Anaphylaxis in children - updated guidelines

Frequently asked questions

1. What is an anaphylactic reaction? Discuss the pathogenesis and management of a child with anaphylactic shock.
2. Pathogenesis and management of anaphylaxis.
3. Mechanism, manifestations, and management of anaphylaxis.

Definition

Anaphylaxis is a serious systemic hypersensitivity reaction that is usually rapid in onset and may cause death. (UK resuscitation council)

Severe anaphylaxis is characterized by potentially life-threatening compromise in the airway, breathing, and/or the circulation, and may occur without typical skin features or the presence of circulatory shock. (World Allergy Organization Anaphylaxis Guidance 2020)

What is an Anaphylactoid reaction then?

In anaphylactoid reaction clinical anaphylaxis is caused by mechanisms other than IgE-mediated reactions namely

1. Direct release of mediators from mast cells by medications and physical factors (morphine, exercise, cold).
2. Disturbances of leukotriene metabolism (aspirin and nonsteroidal anti-inflammatory drugs).
3. Immune aggregates and complement activation (blood products)
4. Probable complement activation (radiocontrast dyes, dialysis membranes).

Anaphylactic vs Anaphylactoid reaction

Anaphylactic reaction	Anaphylactoid reaction
Immune-mediated	Non-immune mediated
IgE plays an important role	No role of IgE
Can be predicted by skin test	Can not be predicted
Sensitization is required	No sensitization required
Histamine released by degranulation of mast cells	Histamine released directly

Pathogenesis

Anaphylaxis is a type I immune-mediated allergic reaction involving mast cells and possibly basophils.

Pathway

The allergen/antigen reacts with allergen-specific IgE. Patients initially must be exposed to the responsible allergen to generate allergen-specific antibodies. (That's why prior sensitization is required).

The complex produced above activates mast cells and basophils, and possibly other cells such as macrophages.

Mast cells degranulate releasing histamine, tryptase, and cytokine leading to symptoms of acute allergy including life-threatening airway, breathing and circulatory problems.

Effects on target organs

• Histamine
  • Vasodilation,
  • Smooth muscle constriction,
  • Direct cardiac effect and
  • Stimulates Nerve end, which could present as erythema, edema, pruritus, and angioedema, bronchial constriction, increased heart rate.
• LTC4 and PGD2
  • Bronchoconstriction
  • Increased vascular permeability

Principal pathologic features in fatal anaphylaxis

1. Acute pulmonary hyperinflation,
2. Pulmonary edema,
3. Intra-alveolar hemorrhaging,
4. Visceral congestion,
5. Laryngeal edema
6. Urticaria
7. Angioedema
8. Acute hypotension due to vasomotor dilation and/or cardiac dysrhythmias.

Diagnosis

Diagnosis is mostly clinical. Anaphylaxis can be clinically diagnosed in presence of the following 3 criteria.

1. Acute onset

Anaphylaxis is essentially an acute or hyperacute response. Sudden onset and rapid progression are classical.

2. Skin or mucosal changes

Erythema, flushing, urticaria, edema, and angioedema are invariably present either alone or in combination. They may be absent in up to 20% of cases or difficult to pick up in dark skin.

The diagnosis is further supported if there is a history of exposure to a known allergen.

3. Life-threatening systemic symptoms

Involvement of any of the following systems alone or in combination.

1. Airway compromise Stridor, difficulty breathing,
2. Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced peak PEF, hypoxemia)
3. Cardiovascular compromise - Reduced blood pressure leads to hypoperfusion of end-organs leading to hypotonia, syncope, incontinence, etc.
   1. Infants and children: low systolic BP (age-specific) or >30% drop in systolic BP
   2. Adolescents and adults: systolic BP <90 mm Hg or >30% drop from patient's baseline.
4. Gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)

World Allergy Organization Anaphylaxis Guidance 2020 criteria for the diagnosis of anaphylaxis.

Article (link)

Treatment

Principles of management

• Withdrawing the trigger.
• Controlling the effects of preformed mediators released.
• Preventing more mediator release

1. Immediate action

Remove allergic trigger

Withdrawing the trigger responsible for anaphylaxis such as drugs, and chemicals in contact.

Position

1. Avoid sudden changes in posture
2. Maintaining a supine position
3. Semi-recumbent position if it helps with breathing difficulty
4. Recovery position if unconscious to prevent aspirations
5. Must not stand or walk

2. Address life-threatening problems

1. The first priority is life-saving measures using the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach.
2. Call for help
3. Give the highest concentration of oxygen possible, using a mask with an oxygen reservoir.
4. Use fluid boluses early to treat hypotension and shock.
5. Intraosseous infusion is an alternative if an intravenous line is not available or delaying treatment.
6. Keeping a patient with cardiovascular compromise flat, with or without the legs raised, increased cardiac venous return and raises cardiac output.

3. Pharmacotherapy

Adrenalin or Epinephrine

Adrenalin (1:1000) is the first line of treatment for severe anaphylaxis. IM route is preferred.

Why IM adrenalin, why not IV as the first line?

1. Required less expertise
2. Does not require access, most of the patients are in the community and do not have access
3. Well tolerated and minimal risk

Preferrable site for IM adrnalin

Inject at the anterolateral thigh.

Concentration of adrenalin

The concentration of adrenaline used is 1:1000. It means 1mg adrenaline per 1mL

Dose of adrenalin

The dose of IM adrenalin is 0.01mg/kg, to a maximum total dose of 0.5 mg. Both resuscitation council Uk 2021 and ASCIA 2021 guidelines mention the doses as per age category.

Infants under 10 kg	0.01 mg/kg = 0.01 mL/kg of 1 mg/mL (1:1000)
Children aged 1–5 years	0.15 mg = 0.15 mL of 1 mg/mL (1:1000)
Children aged 6–12 years	0.3 mg = 1 mg/mL (1:1000)
Adolescents	0.5 mg = 1 mg/mL (1:1000)

When to use IV adrenalin?

Intravenous adrenaline can be used in a hospital setting by those who are skilled and experienced in using it such as ICU setting. IV adrenaline infusion is used to manage refractory anaphylaxis

What is refractory anaphylaxis?

Where respiratory and/or cardiovascular problems persist despite 2 doses of IM adrenaline.

Antihistaminics

1. Antihistamines are considered a third-line intervention.
2. Do not use them to address the initial emergency situations.
3. Oral non-sedating antihistamines (e.g. cetirizine) in preference to sedating can be used to treat persisting skin symptoms like urticaria only after the initial stabilization.

There is no evidence to support the routine use of an H2-receptor antihistamine (e.g. ranitidine) to treat anaphylaxis.

Corticosteroids

1. Steroids are no longer advised for the emergency treatment of anaphylaxis.
2. Steroids can be used for initial resuscitation for refractory anaphylaxis or severe anaphylaxis associated with asthma/shock. Steroids must not be given preferentially to adrenaline.
3. Corticosteroids may be indicated where an acute asthma exacerbation may have contributed to the severity of anaphylaxis.

Almost all guidelines recommend against routine use of steroids.

Inhaled Bronchodilators

1. Clinical presentation of severe anaphylaxis and acute severe life-threatening asthma can be the same.
2. When the diagnosis is not clear and asthma is one of the differentials, inhaled bronchodilators such as salbutamol can be used in addition to intramuscular adrenalin.

4. Long term management

1. Document the episode on the medical record
2. Investigate the cause thoroughly aiming at the prevention of further episode
3. Written action plan
4. Counsel regarding the episode, reasons, and how to address the emergency situation
5. Availability of adrenalin and education about the use of autoinjectors devices if available.

Differential diagnosis

Common dilemma

1. Acute asthma
2. Syncope
3. Anxiety/panic attacks
4. Acute generalized urticariaia

Post-Prandial syndromes

1. Food poisoning
2. Scombroidosis

Excess endogenous histamine

1. Systemic mastocytosis
2. Carcinoid syndrome
3. Pheochromocytoma

Want to read more on immune disorders?

1. Vasculitis in children Long question
2. ADEM Long question
3. JIA Long question
4. Kawasaki disease

Before we end

Lets finish by revising types of hypersensitivity reactions

References

1. Resuscitation council UK - Anaphylaxis guidance. (link)
2. Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) analysis (link)
3. ASCIA Guidelines - Acute Management of Anaphylaxis 2021(link)
4. World Allergy Organization Anaphylaxis Guidance 2020 (link)

Author

Ajay Agade | DNB(Pediatrics), FNB(Pediatric Intensive Care), Fellowship in Pediatric pulmonology and LTV

Ajay is a Paediatric Intensivist, currently working in Pediatric Pulmonology & LTV at Great Ormond Street Hospital NHS, London

Author

Shailesh Gophane | DCH DNB Pediatrics

Shailesh completed his Pediatric residency from Port Trust Hospital Mumbai after completing DCH from J.J. Hospital, Mumbai