Management of soya and peanut allergic patients taking oral isotretinoin. Comment on: ‘Four‐year data from use of the nut and soya testing protocol before treatment with isotretinoin and alitretinion’

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We read with interest the recent article by Alden et al. in Clinical and Experimental Dermatology,1 but have some reservations regarding their conclusions, especially as their protocol was driven by the reaction of their index patient. The index case developed a reaction after taking isotretinoin; however, the cause of this reaction was not clear. First, we question the relevance of the IgE test to the Gly m4 protein. IgE positivity to Gly m4 is not infrequent in the oral allergy syndrome due to crossreactivity to the silver birch pollen protein BetV1, which is found in people with springtime hayfever. This is a mild allergy with very rare extension to systemic anaphylaxis unless significant quantities are consumed, there is concomitant antacid/H2 antagonist/protein pump inhibitor therapy or there is cofactor‐induced anaphylaxis. Second, Gly m4 is denatured by heating and the refined soya oil used in isotretinoin would have been heated to > 200 °C. Third, studies have shown that refined soya oil contains < 10 µg/mL protein2 and each gel capsule of isotretinoin contains < 1 mL of soya oil. In the case of peanut, cashew, milk and egg allergy, significant allergic reactivity requires a minimum of 100 µg protein.3 Thus, the extremely small amount of soya protein in the isotretinoin capsule is unlikely to be sufficient to produce any reactivity. It is possible that the reaction was due to an unrelated allergy, such as the gelatin in the capsule, and had nothing to do with the positive IgE to Gly m4 result or with the cashew allergy. It would have been interesting to know the results of skin prick testing to the content of the isotretinoin capsule and the gel capsule itself. In view of the extremely small, theoretical risk of anaphylaxis to soybean oil in patients with peanut or soya allergy, we previously proposed that patients take a single 20 mg capsule of isotretinoin followed by monitoring in clinic for at least 1 h post‐ingestion.4 We have continued to use this protocol over the past 5 years. Seven patients with known peanut allergy have taken their first capsule in clinic, with resuscitation equipment to hand, and waited for 2 h, and there have been no reactions. We therefore do not agree that patients with nut or soya allergy need to be investigated pre‐isotretinoin with specific IgE to Gly 4, 5 and 6, and we believe that patients with positive results should not be excluded from treatment. Refined soya contains negligible protein, and the European Food Safety Authority has also considered refined soya oil to be of little risk in those with soya and nut allergy.5 We continue to support our suggestion of simply monitoring patients with a known peanut or soya allergy in clinic for 2 h after ingestion of a 20‐mg isotretinoin capsule. If there is anxiety with this approach, then skin prick testing to the capsule contents should be undertaken. Indeed, over the last 5 years we have recorded negative skin testing to isotretinoin in six patients with peanut allergy who all subsequently tolerated isotretinoin therapy. Conflict of interest: the authors declare that they have no conflicts of interest. Linked article: Alden K et al. Clin Exp Dermatol 2020; 45: 627–9.

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