ENTEROPATHIC ARTHRITIS
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
Εtiology
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.
Epidemiology
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.
Race-, sex-, and age-related demographics
The incidence of IBD is higher in whites, especially those of Jewish descent, than
in other racial groups.
IBD-associated arthropathies
Axial arthritis (sacroiliitis and spondylitis) in inflammatory bowel disease (IBD)
has the following characteristics:
- Insidious onset of low back pain, especially in younger persons
- Morning stiffness
- Exacerbated by prolonged sitting or standing
- Improved by moderate activity
- More common in Crohn disease (CD) than in ulcerative colitis (UC)
- Independent of GI symptoms
Peripheral arthritis in IBD demonstrates the following characteristics:
- Nondeforming and nonerosive
- More common in CD with colonic involvement than in UC
May precede intestinal involvement, but usually concomitant or subsequent to bowel
disease, as late as 10 years following the diagnosis
- Type 1 (pauciarticular [< 5 joints] Acute, self-limiting attacks, lasting less than
10 weeks; asymmetrical and affecting large joints, such as the knees, hips and shoulders;
strong correlation to IBD activity, most frequently with extensive UC or colonic
involvement in CD; associated with other extraintestinal manifestations of IBD
- Type 2 (polyarticular [>5 jointsChronic, lasting months to years; more likely symmetrical,
affecting small joints of the hands; independent of bowel activity
Enthesitis affects the following parts of the body:
- Heel - Insertion of the Achilles tendon and plantar fascia
- Knee - Tibial tuberosity, patella
- Others - Buttocks, foot
Extra-articular IBD demonstrates the following characteristics:
- Intestinal - Abdominal pain, weight loss, diarrhea, and hematochezia
- Skin - Pyoderma gangrenosum (in UC), erythema nodosum (in CD)
- Oral -Aphthous ulcers (in UC, CD)
- Ocular - Uveitis, anterior, nongranulomatous
- Systemic low-grade fever, secondary amyloidosis (in CD)
Physical Examination
The physical examination should include the following:
- Articular – (1) Examine the joints for signs of inflammation and note the pattern
and symmetry of involvement; (2) test the spine for range of motion, flexibility,
and sacroiliac tenderness; (3) look for periarticular soft-tissue swelling and/or
tenderness, especially at the heel (eg, enthesitis)
- Skin - Look for pyoderma gangrenosum (ulcerative colitis [UC]) and erythema nodosum
(Crohn disease [CD])
- Eyes - Look for acute anterior uveitis or conjunctivitis
Approach Considerations
Lab studies reveal the following:
Complete blood count (CBC) - May reveal iron deficiency anemia, leukocytosis, and
thrombocytosis
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentration -
Usually elevated
Rheumatoid factor (RF) - Absent
Synovial fluid analysis - Shows mild to moderate inflammatory fluid, mononuclear
cell predominance (often), negative cultures, and no crystals
Antiendomysial and antitransglutaminase antibodies - Usually elevated in celiac disease
Approach Considerations
Treatment of inflammatory bowel disease (IBD), including surgery, should always be
the initial strategy to induce remission of peripheral arthritis.
Although nonsteroidal anti-inflammatory drugs (NSAIDs) are usually recommended as
first-line therapy for spondyloarthropathies, in patients with IBD, these agents
may exacerbate GI symptoms.Selection of more cyclooxygenase (COX)-selective NSAIDs
may reduce the risk of bowel flares.Corticosteroids may be used systemically or by
local injection.
Sulfasalazine (2-3g/day) has been shown to be effective for treatment of the peripheral
arthropathy associated with IBD, but not axial disease. While methotrexate can be
useful to treat bowel activity in Crohn disease (CD), its effect on joint disease
with IBD is less certain.
Although not specifically indicated for an enteropathic arthropathy, the tumor necrosis
factor (TNF) antagonists infliximab and adalimumab are indicated to treat ankylosing
spondylitis (AS) and IBD, and may be effective for IBD spondyloarthropathy (including
axial involvement).Etanercept and golimumab are indicated to treat AS, but neither
has been shown to be helpful with bowel disease, and there have been reports of new-onset
IBD with these 2 agents.
Whipple disease is treated with long-term tetracycline antibiotics. Celiac disease
is treated with a gluten-free diet, although response is not always complete.