Introduction

Chronic vomiting in cats is a common complaint of owners, defined as vomiting that lasts approximately 2 wk (1–3 wk) and has failed to respond to initial symptomatic therapy.^1,2 The purpose of this review article is to delineate logical steps for evaluation of chronic vomiting in cats, including the classification, causes, and diagnostic approach for the small animal clinician.

Vomiting is an active process of the upper gastrointestinal (GI) tract expelling contents when it becomes irritated, inflamed, or overly distended. The act of vomiting can be divided into three phases.³ The initial phase starts with nausea, and cats may exhibit signs of lip-licking behavior, hypersalivation, and food aversion. The second phase of vomiting is retching, which consists of powerful contractions of the abdominal muscles and diaphragm. In the final phase, gastric contents are forcefully expelled by the contraction of the abdominal muscles, stomach, and the diaphragm, with concurrent relaxation of esophageal sphincter.

Vomiting is defined as a neurologically mediated reflex initiated when the emetic center is stimulated either by a humoral pathway or by activation of neural receptors and pathways such as the afferent vagal, sympathetic, vestibular, and cerebrocortical pathways.¹ However, further research in cats has established that there is no well-defined “vomiting center,” and that instead there is a wide distribution of neurons involved in the reflex.⁴ In this review article, we will continue to use the term emetic center for ease of clinical discussion.

The area postrema (AP), located on the floor of the fourth ventricle, receives signals from blood-borne triggers and communicates with the emetic center to initiate vomiting. The blood–brain barrier is less effective in this area, permitting exposure of the AP to blood-borne substances that may include uremic toxins, drugs, and metabolic derangements in addition to electrolyte, osmolar, and acid-base disorders.¹ The neuronal pathway is the second pathway in which vomiting is initiated. Peripheral sensory receptors that belong to the afferent, vagal, sympathetic, and glossopharyngeal pathways can activate the emetic center. Afferent neurons arise from the GI tract, predominantly in the duodenum, and also from other areas of the body including the urinary tract, reproductive tract, liver, pancreas, and peritoneum.⁵ Peripheral sensory receptors located at these sites in the body include dopamine, norepinephrine, 5-hydroxytryptamine, histamine, substance P, opioid, and acetylcholine receptors. Antiemetic therapy is directed at blocking the vomiting reflex by inhibiting neurotransmission at central (AP, emetic center) and peripheral sensory receptor sites.⁵ Cats are reported to have few central nervous system dopamine receptors, and, consequently, metoclopramide may be a poor antiemetic choice for this species, although it may have a prokinetic effect that could be beneficial for ileus.¹

History and Physical Examination Findings

History obtained should include the signalment, environment (indoor/outdoor), concurrent systemic illnesses, current and past diets, retroviral status, exposure risk to toxins, travel history, episodes of dietary indiscretion, and if any other pets in the household are exhibiting similar clinical signs. It is important to determine when the vomiting first started and the progression, including the frequency, duration, and severity. Vomiting, which is most often an active process with significant abdominal effort (usually preceded by nausea), should be differentiated from regurgitation, a passive process in which an undigested food bolus or liquid is expelled (discomfort on swallowing may be seen). This differentiation may be more difficult to make in cats compared to canine patients. A retrospective study performed by Frowde et al. investigating esophageal disease in cats showed that esophageal disease is rare in this species and that regurgitation can be mistaken for vomiting or may be accompanied by it, which may confuse body system localization.⁶ Clients should be asked about factors that may improve or worsen the vomiting and any noticeable triggers. Description of the vomitus should also be obtained, including the form (food and state of digestion, bile, blood, hair), volume, and color. The contents of the vomitus and the time elapsed between eating and vomiting can be extremely variable. Concurrent signs, such as change in appetite and presence of diarrhea, can help prioritize the differential list.

A complete and thorough physical exam is warranted in all feline patients that present with a history of vomiting. Physical exam findings may include signs of chronic malnutrition such as weight loss, muscle wasting, and poor hair coat. Cats may have an unremarkable abdominal palpation or exhibit signs of nausea or discomfort. Intestinal thickening, lymphadenopathy, or concern for an abdominal mass may be identified. The sublingual region should be closely evaluated for a linear foreign body, and neck palpation should be performed to screen for a thyroid nodule. Icterus may be present with underlying liver, biliary, pancreatic, or hemolytic disease. If there is evidence of dermatitis, skin lesions, and/or pruritus, then food allergy should be investigated, although these signs are not required for a diagnosis of food allergy.

A brief summary of causes for chronic vomiting in cats is summarized in Table 1.

Table 1 Summary of Causes of Chronic Vomiting in Cats

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Infectious Disease

Several infectious diseases can lead to chronic vomiting if not identified and treated appropriately. See Table 2 for an extensive list of causes. Although the more common causes of chronic vomiting in cats observed in clinical practice typically include inflammatory bowel disease, adverse food reactions, or extra-GI disease such as hepatic, renal, pancreatic, and endocrine disease (hyperthyroidism), it is important to consider infectious disease based on the patient's history, environment, and exposure risk. For example, cats that spend time outdoors, exhibit predatory activity, or that live in a multiple-cat environment likely have a higher risk for exposure to infectious diseases such as parasites and viral infection (feline infectious peritonitis [FIP], feline leukemia virus [FeLV], and feline immunodeficiency virus [FIV]).

Table 2

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Feline heartworm infection is much less common than in our canine patients, but cases have been diagnosed in all 50 states in the United States, and the prevalence of adult heartworm infections in cats is estimated to be 5% to 15% of the rate in unprotected dogs in a given area.⁷ Diagnostic testing for feline heartworm disease should include antibody testing, since it has the advantage of being able to detect infection by both male and female worms, as larvae of either sex can stimulate a detectable immune response as early as 2 mo post-infection.⁷ However, since both juvenile and adult worms are capable of causing clinical disease in the cat, both antibody and antigen tests are useful tools and, when used together, increase the probability of making appropriate diagnostic decisions.⁷ Additional diagnostic tests for feline heartworm disease include thoracic radiographs and echocardiography. Gastric parasites such as Ollulanus tricuspis and Physaloptera spp. are uncommon causes of chronic vomiting and difficult to diagnosis antemortem, but can be empirically treated with anthelminthic therapy such as fenbendazole (extra-label use for these infections).

Cats can become infected with Toxoplasma gondii bradyzoites during predatory feeding, although clinical disease associated with the intestinal phase of infection is uncommon. Serum antibody testing should be considered if there is concern for T. gondii infection based on the patient's history, environment, and clinical signs. Although chronic GI disease in cats from toxoplasmosis is uncommon, involvement of the organism in hepatic and pancreatic tissue may lead to the clinical sign of vomiting.⁸ Serum antibody testing has shown that IgM titers may correlate best with clinical infection.⁸

Viral infections, such as FIP, FeLV, and FIV, should be considered based on the indoor/outdoor status of the patient and exposure to multiple cat environments including households, catteries, shelters, and outdoor colonies. Even though retroviral infections such as FeLV and FIV are not a direct cause of vomiting, they may increase the patient's risk for an infectious disease that could lead to vomiting. FeLV has been associated with the development of lymphoma, although it has less commonly been linked to GI lymphoma and more typically with mediastinal or multicentric lymphoma. Suspicion of FIP in a cat should be based on a combination of history (cats younger than 3 yr or older than 10 yr of age, especially living in crowded conditions), clinical signs, and clinic-pathological (hyperglobulinemia, leukocytosis, non-regenerative anemia, hyperbilirubinemia) or pathological changes such as pyogranulomatous inflammation.⁹ FIP must be diagnosed by applying a workable knowledge of the disease with sensible weighing of signalment, history, clinical signs, clinic-pathologic findings, serology, and ante- or post-mortem examination of affected tissues by histopathology and immunohistochemistry.¹⁰ Diagnostic tests to consider in support of a diagnosis of FIP include cytological evaluation of effusions, serum electrophoresis, serum α₁-acid glycoprotein, serology for anti-feline coronavirus (FCoV) antibodies, Rivalta's test on effusion, direct staining of FCoV within macrophages by immunofluorescence in effusions, and histopathology. It is important to remember that coronavirus antibodies do not differentiate between corona-virus-exposed cats and diseased cats, and although cats with very low or negative FCoV antibody titers are less likely to have FIP, the diagnosis should not be made on antibody titers alone.¹⁰ The present gold standard for FIP diagnosis is immunohistochemistry on effusions or lesions containing infected macrophages.¹⁰

Fungal infections such as disseminated histoplasmosis and pythiosis in cats are rare, but suspicion for infection may be raised based on location and travel history. Histoplasmosis is more commonly seen in the central United States and near the Ohio, Missouri, and Mississippi River Valleys, and pythiosis is more commonly identified in the southeastern United States. GI pythiosis is rare in cats, but has been reported in two young adult male cats with focal intestinal lesions that were amenable to surgical resection.¹¹ Histologically, pythiosis is characterized by eosinophilic pyogranulomatous inflammation, and organisms typically are found within areas of necrosis or at the center of granulomas.¹² Additional testing for diagnosis of pythiosis may include culture, polymerase chain reaction (PCR) amplification, and serology. Histoplasmosis in cats more commonly presents as the disseminated form and also more commonly occurs in cats younger than 4 yr of age. Organism identification for histoplasmosis with either cytology or histopathology is required for a definitive diagnosis.¹³

Inflammatory Bowel Disease (IBD)

IBD is a common primary disease of the GI tract in cats that often causes chronic vomiting. Patients with IBD usually have a combination of persistent or recurrent vomiting, hyporexia, weight loss or diarrhea, and a histopathologic finding of inflammation on gastric and/or intestinal biopsies. It has been reported that IBD predominantly affects middle-aged animals and that there may be certain breed predispositions, including Siamese and other Asian breeds, but any breed may be affected.¹⁴ IBD is characterized as idiopathic if no underlying cause of inflammation can be found and other causes have been ruled out. IBD is reported to be the most common histopathologic diagnosis in cats with chronic GI disease, although its true prevalence is unknown.¹⁵

The most common type of inflammation reported in cats is lymphoplasmacytic (LP), followed by eosinophilic inflammation. Pyogranulomatous inflammation is a cause of primary GI disease in cats with FIP. The etiology of idiopathic IBD is unknown, but current hypotheses suggest that feline IBD, similar to IBD in humans and dogs, involves complex interactions between environmental factors (intestinal microbial imbalances, dietary components) and the mucosal immune system, resulting in chronic inflammation in susceptible cats.¹⁴ Gastric and intestinal biopsies are an essential step for the definitive diagnosis of IBD, and the World Small Animal Veterinary Association International Gastrointestinal Standardization Group has developed endoscopic, biopsy, and histopathologic guidelines for the evaluation of GI inflammation in companion animals.² A feline chronic enteropathy activity index has been developed to aid clinicians in defining disease activity in cats at the time of diagnosis and the response to medical treatment.¹⁶

Cats may also be affected by secondary small intestinal dysbiosis as a result of a primary GI disease, such as a motility disorder, partial obstruction, spontaneous/atrophic gastritis, neoplasia, or mucosal disease (IBD).¹⁷ Exocrine pancreatic insufficiency (EPI) may also be a cause of small intestinal dysbiosis in cats.¹ It is important to identify the underlying cause of secondary small intestinal dysbiosis, and even though diarrhea is the predominately reported clinical sign, vomiting may still occur from the primary GI disease. Small intestinal dysbiosis, or dysbacteriosis, is a clinical syndrome caused by alteration of the microbial balance of the small intestines, and it more commonly occurs secondary to a primary GI disease. Small intestinal dysbiosis is a difficult disorder to diagnosis in both dogs and cats, and testing may include culture of duodenal juice or several other noninvasive diagnostic tests, such as serum folate concentration, serum cobalamin concentration, unconjugated bile acid concentration in serum, breath hydrogen concentration, and C-xylose and C-bile acids tests. A combination of low cobalamin and high folate serum concentrations is highly specific for small intestinal dysbiosis, but rather insensitive.¹⁸ However, folate and cobalamin may be the most practical diagnostic tools suggestive of small intestinal dysbiosis in a private practice setting.¹⁸

Dietary/Adverse Food Reactions

Adverse food reactions and dietary problems can be divided into the two main categories of food allergies and food intolerance. Food intolerance is an abnormal physiologic response to food that does not have an immunologic basis.¹⁹ Food allergy is an immunologically mediated adverse food reaction. GI biopsy specimens may show the presence of eosinophils, suggestive of both food allergy and possible parasitic infection. LP enteropathy has also been associated with food allergy, parasitic infection, and feline hyperthyroidism.¹⁵

Clinical signs of a food allergy may manifest as GI disease and/or dermatological disease. It is likely that the majority of food allergies are a type-I IgE mediated hypersensitivity involving mast cell degranulation.²⁰ Due to the large number and variety of protein sources in commercial diets, it is often difficult to identify exact food allergens. A feline study has shown that 80% of adverse food reactions (cutaneous lesions and/or GI signs) were associated with diets containing beef, dairy products, or fish.²¹ The role of food allergy in feline IBD is unknown, but hypersensitivity to food may be involved in the pathogenesis.

Delayed Gastric Emptying/Motility Disorders

Delayed gastric emptying and GI motility disorders can lead to upper GI signs such as vomiting and anorexia. Gastric emptying disorders can be fairly common in both dogs and cats as the result of a variety of primary and extra-GI disease processes that may alter normal GI motility. A common history in cats with delayed gastric emptying is vomiting of undigested or partially digested food greater than 12 hr after eating. Other clinical signs may include gastric distension and abdominal discomfort, eructation, and weight loss. GI motility disorders may occur from mechanical obstruction from a polyp, tumor, granuloma, foreign body, stenosis or hypertrophy, extramural mass, or from functional obstruction from inflammation or infection. It is important to first rule out a mechanical obstruction leading to delayed gastric emptying or a motility disorder. Secondary disorders that may lead to delayed gastric emptying include electrolyte disturbances (hypokalemia or hypocalcemia), metabolic disorders (diabetes mellitus, hypergastrinemia, and uremia), medications (anticholinergics, beta-adrenergic agonists, and opiates), constipation/obstipation, peritonitis, or pancreatitis.²² Idiopathic delayed gastric emptying is suspected if no underlying primary cause can be found.

GI Neoplasia

Lymphoma is reported as the most common feline cancer, and the GI tract is the most common location.²³ The GI tract harbors the largest population of lymphoid and accessory immune cells in the body, and the diffuse, mucosal associated lymphoid tissue is largely populated by CD3⁺ T-cells.²⁴ T-cell lymphomas of diffuse mucosal associated lymphoid tissue of the small intestine are the most predominant GI lymphomas, which often co-exist with LP IBD or occur following a clinical history of IBD.²⁵ Results of a study performed by Moore et al. showed that the majority of cats with mucosal T-cell lymphoma had small cell lymphoma and a median survival of 28 mo.²⁴ The study also indicated that transmural T-cell lymphoma had a much shorter median survival of 1.5 mo, and that most of these cats had large cell lymphoma, specifically of the large granular lymphocyte type.²⁴ Feline GI B-cell lymphoma was also characterized as diffuse, large B-cell lymphomas, and they tended to occur with higher frequency in the stomach and ileocecocolic junction of cats.²⁴ In conclusion, their results showed that mucosal T-cell lymphoma of the small to intermediate cell type is the dominant form of lymphoma in the GI tract of cats and that it has a relatively long median survival time.²⁴

Adenocarcinoma is a rare GI tract neoplasm in cats, with the stomach the least affected region and the colon the most commonly affected region of the GI tract. Other types of cancer that have been identified in the GI tract of feline patients include mast cell tumor and leiomyosarcoma. Siamese cats are overrepresented in studies of intestinal adenocarcinoma and lymphoma, suggesting a breed predisposition.²⁶

Extra-GI Disease

Concurrent disorders such as IBD, pancreatitis, and cholangiohepatitis, also referred to as feline triaditis, may cause chronic vomiting. Other extra-GI disorders that should be considered include chronic kidney disease/uremia, hepatobiliary disease, toxin exposure, medications (nonsteroidal anti-inflammatory drugs, antibiotics, chemotherapy) and endocrine disease (hyperthyroidism, diabetic ketoacidosis).

Diagnostic Plan

Initial diagnostic testing should include a complete blood count, biochemical profile, total T4 (middle-aged to older cats), urinalysis, and fecal examination initially via zinc sulfate centrifugal flotation (may also consider cytology, culture, and/or PCR). A fecal exam should always be performed to look for parasites, especially when a peripheral eosinophilia is present, the patient is exposed to an outdoor environment, if there is a new young or foster cat introduced into the household, or if the patient comes from a multiple-cat environment. Abdominal radiography should also be considered and is most helpful in evaluating for gastrointestinal obstruction, but may also be helpful in defining extra-alimentary tract disorders that may lead to vomiting in cats. Please see the previous Infectious Disease section for further discussion of diagnostic testing for feline infectious diseases. If peritoneal effusion is present, then a sample should be obtained for pathology review and cytological interpretation and analysis including protein level, specific gravity, red blood cell, and nucleated cell count. If there is suspicion for primary hepatic disease with the absence of icterus, then pre- and post-bile acids can be evaluated to determine if liver dysfunction is present. Cats that have a history of hematemesis should have a coagulation profile (prothrombin time, activated partial thromboplastin time), platelet count, and buccal mucosal bleeding time performed.

Survey radiographs may detect abnormalities such as organomegaly or intestinal obstruction that might cause clinical signs of vomiting and decreased appetite.¹⁴ If there is concern for a GI obstruction from a foreign body, then contrast radiography or abdominal ultrasound can be considered for further evaluation. Ultrasonography may also be helpful to determine the cause of organomegaly if identified on radiographs. In addition to utilizing ultrasound to identify an obstructive process, a GI mass lesion, or extra-GI organ abnormalities, it may be beneficial in helping the clinician determine the most appropriate biopsy technique. For example, regional thickening of the jejunum or ileum, mesenteric lymphadenopathy, or a mass in an organ outside of the GI tract may indicate that an exploratory laparotomy or laparoscopy may be preferred to endoscopy.

When considering abdominal ultrasonography, it is important to remember that LP enteritis and lymphoma of the small intestine share similar features. Neoplastic infiltration is often characterized by more severe thickening of the GI tract with loss of wall layering, and lymphadenopathy tends to be larger when involved in neoplastic disease. In a study performed by Zwingenberger et al., findings indicated that ultrasonographic thickening of the muscularis propria of the small intestine of cats was significantly associated with lymphoma (98% T-cell) and that lymphadenopathy was associated with both lymphoma and IBD.²⁷ Their findings established a relationship between muscularis propria thickening and lymphoma and an increased diagnostic importance of abdominal ultrasound. However, due to the overlap of the ultrasonographic appearance of neoplastic disease and intestinal inflammation, histopathology is necessary for differentiation of the two.²⁸

With regards to gastric outflow obstruction, endoscopy is useful to help identify gastric abnormalities such as neoplasia, inflammatory lesions, and foreign bodies. Exploratory surgery may ultimately be needed for extramural lesions that are causing gastric outflow obstruction.

Additional diagnostics may include a feline GI Panel that consists of a pancreatic lipase immunoreactivity assay (PLI) for pancreatitis, cobalamin (Vitamin B12), and folate levels to evaluate small intestinal function. Consideration should also be given to running a trypsin-like immunoreactivity assay (TLI) to evaluate for EPI (Table 3). EPI is somewhat rare in cats, and if associated with chronic vomiting, then likely is a consequence of chronic pancreatitis. A radioimmunoassay for measurement of PLI has been developed and validated for pancreatitis, and the study concluded that the assay is sensitive, accurate, and precise.²⁹ The specificity and sensitivity of PLI in cats is reported as 82% and 79%, respectively.³⁰ A feline pancreatic lipase immunoreactivity assay (fPL) has recently become available for rapid screening as a semi-quantitative assay.^a If the fPL is suggestive of pancreatitis, then a PLI can provide additional quantitative information; if the fPL is negative, then pancreatitis is unlikely. TLI is specific for EPI, but the sensitivity of TLI concentration for pancreatitis in cats is only approximately 30–80%, making it a suboptimal diagnostic test for pancreatitis.³¹

Table 3 Feline GI Panel

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Several studies have investigated the concentration of cobalamin in cats with chronic GI disease and the clinical response to supplementation. Simpson et al. found that cats with subnormal cobalamin concentrations were middle-aged or older and presented for weight loss, diarrhea, vomiting, anorexia, and thickened intestines. Definitive diagnoses included IBD, intestinal lymphoma, cholangiohepatitis or cholangitis, and pancreatitis.³² A second study performed to evaluate the response to cobalamin supplementation found that after therapy, mean body weight increased significantly.³³ Chronic GI disease can also change folate levels. Mucosal disease in the proximal small intestine may reduce folate absorption, or small intestinal dysbiosis may cause an increase in the folate level.

More invasive diagnostic techniques may be required to reach a definitive diagnosis. Ultrasound-guided fine needle aspiration or biopsy can be used to obtain samples of enlarged lymph nodes, organomegaly, and masses. While changes in intestinal wall thickness and architecture can help to raise suspicion of disease, as previously stated, ultrasound alone cannot diagnose or differentiate IBD from lymphoma. GI biopsies are necessary for definitive diagnosis and may be obtained either with upper/lower GI endoscopy or an exploratory laparotomy.

Scott et al. performed a retrospective study to evaluate the agreement between endoscopic biopsies of the duodenum and ileum in cats with primary GI disease. Cats within their study population frequently had different endoscopic diagnoses depending on the location of biopsies. These results suggested that there is a population of cats in which a diagnosis of lymphoma can only be found by evaluation of ileal biopsy specimens. Therefore, clinicians should consider performing both upper and lower GI endoscopy to help increase diagnostic yield.³⁴

A second prospective study that compared endoscopic and full-thickness biopsy samples for the diagnosis of IBD and alimentary lymphoma in cats determined that endoscopic biopsy specimens were useful for the diagnosis of gastric lymphoma but were not adequate for differentiating between IBD and lymphoma in the small intestine.³⁵ Limitations of this study include the fact that only half the cats undergoing endoscopic biopsy had the duodenum included in sampling, and, in a few of the cases, duodenal biopsy was performed blindly. The authors of this study concluded that since the most common sites of alimentary tract lymphoma in cats are the jejunum and ileum, then full-thickness biopsy specimens of these sites should be obtained via laparotomy or laparoscopy for accurate diagnosis.

The decision as to whether to perform endoscopic versus full-thickness GI biopsies remains debatable. Factors such as the location of intestinal thickening, abnormalities of other abdominal organs on ultrasound, low folate or hypocobalaminemia, and the cost and availability of the different procedures should be considered.

Despite histopathologic review of gastric and small intestinal biopsy specimens, it can still be difficult to distinguish mucosal inflammation and small cell lymphoma. Kiupel et al. performed a retrospective study showing that combining histologic evaluation of small intestinal biopsy specimens with immunophenotyping and analysis of clonality of lymphocytes results in more accurate differentiation of neoplastic versus inflammatory disease. Based on the authors' results, they devised a stepwise diagnostic algorithm that first uses histologic assessment, followed by immunophenotyping and then PCR to determine clonality of the lymphocytes to more accurately differentiate between intestinal lymphoma and IBD.³⁶

A therapeutic plan should be developed based on the primary etiology or concurrent disorders leading to chronic vomiting. Treatment strategies for primary GI and extra-GI diseases in cats are beyond the scale of this discussion.

Conclusion

We have reviewed causes for chronic vomiting in cats and a diagnostic approach to determine the etiology. An extensive evidence-based review of the mechanisms, causes, investigation, and management of vomiting in cats by Batchelor et al. has been published in the Journal of Feline Medicine and Surgery for interested readers to gain further information on this subject.³⁷ Initial diagnostic tests for cats should include screening for hyperthyroidism, heartworm, hepatobiliary, and renal disease. Testing for concurrent problems such as hypocobalaminemia and pancreatitis are recommended. Abdominal imaging with radiographs and ultrasound are often helpful. Upper/lower GI endoscopy or an abdominal exploratory for GI biopsies may be necessary for a definitive diagnosis. The therapeutic approach for a feline patient with chronic vomiting should then be developed based on primary and concurrent etiologies identified.