Infectious Issues in Idiopathic 

Inflammatory Bowel Disease

Mary P. Bronner, M.D.Division Chief, Anatomic PathologyUniversity of Utah & ARUP Laboratories 

IBD and Infection1. Flares2. Immunosuppression3. C. difficle4. CMV5. Infectious Mimics 

• 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.

Immunosuppressing Drugs in IBDCorticosteroids         Prednisone  Immunomodulators Thiopurines

(azathioprine, 6‐mercaptopurine)Methotrexate               

Biologics                     Anti‐TNF‐a     (infliximab, others)Leukocyte adhesion inhibitors

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

C. difficile

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.

Amebiasis

CMV

Blood CMV viral load by qPCR versusCMV IHC

Yan Z, et al. IntJ Surg Pathol2014;22:492.

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.

Viral Mimicry

Granulomas

© 2013 ARUP Laboratories

Infectious Granulomas• Any usual enteric bacterial 

pathogens• Campylobacter, Salmonella, 

Shigella, Yersinia, etc.• Mycobacterium tuberculosis• Fungi• Syphilis• Helminths and Parasites

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.

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.

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.

Histoplasmosis

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.

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.

© 2013 ARUP Laboratories

“The diagnosis of histoplasmosis begins with the thinking of it.”

Goodwin RA, Loyd JE, Des PrezRM. Histoplasmosis in normal hosts. Medicine. 1981;60:231.

Strongyloides

IBD and Infection1. Flares2. Immunosuppression3. C. difficle4. CMV5. Infectious Mimics