, JE vaccines.

GELATIN CONTENT OF VACCINES

EGG

Concern has existed over administration of vaccines ‘grown in eggs’ to egg-allergic recipients.

: MMR vaccine

: PCEC rabies vaccine

: Influenza vaccine

: Yellow fever vaccine

EGG CONTENT IN VACCINE

Vaccine Grown inEgg protein

contentApproach in egg-allergic patient

Measles and mumps Chick embryo fibroblast cell cultures

Picograms to nanograms

Administer in usual manner

Purified chick embryo rabies

Chick embryo fibroblast cell cultures

Picograms to nanograms

Administer in usual manner

Influenza (killed injected and live attenuated nasal)

Chick extra-embryonic allantoic fluid

Micrograms Skin test with vaccine prior to administration

Yellow fever Chick embryos Micrograms Skin test with vaccine prior to administration

LATEX If a person reports a severe (anaphylactic) allergy to latex, vaccines supplied in vials

or syringes that contain DNR should not be administered. For other latex allergies (e.g., a history of contact allergy to latex gloves), vaccines

supplied in vials or syringes that contain DNR or rubber latex can be administered.

YEAST HBV prepared by harvesting hepatitis B surface Ag from culture of Saccharomyces

cerevisiae contain up to 5% of yeast protein. Yeast associated anaphylaxis after HBV in sensitized patient appear to be rare event. HBV & HPV4 contained yeast protein.

YEAST CONTENT OF VACCINES

ANTIMICROBIAL AGENTS Neomycin, polymyxin B, and streptomycin. A single report of immediate-type allergic reaction to MMR vaccine in person with a

history of MP rash to topical neomycin. If a patient gives a history of an immediate-type reaction, it is appropriate to

investigate before immunization with vaccine containing this antibiotic.

DIPHTHERIA-TETANUS-PERTUSSIS DTP vaccines induce production of IgE in substantial percentage of recipients

who go on to receive subsequent dose without systemic reaction.

CRM 197 Mutant diphtheria protein H influenzae vaccine (HibTITER), Pneumococcal vaccine (Prevnar),

Meningococcal vaccine (Meningitec, Menjugate, Menveo)

JAPANESE ENCEPHALITIS VACCINE Immediate-type allergic reactions, consisting of urticaria with or without wheezing

occurring 5–60 minutes after vaccination.

Unusual, late-onset urticaria and angioedema reaction 1% of recipients, median interval = 2–3 days Usually confined to the skin, some cases have involved hypotension or

respiratory distress.

HBV VACCINES Risk to be 1:600,000 vaccine doses. 180,895 reports to VAERS 107 reports of pre-existing yeast allergies The possible association between reaction to HBV and yeast allergy.

MMR & VARICELLA VACCINES

MMR VACCINE

Anaphylactic reactions: 2–10 per million doses.

Allergy to gelatin has been determined to be likely cause (27–92%).

No relationship with egg allergy.

VARICELLA VACCINE

Anaphylactic reactions : 3 per million doses.

Gelatin allergy is the cause of some of these reactions.

INFLUENZA & YELLOW FEVER VACCINES

YELLOW FEVER VACCINE

Anaphylaxis reactions 7 per million doses.

Related to egg, chicken, and gelatin.

INFLUENZA VACCINE

Anaphylaxis 0.024 per 100,000 doses.

None of which was fatal, and none of which occurred in persons known to be allergic to eggs.

NON-IgE-MEDIATED REACTION TO VACCINES

NEOMYCIN 1% of the general population demonstrates DTH by patch testing to neomycin. Skin patch testing: 100-1000 mcg of neomycin. Delayed-type contact dermatitis to neomycin

Small, temporary erythematous, pruritic papules at the injection sites 48-96 hours after vaccination.

Immunization can proceed in the usual fashion.

NEOMYCIN CONTENT OF VACCINES

ALUMINUM Enhance immunogenicity of vaccines. Subcutaneous nodules are relatively common but usually resolve within a few

weeks to months. Higher incidence of contact allergy to aluminum. No reports of anaphylaxis have been attributed specifically to aluminum.

TETANUS TOXOID Mild local reactions are relatively common. Arthus reaction has been postulated. In such individuals antitoxin levels should be evaluated before determining

the need for a subsequent booster.

RABIES VACCINE

Many cases consistent with serum sickness have been reported. The timing of the reactions is from 2 to 21 days after vaccine administration. The symptoms have included those typical of serum sickness such as arthralgia,

fever, malaise, urticaria has been prominent feature.

SUGGESTED APPROACH TO SUSPECTED ADVERSE VACCINE REACTION

MANAGEMENT 1) If itching and swelling are confined to the injection site where the vaccination was given, observe

patient closely for the development of generalized symptoms. 2) If symptoms are generalized, activate the medical emergency and notify patient’s physician. This

should be done by a second person, while the primary healthcare professional assesses the airway, breathing, circulation, and level of consciousness of the patient. Vital signs should be monitored continuously.

3) drug dosing information: The first-line and most important therapy in anaphylaxis is epinephrine. There are NO contraindications to epinephrine in the setting of anaphylaxis.

a. First-line treatment: Administer aqueous epinephrine 1:1000 dilution (i.e., 1 mg/mL) intramuscularly; the standard dose is 0.01 mg/kg body weight, up to 0.5 mg maximum single dose in children and adolescents.

b. Optional treatment: H₁ antihistamines for hives or itching, you may also administer diphenhydramine (either orally or by intramuscular injection; the standard dose is 1–2 mg/kg body weight, up to 50 mg maximum dose in children and adolescents*) hydroxyzine (orally; the standard dose is 0.5–1 mg/kg/dose up to 50–100 mg maximum per day in children and adolescents). *According to AAP’s Red Book, for children age ≥12 years, the diphenhydramine maximum single dose is 100 mg.

4) Monitor the patient closely until EMS arrives. Perform cardiopulmonary resuscitation (CPR), if necessary, and maintain airway. Keep patient in supine position (flat on back) unless he or she is having breathing difficulty. If breathing is difficult, patient’s head may be elevated, provided blood pressure is adequate to prevent loss of consciousness. If blood pressure is low, elevate legs. Monitor blood pressure and pulse every 5 minutes.

5) If EMS has not arrived and symptoms are still present, repeat dose of epinephrine every 5–15 minutes for up to 3 doses, depending on patient’s response.

6) Record the adverse event (e.g., hives, anaphylaxis) to the vaccine, all vital signs, medications administered to the patient, including the time, dosage, response, and the name of the medical personnel who administered the medication, and other relevant clinical information. Report the incident to the Vaccine Adverse Event Reporting System (VAERS).

Needed medications for a community immunization clinic first-line medication Epinephrine, aqueous 1:1000 dilution, in ampules, vials of solution, or prefilled syringes, including epinephrine autoinjectors (e.g., EpiPen and Auvi-Q). If autoinjectors are stocked, at least three should be available (both pediatric and adult formulations). Optional medication: H₁ antihistamines Diphenhydramine (e.g., Benadryl) oral (12.5 mg/5 mL liquid, 25 or 50 mg capsules/tablets) or injectable (50 mg/mL solution). Hydroxyzine (e.g., Atarax, Vistaril) oral (10 mg/5 mL or 25 mg/5 mL liquid, 10 mg or 25 mg tablets, or 25 mg capsules

There are NO absolute contraindications for epinephrine use in anaphylaxis.

CAUTION:

1. Patients with cardiovascular diseases

2. Patients receiving MAO and tricyclic antidepressants

3. Recent intracranial surgery, aortic aneurism, uncontrolled hyperthyroidism

4. Patients receiving stimulants

5. Cocaine abused

REFERENCES

Kelso JM. Adverse reactions to vaccines for infectious disease.In: Middleton’s Allergy Principles and Practice. 7 th ed.2009:1189-1204