Pediatr Allergy Immunol 2003: 14: 420428 Printed in UK.

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Copyright 2003 Blackwell Munksgaard

PEDIATRIC ALLERGY AND IMMUNOLOGY

Review Article

Kiwi fruit allergy: A review

Lucas JSA, Lewis SA, Hourihane JOB. Kiwi fruit allergy: A review. PediatrAllergyImmunol2003:14:420428.2003BlackwellMunksgaard Allergy to kiwi fruit was rst described in 1981, and there have since been reports of the allergy presenting with a wide range of symptoms from localized oral allergy syndrome (OAS) to life-threatening anaphylaxis. The article reviews the available information concerning the clinical features of kiwi fruit allergy and the role of clinical investigations for diagnosis. Work identifying the major allergens in kiwi fruit has resulted in conicting results, the possible reasons for which are discussed. The clinical associations of kiwi fruit allergy with allergies to pollens or latex are reviewed. Jane SA Lucas, Stella A Lewis and Jonathan O'B Hourihane
Division of Infection, Inflammation and Repair, University of Southampton, Southampton, UK Key words: kiwi fruit; allergy; OAS; anaphylax; latex; Actinadia Dr Jane Lucas, University Child Health (MP 803), University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK Tel.: +44(0)23 80 796867 Fax: +44(0)23 80 796378 E-mail: jlucas1@soton.ac.uk Accepted 30 July 2003

Kiwi fruit (Actinidia) is a plant native to the Yangtze Valley of China. Seed was taken to New Zealand in 1904, and almost all kiwi cultivars outside China are descended from the two female and one male plant grown from this single introduction of seed (1). Commercial plantings began in New Zealand in the late 1930s, and exports to the USA started in 1962. Californian kiwi fruit found their way onto the US market in 1970, and for the past three decades kiwi fruit has been increasingly available worldwide, with producers now in New Zealand, USA, Japan, Italy, Greece, Spain, Australia and Chile. Acute allergy to kiwi fruit was rst described in 1981 (2) and there have since been reports of the allergy presenting with a wide range of symptoms from localized oral allergy syndrome (OAS) to life-threatening anaphylaxis (3, 48). The association of kiwi fruit allergy with allergies to pollen and latex has been widely reported in recent years and cross-reactivity has been conrmed by inhibition studies with birch pollen (912), timothy pollen (11), avocado (13, 14), banana (14), latex (13, 14) rye (15) and hazelnuts (15). Three of the possible major allergens responsible for kiwi allergy have recently been isolated and characterized (10, 16, 17), but much remains unknown about this increasingly common allergy.

In the preparation of this review article, PubMed was used as a search engine using the terms kiwi fruit, Actinidia, latex allergy and oral allergy syndrome. The Allergen Data Collection: Kiwi Fruit by Matthias Besler, Internet Symposium on Food Allergens, 2000: 2 (Suppl. 2) was also referred to (http://www.food-allergens.de). All articles published in the English language associated with kiwi fruit allergy were included for review. References in other languages have been included when the authors could obtain the article, and accurate translation could be ensured. Published work involving other fruits and allergens was included if important and relevant, particularly if information specic to kiwi fruit was lacking. The article will review the available information concerning the clinical features of kiwi fruit allergy and the relevance of clinical investigations. It will detail the known allergens and discuss the relevance of crossreactivity of kiwi allergens with pollens and latex.
Clinical characteristics

Funding: Jane Lucas and Stella Lewis receive funding from The Food Standards Agency.

Clinical information about kiwi fruit allergy is mostly based on a handful of case reports and small case series, in addition to extraction of data from scientic papers primarily written to explore cross-reactivity. The rst reported case of kiwi fruit allergy was on a 53-year-old atopic woman who developed urticaria, wheeze and laryngeal oedema on handling the fruit (2). Since

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Kiwi fruit allergy: A review

then there have been a number of reports of kiwi allergy in adults, mostly presenting with oral symptoms (38). In addition some of these individuals have had more generalized reactions including urticaria (4), vomiting (4, 7) respiratory compromise (6) and cardiovascular collapse (6). All case reports but one (4) involved atopic subjects. Case reports of children remain very limited. A 12-year-old atopic boy in Japan developed localized oral symptoms, urticaria and dizziness having eaten the fruit (7), and a hypotensive response to kiwi has been described in a 3-year-old boy (18). There have been a number of studies investigating cross-reactivity of kiwi fruit with pollens, and these publications may have over-emphasized the mild reactions to kiwi fruit, most subjects with pollinosis having symptoms localized to the oral mucosa. A German study of 25 subjects with birch pollen and kiwi allergies reported that 23 had localized oral symptoms and two had urticaria (19). In the same year, a Danish study of eight subjects with allergies to birch pollen and kiwi fruit had oral allergy syndrome as an entry requirement (12). DiezGomez et al. recruited 29 subjects with allergy to plant derived foods, including 12 individuals with symptoms to kiwi, and investigated the subjects for pollen allergy (20). The subjects with associated pollen allergy were likely to have oral allergy syndrome, whilst four of ve subjects with no pollen allergy had anaphylaxis or wheeze. It appears that subjects with allergy to Rosaceae fruit are more likely to have systemic symptoms and anaphylactic shock in the absence of pollinosis (21). There have not been any studies of adequate size to investigate further the dierences between subjects with mono-allergy, pollinosis or latexassociated allergy. We do not know if children respond dierently to adults with kiwi allergy, and there are no data about the natural history of the allergy.

Clinical investigations Skin tests

Skin testing with fresh kiwi is the most common clinical investigation reported (3, 6, 8, 9, 12, 22, 23), the main limitation being that skin testing with fresh fruit lacks standardization. Some authors have produced an extract of kiwi pulp (2, 7) or of fruit skin for skin testing (2), and others have used commercially available skin test solutions (22, 24). Prick to prick with fresh kiwi or skin testing with home-made kiwi extract was

positive in reports of all subjects in whom kiwi allergy was suspected. Commercial skin test extracts are signicantly less sensitive. In a study of 43 subjects with kiwi allergy, only 40% of subjects had positive skin reactions to one commercial extract, and 28% to another make of skin test solution; all subjects had positive reactions when tested by prick to prick with fresh kiwi (22). Although highly sensitive, the specicity of fresh kiwi fruit for skin testing appears poor in subjects allergic to cross-reacting pollens or latex. Gall et al.s study (9) included seven controls allergic to birch pollen but not kiwi fruit, all of whom had positive skin test responses to fresh kiwi fruit. Similarly, two latex allergic individuals with no symptoms on eating kiwi fruit have been reported to have positive skin reactions to fresh kiwi and a commercial skin test extract (27). Beezhold described 47 latex allergic individuals, eight of whom had positive skin tests with fresh kiwi, but only one had symptoms to kiwi fruit (28). The converse also occurs: asymptomatic sensitization to latex may be as high as 86% in fruit allergic patients, but only 11% suer clinically relevant latex allergy (4). Screening subjects with fruit allergy by skin test or measuring foodspecic immunoglobulin E (IgE) levels to other fruits that might share cross-reactive antigens results in an unacceptable number of false-positive reactions (29). However, when combined with a detailed symptom history of oral allergy syndrome, skin prick testing with fresh apple in pollen allergic subjects has showed a good positive predictive value of over 90% (30). The use of puried fruit allergens in diagnostic tests could improve their specicity, but the major allergens responsible for kiwi fruit remains controversial. The relevance of asymptomatic sensitivity to cross-reacting allergens remains unclear, and continued follow-up of such subjects is required to clarify the signicance. In conict with Gall et al.s study (9), other groups have found kiwi skin tests to be highly specic, with negative skin tests in all pollen allergic (2, 4), mite allergic (4) and atopic (7) subjects. There are therefore discrepancies in the literature concerning the specicity of kiwi fruit skin tests in atopic groups. The negative predictive value in non-atopic controls approaches 100% (2, 4, 7, 9). Prick to prick testing with fresh kiwi is simple and sensitive, but as with all skin test procedures there is a small risk of reaction. A 57-year-old man who had suered two anaphylactic reactions when eating kiwi, had a severe systemic reaction on skin testing (6) performed at home by his daughter. 421

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Table 1. In vitro investigatons to confirm kiwi allergy Author (reference) Aleman and Quirce (22) Gall et al. (9) Garcia et al. (4) Gastraminza et al. (24) Gavrovic-Jankulovic et al. (16) Mancuso and Berdondini (5) Mller et al. (19) Specific IgE to kiwi-method CAP (Pharmacia, Sweden) ELISA Home-made allergen discs. Phadebas RAST (Pharmacia Diagnostics AB, Uppsala, Sweden) Kallestad CAP (Pharmacia, Sweden) CAP system FEIA (Pharmacia Diagnostics) RAST Home-made allergen discs. EAST (Allergopharma) RAST Pharmacia CAP system RAST (Pharmacia, Sweden) Maxisorp RAST CAP system (Pharmacia, Sweden) Specific IgE kiwi result 45% (18/40) positive 48% positive Positive in 100% with severe symptoms, negative in 100% with mild local symptoms Negative (0.37 AEU/ml) Negative <0.35 kU/l (1/1) 4/6 positive `positive' Sp IgE < 0.35 7/25; Sp IgE > 0.35 18/25. IgE was generally higher to BP and apple than to kiwi Positive 5.7 kU/l Positive 0.9 PRU/ml 4/9 positive 5/9 were positive by the CAP system-the subjects positive with CAP and Maxisorp did not correlate Specific IgE in controls

Negative 100%

Positive in 100% of birch pollen allergic controls

Novembre et al. (6) Shimizu and Morikawa (7) Voitenko et al. (12)

6/7 negative 6/7 negative

Specific IgE

The role of measuring specic IgE to conrm kiwi fruit allergy is less clear (Table 1). Although positive in some case reports of patients with kiwi allergy (57, 23), other authors have found it unhelpful (4, 24). In his study of 22 subjects with kiwi fruit allergy (9), Gall found that although he was able to detect specic IgE in all subjects with severe symptoms, the results were negative in subjects with mild local symptoms. It is possible that his subjects with oral allergy syndrome had IgE conned to the oral mucosa with no detectable circulating specic IgE, or were allergic to a labile allergen not present in the specic IgE kit. However, other studies have found that at least some subjects with oral allergy syndrome have detectable circulating IgE to kiwi fruit (11, 12, 14, 19). Reports of sensitivity of measuring IgE vary between 13% (31) to over 70% (19). Variation in sensitivity may reect the dierent kiwi allergic populations being studied, and the dierent techniques used to measure specic IgE, with some groups using the CAP system (22, 24, 16), but others using home-made allergen discs (9, 19). The specicity of in vitro tests is also unclear. Using the CAP method to detect specic IgE to kiwi in 136 latex allergic patients, Breler et al. (31) found relatively high specicity (83%). Likewise, Gall et al. (9) found no specic IgE to kiwi fruit in non-kiwi allergic controls with birch pollen allergy, despite having positive skin tests with fresh kiwi fruit. This is in contrast to reports of four of four subjects with no symptoms to kiwi, but symptoms of birch pollen allergy, who had detectable IgE to kiwi fruit (19) 422

and a case report of two subjects with latex allergy who had positive RAST to kiwi despite being asymptomatic (27). It has been suggested that each individual has a threshold for antibirch pollen titres to cause oral allergy intolerance with apple (32) and indeed several studies have demonstrated higher specic birch pollenspecic IgE or larger skin test reactions in subjects with oral allergy syndrome (3335). The present information about the role of clinical investigations in kiwi allergy is therefore confusing and requires further evaluation.
Food challenges

Double-blind food challenges (DBFC) are the gold standard for conrming food allergy (36,37), but blinded food challenges have rarely been used in the context of oral allergy syndrome, and further work is required to evaluate their role. Only one group has published (in abstract) DBFC data concerning kiwi fruit (22). In their study of 33 subjects, DBFC conrmed allergy to kiwi in only 66%, despite all subjects reporting symptoms and all having positive skin tests. Most of their subjects had oral allergy syndrome, and the results may reect the diculty of performing challenges in a group who by denition have predominantly subjective symptoms. There is also evidence that such subjects may only have reactions to the cross-reacting fruit during the pollen season (38). In a case series of patients reporting mostly oral allergy symptoms to melon (39), DBFC conrmed only 68% of 25 positive open challenges. All subjects with negative blind food challenges were again given an open provocation, all of which were negative. Some research groups

Kiwi fruit allergy: A review

have used open oral challenges to conrm OAS (11, 12, 30).
Management of kiwi fruit allergy

As with other food allergies, avoidance of kiwi fruit is the mainstay of treatment, with rescue therapy determined by the severity of reactions. Evidence based data on the management of fruit allergy are lacking, so advice varies from just avoiding the fruit, to restrictive diets of an entire food group. In subjects with a diagnosis of IgE mediated fruit allergy, SPT and measurement of specic IgE to known cross-reacting fruits will result in excessive positive tests results in the absence of clinical symptoms (29). Unnecessary food restriction may occur if incompletely validated allergy test systems are used as a basis for prescribing elimination diets. This stance needs to be balanced against the lack of information about the long-term outcome of subjects with asymptomatic sensitization in the absence of clinical allergy. Successful treatment of OAS to fennel, cucumber, melon and apple by pollen-specic injection immunotherapy has been described (40,41).
Allergens

With regard to identifying major allergens, work has resulted in conicting and confusing results (Table 2). Dierent studies have reported dierent dominant allergens. This could be due to dierent experimental procedures and/or dierences in the study population used (e.g. genetics,

diering eating habits). Pastorello (11) studied 27 Italian subjects with kiwi fruit allergy, diagnosed by clinical history of OAS, a positive skin test, and a positive open challenge. Eighty-seven per cent of subjects also had IgE antibodies to timothy pollen, and 73% to birch pollen. They identied 12 IgE-binding proteins, one of which, a 30 kDa protein, was recognized by all of the subjects. Other allergens with molecular weights of 28, 24 and 12 kDa appeared important either because of the large number of subjects reacting to them or for their part in the clinical crossreactivity of kiwi allergy with birch and timothy pollinosis. A Danish study (12) using the sera of eight subjects with pollinosis associated kiwi allergy, and one subject with isolated kiwi allergy had conicting ndings. Their one subject with kiwi fruit allergy but no pollinosis, had a band at 30 kDa and one at 18 kDa. However, none of the other subjects sera recognized the 30 kDa protein. Instead, they showed proteins in the 1012 and 2224 kDa regions to be the most common allergens in kiwi extract. Mollers studies (14,19) found that proteins of molecular weight 43 and 67 kDa were recognized by over 50% of 22 German subjects with birch pollen allergy, ve of whom also had latex, avocado or banana allergy. In addition they detected minor allergens of 13, 22 and 30 kDa. The major allergens, 43 and 67 kDa, are only slightly detected by total protein staining of the blot with Indian ink or by silver staining of the gel, indicating the low amount of these allergens in kiwi extract. On the other hand, proteins

Table 2. Kiwi allergens Country where the study was based Italy Molecular weights of IgE binding proteins (kDa) 12, 14, 17, 20, 22, 24, 28, 30, 32, 38, 41, 64 1012, 1518, 2025, 30, 3840 (30 kDa recognized by only 1 subject with mono-allergy) 13, 22, 30, 43, 67

Author (reference) Pastorello et al. (11)

Subjects 30 subjects with OAS to kiwi (27 localized symptoms, 3 systemic) 9 kiwi allergic subjects (8 kiwi allergic and birch pollen allergy, 1 kiwi allergic only) 22 subjects with birch pollen allergy and sp IgE to kiwi > 0.7 (1 urticaria, 20 OAS, 1 asymptomatic) 7 subjects with kiwi allergy, 5 also allergic to banana, avocado and/or latex (6 OAS, 1 asymptomatic) 9 subjects with kiwi allergy, 5 also allergic to birch pollen 7 subjects with kiwi fruit allergy

Dominant allergens 30 (100%)

Voitenko et al. (12)

Denmark

1012 (56%) 2025 (56%)

Mller et al. (19)

Germany

43 (68%) 67(55%)

Mller et al. (14)

Germany

See Mller et al. (19)

43 (71%) 67 (57%)

Fahlbusch et al. (42) Gavrovic-Jankulovic et al. (16)

Germany Yugoslavia

23, 30, 43, 80, >80 24, 25, 27, 30, 43, 67, >67

30 (89%) 23 (56%) 24 (100%), 25 (100%), 27(100%), 30 (100%)

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found in larger amounts in their extract, with molecular weights of 20, 23 and 26 kDa, do not represent potent allergens. Fahlbusch (42), using sera from nine kiwi allergic subjects, ve with birch pollen allergy, reported that eight subjects recognized a 30 kDa protein. IgE-binding proteins were also seen at 23, 43 and 80 kDa. Allergens with a wide range of molecular weights from 1267 kDa (11, 19) are considered responsible for the cross-reactivity between kiwi fruit and birch pollen. It has also been shown that the 43 and 67 kDa allergens in kiwi fruit cross-react with allergens from avocado, banana and latex (14). Although fruit allergens in patients allergic to pollens have attracted much attention, very little is known about kiwi allergens in non-pollen allergic individuals. The allergens involved in patients allergic to fruits may dier between subjects with and without pollinosis (21). The IgE-binding pattern may reect dierent symptom patterns. In hazelnut allergic subjects, an IgE response towards a 9 kDa protein specically occurred in subjects with severe anaphylaxis (43). Dierent extraction methods may account for some of the discrepancy between major allergens identied by dierent groups (Table 2). Voitenko (12) used two dierent extraction procedures for kiwi fruit, producing similar protein proles in SDSPAGE but a dierent antigen prole by crossed immunoelectrophoresis. They therefore used a mixture of both extracts in an attempt to provide a more complete allergen extract. The same group also found protein patterns varied according to whether reducing or non-reducing running conditions were applied during electrophoresis. When non-reducing conditions were used the 30-kDa band of the BBS kiwi extract split into two bands: a weak band corresponding to 30 kDa, and a stronger 27 kDa band. The groups working on kiwi fruit allergens have reported using dierent gels, blockers, dilutions of sera and probing methods. However, the precise methodology is unclear in some reports. This emphasizes the need for very clear reporting of laboratory techniques by authors working in this eld and, where appropriate, a need for standardization of techniques between groups working in the same eld. So far, three kiwi allergens have been isolated and characterized (16): Act c 1 (30 kDa), Act c 2 (43 kDa) and a thaumatin-like allergen (24 kDa). Act c 1 is an unglycosylated thiol protease with a mean isoelectric point of 3.5 (17). The protein has been partially sequenced and comparison with 424

the Swiss Protein bank showed that this was actinidin. The structure of actinidin has been described (44). Actinidin is secreted in an inactive form as actininidin, which has a molecular weight of 39 kDa. It has been suggested that actinidin might only express its allergenicity after cleavage of the pro-sequence (17). Bromelain (from pineapple) and papain (from papaya) are also thiol proteases, with similar modes of action. Although amino acid composition, isoelectric points and molecular weights dier, there are many structural similarities, as demonstrated for actinidin and papain in which polypeptide backbones are extremely similar (45). However, only a very weak cross-reactivity has been found between these thiol proteinases (46). Act c 2 has also been N-terminal sequenced and the isoelectric point determined to be 6.9 (10). The quantity of Act c 2 as a percentage of the total protein in kiwi fruit is estimated to be as low as 0.1%. A recent study has suggested that a protein with a molecular weight of 24 kDa and isoelectric point of approximately 9.4 is a major allergen (16). N-terminal amino acid sequencing has shown that this protein corresponds to thaumatin-like protein.
Kiwi allergens associated with pollen allergy

The clinical association of pollinosis with allergy to fresh fruit including kiwi is well-recognized (47). Initial respiratory sensitization results in IgE antibodies to pollen proteins which are homologous to those found in some fruits or vegetables. For example, antigens in birch pollen and apples share allergenic epitopes leading to cross-reactivity that may cause clinical symptoms of OAS when a birch pollen allergic subject eats an apple (32). Many allergens in kiwi fruit are readily digested by simulated gastric uid (48), and per oral sensitization is unlikely to these unstable allergens. However, pre-sensitization by inhaling birch pollen allergens will predispose to allergic symptoms to kiwi fruit. The lability of the kiwi allergens may explain why allergic reactions are restricted to the oral cavity (OAS) in many patients with pollen allergy. The allergenic components of kiwi fruit that cross-react with allergens from timothy and birch pollen have been characterized. Kiwi allergens of 41, 38 and 22 kDa were completely inhibited by timothy grass extract grass pollen, and kiwi allergens with mw 41, 38, 24, 22 and 14 kDa were completely inhibited by birch pollen, suggesting complete identity between the relevant kiwi and pollen allergens (11). Other kiwi aller-

Kiwi fruit allergy: A review

gens, for example the 30 kDa allergen (actinidin, Act c 1), were only partially inhibited, suggesting much weaker cross-reactivity. In another study (12), cross-reactivity between birch pollen and kiwi allergens was partly explained by a protein of 1012 kDa, however, the inhibition was poorly expressed in only half the subjects, perhaps suggesting that only a minor allergen was involved in the cross-reactivity. Recently, complementary DNA coding for the Betv1 homologous allergens from apple Mal d 1 (49), celery (Api g 1) (50) and carrot (Dau c 1) (51) were isolated and shown to share an average sequence identity of approximately 45% with Bet v 1. It has been shown that T cells and T cell clones with specicity for Mal d 1 cross-react with the major birch pollen allergen Bet v 1 (52). Immunization of rhesus monkeys with recombinant birch pollen allergens rBet v 1 and rBet v 2 induced immediate-type skin reactions to food containing Bet v 1 and Bet v 2 related allergens (53). Recombinant allergens from kiwi are not yet available. It remains uncertain whether pollinosis precedes food allergy in oral allergy syndrome. Most of the cross-reacting allergens are more abundant in the pollen than in fruits, giving support to the hypothesis that OAS is caused by a primary sensitization to pollen allergens (54). In a study of adults with OAS (55), a combination of recombinant and natural pollen extracts almost completely inhibited IgE binding to plant extracts, whereas IgE reactivity to pollen allergens was poorly inhibited by recombinant plant food allergens. Based on an assumption that the primary sensitizing molecule will carry most if not all the relevant IgE epitopes, whereas the secondary cross-reactive allergen will have less-reactive epitopes, the authors concluded that the pollen allergens are responsible for the elicitation and maintenance of OAS.
Latex-associated allergy

Most of the natural rubber in the world is manufactured using the sap of Hevea brasiliensis. Latex allergy is particularly prevalent in health care workers (56), rubber industry workers (57) and children with spina bida (58), but has a very low prevalence in a general paediatric population (59). Of the more than 150 polypeptides in natural latex, 35 or more can act as allergens and are recognized by IgE antibodies in the sera of latex allergic subjects (60). Dierent groups of patients appear to be sensitized to dierent groups of latex proteins, children with spina

bida showing dierent IgE binding to health care workers (61). Approximately 3050% of individuals who are allergic to natural rubber latex show hypersensitivity to some plant derived food, especially fruits such as avocado, banana and kiwi fruit. The association between latex and these food allergens has been named latex-fruit syndrome (62). MRaihi et al. (63) were amongst the rst to describe how fruit allergens, in this case banana, could bind latex-specic IgE in vitro. More recently it has been shown that an avocado protein (a class I chitinase) could bind specic IgE in the serum of latex allergic patients (64). This protein had signicant structural homology to a latex antigen, supporting the hypothesis that foods (e.g. chestnut, avocado, banana and kiwi) are able to cause clinically relevant reactions by immunological cross-reactions, in individuals allergic to latex. A study of fruit and vegetable allergic subjects from Spain found that subjects with pollinosis showed a high frequency of IgE reactivity to Bet v 2 (20) and all subjects with positive IgE to Bet v 2 also had reactivity to latex. It is possible that Bet v 2 is a pan-allergen causing cross-reactions between latex, fruits and pollens. It has been hypothesized that conserved defence proteins in higher plants are the cause of latex allergy with accompanying fruit crossreactivity (66). Because of their evolutionary role in host defence mechanisms these proteins are widely distributed throughout the plant kingdom and may form the basis for cross-reactivity. Latex allergens including Hev b2, Hev b7 and chitinase/lysozyme, are likely to be related to the defence responses of a rubber tree. Class I chitinases are panallergens in latex-fruit allergy, and its antifungal activity has been demonstrated. Kiwi fruit is recognized as part of the latex fruit syndrome (28,62), and cross-reactivity has been conrmed by inhibition techniques (14,31). Using immunoblot inhibition, Moller showed that allergens from kiwi fruit share common epitopes with allergens from latex, avocado and banana, and the major kiwi allergens of 43 and 67 kDa are involved in these cross-reactions (14). In a study of fruit allergic subjects (65) 86% had latex sensitization (SPT and/or CAP) although only 12% had a clear history of latex allergy. In this population, food allergy preceded the development of latex reactions clinical sensitization to latex was associated with clinical anaphylaxis to kiwi fruits (65). It has been suggested that sensitization to latex occurs by inhalation of allergen adsorbing powder and direct contact with latex products (48) followed 425

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by allergic symptoms to digestible kiwi proteins. Although the parallel hypothesis in pollinosis associated kiwi allergy appears plausible, evidence that fruit allergy frequently precedes latex allergy and that latexfruit allergy is often severe (66) would suggest that indigestible kiwi allergens, dierent to the allergens in fruitpollinosis allergy, are responsible.
Future directions

13.

14.

15. 16.

Although kiwi fruit allergy appears to be increasing in frequency, systematically collected clinical information remains sparse. A full characterization of the allergy is required, describing the clinical features occurring in isolated allergy, with latex-associated allergy, and with latexfruit syndrome. The IgE binding patterns in each of these clinical groups will then need evaluation. The identication of epitopes specic for kiwi fruit might prove useful to enhance the diagnostic value of skin prick tests and RASTs. Basic information including natural history of subjects with kiwi allergy is required, along with followup information of subjects with skin test positivity in the absence of clinical symptoms.
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