lgE-mediated anaphylaxis
• It is a sudden onset systemic hypersensitivity reaction caused by mediators released from mast cells and basophils as a result of IgE-mediated immunological reaction.
- IgE mediated
- Not on the first encounter
- Cannot be blocked.
NON-IGE-MEDIATED ANAphylaxis (Anaphylactoid reaction)
• IgE is not of antibody/antigen origin. Mast cells and basophils are directly activated and mediators are released. Non-IgE-induced mast cell and basophil activation occurs with drugs such as opiates, vancomycin, etoposide, radiocontrast agent, content of some foods, dextran and complement components.
- Not IgE mediated
- Occurs on the first encounter
- Can be prevented with premedication
Etiology
• Food is the most common cause in children in the home environment.
• In adults, drugs are the most common cause.
• Bee sting is the 3rd most common cause in children and adults.
• Medications and latex are the most common causes in the hospital setting.
• Patients with systemic mastocytosis and mast cell activation syndrome with increased basal serum tryptase levels have an increased risk of anaphylaxis.
Etiology of anaphylaxis
1. Allergen-triggered (IgE-dependent)
• Nutrients and nutritional additives
• Medicines
• Insect and bee stings
• Vaccines
• Latex
• Biological agents (monoclonal antibodies [infliximab, omalizumab, immunotherapy])
• Inhaled allergens (RARE)
2. Anaphylactoid reactions (IgE independent)
• lgG mediated
- infliximab
- Dextran
- Immune aggregates (IVIG)
- Complement activation
• Medicines
- NSAID
- Aspirin
- Opiates
- contrast agent
- Ethylene glycol
- Ethanol
• idiopathic
• Physical factors
- Exercise
- Cold
- Hot
- Ultraviolet
- Radiation
Clinical manifestations of anaphylaxis
• The reaction develops in 5-30 minutes if the antigen is given parenterally, and in the first two hours if it is taken orally. It should not be forgotten that a very rapid reaction can develop with orally ingested antigens and the faster the reaction development, the more severe the attack will be.
• Biphasic anaphylaxis: A new episode may start hours after the attack is completely resolved, and this situation is called biphasic anaphylaxis. Biphasic anaphylaxis can be seen in 6%. It may develop 1-28 hours after the first symptoms resolve. It is usually seen in the first 4 hours. The most common reason is late initiation of treatment (late administration of epinephrine) and severe initial reaction.
Symptoms and signs------------------------------------------------ ----%
• Skin ------------------------------------------------ --------------------------90
Urticaria and angioedema ----------------------------------------------- --85-90
Redness------------------------------------------------- ------------------45-55
Itching without redness -------------------------------------------2-5
• The respiratory system ----------------------------------------------- --------40 -60
Dyspnea, "wheezing" --------------------------------------------- ---------45-50
Angioedema of the upper airways ---------------------------------------50-60
Rhinitis ------------------------------------------------ --------------------------15-20
• Dizziness, fainting, hypotension ---------------------------30-35
• Abdominal ------------------------------------------------ ---------------25-30
Nausea, vomiting, diarrhea, abdominal pain
• Dier
Headache ------------------------------------------------ ---------------------5-8
Substernal pain ------------------------------------------------ --------------4-6
Convulsion ------------------------------------------------ -----------------1-2
Anaphylaxis diagnostic criteria
Presence of one of the following 3 criteria is sufficient for diagnosis
1. Acute (min to several hours) onset of symptoms such as urticaria, itching, swelling of the lips, tongue and uwla involving the skin, mucous membranes, or both, and at least one of the following
a. Respiratory problem (dyspnea, wheezing-bronchospasm, stridor, decrease in PEF (peak expiratory flow), hypoxemia)
b. Symptoms associated with low blood pressure or end-organ dysfunction (hypotonia [collapse], syncope, incontinence)
2. The occurrence of at least two of the following (minutes-hours) after exposure to a possible allergen:
a. Sudden onset of symptoms involving the skin, mucous membranes, or both, such as urticaria, itching, swelling of the lips, tongue, and uvula
b. Respiratory distress (dyspnea, wheezing, bronchospasm, stridor, decrease in PEF (peak expiratory flow), hypoxemia)
c. Symptoms associated with low blood pressure or end-organ dysfunction (hypotonia [collapse], syncope, incontinence)
D. Gastrointestinal symptoms (cramping abdominal pain, vomiting)
3. Blood pressure drop immediately after exposure to a known allergen for the patient
a. Infants and children: Low systolic pressure or more than 30% drop in systolic pressure
b. Adults: systolic blood pressure less than 90 mmHg or a 30% or more drop from that person's normal
Differential diagnosis
• Vasodepressor reaction mimicking anaphylaxis (vasovagal syncope) is observed as a result of activation of Bezoldlarish reflex. The characteristic signs of vasodepressor reactions are bradycardia, hypotension, pallor, weakness, nausea, vomiting, and in severe cases, loss of consciousness. It usually develops after emotional trauma and fear.
• In the vasodepressor reaction, pallor and the presence of bradycardia are characteristic instead of the skin findings observed in anaphylaxis such as urticaria, angioedema or flushing (sudden flushing of the face).
• Flushing conditions are also important in the differential diagnosis. Flushing can be observed in carcinoid syndrome, pancreatic tumors, medullary carcinoma of the thyroid, hypoglycemia, pheochromocytoma, alcohol consumption, autonomic epilepsy, panic attacks, and systemic mastocytosis.
• Postprandial syndromes similar to anaphylaxis are "restaurant syndromes" caused by monosodium glutamate (MSG), sulfites or histamine.
• The incidence of histamine poisoning following eating spoiled fish is gradually increasing. The reaction is associated with the formation of histamine and cis-urocanic acid from histidine by the histidine carboxylating bacteria in spoiled fish. Cis-urocanic acid increases mast cell degranulation. Fish with high histamine levels have a completely normal odor and appearance. Cooking the fish does not prevent reaction development.
Laboratory findings in differential diagnosis
• Determination of histamine and tryptase levels is important in the diagnosis and differential diagnosis of anaphylaxis. Plasma histamine level starts to increase in 5-10 minutes and remains high for 30-60 minutes. If the patient is seen one hour after the reaction, the histamine level is not expected to be high. However, urinary histamine and its metabolites may help in the diagnosis.
• The serum tryptase level peaks 30-60 minutes after the onset of anaphylaxis and may remain high for up to five hours. In the diagnosis of anaphylaxis, serum tryptase should be measured within one to two hours (less than six hours) and serum histamine level should be measured between 10 minutes and 1 hour.
• Specific IgE levels should be investigated with suspected foods in anaphylaxis of unknown origin.
Treatment
• The first drug to be given in the treatment is epinephrine:
- Increases blood pressure by stimulating α-adrenoreceptors and increasing vascular resistance.
- Reduces angioedema while improving coronary blood supply.
- It creates an inotropic and chronotropic effect in the heart by stimulating β1-receptors.
- It creates bronchodilation by stimulating β2-receptors.
- Inhibits the release of inflammatory mediators from mast cells and basophils.
- Generally, the intramuscular (IM) route is preferred initially. Studies have shown that faster and higher plasma levels are achieved with IM injection than with the subcutaneous route. In the presence of severe hypotension, epinephrine can be administered intravenously.
• Antihistamines can be given in addition to epinephrine. Although not life-saving, it is especially good for itching and urticaria symptoms. Concomitant use of H1 and H2 receptor antagonists has been shown to be superior to H1 receptor antagonist alone in improving skin symptoms and hypotension.
• The exact role of corticosteroids in the treatment of anaphylaxis is not known.
It is used in anaphylaxis based on the information that corticosteroids are useful in other allergic diseases.
- Corticosteroids stabilize cell membranes, prevent arachidonic acid metabolism.
- Decreases the number of eosinophils, mast cells and dendritic cells.
- Decreases cytokine release from T lymphocytes and macrophages.
- It reduces the release of cytokines and mediators from epithelial cells.
- It reduces fluid leakage from endothelial cells, decreases mucus secretion and increases the number of β2 receptors in smooth muscles of the airway.
• In the presence of wheezing unresponsive to epinephrine, inhaled β2-agonist can be given to the patient. If the patient is taking beta-blockers and does not improve despite bronchospasm, epinephrine and inhaled beta agonist, aminophylline is used. Both groups of drugs inhibit the release of mediators from mast cells. For mediator release, the cAMP level must decrease. B2- agonists increase the intracellular cAMP level, aminophylline and other phosphodiesterase inhibitors prevent the degradation of cAMP.
• Patients taking beta-adrenergic blockers have refractory hypotension, bradycardia and recurrence of symptoms due to inotropic and chronotropic suppression. In the treatment of these patients, epinephrine should be used as the first drug, but if there is no response, atropine and glucagon should be used. Aminophylline is used if there is treatment-resistant bronchospasm. Atropine is effective only for bradycardia.
