Crohn’s disease is a form of inflammatory bowel disease (IBD) characterized by chronic inflammation of the digestive tract. While its primary symptoms are gastrointestinal, the inflammation can affect other parts of the body, leading to non-digestive symptoms. These occurrences are known as extraintestinal manifestations (EIMs). They reflect the systemic nature of the underlying immune dysregulation and can significantly affect quality of life, appearing in up to one-third of patients.
The Link Between Gut Inflammation and Systemic Symptoms
The development of symptoms outside the intestine in Crohn’s disease stems from the same issue causing the bowel inflammation: a dysregulated immune response. Crohn’s is a systemic inflammatory condition, not merely a localized intestinal disorder. The immune system mistakenly attacks the digestive tract, and this inflammatory response can extend to or trigger parallel inflammation in other organ systems.
One proposed mechanism involves the loss of intestinal barrier integrity. When the gut lining is compromised by chronic inflammation, bacterial components can leak from the intestines into the bloodstream. This can provoke an immune reaction in distant parts of the body, such as the joints or skin.
Genetic factors also play a part, as certain genetic predispositions are shared between IBD and some EIMs. This suggests that for some individuals, the same inherited susceptibility for Crohn’s also makes them vulnerable to conditions like arthritis or skin disorders. These shared inflammatory pathways help explain why a disease centered in the gut can have widespread effects.
Common Musculoskeletal and Skin Manifestations
Among the most frequent extraintestinal manifestations are those affecting the joints and skin. Musculoskeletal issues are the most common EIM, ranging from mild joint pain (arthralgia) to defined forms of inflammatory arthritis that cause pain, swelling, and stiffness.
Two main types of peripheral arthritis are associated with Crohn’s. Type 1 peripheral arthritis typically affects large joints like the knees and elbows, is often asymmetric, and its activity usually mirrors intestinal disease flare-ups. A more persistent form, Type 2 peripheral arthritis, can affect smaller joints symmetrically and may progress independently of gut inflammation. Separately, axial spondyloarthritis can cause inflammation in the spine and sacroiliac joints, leading to chronic back pain.
Dermatological manifestations are also common. Erythema nodosum presents as tender, red nodules, typically appearing on the shins and ankles. These lesions often coincide with active bowel inflammation and tend to improve as the underlying Crohn’s is controlled.
A more severe, though less common, skin condition is pyoderma gangrenosum. It begins as painful pustules or blisters that rapidly break down to form deep, open ulcers with purplish borders. These ulcers most commonly appear on the legs and can occur independently of IBD activity, requiring specific wound care.
Ocular and Oral Complications
The inflammatory processes of Crohn’s disease can also impact the eyes. Ocular complications require prompt attention from an ophthalmologist to prevent lasting damage, so symptoms like eye pain, redness, or blurred vision should not be ignored.
Three primary inflammatory eye conditions are associated with Crohn’s. Episcleritis is an inflammation of the tissue covering the white of the eye, causing redness and mild discomfort that often correlates with IBD flares. Scleritis is a deeper, more severe inflammation of the sclera itself, resulting in intense pain that may lead to vision loss if not treated.
Uveitis involves inflammation of the uvea, the eye’s middle layer. This condition can cause a sudden onset of pain, light sensitivity, and blurred vision. Its activity is often independent of intestinal flare-ups, and prompt treatment is necessary to protect vision.
The mouth is another site where manifestations can occur, often as aphthous stomatitis, or canker sores. These painful ulcers on the soft tissues inside the mouth can be more frequent or persistent in individuals with Crohn’s disease. Their presence sometimes aligns with periods of active intestinal disease.
Impact on the Liver, Bile Ducts, and Kidneys
While less common, EIMs can affect internal organs like the liver, bile ducts, and kidneys. One of the most significant is primary sclerosing cholangitis (PSC), a chronic disease that causes inflammation and scarring within the bile ducts, which carry bile from the liver to aid digestion.
PSC is strongly associated with IBD, and the inflammation leads to hardening and narrowing of the bile ducts. This can obstruct bile flow and eventually cause serious liver damage, cirrhosis, and liver failure. The course of PSC is progressive and independent of the Crohn’s disease activity in the gut.
The kidneys can also be affected, most commonly through an increased risk of kidney stones. This risk is heightened in people with Crohn’s involving the small intestine. Malabsorption of fat is a factor; unabsorbed fats bind to calcium, leaving oxalate free to be absorbed and form stones in the urine. Chronic diarrhea can also lead to dehydration, further contributing to stone formation.
Diagnosis and Management Strategies
Diagnosing an EIM requires a clinician to connect a symptom outside the gut to the underlying Crohn’s disease. This often involves collaboration between a gastroenterologist and other specialists, such as a rheumatologist or dermatologist. Tests and imaging may be used to rule out other causes.
The primary approach to managing most EIMs is to control the systemic inflammation driving Crohn’s disease. Effectively treating the bowel inflammation often leads to the resolution of associated manifestations, particularly those whose activity parallels IBD flares. This is typically achieved with systemic medications that modulate the immune system.
Therapies such as immunomodulators and biologic agents, particularly anti-TNF drugs, are frequently used. These medications work throughout the body to suppress the overactive immune response, simultaneously treating the gut and the extraintestinal sites of inflammation.
Some EIMs may require targeted treatments in addition to managing the underlying Crohn’s. For instance, severe uveitis might be treated with corticosteroid eye drops, while pyoderma gangrenosum may need specialized wound care. Management is tailored to the specific manifestation and its severity, with the goal of controlling the systemic inflammatory response.