Salicylate intolerance T 88.6; T88.7

Hirschberg, 1902

Worldwide increasing intolerance reaction to salicylates and/or acetylsalicylic acid.

In 1902 Hirschberg described the first anaphylacticidal reactions after taking ASA. Such intolerance reactions are also described to salicylates from food and to other non-steroidal anti-inflammatory drugs(NSAIDs).

The inhibition of cyclooxygenase type I (COX I) restricts the synthesis of regulatory and anti-inflammatory prostaglandins of the type PEG2. As a result of the deficiency of PEG2 and an overexpression of the cysteinyl-leukotriene synthase, an oversupply of pro-inflammatory leukotrienes results. An increased number of leukotriene receptors on mast cells and granulocytes leads to a massive release of inflammatory mediators with anaphylactoid consequences. S.a. NSAR hypersensitivity.

Clinical correlate is intrinsic bronchial asthma, chronic rhinosinusitis (often with polyposis nasi), chronic urticaria, possibly with angioedema and gastroenteropathy.

• As an alternative to oral dosing, an i.v. provocation (under stationary conditions) can be performed.
• Patients receive an infusion of 250 ml saline solutions with 500 mg lysine in acetylsalicylic acid. Application of the solution via an automatic infusion machine with a flow rate of 125 ml/h, corresponding to an acetylsalicylic acid quantity of 250 mg/h.
• Intolerance reactions during the i.v. provocation are initially nasal in about 50 % of the patients, pharyngeal in 30 %, cutaneous in 20 % and pulmonary in 5 %.
• The initial nasal reaction is observed after an infusion of 17o-250 mg. The pharyngeal reaction is expected after an infusion of 170-260 mg acetylsalicylic acid.
• Important: After completion of the provocation, a primary late reaction is expected in 2% of the patients, and a secondary late reaction in about 15% (relapsing worsening of the acute symptoms observed during the provocation).
• With i.v. application, the half-life of circulating acetylsalicylic acid is about 15 minutes (good controllability of the intolerance reaction is possible).
• Converted into time units, the first reactions can be observed 38 minutes after the start of the infusion.

• Based on the pathomechanism described above, a causal treatment of salicylate intolerance by daily administration of ASA after controlled dosing was developed. This therapy in the form of an adaptive deactivation is currently the only causal treatment option for salicylate intolerance.
• Oral on dosage: Start with 20-30 mg acetylsalicylic acid. Up-dosage in 4-5 dosage steps up to 100 mg and 7-10 dosage steps up to the maximum dosage of 300 mg in Europe (USA: 325-1300 mg).
• After the dosage has been adjusted, patients in Europe usually continue to take maintenance doses of 100-300 mg of acetylsalicylic acid per day. (Dosages in USA: 325-1300 mg ASA per day).

1. Hirschberg A (1902) report about a case of side effects of Aspirin.Dtsch Med weekly 28: 416-417
2. Mühlmeier G et al (2014) Determination of organ-related threshold values for ASA/salicylate intolerance by intravenous provocation. Allergo J 22: 252-258
3. Wöhrl S (2018) NSAID hypersensitivity. Allergo J Int 27: 114-121