Sometimes the problems are allergic in nature. Every spring and summer there are countless people suffering from hay fever caused by pollen from ragweed, birch, hazel, timothy grass or ryegrass. Urticaria resulting from eating strawberries is a known condition. Allergy to peanuts can be very severe, even fatal. Certain forms of extrinsic allergic alveolitis are caused by plant substances. Gluten enteropathy (hypersensitivity to gliadin) can be treacherous. Latex allergy is a significant problem for some doctors and nurses. Pyrethrum allergy is a known problem on the plantations of Chrysanthemum cineriaefolium in East Africa. In the Far East the Japanese cedar (Cryptomeria japonica) is a source of much annual misery because of the massive amounts of highly allergenic pollen which it produces every spring. This problem has increased greatly in recent decades. Due to the great shortage of wood for home building after the Second World War, the government in Japan started a large-scale reforestation campaign. The emphasis was on only one species of tree, however. The Japanese cedar is a magnificent species of tree which grows to 40 metres and has a pleasant perfume. It has a special place in Japanese culture. The wood is of high quality. At present a large percentage of the newly planted Japanese forest consists of this species. The trees are now mature, shedding massive amounts of pollen each year. To deal with the problem, in 1998 a research centre in Chiba began to develop a cedar variety which produces much less pollen.

*

*

Peru balsam is a brownish yellow to vanilla coloured balsam, obtained by crushing and heating (roasting) the stem of the Central American tree Myroxylon balsamum var. pereirae (Papillionacae). Peru balsam can also be produced synthetically. It consists of benzyl esters of cinnamic and benzoic acid. It also contains free cinnamic acid, resins, vanillin and coumarins. Peru balsam is used as a fixing agent in the perfumery and soap industry. In medicine it was (and is) used to promote wound healing and as a mildly antiseptic anti-irritant. The risk of hypersensitivity is very high, however. In contact dermatitis of uncertain origin, Peru balsam is among the substances which should be included in epicutaneous tests.

*

Normally, wheat proteins undergo proteolysis in the intestinal lumen, and single amino acids or oligopeptides will be absorbed. There is a certain peptide ("33-mer") which seems to be resistent to digestion by brush border enzymes and which contains three epitopes that are immunogenic. This 33-mer has a very high affinity for tissue transglutaminase. This enzyme deamidates the glutamine-residues in gliadin, resulting in glutamic acids. These deamidated peptides adhere strongly to the binding grooves of HLA-DQ2 and HLA-DQ8 and elicit strong T-cell responses. Tissue transglutaminase was identified as the chief target of the auto-antibodies in gluten-enteropathy. The presence of anti-endomysium antibodies correlates well with gluten enteropathy. Endomysium -the thin connective tissue layer around individual muscle cells- contains a lot of tissue transglutaminase.

*

The immune respons leads to shortening of the intestinal villi. Symptoms can be typical (chronic diarrhoea, short stature) or more frequently, atypical (anaemia, osteoporosis, fatigue, depression, …). Dermatitis herpetiformis is frequent in these patients. They have an increased risk of lymphoma. IgA-antibodies against gluten have a low specificity and IgG-antibodies have a low sensitivity. The gold standard for diagnosis is endoscopic intestinal biopsy.

*

Treatment is based on the avoidance of wheat, rye, barley, spelt, einkorn, oats and triticale. Corn and rice are safe. There are some recent data which suggest that pure oats is safe after all. Members of the grass family that are taxonomically more closely related to corn and rice than to wheat are likely to be safe. Such grasses include sorghum, the different millets (e.g. pearl and foxtail millet), ragi (finger millet), white and black fonio (esp. Western Africa), teff (esp. in Ethiopia), and Job's tears, which are reasonably closely related to corn. Wild rice is closely related to cultivated rice (see chapter on "beriberi"). In some cases, there are protein-structure studies that support of this conclusion, although the studies are not sufficiently complete to provide more than guidance. All grasses are monocotyledons. Buckwheat, amaranth and quinoa are dicotyledons. Because of their very distant relationship to the grass family and to wheat, it is highly unlikely that they will contain the same type of protein sequence found in wheat proteins that causes problems for coeliac patients. Amaranth seeds contain a high concentration of lysine, an essential amino acid lacking in all of the world’s main cereal crops.

Latex allergy, whether or not dangerous, is an uncomfortable situation for many doctors and paramedics, as well as some patients who have regular contact with natural rubber.

Rubber became known in Europe after the journeys of Columbus. It was long seen as a curiosity, without any practical use. In 1736 the French explorer Charles de la Condamine, after a journey through Brazil, brought the potential of rubber to the notice of the scientific world. The name rubber was given by Sir Joseph Priestley, when he discovered that solidified latex from the rubber tree could be used to rub out lead pencil. In 1823 the Scot Charles Macintosh discovered that rubber was soluble in hexane, a distillation product of petroleum. This enabled coagulated latex to be dissolved after being shipped and then to be applied to textiles. After evaporating the solvent a thin layer of rubber was left on the textile, which made it waterproof. The name Macintosh quickly became synonymous with a certain kind of raincoat. One huge disadvantage of natural rubber was that it became sticky in summer and brittle in winter. This problem disappeared with the discovery of the American Charles Goodyear. After lots of experimentation, he discovered in 1839 that rubber became tougher and lasted longer if it was heated with sulphur and lead oxide. Some say that the discovery was an accidental one, after spilling a mixture onto a hot stove, but this kind of "chance discoveries" are only made by people with a prepared mind (cfr Louis Pasteur). The sulphur bound the different polymer chains (cross-linking). The process was called vulcanisation after the Roman god of fire Vulcan. The Englishman Thomas Hancock seized Goodyear's discovery and launched the British rubber industry by inventing a method for processing rubber on an industrial scale. In 1888 the British veterinary surgeon John Boyd Dunlop took out a patent for the production of rubber tyres, which had an enormous influence on the use of the bicycle and the motor car. The future for rubber had opened up. One of the reasons Belgium became rich as a colonial power under King Leopold II, was via the tapping of wild rubber in the Congo.

*

Until 1880 rubber was obtained only from wild trees. In the forest individual trees grow quite distant from each other (not more than one tree per hectare). In this way they are at less risk of becoming diseased. Attempts to set up plantations in South America frequently failed due to a fast-spreading and deadly tree disease. In the 19^th century Brazil kept the monopoly in rubber production, with the state of Para as the centre. It was rubber that helped to open up the Amazon region and gave towns such as Manaus and Belem their riches. The colonial powers were very interested in breaking this monopoly. In 1872 Joseph Hooker, director of the Botanical Gardens in London, sent Henry Alexander Wickham to collect seeds. In 1876 Wickham, with the approval of the Brazilian authorities, brought 70,000 seeds of Hevea brasiliensis to England from the regions of the Rio Tapajos. In Kew Gardens a few thousand (maybe 2000) of the seeds germinated. These were shipped in special cases (called Wardian cases) to Malacca, Sumatra, Singapore, Java and Ceylon. Thanks to these portable miniature greenhouses a number of small plants survived the long journey and were planted out. By about 1900 most of the techniques had been developed that were necessary to set up plantations on a large scale, including grafting, an essential cloning technique which can supply countless trees, all genetically the same. Rubber production in Asia began in 1910. In 1914 the new plantations in Southeast Asia had far exceeded the old production regions. In 1930 there was a great epidemic of the South American tree disease (Microcyclus ulei, previously Dotidella ulei). It completely destroyed the trees on the plantations in South America, where trees were closely planted. Asia has to date managed to avoid this fungus. That Brazil now has rubber plantations again, is thanks to crossing sensitive high-producing Hevea brasiliensis with other resistent but low-producing Hevea species. Due to countless repeat crossings, reasonable production has been revived.

*

Natural rubber and caoutchouc (ca-o-chu = weeping wood) are elastic polymers obtained from a milky liquid (latex) from certain plants. No one knows just why many plants produce latex. One hypothesis says that it is a mechanical defence against gnawing insects. The most important source of natural rubber is Hevea brasiliensis, a species of South American tree (Euphorbiaceae). Other, much less important species are Hevea benthamiana and H. nitida. Hevea brasiliensis occurs in the wild in South America in regions between 10° N and 10° S. The regions have heavy rainfall and are preferably at 50 to 200 metres above sea level, with a temperature between 24 and 35°C. In plantations the trees reach a maximum height of 24 metres. Tapping of a tree is begun when it is 5 to 7 years old. Tapping can be carried out for 6 months a year. With care a tree may live to 30 years.

Latex is sometimes described as the sap of the Hevea. This is in fact not correct. The sap runs deeper, in the xylem and the sieve elements of the phloem. The latex runs in the laticifers (lactifers) that lie in anastomosing concentric circles in the bast directly outside of the cambium. The latex veins are bound to the cambium and the phloem by radiating vessels. The bast and latex veins are cut diagonally at an angle of 30°. Using a sharp knife, the tapper cuts a shaving from the intact bast. Great care is needed when doing this, so as not to touch the thin cambium. This is because the new cells for the plant are produced from this growth layer. If the latex tapper makes the incision too deep, the cambium is injured and the tree will be permanently damaged. The latex flows from the laticifers in droplets. To prevent the latex from coagulating, ethrel or ethaphon (Flo-Tex) are applied to the bast. This substance releases ethylene, a natural plant hormone. In this way production can be doubled. At present 2 tons of latex per tree can be harvested annually. The latex runs into a small cup, coconut shell or other receptacle. Afterwards it is filtered to remove impurities. Later the latex is coagulated by adding formic acid or vinegar. The latex can also be coagulated by smoking, but this is not practical for large amounts. Then the water is squeezed out. The rubber chains of Hevea contain 50 to 6000 isoprene units. They do not contain side chains but consist of long chains of exclusively cis-1-4-polyisoprene (C₅H₈)_n. This stereospecificity contributes to a large extent to the unique mechanical properties.

Rubber can also be obtained from plants other than Hevea brasiliensis. Other rubber-supplying species have no continuous veins. Latex veins are not present in Gymnosperma. They occur sporadically in Angiosperma, chiefly in dicotyledons. Guayule (Parthenium argentatum, fam. Asteraceae) is a shrub that grows in the Chihuahua dessert in southwest Texas and adjacent parts of Mexico. The shrub makes few demands on its environment and survives in semi-arid regions. The plant contains latex which is found in individual cells in the stem and roots. Approximately 7 to 20% of the dry weight is rubber, of the same quality as Hevea rubber. The plant must be 7 years old before it can be harvested. Since tapping is not possible, the shrub is felled and processed in its entirety. James Bonner discovered that the production of rubber is encouraged by low night-time temperatures (below 10°C, and preferably below 7°C). Harvey Firestone and Thomas Edison investigated the possibilities of this plant before World War II as an alternative source of rubber. Guayule was the focus of the American "Emergency Rubber Program" during WW II. In Latin America rubber can also be obtained from Castilloa elastica (the mulberry family). Koksagyz rubber was obtained in Central Asia from Taraxacum scariosum (Compositae). Manicoba or Cerea rubber refers to the Brazilian federal state of Cerea and comes from Manihot glaziovii. Bambong rubber comes from Ficus elasticus. African rubber is obtained from Funtumia elastica (Apogynaceae). Another source in the Old World is Landolphia gummifera (Apogynaceae). Some plants such as the sorva tree (Couma utilis) have become rare because the whole tree was felled for the extraction of the latex. Gutta-percha is obtained from the tree Palaquium gutta (Sapotaceae), a plant from Malaysia and the South Pacific. Payena leeri is another source of this material. The rubber is chemically different from Hevea rubber. It is thermoplastic above 60° and cannot be vulcanised. Eventually gutta-percha rubber disintegrates in the air, but it is a good insulator and is resistant to seawater. It was previously used to coat undersea cables and for golf balls. Balata rubber is obtained from Manilkara bidentata (Sapotaceae). Before production of the synthetic Surlyn in 1970, balata rubber replaced gutta-percha in golf balls. The isoprene-units in balata rubber have a "trans" configuration instead of "cis", and this rubber has therefore different properties.

The raw rubber is processed in different ways, depending on the desired end product. In dry rubber manufacture the large rubber molecules are broken down to smaller polymers via mixing rolls (plastication) under the influence of mechanical power, heat and oxygen. Then various other substances are added, such as fillers (carbon soot, clay, silica), colourants, softeners (oil, vaseline, resins, wax), antioxidants, zinc oxide or zinc stearate, accelerators (catalysts for vulcanisation) and sulphur. Wet rubber manufacturing is based in principle on direct production from latex to which the desired ingredients have been added. Shaping is done via immersion (e.g. gloves, condoms, balloons), syringes or other techniques.

Natural rubber contains approximately 6 to 8% of non-poly-isoprene constituents, such as water, proteins, ash and various fats and fatty acids. It is these proteins that may be allergenic and cause medical problems. Approximately 240 peptides have been isolated from latex. Luckily only a few of these are sensitising. The protein content and allergen content are therefore two different matters. Sometimes the accelerators or anti-oxidants are responsible for the allergy. The material should be leached out to remove the allergenic proteins. Latex gloves contain maize starch or talc to make them slip on more easily. This may cause irritating dermatitis, similar to repeated small abrasions due to washing, cold or prolonged heat. The maize starch binds to the proteins of the latex, which may play a role in the allergic process. Type IV hypersensitivity may develop, resulting in contact dermatitis. More rare is type I allergy with anaphylaxis, urticaria, rhinitis, conjunctivitis and asthma. Type I allergy occurs in fewer than 1% of the population. Not all type I allergic patients form antibodies to the same peptides. There are major peptides, which induce antibody formation in approximately half of allergic patients. There is an increased risk in people who come into regular contact with natural rubber products: health workers, patients with chronic urological or neurological problems, or who undergo repeated surgery, atopic people and children with an associated food allergy. Since some latex peptides are similar to peptides from other plants, cross reactions can be expected. Banana, kiwi and avocado pose the most problems. Many other fruit species (nuts, melon, passion fruit, peach, apple), vegetables (tomato, potato, pulses, spinach) and plants (ficus, fig, cannabis) can also trigger symptoms. Symptoms include urticaria or contact dermatitis on the hands or the genitals.

The symptoms vary greatly, from no symptoms to type I allergic symptoms, even to death. It is possible that the patient is not aware of the allergy. A positive prick test is then a surprise, and sometimes a use test (see below) is necessary to convince the patient. The symptoms may be only minimal, limited for example to a tingling feeling in the hands while washing raw potatoes. In some patients, especially health workers, the symptoms are mainly chronic eczema of the hands.

Additional investigations consist of RAST tests and skin tests. The RAST [Radio AllergoSorbent Test] for latex and determination of the total IgE are only 60-70% sensitive. A negative RAST does not rule out the diagnosis. Nevertheless it is sensible to carry out a RAST, since it correlates well with the severity of the symptoms. The RAST is highly specific, although some cross-reactivity exists (certainly in children with associated food allergies). A RAST test is always evaluated together with the total IgE and the entire symptomatology. Skin-prick testing is the gold standard for diagnosis. It is the best method for screening and diagnosis of type I latex allergy. The sensitivity and specificity of the prick test depend on the extract used, but are always much higher than those of the RAST. The use test is the only way to test conclusively, and the only test to prove the true relevance. This test is indicated if there is any discrepancy between the case history and the RAST or prick test. The use test may appear to be without risk but it can be dangerous, especially for damaged skin. For this reason a "staged use test" is always carried out. The skin is first made wet under running water. Then one finger of a latex glove with high protein content and no casein is put on for 15 minutes. If there is no reaction, a complete glove may by kept on for 15 minutes. The period of exposure may be prolonged (1 hour or more). On the other hand a control is always carried out, with a vinyl glove. The use test is regarded as positive if there are weals at the site of contact.