Route Of Exposure

The silkworm family Bombycidae belongs to the insect order Lepidoptera, suborder Glossata (the latter containing 99% of moths and butterflies). Wild and oak silkworms of the genus Anteraea belong to Saturniidae, the giant silk- worm family.

The B. mori moth is the adult phase of the life cycle of this insect. Silk moths have a wingspan of 3-5cm and have a white hairy body, but cannot fly. Females are about two to three times bulkier than males (as they carry many eggs). Eggs take about 10-14 days to hatch into larvae. The larvae eat continuously, with a preference for white mulberry leaves; although they will feed on other plants besides white mulberry, such as red mulberry and osage orange, but the silk produced thereby is of lesser quality. Hatchlings and second-instar larvae are covered with tiny black hairs. After moulting, the instar phase of the silkworm emerges: white, naked, and with little horns on its back. After moulting four times (i.e. in the fifth instar phase), its body turns slightly yellow and the skin becomes tighter. The larva then enters the pupa phase of its lifecycle, and encloses itself in a cocoon made of raw silk produced by the salivary glands. At the end of the pupa phase it releases proteolytic enzymes in order to make a hole in the cocoon so that it can emerge as a moth.

The proteolytic enzymes are destructive to the silk, and can cause the silk fibres to break down from lengths of 300 to 900m to segments of random length, which ruins the silk threads. To prevent this, silkworm cocoons are boiled. The silkworm may itself be eaten as a food. The fibre is produced in two large glands running the length of the body and terminating in spinnerets in the mouth. The fibre has a core of a complex protein, fibroin. Natural silk is yellow, but easily bleached and dyed.

B. mori is fully domesticated and cannot survive in the wild, adults being unable to fly and not feeding due to reduced mouth parts. B. mandarina is a closely related wild species, which can hybridise with B. mori.

Increasing evidence indicates that moths are potentially a significant source of both indoor and outdoor inhalant allergens. Moths are characterised by wings covered with scales, and these are suggested to be the major vectors in airborne exposure.

The cuticles and scales of the insect are a mixture of chitin and other proteins making up to 25 per cent of weight, and are the product of a single layer of epidermis. The cuticle of the insect produces different types of scales depending on the stage in the life of insect; hence the protein composition may vary during these phases, and the discarded wings become potential aeroallergens.

Other moths are responsible for occupational moth allergy, as reported in bakers, in laboratory workers involved in gypsy moth research, and in workers in biological pest control factories engaged in the production of beneficial arthropods.

‘Wild silk’, unlike cultivated (mulberry Bombyx mori) silk, is the product of wild silk moths (of the genus Antheraea) feeding on oak leaves. Silk waste is a by-product of silk manufacturing, consisting of short silk threads (e.g. the end or the beginning of a cocoon), and make suitable filling material.

B. mori should not be confused with the Japanese Silk Moth, also known as the Japanese Oak Silkmoth (Antheraea yamamai). A moth of the Saturniidae family, it is endemic to Japan. The cocoons of the saturniid silkmoth Antheraea yamamai are yellow-green, and may be made more green by growing the larvae under intense light, which induces a blue bilin in the larval hemolymph.

Clinical Relevance

Allergen Description

This review is of allergens present in the wings of the B. mori moth; however the pupae and silk are also sources of allergens.

Although the main allergen of B. mori derives from the wings, allergens are also present in the scales and cuticles of the abdomen and wing of the moth, and these are implicated as aeroallergens. The allergen composition of abdomen and wing scales differs. Major allergens were reported to have molecular weights of 14 kDa to 65 kDa. The cuticle of the insect produces different types of scales depending on the stage in the life of the insect; hence, the protein composition may vary during these phases. As a result of these changes, moth allergens become present in house dust.

In Japanese subjects, 15 IgE-binding components have been found to be present in moth extract. The most frequent IgE-binding protein was the 79kDa (84.2%), followed by the 72kDa (78.9%), the 82kDa (57.9%), and the 76kDa (57.9%) proteins. These were considered to be major allergens of the B. mori moth.

‘Wild silk’ is the product of the wild silk moth of the genus Antheraea which feeds on oak leaves, unlike the cultivated silk produced by B. mori feeding on mulberry leaves. Silk wastes are a by-product of silk manufacturing and are used as filling material, in particular for bed quilts. Allergens from this moth have been shown to have contaminated silk waste resulting in allergic symptoms; and by inference, this may occur with silk waste derived from B. mori.

The following allergens have been characterised to date:

In an evaluation of the sera of 10 patients with a positive skin-prick test to silkworm crude extract, all reacted to Bomb m 1, indicating that this allergen is a major allergen.

Potential Cross Reactivity

Cross-reactivity between different moth species, and with other insects, has been extensively reported. Tropomyosin has been suggested as the so-called pan-allergen behind this cross-reactivity, although arginine kinase has been shown to play a role. However, species-specific allergens exist.

Arginine kinase (Bomb m 1) cross-reacts with cockroach arginine kinase.

Cross-allergenicity between extracts of B. mori and the midge Chironomus yoshimatsui has been shown, as well as species-specific allergens.

Clinical Experience

IgE-mediated reactions

Allergic rhinitis and asthma following exposure to B. mori has been described. However, occupational exposure is the main source of atopy and asthma from silkworms. Occupational hypersensitivity pneumonitis has been reported.

A range of studies, mostly from Japan, have suggested B. mori to be an important allergen in asthma and allergic rhinitis. In a study, patients with asthma and severe allergic rhinitis showed a prevalence of sensitisation to moth (asthma 69%, rhinitis 46.8%) comparable to that of cedar pollen and mite, recognised as the most common sensitisers in Japan. The clinical relevance of IgE antibodies to moth was confirmed with broncho-provocation tests.

Another Japanese study found that a third of 267 Japanese patients with allergic rhinitis have IgE against silkworm. A Japanese study of 80 nasal-allergic medical students showed that 18 (22.5%) were positive to silkworm moth allergen, a positive rate as high as those for Candida or ragweed. Of the symptomatic group of 26 patients, 5 (19.2%) were shown to have positive reactions to silkworm moth; while of the 48 asymptomatic subjects, 6 (12.5%) were positive to silkworm moth.

A Japanese study investigating the prevalence of IgE antibodies to chironomid midges in bronchial asthmatic patients around the Lake Suwa area, in comparison with those of the Matsumoto area (control area), found that of 123 Japanese adult patients with bronchial asthma, 33 (50.8%) were positive to mite and 28 (43.1%) to silkworm. The prevalence to the chironomids was 11 (16.9%) to Chironomus yoshimatsui, 8 (12.3%) to Chironomus plumosus and 3 (4.6%) to Tokunagayusurika akamusi. The number of positive tests to silkworm in the Lake Suwa area was higher than in other areas.

However, other studies suggest that cross-reactivity between silkworm and Chironomid may play a role. In a Japanese study evaluating specific IgE to B. mori and Chironomus yoshimatsui in 51 house-dust-mite-sensitive asthma patients, none of whom had definite histories of exposure to these insects or evidence of insect-induced asthma, 30 (59%) had raised serum-specific IgE to moth and 25 (49%) showed positive IgE antibodies to midge (similar frequency to Japanese cedar pollen, a well-known cause of allergy in Japan). RAST-inhibition studies indicated cross-allergenicity between these two insects, and also the existence of species-specific allergens.

Of 56 randomly-selected Japanese patients with asthma, but without any occupational exposure to insects, on intracutaneous tests 69.6% and 53.6% were positive to silkworm wing and caddisfly wing extract respectively. In addition, 57.1% had positive intracutaneous reactions to a chironomid whole-body extract. Of those with positive skin tests to silkworm, serum IgE to silkworm wings, caddisfly wings, and chironomid whole bodies was detected in 82% (32 of 39), 83% (25 of 30), and 81% (26 of 32) of patients respectively.

Two studies showed occupational asthma and sensitisation to silkworm in 29% and 34% of silk filature workers, with the higher percentage in those who twisted the silk threads. Sensitisation to silkworm needs to be differentiated from sensitisation to silk per se. This is further illustrated by a clinical survey of two silk filatures that showed that 36.2% of the persons engaged in the processing of natural silk were suffering from bronchial asthma, while 16.9% of the total subjects had asthma of occupational origin. Skin-prick tests using crude silkworm cocoon and pupal allergen extract demonstrated that 28.8% of the subjects were sensitive to the silkworm-derived allergens. IgE antibodies specific to both cocoon and pupal allergens were demonstrable in the sera of patients with positive skin reactions and occupational asthma.

In a study from mid-western USA, 43% of a group of asthmatic allergic children were RAST-positive to moth.

Other reactions

B. mori is not only a source of aeroallergens; silk, excrement, dander of silkworm, silk products and even silkworm pupae can cause allergic reactions. Sensitisation to silkworms frequently develops in those who work in sericulture. It is estimated that each year in China there are over 1 000 patients who suffer anaphylactic reactions after consuming silkworm pupae, 50 of whom received emergency room treatment for severe anaphylactic reaction.

Immunoblot analysis has reported a protein of approximately 30 kDa to be the silkworm pupa's major allergen.

A number of case reports are illustrative.

A 37-year-old French national visiting China developed anaphylactic shock after consuming oil-fried silkworm chrysalis. Thirty minutes later, he felt an itchy sensation in his mouth and on his face, accompanied by mild nausea and by flushing and swelling of his face. He began to experience difficulty breathing. The authors also list a summary of 13 prior cases of severe anaphylactic reaction caused by silkworm pupa consumption.

A 21-year-old male was reported to have developed pruritus, urticaria, flushed appearance, hypotension, fainting and loss of consciousness 30 minutes after ingestion of silkworm pupae for the first time. Similarly, a 20-year-old male experienced pruritus, urticaria, a flushed appearance, headache, hypotension, abdominal pain, vomiting and dyspnoea after ingestion of silkworm pupae for the first time. Onset of symptoms occurred within 30 minutes.

Many reports describe adverse reactions occurring following the first ingestion of pupae, as demonstrated in a report of a 19-year old male and two females aged 37 and 54 who developed anaphylaxis after ingesting silkworm pupae for the first time. Onset of symptoms varied between 2 and 3 hours. Symptoms included urticaria, flushed appearance, headache, hypotension, abdominal pain, vomiting and dyspnoea.

Five males and 3 females all aged 9 to 46 years of age were diagnosed with anaphylaxis following the ingestion of silkworm pupae for the first time. Symptoms included pruritus, urticaria, a flushed appearance, angioedema, abdominal pain, vomiting, nausea and dyspnoea. Onset of symptoms occurred within 30 minutes to 4 hours. (32, cited in 28)

Vegetable worm (Cordyceps sinensis), a medicinal fungus (not a worm) used in traditional Chinese medicine, has been shown to be cross-reactive with a protein present in silkworm pupae, with a study showing that patients reacting to the ingestion of B. mori pupae all experience allergic symptoms similar to those produced by the vegetable worm. Four of the five patients showed high levels of a serum-specific IgE to vegetable worm and silkworm pupae extracts.