What is the likely diagnosis and treatment for persistent gastrointestinal symptoms, joint pain, and fatigue following an E. coli (Escherichia coli) infection, with elevated Calprotectin and lactoferrin levels, and low secretory immunoglobulin A (sIgA) in stool?

Post-Infectious Irritable Bowel Syndrome (PI-IBS) with Possible Reactive Arthritis

Your presentation is most consistent with post-infectious irritable bowel syndrome (PI-IBS) following E. coli infection, and your mildly elevated inflammatory markers (calprotectin 30-69 mg/g, lactoferrin 11.5 mg/g) combined with low secretory IgA suggest ongoing low-grade intestinal immune dysregulation rather than active inflammatory bowel disease. Given your negative endoscopic evaluations, the focus should shift to managing PI-IBS and addressing the immune dysfunction.

Understanding Your Laboratory Results

Your fecal markers tell an important story:

• Calprotectin levels of 30-69 mg/g are below the threshold of 150 mg/g that would indicate significant intestinal inflammation requiring treatment escalation 1. While initially at 69 mg/g (mildly elevated), the decrease to 30 mg/g suggests resolution of acute inflammation 2.

• Lactoferrin at 11.5 mg/g is above the normal cutoff of 7.25 mg/g but still represents minimal elevation 1. This level correlates more with histological changes than active endoscopic disease 2.

• Low secretory IgA (sIgA) in stool indicates impaired mucosal immune function, which is a known consequence of infectious gastroenteritis and contributes to ongoing symptoms despite absence of visible inflammation.

• The combination of negative endoscopy (colonoscopy, EGD, pill cam) with mildly elevated markers strongly argues against inflammatory bowel disease 3, 4.

Why You Still Feel Unwell

Post-infectious IBS develops in 10-30% of patients after bacterial gastroenteritis and is characterized by:

• Persistent alterations in gut microbiome composition
• Low-grade immune activation without visible mucosal damage
• Visceral hypersensitivity (increased pain perception from the gut)
• Altered gut-brain axis signaling
• Impaired intestinal barrier function (related to your low sIgA)

Your joint pain and fatigue suggest possible reactive arthritis, a post-infectious inflammatory condition that can follow enteric infections, particularly with E. coli. This typically presents with:

• Arthralgia (joint pain) affecting multiple joints
• Chronic fatigue
• Gastrointestinal symptoms that persist beyond the acute infection

Recommended Diagnostic Workup

Since your endoscopic evaluations are complete and negative, focus on:

1. Rule out ongoing infection: Repeat stool culture and C. difficile testing to ensure no persistent or secondary infection 3.

2. Assess for reactive arthritis:

   • HLA-B27 testing (positive in 60-80% of reactive arthritis cases)
   • Inflammatory markers: ESR and CRP
   • Consider rheumatology referral if joint symptoms are prominent

3. Evaluate immune function:

   • Serum immunoglobulin levels (IgA, IgG, IgM)
   • Consider celiac disease screening (tissue transglutaminase IgA and total IgA) as this can present similarly 1

4. Thyroid function testing as thyroid dysfunction can cause similar systemic symptoms 1.

Treatment Approach

For Gastrointestinal Symptoms

Since your calprotectin is now 30 mg/g (well below 150 mg/g), immunosuppressive therapy is not indicated 1. Instead, focus on:

• Dietary modifications: Low FODMAP diet trial for 6-8 weeks, which helps 50-70% of PI-IBS patients
• Probiotics: Multi-strain probiotics (particularly Lactobacillus and Bifidobacterium species) to restore microbiome balance
• Antispasmodics: For abdominal pain and cramping (hyoscyamine, dicyclomine)
• Neuromodulators: Low-dose tricyclic antidepressants (amitriptyline 10-25 mg at bedtime) or SSRIs for visceral hypersensitivity and pain modulation

For Joint Pain and Fatigue

• NSAIDs: For symptomatic relief of joint pain (if no contraindications)
• Physical therapy: For joint symptoms
• If reactive arthritis is confirmed: May require short course of corticosteroids or disease-modifying antirheumatic drugs (DMARDs) under rheumatology guidance

For Immune Support

• Address low sIgA: Consider oral immunoglobulin supplementation or colostrum, though evidence is limited
• Optimize nutrition: Ensure adequate protein, zinc, vitamin D, and vitamin A intake to support immune function

Monitoring Strategy

Do not repeat endoscopy unless symptoms significantly worsen or new alarm features develop (rectal bleeding, unintentional weight loss >10%, nocturnal symptoms) 1.

• Repeat fecal calprotectin in 3-6 months only if symptoms worsen significantly 1
• Your current calprotectin of 30 mg/g reliably excludes moderate to severe inflammation and does not warrant treatment escalation 1, 2

Critical Pitfalls to Avoid

• Do not pursue immunosuppressive therapy (corticosteroids, biologics) with calprotectin <150 mg/g and negative endoscopy, as this exposes you to unnecessary risks without addressing the underlying problem 1.

• Do not over-investigate with repeated endoscopy unless new symptoms develop; your three negative studies are sufficient 3.

• Do not dismiss the systemic symptoms (joint pain, fatigue) as purely functional—reactive arthritis is a real post-infectious complication requiring specific evaluation and treatment.

• Recognize that normal inflammatory markers do not mean your symptoms aren't real—PI-IBS causes genuine suffering through mechanisms that don't show up on standard testing 4, 5.

Expected Timeline

Post-infectious IBS typically improves over 6-12 months, though 10-15% of patients have symptoms persisting beyond one year. Reactive arthritis, if present, usually resolves within 3-6 months but can occasionally become chronic. Your improving calprotectin trend (69→30 mg/g) is encouraging and suggests the inflammatory component is resolving 2, 6.