Summary

Italian cypress (Cupressus sempervirens), also named as Mediterranean or funeral cypress is a traditional, ornamental tree often used in cemeteries. This evergreen, wind-pollinated, monecious tree can grow up to a height of 35-40 m and is capable of producing pollens in huge quantities. This tree is drought and heat tolerant and is commonly seen in areas, such as farmlands and forests. The tree is commonly found in the US, Europe, Japan, Australia, North-East African countries and Middle-Eastern countries. The prevalence rate of cypress pollen allergy has been reported between 0.6% and 32%, according to the studies conducted in various geographical region. Exposure to Italian cypress tree pollen can induce symptoms, such as allergic rhinitis, rhino-conjunctivitis, asthma, and contact dermatitis in rare cases. Cup s 1 and Cup s 3 have been identified as the major allergens in the Italian cypress tree pollen. Studies have demonstrated high cross-reactivity between pollens from Italian cypress and other related species, such as Arizona cypress, mountain juniper, Japanese cypress, and Japanese cedar. This species pollen has also exhibited cross-reactivity with scrub cypress pine, African fern pine and peach.

Epidemiology

Worldwide distribution

Pollens from Italian cypress trees are considered as a primary contributor to seasonal allergic rhinitis (AR) in the Mediterranean areas. It has been reported that almost half of the total pollination level is accounted by this pollinating species in this region. Cypress pollinosis is represented by asthma, conjunctivitis, and AR.

Wide variation in the prevalence rate of allergy to cypress pollen has been reported in the studies mentioned below, that ranged from 0.6% to 32%. The prevalence rate in these studies was identified, either by conducting questionnaire surveys or through SPT results.

In a cross-sectional study conducted in France, the prevalence of cypress pollen allergy was reported between 0.6%-2.4%, among patients with AR (hay fever).

Another study conducted in Greece reported 12.7% (166 out of 1311) of patients with respiratory allergy, being sensitized to cypress pollen.

Furthermore, in a study conducted in Israel, a relatively higher prevalence (24%- 32%) of sensitization to cypress pollen was reported in patients suffering from AR.

A retrospective study was conducted in Italy among 1397 patients who complained of having conjunctival or respiratory disorders between the year 1995 and 1998. The results showed an annual increase in the rate of sensitization to Italian cypress pollen, that ranged from 7.2% to 22% between these years.

In a study conducted among school-going children (6 to 17 years) in Greece, the prevalence rate of sensitization to various pollens was determined. Among 675 children who participated in the study, 231 (34.2%) were diagnosed as having AR. Of 231 patients, 4.8% (11 out of 231) of patients reported sensitization to cypress pollen. Interestingly, children aged 6 to 11 years showed higher sensitization to these pollens in comparison to children aged 12 to 17 years (6-11 years: 63.6% vs 12-17 years: 36.4%). Furthermore, a significant co-sensitization was seen between pine and cypress allergens (p=0.006).

Route Of Exposure

Main

One of the significant routes of exposure to Italian cypress pollen is through airway inhalation. Pollens from Italian cypress trees are wind-pollinated and can spread across large distances. The pollen grains are considered as the carriers of allergens, since they contain small particles, known as orbicules on their surface, that are responsible for containing these allergens.

Secondary

Direct skin contact is another route of exposure. This was evidenced in a case study, where a 56-year-old woman, after coming in contact with the resin of Italian cypress leaves, developed contact dermatitis.

Clinical Relevance

Cypress pollen hypersensitivity is a significant contributor to pollinosis, particularly in countries of Mediterranean region. Cypress pollinosis is responsible for inducing allergic symptoms, such as rhino-conjunctivitis, AR, and asthma in sensitive individuals. Genetic susceptibility, elevated pollen exposure and past experience of cypress allergy are considerable risk factors for determining allergic and atopic patients. Interestingly, AR is the most frequently observed symptom, whereas rhino-conjunctivitis is the most debilitating symptom of cypress pollen allergy.

Allergic rhinitis (AR) and allergic rhino-conjunctivitis (ARC)

A steady rise in the prevalence of allergic conditions, such as AR, rhino-conjunctivitis and asthma has been observed in elderly patients sensitized to allergens. In a case-control study conducted in Italy, elderly patients (>65 years) with AR and/or rhino-conjunctivitis (cases) were compared to young adults (15 – 40 years) who acted as control. According to the results, among all the allergens extracts analysed by SPT, cypress pollen was the most common sensitizing allergen in the elderly.

In a study performed in Turkey on 455 patients diagnosed with AR and/or asthma, 81.3% (370 out of 455) of patients had AR, and 18.7% (85/455) of patients had asthma as well as AR. Out of these patients, 14.3% (65 out of 455) were found sensitized to cypress pollen.

In a study conducted on 47 cypress pollen-allergic patients in France, an association between cypress pollen concentration levels, rhino-conjunctivitis symptoms (itching, redness, teary eyes, sneezing, runny/stuffed nose, wheezing, cough or asthma) and quality of life (QoL) was reported. According to the study, a logarithmic curve was reported between cypress pollen count and rhino-conjunctivitis symptoms. This evidence was supported by the results that revealed a remarkable elevation in rhino-conjunctivitis symptoms, when the pollen count increased from 0 to 500 grains/. However a gradual decrease in these symptoms were noted, in spite of an exposure to increased number of pollen grains (>500 grains/), displaying a plateau effect at increased level of pollen exposure. Furthermore, a linear association was observed between cypress pollen count and QoL score, which indicated that, with every increase in 500 grains of cypress pollen, an increase in QoL score was reported. The study, however could not identify the threshold level for the occurrence of allergic symptoms or QoL in these allergic individuals, indicating larger studies to be conducted for determining this potential threshold.

A retrospective study was conducted over a period of 4 years in Italy on 1397 individuals complaining of respiratory tract or conjunctival disease. According to the results, the prevalence of positive SPT in patients allergic to Italian cypress pollen was found to be 17.4% (243 out of 1397). Among these individuals, 64.6% (157 out of 243) had rhino-conjunctivitis, 27.2% (66 out of 243) had asthma and 8.2% (20 out of 243) had both asthma as well as rhino-conjunctivitis.

Contact dermatitis

A case of a 56-year-old woman in France who suffered lesions on her body, after coming in contact with the resin of Italian cypress leaves. The patient had a past history of developing a skin response towards adhesive bandages. The patch test performed showed positive association between the leaves, cone, resin of the tree species and colophonium derivates used in adhesive bandages samples. This concluded that contact dermatitis developed in the patient could be a result of cross-reactivity between colophonium and Italian cypress allergen.

Prevention And Therapy

Allergen immunotherapy

A double-blind, placebo-controlled study was conducted among 40 patients, where 20 patients with rhino-conjunctivitis and cypress pollen allergy were administered with either sublingual-swallow immunotherapy (SLIT; n=10) or subcutaneous immunotherapy (SCIT; n=10), using Juniperus ashei extract and 20 patients were administered placebo. According to the results, treatment with SLIT and SCIT showed good improvement in the clinical symptoms as well as decrease in the inflammation parameters (serum levels of eosinophilic cationic protein and nasal levels) in patients with rhino-conjunctivitis due to cypress allergy.

Prevention strategies

Avoidance

Italian cypress pollen allergy can be prevented or reduced by using a few precautionary measures, such as washing hair before sleeping, using protective sunglasses while stepping out of the house, restricting oneself from doing exercise outside the home, keeping doors and windows closed, and avoiding drying of linen clothes outside.

Furthermore, to minimize the amount of pollen into respiratory system, it is suggested to either stay indoors or wear a mask, while moving outdoors. If the patient’s health condition deteriorates, it is further advised to move to an area, where there is less pollination.

Cross-Reactivity

Italian cypress pollen has shown to cross-react and share high sequence homology with closely-related species, such as Arizona cypress, mountain juniper and Japanese cypress, belonging to the same family Cupressaceae and Japanese cedar which belongs to the same class Pinopsida as Italian Cypress.

High degree of sequence similarity i.e. 95.1% has been reported between Cup s 1 (Cupressus sempervirens) and Cup a 1 (Cupressus Arizonica). Furthermore, Cup a 1 has shown to exhibit high sequence homology of 91% with Jun a 1 (Juniperus ashei), 75% with Cry j 1 (Cryptomeria japonica) and 81% with Cha o 1 (Chamaecyparis obtuse). These major allergens from the same family and class, are highly cross-reactive, as they share between 70% to 95% of sequence similarity.

Another major allergen from C. sempervirens species, Cup s 3 has revealed to have 95% sequence homology and strong cross-reactivity with Jun a 3 (J. ashei).

Limited cross-reactivity was displayed between Italian cypress pollen, scrub cypress pine (Callitris verrucosa) and African fern pine (Podocarpus gracilior).

Olive pollen has shown to cross-react with cypress pollen, pine pollen, mugwort, and birch in a study, where IgE binding to these pollen extracts was completely inhibited by extract of olive pollen. This showed that proteins of olive pollens share allergenic epitopes that are in common with the proteins of the other pollen extracts, and hence the cross-reactivity.

Cross-reactivity through IgE binding has been demonstrated among Italian cypress, white cypress pine, rye grass, ragweed, olive, birch, couch grass, plantain, lamb’s quarters, cocksfoot and wall pellitory.

Cross-reactivity has also been reported between peach and cypress pollen. This was evidenced in a case series of seven cypress pollen-allergic patients, who immediately after consuming peach developed OAS, urticaria or Quincke edema.