Inflammatory bowel disease and its associated uveitis

　　First, the cause of the disease

　　The etiology is unknown, and it is speculated to be related to various factors, possibly including infection, autoimmune factors, psychological factors, and toxic factors.

　　1. Infection factors:Due to the pathological changes and clinical manifestations of this disease being similar to dysentery, it is considered chronic dysentery; it has also been suspected of other bacteria or viruses, but none have been fully confirmed. Mitchell used small intestinal tissue from Crohn disease patients transferred to animals to cause changes similar to Crohn's disease, and some have studied that the factor for this transfer may be a virus or variant bacteria.

　　2, Immune Factors:It has been reported that this disease is caused by food allergy, such as milk or other proteins, and excluding this food can improve the condition. Some have found that patients with this disease have anticolon antibodies in their serum, and therefore it is considered an autoimmune disease. It has also been proven that other antibodies such as RF, ANA exist, and it has been found that immune complexes are high, with unknown antigen properties, and antibodies are IgG. Pedmann proved that there are cytotoxic lymphocytes (cytotoxic lymphocytes) in the blood circulation of patients with this disease, which disappear after the colon is surgically removed. Shorter et al. pointed out that IgM binds to these cells and proved that these cells have cross-reactivity with colonic cells and intestinal bacterial antigens. This can be explained as the destruction of the normal mucosal barrier in patients with insufficient blood or trauma, forming sensitization to certain intestinal microbial antigens. Normal immune factors can suppress this hypersensitivity reaction, but when patients are unable to suppress this inflammatory reaction, it can be due to new bacteria or periodic stimulation of intestinal mucosa, leading to the recurrence of the disease. Severe cases may be accompanied by polyarthritis and rash, and therefore it is considered a chronic collagen disease caused by autoimmune reactions.

　　3, Mental Factors:This disease is often caused by emotional tension or mental trauma in patients, leading to onset or exacerbation of the disease. Some believe that neuro-psychological factors may be one of the causes of the disease. Disordered activity of the cerebral cortex can produce colonic and vascular smooth muscle spasm through the functional disorder of the autonomic nervous system, leading to erosion and ulceration of the colonic mucosa.

　　4, Immune Genetic Genes:The Asguith study found that HLA-A11 and HLA-B7 increased in IBD patients; Nahir found that HLA-A2, HLA-BW35, and HLA-BW40 increased, with no significant difference from the normal control group, but in IBD patients with AS or sacroiliitis, HLA-B27 increased. This suggests that the disease may be related to immune genetic genes.

　　Second, Pathogenesis

　　It is not yet clear. It may be that when colonic inflammation is active, the basal membrane of the choroid and sclera vessels combines with intestinal bacterial antigens or mucosal antigens. This combination of the basal membrane antigens causes periodic activity, due to the action of cytotoxic lymphocytes that bind IgM. It can cause complement deposition and attract inflammatory cells, leading to inflammatory manifestations. It has been found that the following factors are related to uveitis in patients with inflammatory bowel disease: ① intestinal lesions: when intestinal lesions are quiescent, the likelihood of uveitis decreases, but when intestinal lesions are active, the likelihood of uveitis increases; ② sacroiliitis: in patients with sacroiliitis, the likelihood of uveitis is significantly increased. It is reported that in 25 patients with sacroiliitis, 52% developed iridocyclitis, but in 119 patients without sacroiliitis, only 3.4% developed uveitis; ③ age of the patient: patients in the 20-39 age group are prone to develop uveitis; ④ nodular erythema and oral ulcers: patients with nodular erythema and oral ulcers are prone to develop uveitis.

　　Inflammatory bowel diseases can also cause or be accompanied by other lesions, such as liver and gallbladder diseases, fallopian tube obstruction, pancreatitis, pulmonary vasculitis, fibrotic alveolitis, myocarditis, pericarditis, prostatitis, kidney stones, amyloidosis, clubbing (of fingers or toes), thrombophlebitis, and other conditions. Due to absorption and nutritional disorders caused by intestinal lesions, it can also cause non-specific manifestations such as anemia and weight loss.

　　1. Gastrointestinal lesions:The characteristic of ulcerative colitis is diffuse superficial mucosal ulcers, which is typically manifested clinically as spastic pain in the lower left quadrant of the abdomen, recurrent mucous stools or bloody stools, or diarrhea or watery stools. It is easy to have dehydration, electrolyte disorder, toxic megacolon, fever, decreased appetite, weight loss, anemia, and other symptoms. Long-term chronic ulcerative colitis patients, especially children, are prone to colon cancer.

　　The characteristic of Crohn's disease is the appearance of non-caseating necrotic granulomas, which is typically manifested clinically as severe pain in the lower right quadrant of the abdomen, accompanied by diarrhea or constipation, frequent nausea and vomiting, a mass in the lower right quadrant of the abdomen, fever, weight loss, anemia, and other symptoms. Some patients may have complications such as intestinal stricture, intra-abdominal abscess, psoas abscess, perianal fistula, and perianal abscess.

　　2. Ocular lesions:In patients with inflammatory bowel diseases, 1.9% to 23.9% have ocular damage, mainly manifested as uveitis, episcleritis, scleritis, and keratitis. In addition, it can also cause orbital inflammatory pseudotumor, retrobulbar neuritis, and other conditions. Due to absorption and nutritional disorders caused by intestinal lesions, it can also cause non-specific manifestations such as anemia and weight loss.

　　1. Uveitis:Uveitis is the most common ocular lesion in inflammatory bowel diseases, with up to 17% of patients with inflammatory bowel diseases reported to have uveitis. Another report shows that about 14% of patients with ulcerative colitis develop uveitis, and about 8% of patients with Crohn's disease develop uveitis. Uveitis usually occurs after intestinal lesions, but in a few patients, it can also occur before intestinal lesions. Uveitis often affects both eyes, but the inflammation in both eyes usually appears sequentially and alternately.

　　Although inflammatory bowel diseases can be accompanied by various types of uveitis, uveitis was the most common in the past. Crohn's disease is more likely to develop anterior uveitis than ulcerative colitis, and the anterior uveitis associated with both diseases is mainly manifested as acute non-granulomatous inflammation, but granulomatous inflammation can also occur, especially in Crohn's disease patients, where this type is more likely to appear.

　　The anterior uveitis associated with this disease can be acute inflammation or chronic inflammation; it can cause severe eye redness, eye pain, photophobia, lacrimation; examination may reveal significant conjunctival injection, a large number of inflammatory cells in the anterior chamber, and obvious anterior chamber flash. In severe inflammatory patients, there may also be macular cystoid edema. It can also be insidious in onset, presenting as mild to moderate anterior uveitis, with dust-like or medium-sized KP, anterior chamber inflammatory cells, and anterior chamber flash. It can also present as granulomatous anterior uveitis, with lipid-like KP, iris Koeppe and Bussuca nodules, and these patients are prone to posterior iris adhesion.

　　Iridocyclitis is the most common type of uveitis associated with inflammatory bowel disease, accounting for 85%, mainly presenting as chronic non-granulomatous iridocyclitis, with insidious onset and a long duration. There are also reports that 60% of uveitis associated with inflammatory bowel disease presents as acute non-granulomatous iridocyclitis. The typical manifestations are: ① Patients usually have obvious symptoms such as eye pain, photophobia, and headache. ② Marked conjunctival injection. ③ Easy to appear a large amount of fibrinous exudation in the anterior chamber, with significant anterior chamber flash. ④ Easy to develop anterior chamber abscess and angle abscess. ⑤ KP is slightly larger and has a tendency to fuse. ⑥ Iris nodules are rare. ⑦ Easy to develop posterior iris adhesion. ⑧ Inflammation is prone to recurrence. ⑨ Sensitive to corticosteroids. ⑩ Most patients have a good visual prognosis.

　　The involvement of the posterior segment of the eye can manifest as various types of posterior uveitis, such as choroiditis, choroidoretinitis, neuroretinitis, retinal vasculitis, optic disc inflammation, intermediate uveitis, and panuveitis. In patients with involvement of both the anterior and posterior segments of the eye, granulomatous panuveitis is often observed. Among the aforementioned posterior uveitis, choroiditis is a common change in the posterior segment of the eye in inflammatory bowel diseases, often presenting as bilateral multifocal yellowish-white choroidal infiltration, 1/8 to 1/2 disc diameter in size, with blurred edges in the active phase, which can lead to fusion phenomena, and the appearance of pigmented proliferation and choroidal scars. Fluorescein fundus angiography shows early occlusion of fluorescence, late staining, and as the course of the disease extends, the boundary of the lesions gradually becomes clear.

　　The involvement of retinal vessels manifests as two types: vascular thrombosis or occlusion and vasculitis. The former can occur alone in the absence of other retinal lesions, while the latter often presents as unilateral or bilateral asymmetric occlusive arteritis or venulitis. Clinical examination may reveal retinal edema (caused by capillary diffuse leakage), cotton wool spots, vascular sheath, vascular occlusion, retinal hemorrhage, vitreous hemorrhage, inflammatory cells in the vitreous and turbidity, etc.

　　Compared with ulcerative colitis, Crohn's disease is more likely to cause optic nerve lesions, which can affect either one side or both sides; it can be inflammatory or ischemic damage; it can be optic disc inflammation or retrobulbar optic neuritis; it can leave no sequelae or cause optic atrophy and permanent visual field defects.

　　In patients with posterior segment involvement caused by inflammatory bowel disease, serous retinal detachment is prone to occur, and in some patients, it can also cause macular cystoid edema.

　　Uveitis usually occurs after intestinal lesions, that is, the average age at the onset of inflammatory bowel disease is less than the average age at the onset of uveitis. However, in a few patients, uveitis can occur before or simultaneously with intestinal diseases.

　　2. Scleritis or episcleritis:Episcleritis or scleritis is another common ocular lesion of inflammatory bowel disease. Women are more prone to this ocular lesion, which can manifest as acute episcleritis and acute scleritis. Episcleritis may involve one side or both sides, and it can be nodular inflammation or diffuse inflammation. There is a close relationship between episcleritis and the activity of intestinal lesions, and it is almost always seen in Crohn's disease, often occurring several years after the appearance of intestinal lesions. It is more likely to occur in patients with arthritis and other systemic changes (such as anemia, skin lesions, oral ulcers, liver and biliary diseases). The incidence rate of episcleritis in patients with inflammatory bowel disease is 2.06% to 9.67%, and it can manifest as nodular, necrotic, or diffuse. Scleritis can recur, and severe cases may cause scleral softening or even perforation, and it often causes uveitis. Scleritis is also more common in patients with arthritis and other systemic diseases, and it often occurs when intestinal diseases worsen.

　　3. Conjunctivitis:Conjunctivitis is also a common ocular manifestation of inflammatory bowel disease, which may be accompanied by uveitis, keratitis, and keratoplasty inflammation.

　　4. Corneal lesions:It is relatively rare, may be accompanied by or without episcleritis, and may manifest in two types: one is an epithelial or subepithelial grayish white dot infiltration, and the other is a subepithelial or anterior stroma layer with plaquelike infiltration. The lesions often appear in the peripheral cornea, and severe cases may cause corneal ulcers.

　　5. Other:Orbital inflammatory pseudotumor is a rare ocular lesion, more common in women; other conditions may include ophthalmoplegia, orbital inflammation, and orbital cellulitis, etc.

　　3. Arthritis:Arthritis is a common manifestation of inflammatory bowel disease, characterized mainly by two types: peripheral arthritis and sacroiliitis and spondylitis.

　　Periparticular arthritis usually appears six months to several years after the occurrence of intestinal lesions, and in a few patients, arthritis can occur before or simultaneously with intestinal lesions. Arthritis often presents acutely, characterized by oligoarthritis or monoarthritis, with any joint being susceptible, but the knee and ankle joints are most commonly affected. Arthritis commonly manifests as joint erythema, swelling, and pain, which may be migratory. The inflammation generally lasts for 1 to 2 months, with a few cases lasting more than a year. Generally, it does not leave permanent joint damage. There is often a close correlation between arthritis and intestinal lesions, and it is more common in patients with other systemic diseases (such as skin lesions, oral ulcers, uveitis, etc.). In patients with ulcerative colitis, those with colonic involvement are more prone to arthritis than those with only rectal involvement. In Crohn's disease patients, those with colonic involvement are more prone to arthritis than those with small intestinal involvement.

　　The incidence of sacroiliitis and spondylitis is roughly similar to that of peripheral arthritis, and their clinical manifestations are similar to those caused by ankylosing spondylitis. Their progression is not obviously related to intestinal lesions. Patients with this kind of arthritis are mostly positive for HLA-B27 antigen, prone to uveitis, especially prone to acute non-granulomatous anterior uveitis.

　　Four, other changes

　　1. Skin lesions:The skin lesions caused by inflammatory bowel disease mainly manifest in two types, one is nodular erythema, and the other is necrotizing pyoderma, and these skin lesions are mainly caused by vasculitis of small blood vessels.

　　2. Oral ulcers:This disease can also cause oral ulcers, but the incidence rate is low, about 4.9%, manifested as painful oral ulcers.

　　The main prevention is to maintain a pleasant mood, avoid excessive emotional fluctuations, and the main trigger factor for glaucoma is long-term adverse mental stimulation, such as bad temper, depression, anxiety, and fear. Live a regular life, combine work and rest, do moderate physical exercise, do not participate in intense sports, maintain sleep quality, eat light and nutritious food, refrain from smoking and drinking, avoid strong tea and coffee, pay attention to eye hygiene, protect eyes, do not read under strong light, do not stay in a dark room for too long, and the light must be sufficient and soft, do not overuse eyes.

　　1. Routine stool examination:Clarify whether there is mixed blood, pus, and mucus, and pay attention to the nature of stool.

　　2. Routine blood and electrolyte tests:Clarify whether there is electrolyte disorder and anemia.

　　3. Ulcerative colitis:The lesions mainly involve the rectum and sigmoid colon, and can also extend to the entire colon. In the early stage, the intestinal mucosa is edematous, congested, and bleeding, initially forming superficial small ulcers, which then fuse into large ulcers with inflammatory exudates on the surface; there is cell infiltration at the edge of the ulcers, mainly lymphocytes and plasma cells, and a large number of neutrophils can be seen when there is secondary infection.

　　4. Granulomatous ileocolitis (Crohn's disease):It mainly involves the distal ileum, with the basic lesion being granuloma. During the acute phase, there is edema and congestion of the intestinal wall, dilatation of veins and capillaries, and serous exudation. During the chronic phase, there is a large amount of granulomatous hyperplasia and lymphoid tissue hyperplasia in the submucosa, infiltration of lymphocytes and plasma cells, and may also be macrophages, fibrosis or calcification, but without caseous necrosis.

　　5. Sacroiliac joint X-ray examination:exclude its inflammation.

　　6. Slit lamp examination and fundus examination of the eyes:Can clearly identify the anterior uveitis lesion, fundus examination can clearly identify the choroidal and fundus lesions.

　　1. Gypsum Congee:50g of raw gypsum, 100g of glutinous rice. First, the gypsum is decocted for half an hour, then the residue is removed and the glutinous rice is cooked into congee. Take one dose per day. It can release heat and cool the body, relieve thirst, and is suitable for patients with eye redness and pain, and dry mouth.

　　2. Er Ren Congee:30g of raw Coix seed, 6g of bitter almond (crushed), 100g of glutinous rice. The three ingredients are cooked together in water until the rice is cooked and the congee is thick, and then it can be eaten. Take one dose per day. It can clear heat and drain dampness, promote the flow of Qi, and is suitable for recurrent uveitis.

　　First, treatment

　　1. Treatment of systemic lesions:Intestinal lesions in inflammatory bowel disease are generally treated with corticosteroids or sulfasalazine. In severe cases, methotrexate, azathioprine, cyclophosphamide, benzyloxazone, cyclosporine, mycophenolate mofetil, tumor necrosis factor antibody, or soluble tumor necrosis factor receptor may be used. Due to the absorption disorders caused by intestinal lesions, patients may experience anemia, electrolyte disorders, and nutritional disorders, which should be corrected during treatment. For severe and refractory intestinal lesions, consideration may be given to surgical resection of the affected intestinal tract.

　　Gastrointestinal manifestations caused by inflammatory bowel disease belong to the categories of 'Diarrhea', 'Loose stools', 'Runny stools', 'Borborygmus', and 'Dysentery' in traditional Chinese medicine. Traditional Chinese medicine has a good therapeutic effect on intestinal lesions. According to TCM differentiation, it can be roughly divided into damp-heat type, spleen deficiency type, deficiency and sinking of middle Qi type, spleen and kidney Yang deficiency type, and liver Qi stagnation type.

　　(1) Damp-heat type: Symptoms include abdominal绞痛, diarrhea at the time of pain, or with mucus or pus in stools, tenesmus, burning sensation around the anus, restlessness, thirst, short and dark urine. This type is more common in the early stage of inflammatory bowel disease. Treatment principle: Clear heat and drain dampness, promote Qi and relieve pain. Prescriptions: 10g of Scutellaria, 15g of Pulsatilla, 10g of Pueraria, 8g of Coptis, 12g of Coix, 12g of Plantago, 10g of Magnolia, 6g of Moschus, 3g of Licorice.

　　(2) Spleen deficiency type: Symptoms include loose stools, or with indigestible food residue, or with pus and blood in stools, fatigue and lack of strength, decreased appetite, abdominal distension or pain that is preferred to be pressed, pale yellow complexion, pale tongue with thin white fur, and slow and weak pulse. This type is more common in patients with recurrent inflammatory bowel disease. Treatment principle: Strengthen the spleen and tonify Qi. Prescriptions: 15g of Codonopsis, 15g of Atractylodes, 12g of Poria, 15g of Yam, 12g of Dolichos, 12g of Coix, 8g of Tangerine peel, 8g of Amomum, 9g of Alisma, 3g of Licorice.

　　(3) Deficiency and sinking of middle Qi: Symptoms include loose stools, frequent diarrhea or incontinence, shortness of breath, lack of strength, pale and without luster complexion, pale tongue with thin white fur, and weak pulse. Treatment principle: tonify the middle and strengthen Qi, astringe and consolidate. Prescriptions: 15g of Codonopsis, 12g of Atractylodes, 12g of Poria, 12g of Bupleurum, 12g of Cimicifuga, 15g of Yam, 20g of Haematite, 9g of Voung, 5g of Myrobalan (roasted), 5g of Moschus, 20g of Dragon bone, 20g of Oyster shell, 3g of Licorice.

　　(4) Spleen and Kidney Yang Deficiency Type: Symptoms include abdominal pain and intestinal sounds before dawn, pain leads to diarrhea, comfortable after diarrhea, cold limbs, fatigue, softness of the waist and knees, pale tongue, deep and fine pulse. Treatment principle: Warm the spleen and kidney, astringe and stop diarrhea. Formula: Eucommia 12g, Schisandra 12g, Prepared Aconite 9g, Codonopsis 12g, Cinnamon 3g, Dragon Bone 20g, Oyster 20g, Nutmeg 6g, Licorice 3g.

　　(5) Liver Qi Stagnation Type: Symptoms include irritability and anger, anger leads to diarrhea or purulent blood, frequent intestinal sounds, abdominal pain, and flatulence, fullness in the ribs, belching, nausea, lack of appetite, red tongue with thin white fur, wiry pulse. Treatment principle: Soothe the liver and regulate the qi, strengthen the spleen. Formula: Bupleurum 12g, White Peony 10g, only shell 10g, White Atractylodes 10g, Yunling 10g, Green Tangerine Peel 9g, Orange Peel 9g, Musk 5g, Green Barley 20g, Licorice 3g. Add Scutellaria 10g and Gardenia 10g for liver stagnation transforming into heat.

　　Arthritis is usually treated with corticosteroids and non-steroidal anti-inflammatory drugs, resection of the diseased intestinal tract also has a relieving effect on arthritis, and traditional Chinese medicine and herbs also have a good therapeutic effect on arthritis.

　　2. Treatment of uveitis

　　(1) Anterior uveitis: For acute severe anterior uveitis, 0.1% dexamethasone eye drops can be used to instill the eyes, 6-12 times/d;普拉洛芬眼药水点眼，6-8次/d；2% posterior tropicamide ointment or eye drops can be used to instill the eyes, 1-2 times/d; after the anterior uveitis is controlled, the frequency of instillation should be adjusted according to the severity of the inflammation; for patients with reactive optic disc edema or macular cystoid edema, short-term oral corticosteroids (prednisone 30-50mg/d) or subfascial injection of 2.5mg dexamethasone can be given, or non-steroidal anti-inflammatory drugs (such as indomethacin 50-100mg/d) can be used in combination with oral treatment; for patients with recurrent refractory anterior uveitis, oral corticosteroid treatment and (or) other immunosuppressive drugs (such as cyclophosphamide, phenylbutazone, cyclosporine, azathioprine, methotrexate, etc.) should be used.

　　(2) Intermediate, posterior, and panuveitis: For patients with intermediate uveitis, choroiditis, retinitis, retinal vasculitis, and other posterior segment involvement, long-term medication is generally required. Oral corticosteroids such as prednisone 40-60mg/d can be used first, taken in the morning, and gradually reduced in dose after the inflammation subsides, reaching 20mg/d should be treated for a period of time (usually more than 4 months), and then gradually reduced. If the treatment is ineffective, other immunosuppressive drugs such as phenylbutazone can be added or changed, taken orally at a dose of 0.05-0.1mg/(kg·d), this kind of treatment generally needs to be continued for more than half a year, sometimes more than a year; if the patient has arthritis, methotrexate can be taken orally at 7.5-1.5mg per week; cyclosporine, azathioprine, cyclophosphamide, and other immunosuppressive drugs can also be used. Studies have shown that biological agents targeting tumor necrosis factor have a good therapeutic effect on inflammatory bowel disease and its associated refractory uveitis.

　　For patients with serous retinal detachment and severe retinal vasculitis, high-dose corticosteroid treatment such as prednisone oral 1-1.2mg/(kg·d) should be given, and combined treatment with the aforementioned other immunosuppressants can also be considered.

　　For patients with refractory uveitis accompanied by severe intestinal lesions, resection of the diseased intestinal tract may improve uveitis and may reduce or prevent the recurrence of uveitis.

　　3. Other ocular lesions:Scleritis and periscleritis can be treated with corticosteroid eye drops (such as dexamethasone), non-steroidal anti-inflammatory drugs (such as piroxicam), and other eye drops. Intractable scleritis often requires oral corticosteroid treatment (prednisone 30-60mg/d) or combined treatment with azathioprine (100mg/d), cyclophosphamide (100mg/d), phenylbutazone [0.1mg/(kg·d)], and cyclosporine [2-5mg/(kg·d)].

　　Corneal lesions can be treated with corticosteroid eye drops, and optic neuritis, orbital inflammatory pseudotumor, and others can be treated with systemic corticosteroids or other immunosuppressants.

　　II. Prognosis

　　The prognosis of uveitis associated with inflammatory bowel disease mainly depends on whether the treatment is timely and correct, and whether complications occur. Generally speaking, most patients can obtain a good prognosis after proper treatment, and the recurrence of uncontrollable uveitis and secondary glaucoma can lead to vision loss.