A 32-year-old woman with ulcerative colitis (UC) of 8 years' duration presents with bloody diarrhea and abdominal cramping. She is on mesalamine and azathioprine. Colonoscopy shows continuous mucosal inflammation limited to the colon with crypt distortion and surface ulceration. Regarding the extraintestinal manifestations (EIMs) of UC, all of the following are associated with disease activity EXCEPT:

Explanation

## Extraintestinal Manifestations of UC: Activity-Dependent vs. Independent ### Classification of EIMs **Key Point:** EIMs in UC are broadly divided into two categories based on their relationship to bowel disease activity. | EIM | Activity-Dependent | Activity-Independent | Mechanism | |-----|-------------------|----------------------|----------| | Erythema nodosum | Yes | — | Immune complex deposition; parallels GI inflammation | | Pyoderma gangrenosum | Yes | — | Neutrophilic dermatosis; flares with colitis | | Anterior uveitis | Yes | — | HLA-B27 independent; correlates with bowel activity | | Ankylosing spondylitis | — | Yes | HLA-B27 associated; independent of GI disease activity | | Primary sclerosing cholangitis (PSC) | — | Yes | Progressive; unrelated to colitis remission | | Arthropathy (peripheral) | Yes | — | Immune-mediated; improves with bowel control | ### Why Ankylosing Spondylitis Stands Apart **High-Yield:** Ankylosing spondylitis (AS) is **activity-independent**. It: - Occurs regardless of whether UC is in remission or active - Is strongly associated with HLA-B27 (>90% of AS patients with IBD are HLA-B27+) - Progresses independently of GI inflammation control - Does NOT improve with treatment of the underlying colitis **Clinical Pearl:** A patient with UC in complete remission on therapy may still develop or progress with ankylosing spondylitis, making it fundamentally different from erythema nodosum or pyoderma gangrenosum, which typically flare during active colitis. ### Activity-Dependent EIMs (The Correct Three) 1. **Erythema nodosum** — painful nodules on shins/legs; flares with active colitis; resolves with disease control 2. **Pyoderma gangrenosum** — rapidly progressive ulcers; parallels intestinal inflammation; improves with immunosuppression 3. **Anterior uveitis** — eye pain, photophobia, blurred vision; correlates with bowel activity in ~50% of cases **Mnemonic:** **ASPEN** = Activity-dependent EIMs: **A**rthropathy (peripheral), **S**kin (erythema nodosum, pyoderma), **P**yoderma, **E**rythema, **N**one of these are AS (ankylosing spondylitis is independent). ### Key Distinction for Exam **Warning:** Do NOT confuse peripheral arthropathy (activity-dependent) with ankylosing spondylitis (activity-independent). Both are joint manifestations, but only AS is HLA-B27–driven and independent of colitis control.