Route Of Exposure

Allergen Exposure

Confusingly, three unrelated types of food are all called ‘peppers’. Ordinary, non-flavourant vegetables of the Solanacea or potato family may be called ‘peppers’. These include the green pepper. Also known as peppers are some hot, spicy vegetables of the Capsicum family such as paprika, cayenne pepper, chilli pepper and red pepper. The Piperacea or pepper family, however, is the one that contains Piper nigrum, true pepper, the world’s most popular spice. Similarity of colours and names can make for additional confusion between these 3 groups; ‘red pepper’, for example, is a term applied to certain members or products of all of them.

Piper, a very large genus, is distributed throughout the tropical and subtropical forest regions of the world. True pepper comes from a perennial climbing vine indigenous to the Malabar Coast of India; the habitat of wild pepper is the damp jungles on the slopes of Western Ghats on the Malabar Coast. (India and Indonesia still make up about 50% of the world production.) This spice is one of the oldest known in the world, used since at least 1000 BC. It was a medium of exchange in ancient times, and a major motivation for opening trade routes from Europe to both the East and West.

About 30 species of Piper L are known in India, of which only a few – including P. nigrum L (pepper), P. longum L (long pepper), P. cubeba L (cubeb), and P. betle L (pan, the leaves used for chewing) – are known to be cultivated. P. nigrum L (from which pepper is derived) is a perennial climbing vine or shrub with a smooth, woody stem and alternate, dark green, ovate, acuminate, and thickish leaves. The vines reach heights of 4.5 to 7.5 m, climbing on supports (tree trunks or artificial props) through adventitious roots developing at swollen joints. Lateral hanging branches eventually form a dense cylindrical canopy of foliage. The inflorescence is borne on spikes of lengths varying from 5 to 20 cm, terminally on secondary and tertiary branchlets. Flowers are minute, and are dioecious in wild and a few cultivated varieties, or wholly perfect in many cultivated varieties. Fruits (botanically called drupes, but generally called berries) are ovoid or globose, dark green turning bright orange and red when ripe. The berry-like fruits, about 0.5 – 1.0 cm in diameter and borne on short, hanging spikes 4 – 12 cm. long, are known as peppercorns. Different harvest times and processing methods yield 4 types of pepper: black, green, white and red. The varieties under cultivation have evolved by unconscious selection and show considerable variation in habitat, size and shape of fruit and fruiting behaviour.

Black pepper is the slightly unripe fruit, which is dried. This spice is quite aromatic. White pepper is the same fruit, but harvested ripe and dried only after the hull is removed with the aid of soaking. The hull contains part of the volatile aroma compounds, while the pungency is located in the kernel only. (The main pungency principal, separate from the essential oils, is known as piperine.) White pepper therefore retains the full pungency of black pepper - or more, because of its ripeness – but it has an altered, less aromatic flavour.

Green pepper is harvested very early and pickled or freeze-dried. Because of its lack of ripeness, green pepper has only light pungency; but it has a fresh, herbal, ‘green’, very aromatic flavour.

Pickling of ripe peppercorns creates the rare red pepper (not to be confused with unrelated pink pepper), which combines the spicy, mature flavour of black pepper with the freshness of green pepper.

Peppercorn is marketed whole or ground. Black pepper, the dominant pepper, is a spice with almost universal application, even in fruit cake and gingerbread. It is an ingredient in sauces, gravies, processed meats, poultry, and snack foods. Along with White pepper, it is also a table condiment.

White pepper is good for white (cream-based) sauces where black pepper could spoil the colour. It is also used whenever pungency takes predominance over pepper flavour. The flavour of white pepper has become popular in Japan, particularly in fried foods of the sukiyaki style.

Green pepper is often used in mustard or other condiments, as a garnish for cold foods, and on pepper steak and in sauces for other broiled or fried meats. It is excellent in Thai stir fries and curry pastes.

For millennia it has been known that black pepper can stimulate the appetite and relieve nausea. It has a number of other therapeutic applications, particularly in India. The essential oils extracted from black pepper are used in piperazine elixir, a drug for the removal of round-worms in the human intestinal tract.

Clinical Relevance

Allergen Description

No allergens from this plant have yet been characterised.

Two major allergens of 28 and 60 kDa have been detected. In a study evaluating these allergens, IgE binding to pepper antibodies occurred to the sera of 15 out of 16 pepper-allergic individuals. Minor allergens of 14, 25, 30, 35 and 40 kDa have been reported; and in one individual, IgE binding was demonstrated to the 60 kDa allergen alone. Analysis of the 14- and 28-kDa pepper allergens has demonstrated no homology to known allergens; however, the 28-kDa pepper allergen showed homology to a wheat germin protein.

Two IgE-reactive protein bands of 11.8 kDa and 13.6 kDa able to bind to IgE from white pepper extract, and one band from black pepper extract of 11.8 kDa, were detected in a woman with occupational rhinoconjunctivitis from white pepper. IgE binding to white and black pepper extract could be inhibited by preincubation of patient serum with black pepper extract.

Potential Cross Reactivity

Cross-reactivity has been reported between green and black pepper and other foods and pollens involved in cross-reactivity in the "Mugwort-Celery-Spice-syndrome". The pepper allergens responsible were found not to be homologues to Bet v 1 or profiling; but pre-incubation of patient sera with extracts of birch pollen, mugwort pollen or celery extract led to complete blocking of IgE binding, indicating the existence of cross-reactive allergens. Nevertheless, the panallergens profilin and Bet v 1 have been detected, and an author concluded that “allergy to spices rarely represents an autonomous sensitization, but is rather a consequence of pollen allergy on the basis of immunologic cross-reactivity”.

Clinical Experience

IgE-mediated reactions

Spices may uncommonly induce symptoms of food allergy in sensitised individuals. Symptoms are usually mild but may vary from itching and smarting of the lips and mouth to anaphylaxis. Most allergic reactions produced by spices are the result of ingestion, and spices usually act as ‘hidden’ allergens. Spices as ‘hidden’ allergens are potentially very dangerous, because minute amounts can cause systemic reactions and even anaphylactic shock.

The increasing use of spices in cosmetics has increased reports of allergic skin reactions, including contact dermatitis and contact urticaria. Powdered spices may cause occupational allergic respiratory symptoms even in non-atopics.

It must be kept in mind that besides allergens, spices contain a number of pharmacologically active and/or toxic compounds, which may cause irritation and inflammation leading to intolerance reactions; these must not be mistaken for a food allergy.

Black pepper may uncommonly induce symptoms of food allergy or cutaneous allergy in sensitised individuals; but it is possible that the allergy occurs more frequently than has been reported. A few studies have reported on the prevalence of allergy to pepper. In a study of 867 atopic patients tested for skin specific IgE to white pepper, 5 were positive, as was 1 of 359 non-atopic patients. In a study assessing 402 patients with food allergy, 23 (5.7%) had food allergy to bell pepper and four (1%) to pepper. However, in an investigation of patients allergic to mugwort pollen, specific IgE directed at black pepper and paprika was found in 52%.

In a French series of 202 labial food challenges performed over two years in 142 children with suspected food allergy, 156 were positive. Pepper provoked reactions in one child. A cross-sectional study aimed at investigating the prevalence and characteristics of IgE-mediated food allergies in 3 500 randomly-selected 6- to 9-year-old urban schoolchildren in the eastern Black Sea region of Turkey found that 5 children (1.9%) reported adverse reactions to black pepper, of which 4 were skin-prick test positive and 1 positive following DBPCFC.

In an Indian investigation of the prevalence of legume allergy and concomitant sensitisation to different allergens of patients with asthma and/or rhinitis, skin-prick test with 27 common food allergens and 61 aeroallergens was performed on 76 subjects. Of these, 4 (5.3%) were found to be positive for black pepper. An Indian study of 24 children aged 3 years to 15 years with documented deterioration in control of their perennial asthma during August and September, evaluated for possible effect of a specific elimination diet on symptoms, found raised serum-specific IgE levels for black pepper in 22 (92%).

In a German study of 419 adults evaluated for suspected food allergies, 214 patients (51.1%) were found to have an IgE-mediated food allergy, of which almost half (24.3% of the overall group) had previously experienced food-induced anaphylaxis. Common allergens identified were seasonings (n=81) (paprika, pepper, mustard, curry mixture), tree nuts (n=144) (hazelnut, walnut, almond), fruit and vegetables (n=117) (celery, tomato, carrot, apple, banana), grains (n=45) (rye and wheat flours), soy (n=31), peanut (n=31), cod (n=15), shrimp (n=18), egg (n=9), and cow's milk (n=5).

In a study conducted at 17 participating clinics in 15 European cities in order to describe the differences between some Northern countries regarding what foods (according to the patients) elicit hypersensitivity symptoms, 1139 patients with a history of food hypersensitivity reported their experience of 86 foods using a questionnaire. Pepper was the 65 (th) most common food to which adverse reactions were reported, affecting 7.3% of respondents.

The spectrum of specific allergic sensitivities to environmental and food allergens was investigated in adult patients with eosinophilic esophagitis (EE). Seventeen of 21 patients were polysensitised to several different environmental allergens, and 19 of 23 (82%) had serum IgE specific for one or more food-associated allergens (median, 5 foods), with wheat, tomato, carrot, and onion identified most commonly. Serum IgE was positive for black pepper in 4 (17%).

Scratch tests to detect skin-specific IgE using powdered commercial spices performed on 70 patients with positive skin-specific IgE to birch and/or mugwort pollen, as well as celery, detected skin-specific IgE for spice and herbs of the Apiaceae family, as well as for celery, in more than 24 patients. Skin-specific IgE for spices from unrelated families (red pepper, white pepper, ginger, nutmeg, cinnamon) were detected in only three of 11 patients.

Allergy to spices occurs more commonly in an occupational setting, in particular in the spice industry.

In a study of 4 men and 18 women working in the spice industry, the spice that induced symptoms the most frequently was clove; 16 workers (76%) had symptoms while handling cloves, the commonest being smarting of the nostrils and eyes, and cough. Pepper produced the same type of symptoms in 44% (4 out of 18) of this group.

Occupational rhinoconjunctivitis as a result of contact with White pepper while working in the food industry was described in a 44-year-old woman. Symptoms resolved over the weekend while she was not at work. Skin-specific IgE was detected to white and black pepper extracts, and serum-specific IgE antibodies to white and black pepper were demonstrated by ELISA. A conjunctival provocation test was positive with a white pepper extract.

Similarly, a patient with rhinitis and asthma occurring at work was shown to have specific reactivity to fennel. Investigation demonstrated skin-specific IgE to grass, ragweed, and freshly-prepared fennel seed. Further studies showed serum reactivity to two components in fennel extract, as well as to components in mugwort, paprika, short ragweed and black pepper. The authors concluded that this individual displayed sensitivity to unique allergens in fennel, and that the patient was also sensitised to black pepper.

Delayed-type adverse reactions to pepper may be experienced. In a study of workers in a Swedish spice factory, 50% of the 70 workers reported skin symptoms. Patch-test reactions were seen from powder of cardamom, paprika and white pepper.

In a study of dermatological patients, 4 of 116 patients allergic to balsam of Peru were patch-test positive for white pepper, but none out of 219 not allergic to balsam of Peru.

Other Reaction

Ground pepper may contain fillers. Anaphylaxis caused by buckwheat as an additional constituent in pepper has been reported.

Piperine, a major component of black pepper, has been reported to inhibit drug-metabolising enzymes, increase plasma concentrations and delay elimination of several drugs, including phenytoin and rifampin.

Asphyxia and death as a result of aspiration resulting in mechanical obstruction and oedema of the tracheobronchial tree has been reported; in some instances caused deliberately and regarded as homicide.