This report describes the case of a 38 years old female who reported systemic anaphylactic symptoms after her first oral ingestion of supplemental lactase enzyme-containing tablet. Enzymes are known to be high molecular weight sensitizers, and evidence of allergic symptoms has been previously reported most commonly as respiratory allergic symptoms including asthma and/or rhinitis at variable levels of exposure . Previous studies have described occupational rhino conjunctivitis, asthma, and contact dermatitis in pharmaceutical workers exposed to lactase powder for commercial use [4, 8, 9]. The earliest study reported lactase enzyme sensitization in 31% or 65 of 207 workers involved in the handling of lactase containing products . Another study elaborated on a cross-sectional survey of 94 pharmaceutical workers exposed to lactase, of which 29% or 27 had positive skin testing . Finally, a study involving 13 employees at a lactase tablet manufacturing plant demonstrated lactase sensitization in 69% or 9 employees . Unlike these reports, our patient developed solitary skin involvement, but denied respiratory symptoms of rhino conjunctivitis or asthma after repeated dermal exposures that occurred during handling of lactase enzyme tablet. Instead, she experienced involvement of respiratory tract as part of systemic anaphylactic reaction after her first oral ingestion of supplemental lactase enzyme.
In addition to studies describing occupational exposure to lactase enzyme preparations, there have been two case reports in the literature documenting more specific allergic reactions to lactase enzyme [5, 6]. The earliest case report by Binkley , described an IgE mediated allergic reaction to Aspergillus oryzae derived lactase, with the patient experiencing allergic symptoms confined to the oropharynx after oral ingestion of lactase supplements. The author suggested that the sensitization of this patient occurred either due to prior exposure to cross-reacting Saccharomyces fragilis found in the specific brand of lactase tablet, or as a result of the patient’s inhalant allergy to Aspergillus species, with a similar mechanism to an “oral allergy syndrome”. Unlike this case report, our patient did not demonstrate an IgE mediated sensitivity to inhalant Aspergillus species and she also denied known previous consumption of other supplemental lactase products to account for the sensitization. Therefore, to the best of our knowledge, the most likely route of sensitization to synthetic lactase enzyme was with repeated prior dermal exposure when handling lactase tablets to her children. Eventually she experienced contact urticaria when handling the lactase tablets and later on suffered a systemic reaction compatible with anaphylaxis upon first oral ingestion of the lactase tablet. The sensitization pattern of our patient was similar to the case report published in 2007 by Laukkanen et al. . He described the presence of serum lactase specific IgE antibodies in a pharmaceutical worker exposed to powdered form of lactase enzyme who suffered from contact dermatitis and allergic rhino conjunctivitis. However, in our case report, confirmation of IgE mediated sensitization was obtained via positive SPT to the slurry of crushed lactase tablet and concentrated lactase enzyme, as well as lack of sensitivity to other non-lactase ingredients of the lactase tablet. The negative SPT responses in two healthy volunteers and the appropriate controls we obtained during the SPT procedure confirmed that positive skin tests were specifically attributed to IgE mediated sensitivity to lactase enzyme and not due to skin irritation. In addition, although to a milder degree, patient experienced similar symptoms in clinic after the positive skin testing with the crushed lactase tablet confirming that lactase enzyme allergy was the culprit.
Pharmaceutical molds are widely used in industry as a source for producing supplemental lactase enzyme preparation. In our case report, the manufacturer confirmed that the lactase enzyme concentrate used to make the lactase tablet was derived from cultures of Aspergillus oryzae. Aspergillus oryzae is an aerobic, filamentous fungus with many applications in the food industry including its traditional use in China and Japan to produce koji, a complex enzyme preparation used in the production of soy sauce, miso, and sake [10, 11]. Its ability to secrete large amounts of proteins has facilitated its use in modern biotechnology including large scale production of enzymes including lactase . Antigenic determinants identified from Aspergillus include α-amylase—the major cause of Baker’s asthma—and lipase, and previous reports of sensitization were thought to be due to repeated inhalational exposure to the enzyme [4, 5, 11]. Since our patient did not demonstrate IgE mediated sensitivity to inhalant Aspergillus species upon SPT, but reacted to the lactase ingredient derived from Aspergillus oryzae, the likely mechanism of sensitization remains repeated dermal exposure to the same lactase tablet, but possible prior oral consumption of foods that may have contained lactase enzyme derived from Aspergillus oryzae cannot be excluded. The patient was educated about the risk of future accidental exposures with consumption of supplemental lactase-containing products and the need to carry an epinephrine auto injector, although she denied any allergic-like symptoms outside of the context of the above mentioned episodes.
Finally, this patient was self-diagnosed with lactose intolerance. Subsequently to our assessment, she was able to re-introduce the dairy products in her diet. Therefore, there was no need for further investigation of lactose intolerance and future consumption of alternate supplemental lactase enzyme.