Mugwort
Summary
Mugwort (Artemisia vulgaris), belonging to the family Asteraceae or Compositae, is a perennial root stalk weed that grows along the roadsides, in waste area and infests nursey crops. It is found troublesome in about 25 crops in 56 countries. Mugwort is distributed widely across Europe, Canada, United States and parts of Asia. Mugwort is usually wind-pollinated and inhalation of the pollen grains (spheroidal in shape) is responsible for its allergic reactions. The prevalence of its allergy has been found in several parts of Europe as well as parts of Asia, especially China and Korea. Mugwort pollens are known to trigger type 1 allergic reactions like allergic rhinitis, conjunctivitis and asthma. Besides this, mugwort is also linked with plant-derived food allergies (pollen-food-allergy syndrome). It is clinically manifested as oral allergy syndrome, angioedema, urticaria or even anaphylaxis. The mugwort proteins, namely Art v 1, Art v 2, Art v 3, Art v 4, Art v 5 and Art v 6 have been identified as having allergenic potential. Mugwort and ragweed pollens show high level of cross-reactivity since they are related weeds. Further, mugwort also cross-reacts with many food allergies leading to pollen-food allergy syndrome like mugwort-celery-spice, mugwort-fennel, mugwort-mustard, mugwort-peach, mugwort-sunflower syndrome etc.
Epidemiology
Worldwide distribution
Mugwort is one of the most significant members of the Asteraceae or Compositae family. In Europe, pollen from mugwort is among the principal causes of allergy and sensitization rates among suspected allergy patients have been shown to vary between 15 % (Northern Europe) and 10 % (Southern Europe).
In Germany, mugwort is one of the most significant weeds causing pollinosis. In a prospective study conducted in Northern Spain, 36% of 72 patients having IgE-mediated allergic reactions to plant foods were found to be mugwort pollen sensitized. In a cohort of 29 rhino-conjunctivitis patients in Strasbourg, France, 55.2% were sensitized to mugwort pollen extracts. In a cross-sectional study in Southern Italy, 16.7% of 350 adolescents (14 to 18 years) with respiratory allergy in the form of asthma and/or rhinitis, were sensitized to mugwort. Further, in a prospective follow-up study on 401 Italian children with a history of seasonal allergic rhino-conjunctivitis (SAR), sensitization to mugwort was found to be significantly reduced (p=0.009) from 27.2% at baseline (2009-2011) to 20.7% (2015-2017).
In China, mugwort pollen is among the leading causes of rhino-conjunctivitis and asthma during late summers and autumn. In another Chinese study, 402 patients with seasonal pollinosis (allergic rhinitis, bronchial asthma, or allergic conjunctivitis) were categorized into three groups: Spring, Autumn, and Combined Season group. Mugwort was the major allergic source in 94% (n=63) of the Autumn Symptom group and in 85% (n=302) of the Combined Season group. Mugwort pollinosis is also common in Korea.
Risk factors
The pollination season for mugwort is primarily between the end of summer and the beginning of autumn when patients sensitized to mugwort experience allergic reactions, especially in Europe and China.
Route Of Exposure
Main
Mugwort is wind-pollinated and inhalation of the pollen grains or pollen grain fractions is the main route of exposure. Pollen grains from mugwort enter the body through the upper respiratory tract, the mucosa of oral cavity and the eyes.
Clinical Relevance
Pollen is among the leading causes of allergic conjunctivitis, allergic rhinitis (AR), and bronchial asthma. Mugwort pollens are known to trigger type 1 allergic reactions like allergic rhinitis, conjunctivitis, and asthma. In Europe, pollen from mugwort is among the principal causes of allergy. The sensitization rates among suspected allergy patients for AR varies between 15 % (Northern Europe) and 10 % (Southern Europe).
Apart from specific symptoms (like rhino-conjunctivitis and asthma), pollen allergies also cause sleep disorders, fatigue, depression, and impaired cognition in allergic patients. These symptoms increase during pollen season and decrease the quality of life in allergic patients.
Allergic rhinitis
Allergic rhinitis was reported in 95% (n=240) and conjunctivitis in 53% (n=126) of patients with a positive history or specific IgE tests to mugwort in a study in China. Among 401 Italian children (mean age- 10.4 ± 3.4 years at baseline) with a history of seasonal allergic rhino conjunctivitis (SAR), AR was found in all (100%) of them at baseline and 93.3% (n=374) patients (mean age- 16.2 ± 3.6 years) at follow-up. Out of these, 27.2% were found to be allergic to mugwort at baseline, which decreased to 20.7% at follow-up. The patients also presented with oral itching with or without lip and/or tongue angioedema [Oral allergy syndrome (OAS)] after food ingestion, at baseline. At follow-up, food‐related allergic symptoms, particularly urticaria/angioedema and gastrointestinal symptoms were found to be increased. Out of 402 adult Chinese AR patients (mean age of 30.4 ±14.1 years), mugwort was found to be the primary allergic source affecting 94% (n=63) patients in the autumn season and 85% (n=302) patients in both spring and autumn season. Pollen-related food allergy was seen in 30% (n=119) of the study population; fruits were the most common food items triggering pollen-related food allergy.
Asthma
Exposure to mugwort pollen triggers asthma in mugwort sensitized patients. Out of a total of 240 Chinese patients allergic to Artemisia pollen who had either positive history or specific IgE tests to mugwort, 43% patients exhibited allergic asthma. Patients with allergic asthma presented with a history of dyspnea, wheezing, and/or episodes of cough. The most commonly identified allergen was Art v 1 (53-93%), followed by Art v 3 9-66%) and Art v 2 (9-48%). It was suggested that sensitization to three or more allergens of mugwort caused a greater risk for allergic asthma.
Atopic Dermatitis
In the Chinese population, atopic eczema was observed in 19% patients out of a total of 240 patients who had either positive history or specific IgE tests to mugwort. Patients presented skin rash with red, raised itchy bumps.
Other diseases
Pollen-food allergy syndrome
Plant-derived food allergies are frequently linked with pollen allergens, which act as primary sensitizers. Pollen-food-allergy syndrome (PFAS) is also reported in mugwort-sensitive patients but less than birch pollen-sensitized individuals. These allergic reactions in addition to mugwort-pollen allergy are expressed as oral allergy syndrome (OAS), angioedema, urticaria, and/or anaphylaxis. Lipid Transfer Proteins (LTPs) are found responsible for mugwort-PFAS that is reported in China as well as Korea.
The mugwort association with several food items has been reported like mugwort-celery-spice, celery-mugwort-birch-spice, mugwort-fennel, mugwort-peach, mugwort-mustard and mugwort-chamomile syndrome. The association of mugwort has also been observed with apple, mango, peanut, and hazelnuts. However, the incidence, clinical symptoms, and sensitization profiles of these food allergies might vary from one region to another.
In China, mugwort is the primary allergen associated with LTP-related PFAS. A study involving 148 mugwort pollinosis patients reported food allergies in 72% of patients. The clinical manifestations included OAS (68%, n=73), urticaria (51%, n=55), respiratory symptoms (37%, n=40), gastrointestinal symptoms (35%, n=37), hypotension (11%, n=12) and even anaphylaxis (48%, n=51). Further, the most common food responsible for allergic reactions in 107 PFAS patients were peaches (64%) followed by apples (24%), mangos (20%), peanuts (16%) and hazelnuts (14%). Further, in another study in China conducted on 119 PFAS patients, mugwort allergy was found in 31/33 patients with food-induced anaphylaxis. Further another study in China reported peach allergy to be co-existing in 55% of 69 mugwort pollen-allergic patients.
Cross-Reactivity
Mugwort exhibits widespread cross-reactivity with other Asteraceae (Compositae) family members (ragweed, sunflower seeds, other Artemisia species) due to the presence of pan-allergens like profilin (Art v 4) and calcium-binding proteins (Art v 5) in addition to defensin protein (Art v 1). Mugwort and ragweed (Ambrosia artemisiifolia) are highly cross-reactive due to the presence of common allergenic structures on their pollens This cross-reactivity may be attributed to profilin and calcium-binding allergens. Art v 1 (defensin), Art v 6 (pectate lyase) and Art v 4 (profilin) show considerable cross-reactivity with their homologous proteins in ragweed i.e., Amb a 4, Amb a 1 and Amb a 8 respectively.
Furthermore, cross-reactive non-specific LTPs, profilins, carbohydrate determinants, and high molecular weight allergens of mugwort may be responsible for the numerous mugwort-food allergy connotations. Various allergens were identified for PFAS like celery-mugwort-spice (Art v 4 with Api g 4 of celery and Dau c 4 of carrot), mugwort-fennel (Art v 60kDa with Foe v 5 of fennel), mugwort-mustard (Art v 3 with Sin a 3 of mustard, Art v 4 with Sin a 4 of mustard) and mugwort-peach (Art v 3 with Pru p 3 and Art v 4 with Pru p 4).
The mugwort-pollen profilin (Art v 4) was also found cross-reactive with lychee (Litchi chinensis) profilin (Lit c 1). Mugwort-chamomile cross-reactivity was also reported and possible cross-reactive allergen identified was Art v 1 Moreover, sunflower allergy in patients sensitized to mugwort is caused by cross-reactivity between defensin molecules, Art v 1 with Hel a 4 in addition to LTP, Art v 3 with Hel a 3.
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