Latin name: Cupressus arizonica
Source material: Pollen
Common names: Cypress, Arizona cypress, Arizona rough cypress, Cedro blanco
Synonyms: C. Glabra, C. Arizonica var. glabra
See also: Italian/Mediterranean/ funeral cypress t23 (C. sempervirens).
About 30 Arizona cypress tree varieties exist, recognised on the basis of distribution and of foliage, cone and bark characteristics.
Arizona cypress is the only cypress native to the south-west of North America and has been widely exported, especially to Europe. It is a steeple-shaped, coniferous evergreen that can grow over 25 m tall. Its leaves are pale green to grey-blue. The small, inconspicuous yellow flowers are monoecious (individual flowers are either male or female, but both sexes can be found on the same plant), and are pollinated by wind. The brown bark peels in thin strips and turns grey with age.
The taller, greener, longer-lived but closely related and – where pollen allergy is concerned – very similar Italian funeral cypress tree is indigenous to the Mediterranean and has been introduced in places such as Australia, the US, New Zealand, Chile, China and India. It is the classic ornamental in cemeteries, a usage dating back to ancient times.
The Italian cypress tree is the most common cypress in the countries around the Mediterranean, followed by the Arizona cypress, and their prevalence is reflected in the allergic impact of their pollen. In the US, mountain cedar (another member of the Cupressaceae family, in Europe existing only in the Balkans and the Crimea) is a major cause of seasonal allergy in the south-west, (1, 2) overshadowing the effects of Arizona cypress.
The Arizona cypress, like a number of other cypresses (including Italian funeral cypress), is typically used as a windbreak, privacy screen or ornamental, or for erosion prevention. It is sometimes grown as a Christmas tree in the southern and western United States. The species can be found in coniferous woodlands on rough, very dry and very rocky soils.
Allergens from the Arizona cypress tree have been isolated and characterised, and their diagnostic significance has been established. (3) Cupressaceae pollen in general has 2 important characteristics: a low protein concentration, and a high carbohydrate content.
The following allergens have been characterised:
Cup a 1, a 43-kDa protein, a major allergen, a pectate lyase. (4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
Cup a 2, a polygalacturonase. (6, 16)
Cup a 3, a 21 kDa protein, a thaumatin-like protein. (17, 18, 19, 20)
Cup a 4, a calcium-binding protein. (21, 22)
A 14 kDa protein was recently identified in the closely related species C. sempervirens (Italian funeral cypress) was shown to have heat-stable conformational epitopes, and was expressed at higher levels in C. sempervirens than in C. arizonica and Cryptomeria japonica. No IgE cross-reactivity was found between the 14 kDa pollen protein and proteins from some other non-Cupressaceae pollen allergenic sources. (23) This is probably a lipid transfer protein. (24)
A 35 kDa allergenic protein, a major allergen, was isolated and may be deficient in commercial extracts. (25, 26, 27)
Cup a 1 was demonstrated to be a major allergen: 19 of 33 sera (57%) from patients allergic to cypress showed significant reactivity to purified Cup a 1, (9) and 14 out of 17 to the native allergen. (12)
Cup a 3, a 21 kDa thaumatin-like protein, is a major allergen. (19)
Sixty-three per cent of 104 cypress-allergic patients were shown to have specific IgE against rCup a 3. The enhanced expression of Cup a 3 was reported to be dependent on the pollution in the area where the pollen was collected.
In a study investigating allergens of Italian funeral cypress and Arizona cypress, the former showed a wider diversity of allergens, whereas the latter showed a higher content of the major 43 kDa allergen. (28)
A recent study reported that a large number of the sera from Arizona cypress-allergic individuals that are reactive with the major allergen, Cup a 1, recognise carbohydrate epitopes only. IgE antibodies from these sera were able to induce histamine release from basophils, and the authors suggest that they might play a functional role in the clinical symptoms of allergy. (12) A large portion of the IgE reactivity of Cupressaceae-allergic subjects was reported to be associated with sugar moieties of C. arizonica, which appear to be shared by bromelain and phospholipase A2. (7)
Extensive cross-reactivity among the different individual species of the genus could be expected, and in fact there is a great deal of evidence that it occurs. (29, 30)
Intense cross-reactivity has been reported between Italian funeral cypress, Arizona cypress and mountain cedar. (31) For example, for in vivo diagnosis of cypress allergy, mountain cedar tree pollen extract demonstrated a sensitivity of 95%, a specificity of 100%, a negative predictive value of 96%, and a positive predictive value of 100%. (1) While Italian funeral cypress tree and Arizona cypress tree are commonly encountered in Mediterranean regions, mountain juniper tree is found only in the Balkans and the Crimea in Europe, but is a major cause of allergy in the US.
C. arizonica and C. sempervirens extracts are highly cross-reactive at the IgE level and have a number of common epitopes. Two major IgE-reactive components of approximately 43 kDa and 36 kDa have been shown to be present in both. (32) The 2 have complementary allergenic composition: C. sempervirens shows a wider diversity of allergens, whereas C. arizonica shows a higher content of the major 43 kDa allergen. (28) The cross-reactivity between these 2 family members was reported to be due to the presence of periodate-sensitive as well as periodate-resistant epitopes. (33)
Extensive cross-reactivity also occurs with other family members. These include prickly juniper (J. oxycedrus), Japanese cypress/false cypress (Chamaecyparis obtusa), and western red cedar (Thuja plicata). (10)
Recombinant Cup a 1, the major allergen of C. arizonica pollen, was shown to be highly homologous with the major allergens of mountain cedar (Jun a 1), Japanese cypress (Cha o 1) and Japanese cedar (Cry j 1). The study, indicating different IgE reactivity with the glycosylated and non-glycosylated protein, suggests the importance of carbohydrate moieties in the IgE binding site. (8)
Pollen from Juniperus oxycedrus (prickly juniper tree) has also been shown to have wide cross-reactivity with other family members. (34) Recombinant Jun o 2, one of the allergens from this pollen, was shown to have significant sequence similarity to calmodulins. Immunoblotting inhibition tests showed that J. oxycedrus, J. ashei, C. arizonica, C. sempervirens, Parietaria judaica, Olea europaea, and Lolium perenne pollen extracts were able to inhibit IgE binding to rJun o 2 at different concentrations. (35) The implication is that if close cross-reactivity can be expected between J. oxycedrus and other members of the Cupressaceae, then there is a possibility that individuals allergic to Pareitaria judaica and other members of the Urticaceae (e.g. stinging nettle) could be cross-reactive to trees from this species.
Similarly, a study reported that a high inhibition of IgE binding on olive pollen extract was exhibited by birch, mugwort, pine, and cypress pollens, suggesting the presence of proteins having common epitopes that can be recognised by sera from olive-allergic individuals. (36)
Cup a 2 belongs to the polygalacturonase protein family. Polygalacturonases are major pollen allergens in Cupressaceae trees. (6) Polygalacturonases have also been identified in grass pollen (group 13 grass allergens) and in London plane tree pollen (Pla a 2). (37)
Cup a 3, a thaumatin-like stress-activated protein, has homology with a similar allergen found in mountain cedar tree (Jun a 3), Cherry (Pru a 2), apple (Mal d 2), and viral-infected tobacco leaves. (19) The amino acid sequence of Cup a 3 was found to have a high degree of homology to Jun a 3. (19)
A 14 kDa protein has recently been identified which may be responsible for individuals with allergy to Arizona cypress tree also being allergic to peach and other lipid transfer protein-containing foods. (24)
The similarities of amino-acid sequences and some complex glycan stuctures have been suggested as explaining the high degree of cross-reactivity between the Cupressaceae and Taxodiaceae families. (9)
Arizona cypress, in common with the other members of the Cupressaceae family, is an important source of allergens, causing winter respiratory allergies and commonly inducing symptoms of asthma, hayfever, and allergic conjunctivitis in sensitised individuals. (8, 34)
Authors have suggested that the real prevalence of cypress allergy is underestimated, and could partly be explained by 1) the lack of satisfactory diagnostic extracts; 2) the influence of environmental and anthropogenic factors on pollen allergenic properties; 3) the overlapping of symptoms with those induced by common winter diseases; and 4) the presence in the atmosphere of sub-micronic vectors of allergens originated from the cypress pollen sac called orbicules. (38)
Symptoms from the winter flowering may create confusion with symptoms from perennial allergens such as house dust mite. (39) The Cupressaceae pollen season has gained an earlier onset as a result of the vastly wide distribution of C. arizonica, which pollinates in January and February and partially overlaps with the very highly cross-reacting C. sempervirens, which pollinates from February to the end of March. (40) In a study over an 8-year period (1982-1989) in southern Italy, Cupressaceae pollen was noted as being at its highest concentrations during winter and early spring. “Remarkable” fluctuations of Cupressaceae pollen counts were noted over a 2-year cycle. (45)
To initially demonstrate the cosmopolitan nature of C. arizonica and of its effects, we can point to a report of a 37-year-old man from Lithuania working in Switzerland who presented with typical symptoms of allergic rhinoconjunctivitis that appeared in spring. A detailed history revealed that the patient was working in a building of a United Nations agency surrounded by a park with numerous Arizona cypress trees. Skin-specific IgE for C. arizona was strongly positive. (41)
In general, species of the Cupressaceae family (genera Cupressus, Juniperus, Chamaecyparis, Callitris, Thuja and Libocedrus) are a very important cause of allergies (especially oculo-rhinitis) in various geographical areas, especially North America, Japan, and Mediterranean countries such as France, Italy and Israel. (42) Of particular importance is the wide diffusion in these countries of trees belonging to the genus Cupressus, especially C. sempervirens and C. arizonica. (4) Cypress allergy has been reported since 1945. (43) C. arizonica and Juniperus sabinoides, or mountain cedar, are key causes of respiratory allergies in Texas and the south-western United States. In Australia, the culprit species is predominantly C. sempervirens. In Japan, the major pollen allergen source is the Japanese cedar (Cryptomeria japonica), a member of the closely related family of Taxodiaceae.
Clinical and aerobiologic studies show that the pollen map of Europe is changing as a result of cultural factors (e.g. wider international travel and evolving environmental management). During the last 30 years, C. arizonica has been widely used for reforestation, for wind and noise barriers, and ornamentally in gardens and parks. C. sempervirens and C. arizonica are common in southern Italy and France, C. alba is present in most parts of Italy, and C. lasoniana is used in the UK as a fast-growing evergreen. (44) Of the Cupressaceae, the most widespread genus in southern Italy was found to be Cupressus, represented in particular by C. arizonica Green and C. Sempervirens L. The authors noted that the employment of these trees for reforestation and garden ornamentation had increased considerably in the last 40 years. (45) An increase in the reactivity to Cupressaceae pollens has been described as well, possibly because the allergenic load is becoming greater. Air pollution may have contributed to this increase. (42)
A recent GA2LEN skin-test study, evaluating the clinical relevance of inhalant allergen sensitisation in Europe, found that the average standardised sensitisation rate (SSR) for Europe was 3.9%, and the clinically relevant sensitisation rate (CRR) was 2.6%. However, these results varied between countries (Country - SSR - CRR): Austria - 1.5 - 0.3; Belgium - 2 - 1.2; Denmark - 5.8 - 3.7; Germany - 2.8 - 0.8; Greece - 5.6 - 3.7; Finland - 0 - 0; France - 8.7 - 5.3; Hungary - 2.9 - 2.9; Italy - 8.1 – 6; the Netherlands - 1.5 - 1.5; Poland - 1.2 - 0.8; Portugal - 5.1 - 2.8; Switzerland - 1.4 - 1.4; UK - 11.1 - 8.7. (46, 47)
Older studies are illustrative.
From the Mediterranean region comes the most dramatic evidence of recent increases in reactivity to Cupressaceae pollen. For example, in a comparative study of Cupressaceae, the annual mean pollen concentration in Lyon-Bron, France (in a temperate region), went from 4.5 pollen grains per cubic metre of air at the beginning of the 1980s to 13.7 pollen grains at the beginning of the twenty-first century (an increase of more than 200%); and in Montpellier, France (in a Mediterranean region), the concentration went from 43 pollen grains per cubic metre of air to 72 pollen grains during the same period. (48)
Similarly, in Rome, the incidence of cypress allergy increased from 9.3% to 30.4% in 3 years. (49) In Italy, the annual sensitisation rate as demonstrated by skin-specific IgE to C. sempervirens increased from 7.2% in 1995 to 22% in 1998. (50) In another large-scale study, allergy to Cupressaceae pollen was also reported to be on the increase in recent years in Italy. (39) In an epidemiological survey, conducted in 12 Italian centres, of 3 057 pollen-sensitised patients, the prevalence of skin reactivity to a panel of tree pollens was found to be 9.2% in northern, 28.2% in central, and 20.1% in southern Italy. Monosensitised patients represented only 14.7% of all Cupressaceae-sensitised patients, their average age being higher than that of the polysensitised ones (43.3 versus 35.86). The most frequent allergens, as shown by prick tests, were Cupressus sempervirens (90%) and Cupressus arizonica (88.9%). The authors concluded that pollen allergy to the Cupressaceae was on the increase in Italy. (39)
A recent Italian study that examined the sensitisation pattern in a population of polysensitised patients with respiratory allergy, living in a restricted geographical area in north-west Italy, found that of the 70 patients evaluated, 11 were skin-prick test-positive to cypress pollen, and 18 were positive for serum-specific IgE for the major allergen, Cup a 1. (13)
Nevertheless, the prevalence of cypress sensitisation appears to vary greatly, even though the data are consistently collected in geographical areas with abundant cypresses. Some authors have stated that cypress allergy is underestimated, as this is a winter pollen and pollen allergy may be characterised by symptoms mimicking “recurrent” viral infections. (42, 51) Other researchers have claimed that the prevalence of sensitisation is low in spite of the high allergenic pollen load in the areas studied. (2, 52) For instance, in the Western Ligurian Riviera, cypresses are part of the indigenous flora and are also cultivated and planted for ornamental and other gardening purposes. Of 1 735 patients, only 18 (1.04%) had skin reactivity to cypress. Of these 18 patients, only 5 were monosensitised, whereas the remaining 13 patients were polysensitised. Rhinoconjunctivitis was the most frequent symptom. In patients with polysensitisation, symptoms were not clearly related to the cypress pollen season, but may rather have had to do with other pollens. The Cupressaceae pollen counts were high during the pollen season, with an increasing trend during the previous 4 years. The data from this study show that the prevalence of sensitisation to cypress, at least in this geographic region, is very low despite the large diffusion of pollens and the high pollen peaks. This contrasts partly with data reported in previous surveys. (53) For instance, in a study performed in another area of the Ligurian Riviera, (53) the rate of sensitisation was higher. (2)
A possible explanation for the underestimation of the prevalence of cypress allergy may be the difficulty of allergen extraction from the grains, which leads to a lack of standardisation of the extracts. Another possible factor is genetic protection, especially in those populations in close contact with cypresses over the centuries. (54)
The majority of studies have evaluated either ‘cypress’ (as a homogenous entity), or Italian funeral cypress. This may have influenced the results of some studies. In a 4-year Italian study of 1 393 patients, utilising SPT to C. sempervirens, an incidence of cypress allergy of approximately 10% was reported in the first 2 years, but rose to over 24% when C. arizonica pollen extract was added to the test. With further improvements in the testing, 35.4% of patients in the final year of the study were shown to be allergic to cypress pollen. The study concluded that allergy to cypress is under-evaluated as a result of its winter seasonal appearance, and that a false-negative diagnosis may be made as a result of poor in vivo allergen extracts. (51) The authors of another study concluded that the use of more than 1 extract of Cupressaceae and Taxodiaceae origin would increase diagnostic sensitivity. (39)
Examining individual regions outside Italy, cypress pollen allergy is also very important in France. In a study of Cupressaceae pollen (C. sempervirens) and allergic individuals in Montpellier, the authors reported that individuals allergic to this pollen present with a high rate of conjunctivitis and a low rate of asthma. (42) A more recent study in the same region reported that 20.7% of patients were sensitised to cypress pollen and 46.4% presented symptoms during the pollen season. The main symptoms were rhinoconjunctivitis and asthma. Oral allergy syndrome to peach was detected in 4% of sensitised and symptomatic patients. Immunotherapy was necessary to control symptoms in 57.9% of cases. (55)
Cypress allergy has also been reported in Spain, and Cupressaceae pollen is by far the most common pollen during the winter period (30%) in Cordoba. From January to April, Cupressaceae pollen is the predominant pollen in areas such as Toledo, Barcelona and Madrid (11%), and it is the main cause of the so-called ‘winter allergic cold’. The prevalence of positive skin-prick tests to C. arizonica extract is 20%. (56, 57, 58, 59) In the study, the absence of monosensitisation was noted. Of adult pollen-allergic patients, 37% were allergic to Cupressaceae, and 18% of those with respiratory allergy. (56)
A study of 121 Spanish patients with nasal polyposis found that skin-prick tests were positive in 63.2%. The allergens that most frequently elicited a reaction from the patients in the prick tests were house dust mites and pollen from olive tree (21.1%). Skin-prick tests for C. arizonica were positive in 15 (7.9%). (60)
In Israel, Italian funeral cypress grows naturally, but millions of these trees were also planted in recent times, as well as Arizona cypress and a variety of other family members. Researchers reported that pollen release in some regions may vary from one locality to another by a month, depending on prevailing winds, water availability and other microclimatic conditions. (61) In another Israeli study, patients with cypress allergy were reported to be symptomatic from February until April; 70% of them had rhinitis, 30% also had asthma, and 18% had conjunctivitis. Sensitisation to this pollen in hay fever patients varied from 26% in Tel Aviv to 32% in Netzer-Sireni and 24% in lower Galilee. In the monosensitised patients, anti-cypress immunotherapy was successful. (62)
Similarly, Arizona cypress pollen has increased in the air of Tucson, Arizona, due to ‘greening’ of the area with ornamentals and barrier plants. (63) However, there is a remarkable shortage of allergy-related studies of this tree where it is indigenous, in the United States.
In a previous study of pollen concentration in Monterrey, Mexico, Cupressus occupied the 3rd place in frequency. An observational, cross-sectional and prospective study assessing potential exposure and allergic symptoms to pollen conducted skin-prick tests on 256 patients – 130 younger than 18 years old, and 126 adults. The skin test was positive in 39 patients (15.2%). Of the 36 aeroallergens tested, Cupressus occupied 7th place in frequency. Patients with a positive skin test to Cupressus had at least one positive skin test to other aeroallergens, in 97% of cases. (64)
A study conducted in Teheran, Iran, aimed at identifying relevant allergens of P. orientalis pollen, evaluated 19 patients with a clinical history of reaction to P. orientalis pollen. On skin-prick tests, all the patients were polysensitised to grass and tree pollen allergens: Ailanthus altissima (16/19), A. longifolia (13/19), C. arizonica (11/19), Fraxinus americana (14/19), Amaranthus retroflexus (17/19), Cynodon dactylon (16/19), Chenopodium album (18/19), Artemisia vulgaris (16/19), Salsola kali (18/19), and Phleum pratensis (17/19). (65)
Seasonal eosinophilic bronchitis due to allergy to C. arizonica pollen has been described. (66)
A 66-year-old woman with symptoms of allergic rhinitis and asthma due to C. arizonica developed palpable violaceous purpuric lesions and pruritus on both legs after 2 years of maintenance immunotherapy, 48 hours after one maintenance dose of 0.8 cc. Biopsy showed leukocytoclastic vasculitis. A type III hypersensitivity immune reaction was suggested by the authors. (67)
Immunotherapy for Arizona cypress pollen allergy is potentially of benefit. (55, 67, 68)
Compiled by Dr Harris Steinman, firstname.lastname@example.org
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