Each individual welt emerges and vanishes within a 24 hour period, but the appearance of new welts implies that the entire episode may persist for a longer duration. Patients typically maintain good overall health, although during severe outbreaks, they may experience systemic symptoms like lethargy, malaise, and indigestion.

Anaphylaxis is characterised by a life-threatening decrease in blood pressure, breathing difficulties, or both. It may also exhibit additional symptoms such as widespread redness, itching, and the development of urticaria. True anaphylaxis is the result of an allergic reaction triggered by allergen-specific immunoglobulin (IgE). In contrast, anaphylactoid reactions present in a similar manner but do not involve IgE.

Anaphylaxis and urticaria

Anaphylaxis occurs when allergen cross-links with membrane-bound specific IgE antibodies, leading to immediate histamine release from preformed mast cell granules. This activation prompts the synthesis of other mediators like leukotrienes, with their cumulative effect developing over four to six hours, potentially causing late reactions after the initial immediate response subsides. Clinically similar reactions can be induced by substances that directly activate mast cells, even without specific IgE presence.

Urticaria and angioedema can manifest together or as components of an anaphylactic reaction, yet either condition can also occur independently, and not all cases are attributed to IgE mechanisms. Anaphylaxis, on the other hand, is a sudden, life-threatening systemic reaction with diverse causes, clinical presentations, and levels of severity. It arises from the rapid release of mediators by mast cells and basophils and can even lead to fatalities.

Anaphylaxis, urticaria, and angioedema share common pathogenic mechanisms involving vasodilation and increased capillary permeability. The symptoms of anaphylaxis can vary based on age, with young children often experiencing vomiting and cough, while older children may have symptoms like chest tightness, dizziness, hypotension, and cardiovascular collapse.

Anaphylaxis can affect anyone, but those with personal or family histories of atopic disease are at a higher risk. Anaphylaxis linked to IgE antibodies, known as type 1 hypersensitivity, represents the most severe form of immediate allergic reaction, requiring prior exposure to the allergen for IgE antibodies to form and trigger anaphylaxis.

Treatment options

The primary treatment for acute anaphylaxis involves administering 1:1.000 epinephrine (0.01mg/kg, up to 0.5mg) intramuscularly in the anterolateral thigh, repeatable every five to 15 minutes if necessary. There are no absolute contraindications for epinephrine use, and its prompt administration is crucial to prevent progression to severe anaphylaxis and potential fatality. It’s important to note that epinephrine is not recommended for the management of urticaria.

Airway protection, cardiovascular support with intravenous fluids, and b-adrenergic agonists like albuterol are essential. Antihistamines can help control urticaria and itching but are not first-line treatment. Limited evidence supports the use of corticosteroids, as they do not reduce the risk of biphasic reactions. Patients should be monitored for four to eight hours, with longer monitoring for asthmatic patients, those with severe anaphylaxis history, or those requiring multiple epinephrine doses.

Idiopathic anaphylaxis presents a challenge, often requiring continuous steroid treatment for patients with repetitive attacks. Patients experiencing frequent urticaria and angioedema attacks may find relief from regular preventive use of non-sedating, long-acting antihistamines, even at doses higher than typically recommended.

For nocturnal symptoms, sedating antihistamines like chlorphenamine and hydroxyzine are options. Cimetidine, with its unique immunosuppressive properties, is considered but offers limited benefit. Doxepin is potent but very sedating, while mirtazapine is effective with fewer side effects. Long-term steroid use should be avoided. For angioedema without urticaria, antihistamines may help, but tranexamic acid (up to 1g four times a day) can provide better results.

Conclusion

While urticaria primarily involves skin manifestations, anaphylaxis is a more widespread and severe systemic reaction, which can include urticaria as one of its symptoms. Therefore, urticaria can be considered one of the signs or symptoms of anaphylaxis, but they are not the same condition, and a differential diagnosis is required.

Tryptase as a diagnostic marker for anyphylaxis

Tryptase serves as a marker of mast cell activation, primarily found in mast cells and to a lesser extent in basophils, with the α and β isoforms being biologically significant. During anaphylaxis, serum tryptase becomes detectable 30 minutes after symptom onset, peaking between 60 to 90 minutes, then declining after two hours, returning to baseline within 24 to 48 hours.

Thus, blood samples for tryptase measurement should be collected within one to four hours of the reaction, with a follow-up baseline measurement 24-48 hours later. Generally, baseline tryptase levels above 8ng/ml are considered elevated, but a precise cut-off for diagnosis is challenging, necessitating an individualised calculation based on the formula 1.2 x baseline +2ng/ml.

Tryptase levels tend to be higher and more persistent in anaphylactic reactions to intravenous drugs and insect venom than with oral triggers like food. Elevated tryptase correlates with hypotension. However, normal tryptase levels do not rule out anaphylaxis due to suboptimal sensitivity, influenced by the absence of α-tryptase genes in about 27% of the population. An alternative criterion for diagnosis is a 20% increase above baseline +2ng/ml within four hours of an allergic reaction.

REFERENCES

Ensina LF, et al. Acute Urticaria and Anaphylaxis: Differences and Similarities in Clinical Management. Front Allergy, 2022.
Grattan CEH, et al. Urticaria, angio-oedema and anaphylaxis. Clinical Medicine, 2012.
Spickett GP, et al. Does this patient with urticaria/angioedema have anaphylaxis? Clin Med (Lond), 2011.