Traditional Chinese medicine understanding of common complications of multiple myeloma

Jiu-Wei Li

Shandong University of Traditional Chinese Medicine,Second Clinical Medical Colleg,Jinan,China.

Abstract Multiple myeloma (MM) is a heterogeneous disease of the hematological system,characterized by different subtypes and different prognosis.Age,tumor burden,biological characteristics and treatment response can affect the prognosis.MM cells accumulate in bone marrow and produce abnormal immunoglobulin.Abnormal immunoglobulin does not participate in immune response and inhibits adaptive immune system is the most significant pathophysiological characteristics of MM.Hyperviscosity,amyloidosis,infection and kidney injury are the important complications of MM.This paper analyzes the traditional Chinese medicine (TCM) understanding of these important complications,and summarizes the commonly used clinical Chinese medicine,in order to provide important basis for the TCM treatment of multiple myeloma.

Keywords:Multiple myeloma,Hyperviscosity,Amyloidosis,Infection and kidney injury

Hyperviscosity

Hyperviscosity must have the hyperviscosity state of blood,that is,the increase of blood viscosity [1].Most of our understanding of hyperviscosity is blood stasis syndrome,which is treated by activating blood circulation to remove blood stasis.The reason is that the abnormal increase of monoclonal immunoglobulin in blood leads to the aggregation of red blood cells by wrapping red blood cells and reducing the repulsive force between negative charges on the surface of red blood cells,and the increase of blood viscosity,especially serum viscosity,resulting in poor blood flow,microcirculation disorder [2].For example,the common symptoms include dizziness,headache,dizziness,visual impairment,limb numbness,and so on.If there is hypercoagulable state of blood,it can be complicated with mesenteric vascular thrombosis,cerebral thrombosis and peripheral vascular multiple thrombosis and other fatal diseases [3].

Is hyperviscosity just blood stasis?

We think that hyperviscosity has the pathological characteristic of hyperviscosity and hypercoagulability,which is basically consistent with the characteristics of heavy adhesion and viscosity of phlegm dampness.So we think that hyperviscosity is a kind of manifestation caused by phlegm and blood stasis,rather than simple blood stasis syndrome.If the cerebral blood circulation is seriously affected,it can lead to disturbance of consciousness,epileptic seizures and even coma,which belongs to "phlegm and blood stasis,blinding and clearing the orifices".

The bleeding caused by MM hyperviscosity is also considered to be caused by phlegm and blood stasis in traditional Chinese medicine,because phlegm and blood stasis block meridians,so that normal blood can not run along meridians and is forced out of blood [4].Modern medicine believes that the bleeding tendency is due to immunoglobulin wrapping the surface of platelets and coagulation factors,which affects its function,and blood flow retardation damages the capillary wall.The bleeding of mucous membrane (nasal cavity,oral cavity,gastrointestinal mucosa) was more common [5].For example,the retinal vein dilates into a pouch like pouch,which looks like a sausage.This is the result of phlegm and blood stasis.

The occurrence of hyperviscosity is related to the concentration of immunoglobulin in blood and the type of immunoglobulin.Among all kinds of immunoglobulin,lgM is the most likely to cause high viscosity syndrome because of its large molecular weight,asymmetric shape and aggregation tendency.Secondly,lgA and lgg3 tend to form polymers,which is also more likely to cause high viscosity syndrome.Therefore,the occurrence of diseases also shows individual differences due to individual constitution [6],which is also in line with our treatment concept of " treating the same disease differently ".

In the treatment,the traditional Chinese medicine of promoting blood circulation and removing blood stasis,resolving phlegm and removing dampness,dredging channels and activating collaterals are mostly used.It mainly plays a role by improving the deformability of red blood cells,reducing the aggregation of cells (especially red blood cells) and platelets,and reducing blood viscosity.It is commonly used in Sumu (Caulis Perillae),Chishao (Radix Paeoniae Rubra),Danggui (Radix Angelicae Sinensis),Chuanxiong (Rhizoma Chuanxiong),Shuizhi (Hirudo).

Through modern pharmacological research,total glucosides of Chishao (Radix Paeoniae Rubra) can significantly reduce platelet and erythrocyte aggregation,enhance erythrocyte deformability,and reduce whole blood viscosity and plasma viscosity [7].It can effectively target the mechanism of hyperviscosity syndrome and reduce the occurrence of bleeding.

Bingcheng Zhang said: "Danggui (Radix Angelicae Sinensis),Chuanxiong (Rhizoma Chuanxiong) warm and moist,can nourish the blood,and the qi in the blood flows." Chuanxiong (Rhizoma Chuanxiong) is the qi medicine in the blood.It can ascend to the top of the head,break the blood stasis and activate qi,and dredge the brain collaterals,so as to make the blood stasis disappear without damaging the body.Ligustrazine,the main component,can inhibit platelet aggregation and reduce blood viscosity.It can improve the hemorheology.In addition,ligustrazine can penetrate the blood-brain barrier,improve cerebral circulation disorder and cerebral ischemia.It can improve head symptoms such as dizziness,headache and disturbance of consciousness caused by blood viscosity [8].

Secondly,ligustrazine has a protective effect on bone marrow.Ligustrazine can promote the repair of bone marrow microenvironment by increasing the expression level of bone marrow stromal cells.It can strengthen the interaction between hematopoietic cells and stromal cells,which is conducive to the proliferation of hematopoietic cells.Improve the bone marrow environment of MM,and to a certain extent improve the anemia caused by MM [9].

At present,the commonly used therapeutic drugs are reducing the whole blood viscosity,such as Taoren (Semen Persicae),Honghua (Flos Carthami),Danshen (Radix Salviae Miltiorrhizae),Yimucao (Herba Leonuri),etc.,reducing the plasma viscosity,such as Huzhang (Rhizoma Polygoni Cuspidati),Shanzha (Fructus Crataegi),Dilong (Pheretima),Puhuang (Pollen Typhae),etc.

Amyloidosis

Amyloidosis refers to a type of disease caused by the abnormal deposition of poorly soluble amyloid substances outside the cell.It belongs to protein conformation diseases.The amyloidosis of this disease is formed by the complexes of immunoglobulin light chains and polysaccharides deposited in tissues and organs [10].

We think that amyloidosis refers to "condensation of phlegm due to yang deficiency".The body of amyloidosis patients is like a rainy day without sunlight.The haze,cold and dampness condenses in the body's viscera.Therefore,clinical manifestations such as tongue hypertrophy,parotid gland enlargement,skin mass,myocardial hypertrophy,liver and spleen enlargement,diarrhea and constipation are all symptoms of cold damp phlegm condensing in different organs [11]."The source of fire-benefiting,to eliminate yin haze",we often use the method of warming yang to dispel cold and dampness.

In addition,amyloidosis often causes autonomic nerve and peripheral nerve damage,such as carpal tunnel syndrome,limb numbness,glove sock like changes,etc.,most of which are manifested as limb numbness [12].For example,reynolds phenomenon is a kind of vascular disease caused by intermittent peripheral arteriole spasm and lumen stenosis,which is a kind of peripheral vascular disease.The three-phase reactions of pallor,purplish and flush appeared in the extremities.We think that this is caused by "Yang deficiency,cold coagulation of meridians,Yang qi can not warm".

We think that the movement of blood is closely related to the movement of Yingwei qi,because "qi is the leader of blood".Yingwei Qi carries blood and connects the whole body meridians and collaterals.Therefore,normally,the whole body is full of Yingwei qi and blood.When Yang deficiency and cold coagulation,Yang qi can not carry qi and blood to warm the extremities,resulting in microcirculation disorder of extremities.

As for the theory of peripheral microcirculation circulation,the ancients have described it for a long time.The theory of tidal movement of blood has been confirmed by professor Ruijuan Xiu microcirculation theory (microcirculation sea wave perfusion hypothesis).

We often use traditional Chinese medicines for warming the meridian,dispelling cold and removing dampness,such as Chuanxiong（Rhizoma Chuanxiong),Chuanwu (Radix Aconiti Preparata),Fuzi (Radix Aconiti Lateralis Preparata),Guizhi(Ramulus Cinnamomi),Wujiapi (CortexAcanthopanacis),and so on.

Recurrent infection

Repeated infection caused by MM,it is precisely because of the cause of deficiency and evil Sheng.Yiqi Shiwei,Qingre Jiedu are the main principles of our treatment.Why is it true? Deficiency of vital energy means the decrease of immunity.Because MM is a disease of immune system,abnormal monoclonal immunoglobulin proliferates greatly,which inhibits the proliferation,differentiation and maturation of normal polyclonal B cells plasma cells,and reduces the production of normal polyclonal immunoglobulin.However,the abnormal monoclonal immunoglobulin lacks immune activity,resulting in the decrease of immunity [13].In addition,the abnormal number and function of T cells and B cells,as well as the application of chemotherapy drugs and adrenocortical hormone,reduce the number of lymphocytes and greatly reduce the body's immunity [14].

"When the evil is gathered together,the qi will be deficient." The healthy qi and the evil qi are opposite and restrict each other.Therefore,when the healthy qi is greatly deficient,the evil qi is more likely to gather and make trouble.When the body's immunity declines,pathogenic bacteria are extremely easy to take advantage of the opportunity to cause infection.Pneumococcal pneumonia was the most common infection,followed by urinary tract infection and sepsis.Herpes zoster and varicella were the most common viral infections.

Therefore,we often use the traditional Chinese medicine,such as Chonglou (Rhizoma Paridis),Jinyinhua (Flos Lonicerae),Huangqi (Radix Astragali),Zhizi (Fructus Gardeniae),Shengma (Rhizoma Cimicifugae),etc.We should also pay attention to the side effects of chemotherapy and hormone,and choose the corresponding Chinese medicine.

Kidney damage,hyperuricemia

In traditional Chinese medicine,kidney damage can be classified as edema,asthenia,lumbago,dysmenorrhea and other diseases.The principles of treatment are different,but we often use diuretic,purgation and kidney protection to treat MM induced renal damage and hyperuricemia.This coincides with the treatment of adequate fluid intake and effective diuretics in modern medicine.

What is the cause of MM kidney damage? Modern medicine believes that renal damage is a common and characteristic clinical manifestation of MM.First of all,MM is a metabolic disease,the synthesis of heavy chain and light chain is out of balance,too much light chain is generated,the molecular weight of light chain is small,it can be filtered from glomerulus and reabsorbed by renal tubules,too much light chain reabsorption causes renal tubular damage [15].In addition,MM is a systemic disease.Hypercalcemia,hyperuricemia,hyperviscosity syndrome,amyloidosis and tumor cell infiltration can cause renal damage.In addition,MM is an immune disease,and the development of the disease will naturally damage the kidney [16].

What is the cause of MM hyperuricemia? Hyperuricemia is closely related to renal function damage.Firstly,the increase of serum uric acid is due to the increase of uric acid produced by tumor cell decomposition and the decrease of uric acid excreted by kidney.Furthermore,elevated serum uric acid can also cause kidney damage.

We think that the kidney dominates water mainly refers to the function of qi gasification in the kidney,which plays an important role in regulating the distribution and excretion of body fluid and maintaining the metabolic balance of body fluid.First of all,if the renal function is damaged,then the water metabolism and excretion dysfunction.And the water excretion dysfunction will aggravate the accumulation of light chain,high calcium,blood uric acid,and eventually aggravate the renal damage.

Therefore,we often use diuretic and purgative traditional Chinese medicine,such as Bixie (Rhizoma Dioscoreae Hypoglaucae),Tufuling (Rhizoma Smilacis Glabrae),Qumai (Herba Dianthi),Zexie (Rhizoma Alismatis) treat MM induced renal damage and hyperuricemia.