In untreated Crohn disease, what is the risk and severity of infections, and how should they be managed?

Infection Risk in Untreated Crohn's Disease

Untreated Crohn's disease carries an inherent infection risk driven primarily by active disease itself, with each 100-point increase in disease activity raising opportunistic infection risk by approximately 30%, independent of immunosuppressive therapy. 1

Baseline Infection Risk Without Immunosuppression

Active disease is an independent risk factor for infections in Crohn's disease. The disease activity itself—measured by the Crohn's Disease Activity Index (CDAI)—directly correlates with infection susceptibility, with a 30% increased risk of opportunistic infections per 100-point CDAI increment even in patients receiving adalimumab monotherapy. 1 This suggests that uncontrolled inflammation creates an immunocompromised state regardless of medication use.

Patient-Specific Risk Amplifiers in Untreated Disease

Even without immunosuppressive therapy, certain intrinsic factors substantially elevate infection risk in Crohn's patients:

• Malnutrition increases opportunistic infection odds by 2.3-fold (OR 2.31). 2, 3
• Obesity modestly raises risk at approximately 1.07-fold per kg/m² of BMI. 2, 3
• Older age (particularly >50 years) significantly increases vulnerability to severe infections. 2, 4
• Comorbidities including diabetes mellitus and chronic organ disease compound infection susceptibility. 2, 3
• Bowel surgery and total parenteral nutrition represent additional external risk factors. 2

Types of Infections in Untreated Crohn's Disease

While immunosuppressive medications shift the infection spectrum toward opportunistic pathogens, untreated Crohn's patients remain at risk for:

• Common bacterial infections related to intestinal barrier dysfunction and translocation. 2
• Parasitic infections, particularly in patients who have traveled to or lived in endemic areas (approximately 12% prevalence in endemic regions). 4
• Strongyloides stercoralis poses concern even before immunosuppression is initiated, especially in patients with travel history to endemic areas. 4

Critical Management Considerations

Pre-Treatment Screening (Before Any Therapy Initiation)

All Crohn's patients should undergo comprehensive infectious screening before starting any treatment, even if immunosuppression is not immediately planned:

• Tuberculosis assessment using tuberculin skin test or interferon-γ release assay (positive defined as ≥5 mm induration even with BCG vaccination). 3
• Viral serologies for hepatitis A/B/C, HIV, Epstein-Barr virus, cytomegalovirus, and varicella-zoster. 3
• Strongyloides serology and eosinophil count for patients with prolonged travel or residence in endemic areas (Latin America, sub-Saharan Africa, Southeast Asia). 4
• Stool examination for bacterial pathogens, ova, and parasites in returning travelers with diarrhea. 4

Vaccination Strategy

Vaccinations should be administered while patients are still untreated or on minimal immunosuppression, as vaccine efficacy decreases once moderate-to-severe immunosuppression begins:

• Pneumococcal series (PCV13 followed by PPSV23). 3
• Annual inactivated influenza vaccine. 3
• Hepatitis B vaccine if non-immune. 3
• HPV vaccination in appropriate age groups. 3

Live vaccines can be safely administered before moderate-to-severe immunosuppression but are contraindicated once systemic steroids ≥20 mg for >2 weeks, anti-TNF agents, or high-dose immunomodulators are started. 3

Disease Progression and Infection Risk

Untreated inflammatory-type Crohn's disease progresses to stricturing or penetrating complications in 37.4% of patients at 5 years, 54.3% at 10 years, and 78.8% at 25 years. 5 This progression is associated with:

• Ileal disease location as the most powerful predictor of complications. 5
• Current smoking as an independent risk factor for progression. 5
• Perianal disease and extraintestinal manifestations predicting more aggressive disease course. 5

These complications (strictures, fistulas, abscesses) themselves increase infection risk through bacterial overgrowth, abscess formation, and need for surgical intervention. 2

Common Pitfalls

• Assuming untreated Crohn's carries no infection risk: Active disease itself is immunosuppressive, with a 30% increased infection risk per 100-point CDAI increase. 1
• Delaying infectious screening until immunosuppression is planned: Screening should occur at diagnosis to identify latent infections (tuberculosis, Strongyloides) that could reactivate with disease progression or future treatment. 3, 4
• Overlooking travel history: Parasitic infections, particularly Strongyloides, require specific screening in at-risk populations before any immunosuppression. 4
• Undertreating active disease to avoid infection risk: Persistent inflammation itself increases infection susceptibility and drives structural complications requiring surgery. 5, 1