In addition to chronic diarrhea, you must know these 4 common extraintestinal manifestations of IBD

*Only for medical professionals to read for reference.
In ancient Greece, ulcerative colitis appeared as "chronic diarrhea".
Today, our understanding of it is no longer limited to the intestine
.

 Inflammatory bowel disease (IBD) was once considered a disease limited to the intestinal tract
.

In recent decades, as scientists continue to explore its pathogenesis, and more and more cases of oral and skin lesions as the first manifestation have been reported, the mystery of IBD extraintestinal manifestations (EIMs) has gradually been unveiled
.

Can EIMs occur before intestinal lesions appear? Does the intestinal inflammation subside, does EIMs get better naturally? What is metastatic Crohn's disease (MCD)? October 14-19, 2021, the 9th Asian Inflammatory Bowel Disease Conference (AOCC) will be held in Guangzhou
.

Professor Wang Yufang from West China Hospital of Sichuan University gave a wonderful report on the extraintestinal manifestations of inflammatory bowel disease
.

Let us learn together
.

Three major features of EIMs 1.
EIMs can be an extension of intestinal inflammation or independent of intestinal inflammation.
Professor Wang first clarified the definition of EIMs to everyone
.

EIMs are inflammatory lesions outside the intestinal tract of patients with IBD.
The pathogenesis may be the extension or ectopic of the intestinal immune response, or it may be independent of intestinal inflammation, or share the same environmental or genetic factors with IBD
.

EIMs can affect multiple organs throughout the body, including bones, joints, eyes, skin, liver and gallbladder and other parts of the body
.

Professor Wang pointed out that epidemiological data show that 6%-47% of IBD patients suffer from at least one EIMs, such as arthritis, aphthous stomatitis, erythema nodosa, uveitis, ankylosing spondylitis, etc.
The incidence is higher
.

It can be seen that timely detection and standard treatment of EIMs has become an important part of IBD management
.

Figure 1.
The green ones are lesions with a higher incidence, and the blue ones are relatively rare lesions.
2.
EIMs can occur months or years before IBD.
Questions for everyone.
Professor Wang explained that EIMs and IBD are not specific.
Time sequence
.

It can occur with IBD, and it can also occur before or after IBD
.

Approximately 26% of EIMs occur before the diagnosis of IBD (median time 5 months)
.

Figure 2.
Time relationship between EIMs and IBD.
Figure 3.
Inflammatory activity of EIMs is not necessarily related to intestinal mucosal inflammatory activity.
For the relationship between EIMs inflammatory activity and intestinal mucosal inflammatory activity, Professor Wang pointed out that there are three main types : Related Parallel Course Independent Separate Course Uncertain May or May Not Parallel Figure 3.
The relationship between EIMs activity and IBD intestinal inflammation activity.
The treatment points of various EIMs.
Professor Wang focuses on common bone joints, skin, eyes, liver and gallbladder EIMs , Introduced the characteristics and treatment points of different parts of EIMs
.

▌ [EIMs of bones and joints] Professor Wang pointed out that bones and joints are the most common site of EIMs in patients with IBD.
About 46% of patients with IBD have EIMs of bones and joints
.

Bone joint EIMs can be divided into peripheral arthritis and axial arthritis
.

Among them, peripheral arthritis is divided into type 1 and type 2.
Axial arthritis mainly includes ankylosing spondylitis and sacroiliitis (Table 1)
.

Table 1.
Characteristics of arthritis EIMs Figure 4.
Peripheral arthritis type 1 Figure 5.
Peripheral arthritis type 2 Figure 6.
Ankylosing spondylitis Figure 7.
Sacroiliac arthritis Professor Wang said, the treatment of bone and joint EIMs The goal is to reduce inflammation, relieve pain and prevent disability
.

According to different types of arthritis, different treatment methods are adopted: peripheral arthritis has a better prognosis
.

Relief of type 1 intestinal inflammation is conducive to the alleviation of arthritis, and type 2 may persist even if the inflammation of the intestine is relieved
.

COX-2 inhibitors may aggravate inflammatory bowel disease, so it is not recommended
.

Sulfasalazine may be considered for patients with mild to moderate ulcerative colitis combined with peripheral arthritis
.

Hormones can be used for short-term, but not as a maintenance remission treatment
.

Patients with persistent peripheral arthritis may consider using MTX or anti-tumor necrosis factor preparations
.

The prognosis of axial arthritis is poor, and early selection of anti-tumor necrosis factor preparations should be considered
.

Newer treatments, such as UST (Usnuzumab) are effective for peripheral arthritis, but are not effective for spondyloarthritis
.

It is also reported that Tofacitinib (tofacitinib) and Upadacitinib (upatinib) also have a certain effect on peripheral arthritis
.

▌ [Skin EIMs] Professor Wang pointed out that skin EIMs have various manifestations, which can be summarized into four categories: related skin and mucosal manifestations, reactive mucosal mucosal manifestations, specific mucosal mucosal manifestations, and skin lesions caused by IBD drugs
.

Among them, each category contains many types of skin lesions
.

Figure 8.
Related skin manifestations: oral aphthous ulcer, nodular erythema, psoriasis, acquired epidermolysis bullosa Figure 9.
Reactive skin manifestations: gangrenous pyoderma, acute febrile neutral Granulocyte skin disease (Sweet's syndrome)
.

Reactive skin manifestations often have one or more pathophysiological mechanisms related to IBD
.

Theoretically, it is the cross-reactive antigenicity between skin and intestinal mucosa
.

The histological feature is that the specific skin and mucosal manifestations of diffuse infiltrating mature neutrophils mainly include persistent CD and metastatic CD, which have the same histopathological characteristics as CD, such as noncaseating granuloma
.

Figure 10.
Persistent CD mainly manifests as oral and perianal lesions, which can be manifested as ulcers, paving stone changes, anal fistulas, etc.
Figure 11.
In the special skin and mucosal manifestations, metastatic CD mainly occurs in the limbs, which can be manifested as plaques, Nodules, ulcers, abscesses
.

The severity of metastatic disease often has nothing to do with the degree of inflammation of intestinal disease, and the response to treatment is slower than the response to intestinal disease.
Figure 12.
Skin EIMs caused by drugs: Anti-TNF antibodies cause psoriasis is more common, and the incidence is about 3%-10%
.

It is more common during maintenance treatment, and the disease can occur within 1 month of the beginning of treatment
.

Smoking and overweight are risk factors.
Because of the various manifestations of skin EIMs, the diagnosis is mainly based on the characteristics of the skin lesions.
Atypical cases can be diagnosed with the help of skin biopsy
.

The treatment of skin EIMs is mainly to control systemic or local inflammation.
Different types of skin EIMs have slightly different treatment methods.
Some skin manifestations such as erythema nodosum and Sweet's syndrome are mostly related to the activity of intestinal lesions.
Treatment goals Mainly to control intestinal inflammation, but the relationship between pyoderma gangrenosum and intestinal inflammation is not clear (Table 2)
.

Table 2.
Main types of skin EIM and treatment options.
Studies have shown that UST is effective in different IBD skin lesions, such as MCD, pyoderma gangrenosum, and erythema nodosa
.

Vedolizumab VDZ is not effective for skin EIMs whose activity is not related to intestinal inflammation
.

▌ 【EIMs of the eye】Professor Wang classified the EIMs of the eyes into three types: episcleritis, scleritis and uveitis
.

Figure 13.
Three types of ocular EIMs: Episcleritis is more common in patients with CD, and its inflammatory activity is related to intestinal inflammatory activity
.

Scleritis is relatively rare, and its inflammatory activity is related to intestinal inflammatory activity
.

Uveitis is more common in patients with UC.
Its inflammatory activity has nothing to do with intestinal inflammatory activity.
The diagnosis of ocular EIMs mainly relies on ocular symptoms, specialist physical examination, slit lamp and other specialist examinations, and usually requires the assistance of an ophthalmologist for diagnosis and treatment
.

Treatment of ocular EIMs: Episclerositis can be relieved after controlling intestinal inflammation and topical application of artificial tears
.

Scleritis can be treated with COX2 inhibitors, corticosteroids, immunosuppressants, and anti-TNF-a biological agents based on the severity
.

Uveitis usually requires topical corticosteroid therapy.
Those who fail can take oral corticosteroids, immunosuppressive agents or anti-TNF-a biological agents
.

▌ [Hepatobiliary EIMs] Professor Wang said that primary sclerosing cholangitis (PSC) is the most typical extraintestinal manifestation of IBD in hepatobiliary EIMs
.

According to reports, 60%-80% of PSC patients can be combined with IBD, and 5% of UC patients can be combined with PSC
.

PSC is rare in patients with CD
.

Male, total colonic UC, non-smoker and history of appendectomy are risk factors for PSC in IBD patients
.

PSC increases the risk of colorectal cancer in patients with IBD by 10 times
.

The diagnosis of PSC is mainly based on the elevated serum AKP and GGT, and the imaging characteristics of MRCP/ERCP
.

Figure 14.
ERCP of PSC showed irregular segmental stenosis and dilatation of intrahepatic and extrahepatic bile ducts
.

Bile duct stricture caused by secondary factors (such as infection, immunodeficiency, ischemia, pancreatic disease and IgG4-related diseases, etc.
) should be excluded during diagnosis.
Although the diagnosis of PSC can be confirmed by imaging methods, unfortunately, there is no specific treatment for PSC.
Although ursodeoxycholic acid is often used clinically, it can partially improve liver function, but it has no significant effect on improving the prognosis
.

Professor Wang pointed out that ERCP is still the first choice for the treatment of severe bile duct strictures
.

Endoscopic treatment can dilate narrow bile ducts, and cholecystectomy should be performed in time when the gallbladder polyps are accompanied by malignant tendencies
.

▌ [Rare EIMs] In addition to the more common EIMs mentioned above, Professor Wang also summarized several rare EIMs, such as pancreatitis and respiratory diseases
.

Figure 15.
The diagnosis of respiratory tract EIMs bronchopulmonary disease depends on clinical manifestations and imaging examinations.
It needs to be differentiated from opportunistic lung infections caused by hormones and immunosuppressants.
If necessary, bronchoalveolar lavage and lung biopsy can be used to confirm the diagnosis
.

Hormones are effective in the treatment of most respiratory diseases related to IBD
.

Inhaled corticosteroids are the first choice.
Systemic corticosteroids are used for airway diseases that are physically affected and resistant to inhaled corticosteroids
.

Patients with hormone resistance or high-dose hormone-dependent refractory lung disease can choose immunosuppressive agents or biological agents for treatment
.

Finally, Professor Wang concluded: (1) About 6%-47% of IBD patients suffer from related EIMs, with bone and joint manifestations being the most common, followed by skin, eyes and liver and gallbladder; (2) In mobility and IBD intestines In EIMs related to tract inflammation, adequate IBD treatment is usually sufficient to improve the symptoms of ElМs; (3) In EIMs whose activity is not related to IBD intestinal inflammation, multidisciplinary treatment methods are usually required; (4) Clinicians must learn Identify EIMs in different parts of the body of patients with IBD, so as to make timely diagnosis and standard treatment
.

  Expert Profile Professor Wang Yufang, Chief Physician and Doctoral Supervisor, Department of Gastroenterology, West China Hospital, Sichuan University, Member of the Asian Crohn's Disease and Colitis Association (AOCC) Epidemiological Society, Deputy Leader of the IBD Group of the Chinese Medical Association Digestive Branch, Sichuan Medical Association The leader of the academic technology of the Sichuan Provincial Health Commission has long been committed to the study of the clinical and pathogenesis of IBD.
"Chinese Journal of Inflammatory Bowel Disease", "Chinese Journal of Practical Internal Medicine" and other journals have gone to Kiel University, Germany for advanced studies, responsible for and Mainly research a number of topics such as the National Natural Science Foundation of China, National Major R&D Projects, Sino-German International Cooperation Projects, and National Science and Technology Support Programs