Hypersensitivity Reactions: Types, Causes, Symptoms & Treatment

Understanding Hypersensitivity Reactions: What You Need to Know

Introduction

Hypersensitivity reactions are considerably harmful or unpleasant. These responses result from the use of a medicinal substance. The adverse effects frequently anticipate risk from future administration and demand prevention, a particular therapy, a change in the dosing regimen, or a product withdrawal.

Types of hypersensitivity reactions

type 1– IgE-mediated (anaphylactic). Type 1 reactions are acute (e.g., penicillin, latex, or peanut allergy) and require immediate recognition and action.
type 2: antibody-mediated. reactions are not usually found in response to dental materials or drugs but are found in autoimmune conditions affecting the oral cavity, such as pemphigus.
type 3: immune complex-mediated. can be seen in response to dental materials, but more commonly in response to viral infections such as recurrent herpes labialis, giving rise to erythema multiforme or Stevens-Johnson syndrome
type 4: cell-mediated or delayed hypersensitivity or contact sensitivite reactions are reactions to dental materials that are very common. these reactions are usually seen in the oral cavity, where an amalgam or gold restoration is in direct contact with the buccal or lingual mucosa.

Type I Hypersensitivity Reactions

Type I reactions are also called anaphylaxis.
It is an acute, life-threatening hypersensitivity disorder defined as a generalised, rapidly evolving, multi-systemic allergic reaction.
Without treatment, anaphylaxis is often fatal due to its rapid progression to respiratory collapse.

Pathophysiology

Reactions require the presence of mast cells with attached IgE.

A patient previously exposed to a drug or other antigen has antibodies (primarily IgE) fixed to mast cells.
When the antigen (in the form of a drug, food, or an airborne substance) is reintroduced into the body, it will react with and cross-link the cell-bound antibody.
This causes an increase in intracellular calcium and the release of preformed mediators, including:
- histamine
- proteases
- leukotrienes and
- prostaglandins.
Cytokines are also released, which attract eosinophils and augment the inflammatory response. These substances cause vasodilation and increased capillary permeability, ultimately leading to fluid and leukocyte accumulation in the tissues and edoema formation.
Constriction of bronchial smooth muscle results when IgE is bound in the pulmonary region. The anaphylactic reaction may be localised, producing urticaria and angioedema, or it may result in a generalised reaction, causing anaphylactic shock.

Diagnosis

The diagnosis of anaphylaxis is a clinical diagnosis; thus, laboratory studies or other diagnostics are not necessary. Most anaphylactic deaths occur within the first hour after antigen exposure.

Consideration for anaphylaxis is appropriate in the presence of 2 or more involved systems, even in the absence of airway involvement or hypotension.

Clinical Criteria for Anaphylaxis (1 of the following with onset within minutes to hours)*

Unknown exposure to an antigen yet rapidly developing urticaria or other skin/mucosal layer symptoms associated with any one of the following:

Respiratory symptoms (dyspnea, wheezing, stridor, hypoxemia, inability to maintain patency; persistent cough and/or throat clearing can be heralding symptoms)
Hypotension (systolic less than 90 mm Hg or a decrease of greater than 30% from baseline)
Signs or symptoms of end-organ dysfunction, for example, hypotonia, syncope, or incontinence

Likely exposure to an antigen and symptoms involving any 2 of the following body systems:

Integumentary symptoms: Skin or mucosal layer (rash, pruritus, erythema, hives, swelling of the face, lips, tongue, or uvula)
Respiratory symptoms: Dyspnea, wheeze, stridor, hypoxemia, inability to maintain patency; persistent cough and/or throat clearing can be heralding symptom
Hypotension: Systolic less than 90 mm Hg or a decrease of greater than 30% from baseline
Gastrointestinal symptoms: persistent, painful cramps or vomiting

Angioedema can also mimic these symptoms. A key differentiation between angioedema and anaphylaxis is urticaria; the oral symptoms and need for airway control can otherwise mimic each other. When in doubt, treat aggressively.

Kounis syndrome (allergic angina): This is a myocardial infarction or ischemia that can occur in the setting of anaphylaxis.

Treatment

Airway

Airway management is paramount. Thoroughly examine the patient for airway patency or any indications of an impending loss of airway. Perioral edema, stridor, and angioedema are very high risk, and obtaining a definitive airway is imperative. Delay may reduce the chances of successful intubation as continued swelling occurs, increasing the risk for a surgical airway.

Decontamination

After the airway is secured, the decontamination of offending agents (if known) is the next priority to prevent continued exposure and clinical worsening. Remove any stingers, if present. Do not attempt gastric lavage in cases of ingestion, as this may not be effective and delay treatment.

Epinephrine

Epinephrine is given through intramuscular injection at a dose of 0.3 to 0.5 mL of a 1:1,000 concentration of epinephrine. Paediatric dosing is 0.01 mg/kg or 0.15 mg intramuscularly (IM) (epinephrine injection for paediatric dosage). Intramuscular delivery has proven to provide more rapid delivery and produce better outcomes than subcutaneous or intravascular delivery. Note that if intravenous (IV) epinephrine is to be given, the concentration required is 1:10,000.

The thigh is preferred to the deltoid when possible. Repeat studies have shown that providers often wait too long before giving epinephrine; it is the treatment of choice, and the rapid benefit much outweighs the risks of withholding treatment. While most patients require only a single dose, repeat doses may be given every 5 to 10 minutes as needed until symptoms improve..

IV Fluid Resuscitation

Anaphylaxis induces a distributive shock that typically is responsive to fluid resuscitation and the above epinephrine. One to 2 L or 10 to 20 mL/kg isotonic crystalloid bolus should be given for observed hypotension. Albumin or hypertonic solutions are not indicated.

Adjunctive Therapies

Often, when anaphylaxis is diagnosed, co-treatment is initiated with steroids, antihistamines, inhaled bronchodilators, and vasopressors. Glucagon can also be used if indicated. These agents can assist in refractory initial anaphylaxis or aid in the prevention of recurrence and biphasic reactions.

Corticosteroids

Corticosteroids are given for the reduction of length or biphasic response of anaphylaxis. There is minimal literature to support this use, specifically in anaphylaxis, but it has been proven effective in reactive airway diseases. Therefore, the use, dosages, and proposed mechanism of action mimic those of airway management protocols.

Methylprednisolone (80 to 125 mg IV) or hydrocortisone (250 to 500 mg IV) are the accepted treatments during the acute phase. After which oral treatment of prednisone (40 to 60 mg daily or divided twice per day) is continued for 3 to 5 days. Again, if the source is unknown and/or there is a concern for a prolonged period prior to physician follow-up, a steroid taper of up to 2 weeks may be provided. Mineralocorticoid activity is responsible for fluid retention; in those at risk, dexamethasone and methylprednisolone are the preferred agents as they induce the least mineralocorticoid effect.

Antihistamines

Antihistamines are often routinely used; the most common is H1 blocker administration of diphenhydramine 25 to 50 mg IV/IM. While the clinical benefit is unproven in anaphylaxis, its utility is evident in more minor allergic processes. In severe cases, H1 blockers such as ranitidine (50 mg IV over 5 minutes) or cimetidine (300 mg IV) may also be used in conjunction with H-blockers, as there is evidence suggesting histamine has crossover selectivity for receptors. Note that cimetidine has multiple precautions in at-risk populations, such as renal or hepatic-impaired patients or those taking beta-blockers. While IV is the initial route during stabilisation, once the patient is stabilised, they may be switched to oral if continued therapy is desired.

Bronchodilators

Bronchodilators are useful adjuncts for patients with bronchospasm. Patients with previous histories of respiratory disease, most notably asthma, are at the highest risk. Treated with inhaled beta-agonists is the first-line treatment for wheezing: albuterol alone or as ipratropium bromide/albuterol. If there is refractory wheezing, IV magnesium is appropriate with a dosage and treatment similar to severe asthma exacerbations.

Vasopressors

Vasopressors may be substituted when a patient requires more doses of epinephrine but has unacceptable side effects from the epinephrine IV infusion (arrhythmia or chest pain). In which case there has been no clear second-line physician identified, treatment guidelines would follow those of any other patient in hypotensive shock.

Glucagon

Glucagon is the reversal agent for beta-blockers and can be used as such if needed in cases where anaphylaxis is resistant to treatment in patients with beta-blockade. Known side effects include nausea, vomiting, hypokalemia, dizziness, and hyperglycemia.

Localized Anaphylaxis –

A localised anaphylactic reaction involving superficial blood vessels results in urticaria (hives).
Urticaria begins with pruritus (itching) in the area where histamine and other active substances are released.
Wheals (welts) then appear on the skin as an area of localised edoema on an erythematous base.
These lesions can occur anywhere on the skin or mucous membranes.
There seems to be little doubt that the oral mucosa is well endowed with mast cells and that type 1 reactions can occur in the oral cavity.
Urticaria of the lips and the oral mucosa occurs most frequently after food ingestion by an allergic individual.
Common food allergens include
1. chocolate, nuts, shellfish, and tomatoes
Drugs such as penicillin and aspirin may cause urticaria, and cold, heat, or even pressure may cause the reaction in susceptible individuals.
Impression compounds, colouring agents, and preservatives, as well as ingredients of mouthwashes, may all cause local swelling or even anaphylaxis

Angioedema –

rapid development of edematous swelling, particularly of the head and neck, sometimes accompanied by urticarial rashes.
It occurs when blood vessels deep in the subcutaneous tissues are affected, producing a large, diffuse area of subcutaneous swelling under normal overlying skin.
Many patients have short-term disfiguring facial swelling, but if the edoema involves the neck and extends to the larynx, it can lead to fatal respiratory failure

Angioedema most commonly occurs on the lips and tongue and around the eyes It is temporary and not serious unless the posterior portion of the tongue or larynx compromises respiration.
Respiratory distress should be treated immediately with 0.5 mL of epinephrine (1:1000) subcutaneously or, better yet, intramuscularly. This can be repeated every 10 minutes until recovery starts.
The patient should be given oxygen, placed in a recumbent position with the lower extremities elevated unless there is a danger of shortness of breath or vomiting, given fluids intravenously, and transported to hospital immediately.
Patients may need intubation to maintain the airway. When the immediate danger has passed, 50 mg of diphenhydramine hydrochloride (Benadryl [Pfizer, Parsippany, NJ]) should be given four times a day until the swelling diminishes.

Type II Hypersensitivity Reactions

It is an antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens, resulting in cellular destruction, functional loss, or tissue damage. Damage can occur via three different mechanisms:

Antibody binding to cell surface receptors and altering its activity
Activation of the complement pathway
Antibody-dependent cellular cytotoxicity

Etiology

type II hypersensitivity reaction develops in response to cell surface modifications or matrix-associated antigens generating antigenic epitopes that are regarded as foreign by the immune system.
The most common causes include medications like penicillin, thiazides, cephalosporins, and methyldopa.
The drug molecule either binds to the surface of cells, resulting in a neoantigen, or alters the epitopes of the existing self-antigen on the cell surface.
This directs the immune system to recognise modified antigens as foreign, leading to the breakdown of immune tolerance and the production of antibodies directed at self-antigens.

Immune tolerance is the phenomenon by which the immune system recognizes its antigens and does not generate an antibody response against its antigens. Factors that contribute to the breakdown of tolerance promote the production of antibodies against self-antigens