Discussion

Kounis syndrome was described as “the concurrence of acute coronary syndromes with conditions associated with mast cell and platelet activation involving interrelated and interacting inflammatory cells in the setting of allergic or hypersensitivity and anaphylactic or anaphylactoid insults”.Reference Kounis ⁶ Of the three variants described, the type I – normal coronary arteries with no predisposing cardiovascular factors – is the most frequent in children.Reference Kounis ^{6 ,} Reference Biteker, Duran and Biteker ⁷ There are numerous pharmacological triggers described, but to the best of our knowledge this is the first case reported of a paediatric Kounis syndrome triggered by atropine.

Kounis syndrome could be infrequently recognised in clinical practice and under-reported in the literature. The diagnosis should be suspected when patients have signs of systemic allergic reactions associated with clinical, electrocardiographic, and laboratory findings of acute and transient myocardial ischaemia. A complete cardiac imaging work-up is necessary to delineate the normal coronary anatomy and to assess myocardial perfusion.Reference Ming-Jui, Hu and Ming-Yow ^{1 ,} Reference Miwa, Nakagawa and Yoshida ² Although coronary angiography is the gold standard for this purpose, we decided to avoid this invasive technique in our patient because of the low probability that he had a coronary artery disease after the broad non-invasive work-up performed. Elevated serum levels of histamine, tryptase, and IgE are observed in Kounis syndrome, and it can lead to diagnosis if increased serum levels are detected in this context.Reference Ebo, Leysen and Mayorga ⁸ We did not determine this because we did not think about the possibility of Kounis syndrome in first instance. Anyway, it is reported that serum histamine and tryptase levels do not necessarily correlate in patients presenting with anaphylaxis – sensitivity of 73% and specificity of 98%.Reference Ebo, Leysen and Mayorga ^{8 –} Reference Brockow, Garvey and Aberer ¹⁰ Skin prick and intradermal tests are helpful for the diagnosis of immediate drug hypersensitivity reactions; however, the chronology of the symptoms was compatible with atropine hypersensitivity reaction and, following the recommendations of the International Consensus on drugs allergy,Reference Brockow, Garvey and Aberer ¹⁰ they were avoided in our case because of the severe life-threatening reaction and the possibility of an equally effective and structurally unrelated safe alternative (glycopyrrolate). Regardless, moderate to low sensitivity and predictive values of skin tests for most of the drugs have been reported, and thus a negative value does not exclude the imputability of the drug.Reference Ebo, Leysen and Mayorga ^{8 ,} Reference Brockow, Garvey and Aberer ¹⁰

Therapeutic management of Kounis syndrome is a challenge. Mast cell stabilisers, steroids, and histamine antagonists are recommended as potential treatment options for the allergic event, even like prophylactic agents before anaesthesia induction of patients with an atopic or Kounis syndrome history.Reference Ming-Jui, Hu and Ming-Yow ^{1 ,} Reference Miwa, Nakagawa and Yoshida ^{2 ,} Reference Kounis ^{6 ,} Reference Biteker, Duran and Biteker ⁷ However, the most important thing is the prevention identifying and avoiding the precipitant agent. In our case, no treatment was necessary because of the short duration of the episode and the spontaneous recuperation with any sequels.

The diagnosis of Kounis syndrome due to atropine is not a certainty in our patient. Thus, atropine by itself has a sympathetic activity that could contribute to the provocation of the CAS. However, because of the reasons mentioned above, we thought that our patient fitted well with possible type I Kounis syndrome as the most probable diagnosis.