Pineapple
Summary
Ananas comosus, popularly known as pineapple belongs to the family of Bromeliaceae and is considered as the second most essential tropical fruit worldwide. The pineapple fruit is widely consumed fresh or cooked or even extracted for its juice. Consumption of pineapple has mostly been associated with allergic reactions, such as oral allergy syndrome (OAS), that may be related to pollens (pollen-food-syndrome). The OAS due to pineapple was found to be prevalent in various regions across the globe (Mexico, Europe, Africa, Asia and Australia), however, the percentage of prevalence was not found to be very significant. Such type of OAS (oropharyngeal, cutaneous, respiratory, or gastrointestinal manifestations) is attributed to the presence of pan-allergen profilin, Ana c 1 in pineapple fruit. Further, systemic immunoglobulin (Ig) E-mediated hypersensitivity reactions are also observed due to pineapple consumption, mainly due to its bromelain content (Ana c 2, a major allergen). Such reactions may even lead to anaphylaxis in few cases. Besides, pineapple has been found to be associated with unpleasant reactions, such as oral mucosal irritation, which is majorly due to its acidic content or bromelain-mediated proteolysis of oral mucosa, so not due to the IgE-mediated allergic reactions. Bromelain or Ana c 2 is a member of cysteine protease enzyme and plays a major role in detecting cross-reactive carbohydrate determinants (CCD) in pollens. Further, Ana c 1 is found to be cross-reactive with profilins present in pollens and fruits due to its high-sequence identity observed (Bet v 2, Phl p 12, Hev b 8, Mal d 4, Pru av 4, peanut, pear, and celery). Also, pineapple has been found to be associated with latex-fruit syndrome and ficus-fruit syndrome due to both its allergens, profilin and bromelain. Additionally, bromelain is highly homologous to other cysteine proteinases, such as papain.
Epidemiology
Worldwide distribution
Consumption of pineapple has been associated with allergic reactions, such as oral allergy syndrome (OAS) that may be related to pollens (pollen-food-syndrome) and systemic IgE-mediated hypersensitivity reactions that may even result in anaphylaxis.
In a cross-sectional study conducted in Mexico that evaluated the prevalence of OAS among 267 children (age: 6-15 years), it was found that 24 of them (8.9%) were having OAS symptoms, of which 23 showed pollen food allergy syndrome (PFAS). Pineapple was considered as the most frequent food associated with OAS or PFAS (62.5%, 15 out of 24).
In another cross-sectional study conducted in Africa, that evaluated the prevalence of food allergy among 1431 school children (age: 5-16 years), 2% of children (n=28) were found to be sensitive to pineapple based on skin prick test (SPT) using fresh pineapple.
A cohort study conducted in Denmark that evaluated the prevalence of food hypersensitivity among young adults (mean age: 22 years), self-reported secondary food hypersensitivity (food allergy-related to pollens) was observed in 141 out of 843 participants. Pineapple was found to be the cause of secondary food hypersensitivity in 4.4% of cases. Also, a study conducted in Germany found the history of immediate allergic reactions to pineapple in 19 out of 380 patients with PFAS.
A study conducted among 437 elementary school children in Korea reported the prevalence of food allergy in 86 children based on a questionnaire survey. The pineapple allergy was reported by only one child. While a nationwide cross-sectional, multicenter questionnaire-based study conducted in Korea among 270 PFAS patients, the pineapple was reported to be the cause in 13.7% of PFAS patients. Further, another study conducted in Japan reported pineapple to be the cause of OAS in 31% of individuals with self-reported OAS symptoms (228 out of 734).
Furthermore, a study conducted in Australia among 163 pediatric atopic patients reported OAS in 24 children, of which 13 reported PFAS. The causative agent identified in the 8 PFAS children by SPT with fresh fruit found pineapple to be a responsible agent in one child. Additionally, the SchoolNuts study (a population-based cross-sectional study) conducted in Australia and evaluating self-reported food allergy among 372 children (10-14 years) reported IgE-mediated (likely) pineapple allergy in 4 of them.
Risk factors
Pineapple has been found to be associated with unpleasant reactions such as irritation of oral mucosa, which is majorly due to its acidic content or bromelain-mediated proteolysis of oral mucosa. These irritational reactions are usually associated with the enzyme activity of bromelain and are not attributed to the IgE-mediated allergic reactions. However, such symptoms usually appear similar to OAS and becomes difficult to distinguish as they may also produce a false-positive SPT result.
Route Of Exposure
Main
Oral ingestion of pineapple (in any form) may induce IgE-mediated allergic reactions, such as OAS or even severe reactions like anaphylaxis.
Secondary
Occupational exposure to bromelain via inhalation (pineapple allergen) may lead to primary sensitization, which could further precipitate systemic allergic reactions on ingestion of pineapple.
Clinical Relevance
Pineapple allergy may be associated with pollen allergy (OAS or PFAS) due to presence of profilin pan-allergen, such as Ana c 1. However, presence of bromelain (Ana c 2), may lead to systemic IgE-mediated allergic reactions and, as mentioned, even anaphylaxis as a result of ingestion of pineapple.
Oral allergy symptoms (OAS) and Anaphylaxis
In a study evaluating 380 patients with PFAS, 18 patients reported with OAS due to ingestion of pineapple, while only one patient reported with systemic allergic reactions. In a questionnaire-based study conducted in Korea, PFAS due to pineapple was reported in 13.7% of patients (n=270), with majority of them displaying oropharyngeal symptoms, followed by cutaneous, respiratory or gastrointestinal manifestations. Further, in a study conducted in Mexico involving OAS patients, pineapple was found to be the major cause of allergic reactions, which include oropharyngeal symptoms and angioedema, besides nasal and systemic reactions observed in some.
Interestingly, a study reported 32 patients who presented with systemic allergic reactions after consumption of pineapple. The major symptoms observed were itchiness, facial edema and rashes, along with gastrointestinal symptoms, such as diarrhea, vomiting and abdominal pain. In addition to this, 20 individuals reported anaphylactoid reactions with reduced heart rate and blood pressure. Furthermore, a review of 141 articles reporting 358 cases of anaphylaxis in China during the period from 1980 to 2007 found pineapple to be the most frequent cause, amounting to 25% (90 out of 358) of cases, including one death as a result of anaphylaxis.
Asthma and Allergic rhinitis
In an Indian study conducted among 575 patients with asthma and/or allergic rhinitis, history of food allergy was reported in 120 individuals. The SPT performed among food-allergic patients reported 1.6% as having positive SPT towards pineapple.
Besides, occupational inhalation of bromelain (major allergen of pineapple), has led to a few cases of asthma as reported in the literature.
Atopic dermatitis
In a questionnaire-based study conducted among 112 children with atopic dermatitis, pineapple was reported to be the cause of allergic reactions in 30% of these children.
Other diseases
Besides the above-mentioned allergic disorders, oral ingestion of pineapple may lead to irritational reactions, mainly restricted to mouth or oral mucosa. Such oral symptoms (irritation on the tongue or oral mucosa, oropharyngeal pain) usually differ from that of OAS, which may also cause pruritis. These irritational symptoms may mainly be attributed to the acidic and bromelain content present in pineapple.
Prevention And Therapy
Prevention strategies
Avoidance
Pineapple allergy can be managed by mainly avoiding the consumption of pineapple. However, consuming it after heating may reduce the allergenicity, due to the destruction of its major allergen, bromelain. Also, treating the pineapple with salt or consuming it with dairy products may help in reducing the allergenic symptoms caused by it.
Cross-Reactivity
Pollen food allergy syndrome has been reported widely as a result of cross-reactivity between pollen and food allergens. Further, one of the pan-allergen majorly responsible for this cross-reactivity includes profilins. This protein, found in different pollens and plant foods, has shown high-sequence homology among them, leading to cross-reactivity. It has been demonstrated in a study where 19 patients of the 380 pollen-allergic patients showed immediate allergic reactions to pineapple. Moreover, it has been documented that pineapple profilin, Ana c 1, shares a sequence identity of 80% with natural rubber latex (Hev b 8), 79% with both apple profilin (Mal d 4) as well as sweet cherry (Pru av 4), 78% with peanut (Ara h 5), 77% with both pear (Pyr c 4) and timothy grass pollen (Phl p 12), 72% with celery (Api g 4), and 71% with birch pollen (Bet v 2). Also, cross-reactivity of pineapple has also been reported with kiwi and lychee (Lit c 1).
Latex-fruit syndrome is a term given to the cross-reactive allergic reactions between latex proteins and allergens of several fruits, such as banana, avocado, kiwi, and also pineapple to some extent. The cross-reactivity among latex and pineapple was reported in a study conducted in Belgium among 42 rubber-latex allergic patients, of whom 33% reported spontaneous allergic reactions due to consumption of pineapple. Further, determination of specific IgE (sIgE) found 43% of the patients to be positive for pineapple.
Pineapple has also been found to be associated with Ficus-fruit syndrome (part of latex-fruit syndrome), due to some degree of cross-reactivity with fig latex (Ficus benjamina). It is said to be associated due to the presence of cysteine proteases like bromelain. This cross-reactivity was found to be independent from the rubber latex. Another study conducted among latex-allergic and latex-sensitized, but pollen-allergic patients, found that both profilins as well as bromelain may be responsible for the false positive latex-sIgE in pollen-allergic individuals. This indicates high latex sensitization in pollen-allergic patients which are clinically irrelevant.
Furthermore, bromelain is said to be highly homologous to other cysteine proteinases, such as papain. These proteolytic enzymes have been found to be cross-reactive, since papain-sensitized patients may show rapid allergic reactions, like asthma to bromelain.
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