In recent years, research related to digestive system diseases has focused on autoimmune-mediated gastrointestinal tract injury. These include systemic rheumatic immune diseases with GI tract injury, autoimmune diseases of the digestive system and autoimmune diseases represented independently by autoantibody positivity, such as IgG4-related GI tract injury.
Systemic rheumatologic diseases can involve all systems including respiratory, circulatory, digestive, urinary, cutaneous, and neurological systems. The representative diseases include systemic lupus erythematosus, leukoaraiosis, multiple sclerosis, scleroderma, ankylosing spondylitis, and vasculitis, all of which have GI tract involvement. It can be said that vasculitis is both a consequence of systemic rheumatologic diseases and a pathological basis for systemic immunologic diseases involving all organs of the body. The involvement of the digestive tract in major systemic rheumatologic diseases is seen
From ancient times to the present, human beings have had a fear of disease and a desire for longevity. As early as the Qin Dynasty, the First Emperor completed the unification of China and became invincible, and death became the only worry. In order to achieve immortality, he spent huge sums of money and sent a fleet of ships to the East China Sea to look for immortal herbs, and finally woke up and scattered his dreams, and said goodbye to the earth and buried his soldiers and horses together.
Inflammatory bowel disease and leukoaraiosis, standardized treatment but difficult to confirm diagnosis Since the diagnostic criteria for inflammatory bowel disease and leukoaraiosis are developed by gastroenterologists and immunologists respectively, it leads to an incomplete understanding of these diseases. Therefore, the applicability of the current diagnostic criteria is questionable and should attract the joint attention of physicians from both disciplines.
Due to the numerous symptoms and complex manifestations of systemic rheumatic immune diseases and the fact that hormones and other commonly used drugs can cause damage to the gastrointestinal tract during treatment, systemic immune diseases that start with gastrointestinal symptoms or develop gastrointestinal symptoms during the course of the disease are common in clinical practice. Among them, it is difficult to distinguish between the intestinal damage of leukoaraiosis and Crohn’s disease, which has become a difficult point of clinical differential diagnosis.
Analysis of clinical data of 43 patients with leukoaraiosis at the Peking University People’s Hospital revealed that the duration of disease spanned from the appearance of GI clinical symptoms to diagnosis, ranging from half a month to 40 years, with an average disease duration of (111.7±129.4) months.
The most common and prominent symptoms were diarrhea (55.8%) and abdominal pain (51.2%). In contrast to Crohn’s disease, clinical manifestations, autoantibodies, markers of inflammatory activity, immunoglobulins, complement levels, microscopic manifestations, and pathologic hints were not characteristic in this group of patients, whereas less than 20% of the pathologic manifestations of vasculitis and Crohn’s disease non-caseating granulomatous inflammatory pathology, which are considered characteristic of leukoencephalopathy, were observed.
However, these two diseases are not easily mismanaged. The international therapeutic agents for both leukoaraiosis and Crohn’s disease are hormones, immunosuppressants, tumor necrosis factor-α antagonists and thalidomide. This suggests that the two diseases may share a common pathogenesis and may be the result of damage to the organism by the same immune injury. Therefore, patients clinically diagnosed with inflammatory bowel disease or leukoaraiosis have the possibility of misdiagnosis and should be followed up for a long time.
Treatment of ankylosing spondylitis, GI tract involvement is common, and treatment of co-morbidities tends to mask the primary disease
In recent years, the GI tract manifestations of ankylosing spondylitis have received much attention. Currently, 2.6% and 6% of patients with ankylosing spondylitis have coexisting ulcerative colitis or Crohn’s disease, respectively; it has also been reported that 10% of patients with ankylosing spondylitis have enteroscopic bowel inflammation.
Studies have shown that patients with co-morbidities have the following characteristics.
(1) 60% of patients with ankylosing spondylitis undergoing colonoscopy have microscopic signs of intestinal inflammation but no GI discomfort;
(2) Only 27% of ankylosing spondylitis patients with endoscopic presence of intestinal inflammation had GI symptoms;
(3) Patients with ankylosing spondylitis with normal intestinal pathology are more likely to be in remission, which is a sign of a better prognosis;
(4) Patients with ankylosing spondylitis who have intestinal inflammatory activity have more joint inflammation;
(5) When ankylosing spondylitis is combined with chronic inflammatory bowel disease, it is more important to treat the intestinal lesions because they can indirectly induce remission of the joint lesions.
This suggests that a high proportion of ankylosing spondylitis combined with chronic inflammatory bowel disease may be without intestinal symptoms in the early stages; patients with ankylosing spondylitis should try to undergo colonoscopy and actively treat intestinal lesions if there are positive indications.
Another study showed that 2.6% of ulcerative colitis is combined with ankylosing spondylitis; 6% of Crohn’s disease is combined with ankylosing spondylitis; 14% to 46% of chronic inflammatory bowel disease has imaging sacroiliac arthritis but no joint discomfort symptoms. This also suggests that chronic inflammatory bowel disease combined with ankylosing spondylitis has a high rate, and that patients with chronic inflammatory bowel disease should be improved with joint imaging.
Targeted treatment has its own focus
Ankylosing spondylitis: methotrexate, leflunomide (effective for ankylosing spondylitis, poor for Crohn’s disease) and non-steroidal anti-inflammatory drugs can be used, the latter has an analgesic and anti-inflammatory effect on ankylosing spondylitis, which is effective, but prone to induce gastrointestinal ulcers, bleeding and activation of chronic inflammatory bowel disease. Lyuzosulfapyridine is effective for mild to moderate Crohn’s disease induced remission, and also relieves peripheral joint pain in ankylosing spondylitis, but may have little effect on spinal symptoms and function.
Crohn’s disease: hormones, mesalazine and azathioprine are available. The former can relieve Crohn’s disease and relieve joint pain in ankylosing spondylitis with shock therapy, but oral hormones cannot stop the progression of ankylosing spondylitis; the latter two are effective in treating Crohn’s disease and respond poorly to ankylosing spondylitis.
IgG4-associated digestive tract diseases, with emphasis on differentiation
It is currently believed that digestive autoimmune disease-mediated intestinal injury has the following main causes.
(1) damage to the intestine by abnormally activated T cells;
(2) intestinal damage caused by blood vessels;
(3) inflammatory immune mediator-mediated intestinal injury;
(4) Damage to intestinal mucosa by abnormal antibodies;
(5) damage to the intestine by therapeutic drugs such as NSAIDs. There are also immune-related factors.
Among them, the involvement of humoral immunity in intestinal immune damage includes two pathways.
One is direct immune damage to intestinal epithelial cells by autoantibodies through cross-immunity;
T cells and their associated cytokines play an important role in the key steps of mucosal injury and immune damage.
In 2010, the definition of IgG4-associated diseases was first standardized as a group of “chronic, progressive autoimmune diseases associated with IgG4 and involving multiple organs or tissues”. The phenotypes of the disease are diverse, including Mikulis disease, autoimmune pancreatitis, interstitial nephritis, and retroperitoneal fibrosis. Due to the unique clinical and pathological manifestations, IgG4-associated diseases have received increasing attention and attention from the academic community in recent years.
Pathogenesis: Foreign studies have shown that elevated IgG4 levels can also be observed in the serum of patients with primary sclerosing cholangitis and chronic inflammatory bowel disease, and the specific mechanism has not been reported. These phenomena suggest that elevated IgG4 levels indicate abnormal immune function in the body, and this may provide new ideas for the study of systemic autoimmune diseases and then help to explore new methods of diagnosis and treatment.
Involved organs The pancreas is the most commonly involved organ in IgG4-related diseases and is often referred to as “autoimmune pancreatitis”. The main clinical manifestations are diffuse enlargement of the pancreas and extensive stenosis of the pancreatic duct. In addition, various glands such as the lacrimal gland, salivary gland and thyroid gland can be the target organs of IgG4-related diseases.
Serologic diagnosis: Serum IgG4 levels have high sensitivity (95%) and specificity (97%) for the diagnosis of the disease, but elevated serum IgG4 levels alone cannot confirm the diagnosis of IgG4-associated disease, and primary cholangitis, pancreatic cancer, and acute pancreatitis should be excluded, even in healthy individuals (3%-10% of healthy individuals have elevated serum IgG4).
Histological features: IgG4-associated pancreatic lesions have typical histological features, including diffuse interstitial fibrosis of the pancreas in a radial pattern, involvement of the portal vein leading to occlusive phlebitis, atrophy of the pancreatic alveoli, and inflammatory cell infiltration of the pancreatic tissue. The above histological examinations should be performed if available, which are important in confirming the diagnosis of the disease.