# Fenugreek: New Therapeutic Resource or Emerging Allergen?
## 4 Discussion
### Allergic Reactions to Fenugreek

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Table 2: _Cont._Rare type IV immune-mediated reactions following fenugreek ingestion have been reported. A lactating woman regularly consumed fenugreek seeds to stimulate milk production and developed toxic epidermal necrolysis. Skin patch tests were not performed due to their low sensitivity in cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). An oral provocation test was not performed due to the risk of serious adverse reactions. Lymphocyte transformation tests (LTTs) were positive for fenugreek without any immune cell proliferation in the presence of metamazole, acetaminophen, and ibuprofen; therefore, based on the LTT results, fenugreek was identified as the most likely causative agent. However, the other drugs taken by the patient, namely, acetaminophen, ibuprofen, and metamazole, also taken after her previous pregnancy without any adverse reactions, were not ruled out with certainty as being responsible for the adverse reactions without provocation testing [41]. Cross-reactivity between fenugreek and other legumes has also been demonstrated in other clinical studies. A study of 195 peanut-allergic children showed simultaneous sensitization to at least one legume, namely, fenugreek, soy, lupin, and lentil, and 10% of the children were allergic to fenugreek. Children with fenugreek sensitization underwent OFC, and half of them tested positive despite never having ingested fenugreek. Moreover, although only one-third of OFC-positive children developed a severe anaphylactic reaction, all OFC-positive children developed the adverse reaction with low cumulative doses of the allergen [43]. Given the positivity found for fenugreek in the six patients, we decided to consider cross-reactivity with other legumes; three out of six patients resulted positive for other legumes (peanut, soy, and green bean). Furthermore, we tested for fenugreek in other patients who visited our operative unit in the same period and reported allergic symptoms after the ingestion of legumes (lupine, soy, peanut, lentil, green bean, pea, and chickpea). We found a further 7 patients positive for both trigonella and at least another Leguminosae, according to the literature, making 10 patients sensitized simultaneously to fenugreek and other legumes. The SDS-PAGE study for the identification of fenugreek proteins showed that the pattern of the protein bands differed slightly from that of the other Leguminosae. However, an immunoblot study using rabbit-derived anti-fenugreek polyclonal antibody showed the ability of the antibody to bind at higher concentrations not only to most fenugreek proteins but also to the 22 kd bands of lupine, 30 kd of bean, 46 kd of peas, and 24 kd of chickpeas, demonstrating a potential cross-reactivity between fenugreek and these legumes [37]. In another case of allergic reaction after the ingestion of spreadable cream containing fenugreek, the patient had a positive history of lentil and fava bean allergy; in this case, appropriate in vitro diagnostic tests were performed using ImmunoCAP, which was positive for both fenugreek seeds and lentils [36]. In a 2009 clinical study, the specificity of fenugreek-specific polyclonal IgE at high concentrations was analyzed, and binding to proteins of different molecular weights from lupin, bean, pea, and chickpea was observed [37]. However, cross-reactivity between fenugreek and other legumes cannot yet be determined with certainty because there are few published cases of adverse cross-reactions, and fenugreek molecular allergens have only recently been characterized [44]. Four molecular allergens of fenugreek were characterized: Tri f1 (7S globulin or vicilin; homologous to Ara h1), Tri f2 (2S albumin), Tri f3 (11S globulin or legumin, homologous to Ara h3, Ara h4), and Tri f4 (Bet v 1-like or PR-10, homologous to Ara h8) [44; 45].