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Infectious Issues in Idiopathic
Inflammatory Bowel Disease
Mary P. Bronner, M.D.Division Chief, Anatomic PathologyUniversity of Utah & ARUP Laboratories
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IBD and Infection1. Flares2. Immunosuppression3. C. difficle4. CMV5. Infectious Mimics
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• Enteric infections common• 237 pt series of IBD flares• 25 (10.5%) enteric infections
• 13 C. difficle (5.5%)• 5 Campylobacter, 3 Ameba,
1 each Salmonella, Plesiomonas, Strongyloides, Blastocystis
IBD Flares
Mylonaki M, et al. Eur J Gastro Hep 2004;16:775.
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Immunosuppressing Drugs in IBDCorticosteroids Prednisone Immunomodulators Thiopurines
(azathioprine, 6‐mercaptopurine)Methotrexate
Biologics Anti‐TNF‐a (infliximab, others)Leukocyte adhesion inhibitors
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Frequent infections in IBDBacterial: C. difficile, Legionella pneumophila, Nocardia species, Salmonella species, Streptococcus pneumoniae, TB Viral: CMV, EBV, HBV (reactivation), HSV, HPV, Influenza, JC virus reactivation natalizumabFungal & parasitic infections: Aspergillosis, Candida species, CoccidiomycosisCryptococcosis, Cryptosporidiosis, Histoplasmosis
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C. difficile
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C. difficle in IBD• IBD flares• C. difficle infection reported
• as high as 47% in adults• as high as 25-60% in kids
• Polarized Rx• Pouchitis: 19% of 115 pt series
Ananthakrishnan A. Gastro Clin N Am 2012;41:339.
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Amebiasis
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CMV
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Blood CMV viral load by qPCR versusCMV IHC
Yan Z, et al. IntJ Surg Pathol2014;22:492.
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Rare CMV+IHC: Significance?- 30 CMV+IHC GI bx
- 100% immunosuppr: IBD, TP, misc
- 73% CMV+IHC had no H&E virus
- 83% of CMV+IHC blood qPCR neg
- 27% showed rare CMV+IHC cells
- 5 rx pts improved; 3 no rx, 2 died Yan Z, et al. Int J Surg Pathol 2014;22:492.
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Viral Mimicry
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Granulomas
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© 2013 ARUP Laboratories
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Infectious Granulomas• Any usual enteric bacterial
pathogens• Campylobacter, Salmonella,
Shigella, Yersinia, etc.• Mycobacterium tuberculosis• Fungi• Syphilis• Helminths and Parasites
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GI Tuberculosis Ileum most common site Increasing: multidrug resistance, HIV Granulomas Caseating 61% Confluent 48% Present 50-80% (cf Crohn’s ~25%) Ziehl-Neelsen AFB ~20% sensitive
Almadi MA, et al. Nat Rev Gastroenterol Hepatol 2011;8:455.
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MTb testing Ziehl‐Neelsen AFB stain ~ 20% sens Tuberculin skin test (PPD) ~ 60% sens QuantiFERON‐TB Gold Sens/Spec/PPV/NPV= 67%,90%,87%,73% INF‐γ
T‐SPOT.TB Release Sens/Spec/PPV/NPV= Assays 86%,93%,88%,91%
Lei Y, et al. J Dig Dis 2013;14:68.
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Anti-TNF Drugs infliximab, adalimumab, golimumab,
certolizumab, etanercept RA, CD, psoriatic arthritis, psoriasis,
ankylosing spondylitis 2-7X > risk of TB, Cocci, Histo Faster TB onset (17 vs 48 wks) More dissem & extrapulm TB (25 vs
10%) Wallis RS. Infect Dis Clin N Am 2011;25:895.
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Histoplasmosis
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GI Histoplasmosis SitesSite No. of 52 %Esophagus 4 8Stomach 8 17Sm bowel (ileum) 37 79Colon 26 55Anus 1 2Appendix 1 2Pancreas 3 6Gallbladder 3 6
Lamps LW, et al. Am J Clin Pathol 2000;113:64.
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GI Histoplasmosis: Pathology Feature Total (52)_Obstructive mass 3Ulceration 23Normal mucosa 11 (21%)Lymphoid hyperplasia 7Well‐formed granulomas 4 (8%)Abundant organisms 24
Lamps LW, et al. Am J Clin Pathol 2000;113:64.
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© 2013 ARUP Laboratories
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“The diagnosis of histoplasmosis begins with the thinking of it.”
Goodwin RA, Loyd JE, Des PrezRM. Histoplasmosis in normal hosts. Medicine. 1981;60:231.
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Strongyloides
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IBD and Infection1. Flares2. Immunosuppression3. C. difficle4. CMV5. Infectious Mimics
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