• FIV and Chronic Diarrhea


  • 1. Background

  • 2. Types of Diarrhea

  • 3. Treatment Options

  • Click here to open a Glossary of Terms in a separate window.


  • 1. Background

  • According to one set of published statistics, 10-20 % of FIV+ cats have chronic or recurrent diarrhea as a symptom of their infection [1], placing it behind oral disease, upper respiratory infection, and eye infection in order of occurrence. No definitive explanation exists for the frequency of FIV-related diarrhea. In one study of 10 FIV+ cats with chronic diarrhea, a specific pathogen could be isolated from only one [2]. So unless the tests used to isolate pathogens are inadequate, there is something about FIV infection that predisposes cats to diarrhea. One classic source writes as follows:

  • FIV-infected cats with chronic diarrhea and wasting often show a characteristic severe and diffuse villous atrophy that is particularly evident in the lower half of the small intestine, and focal areas of mural necrosis with fibrosis in the wall of the intestine. Lymphoid tissue within the intestinal wall is often hyperplastic with pronounced increase in the number of B lymphocytes and plasma cells. Intestinal lesions are reminiscent of those caused by acute panleukopenia virus [feline parvovirus] infection, but they are chronic rather than acute in nature. [2b]

  • Experience with chronic diarrhea in HIV-infected humans and SIV-infected primates may point to a role for direct action of the virus upon gut-associated lymphoid tissue (GALT) as a component (a disproportionate number of HIV relative to the rest of the body inhabit this tissue). Studies have found that GI symptoms that include diarrhea improve significantly as soon as one week after antiretroviral drugs are begun, suggesting that the virus itself has a central role in the GI tract pathology; it is possible, therefore, that any therapy having a significant impact on FIV viral load might have some impact on FIV-related bowel problems. However, an inflammatory immune response is almost certainly involved, as well. One recent source speculates, “IL-6 [interleuken-6] is an important proinflammatory cytokine [i.e., immune-signaling protein] that is believed to enhance HIV replication and is also up-regulated in several chronic inflammatory conditions such as inflammatory bowel disease, rheumatoid arthritis, and numerous neoplastic conditions . . . . In the GI tract, both primary HIV/SIV replication and the cytokines/chemokines elaborated thereafter by inflammatory cells have the potential to activate several signal transduction pathways. Activation of these signaling pathways secondary to virus infection may interfere with the homeostatic signaling events required to maintain normal GI structure and function, thereby leading to compromise of the intestinal barrier. Although the etiology of chronic diarrhea in HIV-infected patients remains complex, proinflammatory cytokine networks may be expected to play a central role.” [19]. TNF-α (tumor necrosis factor alpha), another pro-inflammatory cytokine upregulated by HIV and FIV infection, has been strongly implicated in human colonic inflammatory disease, and the TNF-α suppressor drug infliximab has produced dramatic therapeutic results [23].

  • A clue to approaching the problem may lie in the areas of similarity between ideopathic inflammatory bowel disease and another common inflammatory disease seen in FIV+ cats, chronic stomatitis/gingivitis. The latter:

  • ■    occurs in FIV-cats, but has a stronger statistical association with FIV+ cats.

  • ■    includes predominating lymphocytic-plasmacytic* cellular infiltrates in biopsied mucosal tissue

  • ■    has been theorized (in the case of L-P) to involve disturbance in local lymphocyte populations, which show a shift from a predominant CD4+ Th1 profile to a mixed Th1/Th2 profile and a loss of control of the inflammatory immune response

  • ■    is believed to involve sensitivity to certain food components–whether additives, carbohydrates, or certain types of meat products or byproducts is not clear and may vary from case to case.

  • ■    involves a probable interaction between or cumulative action of other alien antigens and FIV, leading to an abnormal response to normally present bacteria.

  • All except the last have been ruled in with regard to chronic inflammation of the large and/or small bowel, and evidence is accumulating for the last [2a].

  • *Some IBD may be eosinophilic or granulomatous in nature; so, for that matter, may oral lesions. However, in both cases, lymphocytic-plasmacytic is most common.

  • 2. Types of Diarrhea

  • “Simple” Diarrhea. An adult cat can be given 24-48 hours to sort out an episode of diarrhea that may have been sparked by dietary factors or other transient influences, such as stress. However, if the diarrhea is bloody, black, or mucus-laden or if it is accompanied by pain, excessive straining, fever, recurrent vomiting, or depression, a vet should be contacted immediately. Extra caution should always be exercised with kittens (especially those that have not yet received vaccinations), who can dehydrate rapidly. Attention to hydration (and rehydration, if necessary, with lactated Ringers solution) is a consideration in any cat suffering from significant diarrhea.

  • Environmental Diarrhea. A variety of ingested environmental substances can cause diarrhea in a cat. These include aspirin, acetaminophen, and other NSAIDS; coal-tar containing shampoos and disinfectants; insecticides; and antifreeze. In such cases, the diarrhea will be accompanied by other acute symptoms. Immediate emergency care is called for.

  • Nonpathogenic Diarrhea. A variety of other circumstances can involve diarrhea, which will not, however, usually be the only symptom. These include diabetes, hyperthyroidism, kidney disease, liver disease, exocrine pancreatic deficiency (unusual in cats except as a result of chronic pancreatitis), and cancers of the large or small bowel. Dietary allergy or intolerance may play a role in more complex, immune-mediated diarrhea, but sometimes is the sole cause of bowel disorder, which is correctable by dietary means alone. Treatment in all of the aforementioned cases focuses on the element outside the GI tract that is responsible for the GI symptoms.

  • Pathogenic Diarrhea. Diarrhea can be caused by a variety of parasitic, viral, and bacterial pathogens. Although there is no record of particular enteral organisms to which FIV+ cats as a group are liable, it is reasonable to assume that immune deficits can open the way to infections. Infection can also be a complication of inflammatory disorders of nonpathogenic origins

  • Viruses. Among viruses are the panleukopenia (distemper) virus, a panleukopenia-like syndrome found in FeLV+ cats, enteric coronaviruses, and astroviruses, all of which will produce symptoms beyond diarrhea alone. Intensive supportive care is the general prescription for viral enteritises.

  • Bacteria. Loss of normal intestinal bacterial flora and/or overgrowth of pathogenic resistant species as a result of antibiotic therapy directed at other problems is not uncommon. Bartonella henselae has recently been implicated in feline gastrointestinal disease. Clostridium perfringens, part of the normal intestinal flora in cats, can, in some strains and under some conditions of the GI tract, produce enterotoxins that cause either acute or chronic intermittent diarrhea. Primary bacterial causes of diarrhea in cats are usually self-limiting, and often do not require antibiotic therapy. When they do, here is a table of some appropriate drugs and dosages [3].

  • Drug Dose Indications

  • Enrofloxacin............. 5 mg/kg q12h PO................Gram negative bacteria, C.difficile
  • Ampicillin................ 10-20 mg/kg q8h PO ..........Clostridium perfringens
  • Ampicillin.................10-20 mg/kg q8h IV, SC ...Sepsis (use with aminoglycosides)
  • Gentamicin............... 2.2 mg/kg q8h IV, SC........ Sepsis
  • Cephalothin.............. 22-44 mg/kg q8h IV, IM.... Sepsis
  • Metronidazole...........10-20 mg/kg q12h PO........ C. perfringens, C. difficile,
  • Tylosin..................... 20-40 mg/kg q12h PO C..... perfringens,
  • Erythromycin........... 10-15 mg/kg q8h PO...........Campylobacter
  • Trimethoprin-sulfa.. 15 mg/kg q12h PO, IV, SC.. Salmonella

  • Parasites. Many parasitic causes of diarrhea in kittens (e.g., nematodes such as round worms and hook worms) produce little or no diarrhea in adult cats. However, FIV-induced immunosuppression could conceivably encourage their expression. Initial infections of toxoplasmosis are associated with diarrhea; reactivated infections associated with immunesuppression are not. Giardiasis is a notable threat in adult cats. Giardia (a one-celled parasite) infection, which can cause diarrhea, can induce serious weight loss. However, adult cats infected with Giardia often have only soft stools, sometimes even normal ones. Cryptosporidiosis is a usually self-limiting parasitic disease that can persist beyond a few weeks in cats with underlying immune disorders.

  • The following are WSAVA diagnostic guidelines for persisting diarrhea of suspected pathogenic origin:

  • “. . .the minimum database should include a complete blood count (CBC), a serum biochemistry profile, a urinalysis, a fecal flotation for parasitic ova, and a direct smear of saline admixed fresh feces for protozoa. Encysted forms of Giardia organisms in a fecal specimen may be detected most reliably with zinc sulfate flotation, as opposed to examination of fresh saline smears.(1) Preliminary studies in Giardia-infected cats at the University of California, Davis, have revealed that the ProSpecT® Microplate ELISA Assay compares favorably in sensitivity and specificity to the zinc sulfate flotation technique; however, the sensitivity of the ProSpecT® Giardia Rapid ELISA Assay is significantly less than that of the Microplate Assay and zinc sulfate flotation methods. Similar studies have been performed in Cryptosporidium-infected cats at the University of California, Davis, and preliminary findings have revealed that the ProSpecT® Cryptosporidium Microplate Assay is equally sensitive. . . .” [3]

  • Inflammatory Bowel Disease. IBD is, in part, a diagnosis of exclusion. A refractory bowel inflammation for which no other cause can be found is usually labeled as suspected IBD. Like FIV-related diarrhea, IBD is an immune-mediated inflammatory bowel disease of uncertain etiology which is probably a group of diseases involving chronic intestinal mucosal inflammation rather than a single disease with a single cause. In both cases, “clinical signs are attributed mucosal cellular infiltrates and inflammatory mediators”[4], and seem to involve breach of the intestinal epithelial barrier and cytokine dysregulation (i.e., immune signaling and response). Attempts to characterize the dysregulation have found no single pattern. “Pathologic interactions between intestinal bacterial flora and the innate or acquired immune system are suspected to play a role in the pathogenesis of IBD across species” [20].

  • So ideopathic IBD is a good place to go in search of clues about how to regard and treat FIV-related diarrhea for which no other cause is evident. To what extent chronic and recurrent FIV-related diarrhea should be regarded as an IBD is unclear, but a relationship is likely. IBD can involve the small bowel, the large bowel, or both. It is likely that different specific causes or interactions of disease-associated elements are involved with different locales of inflammation. Therapeutics which impact the large bowel may not impact the small bowel, and vice versa. The following table [5] offers diagnostic criteria for locating the inflammation in dogs, but largely holds for cats, as well:

  • Differentiation of Small Intestinal from Large Intestinal Diarrhea
  • The Feces
    		•
  • Small Intestine
    		•
  • Large Intestine
    		•
  • Volume
    		•
  • Markedly increased
    		•
  • Normal or increased
    		•
  • Mucus
    		•
  • Rarely present
    		•
  • Common
    		•
  • Tarry Stools
    		•
  • May be present
    		•
  • Absent
    		•
  • Fecal Blood
    		•
  • Absent except in acute
    hemorrhagic diarrhea
    		•
  • Fairly common
    		•
  • Fatty Stools
    		•
  • Present with maldigestive or
    malabsorptive disease
    		•
  • Absent
    		•
  • Undigested food *
    		•
  • May be present with maldigestion
    		•
  • Absent
    		•
  • Color
    		•
  • Color variations occur, e.g., creamy
    brown, green, orange or clay color
    		•
  • Color variations rare,
    may be bloody
    		•
  • Defecation
    		•
  •  
    		•
  •  
    		•
  • Urgency
    		•
  • Absent except in acute or very
    severe disease
    		•
  • Usually but not invariably
    present
    		•
  • Straining
    		•
  • Absent
    		•
  • Frequent but not invariably
    present
    		•
  • Frequency
    		•
  • 2 to 3 times normal for the patient
    		•
  • Usually greater than 3 times
    normal
    		•
  • Constipation
    		•
  • Absent
    		•
  • Present with distal colonic
    or rectal disease
    		•
  • Ancillary Signs
    		•
  •  
    		•
  •  
    		•
  • Weight loss
    		•
  • May occur in maldigestive or
    malabsorptive disease
    		•
  • Rare except in severe colitis,
    diffuse tumors or histoplasmosis
    		•
  • Vomiting
    		•
  • May be present in inflammatory
    disease
    		•
  • Uncommon, but occurs in up
    to 25-30% of dogs with colitis
    		•
  • Flatulence and
    Rumbling
    		•
  • May be reported with maldigestion
    and malabsorption
    		•
  • Absent
    		•
  • Halitosis in the
    absence of oral
    disease
    		•
  • Present with maldigestion or
    malabsorption
    		•
  • Absent
    		•

  • * One net vet asks his clients to bring him the diarrhetic stools in a cup. One of the things he does is run it through a strainer looking for undigested food particles.

  • Because cats have a common duct exiting the liver and pancreas and emptying into the bowel, chronic bowel inflammation can also cause concurrent inflammation of either or both. This is called triaditis, a problem that is difficult to treat in the liver and pancreas until the bowel inflammation has been successfully addressed.

  • The gold standard for diagnosing the presence and type of IBD is a biopsy of intestinal tissue, although a thorough history, hemograms, blood chemistries, fTLI (pancreatic testing), radiographs (including barium and radiopaque studies when chronic vomiting is present), fecal analysis, and gut function (folate/ B12 or breath hydrogen testing for malabsorption) testing all provide potentially useful information.

  • A generally accepted sequential protocol for diagnosing the cause of unexplained ongoing diarrhea is as follows: Rule out extra-GI causes with appropriate blood testing, fecal testing, and radiography > Rule out undiagnosed parasites with fenbendazole trial > Rule out dietary sensitivity with a food trial > Rule out GI lymphoma with endoscopy and/or full-thickness biopsy > Initiate antimicrobial trial with antibiotics > Initiate trial with immunosuppressive drugs [20].

  • 3. Treatment Options

    • First 48 Hours
    Diet:
  • ■    Withhold food for 24 hours. Reintroduce food in small, frequent feedings..
  • ■    Offer bland diet of boiled meat with no grains or fiber (although some vets recommend rice.)

  • Motility Modulators:

  • ■    Imodium Liquid (.2mg/ml): 1 ml/4 lbs 2 to 3 times daily

  •     *Do not give Pepto Bismol or reformulated Kaopectate, which can be toxic to cats [6]
  •     *Antispasmodics and anticholinergics such as aminopentamide are no longer recommended for control of uncomplicated diarrhea.

  • Intestinal Coaters:

  • ■    Slippery Elm, Plantain, or Flax Seed (for mucilage)

  • ■    Diarsanyl

  • Astringents:

  • ■    Chamomile (control intestinal water uptake)

  • ■    Berberine-containing herbs such as oregon grape, goldenseal, coptis (inhibit intestinal secretory response; also have natural activity against some pathogenic bacteria)

  •     *Viable Pet has a “Support for Diarrhea” product containing agrimony, barberry root, bilberry leaf, bistort, fennel seed, marshmallow root, plaintain leaf, psyllium seed, sage, slippery elm and stevia leaf that may be used for up to seven days.

  • Longer Term

  • Longer-term diarrhea for which no specific cause can be found might be treated in ways suggested by management of chronic inflammatory bowel disease.

  • Diet:

  • ■    Add a fiber source to the normal diet. Options include a food specifically formulated with high-fiber or addition of canned pumpkin (not pumpkin-pie filling) or unflavored Metamucil (psyillium fiber). [4]

  • ■    Change foods. Cats are obligate carnivores. Any food element not part of their natural diet a potential source of allergy or intolerance. Options include any of the following: a food without grains, a food without dyes and other suspect additives, or a raw diet. The last remains somewhat controversial in FIV+ cats, but has many experienced proponents.

  • ■    Add yogurt to the diet intermittently. ( Yogurt may, but usually does not, spark lactose intolerance. If antibiotics are the suspected cause of diarrhea, may be started immediately.)

  • ■    A protein hydrolysate diet such as Hills z/d (involving protein reduction to more absorbable form)

  • Supplements:

  • Many readily available supplements have shown clinical and/or experimental ability to favorably impact large and/or small bowel inflammation of pathogenic or immune-mediated origin and its effects. These include:

  • ■    Probiotics and/or Prebiotics [7] ( protection of intestinal epithelial cell and barrier function, prevention of enterotoxin binding to intestinal epithelial cells, and regulation of intestinal microbial environment. If antibiotics are the suspected cause, may be started immediately.) Sacchromyces boulardii, a probiotic yeast, has specific inhibitory activity against clostridium.

  • ■    Digestive Enzymes (predigest food moving rapidly through the GI tract.)

  • ■    Omega 3 & 6 Fatty Acids/Fish Oil (Inhibits synthesis of leukotrienes responsible for allergic reactions) [8][4]

  • ■    Lactoferrin (Immunomodulates inflammatory cytokine expression in intestines) [9]

  • ■    Colostrum (Promotes cell wall permeability; mechanism uncertain) [10]

  • ■    Glutamine (Improves removal of water from intestines, promotes gut permeability)[10]
  •       *Combined with colostrum, reduced cell wall damage. Combined with probiotics, widely used to control HIV-related diarrhea.

  • ■    Curcumin/Turmeric (Immunomodulates inflammatory response via suppression of transcription factor NF-kB) [15]
  •       *Has successfully controlled HIV-related diarrhea at 1862 mg daily [22]

  • ■    Licorice (Restores the intestinal lining, increases the quantity and quality of mucin, increases the life span of intestinal cells, improves mucosal blood flow) [25]
  •       *Deglycyrrhizinated (DGL) licorice, a nutraceutical extract of licorice, has no dosage restrictions and lacks the adrenal effects of licorice that otherwise require dose monitoring

  • ■    Boswellia (Inhibits inflammatory leukotriene B4; outperformed sulfasalazine in treatment of colitis) [17]

  • ■    AHCC / Active Hexose Correlated Compound (Magnitude of antiinflammatory effect found similar to that of sulfasalazine; higher aerobic and lactic acid bacteria counts, as well as higher bifidobacteria counts) [18]

  • ■    Melatonin (may have a direct effect on many GI tissues by a variety of possible mechanisms, including inhibition of nitric oxide production, COX-2 expression, and NF-κB activation; reduction of proinflammatory cytokines, bacterial translocation, and injurious macrophage activity) [21]
  •  
  • ■    Vitamins, esp. B12. There is evidence that cobalamin supplementation may produce improvement in cats with IBD [24]. A multivitamin can compensate for poor GI absorption or specific vitamins such as Vitamin E to assist in utilization of Fatty acids

  • Antibiotic Anti-inflammatories.

  • Small intestinal bacterial overgrowth (SIBO) is a major secondary complication of many bowel diseases [16]. It has been noted that bacteria characteristically inhabiting the large intestine are found in unusual numbers in the small intestine. Clostridium and e coli have been singled out in a number of studies. Natural antibiotics with activity against these bacteria may be of value.

  • ■    Metronidazole

  • ■    Tylosin

  • Pharmaceutical antibiotics such as metronidazole have anti-inflammatory immunomodulating activity in addition to antibiotic activity, are useful for controlling bacterial overgrowth, and have been shown to be safe for sustained use over extended periods; some inhibition of T-cell recruitment, but acceptable for FIV+ cats. One source has noted instances when fluoroquinolones (enrofloxacin, marbofloxacin, etc.) produced dramatic results after metronidazole and immunosuppressive drugs (see below) had failed to have an impact [20].

  • Inflammatory Bowel Disease

  • This file is not about Inflammatory Bowel Disease as such, only about IBD as a model for approaching FIV-associated diarrhea. Treatment of IBD (or use of an IBD-inspired treatment strategy) should be coordinated with a veterinary practitioner of some sort.

  • Dietary:

  • ■    Elimination Diet–Feeding a novel protein only ( ie., a meat source that the cat is unfamiliar with, such as lamb or rabbit) to establish allergy to or intolerance of a usual dietary component [4].

  • Other Natural Therapies (See Longer Term>Supplements):

  • ■    Teas, Tinctures, Herbs–2 parts slippery elm or plantain, 1 part marshmallow root, 1 part licorice root, 1 part fennel seed [11]

  • ■    Supplements–250mg n-acetylglucosamine, 250mg glutamine, 10mg proanthocyanidin complex, 50mg DMG, 250mg vitamin C [12]

  • Antacids

  • ■    Zantac (ranitidine), more often used for vomiting or megacolon, is sometimes of help with IBD diarrhea, as well.[13]

  • Steroidal Anti-Inflammatories::

  • ■    Prednisolone, Prednisone (1-2mg/kg) [4] (Use with caution in FIV+ cats)

  • ■    Budesonide [14] (Has a localized action that makes it worth trying before systemic steroids such as prednisolone or prednisone)

  • Other Antibiotic Anti-Inflammatories: (See Longer Term> Antibiotic antiinflammatories)

  • ■    Sulfasalazine (10-12 mg/kg every 12 hrs), Azathioprine

    • ■    Mesalamine, Olsalazine (5ASA human drugs now being used with caution on cats)

  • Immunosuppressive drugs: (Stongly inhibit T cell recruitment and amplification; not a realistic alternative for FIV+ cats)

  • ■    Cyclosporin

  • ■    Chlorambucil

    • ____________________________________________________

  • References

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  • http://www.peteducation.com/article.cfm?cls=1&cat=1316&articleid=213
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  • http://www.ncbi.nlm.nih.gov/pubmed/9582958
  • [2a] V. L. Inness, A. L. McCartney, C. Khoo, K. L. Gross and G. R. Gibson. Molecular characterisation of the gut microflora of healthy and inflammatory bowel disease cats using fluorescence in situ hybridisation with special reference to Desulfovibrio spp. Journal of Animal Physiology and Animal Nutrition. 91, Issue 1-2, 48 - 53.
  • http://www.blackwell-synergy.com/doi/abs/10.1111/j.1439-0396.2006.00640.x?journalCode=jpn
  • [2b] Niels Pedersen. The feline Immunodeficiency Virus. The Retroviridae. Jay A. Levy (ed.) (1993), p.215.
  • [3] Stanley Marks. “Diagnostic and Therapeutic Approach to Cats with Chronic Diarrhea.” WSAVA World Congress--Vancouver, 2001.
  • http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00116.htm
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  • http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2002&PID=2585&Category=414
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  • http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2004&PID=pr08667&O=Generic.
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  • http://www.2ndchance.info/diarrhea.htm.
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  • http://www.ncbi.nlm.nih.gov/pubmed/15284393?.
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  • http://www.ajcn.org/cgi/reprint/71/1/339S.pdf.
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  • http://ajpgi.physiology.org/cgi/reprint/00331.2001v1.pdf.
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  • http://www.ncbi.nlm.nih.gov/pubmed/15919136? .
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  • http://www.vetinfo.com/cdiarrhea.html.
  • [14] http://www.marvistavet.com/html/body_budesonide.html.
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  • http://ajpgi.physiology.org/cgi/content/abstract/285/1/G235.
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  • http://www.ncbi.nlm.nih.gov/pubmed/11488449?
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  • J Nutr. 2007 May;137(5):1222-8.
  • http://jn.nutrition.org/cgi/content/full/137/5/1222
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  • http://journal.shouxi.net/qikan/articledes.php?id=347528
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  • http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2009&Category=8072&PID=53492&O=Generic
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  • http://www.ncbi.nlm.nih.gov/pubmed/19051018
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  • http://www.womensportsmedicine.org/professional-conditions_13376.asp
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  • wvc.omnibooksonline.com/data/papers/2010_S23B.pdf
  • [25] Licorice and Deglycrrhizinated Licorice (DGL). Wellvet.Com
  • http://www.wellvet.com/licoricedgl.htm

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