In a patient who completed a 5‑ to 6‑day course of prednisone 20 mg for an underlying inflammatory condition and now presents with new abdominal masses, abdominal pain, and diarrhea, what are the likely diagnoses and their estimated probabilities, excluding corticosteroid withdrawal?

Differential Diagnosis for New Abdominal Masses, Pain, and Diarrhea After Short-Course Prednisone

The most likely diagnoses in this patient are: (1) flare of the underlying inflammatory bowel disease (IBD) with probability ~40-50%, (2) infectious colitis including Clostridioides difficile infection (CDI) at ~20-30%, (3) opportunistic infections (particularly Strongyloides hyperinfection if endemic exposure history exists) at ~5-15%, and (4) less commonly, abscess formation, intestinal perforation, or malignancy at ~5-10% combined.

Primary Diagnostic Considerations

1. Flare of Underlying Inflammatory Bowel Disease (40-50% probability)

The presentation of abdominal pain, diarrhea, and new masses strongly suggests active IBD, particularly if the underlying condition is Crohn's disease or ulcerative colitis. A 5-6 day course of prednisone 20 mg daily is insufficient for adequate disease control in moderate-to-severe IBD 1. Guidelines recommend prednisolone 40 mg daily tapered over 8 weeks for active disease 1. The inadequate dosing and premature discontinuation likely allowed disease progression rather than achieving remission.

• Abdominal masses in Crohn's disease may represent inflammatory phlegmons, strictures, or abscesses 1
• The guideline explicitly states to "consider the site, pattern (inflammatory, stricturing, fistulating) and activity of the disease" and notes that "an alternative explanation for symptoms other than active disease should be considered (such as bacterial overgrowth, bile salt malabsorption, fibrotic strictures)" 1
• Urgent evaluation with imaging (CT enterography or MRI) and endoscopy with biopsies is indicated to assess disease activity and exclude complications

2. Infectious Colitis, Particularly C. difficile (20-30% probability)

CDI screening is mandatory at every disease flare in IBD patients, especially those receiving immunosuppressive therapy 2. Even brief corticosteroid exposure increases CDI risk significantly.

• IBD patients are 3.7-fold more likely to develop CDI than non-IBD patients, and this risk increases to 4.8-fold in population-based studies 2
• Corticosteroids (HR 2.54) and biologics increase CDI risk 2
• CDI occurs in 28.8% of IBD flares versus 5.6% in inactive disease 2
• Two-step diagnostic algorithm: Initial highly sensitive test (GDH antigen or nucleic acid amplification) followed by high-specificity toxin A/B enzyme immunoassay 2
• Stool cultures for bacterial pathogens (Salmonella, Campylobacter, Shigella) and parasites should be obtained simultaneously

3. Opportunistic Infections: Strongyloides Hyperinfection (5-15% probability if endemic exposure)

This is a critical diagnosis that can be fatal if missed. The FDA label explicitly warns that corticosteroids "may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia" 3.

• Any history of residence or travel to endemic areas (Southeast Asia, Latin America, sub-Saharan Africa) warrants Strongyloides screening, even if decades prior 4, 5
• Peripheral eosinophilia may be present but can be suppressed by corticosteroids 4
• Serology (Strongyloides IgG) and stool examination (multiple samples) are indicated
• Duodenal biopsies during endoscopy can establish diagnosis 4
• Untreated hyperinfection carries extremely high mortality

4. Abscess Formation (5-10% probability)

Intra-abdominal or splenic abscesses can occur in immunosuppressed patients, particularly with corticosteroid use 6.

• Presents with fever, leukocytosis, elevated inflammatory markers, and palpable masses
• Contrast-enhanced CT is diagnostic 6
• Requires source control (percutaneous drainage or surgical intervention) plus antibiotics

5. Intestinal Perforation (3-5% probability)

Corticosteroids can mask perforation symptoms and are associated with intestinal perforation, though this is a diagnosis of exclusion 7.

• Presents with acute severe abdominal pain, peritoneal signs, pneumoperitoneum on imaging
• Requires emergent surgical evaluation
• The FDA label notes corticosteroids can "mask some signs of infection" and increase disseminated infection risk 3

6. Malignancy (2-5% probability)

New abdominal masses warrant malignancy evaluation, particularly colorectal cancer or lymphoma in IBD patients.

• IBD patients have increased colorectal cancer risk, and maintenance aminosalicylate therapy reduces this risk 1
• Imaging and tissue diagnosis required

Critical Diagnostic Algorithm

Immediate workup (within 24-48 hours):

1. Stool studies: CDI (two-step algorithm), bacterial culture, ova and parasites (×3 samples), fecal calprotectin
2. Blood work: CBC with differential (assess eosinophilia), CRP, ESR, comprehensive metabolic panel, blood cultures if febrile
3. Imaging: Contrast-enhanced CT abdomen/pelvis to characterize masses, assess for abscess, perforation, or obstruction
4. Serology: Strongyloides IgG if any endemic exposure history
5. Endoscopy with biopsies: Colonoscopy (or flexible sigmoidoscopy if severe) with biopsies for histology, including duodenal biopsies if Strongyloides suspected 2

Treatment approach pending workup:

• Hold further corticosteroids until infection excluded 8, 9, 10
• Empiric antibiotics only if sepsis or high suspicion for bacterial infection
• Do NOT use anti-diarrheal agents (loperamide) until infection ruled out 9, 10
• Maintain hydration and electrolyte balance

Common Pitfalls to Avoid

1. Assuming symptoms are solely IBD flare without excluding infection – This can be fatal with opportunistic infections like Strongyloides 3, 4, 5
2. Inadequate corticosteroid dosing/duration – 20 mg for 5-6 days is insufficient for IBD; standard is 40 mg tapered over 8 weeks 1
3. Failing to screen for CDI – Mandatory at every IBD flare, especially with recent corticosteroid use 2
4. Not obtaining travel/residence history – Strongyloides can reactivate decades after endemic exposure 4, 5
5. Using anti-motility agents before excluding infection – Can precipitate toxic megacolon or worsen outcomes 9, 10