Collaboration seeks to raise awareness of cannabis allergy diagnosis, management

As cannabis use grows with expanded legalization, a group of experts is investigating allergic reactions to cannabis and developing potential policy and treatment to improve care, according to a review published in Allergy.

“A group of interested allergy health care professionals from the U.S., Canada and Europe got together to discuss cannabis allergy,” author Isabel J. Skypala, PhD, RD, a consultant allergy dietician and clinical lead for food allergy in the department of allergy and clinical immunology at Royal Brompton and Harefield hospitals in London, told Healio.

“We wanted to raise awareness about cannabis allergy amongst allergists, and its potential to hugely increase with the increased use of cannabis especially during lockdown,” said Skypala, who is also an honorary senior clinical lecturer at Imperial College in London.

These professionals established the Cannabis Allergy Interest Group and conducted a survey of allergists in the U.S., Canada and Europe on their experiences with cannabis allergy. Also, the group is working to establish a registry and biobank to collect samples from patients with cannabis allergy to enable the development of better diagnostic tests.

“This consortium is supported by the European Academy of Allergy and Clinical Immunology, the American College of Asthma, Allergy & Immunology and the Canadian Society of Allergy and Clinical Immunology, who have also provided funding for the survey and registry/biobank,” Skypala said.

Data so far

Cannabis can provoke type 1 and type 4 allergic reactions, the researchers wrote in the review.

“Colleagues from Canada report that they are now seeing more patients with allergy to cannabis, probably because it is now legal in Canada, so people feel able to disclose this,” Skypala said. “It is possible that cannabis allergy goes unreported in states or countries where it is still illegal.”

Acting as high-molecular weight allergens, the authors wrote, cannabis proteins can contribute to type 1 allergic reactions. The WHO/IUIS Allergen Nomenclature Subcommittee has accepted four of the multiple cannabis allergens that have been sequenced.

Other allergenic proteins in cannabis may include ribulose-1,5-bisphosphate carboxylase-oxygenase; adenosine triphosphate synthase; glyceraldehyde-3-phosphate dehydrogenase; phosphoglycerate kinase; heat shock protein 70; thaumatin-like protein; peptinesterases; and polygalacturonases, according to molecular analyses.

Plant carbohydrates may contribute to IgE-binding and perceived allergy as well, the authors continued, and glycoproteins that cross-react with other carbohydrates, known as cross-reactive carbohydrate domains, may help explain cross-reactivity.

Research has implicated cannabis pollen and smoke in allergic rhinoconjunctivitis, allergic keratoconjunctivitis, hypersensitivity pneumonitis and asthma symptom exacerbation. Cutaneous reactions may include generalized pruritus, contact urticaria, angioedema, upper and lower respiratory tract symptoms and anaphylaxis following cannabis use.

Patients who have touched cannabis leaves or flowers have reported contact dermatitis, and patients who have smoked hemp have reported toxicodermatitis. Recreational consumption has been associated with erythema multiforme. Anaphylaxis to Cannabis sativa with hemp seed ingestion, smoking and injection has been reported as well.

Further physiologic effects that may result from exposure include conjunctival injection, sinus tachycardia, orthostatic hypotension, anxiety or panic reactions and dysphoria. The authors cautioned that these symptoms should not be ignored or misattributed if there are strong suspicions of a serious reaction or anaphylaxis to cannabis.

As a result of cross-reactivity with nonspecific lipid transfer proteins (nsLTPs), patients who have been sensitized to Can s 3, which is the nsLTP in cannabis, may become sensitized and develop relevant clinical symptoms to a wide range of fruits, vegetables and cereals in addition to wine, beer, Hevea latex and tobacco, the authors wrote.

Beyond medicinal and recreational use, the authors noted that allergic reactions due to occupational exposure are growing, as well as due to the increasing number of people involved in its commerce. Allergic symptoms observed from the direct handling of cannabis include respiratory symptoms ranging from rhinoconjunctivitis to bronchial hyperresponsiveness and chest tightness.

However, Can s 3 has not been established as a relevant allergen in the context of occupational exposures, according to the authors, who cited the need for detailed studies into occupational cohorts.

Challenges of diagnosis

Clinical history is the most important test for diagnosing IgE-dependent cannabis allergy, the authors wrote, although patients may not admit consumption where there are legal restrictions against cannabis use. Pollen allergies also complicate the determination of cannabis allergies.

Standard intake forms such as the one developed by ACAAI can help guide diagnosis, the authors continued, but providers may need to rely on unstandardized prick-prick tests. Also, skin prick tests with preprepared cannabis extracts present issues with negative and positive predictive values, availability and cross-sensitization. No commercial sIgE tests for Cannabis sativa or Cannabis indica are currently available.

The authors recommend beginning testing with SPTs using a native extract and/or quantification of sIgE hemp. Calculation of the sIgE/total IgE ratio, molecular diagnostics and/or Basophile Activation Tests/mast cell activation tests can complement diagnosis in difficult cases. When results are negative, the authors wrote, cannabis allergy is highly unlikely.

The authors recommended against provocation challenges with inhaled cannabis, adding that it’s unknown whether oral challenges to edible cannabis products or hemp seed would be useful. Providers need to establish sensitization to other relevant allergens as well.

Avoidance is the only current treatment for cannabis allergy. When symptoms emerge, they can be treated as symptoms resulting from other allergens are treated based on the clinical phenotype, including nonsedating, second-generation antihistamines, intranasal and inhaled corticosteroids and ophthalmic antihistamine/mast cell stabilizers. Auto-injectable epinephrine is recommended for patients with a history of severe systemic symptoms or anaphylaxis. There is little evidence for other therapeutic approaches, the authors wrote.

The authors called for the development of safe desensitization and/or tolerance induction protocols as well as continued education to improve understanding and comfort levels among clinicians so they can better initiate open discussions with their patients.

“We need to develop some educational materials to enable allergists to discuss illegal drug use with patients. Other illegal drugs can also cause allergic reactions,” Skypala said. “This is something the group would also like to develop using the multidisciplinary expertise from around the globe.”

For more information:

Isabel J. Skypala, RD, PhD, can be reached at i.skypala@rbht.nhs.uk.