Ficus-fruit syndrome can be independent of latex allergy

90% of patients with allergic reactions to fig fruits have a ficus plant in their household.

Sensitisation to Ficus latex is found in 2.5% of atopic individuals and mostly occurs independently of latex allergy. Sensitisation is commonly associated with allergic reactions to figs and other tropical fruits.

Ficus benjamina (FB) has been first recognised as a cause of respiratory allergy in occupationally exposed workers. However, also moderate exposure to this plant in private homes or offices may cause sensitisation and respiratory symptoms, and even severe anaphylaxis after contact with Ficus plants has been reported. Because FB allergens accumulate in the house dust over time, symptoms may take a relapsing or chronic course, with patients not always being aware that their house plants are the cause of their problems.

Ficus-fruit syndrome (FFS) (1)

In addition to the role of FB as a new, and possibly underestimated, indoor allergen, evidence has accumulated that sensitisation to this plant is associated with adverse reactions to certain fruits, particularly fig fruit, kiwi, banana, papaya and pineapple that may lead to local as well as systemic reactions. The FFS is a distinct entity independent of Hevea latex allergy. Thiolproteases such as ficin and papain, but not hevein-like proteins, seem to be important cross-reactive allergens involved in this syndrome. FFS is assumed to have its origin in primary sensitisation to FB latex allergens and succeeding cross-sensitisation to various fruits. Indeed, almost 90% of patients with allergic reactions to fig fruit had a weeping fig in their home. Therefore, it is obvious that, in some cases, fig allergy could be a consequence of primary inhalant sensitisation to FB proteins and the perseverance of cross-reactive proteins in fig fruits, similarly to pollen-associated food allergy. This cross-reactivity is mediated at least partly by thiolproteases.
In dried figs, some allergenic components are lost during the drying process revealing less frequent positive skin test reactions than fresh figs. Therefore, a positive skin prick test result to dried figs may signify a high risk to develop severe reactions to any Ficus-related fruit. In tropical areas, also breadfruit and jackfruit may be involved in FFS. Fig clearly is the fruit most closely associated with FB allergens and can cause allergic reactions in subjects sensitised to FB allergens independent of sensitisation to rubber latex allergens. The FB allergen is airborne, and the sensitisation occurs through inhalation.

Latex-fruit syndrome

Another important but still ambivalent point in FB allergy is the proposed relationship with rubber latex. Fig reactions have often been described in the context of “latex-fruit syndrome”, an allergic disease resulting from cross-sensitisation to latex (Hevea brasiliensis) and several types of fruits (2). In this case, the involved allergens seem to be proteins that cross-react with hevein-like domains of Ficus. Several homologous proteins are present in both allergenic plant foods and latex, including Hev b 2 (β-1,3-glucanase), Hev b 11 (class I chitinase) and Hev b 8 (profilin). Hev b 6 (prohevein, hevein) is the latex allergen that has received the most attention as a possible cause of latex-fruit syndrome. On the one hand, in-vitro data suggest a highly significant association between FB and rubber latex (3, 4). On the other hand, when looking at patients with documented FB or fig allergy it becomes evident that concomitant sensitisation to rubber latex is not at all common. This questions the clinical relevance of cross-reactive hevein-like structures in FB allergy and Ficus-associated fruit hypersensitivity.

Case study – Fig allergy due to house dust mite sensitisation (5)

A 10-year-old-girl with a history of no-seasonal rhinitis experienced an immediate reaction after ingestion of a fresh fig. Skin prick tests revealed a sensitisation to house dust mites which was confirmed by specific IgE assay. Fig specific serum IgE levels were 1.08 U/ml and specific IgE for rDer p1 was 16.20 U/ml (total serum IgE = 377 U/ml). In contrast specific IgE levels for latex, LTP, profilin, PR-10 and pollen allergens were negative. The patient had never been exposed to FB and she didn’t experience an adverse reaction after latex exposure. Adverse reactions to fig could be due to four main characterised allergens: Fig c 4—profilin, Fig c Ficin—protease, Fig c—Lipid Transfer protein and a 17 kDa protein, a Bet v 1 homologue. In most cases, however, the ficin belonging to the group of cysteine proteases appears to be the major allergen involved in Ficus-associated reactions. This group also includes the major allergens of some fruits, such as the actinidin (Act d 1) of kiwi, the papain (Car p 1) of papaya and the bromelain (Ana c 2) of pineapple, but also one of major allergens of dust mites (Der p 1), which seem to have a partial homology with these fruit proteins. Since Der p 1 belong to the same molecular family of ficin, it has been hypothesised that the girl’s fig adverse reaction was due to this cross-reactivity.

References

  1. doi: 10.1111/j.1365-2222.2004.02046.x
  2. PMID: 7943998
  3. doi: 10.1111/j.1398-995.1998.tb03912.x
  4. doi: 10.1159/000053641. PMID: 11146386
  5. doi: 10.1186/s12948-020-00125-6