It refers to arthritis caused by two inflammatory bowel diseases, ulcerative colitis and Crohn’s disease.
Enteropathic arthritis is immune-related, often invades the joints of the extremities and spine, and the joints involved are predominantly large joints of the lower extremities and have a unilateral, asymmetric character with negative rheumatoid factor in the blood. Therefore, together with ankylosing spondylitis, reactive arthritis (Reiter’s syndrome), and psoriatic arthritis, they are included in seronegative spondyloarthropathies.
Etiology and pathogenesis
The etiology of enteropathic arthritis is unclear, and the available evidence suggests that genetic factors and alterations in intestinal permeability play an important role in the pathogenesis.
Genetic factors are important susceptibility factors for enteropathic arthritis. Transgenic mice and rats transgenic for the human HLA-B27 gene show manifestations of human spondyloarthropathy, yet they do not develop the disease in a germ-free environment. Knockout mice suggest that IL-2, IL-10, and transfer growth factor-β may be protective factors, while HLA-B27 may affect cytokine expression. Increased intestinal permeability has been shown to be an important factor in the pathogenesis of enteropathic arthritis, and the effect of environmental factors on permeability may be mediated, in part, by bacterial endotoxins.
Clinical manifestations
I. Peripheral joint involvement
Peripheral arthritis occurs in approximately 10-20% of patients in most studies, slightly more in Crohn’s disease than in ulcerative colitis. Arthritis is often nondestructive and reversible, but erosive destruction can occur. Information on the histopathologic manifestations is very limited, with reports suggesting that Crohn’s disease is a granulomatous manifestation, whereas ulcerative colitis is a nonspecific synovitis. In Crohn’s disease, septic hip has been reported, presenting as a rapidly destroyed joint requiring surgical treatment. In ulcerative colitis, joint symptoms tend to be consistent with bowel disease activity, but not necessarily in Crohn’s disease. Total colectomy in half of the patients with ulcerative colitis is associated with remission of arthritis, but paradoxically arthritis also occurs after surgery. This may be a result of short-circuiting arthritis due to altered gut microbiology. Peripheral arthropathy has been reported in almost every 1000 patients with ulcerative colitis and in every 500 patients with Crohn’s disease. Peripheral arthropathy is classified into 2 types, one with oligoarthritis or type 1 (less than 5 joints) and the other with polyarthritis or type 2 (more than 5 joints). The most commonly involved joints are, in order, the metatarsophalangeal, proximal interphalangeal, knee, and ankle joints. Shoulder involvement is more common in ulcerative colitis, and joint involvement is significantly similar in both. Importantly, most patients with type 1 have an acute onset and tend to resolve within 6 weeks, whereas type 2 patients often have persistent disease.
II. Mesial joint involvement
Spinal involvement occurs in 10-20% of patients. It can be asymptomatic, precede the onset of inflammatory bowel disease or appear later. Unlike ankylosing spondylitis, they do not differ by gender. Overall, the spinal involvement in inflammatory bowel disease is similar, if not identical, to that of typical ankylosing spondylitis. There are reports of milder lesions and more square changes in patients with enteropathy, but the vast majority of radiological presentations are not different. The symptomatic presentation of spinal involvement does not vary with the activity of bowel disease. The idiopathic sacroiliac arthritis is often asymptomatic and is not associated with HLA-B27.
III. Other manifestations
Mortar and pestle fingers, uveitis and skin manifestations are seen in inflammatory bowel disease and occur more frequently in Crohn’s disease. Necrotizing pyoderma is a painful ulcerative skin reaction often associated with systemic disease. Erythema nodosum is most likely the body’s response to the systemic manifestations of microbial infection. Studies have shown that erythema nodosum is associated with oligoarthritis. Erythema pigmentosum is a common extra-articular manifestation of spondyloarthropathies, commonly seen in ankylosing spondylitis and reactive arthritis, while in patients with inflammatory bowel disease, erythema pigmentosum is more bilateral, has a more chronic course than ankylosing spondylitis and reactive arthritis, and is slower to respond to topical corticosteroid therapy. As with rheumatoid arthritis, the incidence of amyloidosis in patients with inflammatory bowel disease is very low.
Diagnosis and differential diagnosis
I. Diagnosis
There are no uniform diagnostic criteria for enteropathic arthritis, as the associated arthritis is often of no particular diagnostic value, and therefore the diagnosis of inflammatory bowel disease-associated arthritis can only be made after the diagnosis of ulcerative colitis or Crohn’s disease, based on the accompanying inflammatory spinal manifestations and/or peripheral arthritis. In cases where the manifestations of arthritis or spondylitis precede the manifestations of inflammatory bowel disease, the diagnosis of enteropathic arthritis cannot be made until the inflammatory bowel disease is confirmed. It is important to note that the arthritis associated with inflammatory bowel disease is relatively mild, and patients are often seen in gastroenterology because of intestinal manifestations, and gastroenterologists tend to pay attention to the patient’s digestive problems, thus ignoring joint pathology and leaving enteropathic arthritis undiagnosed for a long time. Therefore, for patients with inflammatory bowel disease with arthritic manifestations or arthritic patients with intestinal symptoms, it is best to be seen by both gastroenterologists and rheumatologists in order not to misdiagnose or miss the diagnosis.
Differential diagnosis
1.Diarrhea as the prominent manifestation of the disease
It is necessary to differentiate from acute gastroenteritis and bacterial dysentery.
2. Diseases in which arthrosis is a prominent manifestation
(1) Ankylosing spondylitis: some patients may have intestinal manifestations, such as intermittent abdominal pain or diarrhea, which are mostly mild. These patients are easily suspected of having enteropathic arthritis, but fiberoptic colonoscopy of the intestine is mostly mild and non-specific inflammatory changes, which is most helpful in differentiation. In addition, a few patients with enteropathic arthritis may present with typical ankylosing spondylitis, or even be diagnosed with ankylosing spondylitis, and the diagnosis of ulcerative colitis or Crohn’s disease is confirmed only when intestinal manifestations are present and fiberoptic colonoscopy is performed.
(2) Reactive arthritis (including Reiter syndrome): Mostly in young men, arthritis mainly in the lower extremities develops 3 days to 1 month after diarrhea (dysentery), genitourinary tract or respiratory tract infection. At the time of prominent arthritic manifestations, intestinal and urinary tract symptoms have mostly disappeared. All these features help to differentiate from ulcerative colitis and Crohn’s disease.
(3) Undifferentiated spondyloarthropathy: Undifferentiated spondyloarthropathy also often has intestinal manifestations such as abdominal pain or diarrhea, but the intestinal lesions in undifferentiated spondyloarthropathy tend to be milder, nonspecific inflammatory changes that can be differentiated by fiberoptic enteroscopy.
(4) Behçet’s disease: It is often not difficult to diagnose and differentiate those with typical manifestations of Behçet’s disease, but for patients with Behçet’s disease with predominantly gastrointestinal manifestations (intestinal white stuffing), it is difficult to differentiate from Crohn’s disease or ulcerative colitis when there is significant abdominal pain, diarrhea, and bloody stools without a definite pinpoint response. Ulcerative colitis and Crohn’s disease also present with the same oral ulcers, vulvar ulcers, and uveitis as Behçet’s disease, but the painful oral and vulvar ulcers in Behçet’s disease are severe, whereas the ulcers in ulcerative colitis and Crohn’s disease are less painful. The most important difference is the difference in colonoscopic changes and pathology; Behçet’s disease is vasculitis in nature, ulcerative colitis presents with extensive inflammation of the mucosa, and Crohn’s disease is a granulomatous change.
Treatment
The principles of treatment for enteropathic arthritis are to control inflammation, eliminate intestinal symptoms, and protect joint function. Try to use drugs that are both good for the intestines and helpful for arthritis.
I. Treatment of intestinal lesions
1.Anti-cholinergic drugs: such as phenylephrine (Emmenthal) opioid tincture or codeine help to relieve abdominal pain and diarrhea symptoms.
2, broad-spectrum antibiotics: for patients with Crohn’s disease, as well as involving the large intestine or causing perianal abscesses or fistulas, toxic megacolon need to use broad-spectrum antibiotics, methotrexate most often used.
3. Salazosulfapyridine: This drug has proven its value in long-term treatment and is a drug that is both good for the intestines and helpful for arthritis. The drug has shown to inhibit the function of NF-κB, and therefore can extremely well affect the expression of pro-inflammatory factors. The dose used for intestinal inflammation is 3-6g/d in 3 doses, while the dose used for arthritis is relatively small, 2-3g/d in 2 doses. Similar drugs are 5-aminosalicylic acid.
4.Glucocorticoids: For patients with moderate to severe inflammatory bowel disease, they are used systemically only to control intestinal lesions. Among them, prednisone is most commonly used, 1-2mg / (kg d), and gradually reduce the amount after the disease control.
5.Immunosuppressants: In order to reduce the dosage of corticosteroids and control the disease, azathioprine and methotrexate are widely used, and the dosage is 50mg of azathioprine 1-2 times a day, and 7.5-15mg of methotrexate once a week.
II. Treatment of arthritic lesions
The clinical application of many drugs for the treatment of arthritis mainly comes from the experience of rheumatoid arthritis treatment, these drugs are effective in the control of arthritis, while the effect on intestinal lesions has not been studied.
1.Lyuzosulfapyridine: It can control intestinal lesions and inhibit the development of arthritis, and is the drug of choice for this group of diseases.
2.Penicillamine: 0.25g, once daily.
3.Anti-malarial drugs: chloroquine 0.25g, 1 time daily; hydroxychloroquine 0.2g, 2 times daily.
4.Small dose glucocorticoid: intra-articular injection or oral treatment can control peripheral synovitis, but it is not effective for medial joint involvement.
Third, biological agents
TNF-α inhibitor infliximab can provide significant relief of symptoms and long-term healing of intestinal damage in patients with Crohn’s disease. This was not the case for ulcerative colitis, which may explain its different pathogenesis. However, there is no strong evidence for their effect on joint symptoms in these patients.
IV. Non-steroidal anti-inflammatory drugs
The treatment of arthritis and spondylitis associated with inflammatory bowel disease is identical to that of ankylosing spondylitis, but the use of NSAIDs in enteropathic arthritis is controversial. NSAIDs are very effective in controlling joint pain, but they exacerbate the symptoms of ulcerative colitis because they inhibit prostaglandin synthesis in the colon.
V. Surgical treatment
Surgery of the intestinal tract is not an indication for the treatment of rheumatoid manifestations of inflammatory bowel disease, because surgery is helpful only for peripheral joints.