What causes erythema nodosum with Achilles tendon enthesitis and sacroilitis?

Inflammatory Bowel Disease (IBD) is the Primary Cause

The triad of erythema nodosum, Achilles tendon enthesitis, and sacroiliitis strongly suggests inflammatory bowel disease (IBD)—either Crohn's disease or ulcerative colitis—as the underlying etiology. 1 This constellation represents extra-intestinal manifestations (EIMs) of IBD occurring simultaneously, which is characteristic of spondyloarthropathy associated with IBD.

Why IBD is the Leading Diagnosis

• Erythema nodosum occurs in 4.2-7.5% of IBD patients, more commonly in Crohn's disease than ulcerative colitis, and typically correlates with intestinal disease activity 1, 2
• Radiological sacroiliitis is present in 20-50% of IBD patients, though progressive ankylosing spondylitis develops in only 1-10% 1
• Enthesitis (including Achilles tendon involvement) is a recognized peripheral manifestation of IBD-associated spondyloarthropathy, classified as part of the peripheral SpA spectrum 1
• The combination of these three features occurring together points specifically to IBD rather than other causes, as this pattern represents both cutaneous (erythema nodosum), peripheral musculoskeletal (enthesitis), and axial (sacroiliitis) EIMs simultaneously 1

Diagnostic Approach

Confirm IBD as the underlying cause:

• Obtain detailed gastrointestinal history: chronic diarrhea, abdominal pain, rectal bleeding, weight loss, or perianal disease 1
• Laboratory evaluation: complete blood count (anemia, thrombocytosis), inflammatory markers (ESR, CRP), fecal calprotectin 1
• Colonoscopy with biopsies is the gold standard for diagnosing IBD if not previously established 1
• MRI of sacroiliac joints using T1-weighted, STIR, and fat-saturated T2-weighted sequences to confirm sacroiliitis, especially in patients under 40 years with inflammatory back pain lasting >3 months 1

Assess for other potential causes (less likely given the triad):

• Behçet's disease: look for oral/genital ulcers, pathergy, uveitis, though Behçet's can cause erythema nodosum and arthritis, the specific combination with Achilles enthesitis and sacroiliitis is less characteristic 1, 3
• Sarcoidosis: obtain chest X-ray, serum ACE levels, though sarcoidosis rarely presents with this specific triad 4, 3
• Post-streptococcal infection: throat culture or ASO titers, but this typically causes erythema nodosum with arthralgia rather than true enthesitis and sacroiliitis 4

Treatment Strategy

Address the underlying IBD:

• Systemic corticosteroids are typically required for severe erythema nodosum associated with IBD flares 1, 2
• Immunomodulators (azathioprine) or biologic agents (TNF-α inhibitors like infliximab or adalimumab) are indicated for frequent relapses or resistant cases 1, 2
• TNF-α monoclonal antibodies (infliximab, adalimumab) are preferred over etanercept for IBD-associated spondyloarthropathy, as they treat both the intestinal disease and musculoskeletal manifestations 1

Manage individual manifestations:

• Erythema nodosum: NSAIDs for symptomatic relief, rest, elevation; treatment of underlying IBD typically leads to resolution 1, 2
• Enthesitis: NSAIDs, physical therapy, local corticosteroid injections if refractory 1
• Sacroiliitis/axial symptoms: NSAIDs as first-line; TNF-α inhibitors if inadequate response (note: sulfasalazine, methotrexate, and azathioprine are ineffective for axial symptoms) 1

Critical Pitfalls to Avoid

• Do not assume erythema nodosum is idiopathic when accompanied by enthesitis and sacroiliitis—this triad mandates investigation for IBD 1
• Do not use NSAIDs liberally without considering IBD, as they can exacerbate intestinal inflammation in some patients 1
• Do not delay colonoscopy if gastrointestinal symptoms are present or if the patient has unexplained anemia or elevated inflammatory markers 1
• Do not use systemic corticosteroids before excluding infectious causes of erythema nodosum, particularly tuberculosis in endemic areas 1, 5, 4
• HLA-B27 testing has limited utility in IBD-associated spondyloarthropathy (prevalence 25-75% vs. 90% in idiopathic AS), so negative results do not exclude the diagnosis 1