Crohn’s Disease Treated by Chinese Medicine

2.1 Clinical manifestations

The clinical presentation of CD depends on the site of pathological changes and the severity of inflammation, which can be divided into four aspects [6]:

(1) Digestive system performance: Spasmodic pain in right lower abdomen or peri-umbilicus, accompanied by borborygmus, aggravation after meals, it can be alleviated after defecation; diarrhea intermittent attacks in early stage, and more persistent in later stage. If the lesions involve the lower colon or rectum, mucinous blood stool and tenesmus may be present. Abdominal mass occurs in the right lower abdomen and around the umbilicus, mostly caused by mesenteric lymph node enlargement, internal fistula or local abscess formation. (2) General performance: Patients with intermittent low or moderate fever, a few show remittent fever, accompanied by toxemia; Nutritional disorders due to anorexia, and chronic diarrhea, including emaciation, anemia, hypoproteinemia, vitamin deficiency, calcium deficiency, osteoporosis, etc. The balance of water, electrolyte, acid and base is disturbed in acute stage. (3) Extraintestinal manifestations: Some patients have iridocyclitis, uveitis, finger pestles, arthritis, erythema nodosum gangrenous pyoderma, oral mucosal ulcer, chronic hepatitis, small bile duct peripheral inflammation, sclerosing cholangitis and so on. Amyloidosis or thromboembolic disease can be seen occasionally. (4) Perianal manifestations: Fistulas, fissures, abscesses, and stenosis around the anus or rectum [7]. It even affects the organs outside the gut.

2.2 Endoscopic examination and diagnosis

Colonoscope is the most sensitive method in the diagnosis of CD, which can improve the accuracy of clinical diagnosis and the efficiency of treatment [8]. Under endoscopy at the early stage of the disease, 2 ~ 3 mm diameter round shallow pitting ulcers or Afta aphthous ulcer can be seen with surrounding mucosa hyperemia and redness. After the disease progresses, the ulcer increases and deepens, and merges with each other to form longitudinal ulcer. The relatively specific endoscopic manifestations include cobblestone changes, annular, multiple, segmental stenosis, and inflammatory polyp hyperplasia. Capsule endoscopy is very sensitive to the judgment of abnormal mucosa, but its specificity is low, and it is not applicable to all CD patients. For patients with stenosis, there is a certain risk. Wireless video capsule endoscope has the advantages of no radiation, no pain, no sedation, easy outpatient use and high patient satisfaction. When traditional diagnostic tools such as endoscope cannot make a clear diagnosis, it can be mainly used. During the development of CD, some patients may involve the upper digestive tract. This type of CD usually presents insidiously without obvious symptoms. Gastroscopy is often used, under which worm etched ulcer, longitudinal ulcer, slub like appearance, stenosis and fistula can be seen [9].

2.3 Pathological diagnosis

Based on the principle of multi-point and multi-segment sampling, CD mucosal biopsy is the most main diagnostic basis of CD. Its pathologic findings are typically non-caseous granulomas that are more easily detected on biopsy in about 30% of cases and are more common in smaller ulcers. In addition, common pathological features include segmental lesions, the presence of inflammatory cell infiltration in the inherent membrane, and submucosal broadening, marked fibrosis, whole-wall inflammation, fissured ulcers, and whole-layer lymphatic follicles in the intestinal wall [10, 11].

2.4 Imaging diagnosis

Imaging also plays a very important role in the diagnosis of CD. CT small intestine imaging or magnetic resonance enterography is the first choice for imaging examination, which is mainly used to evaluate inflammatory lesions in the small intestine. Magnetic resonance enterography is expensive but has the advantage of avoiding radiation and using no iodized contrast agents. The use of contrast-enhanced ultrasound can effectively improve the detection sensitivity of color Doppler ultrasound, which is outstanding in the diagnosis of the combined sensitivity and specificity of CD activity [12]. The sensitivity of small intestinal barium contrast is low and only suitable for dynamic observation in patients with intestinal cavity stenosis, and for the primary medical unit cannot conduct CT small intestinal imaging examination. Barium enema is not used much at present and has been replaced by colonoscopy.

2.5 Laboratory examination and diagnosis

The blood counts are used to monitor anemia in CD patients. The concentration of calcium protective protein in feces was associated with neutrophil infiltration in the intestinal mucosa, it has a strong sensitivity and specificity for CD diagnosis. As an inflammation marker, C-reactive protein and other inflammatory markers are used simultaneously to monitor disease activity to assess disease activity.

4.1 Etiology

CD is associated with a number of pathogenic factors, either alone or in combination. Exogenous pathogenic factors, improper diet, emotional disorders, chronic physical deficiency were the main causes [14]. Exogenous pathogenic factors, such as cold, dampness and heat invade the body, resulting in blood stasis and abdominal pain and diarrhea. Unclean food, or overeating, or eating greasy and cold food can cause damp-heat or cold-dampness accumulating in stomach and spleen, blockage of abdomen Qi, producing diarrhea, bowel carbuncle; Internal injury of emotions, such as moodiness and worry leads to stagnation of qi induce pain easily; Weakness, prolonged illness or excessive fatigue, resulting in weakness of the spleen and stomach, transport and transformation weak that induce abdominal pain and diarrhea. CD mainly occurs in the intestine. In the theory of TCM, CD is also closely related to the spleen, stomach, liver and kidney, and is mainly caused by lesions in middle-jiao and lower-jiao.

4.2 Pathogenesis

The basic pathogenesis of CD is a mixture of deficiency and excess, cold and heat [15]. The deficient root include the deficiency of natural endowments, the deficiency of spleen and kidney, or the prolonged illness and overwork; Damp-heat accumulation, qi stagnation, phlegm and dampness, blood stasis are all belong to excessive superficial. The basic pathogenesis of CD varies according to the main symptoms. If abdominal pain is the main manifestation, the basic pathogenesis is exogenous pathogenic factors of coldness, wetness, heat, it result in qi stagnation, blood stasis, viscera and qi adverse, pain [16]; If the main manifestation is diarrhea, the basic pathogenesis is spleen deficiency and overabundance of dampness [16, 17]; If the main manifestation is intestinal carbuncle, the pathogenesis includes accumulation of dampness and heat, blood stasis, and the accumulation of phlegm and blood stasis [14].

5.1 Syndrome of liver-stagnation and spleen-deficiency

The main symptoms are anorexia, belching, right abdominal pain or periumbilical distension pain and diarrhea while during abdominal pain and relief of pain after diarrhea. Acute abdominal pain, loose stools, belching and eat less, tongue reddish, and pulsed strings. Its attacks or exacerbations are often caused by irritation or nervous tension. The principle of treatment is soothing the liver and strengthening the spleen. The main prescriptions are Chaihu Shugan powder and Shenlinbaizhu powder [20] including bupleurum, Codonopsis pilosula, poria cocos, Chinese yam, white lablab album, atractylodes macrocephala koidz, fructus aurantii, lotus seed, amomum, coix seed, rhizoma cyperi, pericarpium citri reticulatae, raidix paeoniae alba, platycodon grangdiflorum, radix glycyrrhizae. Patients with anorexia can add fried hawthorn, malt; Patients with nausea and vomiting can add pinellia ternate, inula flower.

5.2 Syndrome deficiency and cold of spleen and stomach

The main symptoms are dull abdominal pain, prefer warm and pressing, prolonged diarrhea, bowel bloating and abdominal distension, vomiting of clear water, loss of appetite, sallow complexion, dizziness, cold limbs, fatigue, pale tongue, thin and white coating, and slow and sunken pulse. The principle of treatment is to warm stomach and strengthen spleen. The main prescription is Shenling Baizhu powder and Fuzi Lizhong pill [21], including fried semen coicis, fried atractylodes macrocephala koidz, poria cocos, Codonopsis pilosula, radix paeoniae alba, lotus seed, Chinese yam, bupleurum, giant typhonium rhizome (decocted first), corydalis yanhusuo, common bletilla pseudobulb, amomum (decocted later), honey-fried radix liquiritiae, dried ginger, panax notoginseng powder (take with water). Patient with frequency of defecation can be added nutmeg, Terminalia chebula; Patient with bloody stool can be added roasted ginger charcoal, patient with mucus stool can be added atractylodes.

5.3 Syndrome of deficiency of spleen and kidney yang

The main symptoms are dull abdominal pain, irregular pain attacks and stop, prefer warm and pressing, thin pus around the anus, dull anal pain, loose stool, or diarrhea at dawn, loss of appetite, fatigue, cold limbs, soreness of waist and polyuria, pale tongue, or fat tongue with teeth marks, white coating, sunken or or thin and weak pulse. The principle of treatment is warming kidney and strengthening spleen. The main prescription is Changyangan soup [22], including astragalus membranaceus, poria cocos, Codonopsis pilosula, rhizoma bletillae, pseudo-ginseng, cooked monkshood, fructus psoraleae, Myristica fragrans, epimedium, fructus chebulae, radix glycyrrhizae.

5.4 Syndrome of cold dampness impairing spleen

The main symptoms are acute abdominal pain, loose stool or water stool, or dysentery with blood and pus, heavy head and body, pale tongue, white and greasy coating, soft and slow pulse. The principle of treatment is clearing damp and strengthening spleen. The main prescription is Weiling soup, including atractylodes rhizome, dried tangerine peel, magnolia officinalis, polyporus umbellatus, rhizoma alismatis, cortex cinnamomi, atractylodes macrocephala koidz, radix glycyrrhizae.

5.5 Syndrome of qi stagnation and blood stasis

The main symptoms are immovable abdominal lumps, abdominal distension or pricking, loose or bloody stools, purplish or petechial tongue, string and thin and hesitant pulse. The principle of treatment is regulating qi and dispersing blood stasis. The main prescription is infradiaphragmatic stasis-expelling decoction, including peach kernel, safflower, radix rehmanniae, radix angelicae sinensis, red peony, fructus aurantii, Platycodon grandiflorum, radix glycyrrhizae, radix bupleuri, radix scrophulariae.

5.6 Syndrome of damt-heat accumulation

The main symptoms are abdominal pain refusing to press, brown and smelly stool, or diarrhea with blood and pus, distending pain and scorching hot anus, thirsty and drinking cold, few and yellow urine, red tongue, yellow greasy coating, string and slippery or slippery and rapid pulse. The treatment principle is clearing heat and expelling damp. The main prescription is Baitouweng soup, including pulsatilla, coptis chinensis, phellodendron, ash bark.

Chinese herbal medicine.

6.1 Bolus for strengthening intestines and relieving diarrhea

It has the effect of harmonizing liver and spleen, astringent intestine to relieve pain [23] and commonly used in patients with disharmony of liver and spleen, diarrhea and abdominal pain, and nonspecific ulcerative colitis.

6.2 Salvia ligustrazin injection

It has the effect of activating blood circulation and removing blood stasis, improving microcirculation. The cure rate can be improved by improving the high coagulation state of CD patients [24].

6.3 Warming kidney and invigorating spleen granules

It has the effect of strenthening spleen and tonifying kidney. It can improve the humoral immunity of patients also used todiseases caused by the deficiency of spleen and kidney.

6.4 Tripterygium wilfordii polyglycoside tablet

It has the effect of dispelling wind and detoxifying, dehumidifying and detumescence, relaxing tendons and dredging collaterals. Studies have shown that it can effectively improve the clinical symptoms of CD patient [25], but its toxicity of liver and kidney should be valued.

6.5 Sishen pill

It has the effect of warming kidney and dispelling cold, astringent intestine and relieving diarrhea and commonly used for diarrhea caused by deficiency of kidney yang, the symptoms are borborygmus, intestinal distension, diarrhea at dawn, anorexia and indigestion, continuous diarrhea, yellowish complexion and cold limbs.

6.6 Dark plum pill

It has the effect of smoothing liver and regulating intestine, clearing the upper Jiao and warming lower Jiao and used for patient with chronic dysentery, the symptoms are abdominal pain, dysentery, vertex headache, attack intermittently, irritation and vomiting, extremities cold.

6.7 Peaceful gastroenterology tablets

It has the effect of invigorating spleen and kidney, warming stomach and relieving pain, astringent intestine and relieving diarrhea, and used for patient with diarrhea of deficiency of spleen and kidney Yang, the symptoms are irregular stool, diarrhea at dawn with mucus, abdominal distention and pain, epigastric discomfort, and distention of lower abdominal.

6.8 Buzhong Yiqi pill

It has the effect of invigorating and benefiting spleen qi and lifting collapsed qi, be used for diarrhea caused by weakness of spleen and stomach and collapse of middle qi.

6.9 Guben Yichang tablets

It has the effect of invigorating spleen and warming kidney, astringing intestine to relieve diarrhea, and be used for chronic diarrhea caused by spleen deficiency or Yang deficiency of spleen-kidney, the symptoms are chronic abdominal pain and diarrhea, loose stools, anorexia and abdominal distension, weak waist, fatigue and cold limbs.

6.10 Aucklandia and coptis tablets

It has the effect of clearing away heat and eliminating dampness, promoting qi circulation to relieve pain, and be used for dysentery caused by dampness-heat of large intestine, the symptoms are stool with pus and blood, tenesmus, fever and abdominal pain.

6.11 Fuzi Lizhong pill

It has the effect of warming spleen dispersing cold, relieving diarrhea and pain, and can be used for cold syndrome of spleen and stomach, the symptoms are anorexia and abdominal distension, abdominal pain and nausea, weak pulse, cold limbs, or headache attacked by cold, and any chronic disease caused by cold.

6.12 Zhuche pill

It has the effect of nourishing Yin and blood, tonifying qi and strong intestine, removing blood stasis and generating muscles. The symptoms are dull abdominal pain, persistent diarrhea, stool with pus and blood, low fever in afternoon, dizziness, insomnia, night sweats, irritability, weight loss and fatigue, red tongue, thin and less coating, thin and rapid pulse.

9.1 Crohn’s disease activity index (CDAI)

CDAI can be used to evaluate the disease activity and the efficacy of CD, including five aspects of the patient’s general condition, such as abdominal pain, diarrhea, abdominal mass and complications [34]. The higher the total score, the more serious the disease. A score of ≤4 indicates remission, a score of 5-8 indicates moderate activity, and a score of ≥9 indicates severe activity. It can be scored in three stages before, during and after treatment to dynamically observe the changes of the disease.

9.2 Overall efficacy of TCM syndromes

The total score of TCM syndromes was used to evaluate the clinical symptoms of abdominal pain, diarrhea, pus and blood stool, tenesmus, belching, nausea and vomiting and fever. The total scores before and after treatment was compared, if the total score decreased by ≥90% compared with that before treatment, it is judged as clinical remission. If the total score decreased by ≥70% and < 90%, it is judged as significant effect; if the total score decreased ≥30%and < 70%, it is judged to be valid; if the total score decreased <30%, it is judged to be invalid.

9.3 Endoscopic score

Simplified endoscopy score for CD (SESCD) can be used for diagnosis and efficacy evaluation of CD. The score items mainly include ulcer size, ulcer area, affected intestinal area, intestinal lumen stenosis and the condition of mucosal healing. The lower the score, the better the mucosal healing degree. A score ≤ 3 is remission, a score 4-10 is mild activity, a score 11-19 is moderate activity, and a score more than 20 is severe activity [35].

9.4 Quality of life assessment

Inflammatory bowel disease quality of life questionnaire (IBDQ) was used for CD evaluation, including intestinal symptoms, systemic symptoms, emotional ability and social ability. Scores were recorded for both the pre-treatment and post-treatment stages, with higher scores indicating better quality of life.

9.5 Assessment of anxiety and depression

Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the severity of the anxiety and the depressive symptoms of CD patients. Scores were performed according to the symptoms, and the patients were divided into mild, moderate and severe by 50 score. Scores were recorded before and after treatment. Scores below 50 after treatment indicated efficacy.

9.6 Long-term efficacy

The development of CD is a long-term and progressive process. The clinical efficacy evaluation should combine the short-term with long-term efficacy. In addition to the general clinical symptoms, it is also important to observe the status with the ulcer of intestinal mucosa and actively prevent perianal lesions it should also focus on the observation of intestinal mucosal ulcer and the active prevention of perianal lesions of CD patients.

10.1 Diet control

Improper diet is one of the major causes of CD. In TCM, dampness, heat and cold pathogens easily invade the body through improper diet, damage spleen and stomach, and accumulate in intestines. Therefore, CD patients should pay attention to their daily diet, light and easy digestible food is better, avoid eat irritating food, try not to eat or eat less fat and greasy food, or raw and cold food.

10.2 Psychological adjustment

CD is a chronic disease in the developing course of disease, patients are prone to anxiety or depression that aggravating the symptoms of body and mind. Therefore, in the process of diagnosis and treatment, attention should be paid to the psychological and emotional intervention of the patients to avoid negative emotional stimuli, relieve their anxiety or depression situation, guide the correct understanding of disease with good positive attitude [36, 37].

10.3 Adjust lifestyle

CD is persistent and prone to relapse, so it is important to adjust lifestyle, control risk factors and change improper habits. Smoking is an important factor for CD patient, which often aggravates the disease and more likely to cause complications. For CD patients, the first step is to quit smoking, adjust lifestyle, and eliminate risk factors. In addition, patients should have regular daily life, reasonable work and rest, moderate diet, maintain the spleen and stomach, do proper exercise, avoid fatigue, adjust emotions, comply with four seasons, and maintain healthy energy [38].

10.4 Regular review and follow-up

The development of CD is a long-term process, attention should always be paid to physical changes through outpatient, inpatient follow-up, telephone follow-up, and regular review, to understand the recurrence of disease, cancer prevention.