Panax notoginseng tubers
September 2004
RARE REACTIONS TO A SAFE HERB
Sanqi (Panax notoginseng)
Over the past several years, safety concerns involving several herbs have arisen, sometimes leading to curtailing or discontinuing their use. A common thread in the various cases is that the herbs were being used by a larger number of people than before, and/or were used in either different ways or different contexts (e.g., in the context of taking drug therapies) compared to the traditional methods. Thus, rare and often unpredicted adverse reactions were found with sufficient frequency to generate worries about allowing their continued availability. Potentially damaging effects to the liver, kidneys, or heart have been principal causes of withdrawal of herbs from the market. Ordinary allergic reactions, as can occur with foods and drugs, are a more widespread type of adverse response; these have not yet caused withdrawal of herbs from the market.
Sanqi, also called Tianqi or Tien-chi, is the dried tuber of Panax notoginseng (family: Araliaceae). It is classified as warm in nature, sweet and slightly bitter in taste, and nontoxic. The dose in decoction for clinical use is 5-10 g. It can be ground to powder for swallowing directly or taking mixed with water: the dose in that case is usually is 1-3 grams, each time (a common preparation is tablets, 500 mg sanqi powder per tablet). In the Bencao Gangmu (Compendium of Materia Medica, 1596 A.D.) it is stated: "On account of the fact that sanqi is an herb belonging to the xue (blood) phase of the yangming and jueyin meridians, it can treat all diseases of the blood." Sanqi is an herb that has been used in China quite extensively since the end of the 19th century. It has acquired a very favorable reputation for treatment of blood disorders, including blood stasis, bleeding, and blood deficiency.
With its high level of use have come a few reports of apparent adverse effects, none of them related to toxicity of its herbal constituents. An article appeared recently in the journal Chinese Herbal Drugs (2003; volume 25, number 3, pages 216-218: A Review of the Adverse Effects of Panax notoginseng by Yang Xingang, Lu Benqiang, and Guo Yaping). The following are the reports of the events described in the article (plus two additional cases retrieved elsewhere). There are two basic types of adverse responses reported. One is an esophagitis that appears to occur as a result of consuming tablets of sanqi without drinking much water. The tablet may directly contact the tissues and cause some irritation or might lead to some acid reflux; there were two such cases reported. The other, more frequent, problem is with allergic reactions. These include dermatitis (allergic exanthema), shock, purpura, blisters, or other reactions of idiosyncratic nature; there were 19 such cases reported. After relaying these reports in detail here, the basic information for the allergic reactions is summarized in a table on page 4. The manufacturer of the sanqi products consumed was not known, nor was the botanical identity of the raw materials confirmed for these reaction reports.
Chen Zhengyan (1) reported on a male patient, age 75, who, owing to a sprain of his waist experienced one month previously, had lain in bed and taken sanqi tablets, 3 tablets each time, three times per day, swallowed with only a little water. He stopped taking the tablets due to an occurrence of dysphagia, but his symptoms didn't vanish: he was only able to take liquid foods. Another male patient, age 69, had lain in bed to rest because of a sprain involving his right knee. During that time he took sanqi tablets, 3 grams each time, three times a day; sometimes he took them with only a little water, sometimes he took them without water. Two days later, he felt an obstruction behind his sternum that gradually developed into dysphagia and a pain at the rear of the sternum, as well as a feeling of heartburn. Five days later, he stopped taking the tablets, but his dysphagia remained. The two patients both denied having taken other drugs or foods to which they were sensitive. They were given ametazole orally, 20 mg/day, and fluid infusion was employed intravenously. The dysphagia was first reduced and then vanished. Both patients were rechecked after several weeks; the focus of inflammation at the mid segment of the esophagus disappeared, and a bioassay showed normal.
Liu Ming, et al., (2) reported the case of a female, age 40, who had suffered from rheumatic arthritis for years. After having been injured by riding a bicycle, she was treated with 3 grams of sanqi powder and Danggui Huini Tang together. Two hours later, she suffered from urticaria over her entire body and became alarmed by shortness of breath. She ceased taking the herbs and was administered 20 mg of benadryl intramuscularly, and took 10 mg of prednisone and 4 mg chlorpheniramine orally. The symptoms vanished; the original Chinese herbal prescription was resumed without the inclusion of sanqi powder, and her injury symptoms were improved by the treatment without further allergic response.
Lu Liping, et al. (3) reported three cases of drug exanthema by persons taking sanqi powder. One female patient, age 75, had pain in the upper abdomen accompanied by vomiting. She was seen in the surgical department for the treatment of an infection of the biliary tract. After more than 10 days of treatment, she further displayed arrhythmia, and the electrocardiogram (ECG) presented indications of myocardial infarction, so she was transferred to the department of internal medicine for treating myocardial infarction. She was given sanqi powder, 2 grams each time, three times a day. Two days after beginning the sanqi administration, the patient felt tracing-itches over her body. Parts of her chest and back had measles-like red papules. A male patient, age 36, was entered into the hospital because of a subarachnoid hemorrhagic coma accompanied by pulmonary infections. Emergency treatment with a combination of TCM and modern medicine for more than ten days led to his condition improving somewhat. He then began to take sanqi powder additionally, 2 grams each time, three times a day, by nasal feeding. At noon on the second day, the patient displayed red patches of papules. Another female patient, age 43, was diagnosed with congenital cardiopathy (ventricular septal defect) with functional deficiency and pulmonary infections. She was admitted into the hospital for treatment; during the course of treatment, she took sanqi powder, 3 grams each time, three times per day. Four days later, she presented with trace-itching of her limbs. Physical examination revealed a few patches of scattered red papules, and dense urticaria-like papules appeared at the rear of her head and on her trunk. For all these patients, exanthema occurred in relation to employing sanqi powder. It was noted that when they stopped using the powder, or combined its use with treatment against allergy, the exanthema disappeared gradually; they were all cured after several days.
Sui Qian (4) also reported three cases (two males and a female, ages 20-40) who had soft tissue injuries and were seen in the emergency department; they all took sanqi tablets for the treatment, 3-5 tablets each time, three times a day. After about 24 hours, the patients all suffered from skin rashes, showed various size patches accompanied by itching distributed on the face, limbs, and the trunk. They all denied having taken any other drugs or foods to which they were sensitized. They stopped taking the sanqi tablets and employed a treatment for allergy reaction; several days later, the skin rashes were completely eliminated.
Kou Huirong, et al. (5) reported a female patient, age 33, who was injured falling down the stairs, fracturing her coccyx. She took sanqi tablets for treating the injury, 3 tablets each time, three times per day. After the first administration, after about half an hour, she experienced numbness of the mouth, and stiffness of the tongue, sweating over the whole body, her heart rate slowed (around 50 beats a minute), her limbs became cold, and she experienced double vision. She was treated with anti-allergy drugs and given fluid infusion intravenously, five hours later, her condition improved gradually, but she was still taking the sanqi tablets, so she then stopped taking them. The next day, her symptoms were eliminated. Three days later, she took the sanqi tablets and the above-mentioned symptoms appeared again. She was treated by the foregoing measures and stopped taking the sanqi tablets; her symptoms vanished gradually.
Xiang Weijun (6) reported on the case of a male with trauma to the right limb who took a dose of three tablets of sanqi. About 30 minutes later he experienced itching over his entire body. Also, his skin became flushed and showed a light edema accompanied with oppression in the chest and nausea. Subsequently, his complexion became pale white, he had rapid breathing, and showed of cyanosis of the lips. Physical checks showed that his body temperature was 39.3°C, pulse 108 times/minute, blood pressure 10.7/6.6 kPa (80/50 mm Hg), and varied sizes of wheal-shaped spots were scattered over his whole body. He was treated by IV drip of dexamethasone and other drugs for inhibiting the immune reaction, as well as by injecting adrenaline intramuscularly; his condition improved. Later, a scratch test showed a positive reaction to sanqi.
Ming Jiying, et al. (7) reported on a male patient, age 8, who suffered contusion of the soft tissue with local blue-violet bruising; he was medicated with sanqi powder, 3 grams each time, two times a day. After one day of taking it, there were some red bleeding spots; two days later, there appeared more skin rashes, accompanied by a swelling pain of both knee joints and abdominal pain. He stopped taking any other drugs and potential sensitizing foods. Physical checks showed scattered petechiae and ecchymoses on both of the lower limbs; the heart and lungs were normal; the belly felt soft and flat, but with tenderness around the navel; both the knee joints showed swelling and tenderness. Laboratory exams indicated that his blood platelet level and coagulation time were normal, suggesting that this was a case of allergic purpura. After withdrawal of administration of sanqi powder, he was treated by anti-anaphylaxis drugs. Two days later the purpura was reduced and abdominal pain and joint swelling pain gradually vanished; one week later, purpura was completely eliminated
Zhang Daocheng (8) reported a male patient, age 50, who suffered pain in the right side of his chest due to trauma. For self-treatment, he consumed a sanqi wine (15 grams of sanqi tuber broken in pieces and soaked in 500 grams of white wine). The first time, he consumed three wine-cups (about 90 ml); two hours later he experienced abdominal pain and serious itching during the whole night. The next morning, all the itching parts on his body displayed purpura-spots in varied sizes. He drank the sanqi wine (three wine-cups) once again; the skin at the purpura sites rose higher and formed blisters spreading toward the limbs, which became unbearably itchy. Physical checks: temperature, 37°C; pulse, 74 beats/minute; blood pressure, 18/10 kPa (135/75 mm Hg); respiration, 18 times/minute; on the trunk and the limbs there were scattered purpura and blisters, much more at the belly and the upper limbs in varied sizes with a clear boundary and no reduction of color by pressing; other items of the exams were normal, suggesting this to be a case of allergy to sanqi wine. He stopped drinking the sanqi medicinal wine and was treated with an anti-anaphylaxis therapy; after several days the purpura was reduced completely.
Zhang Fengxiang (9) made a report on a female infant patient, 45 days old, fed with mother's milk. Her mother had a waist injury, and had taken sanqi tablets, 3 tablets each time, three times per day. After medication on the fifth day, the infant patient was presenting pink papules which spread over the entire body within 48 hours, accompanied by fever and crying restlessly, whereas during these events the mother displayed no allergic reaction. Physical checks: temperature 38°C; being conscious, well developed with good nutritional status, and showed no abnormalities in any systems. Dermatological exams: a general diffuse flushed red swelling distention, distributed widely, with red papules and much purplish brown maculae could be seen over the trunk, but the color faded with pressing. After suffering from the reaction for 4 days, many blisters were distributed over the face and limbs in various sizes, most about 1.2 cm × 1.2 cm, the wall appearing strained and the fluid was clear, and gave a positive Nikolsky's sign. Within 30 hours the blisters coalesced together into big relaxed blisters on the face, neck, and the four limbs; the large blisters broke and a big piece of the skin came off to form a fresh, red, bare surface; the eyes and throat showed erosion, with excretion of fluid. This was suspected to be a case of allergy caused by sanqi that passed through the milk during breast feeding. Treatment with dexamethasone by IV drip and a supporting therapy with 10% calcium gluconate and penicillin were administered. Nine days later, the baby improved rapidly. A 30% extracted solution of the sanqi tablet was used to run a scratch test, which then showed positive for allergic reaction.
Chen Biao (10) described a male patient, age 28, treated for low back pain, who took sanqi tablets, which caused serious itching, with the pudenda subsequently having chicken pox-like erythema going on to become eroded, exuding fluid; the herb also appeared to induce an ophthalmecchymosis accompanied by nose bleed (11). He Juying (12) noted that long-term oral administration of sanqi tablet could cause an instantaneous multiplication of mouth-shaped erythrocytes. Liu Qingchi, et al. (13) reported that after taking sanqi powder with water, around 1.5 hours later, abdominal pain and diarrhea could occur. After having the diarrhea, the abdominal pain was alleviated; the feces were unshaped but without purulent blood.
Two cases here added to the review (from Abstracts of Chinese Medicine): A women with lower abdominal pain during menstruation was treated with powder of sanqi, 3 grams each time, twice per day. She took the herbs for two days, and on the next day, she developed scattered macular rash with pruritis over her neck, chest, and back. The powder was withdrawn and the rash disappeared spontaneously in 5 days (14). A woman suffering from a bone fracture took sanqi powder, 1 gram each time, three times per day, and on the second day experienced punctuate erythema, with increasing itching and rashes as medication continued; three days after discontinuing use of sanqi, the symptoms disappeared (15).
Summary of Allergy Reaction Reports for Sanqi
| Patient Data | Disorder Treated | Adverse Reaction | Time To Reaction | Confirmation |
| Female, 40 | bicycle injury + rheumatoid arthritis | whole body urticaria, shortness of breath | 2 hours | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs |
| Female, 75 | upper abdomen pain, myocardial infarct | tracing-itches, measles-like red papules | 2 days | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs |
| Male, 36 | hemorrhagic coma, pulmonary infection | patches of papules | about one day | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs |
| Female, 43 | cardiomyopathy, pulmonary infection | trace-itching, scattered red papules and dense urticaria-papules | four days | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs |
| 2 Males, 1 Female, 20-40 | soft tissue injuries | skin rashes, itching | about one day | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs |
| Female, 33 | coccyx fracture and other injuries | mouth numbness, tongue stiffness, sweating, slow heart rate, double vision | half an hour | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs; symptoms reappeared with second administration of sanqi |
| Male, age? | traumatic limb injury | itching, flushed skin, edema, chest oppression, nausea, rapid breathing | half an hour | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs; scratch test |
| Male, 8 | contusion | bleeding spots, skin rashes, knee swelling and pain, abdominal pain | one day (continued developing after two days) | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs |
| Male, 50 | chest injury | abdominal pain, severe itching, purpura spots, | 2 hours (continued developing next day) | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs |
| Female, infant(breastfeeding) | mother had soft tissue injury at waist | pink papules over entire body, blisters, fever, restless crying | five days | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs; scratch test |
| Male, 28 | low back pain | itching, erythema | a few hours | symptoms alleviated with discontinuing sanqi and use of antiallergy drugs; reaction occurred again, more severely, after trying sanqi a month later |
| 2 cases | n/a | eye bleeding | n/a | n/a |
| 1 case | n/a | distorted red blood cells | n/a | n/a |
| 1 case | n/a | abdominal pain, diarrhea | 1.5 hours | n/a |
| Female, age? | dysmenorrhea | macular rash, pruritis | about 3 days | symptoms alleviated in 5 days after withdrawing sanqi |
| Female, age? | fracture | punctate erythema | about 2 days | symptoms alleviated in 3 days after withdrawing sanqi |
Allergic reactions to herbs have been reported in China for a wide range of commonly used items. In many instances, the herb extracts that cause such reactions are given by injection, a route of administration prone to inducing allergy reactions because there is no degradation or inhibited absorption of constituents before entering the blood stream, as when taken orally. In the cases cited here, the herb was always taken orally, either in powder, tablet, or wine form, and even passed through breast milk.
Sanqi is a species of Panax, and the root (tuber) is used. Panax ginseng (Asian ginseng) is more commonly used; Panax quinquefolium (American ginseng) has also been used extensively. There may be proportionately fewer cases of allergy reaction to those species. A case of urticaria arising 3 hours after taking a soup prepared with 10 grams of American ginseng was reported (16). The symptoms developed to include dizziness and rapid breathing and were alleviated with injection of anti-allergy drugs. A case suggestive of allergy to Asian ginseng was reported (17), in which a 20-year-old male student took a small amount of ginseng syrup and displayed symptoms in about 3 minutes after ingesting the product. He developed widespread erythematosus papules, and had a drop in blood pressure. He was treated with dexamethasone by IV and later by oral prednisone, which alleviated the symptoms.
Sanqi includes some active ingredients different than those found in the other Panax species. Presumably, some of these ingredients are responsible for its reputed ability to inhibit bleeding and enhance blood circulation, properties that are not attributed to the other Panax species. Such ingredients have not been clearly identified. There may also be some pharmacologically inactive constituents of Panax notoginseng that are more likely than the active components to produce allergies.
Severe allergy reactions to commonly used herbs have not yet led to calls for their removal from the market, but these incidents have bolstered the claims by those who are largely opposed to herb use that herbs are not inherently safe and need to be regulated more carefully. Such regulation is unlikely to prevent unexpected allergy reactions, but might involve alerting consumers to the possibility of allergic reactions, as is done in labeling for drug products.
Practitioners of Chinese medicine should be alert to the possibility of allergy reactions to herbs and formulas that have been used safely in the past. Allergic reactions are usually prompt (within hours, sometimes a day or two) and usually, though not always, present common patterns as seen with allergic drug reactions, such as rashes or anaphylaxis. It is difficult to know which herbs are most highly allergenic, because there are such large variations in the numbers of persons consuming the different herbs, the form of herb administration (topical application may yield skin rashes far more than oral applications), and the reporting of adverse effects. In the case of sanqi, published reports often involved quite severe reactions and it would be reasonable to presume that numerous other people have experienced minor reactions that did not result in a hospital visit, or that resolved so quickly that the doctor did not submit a report suggesting a specific herbal cause. There is little doubt that the number of people consuming sanqi each year runs into the hundreds of thousands, if not over a million. The reports of severe adverse reactions appeared during the period 1984-1997 (which is not to imply that none had occurred before or after that time), at a rate of about one case per year. If this is but one tenth of the significant allergic responses to the herb, the incidence rate still may be on the order of less than one in ten thousand users per year.
Allergic reactions are treatable and most will go away on their own without treatment after discontinuing ingestion of the allergen. However, anaphylactic reactions are potentially dangerous, especially if blood pressure drops severely. Persons who experience allergic reactions to an herb do not necessarily have a history of general problems with allergies (e.g., hayfever, food allergies). Thus, knowledge of the potential reactions and their treatment is important for those who prescribe herbs.
September 2004