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Allergic reactions

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Introduction

A hypersensitivity reaction (allergy) is an exaggerated immune response of the body.
These exaggerated responses of the immune system basically proceed along the same pathways as appropriate and normal immune responses.
Allergies can be defined as inappropriate or harmful cellular or humoral immune responses to exogenous antigens that do not occur in all members of a given species.
The quantitative effects of the overreaction can lead to cell and tissue damage. According to the Gell and Coombs classification, the following four types of hypersensitivity reactions are distinguished.
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Type I

Immediate hypersensitivity reactions

Phase 1:
Sensitisation
Initial exposure to the antigen leads to sensitisation of the immune system.

Phase 2:
Re-exposure to the allergen
Re-exposure leads to the release of mediators, mainly histamine.

Phase 3:
Anaphylactic reaction
The latency period may vary from several seconds to several minutes.

The release of mediators (especially histamine) leads to local and systemic reactions.
Histamine (H) binds to two different receptors, referred to as H1 and H2 receptors.

Common features of the two receptors:
  • Vasodilatation of capillaries followed by flushing and a decrease in blood pressure
Clinical pictures:
  • Urticaria:
    Reddening, swelling and itching of the skin
  • Quincke oedema (angioedema):
    Swelling of the eyelids, lips and pharyngeal, bronchial and gastrointestinal mucosa
  • Allergic conjunctivitis:
    Reddening, swelling and itching of the conjunctiva
  • Allergic bronchial asthma:
    Coughing, bronchial spasms, expiratory dyspnoea

Type II

Cytotoxic antibody reactions

Cytotoxic antibody reactions are directed against basement membrane antigens or against own or foreign blood cell membranes, as in transfusion events.

Type III

Immune complex reactions

Type III reactions are characterised by the accumulation of antigen-antibody complexes in tissues, tissue interfaces between body cavities, and vessel walls.

Type IV

These are referred to as either cell-mediated, or delayed-type hypersensitivity reactions (allergies).
Type IV reactions are characterized by the production of cytokines which trigger the activation of cytotoxic T cells, macrophages and fibroblasts.
The release of enzymes that damage body tissues results in the development of necrotic tissue in which scarring (granuloma formation) ultimately takes place secondary to fibroblast activation. Clinical pictures:
- Contact dermatitis (diagnosed by patch test, etc.)

Symptoms and signs

Subjective symptoms include:
  • Scratchy palate
  • Tingling sensation in the hand, foot or genital region
  • Malaise, restlessness
These are often the first signs of anaphylaxis.

An especially typical symptom is
  • Urticaria with the development of extremely itchy wheals and occasionally with
  • Flushing (regional skin reddening) or
  • Angioedema (subcutaneous or submucosal oedema)


Early diagnosis is essential for the appropriate treatment of anaphylaxis. Various conditions such as epilepsy, vasovagal syncope, myocardial infarction, bolus aspiration (café coronary), hyperventilation and pulmonary embolism must be considered in the differential workup.

Risks of treatment

Latex, penicillins and hyaluronidases (most common allergens in wasp and bee venoms) can trigger immediate hypersensitivity reactions.
Metal implants (nickel, cobalt, palladium, and gold), amalgam (mercury), plastic monomers and polymerization accelerators can induce delayed-type hypersensitivity reactions.
Nonsteroidal anti-inflammatory drugs and analgesics, amide-type local anesthetics, and preservatives (sulfites, parabens) can lead to the development of intolerance reactions.
Intolerance reactions are not immune mediated but are hard to distinguish clinically from “real” immune responses.
In the case of intolerance, the body does not form antibodies to an antigen. Intolerance reactions do not require repeated exposure to the offensive substance, but can occur at the time of first contact.

Treatment recommendations

Hypersensitivity reactions are clinically graded according to severity as stage I to IV. Treatment is administered according to the severity of the reactions, regardless of whether the cause is immune-mediated or not.

Clinical features and drug treatment of anaphylaxis


(according to Karow and Lang-Roth 2004)

Since histamine-induced vasodilatation is H1 and H2 receptor-mediated:

A combination of H1 and H2 antagonists should always be used in treatment.

Urticaria

Roughly 25% of the population will suffer from at least one episode of urticaria during one’s lifetime. Adults are more frequently affected than children, and women twice as often as men (Wüthrich 2004).

Urticaria (hives) is a histamine-mediated hypersensitivity reaction of the skin and mucosa that is characterized by the development of itchy wheals.
The wheals are transient skin manifestations that normally disappear without a trace within a few hours.

Treatment
  • Stop allergen exposure
  • Oral H1 antihistamines (e.g. 2 Tavegil ® 1mg tablets)
  • Oral H2 antihistamines (e.g. 1 Tagamet ® 200mg tablet)
  • Oral glucocorticoids (prednisone/prednisolone 50-100 mg)
Antihistamines are normally very good at suppressing itching and edema formation but not erythema, which is induced by neuropeptides.
Avoidance of any clearly identifiable trigger substance (medication, food, etc.).
In any case, tests should be performed to determine the cause of the allergy.

Quincke oedema

Urticaria may or may not occur with focal swelling of the eyelids, lips and other parts of the body (Quincke oedema/angiooedema).
Any sudden occurrence of generalised urticaria with signs of angiooedema and/or large wheals should be treated as follows.
  • Stop allergen exposure
  • Intravenous H1 antihistamines (e.g. 1 Tavegil® 2mg vial) dilute 2 ml Tavegil® =2 mg with 8 ml saline solution and administer via a 10-ml syringe as a slow intravenous injection.
  • Intravenous H2 antihistamines (e.g. Tagamet ® 200mg vial)
  • Intravenous glucocorticoids (prednisolone 125-250mg)

Treatment of severe hypersensitivity reactions (grade III/IV)

  • Stop allergen exposure
  • Administer oxygen via a nasal tube
  • Establish venous access
  • Have the patient lie flat (with legs elevated)
  • Instruct someone to call the emergency medical service/ambulance
  1. Administer epinephrine/adrenaline (Suprarenin)
    Immediate administration of the drug in spray form is possible
    Draw 0.5 mg Suprarenin® and 9 ml NaCl 0.9% into a syringe
    Administer as a slow IV injection; repeat after 1-2 minutes

  2. Rapid fluid replacement
    z.B. Nacl 0,9%, Ringer-Lösung in ausreichender Menge
    2 liters /30 min in adults without heart problems

  3. Corticosteroids
    500 mg Solu-Decortin® IV (2g/24h max.)

  4. Antihistamines
    H1 blockers: 4 mg Tavegil®, slow IV
    H2 blockers: 400 mg IV Tagamet®

  5. For bronchospasms
    Short infusion of 0.24 – 0.48 g theophylline dissolved in 100 ml 0.9% NaCl or metered aerosol spray doses of a beta-2-sympathomimetic (e.g., Berotec®)
Cardiopulmonary resuscitation (CPR) is a basic life support measure in severity grade IV reactions.


sources

  • Karow T, Lang-Roth R (2004)   Allgemeine und spezielle Pharmakologie und Toxikologie   Thomas Karow, Pulheim