Enteropathic Arthropathies

Updated: Feb 16, 2021
  • Author: Pierre Minerva, MD; Chief Editor: Herbert S Diamond, MD  more...
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Practice Essentials

The enteropathic arthropathies are a group of rheumatologic conditions that share a link to gastrointestinal (GI) pathology. However, the term typically refers to the inflammatory spondyloarthropathies associated with inflammatory bowel disease (IBD) and to reactive arthritis caused by bacterial (eg, Shigella, Salmonella, Campylobacter, Yersinia, Clostridium difficile) and parasitic (eg, Strongyloides stercoralis, Giardia lamblia, Ascaris lumbricoides, Cryptosporidium species) infections. (See Etiology.)

Psoriatic arthritis, ankylosing spondylitis (AS), and undifferentiated spondyloarthropathy are the other conditions included in the inflammatory spondyloarthropathies that share common clinical and possible etiologic features. (See Etiology and Presentation.)

Other GI conditions with musculoskeletal manifestations include the following:

Complications and prognosis

Complications of enteropathic arthropathy are primarily related to IBD and include the following:

  • Chronic arthritis - Occasionally extra-articular involvement (uveitis)
  • Secondary amyloidosis - Mainly with Crohn disease ( CD)
  • Toxicity of therapy

Prognosis depends mainly on the prognosis of the underlying GI disease. Severe spinal inflammatory disease may occur, but this is rare. (See Etiology, Presentation, Treatment, and Medication.)



The precise causes of the enteropathic arthropathies are unknown. Inflammation of the GI tract may increase permeability, resulting in absorption of antigenic material, including bacterial antigens. These arthrogenic antigens may then localize in musculoskeletal tissues (including entheses and synovial membrane), thus eliciting an inflammatory response. Alternatively, an autoimmune response may be induced through molecular mimicry, in which the host's immune response to these antigens cross reacts with self-antigens in synovial membrane and other target organs.

Of particular interest is the strong association (80%) between reactive arthritis and human leukocyte antigen (HLA)-B27, an HLA class I molecule. A potentially arthrogenic, bacterially derived antigen peptide could fit in the antigen-presenting groove of the B27 molecule, resulting in a CD8+ T-cell response. HLA-B27 transgenic rats develop features of enteropathic arthropathy with arthritis and gut inflammation.

Sacroiliitis and spondylitis are associated with HLA-B27 (40% and 60%, respectively). HLA-B27 is not associated with peripheral arthritis, with the exception of reactive arthritis.

HLA accounts only for 40% of the genetic risk for spondyloarthropathy (SpA); other polymorphisms in non-HLA genes, involved in innate immune recognition and cytokine signaling pathways, are linked with SpA. [1] Such genes include tumor necrosis factor (TNF) and IL-23, which are shared with IBD and psoriasis. [2]



Occurrence in the United States

The prevalence of ulcerative colitis (UC) and Crohn disease (CD) is estimated to be 0.05-0.1%, with an increasing incidence for each in the last few decades. While extraintestinal manifestations affecting the skin, eyes, and joints, among other systems, develop in about one quarter of patients with IBD, musculoskeletal manifestations are the most common, with approximately 5-20% of individuals with IBD developing peripheral arthritis and/or spondylitis.

The prevalence of IBD in ankylosing spondylitis (AS) is 5-10%, although up to one third to two thirds of patients with AS have been found through colonoscopy to have subclinical inflammation. Axial involvement occurs more commonly in CD than in UC.

International occurrence

The incidence rates of spondyloarthropathy (SpA) vary between 0.48 and 63 per 100,000 population, whereas the prevalence ranges from 0.01 to 2.5%. [2]  The incidence and prevalence rates for UC and CD in northern and western Europe are similar to those in the United States, but rates are lower in other regions of the world.

In a systematic review, Ajene and colleagues estimated that the weighted mean global incidence of reactive arthritis with cases of each of the following infections was as follows [3] :

  • Campylobacter - Nine per 1000

  • Salmonella - 12 per 1000

  • Shigella - 12 per 1000

In an Italian study of 269 patients with IBD and joint pain, the prevalence of enteropathic-related spondyloarthritis (ESpA) was 50.5%. ESpA patients showed a peripheral involvement in 53% of cases, axial in 20.6% and peripheral and axial in 26.4% of cases. [4]

Race-, sex-, and age-related demographics

The incidence of IBD is higher in whites, especially those of Ashkenazi Jewish descent, than in other racial groups. SpA affects both sexes with equal frequency, but axial involvement is more frequent in men. [2]

The peripheral arthritis of UC or CD does not have a sex predilection. IBD-associated AS occurs equally in men and women, while idiopathic AS is 2.5 times more common in men. [5] Whipple disease is more common in men, with a male-to-female ratio of 9:1.

IBD is most common in persons aged 15-35 years. Axial involvement in IBD occurs at any age, in contrast to idiopathic AS, which affects men younger than 40 years.

Sofia and colleagues found significant differences in extraintestinal manifestations and disease characteristics between African-American and Caucasian IBD patients in a cross-sectional study of 1235 CD patients and 541 UC patients. African-American CD patients had higher rates of IBD-related arthralgias and surgery and less ileal involvement than Caucasian patients. African-American UC patients were older at diagnosis than Caucasian UC patients and had higher rates of arthralgias and ankylosing spondylitis/sacroiliitis. [6]