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Exploring the profile and diagnosis of cannabis allergy

Published online: September 28, 2018

Cannabis sativa (CS) allergy research is scarce and mostly comprised of case reports and small case-control series. From these publications it has emerged that Can s 3, the nsLTP (non-specific lipid transfer protein) of Cannabis sativa constitutes an important allergen in Europe but diagnostic tests for cannabis allergy are still poorly standardized. Alternatively, evidence has emerged that cannabis-related allergy can manifest heterogeneously from mild to severe symptoms both on cannabis exposure and ingestion of different plant-derived foods. These findings warrant in depth research on the profile of cannabis allergy and the exploration of a reliable diagnostic test.

In a recent study published by The Journal of Allergy & Clinical Immunology: In Practice, Decuyper et al. explored the clinical profile of cannabis allergy and value of different diagnostics. Overall, 120 cannabis allergic patients and 62 healthy controls were included. Additionally, 189 atopic controls with pollen and/or nsLTP sensitizations were enrolled enabling an interesting comparison between cannabis allergic patients and controls with similar sensitization profiles.

Firstly, Decuyper et al. investigated the performance of five different cannabis allergy diagnostics; a specific (s)IgE quantification for hemp (crude extract) using an ImmunoCAP technique. Secondly, Decuyper et al. developed a sIgE for a recombinant Can s 3 protein using a cytometric bead array. Next to the sIgE assays, they developed a basophil activation test (BAT) with a crude cannabis extract and the recombinant Can s 3 protein. Finally, a skin prick test (SPT) with an in-lab made Can s 3-rich extract was used. Secondly, the authors studied the clinical presentation and prevalence of pollen and nsLTP co-sensitizations in cannabis allergy and compared their observations between the different clinical groups.

Decuyper et al. found a sensitivity of 86% but a low specificity (32%) for the sIgE hemp. In comparison, the BAT with the crude cannabis extract was not superior; nor in sensitivity nor in specificity. Focusing on the Can s 3 based tests, Decuyper et al. found that all three tests (BAT, sIgE and SPT) were equally performant with a positive and negative predictive value around 80% and 60% respectively. The exploration of the cannabis allergy profile revealed that 20% of the cannabis allergic patients included in the study reported anaphylaxis on cannabis exposure, the others reported milder respiratory and/or cutaneous symptoms. Two thirds (66%) of cannabis allergic patients were Can s 3 sensitized. Apart from the Can s 3 sensitization, cannabis allergic patients are often (84%) also sensitized to pollen (mostly to birch pollen, to a lesser extend also to timothy grass pollen) and to nsLTPs other than Can s 3 (72%). Finally, almost half (45%) of the cannabis allergic patients report severe and generalized symptoms to plant-derived foods with a frequency up to 71% in patients reporting anaphylaxis to cannabis.

This article of The Journal of Allergy and Clinical Immunology: In Practice shows that cannabis allergy can manifest as a severe condition and profoundly affects quality of life. It is often associated with pollen and nsLTP sensitizations but also severe and generalized plant-derived food allergies. This study confirms that Can s 3 is a major allergen of Cannabis sativa (66% sensitized). Consequently, Can s 3-based diagnostics display the best performance. The authors propose to use the sIgE hemp assay where there’s a suspicion of a cannabis allergy as a negative result makes a cannabis allergy unlikely. In contrast, a positive sIgE hemp always needs additional diagnostic work-up with a Can s 3 based diagnostic. Additional research is needed to puzzle together the Cannabis sativa IgE reactivity profile.    

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

18-00560, Exploring the diagnosis and profile of cannabis allergy