Inflammatory Bowel Disease of the Dog

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The Inflammatory Bowel Disease (IBD) of the dog is in dogs occurring chronic inflammatory disease of the intestine . The cause is unknown. Presumably it is triggered by an interplay between genetic factors, environmental influences, changes in the composition of the intestinal flora and a pathologically increased response of the immune system. The main symptoms are diarrhea and vomiting , which occurs constantly or repeatedly over a long period of time, and a resulting weight loss. As with chronic inflammatory bowel diseases in humans , inflammatory cells migrate into the intestinal wall, rarely also into the stomach wall . The diagnosis of IBD is made after excluding other intestinal diseases, especially infectious and feed-related intestinal diseases, by examining the tissue of punched samples from the intestinal wall. The disease cannot be cured. With drugs that suppress the immune system (immunosuppressants), dietary measures and the strengthening of the intestinal flora with probiotics , IBD can at least be brought under clinical control in some patients, but the overall prognosis is poor.

Disambiguation

The name Inflammatory Bowel Disease - German 'inflammatory bowel disease' - is conceptually so unspecific that it can be understood as all intestinal inflammations ( enteritis ). In the past, the term was used relatively uncritically, so that there are no reliable figures on the incidence of the disease. Today, however, this term only refers to idiopathic inflammatory bowel disease (idiopathic IBD, IBD in the narrower sense), i.e. bowel inflammation without a recognizable cause. Like the chronic inflammatory bowel diseases in humans with the two main forms Crohn's disease and ulcerative colitis , dogs are probably also a whole group of diseases.

Cause and development of the disease

The cause of the disease has not yet been clarified; one suspects an interplay between genetic factors, environmental influences, changes in the composition of the intestinal flora and an inadequate response of the immune system .

In human Crohn's disease , which also belongs to the group of chronic inflammatory bowel diseases, a number of genes have been identified that contribute to the development of the disease, in particular the genes NOD2 , IL23R and ATG16L1. In dogs, changes in individual base pairs ( single nucleotide polymorphisms ) in the toll-like receptor 5 gene can be demonstrated in diseased animals , regardless of race . However, IBD is a polygenic disease, so many genes are involved in its development. In the German Shepherd Dog , a dog breed that is often affected, single nucleotide polymorphisms were found in 16 different genes, which show a potential relationship to the occurrence of IBD.

Escherichia coli , a type of bacteria that is part of the normal intestinal flora in dogs

A deciding factor in the development of the disease appears to be a reduced tolerance of the intestine to harmless pathogens or food components. Normally, food components are broken down into very small molecules during digestion , which are absorbed through the intestinal mucosa and do not trigger an immune reaction (“oral tolerance”). If the intestinal barrier is damaged, larger exogenous molecules ( antigens ) enter the blood and lead to a sensitization of the immune system . For example, 42% of dogs that developed parvovirus - a viral disease that is associated with considerable destruction of the intestinal villi - as a puppy develop chronic diarrheal diseases later in life.

The entirety of the microorganisms in the intestine - the intestinal flora - also play a role in the development of IBD. The physiological intestinal flora is of great importance for health. It forms a defense barrier against pathogens ( colonization resistance ), supports digestive activity and the release of nutrients, supplies the intestinal epithelial cells with nutrients and stimulates the immune system. In dogs with IBD, the species composition of the intestinal flora is disturbed. As with humans, it is also assumed in dogs that previous antibiotic treatments can lead to a lasting disruption of the composition of the intestinal flora and thus promote the development of chronic intestinal inflammation. In one study the proportion of bacteria of the strains Fusobacteria and Firmicutes was reduced, in the latter mainly representatives of the genus Faecalibacterium . Changes in the intestinal flora in chronic inflammatory bowel diseases have also been described in humans and the Faecalibacterium prausnitzii, which is known for its anti-inflammatory effects, is significantly reduced in patients with active IBD. In a more recent study, however, faecal bacteria such as Escherichia - Shigella , Clostridia , Blautia , Bifidobacterium , Enterococci , Pseudomonads and Lactobacilli occurred more frequently in sick animals, while representatives of the Bacteroidetes , Streptococci , Fusobacteria , Peptoclostridia and Turicibacteria were reduced. However, even the natural composition of the intestinal flora has been little researched and the systematic assignment of many intestinal bacteria is still uncertain. Another aspect that has not yet been studied in dogs is the interplay between intestinal bacteria and antibodies of type A (IgA) and G (IgG). In Crohn's disease patients, these immunoglobulins preferentially bind to certain disease-causing bacteria. A recent study found a 30% increase in the number of IgG-bound intestinal bacteria in dogs with IBD. In particular Actinobacteria species, especially members of the genus Collins Ella are doing increasingly bound to IgG. The immunoglobulins are mainly formed in the intestinal wall and not in the blood. In addition, an increased number of phagocytosed bacteria could be detected in the intestinal wall. In contrast to Crohn's disease patients, dogs with IBD produce less IgA than healthy dogs and the number of IgA-bound bacteria does not appear to be increased either.

The processes involved in the development of the disease ( pathogenesis ) at the cellular and molecular level are at least basically known for the main form of IBD in dogs, lymphocytic-plasmacellular enteritis (see below). Here, T lymphocytes migrate into the intestinal mucosal layer, especially those with the CD4 receptor (CD4 +), an increase in the acute phase protein C-reactive protein and an increased expression of cytokines such as interleukin-2 , interleukin- 12 , interferon-γ , interleukin-5 , tumor necrosis factor -α and transforming growth factor β.

Clinical picture and further diagnostics

As a rule, middle-aged dogs are affected. The main symptoms of IBD are chronic diarrhea and vomiting . The diarrhea can be either small or large intestine in character. Colon diarrhea is characterized by watery faeces, the urge to defecate and frequent defecation, while in the case of small intestinal diarrhea the frequency of faeces is not significantly increased and the faeces are rather mushy. Intestinal bleeding with tar or blood stools may also occur. Eating and weight loss are also common. Due to loss of blood proteins like albumin through the intestines, the water holding capacity of the reduced blood and, for fluid leakage into various tissues ( edema ) or in body cavities ( ascites , Thoraxerguss ) come. It is typical of IBD that the clinical symptoms in a patient are variable and phases of improvement and worsening of the condition alternate.

Hypoproteinemia , an increase in eosinophils, and a stress leukogram are common in the blood . Intestinal bleeding can also lead to anemia ( anemia , initially regenerative ) and an increase in the number of blood platelets . C-reactive protein and alpha-1 acid glycoprotein are increased. The excrement examination serves to clarify parasitic intestinal diseases ( giardiosis , roundworm and tapeworm infestation ). The bacteriological examination of the feces is rarely helpful in dogs; it is not conclusive to prove the disturbance of the intestinal flora. The determination of the α-1-antitrypsin in the feces enables the detection of the protein loss via the intestine, but is so far only possible at Texas A&M University . PLI and TLI tests are used to rule out diseases of the pancreas that can trigger clinical symptoms similar to IBD. Tests to determine the permeability or absorption of substances in the intestine using Cr - EDTA or Iohexol have not yet been established in veterinary medicine. A urine test is only useful for delineating kidney-related protein loss. Imaging methods are important for differentiating between other intestinal diseases, especially malignant lymphoma of the intestine; they are not suitable for confirming the diagnosis of IBD, as there are usually no changes in the intestinal wall that can be identified with imaging methods. The contrast-enhanced ultrasound , with which the blood flow in the intestinal wall can be recorded, is principally suitable for the detection of chronic inflammatory changes in the intestinal wall.

Pathohistology and Diagnosis

Neither the clinical nor the laboratory results nor the imaging give specific indications of the presence of IBD, they rather serve to differentiate other intestinal diseases. The diagnosis of IBD can currently only be made by examining a tissue sample from the intestine. Since the sampling can only be carried out under general anesthesia , the exclusion of other diseases is strongly recommended. Deworming is also useful in the case of negative parasitological findings , because false negative results are particularly common with tapeworm diseases. An exclusion diet with a previously unused or hydrolyzed protein source should also be carried out to differentiate between feeding-related bowel diseases. Under certain circumstances, can probiotics or bowel effective antibiotics are used. These "diagnostic therapies" - that is, treatments that, if successful, indicate a cause of the disease - should only be avoided if the animal is seriously ill and has a pronounced albumin deficiency . In this case, a sample must be taken immediately.

Samples can be taken from the intestine endoscopically or through an opening in the abdominal cavity . The advantage of endoscopic sampling is that no surgery is necessary and therefore no wound healing disorders can occur, and the risk of septic peritonitis is very low. It is also faster and areas with changed mucous membranes can be specifically selected. The disadvantage is that only the anterior small intestine is accessible via the esophagus and stomach , and when accessed via the rectum only the large intestine and also the hip via the ileocecal valve , large parts of the empty intestine are not. In addition, the passage from the large intestine through the ileocecal valve is technically demanding and not always successful, even for experienced people. In addition, the samples obtained are usually only small and only cover the mucous membrane . In surgical interventions, a sample that encompasses the entire intestinal wall can be obtained, but targeted sampling of changed areas is not possible, since only the muscle layer and its serosa coating are visible here.

Histologically ( histopathology ) shows up in the intestinal wall diseased animals an increased number of plasma cells and lymphocytes , less frequently, of eosinophils or neutrophils in the mucosa intrinsic layer . The tissue assessment always has a subjective component and should therefore be carried out by an experienced examiner. According to the localization in the intestine and the predominant type of inflammatory cells, IBD can be further divided:

Histopathological picture annotation
Lymphocytic Plasma Cell Enteritis (LPE) most common form, lymphocytes and plasma cells dominate
Basenji enteropathy breed-specific, probably a sub-form of the LPE
Familial Protein Loss Enteropathy (PLE) and Protein Loss Nephropathy of the Soft Coated Wheaten Terrier breed-specific, probably a sub-form of the LPE
Lymphocytic Plasma Cell Colitis (LPC) Localization in the colon
Eosinophilic enteritis, eosinophilic gastroenteritis, eosinophilic enterocolitis, eosinophilic gastroenterocolitis Eosinophilic granulocytes dominate
Granulomatous enteritis Granulomas as the dominant form of inflammation, rare as an idiopathic disease in the sense of IBD
Regional enteritis locally limited, possibly identical to granulomatous enteritis
Neutrophil enteritis Neutrophils dominate
Histiocytic ulcerative colitis Histiocytic ulcers in the colon, especially boxers , possibly infectious cause

According to the consensus paper of the American College of Veterinary Internal Medicine and the World Small Animal Veterinary Association , the following criteria apply to diagnosing IBD:

  1. chronic course (> 3 weeks) with persistent or recurring gastrointestinal symptoms
  2. histopathological evidence of mucosal inflammation
  3. Absence of other causes of gastrointestinal inflammation
  4. inadequate response to dietary, antiparasitic and antibiotic treatment and
  5. Response to anti-inflammatory or immunosuppressive treatment.
Canine Chronic Enteropathy Clinical Activity Index (CCECAI) according to Allenspach
criteria 0 1 2 3
General condition normal slightly reduced moderately reduced greatly reduced
appetite normal slightly reduced moderately reduced greatly reduced
Vomit no vomiting 1 × per week 2–3 times a week > 3 times a week
Stool consistency normal soft very soft aqueous
Faecal frequency normal 2–3 times a day 4–5 times a day > 5 × per day
Weight loss none <5% 5-10% > 10%
Serum albumin > 20 g / l 15-19 g / l 12-14 g / l <12 g / l
Ascites / edema no minor ascites
or severe edema		 moderate ascites
or mgr. Edema		 severe ascites
or hgr. Edema
itching none Rare Every day wakes up to scratch

Disease indices

To assess the success of the therapy and to compare studies, two indicators were developed that characterize the severity of the disease.

The CIBDAI ( Canine IBD Activity Index ) by Jergens et al. Records some clinical parameters: general well-being, appetite, vomiting, stool consistency, frequency of stool and weight loss. These are evaluated with a point system from 0 (normal) to 3 (marked change). A score of 1–3 is classified as clinically insignificant, one of 4–5 as mild, one of 6–8 as moderate, and one above 8 as severe IBD.

The CCECAI ( Canine Chronic Enteropathy Clinical Activity Index ) of Allenspach and employees considered in addition to CIBDAI criteria and the serum albumin mirror , the occurrence of edema or ascites and the presence of itching (see table). A score of 0–3 is classified as clinically insignificant, one of 4–5 as mild, one of 6–8 as moderate, one of 9–11 as severe, and one of 12 as very severe IBD.

Treatment and treatment prospect

The main pillar of the treatment is the lowering of the inflammatory reaction through strong anti-inflammatory and / or immune system suppressants ( immunosuppressants ) agents . However, this therapy should only be initiated when the diagnostic criteria have been met and all other measures (exclusion diet, parasite control) were unsuccessful. Prednisolone is most commonly used for this . Since this active ingredient, like other glucocorticoids , has numerous effects in the organism, there are relatively many undesirable effects such as greatly increased appetite , increased drinking , increased urination and increased susceptibility to infections, and in the long term also obesity and muscle wasting . The administration of additional immunosuppressants can reduce the glucocorticoid dose; if the response to glucocorticoids is poor, these can be replaced entirely. Ciclosporin is approved as an immunosuppressant for dogs, but treatment is significantly more expensive than prednisolone. In addition, there are positive experiences with chlorambucil and azathioprine before, which are available only as human medicines and therefore reclassified to be.

The use of a hypoallergenic diet - a feed with a single source of protein and carbohydrate that has not been fed if possible, or a feed with hydrolyzed protein and thus small molecules that do not activate the immune system - is another pillar of treatment. This not only excludes feed-related diseases, but also prevents further activation of the already pathologically increased immune system. In Crohn's disease patients, the administration of hydrolyzed food also has a positive effect on the composition of the intestinal flora.

Since IBD is accompanied by a disturbance in the composition of the intestinal flora, the positive influence on the intestinal flora is another pillar of treatment. The administration of a probiotic with several bacterial strains in the course of treatment with prednisolone and a diet could have an additional positive effect on the stabilization of the intestinal barrier. Faecal transplants from healthy dogs could have a similar effect , but no meaningful studies have yet been published. The use of intestinal flora-regulating and immunoregulatory antibiotics such as metronidazole , oxytetracycline or tylosin should only take place in the event of severe damage to the intestinal barrier with the risk of bacteria entering the blood or in the case of secondary small intestine colonization due to the risk of resistance . In histiocytic ulcerative colitis, on the other hand, E. coli penetrating the colonic mucosa play a decisive role in the development of the disease, so that the administration of an antibiotic is absolutely necessary.

Since IBD is associated with a lower absorption of B vitamins , especially folic acid and vitamin B 12 , in the intestine, the additional administration of these vitamins makes sense.

The outlook for treatment ( prognosis ) is poor. The treatment successes presented in the older literature are largely due to the vague use of the term in the past. Even in the animals that show an initial response to treatment, relapses often occur that no longer respond to standard therapy with prednisolone, diet and probiotics and lead to the decision to euthanize in about 20% of patients .

literature

  • Edward J. Hall and Alexander J. German: Inflammatory Bowel Disease (IBD) . In: Jörg Steiner (Ed.): Gastroenterology in dogs and cats . Schlütersche, Stuttgart 2011, ISBN 978-3-89993-060-3 , p. 327-346 .
  • Kathrin Busch et al .: Inflammatory Bowel Disease in Dogs . In: Small Animal Practice . tape 64 , no. 5 , May 2019, p. 291-307 , doi : 10.2377 / 0023-2076-64-291 .

Web links

Individual evidence

  1. ^ A b Edward J. Hall and Alexander J. German: Inflammatory Bowel Disease (IBD) . In: Jörg Steiner (Ed.): Gastroenterology in dogs and cats . Schlütersche, Stuttgart 2011, ISBN 978-3-89993-060-3 , p. 327 .
  2. ↑ a b A. Peiravan et al .: Genome-wide association studies of inflammatory bowel disease in German shepherd dogs. In: PLOS ONE . Volume 13, number 7, 2018, p. E0200685, doi: 10.1371 / journal.pone.0200685 , PMID 30028859 , PMC 6054420 (free full text).
  3. ↑ M. Gajendran et al .: A comprehensive review and update on Crohn's disease. In: Disease-a-month: DM. Volume 64, number 2, February 2018, pp. 20–57, doi: 10.1016 / j.disamonth.2017.07.001 , PMID 28826742 (review).
  4. ↑ A. Kathrani et al .: TLR5 risk-associated haplotype for canine inflammatory bowel disease confers hyper-responsiveness to flagellin. In: PLOS ONE. Volume 7, number 1, 2012, p. E30117, doi: 10.1371 / journal.pone.0030117 , PMID 22279566 , PMC 3261174 (free full text).
  5. ↑ a b c d e f g h i j k Kathrin Busch et al .: Inflammatory Bowel Disease in dogs . In: Small Animal Practice . tape 64 , no. 5 , May 2019, p. 291-307 , doi : 10.2377 / 0023-2076-64-291 .
  6. ↑ E. Kilian et al .: Long-term effects of canine parvovirus infection in dogs. In: PLOS ONE. Volume 13, number 3, 2018, p. E0192198, doi: 10.1371 / journal.pone.0192198 , PMID 29547647 , PMC 5856261 (free full text).
  7. ↑ a b c J. S. Suchodolski et al .: The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease. In: PLOS ONE. Volume 7, number 12, 2012, p. E51907, doi: 10.1371 / journal.pone.0051907 , PMID 23300577 , PMC 3530590 (free full text).
  8. ↑ a b c S. Soontararak et al .: Humoral immune responses against gut bacteria in dogs with inflammatory bowel disease. In: PLOS ONE. Volume 14, number 8, 2019, p. E0220522, doi: 10.1371 / journal.pone.0220522 , PMID 31369623 , PMC 6675102 (free full text).
  9. ^ M. Prosberg et al .: The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis. In: Scandinavian Journal of Gastroenterology. Volume 51, Number 12, December 2016, pp. 1407–1415, doi: 10.1080 / 00365521.2016.1216587 , PMID 27687331 (Review)
  10. ↑ H. Sokol et al .: Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. In: Proceedings of the National Academy of Sciences . Volume 105, number 43, October 2008, pp. 16731-16736, doi: 10.1073 / pnas.0804812105 , PMID 18936492 , PMC 2575488 (free full text).
  11. ↑ H. Sokol et al .: Low counts of Faecalibacterium prausnitzii in colitis microbiota. In: Inflammatory bowel diseases. Volume 15, Number 8, August 2009, pp. 1183-1189, doi: 10.1002 / ibd . 20903 , PMID 19235886 .
  12. ↑ Edward J. Hall and Alexander J. German: Inflammatory Bowel Disease (IBD) . In: Jörg Steiner (Ed.): Gastroenterology in dogs and cats . Schlütersche, Stuttgart 2011, ISBN 978-3-89993-060-3 , p. 339-340 .
  13. ↑ a b c A. E. Jergens et al .: A scoring index for disease activity in canine inflammatory bowel disease. In: Journal of Veterinary Internal Medicine . Volume 17, Number 3, 2003 May-Jun, pp. 291-297, doi: 10.1111 / j.1939-1676.2003.tb02450.x , PMID 12774968 .
  14. ↑ K. Nisa et al .: Evaluation of duodenal perfusion by contrast-enhanced ultrasonography in dogs with chronic inflammatory enteropathy and intestinal lymphoma. In: Journal of veterinary internal medicine. Volume 33, number 2, March 2019, pp. 559-568, doi: 10.1111 / jvim.15432 , PMID 30784123 , PMC 6430930 (free full text).
  15. ↑ a b J. Washabau et al .: Endoscopic, Biopsy, and Histopathologic Guidelines for the Evaluation of Gastrointestinal Inflammation in Companion Animals. In: Journal of Veterinary Internal Medicine. Volume 24, 2010, pp. 10-26. ( Full text )
  16. ↑ M. Cerquetella et al .: Inflammatory bowel disease in the dog: differences and similarities with humans. In: World Journal of Gastroenterology . Volume 16, number 9, March 2010, pp. 1050-1056, doi: 10.3748 / wjg.v16.i9.1050 , PMID 20205273 , PMC 2835779 (free full text) (review).
  17. ↑ a b c K. Allenspach et al .: Chronic enteropathies in dogs: evaluation of risk factors for negative outcome. In: Journal of Veterinary Internal Medicine. Volume 21, Number 4, 2007 Jul-Aug, pp. 700-708, doi : 10.1892 / 0891-6640 (2007) 21 [700: ceideo] 2.0.co; 2 , PMID 17708389 . ( Full text )
  18. ↑ Edward J. Hall and Alexander J. German: Inflammatory Bowel Disease (IBD) . In: Jörg Steiner (Ed.): Gastroenterology in dogs and cats . Schlütersche, Stuttgart 2011, ISBN 978-3-89993-060-3 , p. 336 .
  19. ↑ PJ Mandigers et al .: A randomized, open-label, positively-controlled field trial of a hydrolyzed protein diet in dogs with chronic small bowel enteropathy. In: Journal of Veterinary Internal Medicine. Volume 24, number 6, 2010 Nov-Dec, pp. 1350-1357, doi: 10.1111 / j.1939-1676.2010.0632.x , PMID 21054541 .
  20. ↑ S. Wang et al .: Diet-induced remission in chronic enteropathy is associated with altered microbial community structure and synthesis of secondary bile acids. In: Microbiome. Volume 7, number 1, August 2019, p. 126, doi: 10.1186 / s40168-019-0740-4 , PMID 31472697 , PMC 6717631 (free full text).
  21. ^ Y. Minamoto et al .: Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease. In: Gut microbes. Volume 6, number 1, 2015, pp. 33-47, doi: 10.1080 / 19490976.2014.997612 , PMID 25531678 , PMC 4615558 (free full text).
  22. ^ R. White et al .: Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease. In: Gut microbes. Volume 8, number 5, 09 2017, pp. 451-466, doi: 10.1080 / 19490976.2017.1334754 , PMID 28678609 , PMC 5628651 (free full text).
  23. ^ A b Edward J. Hall and Alexander J. German: Inflammatory Bowel Disease (IBD) . In: Jörg Steiner (Ed.): Gastroenterology in dogs and cats . Schlütersche, Stuttgart 2011, ISBN 978-3-89993-060-3 , p. 337 .