Allergy Capital

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Adverse Reactions to Complementary Alternative Medicines (including Echinacea)

Despite a perception that "natural therapy" is safe, allergic and toxic reactions to complementary alternative medicines are described. People with other allergies are more prone than others to allergic reactions complementary alternative medicines (such as Echinacea), even with first ever exposure.

Use of Complementary Alternative Medicine is common
Fifty per cent of subjects from Australia, Britain and the United States report using some form of complementary alternative medicines (other than vitamins) in any one year. Their use is not confined to adults. A recent survey of children admitted to Adelaide's Women's and Children's Hospital showed that 87 per cent had received at least one CAM in the previous 12 months, and that 16 per cent had received six or more preparations (MacLennan et al, 2002).

Adverse reactions to Complementary Alternative Medicines may occur
Despite a perception that "natural therapy" is safe, toxic and allergic reactions to complementary alternative medicines (CAM) have been described. Allergic reactions are most common in people with other allergies, such as asthma or hay fever. These patients are more likely than others to become sensitive to many different allergens, including those in herbal medicines. This article will focus on one group of plants commonly used as complementary alternative medicines ­ the Asteraceae.

Exposure to Asteraceae is inevitable
The Asteraceae are a group of flowering plants with over 20,000 species of worldwide. Exposure to these plants is not only common; it is inevitable. The most familiar are the cultivated flowering species such as chrysanthemums, dahlias, sunflowers, marigolds, safflower and daisies. Edible plants such as lettuce, safflower, chicory and artichoke are also Asteraceae. Less well known are weeds such as Ambrosia (ragweed) species, Artemisia (mugwort, sagebrush, wormwood) species, Parthenium (feverfew). Some Asteraceae are used as CAM, including Echinacea, dandelion, chamomile, feverfew, milk thistle and wormwood.

Sensitisation to Asteraceae is common
Asteraceae-derived pollens are an important cause of hay fever and asthma. Important plants including Ambrosia (ragweed) in North America, Parthenium (feverfew) in South America and India, Artemisia (mugwort) in Spain, and Chrysanthemum and sunflower in some people who are exposed to heavy concentrations of pollen,, such as flower growers.

Cross-reactivity between plants is important
Being sensitive to one allergen may result in an allergic reaction to a structurally similar allergen from another source, a concept known as "cross-reactivity". One of the most common is oral allergy syndrome. In this condition, itching and swelling of the mouth and tongue occurs, usually after eating uncooked or semi-cooked fruit. Affected patients usually suffer from pollen-induced hay fever or asthma, and are sensitive to "cross-reactive" allergens present within these foods and other plants such as grass or tree pollen.

Allergic reactions to Echinacea
Echinacea is a popular herbal remedy in Australia, with around 1 in 20 people taking it in any one year. As of the end of the year 2000, 26 cases of allergic reactions to Echinacea had been described in Australia (Mullins and Heddle, 2002). Of these patients, 4 had experienced anaphylaxis, 12 suffered acute asthma attacks and ten experienced severe hives and swellings soon after taking Echinacea. Four were hospitalized and Echinacea was the sole implicated medication in 15 cases. Over half were known to have other allergies, consistent with pre-existent allergic disease being an important risk factor. The fact that four reacted after their first ever known exposure suggested that sensitisation to Echinacea must have developed indirectly, by exposure to flowering ornamental Asteraceae, cross-reactive foods, or plants growing in the wild associated with "Australian Bush Dermatitis" (see below).

Cross-reactivity may explain allergic reactions to other Complementary Alternative Medicines as well as foods
Sensitisation to Asteraceae has also been associated with allergic reactions to other CAM such as Royal Jelly, bee pollen extracts and chamomile, as well as foods like celery, honey, sunflower seeds, carrot, lettuce, watermelon and nuts. Some of these reactions have occurred after first known exposure.

Other adverse reactions to Echinacea
Transient burning / stinging of the tongue is commonly observed after taking Echinacea. Administration by injection has been associated with shivering, fever and muscle weakness. Hepatitis has been described in American as well as in 7/51 Australian adverse drug reports involving Echinacea by the end of 2000. Other symptoms reported in association with Echinacea include other types of rashes, delayed asthmatic reactions, muscle aches and pains and stomach upset

Contact Allergic Dermatitis
Asteraceae may cause contact allergic dermatitis. Echinacea, daisies, chrysanthemum, chamomile, tansy, dandelion, feverfew and sunflowers have all been associated with contact allergy in gardeners and florists. Similar symptoms may be triggered by plant extracts in cosmetics, shampoos and massage oils. Contact with airborne plant-derived allergen can also trigger rashes, a condition commonly known as Australian bush dermatitis. The exposed areas of the face, eyelids, sides of neck and "V" area of the neck are mainly affected.

Use In Pregnancy, Breast Feeding And Children
Given that there are few published studies examining the safety of CAM during pregnancy or lactation, the potential risks and benefits are difficult to assess. Up to 1 in 6 pregnant women in the developed world use these medications. Unfortunately, toxicity (such as a baby born with lead poisoning) and serious allergic reactions (such as to chamomile) have been described. Only one very small study of 206 pregnant Canadian women has examined whether Echinacea is safe to use during pregnancy. While no adverse reactions were noted, this study of had only the power to detect a major cause of deformities.

The properties of some other Asteraceae- suggest they should be avoided. For example, feverfew can trigger abortions in cattle and stimulate uterine contractions in pregnant women. Chamomile is teratogenic in animal studies. Safflower, tansy, feverfew, calendula, chamomile, yarrow, milk thistle and wormwood promote menstruation, stimulate uterine contraction and can trigger abortions in animals (Ernst, 2002a; Newall et al., 1996). Taken together with the potential for allergic reactions in susceptible individuals, the use of Asteraceae-containing CAM during pregnancy seems unwise.

Drug interactions , contraindications and precautions
Around 20 per cent of patients from Canada, the USA and Australia use prescription drugs at the same time as CAM. The risk of adverse events is increased if these have drug-like activity or interfere with the way in which the body deals with these drugs.

For example, CYP3A4 liver enzymes play a major role in drug breakdown and detoxification by the liver. Echinacea, milk thistle and chamomile all interfere with this enzyme and thus increase or decrease the effects of some medications, leading to increased side-effects or reduced benefit from taking these drugs.

Feverfew has aspirin-like activity and may increase the risk of bleeding while taking blood thinners like warafarin or aspirin. Chamomile contains natural warfarin-like "coumarins" which increase the risk of bleeding in those taking warafarin as a medication.

Because of its purported short-term alleged stimulatory effect on the immune system, some authorities recommend that echinacea be avoided in patients with autoimmune disease (eg. lupus, multiple sclerosis), or in those with chronic HIV infection or tuberculosis. For similar reasons, it is commonly recommended that echinacea be avoided in patients undergoing organ transplantation, to reduce the risk of rejection. Similarly, echinacea is thought to inhibit wound healing and should be avoided if surgery will be performed in the near future.

Conclusions
The safety of any product is a relative concept which takes into account the potential for side-effects in the entire population, as well as those at particular risk by virtue of age, sex, or other medical conditions such as allergies. Allergic patients appear to be at particular risk of allergic reactions of variable severity to Asteraceae-derived CAM and should be warned appropriately. The popularity of CAM, its largely unsupervised use, and use with conventional medication makes it likely that otherwise rare side-effects or drug interactions will occur. The difficulty for patients and their doctors to distinguish disease-related symptoms from adverse reactions to treatment, together with ignorance of the potential toxicities, may contribute to underreporting of adverse events to CAM.

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