Traditional,Chinese,Medicine,syndrome,and,treatment,of,brucellosis,in,chronic,stage

Lv-xin Zhang, Wei Leng, Yu-pei Chen

1 Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China

2 First Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, Shaanxi Province, China

Funding: Shaanxi Province Traditional Chinese Medicine Academic Schools Inheritance Studio(Construction) Project

Abstract Brucellosis is a serious infectious disease. In recent years, the incidence of brucellosis has been on the rise. When the disease is found, it has entered the chronic phase, which is complicated and difficult to recover. Western medicine treatment of antibiotics often has poor clinical curative effect. Traditional Chinese medicine points out that the key pathogenesis of chronic brucellosis lies in “dampness-heat” and “blood stasis”, emphasizing the deficiency of vital qi and lingering pathogen as the root cause. It puts forward the treatment methods of regulating qi and blood,clearing dampness and dredging collateral, promoting blood circulation and removing blood stasis, which can acquire remarkable clinical effect.

Key words: Chronic Brucellosis; Vital qi deficiency and lingering pathogen; Dampness-heat and blood stasis; Obstinate arthralgia

Brucellosis is a serious zoonotic infectious disease,which is mainly caused by occupational contact and environmental exposure to the virus or products carried the virus. More than 500,000 people worldwide are infected with brucellosis each year. In the summary of the incidence of notifiable infectious diseases in 2013,the number of reported cases of brucellosis is ranked the sixth, and the incidence rate is rising[1]. There are still reports of outbreaks in northern China, especially in pastoral areas such as Inner Mongolia, Northwest,Northeast, Heilongjiang, Xinjiang, and Tibet. Pathogens can cause damage to multiple systems after invading the human body. The clinical manifestations are fever,hyperhidrosis, fatigue, headache, joint muscle pain and the swelling of liver, spleen, and lymph node. The main manifestations of the joints involved are pain, swelling,fever and erythema. The onset of the disease is hidden,and more than 90% of the disease appears slowly[2]. In the early stage of onset, it is often misdiagnosed with influenza, typhoid fever, rheumatism, rheumatoid arthritis and so on. Due to improper treatment, nearly 10%-30% of patients turn to chronic stage and are accompanied with large joint disease. Among them, brucellosis spondylitis is a common complication. It mainly manifests specific infections with inflammatory disease of the intervertebral disc, destruction of the vertebral body, and abscess formation. According to statistics, among patients with brucellosis, patients with brucellosis spondylitis account for approximately 20%-53%, the recurrence rate is 6%-10%[3]. Antimicrobial therapy has poor efficacy due to high drug resistance, high recurrence rate and many adverse reactions. Surgical treatment increases the risk of infection and affects the effect of anti-Brucella drugs, on the other hand, it may accelerate degeneration between adjacent normal vertebrae[4]. In the theory of traditional Chinese medicine (TCM), “damp-heat and blood stasis” is considered the main pathogenesis of chronic brucellosis.It also puts forward the view that healthy qi deficiency and lingering pathogen are its roots, the latency of damp-heat and the stagnation of blood stasis are its manifestations,and the general principle of treatment should be to strengthen the body and eliminate evil[5].

Brucellosis does not have a name in the theory of traditional Chinese medicine. The most common clinical symptoms of brucellosis are fever, hyperhidrosis, and joint pain. Traditional Chinese medicine believes that it is the category of consumptive disease and obstinate arthralgia.In “Plain Questions · Vitality of Human Communicating and Corresponding to the Universe”, there is a statement that “Yang Qi, as important as the sky and the sun, if you lose it, you will lose your life”; “for those with Yang Qi,the refined Qi could nourish and calm the spirit, while the gentle Qi could nourish muscles and tendons”. In the early stages of disease development, it is usually caused by the pathogenic qi of “Pestilence”, which invades the human body. Therefore, we should focus on encouraging the body’s Yang Qi to block the pathogenic Qi. As stated in “Plain Questions”, “when the pathogenic Qi accumulates, the Qi deficiency certainly occurs”; “vital Qi is reserved in the body, and pathogenic Qi cannot affect it.” The dominant position of vital Qi and the external pathogenic condition of pathogenic Qi determine that we should pay attention to maintaining vital Qi and eliminating pathogens in clinical treatment of diseases.The human body itself has the ability to expel external pathogens and restore balance, the purpose of using medicine is to promote and support this function, but not to restrain and disturb it[6]. Xiao Chai Hu Decoction has the power of reconciling Shaoyang cardinal, clearing away heat, regulating qi and replenishing deficiencies,and it embodies the idea of “when it’s in place, it’s vital“. In prescriptions, Chinese thorowax root harmonizes Shaoyang with slight nature and bitter cold flavor, baical skullcap root clears pathogenic heat with bitter flavor and heavy nature, both are used together to clear heatdampness in Sanjiao and regulate the whole body; pinellia tuber and fresh ginger harmonize stomach-qi, lower adverse qi and stop vomiting; ginseng, roasted licorice and Chinese date benefit qi and harmonize the energy,strengthen vital qi to eliminate pathogenic factor. The preion has reinforcement and elimination in combination,harmonizes ascending and descending, disperses internal and external, it is a good recipe for reconciliation. Xiao Chai Hu Decoction is commonly used to treat repeated chills, fever, sweating and pain in the whole body muscles and joints in early stage of the disease, and has achieved good clinical efficacy[7]. As the disease enters the chronic phase, the body’s qi, blood and fluid will be depleted coupled with the side effects of antibacterial drugs, and the syndromes of qi-yin deficiency will often appear. The systemic distress, dizziness, short of breath, spontaneous sweating and night sweating are obvious. “Bazhen Decoction” is used to nourish qi and blood, so as to treat the root cause[8]. In the preion, ginseng and rehmannia root are sovereign drugs, ginseng benefits qi, invigorates the spleen and nourishes the stomach; rehmannia root benefits the essence, nourishes blood and relieves rigidity of muscles, and the two drugs are compatible, which greatly increase the effect of nourishing qi and blood;largehead atractylodes rhizome, lndain bread, Chinese angelica, and peony root are minister drugs; largehead atractylodes rhizome and lndain bread invigorate the spleen, eliminate dampness, nourish qi. The combined use of lndain bread and largehead atractylodes rhizome can enhance the effect of invigorating the spleen and eliminating dampness, helping minister drug ginseng to nourish qi and invigorate the spleen; Chinese angelica nourishes blood and harmonizes the nutrient, promotes blood circulation and dredge collaterals; white peony root nourishes blood and harmonized the nutrient, relieves emergency and pain. The combination of Chinese angelica and white peony root can enhance the nourishing effect and help the sovereign drug rehmannia root to nourish the heart and liver; szechwan lovage rhizome is an adjuvant,it enters the blood to regulate qi and promotes blood and qi circulation, preventing the rehmannia root, Chinese angelica, and white peony root from being greasy and obstructing the stomach. The combined use of all drugs plays the power of benefiting qi, strengthening spleen,nourishing and harmonizing blood. Adding fresh ginger and Chinese date during decocting drug can harmonize the spleen and stomach, it has the advantages of enriching blood without stagnating blood and harmonizing blood without hurting blood.

On the basis of vital qi deficiency and lingering pathogen,“pathogenic dampness” plays a significant role in the occurrence and development process of this disease.Dampness is heavy and turbid and has the characteristic of stickiness and tending downwards. Dampness is prone to stagnate in the joints and meridians, and the Yang-Qi is not smoothly spreading. The visible symptoms include that the limbs and joints are painful and turbid, and the skin is insensitive[9]. As stated in “Plain Questions · Vitality of Human Communicating and Corresponding to the Universe”, “pathogenic dampness and heat gluing without being removed can lead that the big tendons are soft and short, the small tendons are flabby and long.” Pathogenic dampness is easy to damage the Yang Qi, as “Synopsis of Golden Chamber” says that “in Taiyang disease, the patient has the performance of arthralgia, irritability and the deep-thready pulse, which is arthralgia due to dampness”.Combined with the classical theory, chronic brucellosis disease is lingering and recurrent. The course of the disease is long, and the main manifestation is joint pain, all of which are caused by pathogenic dampness. In addition,traditional Chinese medicine believes that internal factors in the body play a leading role in the onset of disease. The theories of “Yin and Yang of a disease vary from person to person” and “the pathogens follow humanization”emphasize the importance of internal pathogenic factors in the onset of disease. Due to the difference between the Yin and Yang of the patients, the pathogenic dampness can often be the syndrome of dampness-heat and dampnessstasis[10]. This kind of patient has longer course of disease and body weakness, the preferred medications are peaceful medicine, which nourishes Yin without hindering the digestion and absorption of the stomach; the drug of dissipating blood stasis can not be too severe to harm the body’s vital energy; doctors try to avoid the use of hot and dry medicine and always pay attention to nourishing the spleen. For example, a patient has been infected with brucellosis for two years, but the aversion to cold with fever has not been eliminated. The patient has symptoms such as cold and heat exchange, thirst, sticky sweating,

knee swelling, chill-heat alternating, yellow urine, and dry stool. Combined with medical history and Six Meridian differentiation, it is believed that this patient belongs to the pattern of damp-heat, which stagnates and violates Shaoyang and Yangming meridians. The damp-heat flows down to the joints and travels along the surface skin,leading to poor circulation of qi and blood and symptoms such as muscles, bones, joint pain, numbness, adverse movement, or even joint swelling and burning. For this disease, Chailing Decoction and Sanmiao San are used to add and subtract.The specific prescriptions are as follows:Chinese thorowax root 15 g, Chinese date 6 g, baical skullcap root 10 g, ginseng 6 g, largehead atractylodes rhizome 10 g, Polyporus Umbellatus 15 g, lndain bread 15 g, Radix Actinidiae Chinensis 30 g, largeleaf gentian root 15 g, Cassia twig 10 g, atractylodes rhizome 10 g, Twotoothed achyranthes root 10 g, amur cork-tree 6 g. Ten doses decocted in water are a course of treatment, one dose daily is taken in morning and evening.

In the prescription, Chinese thorowax root, baical skullcap root, anemarrhenae and pollen are used to clear the heat of Shaoyang and Yangming meridians; atractylodes rhizome and twotoothed achyranthes root are combined to form Sanmiao San, which clear and eliminate the damp-heat of lower Jiao; largeleaf gentian root, Chenopodium Album and Fructus Chaenomelis expel pathogenic wind and remove dampness, relieve rigidity of muscles and activate collaterals, and are good at removing evils on the surface of the limbs. The prescription can nourish qi-yin, remove damp-heat, dredge collaterals and relieve pain. After two courses of treatment, all symptoms may disappear.In clinical diagnosis and treatment, two Chinese drugs,“Chenopodium Album” and “largeleaf gentian root”, can be added. Chenopodium Album is the root of Actinidia chinensis, which is mostly produced in Shaanxi. When it is used to treat brucellosis, the dosage can be more than 30 g[10]. Chenopodium Album is sweet and slightly acidic.It enters Shaoyin and Yangming meridians and has the effects of invigorating the stomach, clearing heat-toxicity and eliminating dampness, which is good at dispelling wind-dampness, eliminating carbuncle and treating ulcers,promoting blood-circulation for detumesecence. The drug is suitable for rheumatism arthralgia and joint swellingpain. Largeleaf gentian root has the effects of dispelling rheumatism, clearing dampness-heat and relieving arthralgia. The combination of the two drugs is suitable for rheumatic arthralgia. These two drugs are added to the prescription for the treatment of chronic brucellosis and achieve better curative effect.

In “Plain Questions·Arthralgia Spasm Lun”, the pathogenesis of arthralgia is described by “nourishing the nutrient for astringent”. The course of the disease is prolonged and the disease is refractory, blood flow is stagnant, which is considered to be the pathological product of arthralgia in the middle and late stages[11]. In the syndrome differentiation of brucellosis, blood stasis is also considered to be its main pathogenesis. Therefore,in clinical treatment, more attention should be paid to the application of drug for invigorating blood circulation and elimination stasis[12]. Wang Qing-ren believes that the arthralgia with poor therapeutic effect is caused by the pathogen of wind, cold, dampness and heat, which enters the blood vessels, resulting in stagnation of qi and blood.It is not healed with warm-heat divergent drug, dampnesslowering gunpowder drug and yin-nourishing drug. In the treatment, we should promote stasis, activate blood circulation, dredge collateral for eliminating pathogenic factor. The preion “Shentong Zhuyu Decoction” is used in combination with the drugs for removing blood stasis and removing wind-dampness, which has achieved good clinical effects[13]. For example, a patient went to the doctor due to joint pain and swelling with hepatomegaly for half a year, after inquiry of the medical history, he had a history of assisting in sheep abortion, and suddenly felt chills,fever, and sweating for more than ten days, especially at night. The joints of waist, legs and upper limbs were painful, the right foot was swollen, and the fingers were swollen and painful. The initial diagnosis was “brucellosis”.After 20 days of intramuscular injection of streptomycin(1 gram per day) and oral tetracycline and other drugs,fever was relieved and sweating disappeared, but at this time, shoulder joint appeared acupuncture-like pain,and all other pains were relieved. Physical examination was generally acceptable, and the liver enlargement was palatable at 2 cm below the rib of the right midclavicular line, with hard nature and tenderness. The upper limbs and shoulder joints had tenderness, and the movement was restricted to a certain extent, and the fingers were slightly swollen. TCM diagnosis: the patient had fatigue,shortness of breath, heart palpitations, shoulder stabbing pain, low back pain, swelling and pain of fingers. The lump under the right rib had tenderness. The complexion was flushed, the mouth was dry and thirsty, the urine was yellow, the tongue was dull, the fur was thick-white and slightly-yellow. The pulse was deep and frequent. In TCM,it was diagnosed as stubborn numbness and subcostal lump with syndrome of static blood blocking collaterals based on the tongue, pulse and clinical manifestations.The prescriptions used are as follows: Chinese thorowax root 12 g, baical skullcap root 9 g, prepared common monkshood branched root 9 g, largeleaf gentain root 30 g,common floweringqince fruit 12 g, largeleaf gentian root 9 g, Chinese angelica 15 g, sichuan lovage rhizome 12 g,Salvia miltiorrhiza 24 g, myrrh 7 g, Peach seed 12 g, peony root 15 g, motherwort herb 30 g, garter snake 5 g (grinded into aliquots for drench). Ten doses decocted in water are a course of treatment, one dose daily was taken in the morning and evening.In the prescription, Chinese angelica can promote blood circulation and dispel stagnation. Szechwan lovage rhizome has pungent fragrance, promotes the qi circulation to dispel depression, invigorates the blood and relieves pain, and it is a “qi medicine in blood”. The two drugs are the classic compatibility of promoting blood circulation and removing blood stasis. This is consistent with the etiology and pathogenesis of blood stasis[14].Motherwort herb is pungent and slightly bitter, returning to the liver and kidney meridians. It can promote blood circulation, remove blood stasis, regulate menstruation and diuresis. The dosage of Motherwort herb in the prescription is up to 30 g and effective at high dose, it can be used for treating both stasis and water. Aconitum nagarum Stapf warms yang to dredge the collaterals, so that all kinds of drugs can reach the disease site quickly and play a better role. Pueraria Lobata reduces swelling and removes toxins; Semen Persicae and Carthamus Tinctorius invigorate blood circulation and remove blood stasis, induce menstruation and relieve pain; Pheretima and Myrrh can clear heat and dredge collaterals, remove wind-dampness, strengthen muscles and bones, and clear heat and toxins; Radix Gentianae Macrophyllae and Angelica Pubescens can remove wind-dampness, clear damp-heat and relieve paralysis pain; Radix Cyathulae expels blood stasis and dredges menstruation, induces diuresis for treating strangurtia; Radix Glycyrrhizae preparata can tonify the spleen and benefit Qi, clear heat and relieve toxins, relieve urgency and pain, and harmonize all medicines. After taking the above drugs for two courses, the patient’s shoulder joint pain was alleviated and can moderately exercise, his heart palpitations and shortness of breath were also alleviated. The patient had consciously fever after taking the drug, with hot breath from mouth and nose. The original preion except the Aconitum nagarum Stapf was given for additional 14 doses, the patient only had slight pain in the right shoulder joint, and the other symptoms disappeared, and he was able to participate in normal housework. In clinical application, the medication can be adjusted according to the actual condition of the patient. For patients with longterm blood stasis and deep retention in meridians, zaocys dhumnades and Bombyx Batryticatus were added to dispel wind and dredge collaterals, for severe joint pains,suberect spatholobus stem and dutchmanspipe vine were added to dredge collaterals and dispel stasis.

Patient Dong, female, 51 years old. Due to joint pain accompanied by repeated fever and cold for more than two years, she came to outpatient clinic. Inquiring about the medical history, after the abortion of the milk sheep raised in the family, the patient became ill due to the exposure to infection. At that time, she had fever and cold,sweating, and her muscles and joints all over her body showed migratory pain. The treatment been diagnosed as “severe cold” and “rheumatoid arthritis” was invalid.Later, she was diagnosed as “brucellosis” by the county and provincial epidemic prevention departments, and received a combined treatment with antibacterial drugs.For more than two years, the symptoms have been severe and repeated. The patient still feel drowsiness, fatigue,chills and fever, spontaneous sweating, dizziness, shortness of breath, mental weakness, pain in the joints of the upper and lower limbs, especially in the knee joints, unable to participate in labor, has normal appetite, and the stool and urine are normal. The lips are pale, the tongue is pale red and slightly fat with teeth print, and the pulse is thin and weak. According to the tongue pulse and clinical manifestations, she was diagnosed as stubborn numbness, which was caused by deficiency of both qi and yin and stagnation of damp-heat and residual pathogen.It is suitable to replenish qi and nourish yin and eliminate the remaining pathogen. The Chinese drugs used are as follows: milkvetch root 30 g, tangshen 15 g, largehead atractylodes rhizome 12 g, szechwan lovage rhizome 6 g,common floweringqince fruit 6 g, dwarf lilyturf tuber 9 g,unprocessed rehmannia root 12 g, suberect spatholobus stem 15 g, and amur cork-tree 9 g. Twenty doses were decocted in water, one dose daily was taken in morning and evening. After taking 20 doses, she felt that all her symptoms were significantly relieved and she was able to participate in part of the labor. After additional 20 doses of original prescription, the patient only felt fatigue after exertion, and the other symptoms had disappeared. The patient discontinued the drugs and was followed up for one year later without any recurrence symptoms.

Brucellosis remains the most widespread zoonotic disease in the world, causing great harm to human and animal health. Pathogens can invade various systems and organs of the body, leading to complex, diverse and non-specific clinical symptoms. Therefore, the treatment of brucellosis is complicated and difficult due to recurrent attacks.Traditional Chinese medicine believes that the basic pathogenesis of chronic brucellosis is deficiency of vital qi and internal stagnation of damp-heat and blood stasis. The vital qi deficiency and lingering pathogen are fundamental factor, while the secondary factors are latent damp-heat and internal stagnation of blood stasis. Therefore, the treatment principle should start with damp-heat and blood stasis by strengthening the body to relieve pathogens,dispelling dampness, activating blood and removing blood stasis, so that the healthy qi is restored and the meridians are unblocked to increase the success rate of treatment, reduce the recurrence rate of brucellosis, lower the incidence of complications, shorten the treatment cycle and reduce adverse reactions, which will obtain satisfactory clinical effects and benefit more patients with chronic brucellosis.