TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSIS (SLE)
WITH CHINESE HERBS
Lupus is an autoimmune disease involving antibodies that attack connective tissue. The disease is estimated to affect nearly 1 million Americans, primarily affecting women and arising mainly between the ages of 20-40. In China, lupus is even more prevalent than in the West, affecting about 5 million people. The principal disease form is a systemic one (systemic lupus erythematosis; SLE), which is the subject of this article, though a more circumscribed form, discoid lupus, sometimes occurs. The systemic disease includes production of antinuclear antibodies (ANA; mainly targeting the nucleic acid guanosine), generation of circulating immune complexes, and activation of the complement system. Most cases of lupus are mild; however, in some severe cases, untreated lupus can be fatal as it progresses from attack of skin and joints to internal organs, including lung, heart, and kidneys (with renal disease being the primary concern). Lupus mainly appears as a series of flare-ups, with intervening periods of little or no disease manifestation. Triggers for the flare-ups include emotional distress and ultraviolet light exposure; infections may also serve as triggers.
Modern medical treatment involves immunosuppressive strategies, mainly the use of corticosteroids such as prednisone, which are given during periods of flare-ups, but may also be given persistently for those who have experienced frequent flare-ups. Even with effective treatment, which reduces symptoms and prolongs life, the combination of drug side effects and continued low-level manifestation of the disease can cause serious impairment and premature death. New disease management strategies include cyclophosphamide, methotrexate, antimalarials, hormonal treatment (e.g., DHEA), and antihormonal therapy (e.g., the antiprolactin agent bromocriptine).
Antimalarial therapy has a long and successful track record in the management of patients with mild SLE, especially for patients who manifest cutaneous symptoms (it is usually effective for discoid lupus, which is characterized by cutaneous symptoms). Medium to long-term use of hydroxychloroquine, alone or in combination with mepacrine, ameliorates lupus and may reduce the relapse rate. The dose of corticosteroids given for lupus patients may be reduced when antimalarials are used, and the side effect profile of these antimalarials is quite limited (though overdosing can cause significant reactions). Antimalarials have certain beneficial effects on lipid and glucose metabolism as well as having weak anticoagulant activity. One of the main Chinese herb therapies for lupus is the antimalarial herb ching-hao (qinghao, Artemisia annua) and its active component arteannuan.
Traditional Chinese texts from the Qing Dynasty period indicate an awareness of the disease, suggesting that summer heat causes the red patches to appear because of an underlying heat toxin in the blood that is activated by the heat. In fact, it could be that the sunlight (a natural and strong ultraviolet source) is the primary trigger, rather than heat. Herbs that clear heat and toxin, nourish yin (to control heat), or reduce the impact of damp-heat (associated with late-summer weather conditions) were recommended. The herbs and formulas for lupus were based on the treatments for warm diseases. Such formulas had been popularized by Wu Youxing and others as a response to numerous serious epidemic diseases that occurred toward the end of the Ming Dynasty period. Lupus, which often presented with fever as well as reddened skin, was considered one of the warm diseases.
Chinese medical journals have relayed information about lupus treatment throughout the 20th Century and it remains a subject of intense interest. In most cases, lupus is treated in China with corticosteroids; in addition, herbal therapies are frequently employed as an adjunct to steroids. The modern Chinese literature focuses on two primary means of treating lupus with herbs: using antitoxin herbs (usually in conjunction with herbs that vitalize blood circulation) and using ching-hao or its active components.
Because the Chinese medical literature on lupus is so extensive, only sample information from recent clinical trials will be presented here to illustrate the practices that have evolved after several decades of experience. Because it is difficult to interpret clinical results with lupus treatments due to the high variability of the disease manifestation in each person over time, only the details of the treatment methods and some laboratory measurements will be relayed here. In all cases, the study authors determined that the patients who were treated with herbs plus prednisone responded better than those who were treated with prednisone alone (e.g., quicker response time, more complete resolution of symptoms, less prednisone required so fewer side effects). The basic treatment time in each case is 3 months, which would often be repeated for a total of six months treatment duration.
Trial I. Over the period 1993-1998, doctors at the Zhejiang College of TCM (Hangzhou) treated 149 cases of SLE (1). The patients were randomized into two groups:
The two groups resembled each other in sex, age, course of disease, and pathological activity. Symptoms frequently identified were oral ulceration, skin lesions, fever, joint pain, irregular menstruation (excessive bleeding), and photosensitivity. The prednisone therapy was administered in the same way for both groups, with dosing in the range of 10-60 mg of prednisone per day depending on the pathological status. When the symptoms improved, the prednisone dose was tapered until it could be stopped entirely.
The basic herb formula was composed of the toxin-cleaning, stasis-resolving, and yin-nourishing agents (the latter help control the heat syndrome): 30g buffalo horn slice (decocted before adding the other ingredients), 30g isatis leaf, 30g oldenlandia, 12g red peony, 12g moutan bark, 6g cimicifuga, 18g rehmannia, and 12g ophiopogon. This formula is based on the traditional Xijiao Dihuang Tang (Rhino Horn and Rehmannia Combination) with a high dose of buffalo horn replacing a small dose of rhino horn, as is common in modern Chinese practice. Aside from the formula's named ingredients, the other two components of the traditional formula are moutan and red peony; it is indicated for erythema due to feverish diseases. In this case, isatis leaf, oldenlandia, and cimicifuga are added to the traditional formula as antitoxin herbs, based on the theory that a hidden toxin remains in the blood and is activated by summer heat. Ophiopogon is added to extend the yin nourishing and heat clearing effects of rehmannia.
Modifications to the base formula were made as follows:
Trial II. In a follow-up study at the same institute (2), the researchers evaluated 45 SLE patients during the period 1995-1999, divided into two groups (2):
The two groups resembled each other in sex, age, and pathological condition, without significant difference. Additionally, a healthy-person control group of 30 healthy blood donors, aged 18-56, mean 29 years, was included for evaluation of blood components. For the prednisone group, according to the pathological state, prednisone was used at a dose of between 10 mg and 60 mg; when the condition improved, the prednisone was decreased gradually. The herb group took a formula called Langchuangding as well as prednisone. Langchuangding was similar to the previously reported formula, with 18g rehmannia, 12 g ophiopogon, 9g ching-hao, 30g isatis leaf, 30g oldenlandia, 12g red peony, 10g moutan, 30g lithospermum, and 9g campsis, decocted in water, taken two divided doses, morning and at night. Lithospermum is an herb commonly employed when there is redness of the skin; it is included in formulas for erythema and acne.
One of the objectives of the study was to measure blood levels of neopterin, a substance metabolized from the nucleic acid guanosine. It is produced from macrophages stimulated by ?-interferon and released by activated T-lymphocytes. The neopterin level can sensitively reflect an activated state of the cell mediated immune system, which can be widely employed for monitoring autoimmune diseases, transplantation immune rejection, tumors, and acute or chronic infectious ailments. This study revealed that the serum neopterin level of SLE patients was distinctly higher than that of the healthy control group (655 vs. 265 µg/liter), as had been shown in other evaluations, supporting the view that activation of the cellular immune system was involved in the SLE flare-ups. The addition of Chinese herbs to the treatment helped lower neopterin levels (to 354 µg/liter), as well as reducing erythrocyte sedimentation rate, complement C3 levels, and symptoms of facial erythema and oral ulceration. Similarly, it was shown that the immunostimulant soluble blood component interleukin-2R (sIL-2R) is elevated in patients with lupus, and declines during periods of remission and upon treatment with the Chinese herb formula.
Trial III. In a small trial conducted in 1997 at the First Affiliated Hospital of Guangzhou University of TCM, patients were similarly divided into two groups (3):
The two groups were comparable each other, with an average 3.5 years duration of disease. The group receiving herbs were given Lingdan Pian, which was composed of ching-hao, moutan, chin-chiu (qinjiao), turtle shell, buffalo horn, rehmannia, licorice, scrophularia, and other herbs. Each tablet contained 0.5 g crude herbs made by the pharmacy of the author's hospital, 5 tablets a time, 3 times per day. The patients also received arteannuin (in the form of succinic ester), 50 mg a time, twice a day, and a low dose of prednisone, 0.25-0.80 mg/kg (i.e., for a woman of about 50 kg, 10-40 mg/day), taken once upon rising in the morning. The control group received only prednisone, but at a higher dose of 0.81-1.25 mg/kg (i.e., for a woman of about 50 kg, 40-60 mg/day), taken once upon rising. The patients would also be treated with stomach-protectant (to avoid damage due to steroids), vitamins, and symptomatic treatments.
As can be seen, all patients in the three evaluations took rehmannia and moutan, the classic herbs for treating redness due to heat in the blood. Ching-hao was included in most treatments and is reported to improve the T-cell activities by promoting the suppressor cells (T-8 cells) so as to reduce the hyperactivation of the T-4 cells that promote the autoantibody production. The herb chin-chiu was also used frequently; this herb is thought to provide a powerful anti-inflammatory action, thereby lowering the required dosage of prednisone to be used. All patients took prednisone, the standard Western medical treatment for inflammatory autoimmune diseases. Together, the herbs and drugs were said to provide prompt alleviation of symptoms, improve immunological parameters, and reduce the dosage requirement for drugs.
The nephrotic syndrome that often accompanies lupus after several years of flare-ups is one of the life-threatening complications, though modern drug therapy and renal transplant technology can prevent loss of life. the syndrome is usually marked by a large quantity of albumin (protein) in the urine, with corresponding decline of serum albumin, and with some edema. From the perspective of traditional Chinese medicine, most of these patients suffer from qi and/or yang deficiency of the spleen and kidney, often with complications of blood stasis.
As with the general treatment of lupus, all patients receive Western medicine and some also receive Chinese medicine. The Western medicine therapy used most often is cyclophosphamide, a highly toxic drug that must be used carefully; it is often given in pulsed therapy to avoid continuous exposure. Prednisone could also be used along with cyclophosphamide. As an example of evaluating the mixed drug and herb therapy, a study at the Department of Nephrology at the Second People's Hospital of Fujian (4) compared use of the drug therapy alone (75 patients) or accompanied with Chinese herbs (80 patients). The Chinese herb therapy was based on differential diagnosis of the patients, with most patients receiving either a modification of the traditional Zhen Wu Tang (Vitality Combination) or a modification of the traditional Shen Ling Baizhu San (Ginseng and Atractylodes Formula).
The base formula derived from Zhen Wu Tang contained 9g aconite, 6g atractylodes, 10g hoelen, 10g peony, and 9g fresh ginger. The base formula derived from Shen Ling Baizhu San contained 12g codonopsis, 12g hoelen, 12g atractylodes, 15g rehmannia (cooked), 10g coix, 15g eucommia, and 10g cornus. To these base formulas, additional herbs could be used to address blood stasis (e.g., leonurus, salvia, persica, carthamus, cnidium, red peony), renal obstruction (e.g., rhubarb and oyster shell), or toxic heat syndrome (e.g., oldenlandia, scutellaria, lithospermum). During the 3-month course of therapy, if certain other syndromes arose (such as yin deficiency or yang deficiency), appropriate herbs could be added to address these disorders. According to the authors of the study report, symptoms of fever and edema cleared up more quickly when the herbs were used (10 days vs. 22 days for fever; 15 days vs. 32 days for edema), while there was no difference in the rate of improvement for skin rashes (32 days) and arthritis (16 days). Further, those taking the herbs had a more complete resolution of imbalances in plasma and urinary albumin and blood creatinine. It was further claimed that the side effects of cyclophosphamide and prednisone were less in the group treated with Chinese herbs.
In conclusion, Chinese medicine appears to be suitable as an adjunct to modern medical therapies when used for a period of about 3 months, a course of therapy that is to be repeated if necessary. While earlier Chinese reports suggested that Chinese herbs alone could function reasonably well as a treatment for lupus (5), this approach appears to have been largely abandoned, at least for the more serious cases seen in Chinese hospitals. For mild cases of lupus, using Chinese herbs as a sole remedy may be a reasonable choice, so long as modern medications are added in the event of a worsening syndrome. It is important that the treatment be sufficiently effective so as to minimize the chance of damage to the internal organs.