Route Of Exposure

There are an estimated 1.5 million species of fungi, of which approximately 140 000 might qualify as mushrooms, which can mean simply fungi with a large, above-ground fruiting body. However, there are only approximately 14 000 described species of mushrooms. The main types of these mushrooms are agarics (e.g. the button mushroom), boletes, chanterelles, tooth fungi, polypores, puffballs, jelly fungi, coral fungi, bracket fungi, stinkhorns, and cup fungi. ‘True’ mushrooms are classified as Basidiomycota (also known as club fungi), and have a fruiting body known as a basidiocarp, with the stereotypical umbrella shape. The morel and truffle are classified as Ascomycota (‘sac fungi’). ‘Toadstool’ refers to those mushrooms with poisonous fruiting bodies, and to other minor macrofungi.

The reproductive structure – the mushroom itself – is analogous to the fruit of a plant, except that the ‘seeds’ it produces are millions of microscopic spores that form in the gills or pores underneath the mushroom's cap. The spores are spread by the wind, or by other means such as animal feeding. Landing on a suitable substrate (such as wood or soil) results in germination of the spores to form a network of microscopic rooting threads (mycelia), which penetrate their new food source. Unlike the mushroom, which pops up and then passes away quickly, the mycelium persists, often for many years, extracting nutrients and sending up its annual crop of mushrooms.

Mushrooms were grown in the underground caverns of Paris in the 17th century. Taiwan and China have a large export trade in Mushrooms. In order of decreasing cultivated tonnage in the East are Lentinus (Shiitake), Pleurotus (Oyster), Auricularia (Bai mu er), Flammulina (Enokitake), Tremella (Yin er), Hericium, and Grifola (Maitake). The Champignon mushroom (Agaricus bisporus) originated in France. Today's commercial variety of the Champignon (also known as the button mushroom) was originally a light brown colour, but mutated into the type with white caps which has now become the predominant commercial variety.

Except for the toadstools, mushrooms have various degrees of immunomodulatory, lipid-lowering, anti-tumour and other beneficial health effects, without any significant toxicity. But a mushroom characteristically contains many different bioactive compounds, and the content and bioactivity of these compounds depend on how the mushroom is prepared and consumed.

Some mushrooms have toxic compounds present. However, few mushrooms are toxic: of 1 500 different types of Norwegian mushrooms, 60-100 are considered poisonous. The most poisonous mushroom toxins (amatoxins, phallotoxins and virotoxins) are produced by Amanita phalloides (death cap). The concentration and distribution of toxins in certain species may vary.

Mushrooms are purchased fresh or canned or pickled. They can be found cooked in pizzas and casseroles, raw on salads, and in a variety of other dishes. Although the mushroom is a fungus, it is used as a vegetable in cooking. ‘Stuffed mushrooms’ form a dish in themselves.

Clinical Relevance

Allergen Description

No allergens from this food have yet been characterised.

Using serum of an A. bisporus-allergic individual, relevant protein bands were found at the 43 and 67 kDa range for raw mushroom but were absent in cooked mushroom.

It is not known whether allergens in the spores are similar to those in the mushroom itself. In a study of Coprinus quadrifidus, common allergenic epitopes were demonstrated by inhibition of spore RAST by spore, cap, and stalk extracts, suggesting that cap and stalk extracts contain allergens similar to those in spore extract. It may well be that common and unique allergens are found in spores, caps and stalks.

In a study of batches of Pleurotus ostreatus spores obtained from different locations and at different time periods, spores harvested from the species in different areas varied in allergen content (as shown by RAST analysis) and general protein content (according to the HPLC profile). This may well hold true for this mushroom.

Potential Cross Reactivity

The cross-reactivity of this allergen has not yet been fully explored. Enolases are considered to be highly conserved major fungal allergens, but whether these panallergens occur in the Champignon mushroom has not been evaluated yet.

An unusual relationship was shown between allergenicity to moulds (Alternaria alternata, Cladosporium herbarum and/or Aspergillus fumigatus), and the presence of skin-specific IgE to Champignon mushroom and/or spinach. A protein with a molecular weight of approximately 30 kDa present in both spinach and mushroom extracts was recognised in immunoblots of serum from 7 patients allergic to these moulds. Inhibition assays showed that the 2 proteins were related.

Mannitol is present in Champignon mushrooms. As sensitisation may occur to mannitol, a potential cross-reactivity with mannitol used as an excipient in pharmaceuticals is possible (see below).

Clinical Experience

IgE-mediated reactions

Mushroom may uncommonly induce symptoms of food allergy in sensitised individuals. Fungal components can cause allergic symptoms through inhalation, ingestion or skin contact. Whereas respiratory allergy is thought to be induced by spores, allergic reactions following ingestion are attributed to other parts of the mushroom. The prevalence of mushroom allergy is not known. The food allergy may be very slight (1%), but could, alternatively, be as common as the pollen and mould allergy (10-30% of an allergic population). Reports of allergy to Champignon mushroom are very uncommon, which could indicate either that reactions are uncommon to this particular mushroom or that reactions have been rare because until recently this mushroom was not frequently used in meals.

Four episodes of oral allergy syndrome (OAS) were reported in a 31-year-old woman; she had experienced anaphylaxis to spinach and oral allergy syndrome to mushroom. Cross-reactivity was demonstrated between spinach and Champignon mushroom. The authors suggested that this was due to common epitopes.

A related article published at the same time convincingly reported OAS involving cross-reactivity between raw fruits and vegetables and a number of pollens. However, OAS has not been associated with mould spore sensitivity and mushrooms. A study evaluated a patient with oral allergy symptoms to raw (but not to cooked) Champignon mushroom who also had positive skin testing to moulds. The patient had skin-specific IgE to raw mushroom and 4 types of moulds. Immunoblot assays showed that IgE was directed against similar molecular-weight proteins in both the raw mushroom and 3 of the 4 molds: Alternaria tenuis, Fusarium vasinfectum, and Hormodendrum cladosporioides (an obsolete name for Cladosporium cladosporioides). The protein bands on protein electrophoresis were absent in the cooked mushrooms. The authors concluded that cross-reactivity had occurred between mushroom and moulds in a patient with oral allergy syndrome to raw mushroom, and allergic rhinitis to moulds as a secondary condition.

In a study of another edible Mushroom species, Boletus edulis, the sera of 2 subjects were analysed, one with recurrent anaphylaxis and the other with (predominantly) oral allergy syndrome following ingestion of Boletus edulis. At least 4 water-soluble proteins were detected, the most reactive at 55 kDa and at 80 kDa. In a time-course digestion assay, IgE binding was found to a 75 kDa protein, but only if the serum of the subject with recurrent anaphylaxis was used. The study suggested that Boletus edulis can cause an IgE-mediated food allergy due to a digestion-stable protein at 75 kDa, but no IgE immune response to this protein was detected in the serum of a subject with respiratory allergy and oral allergy syndrome to Boletus edulis, or in control sera. This situation may be found to hold true for Champignon mushrooms as well.

Anaphylaxis to mushroom has been reported. A 13-year-old boy was described who experienced anaphylaxis following ingestion of mushroom. For two years he complained of increasing nausea, discomfort in the mouth and throat and itching of the ears whenever he ingested mushroom present in food. A year prior to evaluation, after ingesting mushroom in pasta, he rapidly developed discomfort in the mouth, itchy ears, nausea and diaphoresis. Profuse vomiting developed after 20 mins, after which symptoms resolved. Also clinically relevant was that 6 months prior to this evaluation he developed pruritus of the face, ears and neck, discomfort in the throat and became distressed while his mother was cooking white button mushroom at home in an adjacent area. Onset of symptoms was within 2 minutes of cooking the mushrooms. Skin-prick test was positive for raw and cooked mushroom.

An evaluation of 102 patients with the initial diagnosis of idiopathic anaphylaxis found that in 7 patients, 10 different allergens provoked anaphylaxis: aniseed, cashew nut, celery, flaxseed, hops, mustard, mushroom, shrimp, sunflower, and walnut. The authors concluded that many instances of ‘idiopathic’ anaphylaxis diagnosed historically may not have been truly idiopathic. Therefore, although instances of anaphylaxis to Champignon mushroom appear rare, many instances may simply not have been recognised. Recently, anaphylaxis to mannitol (present naturally in pomegranate and cultivated mushroom) in a sensitised subject was described. The authors proposed an IgE-mediated mechanism to mannitol, a sugar alcohol. The allergenic potential of mannitol was confirmed through skin-specific IgE assessment and ELISA studies, and through a hapten affinity-purified allergic serum that demonstrated the presence of mannitol-specific serum IgE in an allergic subject.

Airborne occupational allergic contact dermatitis from Champignon mushroom in a 31-year-old mushroom picker was reported. She had been involved in the commercial production of Champignon mushrooms for 5 years and had developed skin symptoms from occupational exposure to the mushroom. She developed erythema and dermatitis around the eyes, on the cheeks, around the nose, and around the lips. Skin-specific IgE to Champignon was negative, but patch testing with raw Champignon resulted in a delayed-type response.

Occupational allergic contact dermatitis from Champignon and Polish mushroom has been reported, but not as commonly as for shiitake (Lentinus edodes) dermatitis.

Other reactions

Notes on the inhalation of spores

Hypersensitivity pneumonitis (allergic alveolitis) and eosinophilic bronchitis are important occupational diseases in mushroom workers, affecting those active in cultivation, picking, and packing of commercial mushroom crops. In the past, mushroom cultivation was associated mostly with Asian countries; but both imports and cultivation have become common in EU countries and the USA, so more adverse reactions can be expected. Workers cultivating mushrooms are exposed to various fungi when handling the mushroom compost and develop a condition known as mushroom grower's lung, manifestations of which are pneumonitis and bronchitis.

Similarly, a 36-year-old man and 40-year-old man, employed for several years in the spawning shed of an A. bisporus mushroom farm, developed mushroom worker's lung following inhalation of the spores. The first patient presented in respiratory failure, with radiological features characteristic of hypersensitivity pneumonitis. The condition of the second patient was subacute on presentation, with the diagnosis being made using a computed tomography scan.

Twenty-eight Champignon mushroom (Agaricus bisporus) workers, 4 oyster mushroom (Pleurotus ostreatus) workers and 6 shiitake mushroom (Lentinus edodes) workers, whose medical history indicated possible extrinsic allergic alveolitis, were evaluated for Mushroom grower’s lung. Eighteen of the 28 people employed on the Champignon mushroom farm, all 4 Pleurotus workers and 4 of the 6 shiitake workers were diagnosed as having extrinsic allergic alveolitis.

Other mushrooms associated with hypersensitivity pneumonitis resulting from inhalation of mushroom spores include those from Hypsizigus marmoreus (Bunashimeji mushroom), Pleurotus eryngii, Thermoactinomyces spp., shiitake mushroom, Pleurotus ostreatus (oyster mushroom), Pleurotus floridae, and Pholiota nameko. Hypsizigus marmoreus is also known by the name Lyophyllum aggregatum. A potential increased risk has been reported of hypersensitivity pneumonitis in complementary medicine practitioners who handle exotic mushroom varieties.

Asthma and rhinitis to mushroom spores may occur. But occupational bronchial asthma in Champignon mushroom workers is unusual. Two cases of Champignon mushroom workers suffering from asthma caused by hypersensitivity to the basidiocarp and spores of this mushroom were reported. Serum-specific IgE of the 41-year-old male and 40-year-old male for A. bisporus spore were 72.5 kU/L and <0.35 kU/L respectively; and for A. bisporus basidiocarp, 34.5 kU/L and 0.8 kU/L respectively.

Insufficient data is available to indicate whether allergic symptoms to A. bisporus occur commonly. In an early study of 200 asthmatics tested with basidiospore extracts of Agaricus bisporus, Armillaria mellea, Coprinus micaceus, Hypholoma fasciculare, Ganoderma applanatum, Serpula lacrymans, Polyporus squamosus and Sporobolomyces, and with ascospores of Daldinia concentrica, the greatest number of positive reactions (16%) was reported for Coprinus micaceus, whereas Agaricus bisporus was positive in only 1.5-1.6% of those tested.

In an early study conducted in the United Kingdom to evaluate sensitisation having occurred to A. bisporus in 19 asthmatics as a result of aeroallergen contact, 5 were skin-prick test-positive to the A. bisporus mushroom; and of 15 tested by bronchial provocation for this allergen, 7 were positive.

Other case reports of rhinitis and/or asthma subsequent to inhalation of A. bisporus spores has been reported. A 28-year-old man working as an A. bisporus (AB) cultivator developed rhinitis and asthma coinciding with peaks of AB spore counts in the air of the work site. Skin-prick test with extract from AB spores was positive. A bronchial challenge test with AB spores was positive.

A 52-year-old man, working as a Champignon cultivator, experienced rhinoconjunctivitis and asthma whenever he entered the Champignon caves where the mushroom was being cultivated. In this instance the causative allergen was not the mushroom per se, but IgE-mediated allergy to flies that frequent these mushrooms. These comprise 2 families of the order Diptera: 98% from the Phoridae family (Brachycera suborder) and 2% from the Sciaridae (Nematocera suborder). IgE-mediated hypersensitivity to these flies was demonstrated by (among other means) skin- and serum-specific IgE and a conjunctival provocation test.

Similarly, rhinoconjunctivitis and asthma may occur to the spores of other edible Mushrooms, including Boletus, Coprinus, and Pleurotus. Allergy to Boletus edulis may present as an occupational allergy or anaphylaxis.

Eight workers employed in a food factory were reported to have presented with symptoms of rhinorrhoea, dyspnoea and wheezing, occuring during the preparation of dried mushroom soup. Five had positive immediate skin tests to dried mushroom extract, and in 4 the FEV1 fell by over 30% following a bronchial challenge with mushroom dust. The clinical features were those of a type I allergic response.

Notes on poisoning

Since the 1950s, the rate of reporting of severe and fatal mushroom poisonings has increased worldwide. Clinicians must consider mushroom poisoning in the evaluation of all patients who may be intoxicated by natural substances. The most severe poisonings and fatalities are usually due to hepatic failure from accidental ingestion of Amanita phalloides (death cap) and other cyclopeptide-containing species, or to renal failure from ingestion of orellanine-containing Cortinarius (Corts) mushrooms. The American Association of Poison Control Centers reported that over a 16-year period, out of all reported mushroom poison patients, half exhibited no symptoms and only 25% required treatment – less than 5% for moderate toxicity, and 0.3% for major toxicity. During this period, 17 adults died from mushroom poisoning, 12 as a result of cyclopeptide-containing species (primarily Amanita phalloides), with the remaining deaths due to unidentified species (n=3); an edible Boletus mushroom (n=1); and Clitocybe (funnel cap) mushrooms (n=3). No poisoning from Champignon mushrooms has been reported to date.