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E-IJD® - ORIGINAL ARTICLE
Year : 2022  |  Volume : 67  |  Issue : 5  |  Page : 625
Contact sensitization to allergens of biological origin from the compositae family and original extracts of ubiquitous weed plants of vojvodina among patients with chronic venous insufficiency


Departments of Dermatovenereology, Faculty of Medicine Novi Sad, University of Novi Sad, Clinic of Dermatovenereology Diseases, Clinical Centre of Vojvodina, Novi Sad, Serbia

Date of Web Publication29-Dec-2022

Correspondence Address:
Vujanović Ljuba
Hajduk Veljkova 1-9, 21000 Novi Sad
Serbia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_705_21

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   Abstract 


Background: The use of alternative treatment methods, particularly medicinal herbs from the family Compositae, significantly contributes to the increase in the incidence of allergic contact dermatitis among patients with chronic venous insufficiency. Objective: Estimating frequency of contact sensitization among patients with chronic venous insufficiency and determining the most common contact sensitizers from the series of bio-origin allergens from the Compositae family and ubiquitous weeds of Vojvodina. Materials and Methods: The total number of 266 patients with suspected contact dermatitis was divided into two groups: the experimental group consisted of patients with chronic venous insufficiency (EG), and the control group consisted of patients without chronic venous insufficiency (CG). All subjects were tested with allergens of biological origin from the family Compositae, screening allergen SL-mix and original extracts of ubiquitous weed plants of Vojvodina. Results: Patch test revealed a positive reaction to allergens of the Compositae family in 6.69% in the experimental group, and in 4.17% in the control group. The standardized response rate to the SL-mix in the experimental group was 2.07%, while in the control group, it was 1.51%. The presence of a positive reaction to at least one extract of ubiquitous weed plants of Vojvodina was determined in 6.11% in the experimental group, and in 3.23% of patients in the control group. No statistically significant difference in response rates was found between the examined groups. Conclusions: Establishing the diagnosis of Compositae dermatitis can be supplemented by additional testing with weed plant extracts from a specific geographical area, resulting in the detection of novel unknown allergens.


Keywords: Allergic contact dermatitis, chronic venous insufficiency, Compositae dermatitis, ubiquitous weed plants of Vojvodina


How to cite this article:
Ljuba V, Sanja J, Zoran G, Olivera L. Contact sensitization to allergens of biological origin from the compositae family and original extracts of ubiquitous weed plants of vojvodina among patients with chronic venous insufficiency. Indian J Dermatol 2022;67:625

How to cite this URL:
Ljuba V, Sanja J, Zoran G, Olivera L. Contact sensitization to allergens of biological origin from the compositae family and original extracts of ubiquitous weed plants of vojvodina among patients with chronic venous insufficiency. Indian J Dermatol [serial online] 2022 [cited 2023 Jan 31];67:625. Available from: https://www.e-ijd.org/text.asp?2022/67/5/625/366139





   Introduction Top


Chronic venous insufficiency (CVI) is a disease of chronic recurrent course that requires long-term therapy and monitoring. Side effects and complications are quite frequent during the treatment of CVI. The most prevalent among them is allergic contact dermatitis (ACD) due to local therapy that occurs in 60–80% of CVI cases.[1],[2],[3] The underlying mechanism for the development and progression of allergic contact dermatitis in patients with CVI is still not completely clarified. It has been proved that the monocytes from the blood of patients with CVI, secrete abundant quantities of tumour necrosis alpha, interleukins 1-β and 6, which further play essential role in immunological activation, stimulation of other T cells, and release of different cytokines result in the appearance of allergic contact dermatitis.[4],[5]

Possible triggers for ACD encompass a wide range of different local therapeutics, from disinfectants to hydrocolloid compresses and moist compresses, due to the accelerated development of pharmaceutical technology.[6],[7],[8],[9],[10] In addition, the use of alternative treatment methods in therapy of CVI, particularly medicinal herbs from the family Compositae (lat. Asteraceae) that belong to ubiquitous weed plants in Vojvodina, which are known to have allergenic potential, markedly contributes to the increase in the incidence of contact sensitization in patients with CVI.[11],[12],[13] Compositae dermatitis is in the ten most common in Europe.[11],[14],[15],[16] but there are no data about its prevalence in CVI patients. For that reason, the aim of this study was to determine the role and clinical significance of contact sensitivity to plants from this family in patients with CVI.


   Materials and Methods Top


Patients

The study had the character of a prospective study for a period of three years. All patients were of Caucasian race, age above 18 years, with residential address in Vojvodina, Serbia, who were admitted at the Clinic of dermatovenereology, Clinical Centre of Vojvodina, Serbia, according to the order of appearing for examination. The total number of examined patients was 856, of which 188 patients with CVI without any sign of contact dermatitis, 272 patients with atopy, 89 patients who did not meet the inclusion criteria regarding therapy and UV exposure, 17 patients who voluntarily withdrew from the study or did not complete patch testing, 24 women who were pregnant or in lactation period, and 266 patients who continued to participate in trial and further presented a study sample [Flowchart 1]. Following the application of inclusion and exclusion criteria, two groups were formed: the experimental group (EG) consisted of 150 subjects with chronic venous insufficiency with suspected contact dermatitis (96 women and 54 men, mean age 64.24 ± 120.066 years), and the control group (CG) which numbered 116 subjects with suspected contact dermatitis without chronic venous insufficiency (89 women and 27 men, mean age 45.55 ± 17.001 years). Patients with CVD were older than the control group (P < 0.001), the difference was small but statistically important. There was a statistically significant difference in the gender structure between the examined groups (P < 0.001), and in the control group, the percentage of women was noticeably higher than in the group of patients with CVI.



The examination of each patient included: duplex sonography of lower extremity veins, assessment of ABPI (Ankle Brachial Pressure Index), and CEAP classification (Clinical-Etiological- Anatomical-Pathophysiological classification) for patients with chronic venous insufficiency (CVI). Informed consent was obtained from all patients in accordance with the policy of the Institutional Audit Committee, and the study protocol followed the ethical guidelines of the 1975 Declaration of Helsinki.

Inclusion criteria for the study were: the existence of CVI for the experimental group and the absence of CVI for the control group; ABPI >0.9; skin lesions indicative of contact dermatitis; the absence of atopic diathesis; the absence of active dermatitis at the time of testing; period of at least four weeks without systemic corticosteroid therapy, at least four weeks without local corticosteroid therapy on the testing site (the upper part of the back and forearms) and three days without any other local therapeutics, at least six months without immunosuppressive therapy, at least seven days before allergy testing without systemic antihistamines, at least four weeks before allergy testing without UV exposure. Exclusion criteria for the study were: data on atopic diathesis (includes the presence of allergic conjunctivitis, rhinitis, asthma, atopic dermatitis); patients with systemic disease; patients on immunosuppressive therapy during the previous 6 months; patients who were intensely exposed to the sun for 4 weeks before testing; systemic and topical administration of corticosteroids for 4 weeks before testing; active dermatitis at the time of testing; pregnancy and lactation.

Patch test

Patch test (epicutaneous test) was performed with allergens of biological origin from the family Compositae and screening allergen SL-mix (sesquiterpene lactones) produced by Chemotechnique Diagnostics (Vellinge, Sweden) and original extracts of ubiquitous weed plants of Vojvodina. The test site was the intact skin of the upper half of the back. The tested allergens were placed on the skin using special chambers and hypoallergenic adhesive test strip: Curatest® (Lohmann and Rauscher, Neuwied, Germany). They were removed and read at D2, D3, D4, and D7. Reactions of + and above were regarded as positive, according to the guidelines of the International Contact Dermatitis Research Group (ICDRG).

Data analysis

Statistical analyses covered: the calculation of percentage structure (%), arithmetic mean (X), standard deviation (SD), χ2 test in order to compare means proportions, t test for independent samples to determine differences in contact sensitization between study groups, and PAFS (population-adjusted frequency of sensitization) standardization to overcome the differences in relation to gender and age of respondents (IBM SPSS Statistics, version 20).


   Results Top


Patch test revealed the presence of a positive reaction to allergens of biological origin from the Compositae family in 6.69% of patients with CVI and in 4.17% of patients in the control group, without statistically significant difference (z = 0.73 < 1.96: P > 0.05).

Allergens with the highest standardized reaction rate in the experimental group were CM-mix 3.69%, feverfew flower 2.87%, and tansy extract 2.71% [Table 1], whereas in the control group, they were Arnica extract 2.78%, sorbitan sesquioleate 1.94%, and chamomile extract 1.11% [Table 2].
Table 1: Standardized response rates to allergens of biological origin from the Compositae family in the experimental group (EG)

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Table 2: Standardized response rates to allergens of biological origin from the Compositae family in the control group (CD)

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Regarding gender-standardized sensitization rates, it was found that the male subjects showed a higher incidence than the female subjects for all the tested allergens in the experimental group. On the other hand, women were more sensitive than men to arnica extract in the control group, while the male subjects presented a higher response rate for all other tested allergens.

The standardized response rate to the SL-mix in the experimental group was 2.07% [Table 3], and 1.51% in the control group [Table 4].
Table 3: Standardized response rates to original extracts of ubiquitous weed plants of Vojvodina and SL-mix in the experimental group (EG)

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Table 4: Standardized response rates to original extracts of ubiquitous weed plants of Vojvodina and SL-mix in the control group (CD)

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Epicutaneous testing showed a positive reaction to at least one extract of ubiquitous weed plants of Vojvodina in 6.11% of patients with CVI, and in 3.23% of patients in the control group. The difference was not statistically significant (z = 0.64 < 1.96; P > 0.05).

The first five allergens that were distinguished by the highest standardized reaction rate in the experimental group were: 10% Artemisia absinthium extract (diaper) 3.26%; 10% extract of Ambrosia artemisiaefolia (diaper ragweed) 2.31%; 3% Artemisia vulgaris extract (wild diaper) 1.72%; 3% extract of Ambrosia artemisiaefolia (diaper ragweed) 1.18%; and 1% essential oil of Ambrosia artemisiaefolia (diaper ragweed) 1.14% [Table 3].

In the control group, the most common contact sensitizers were: 10% Artemisia vulgaris extract (wild diaper) with a standardized response rate of 2.12%; 10% extract of Artemisia absinthium (diaper) with a standardized response rate of 1.59%; and 3% Artemisia absinthium extract (diaper) with a standardized response rate of 1.03%, while the remaining tested allergens such as 0.1% Taraxacum officinale extract (dandelion); 3% Taraxacum officinale extract (dandelion); 3% extract of Artemisia vulgaris (wild diaper); 1% Artemisia absinthium extract (diaper); 1% extract of Ambrosia artemisiaefolia (diaper ragweed), and 3% extract of Ambrosia artemisiaefolia (diaper ragweed) showed a standardized response rate of 0.56% [Table 4].

After standardization of relative incidences of contact sensitization by gender and age in the experimental group, significantly lower values of standardized eczema response rates were obtained for all allergens with preserved order of the most common allergens, while a higher degree of sensitivity among the male subjects was estimated for all the tested allergens. Analysing gender- and age-standardized eczema response rates in the control group, females were more sensitive than men to 10% diaper extract, but a higher degree of sensitivity to all other tested allergens was found among the male subjects.


   Discussion Top


The family Compositae, in Latin Asteraceae, comprises more than 1,000 genera with over 23,000 different species distributed worldwide, whose use can trigger allergic contact dermatitis known as Compositae dermatitis.[17] Testing with two screening allergens, a mixture of sesquiterpene lactone (SL-mix) and a mixture of ether extracts of five different Compositae plants (CM-mix), is recommended for diagnosing Compositae dermatitis.[16],[18],[19],[20]

Since 1990, SL-mix has been in the standard series of most European countries in a concentration of 0.1% in Vaseline.[6],[21] The SL-mix consists of equimolar amounts of three sesquiterpene lactones, allantolactone (eudezmanolides), dihydrocostuslactone (guanolide), and costunolide (germacranolis).[22] Allantolactone was obtained from oman extract—Inula helenium, and dihydrocostuslactone and costunolide from Saussurea lappa extract—costus.[21] SL-mix has a low risk of irritation (0–0.12%) and active sensitization (0–0.09%), so the routine testing is safe but not sensitive enough.[21],[23],[24],[25],[26],[27],[28] Testing with SL-mix alone reveals only 1/3 to 2/3 of Compositae—hypersensitive individuals.[23],[24],[25],[26],[27],[28],[29]

The CM-mix has been on the market since 1997. It is a mixture of six different components. CM-mix is a screening allergen used in a concentration of either 6%, 5%, or 2.5% in Vaseline.[16] The mixture consists of 1% essential oil extract of Tanacetum parthenium, 1% Tanacetum vulgare, Achillea millefolium 1% Vaseline, Chamomilla recutita 2.5% Vaseline, and Arnica Montana 1% in Vaseline.[21] The sensitivity of CM-mix is twice as high as the SL-mix reaching almost 90%, but with significantly higher chance for irritation and sensitization.[23] According to the literature data, irritation rate of the CM-mix is up to 1.37%, and active sensitization is between 0.5 and 0.86%, so for these reasons it is used selectively.[29],[30]

Simultaneous testing with both screening allergens can detect 76–90% of people who are hypersensitive to Compositae plants.[23],[25] Considering the possibility of obtaining false-negative results, apart from testing with standard allergens, additional testing with parts of the fresh plant or its extracts is highly advisable.[25],[31]

Since we did not find comparable results of gender/age-standardized rates among EG patients in recent publications, we compared our relative incidence rates with those in the available literature data. The relative incidence of contact sensitization in this series of allergens was 14%. Within the series of standard biologic allergens from the Compositae family, apart from the relative incidence of CM-mix of 8.0%, the highest relative incidence was found for Yarrow extract (6.67%). The relative incidences of tansy extract and feverfew flower were 5.33% each, chamomile with 4.67%, 4.0% for sorbitan sesquioleate, and 3.33% for extract of arnica. Jovanovic et al. conducted a study among patients with non-allergic chronic inflammatory dermatoses (venous ulcers, psoriasis, and acne vulgaris). According to the results from their study, the presence of contact sensitization to the examined CM-mix, its individual constituents, SL-mix, and original weed plant extracts was not registered among patients with venous ulcers.[15]

All subjects in the control group were also tested with two screening allergens: SL-mix and CM-mix (including extracts of six plants that are constituents of CM-mix). In our study, the prevalence of standard allergens of biological origin from the Compositae family was 4.31%, which is in line with the results of Paulsen at al. who found a prevalence of 4.5% in their study, to wit 4% for overall studied period.[16],[24] In the literature available to us, the prevalence of hypersensitivity to Compositae in the general population ranges from 0.7 to 1.4%, and it can be up to 4.5% in occupationally exposed individuals. It is known that in northern Europe, plants induce up to 4.5% of all cases of occupational allergic contact dermatitis.[14]

Within the standard series of biologic allergens from the Compositae family, contact hypersensitivity was found in four patients. Two respondents (1.7%) were diagnosed with allergic hypersensitivity to the CM-mix and reacted to individual standard allergens at the same time. One of the examinees presented allergic hypersensitivity to yarrow, and the other was polysensitized and showed allergic hypersensitivity to all individual allergens. Allergic hypersensitivity to individual allergens of the standard series of bio-origin was determined in two subjects, without showing contact sensitization to CM-mix as a screening allergen. It further justifies the importance of testing individual components of the CM-mix in order to precisely assess relevant hypersensitivity to Compositae plants.

Hypersensitivity to the SL-mix was proven in two patients who did not show contact sensitization to any of the allergens from the standard series of biologic allergens from the Compositae family.

Screening with SL-mix and CM-mix, registered 2/3 of sensitized patients, and another 1/3 of Compositae hypersensitive individuals was detected by testing with individual allergens from the composition of CM-mix.

Having analysed standardized response rates by gender, in both the experimental and control groups, what was indicative is that men were more sensitive to all the tested allergens (with the exception of arnica). This may be explained by the fact that more than a half of the male subjects in this group were countryside residents, being often professionally exposed to these allergens (farmers and pensioners). Unfortunately, we could not find any analogous research that could provide us with comparable data.

In accordance with the suggestions that testing should be extended with parts of fresh plants or their extracts, all of our subjects, in both experimental and control groups, were assayed with original plant extracts.

The prevalence of contact sensitization in this series of original extracts of ubiquitous weed plants of Vojvodina in the experimental group was 10.67%. Within this series, the highest relative incidence of 4.7% was estimated for 10% diaper ragweed extract and 10% diaper extract. Simultaneous reactivity to ragweed extract and wild wormwood may be the result of cross-reactivity.[32] After standardization of relative incidences of contact sensitization by gender and age, significantly lower values of standardized eczema response rates were obtained for all allergens with the preserved order of the most common allergens. We did not find any other similar publication presenting the prevalence of contact sensitization to extracts of ubiquitous weed plants in patients with CVI.

The prevalence of contact sensitization in this series of allergens in the control group was 5.17%. This prevalence is close to the rates from a study conducted by Werth et al.[23] in which the frequency of contact sensitization to Compositae in routinely tested individuals with suspected contact dermatitis was 5.9% by using only screening allergens.[21] The prevalence found in our study is lower than the prevalence of 8% in research performed by Petrović et al.,[33] which included patients with allergic contact dermatitis in Vojvodina in the period from 2003–2005. The reduction of contact sensitization to weeds in Vojvodina was probably contributed by the organized eradication of primarily ragweed and other weeds of the genus Compositae. In our research, the highest relative incidences of 3.4% were found for 10% wild diaper extract, and 2.6% for 10% diaper extract.

Contact hypersensitivity to the original extracts of ubiquitous weed plants of Vojvodina was determined in eight patients from experimental group. Two patients (1.7%), already diagnosed with allergic hypersensitivity to CM-mix and individual standard allergens in the CM-mix, also reacted to the original extracts of ubiquitous weeds. Testing with original extracts of ubiquitous weed plants detected six subjects sensitized to these allergens, without being hypersensitive to the screening allergen (CM-mix) and individual allergens from the composition of CM-mix.

In the control group, patch test with CM-mix as a screening allergen, individual allergens from the composition of CM-mix, and original extracts of ubiquitous weed plants of Vojvodina, revealed contact hypersensitivity in 10 patients (8.62%). Among subjects hypersensitive to Compositae, 40% were hypersensitive to 10% wild diaper extract, and 30% were hypersensitive to 10% common diaper extract. Of the total number of patients with contact hypersensitivity to Compositae, 20% were detected by testing with CM-mix, 20% by testing with individual allergens from CM-mix, and 60% by testing with original extracts of ubiquitous weed plants of Vojvodina, which further implies the essential need for additional testing to allergenic plants with which respondents have direct contact.


   Conclusion Top


Statistical analysis of the obtained results did not reveal a statistically significant difference in contact sensitization to allergens of biological origin and to individual extracts of ubiquitous weed plants of Vojvodina among patients with chronic venous insufficiency. Over and above, additional testing with weed plant extracts from a certain geographical area is of the utmost importance not only because of geographical differences, but also for the purpose of discovering the possible presence of potential, unknown allergens in ether preparations, relating to either individual differences in allergen exposure or individual cross-reaction.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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