f5 Rye

Rye is one of the unique and the hardiest cereals among all grains. Rye grain (Secale cereale) is different from ryegrass pollen (Lolium perenne), wild rye grass pollen, and cultivated ryegrass. Rye is extensively used in bread-making, alcohol fermentation, paper making, wood industry, used as fuel, and feed for livestock.  Believed to have originated in Afghanistan and Turkish areas, rye is now grown in a cool region and is adapted to various adverse environmental conditions. Nevertheless, rye is also one of the most common sources of allergy, especially in Europe, where bread is extensively consumed.

Inhalation of rye flour may cause respiratory symptoms and elicit an allergic response. Rye flour allergy is reported among people working or associated with bakeries and are exposed to rye flour. Depending on the route of exposure, rye allergy may have different clinical manifestations including classical food allergy symptoms that affect the skin, gastrointestinal system, or respiratory tract; occupational rhinitis or asthma and contact dermatitis; and even exercise-induced anaphylaxis. Allergens from rye grain have been characterized and Sec c 38 is found to be the major allergen, belonging to the family of α- amylase inhibitors.

Allergens from rye show profound cross-reactivity with other cereal grains like wheat, barley, and limited cross-reactivity with oat and even potato extracts. Besides cereals, allergens of rye also exhibit cross-reactivity with allergens from poppy seeds, hazelnut, soya, fungal α-amylases, and with grass and tree pollens.

Sensitized individuals are advised to avoid rye flour in diet and strict labeling laws to label gluten-containing cereals have been established in various countries. 

Worldwide distribution

Baur et al. (1998) studied the frequency of work-related asthma in 89 bakers from the Bochum area (Group A). They summarized the data from a previous study involving 104 bakers (Group B) filing compensation claims for the baker’s asthma. The study involved a control group with 43 healthy people of the same area who did not work in the bakeries. They found that 34% of the subjects from Group A, 50% from Group B, and only 10% of the Control group were positive for rye flour in IgE determination tests (11). A study on 24 Spanish employees (92% males) from the baking industry with a history of baker’s asthma showed that 71% of the workers were positive for rye flour in skin prick tests (SPTs), and 67% showed positive IgE to rye flour (12).

A cross-sectional study was performed across 31 bakeries involving 517 workers across supermarket stores in South Africa to study the asthma phenotypes in these workers exposed to flour dust in the bakery. It was found that about 33% of workers documented work-related asthma due to rye flour specifically. However, these workers handled only a small proportion of products made up of rye flour (13).

A study from a Korean allergy clinical center involving 5340 patients with different allergic diseases demonstrated the IgE sensitization rate and cross-reactivity to different home-made agricultural products and observed that rye grain sensitization rate was 9.5% (14).

Allergy to rye has also been reported in Japan and other western countries (15).

Risk factors

Bakers are at a very high risk of developing occupational asthma from exposure to rye flour used in making bread and other bakery products (16). A study also showed that woodworkers with occupational allergy represent a risk group to rye flour allergy since rye flour is used as a glue in the woodwork (17).

Pediatric issues

Out of different cereal allergens known to cause allergy in children, a study on 40 newborns aged between 3 to 6 months detected rye as one of the potential sources of allergens. Symptoms such as diarrhea, vomiting, eczema, and weight loss were elicited on feeding the babies with cereal formula (18).

Living environment

Rye grain shows excellent growth in poor soils (7). Rye can be cultivated in a variety of adverse environmental conditions (1). Rye can be grown on infertile, acidic, sandy, or poorly prepared lands as well (2).

Worldwide distribution

Rye is considered to have originated in Afghanistan and Turkish regions. The primary domestication of rye is seen in Turkey, Iran, Central Asia and Transcaucasia. It was introduced into Europe and can be found along the Mediterranean route. It is a stable and popular crop in Central Europe, Northern Europe, and Russia. Related wild rye is grown in Southwest Asia, the Mediterranean basin, Central Asia, and Caucasus (1).

Main

Inhalation of rye flour can cause respiratory symptoms and elicit an allergic response (19).

Secondary

Ingestion or even skin contact with cereal rye can cause allergic symptoms, contact dermatitis, exercise-induced anaphylaxis, or gut-related symptoms (5, 20).

Allergic rhinitis and rhino-conjunctivitis (ARC)

Depending on the route of exposure, rye and wheat allergy may have different clinical manifestations including classical food allergy symptoms that affect the skin, gastrointestinal system, or respiratory tract; occupational rhinitis or asthma and contact dermatitis; and even exercise-induced anaphylaxis (5). Moreover, allergens in rye flour, similar to other cereals are resistant to gastrointestinal enzymes and can provoke a reaction upon ingestion (5).

A 38-year-old male baker presented with a two-month history of rhinitis, asthma, and urticaria on arms by exposure to rye flour. The patient showed heightened sensitivity to rye than to other cereals. Rye has been studied to elicit a more robust physiological bronchial response than other grains like wheat (21).

A 35-year-old man working in a bakery for seven years reported aggravation of allergic rhino-conjunctivitis (ARC) upon exposure to rye flour. A 32-year baker from Cuba complained of ARC on rye flour exposure in the bakery where he worked for three years (22).

A 32- year old male baker with a history of smoking and ARC in Japan presented aggravation of ARC, chest tightness, cough, and wheezing while handling rye flour (23).

In a study on rye allergy to woodworkers (since rye four is used in the wood industry), all nine subjects exposed to wood dust and having a history of occupational allergy showed a positive response to commercial rye flour extracts in skin prick and conjunctival tests (17).

Asthma

Inhalation of flour from rye, wheat, barley, soya bean, and buckwheat are reported to trigger respiratory allergic symptoms and asthma and among them, rye, wheat, or barley are mostly known to be responsible for these allergies (19)Allergens in rye flour are known to cause occupational asthma, particularly Baker’s asthma since rye flour is popularly being used to produce “special bread” (5, 16).

A 38-year old baker exhibited asthma and other respiratory symptoms on exposure to rye flour or mixes of rye flour only, and not any other cereal (21).

An old, asymptomatic baker who shifted to working from a bakery in Cuba to Spain complained of developing respiratory symptoms, including asthma, which aggravated with rye flour exposure. He reported severe and more frequent asthma attacks requiring immediate emergency hospital admission due to rye four allergy (22).

Food allergy syndrome and Anaphylaxis

Ingestion of rye can trigger food allergy symptoms in the gut and skin and may cause anaphylaxis (5). Anaphylaxis following the ingestion of rye has been documented. A case of a 61- year old woman without any history of drug allergy, suffering from rye-dependent exercise-induced anaphylaxis upon ingestion of toasted rye bread, has been reported. The woman developed generalized erythema, dizziness, hypotension,and facial angioedema after a 30-minute walk, one-hour post-ingestion of rye (24). A 32-year old Japanese baker with a history of ARC presented with anaphylactic symptoms including urticaria in the upper body, facial swelling, dyspnea, and angioedema on eyelids after consumption of bread containing 50% rye flour (23). Similarly, another study demonstrated a case of a 38-year old male baker with a history of urticaria on arms after exposure to rye flour (21).

Contact dermatitis

Flour-associated contact dermatitis is frequently reported in sensitized individuals. The most commonly responsible agents are wheat and rye. A woman with a history of atopic eczema on fingers since childhood reportedly developed itchy rashes on her hand upon handling a dough made of both wheat and rye and wet chapatis. Dry flour did not trigger any symptoms. Also, the patient did not develop symptoms of allergy or AR after eating cooked chapatis. She tested positive in SPTs for both wheat and rye individually and together (25).

Prevention strategies

Avoidance

Dietary elimination of allergic food has been shown to improve the status of symptoms due to food-borne allergies. In most countries, it is mandatory to have proper labeling for all gluten-containing grains, including rye (9).

Other topics

The potential of a selected cohort of sourdough lactic acid bacteria in hydrolyzing the allergens in wheat and rye cereal proteins during fermentation, followed by treatment with digestive enzymes has been evaluated. Serum studies from sensitized individuals showed that during the treatment of sourdough wheat and rye bread, the potential IgE- binding proteins were degraded. The decrease in the allergenicity potential of treated rye and wheat bread was ascribed to the selected sourdough lactic acid bacteria's proteolytic activity in producing pre-digested flours with IgE-binding proteins, no longer resistant to digestive enzymes (5).

Allergenic molecules

According to the WHO/IUIS nomenclature, the allergens in rye include:

1.  Sec c 38 (renamed from Sec c 1): a 13.5 kDa, dimeric α-amylase/trypsin inhibitors / α-amylase inhibitor  (20, 26).
2. Sec c 5: a 30 kDa, group 5 grass pollen allergen (20).
3. Sec c 20: a 70 kDa, gamma-secalin (20).

Sec c 38 is the major allergen from rye flour with a positive SPT in 71% of patients with baker’s asthma (26).

91% of patients reporting wheat-dependent exercise-induced anaphylaxis exhibited IgE antibodies to Sec c 20. Similarly, 67% of patients showed Sec c 20 in their sera as per the STPs (20).

Other allergens with limited characterization include RDAI-1 and RAI-3 which elicited an allergic response in 86% and 57% of patients in a study. These allergens are members of α- amylase/ trypsin inhibitor family (27).

Cross-reactivity

An extensive cross-reactivity is observed between rye flour, wheat, and barley flour. This cross-reactivity is attributed to the family of proteins gliadins and glutenins (28). Sec c 38, a key allergen from rye, and Barley dimeric protein (BDP) show a 70% identical N-terminal sequence (Garcia-Casado1995).

A study demonstrated that  γ-70 and γ-35 secalins of rye cross-react with ῳ-5 gliadin, a major allergen in wheat-dependent exercise-induced anaphylaxis, indicating that rye can induce symptoms in patients with wheat-dependent, exercise-induced anaphylaxis (29).

Fungal α-amylase is used as a dough additive in numerous bakeries and is another potential cause of baker’s asthma. A study assessing the case reports of two different bakers with an allergy to wheat, barley, and rye showed that both the cases were also sensitive to fungal α- amylase, thereby implying that some, if not broad, cross-reactivity exists between cereal amylases and fungal amylases (22).

Rye grain also shows weak cross-reactivity with oat allergens (30).

Inhibition tests in potato sensitized subjects have demonstrated that rye grain, wheat flour, soya bean, Hop. J and corn extracts inhibited IgE binding to extracts from potato (14).

Allergens in sesame show cross-reactivity with rye, although this cross-reactivity's clinical significance has still not been established (31). Cross-reactivity of rye is seen with allergens in poppy seed, hazelnut, and soya (19, 32, 33).

Merget et al. (2011) demonstrated a significant cross-reactivity between rye flour and grass and tree pollens. Study subjects positive to challenge tests for rye flour also exhibited the highest concentration to ryegrass IgE and IgE to tree pollen (34).

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Fabio Iachetti

Last reviewed: November  2020