Treating IBD and lymphoma without a biopsy

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Megan McClosky, DVM, DACVIM (SAIM), an internist and assistant professor at the University of Pennsylvania School of Veterinary Medicine, shared her insight and knowledge on inflammatory bowel disease (IBD) and its link to small cell lymphosarcoma (SCLSA), during the 2022 American Association of Feline Practitioners annual conference in Pittsburgh, Pennsylvania.¹ “IBD, small cell lymphoma–and likely large cell lymphoma–represent a spectrum of disease,” she explained to attendees.

McClosky compared these diseases to moving targets that require veterinarians to alter therapies as cats progress. This relative unpredictability makes ruling out certain, and sometimes more serious, gastrointestinal (GI) differentials more important than getting a biopsy in some instances, she added.

What is IBD?

IBD is a clinical definition that requires the presence of clinical signs and the demonstration of inflammation on intestinal biopsies. Before biopsy, McClosky explained the inflammation shown is chronic enteropathy, which is further characterized by its response to therapy as diet-responsive, antibiotic-responsive, steroid-responsive, and fiber-responsive.

“Ultimately, the underlying etiology of IBD is unknown for cats, but the disease may share some similarities to human IBD. We think that it comes from a breakdown of tolerance within the GI immune systems to antigens in the diet, antigens in bacteria, and, potentially, self-antigen,” she explained.

Biopsies from cats with IBD–or chronic enteropathy–most commonly reveal lymphoplasmacytic enteritis as the most common type of inflammation regardless of the cause, according to McClosky. However, lymphoplasmacytic enteritis is not limited to cats with IBD, McClosky clarified. It is also present in cats with hyperthyroidism, parasitic infections, or asymptomatic felines. Less common types of inflammation can also occur, including eosinophilic, neutrophilic, granulomatous, or pyogranulomatous inflammation.

What is SCLSA?

SCLSA is cancer that specifically affects the lymphocytes in the GI tract. Although less aggressive than large or intermediate cell lymphoma, SCLSA shares many clinical similarities with feline IBD. “The clinical signs may actually be identical,” she clarified.

Upon hearing the term lymphoma, clients–especially those with loved ones with cancer–are instinctively scared. “I like to talk to them about the differences between small versus large cell,” she said. McClosky noted that small cell lymphoma will be less aggressive and will cause diffused small intestinal thickening on ultrasound. Large cell lymphoma is more likely to cause mass-like lesions in the stomach, small intestine, and colon.

“The median survival time for small cell lymphoma, if it is reached in studies, is usually 2 to 3 years. If we are talking about cats diagnosed later in life, they may go on to die from something other than their cancer. Large cell lymphoma has a pretty poor prognosis, even with treatment. The median survival time is only about 6 to 8 months,” she said.

Diagnostic workup

“The signs of GI disease are pretty vague,” McClosky said. These signs include vomiting, diarrhea, weight loss, and changes in appetite. She told attendees that she makes a point to remind her students that cats with significant intestinal disease do not always present with vomiting and diarrhea. Weight loss in the face of a typical or increased appetite may be the only indication that something is awry in the GI tract.

“Similar to working up pancreatitis, the baseline blood work is to rule out other causes of GI signs,” she explained. Feline patients with chronic enteropathy may have mild anemia or mild leukocytosis on a complete blood count (CBC), but it could be normal. Hypocholesterolemia is common on the chemistry panel, whereas panhypoproteinemia is possible but less common than in dogs.

Another important part of the workup is fecal testing to rule out intestinal parasites, nematodes, and Giardia, especially in cats with weight loss and diarrhea. “Even if the fecal is normal–because the sensitivity of fecal floats is pretty poor if cats are not having active diarrhea–empiric deworming should also be performed,” McClosky advised.

A 2010 study published in the Journal of Veterinary Internal Medicine² established a feline chronic enteropathy activity index (FCEAI) to evaluate the severity of disease and response to therapy. The FCEAI scoring system includes scores for attitude/activity, appetite, vomiting, stool consistency, stool frequency, and unintended weight loss.

Monitoring of this value may be helpful as an objective way to assess response to therapy, McClosky said. However, one of the faults of the index, she pointed out, is that it does include endoscopic biopsy scores, which would not be available when treating a patient without a biopsy diagnosis.

Is diagnosis possible without a biopsy?

According to McClosky, GI biopsy remains the gold-standard diagnosis to differentiate between IBD and SCLSA. While some clinical features are more consistent in one disease than the other, there is too much overlap for these to be useful in individual patients.

McClosky encouraged attendees to advocate for biopsies for younger patients with refractory disease, patients that may be intolerant of oral medications, those with comorbidities that require dietary therapy, and patients that may respond poorly to steroids.

Still, forgoing a biopsy does not mean that treatment is impossible. To hit the moving target, special care and consideration must be taken.

Important differentials to rule out

“If a sick GI cat looks like a sick GI cat and we think that we are not going to be able to biopsy, are there other things to think about that may be made worse with therapy,” McClosky explained.

Infectious diseases that cause GI signs are most likely to present in younger patients or those with a compatible travel history. “Many infectious conditions can be made much worse by starting steroids, so ruling them out is important; and in some cases, more important than a GI biopsy,” she warned.

“If you know that you are not going to get a biopsy, some things to consider would be infectious disease testing, fungal testing, fecal polymerase chain reaction (PCR) panels, fecal cultures, and abdominal imaging,” she encouraged.

Infectious diseases to test for include Giardia, clostridial infections, infiltrative fungal disease, histoplasmosis, and salmonellosis. Further diagnostics should include a malabsorption/maldigestion panel, pancreatic lipase immunoreactivity, and trypsin-like immunoreactivity.

Lastly, abdominal imaging is recommended to rule out mass-like lesions in the GI tract or other organs and may even lead to a more positive discovery. For example, polyps confirmed via ultrasound may cause vomiting due to partial obstruction and changes in appetite but are often benign and can be removed.

Management

Pharmacologic interventions for IBD and SCLSA are nearly identical, especially if the IBD is refractory to dietary management, McClosky said. Patients that can maintain a good appetite, have no or minimal weight loss, and minimal vomiting or diarrhea should undergo empiric trials of a novel protein or hydrolyzed protein diet and/or an antibiotic trial with metronidazole or tylosin. Typically, it takes between 4 and 8 weeks to observe a response.

If a patient is inappetent, rapidly losing weight, or presents with severe clinical signs, a faster-acting therapy should be prescribed. Once GI differentials have been ruled out, a steroid trial can be initiated for chronic enteropathy. If there is a partial response to steroids, adding chlorambucil may achieve complete control of the disease.

The initial therapies for SCLSA are prednisolone and chlorambucil, so the treatment ends up being the same, she pointed out. The goal in either instance is to reduce the clinical signs of disease, but it is unlikely to eliminate them.

"These are diseases that are managed, not cured," McClosky concluded.

References

1. McClosky M. IBD to Lymphoma: How Do I Manage if the Client Won’t Biopsy? Presented at: 2022 American Association of Feline Practitioners Conference, Pittsburgh, Pennsylvania. October 27-30, 2022.
2. Jergens AE, Crandell JM, Evans R, et al. A clinical index for disease activity in cats with chronic enteropathy. J Vet Intern Med, 2010;24(5):1027-1033.