Route Of Exposure

Probably the world’s most widely used salad vegetable, Lettuce is thought to have originated in the Mediterranean region in the form of Prickly lettuce. It is recorded as having been served in Persia in 400 BC.

Annual and biennial Lettuce is cultivated in many parts of the world for its edible leaves. Of the many varieties, basic forms have been classified as follows: heading or head varieties, cutting or leaf varieties, and Cos or Romaine. A fourth, very minor type, is the so-called Stem, Celery or Stalk Lettuce.

Lettuce grows in cultivated beds. Its most common use – as leaves, but sometimes also as spouted seeds – is in salads and sandwiches, but it may also appear in soups and stews. Edible oil is obtained from the tiny seeds, but extraction of the oil on any scale would not be feasible.

The sap of the plant contains lactucarium, which is used in medicine and folk medicine for its anodyne, antispasmodic, digestive, galactogogue, diuretic, hypnotic, narcotic, sedative, anaphrodisiac, carminative, emollient, febrifuge, hypoglycaemic, and parasiticide properties. Lactucarium has the effects of a feeble opium, but without tendency of opium to cause digestive upsets; nor is lactucarium addictive. It is taken internally in the treatment of insomnia, anxiety, neuroses, hyperactivity in children, dry coughs, whooping cough, rheumatic pain, etc. The sap has also been applied externally in the treatment of warts. Even normal doses can cause drowsiness, while excess doses cause restlessness, and overdoses can cause death through cardiac paralysis.

Clinical Relevance

Allergen description

Four protein bands with molecular weights of 50, 43, 39 and 16 kDa have been detected in Lettuce, and these exhibited IgE-binding properties. A second study reported detecting 14 allergens in Iceberg lettuce, with weights between 13 and >113 kDa. A 42-year-old female presented with widespread erythema and a subsequent episode of anaphylaxis after ingesting “Tudela” lettuce hearts (Lactuca sativa var.); serum from this patient revealed several bands, predominantly in the range of 15–65 kDa. Researchers have reported predominant reactivity to a protein of 42-48 kDa.

The following allergen has been characterised:

Two Lac s 1 isoforms were identified, with an amino-acid identity of 62% to each other, up to 66% to Pru p 3 from Peach, and 72% to the N-terminal peptide of the London plane pollen LTP Pla a 3. The prevalence of IgE binding to nLac s 1 was 90%, as shown in immunoblotting experiments with Lettuce extract.

No differences in the protein profiles of several Lettuce varieties (Chicory, Butterhead, Iceberg, [mini]-Romaine, Frisée) were found, or between younger (inner) and older (outer) leaves, but the authors could not exclude slight differences in the level of LTP accumulation in the leaves.

IgE binding to a 24 kDa protein and HMW proteins (> 50 kDa) was due to cross-reactive carbohydrate determinants (CCDs).

Potential Cross Reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected, as well as to a certain degree among members of the family Asteraceae.

A patient allergic to Chicory reported reactions to botanically related Endive (Cichorium endivia) and Lettuce (Lactuca sativa). No cross-reactivity was found with pollen from Mugwort, a member of the same family. This is contradicted by a report on subjects allergic to Artemisia, who appeared to be at a higher risk of concomitant sensitisation to various foods, including Lettuce. A common allergen may be responsible. Four patients with occupational contact dermatitis to Lettuce were shown to be cross-reactive with endive.

Lettuce contains a lipid transfer protein (Lac s 1), which may result in cross-reactivity with other lipid transfer protein-containing foods.

Lac s 1 was shown to have a high amino acid sequence identity with other lipid transfer proteins, from Peach and Cherry, among others. A clear partial cross-reactivity was observed between Lettuce LTP and London plane tree- (Platanus) pollen extract. Although a partial IgE cross-reactivity between Lac s 1 and Platanus pollen exists, a more pronounced cross-reactivity occurs with the LTPs from the Rosaceae family, e.g., Pru av 3 from Cherry, and Pru p 3, the major allergen from Peach. Lac s 1 also showed broad IgE cross-reactive properties with Walnut and Peanut extract, LTPs from Mugwort and Chestnut. Vit v 1 from Grape, Zea m 14 from Maize, Cor a 8 from Hazelnut, and Mal d 3 from Apple. Although the highest degree of sequence identity of the N-terminus of Lac s 1 was found with Mal d 3, only a single subject in the Lettuce-allergic group reported Apple allergy. The authors therefore postulated a lack of correlation between sequence identity and clinical cross-reactivity.

RAST inhibition demonstrated that Carrot does share allergens with Lettuce, although Carrot allergens are more potent than those of Lettuce.

One study concludes that cross-reactivity was observed between Platanus acerifolia pollen and plant-derived foods. OAS in these patients may have been caused by primary respiratory sensitisation to Plane tree pollen, and the authors propose profilin as the cause.

Approximately 22% of the Spanish patients with Plane tree pollen allergy and food allergy had allergy to vegetables, including Lettuce.

Clinical Experience

IgE-mediated reactions

Lettuce allergy is not frequently reported in the literature, but is found in clinical practice, predominantly in the southern part of Europe. Lettuce may induce symptoms of food allergy, in particular oral allergy syndrome, in sensitised individuals. Adverse reactions may be severe, resulting in anaphylaxis. Lettuce and Carrot can account for clinically significant IgE-mediated allergic reactions, including prolonged nasal obstruction. This finding is supported by a Mexican study, in which, among 1,419 allergic patients aged between 1 and 18 years, 442 (31%) had positive skin prick test (SPT) results to 1 or more among 33 tested foods. Fish, milk, seafood, beans, Orange, Onion, Tomato, Chicken, nuts, Lettuce and Strawberry were responsible for 58% of the total of allergic reactions. Of those, fish, milk, seafood, Soy and Orange (39%) had the highest frequency.

In a study of 29 Lettuce-allergic patients, with or without concomitant Peach allergy, and 19 Peach-allergic patients without Lettuce allergy, it was concluded that the data provided indirect evidence that Pru p 3, a lipid transfer protein, might act as the primary sensitising agent in patients allergic to both Lettuce and Peach. Of those with Lettuce allergy, anaphylaxis was reported in 15, gastrointestinal symptoms in 2, OAS in 8, urticaria in 3, and angioedema in 3. Skin prick testing was positive in 17, and prick to prick testing in 18, (a number of SPT-positive cases were prick to prick-negative, and vice versa); IgE antibody levels for Lettuce were negative in 7, and for nLac s 1 negative in 2 but positive in 27 of the 29.

A study of 14 patients with allergy to Lettuce described how all were sensitised to Platanus pollen. Ten were allergic to a lipid transfer protein in Lettuce. Fifty percent of the subjects experienced anaphylaxis to Lettuce. Symptoms of oral allergy syndrome was followed by more severe symptoms in the majority of cases. Lac s 1, the lipid transfer protein, was the responsible allergen.

A 42-year-old female presented with widespread erythema with pruritus after ingesting “Tudela” lettuce hearts (Lactuca sativa var.). She experienced an anaphylactic shock episode a few days later after eating the Lettuce hearts dressed with Olive oil. She had concomitant seasonal rhinitis, which coincided with the pollination of Platanus acerifolia. Skin prick tests were positive to “Tudela” lettuce heart, Lettuce, endive, pollen from P. acerifolia and Artemisia vulgaris; but negative to Leek, Potato, Carrot and Latex. In spite of her tolerating the ingestion of Leeks, Potatoes and Carrots, presence of IgE antibodies to these foods was demonstrated.

However, IgE antibodies may be found in asymptomatic patients. Skin-sensitising allergens have been identified, but reactions do not appear to be IgE-mediated.

Food-dependent exercise-induced anaphylaxis has been reported.

Generalised, pruritic, papular and erythematous eruption, associated with facial and lingual oedema and a tight throat, due to Lettuce, has been documented in a patient.

Previously unsuspected Lettuce allergy in a patient with delayed metal allergy has been reported.

Other reactions

Occupational eczema or contact dermatitis, combining delayed and immediate-type reactions, has been reported, including contact hypersensitivity to Lettuce in a chef. A 35-year-old woman complained of an itchy rash on her fingers, which occurred for the first time 3 months after commencing work at a vegetable packing plant. The rash then spread to her arms and neck. Despite a negative standard battery, targeted patch testing revealed Lettuce as the offending agent.

Greenhouse workers and gardeners are at risk of Compositae-related allergy to Chrysanthemum (Dendranthema), Daisy (Argyranthemum frutescens) and Lettuce (Lactuca sativa). Ingestion of Lettuce was reported to result in lip and facial swelling, and in aggravation of pre-existing Compositae dermatitis.

Other substances, including allergens, may be present that result in adverse effects. Powdered Latex glove use in salad preparation may result in measurable amounts of Latex protein on Lettuce, with an exposure-dependent increase in the Latex protein levels. Sulphite-treated Lettuce (sulphite is used as a preservative) is capable of provoking bronchospasm in sulphite-sensitive asthmatics and may be a cause of restaurant-provoked asthma in these individuals.

Lettuce contains high levels of naturally occurring nitrates.