Infectious Mimics of Inflammatory Bowel Disease [Hot Topic]


Dora Lam-Himlin, M.D.

Inflammatory bowel disease (IBD) is a diagnosis of exclusion and requires ruling out infectious causes that may mimic IBD. When an elderly patient presents with previously diagnosed Crohn disease and abdominal pain, it’s critical that the workup includes excluding any active infection that may be diagnostically misleading.

Presenters and Credentials:
Dora Lam-Himlin, M.D., Consultant Anatomic Pathology
Assistant Professor Laboratory Medicine and Pathology at Mayo Clinic in Phoenix, Arizona.


Welcome to Mayo Medical Laboratories Hot Topics. These presentations provide short discussion of current topics and may be helpful to you in your practice.


Our speaker for this program is Dr. Dora Lam-Himlin, MD, from the Division of Anatomic Pathology and Laboratory Medicine at Mayo Clinic Arizona. Dr. Lam-Himlin discusses a recent case demonstrating the difficulty of distinguishing between inflammatory bowel disease and infectious mimics.

Thank you for the kind introduction.  It’s a privilege to speak to you today about infectious mimics of inflammatory bowel disease. Today, I will be sharing a case presentation with a challenging diagnosis and will briefly discuss infectious mimics of inflammatory bowel disease. The content of this lecture is intended for pathologists, but may also be of interest to clinical gastroenterology staff.


I have no conflicts of interest to disclose.


There are 3 primary objectives that viewers should achieve at the end of this presentation.  The first is the ability to recognize that a diagnosis of inflammatory bowel disease requires exclusion of infectious etiologies.  Next, viewers should be able to list at least 1 potential infectious mimic of Crohn disease. In doing so, viewers should be able to describe the importance of performing a Grocott methenamine silver (GMS) special stain on GI mucosal granulomata.

Case Presentation

Let’s begin with our case presentation. This case involves a 71-year-old woman who presented with a chief complaint of a 20-pound weight loss, abdominal pain and fevers for the past 6 months. She was admitted for diffuse abdominal pain, rated as 8 out of 10, which was exacerbated by oral intake.

Other pertinent history included complaints of diarrhea and odynophagia, but no dysphagia, nausea, vomiting, or evidence of GI bleeding. Her fevers were described as daily, spiking up to 101 F, and accompanied by night sweats. She denied any recent travel outside the United States and had no recent sick contacts.

The patient had been previously evaluated 5 months prior and was presumptively diagnosed with Crohn disease based on findings of segmental wall thickening and inflammation of the small bowel on CT scan. At the time, no endoscopy or biopsy was performed.

Past Medical/ Surgical History

As a result, the patient’s past medical and surgical history upon admission included Crohn disease of the small bowel, rheumatoid arthritis, hypertension, migraine headaches, herpes simplex with oral outbreaks, and hysterectomy.

Social and family histories were unremarkable.

Physical exam and laboratory values revealed a stable patient in mild distress.

CT Abdomen/Pelvis

CT of the abdomen and pelvis showed an abnormal short segment of small bowel wall thickening, seen in the red oval. Additionally, numerous lymph nodes in the abdomen and pelvis were enlarged, some of which were greater than 2 cm.

Differential Diagnoses

At this time, the clinical differential diagnoses included inflammatory bowel disease, malignancy, and infection.


Esophagogastric duodenoscopy was performed, which revealed esophagitis and multiple clean-based duodenal and jejunal ulcers as seen here.

Duodenal Biopsy

Biopsies of these areas showed abnormal small intestinal mucosa with abnormal architecture consistent with chronic damage. The villi are essentially missing from this small bowel, while the crypts show areas of dropout.

Higher magnification of these areas of crypt dropout show a fullness in the lamina propria with the presence of loosely aggregated histiocytes creating a mucosal granuloma. Note the mucosal surface at the top right shows erosion and acute inflammation. In summary, the small bowel biopsy shows both active inflammation and chronic damage with the presence of a mucosal granuloma. These findings are certainly compatible with Crohn disease and it would be easy for this case to stop here with a pathology report stating such. However, the findings are not specific for Crohn disease, and we as pathologists have an opportunity to make a significant clinical impact by continuing to work this case up in surgical pathology.

Duodenal Biopsy, GMS Stain

A diagnosis of chronic idiopathic inflammatory bowel disease should only be made in the proper clinical context and following exclusion of infectious etiologies. In all cases of mucosal granulomata, and especially in a new diagnosis of Crohn disease, it is worthwhile to perform special stains to exclude infectious etiologies. Although typically low yield for a surgical pathologist, these stains may reveal a treatable infectious condition, such as seen here. This GMS stain highlights yeast forms 2 to 4 microns in diameter, consistent with Histoplasma capsulatum.

Another field is seen here with the arrows pointing at the intracellular Histoplasma yeast forms.

Histoplasma Capsulatum

Histoplasma capsulatum was first described by Samuel Darling in 1908 and is found in soil enriched with bat, chicken, and blackbird droppings, particularly in the Ohio and Mississippi River valleys. The inhaled mold transforms to yeast, which is responsible for the granulomatous disease. Hematogenous spread results in disseminated disease in 10% of patients, found more commonly among immunosuppressed patients.

Gastrointestinal Histoplasmosis

This infection commonly presents as a pulmonary disease and involvement of the gastrointestinal tract always reflects disseminated infection. Gastrointestinal histoplasmosis can affect any area of the gastrointestinal tract and can cause ulceration leading to GI bleeds, strictures, obstructions, and polyp or mass formation. Enlarged mediastinal lymph nodes can cause esophageal compression resulting in dysphagia or odynophagia, as seen in our patient.


Granulomata are the histologic clue to this diagnosis, and are typically poorly formed with or without the presence of caseous necrosis. The organisms are found within the cytoplasm of these histiocytes and are 2-4 microns in diameter (for a reference point, I find it helpful to use a lymphocyte nucleus in the field, which is typically about 10 microns in diameter). The organisms are uniformly round, with little size variation and are visible on GMS stain.

Laboratory Diagnosis

Sensitivity on tissue biopsy is relatively low, and serum studies can be useful for both diagnosis and monitoring therapy. Since this is often an opportunistic infection, it is worth noting that antibody testing may not be as useful among patients with AIDS.


The importance of diagnosis is readily apparent as untreated disseminated histoplasmosis has a mortality rate of 80%. Treatment protocols are listed here for your reference.

Back to Our Patient

Returning back to our patient; she was appropriately treated by infectious disease specialists and showed marked clinical improvement. While the mucosal ulcers and inflammation resolved, areas of established stricture resulted in obstruction requiring segmental resection. This outcome underscores the importance of early intervention and the pathologist’s critical role in diagnosis of infectious diseases masquerading as inflammatory bowel disease.


Some references are provided for additional reading.

2016 Mayo Clinic Pathology Update Conference

If you liked today’s presentation, or even if you didn’t, please consider attending the upcoming Mayo Clinic pathology conference: The “2016 Mayo Clinic Pathology Update: A Tribute to the Career of Thomas V. Colby, MD”. This 2 and a half day conference will feature presentations from expert speakers covering a broad range of diagnostic pathology subjects, including pulmonary and mediastinal, soft tissue, gastrointestinal, genitourinary, cytology, and hematopathology topics.  Each lecture topic is carefully selected to celebrate the distinguished career of Professor Thomas V. Colby, who has published many of the seminal articles related to these entities. At the course, I will be presenting a lecture dedicated to the various infectious mimics of inflammatory bowel disease, including basidiobolomycosis, a rare fungal infection described by Dr. Colby. A very special session will be held on the second day of the course, during which Dr. Colby will personally share some of the index cases that inspired his groundbreaking work. Engaging case review sessions will follow didactic lectures, and the interactive audience response system will bring out your inner gamer.  Join us for CME, SAMs, celebration and sunny skies on the Phoenix campus February 4th through 6th, 2016. Online registration is now open.
Thank you for listening today. It has been my pleasure and privilege.




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