veterinary clinics “Dobro hrumvane!”- Sofia, Bulgaria
Histiocytic ulcerative colitis (HUC) is an inflammatory bowel disease that causes tenesmus, hematochezia, and profound weight loss. The disease is most commonly described in young Boxer Dogs but it has also been reported in other breeds of dogs, including Mastiff, Alaskan Malamute, Doberman Pinscher, French Bulldogs. One cat with HUC also has been described. HUC differs from other forms of inflammatory bowel disease in dogs because it is characterized histologically by periodic acid-Schiff (PAS)-positive macrophages; it is more likely to be associated with mucosal ulcerations; it is less responsive to therapy, and has a poorer long-term prognosis. HUC in Boxer Dogs was 1st described by Van Kruiningen et al in 1965. Since that time, the gross histopathologic and ultrastructural findings have been well characterized. The pathognomonic lesion of HUC is the accumulation of distinctive, PAS-positive macrophages (indicative of glycoprotein within the macrophages) in the lamina propria and submucosa of the colon with loss of the associated epithelial surface. The PAS-positive material may be derived from remnants of bacterial cell wall glycoprotein, and accumulation of PAS-positive material in macrophages may occur because of abnormal lysosomal activity, exhaustion of lysosomal activity, or inhibition of lysosomal activity by toxic substances. The cause of HUC has yet to be determined. Early studies proposed an infectious etiology on the basis of the presence of chlamydia-like organisms in macrophages on electron microscopy and clinical improvement after chloramphenicol therapy. In a subsequent ultrastructural study, organisms were not conclusively demonstrated. Attempts to create the disease experimentally by mycoplasma infection failed. Management of HUC consists of various combinations of the following: dietary modifications; antibiotics such as chloramphenicol, metronidazole, and tylosin and anti-inflammatory or immunosuppressive drugs such as sulfasalazine, prednisone,cyclosporine and azathioprine. Response to treatment is generally poor, frequently resulting in euthanasia of affected animals
Representative histologic images in the dog (HE, bar = 50 μm). A: Lymphocytic-plasmacytic colitis. Note the interstitial diffuse pattern of infiltrate represented by a large amount of lymphocytes mixed with plasma cells and some macrophages; B: Lymphocytic-plasmacytic colitis (follicular variant); C: Histiocytic colitis. Severe mucosal abnormalities with loss of crypts and diffuse infiltration by large macrophages (arrows) that in the insert (PAS stain) are shown as the main cells infiltrating the lamina propria; D: Eosinophilic colitis. Note the presence of a large number of eosinophils (arrows).
- Report and history of the patient
We had a patient dog, named Robin, French Bulldog, male, noncastrated, 2 years old, vaccinated, with chronic diarrhea dating back about a year and a half. Everything started with minor episodes of diarrhea when the dog was about 6-7 months old, the owners also mentioned itching and licking of paws. Аll tests for infectious diseases were negative (CPV/CCV/Giardia) and blood samples were normal. The faecal sample was negative for any parasites. At that time, the patient was treated with probiotics, chemotherapeutics and sulphonamides, gastrointestinal and hypoallergenic diets without any effect. During this time, the owners refused colonoscopy or diagnostic laparotomy combined with a histopathological examination аnd a test for pancreatitis (Idexx cPL).
On April 12, 2019, the dog came to the clinic again with complaints of persistent diarrhea accompanied by blood and tennesms. Robin’s condition had become more serious since the owners had given BARF at their discretion. On the same day we did the CBC and biochemical blood tests and ultrasound of the abdomen. The ultrasound examination showed a high degree of thickening of the layers of the colon and some of the small intestine divisions, as well as enlarged mesenterial limph nodes.
We placed an intravenous catheter and included fluid therapy NaCl 55 ml/h, antiemetics (famotidine and pantoprazole), vitamins (vit C, B- complex, arginine ,ornithine, citrulline), antioxidants (duphalyte, amynoplasmal), probiotics (Fortiflora and Pro-kolin paste), painkillers (buprenorphine), haemostatic drugs (Vit K1 and etamsylate) and tylosinum 25 mg/kg/24h/p.o. Аfter 3 days we took blood tests, which again showed low-grade anemia, leukocytosis and neutrophilia. We also added injectable erythropoietin to therapy.
On April 16, 2019, we performed a diagnostic laparotomy with full thickness biopsy of thr large and small intestine. The material taken was prepared and sent for patho-histological examination in Laboklin Germany. The result was sent by email on May 24, 2019 :
1: moderate to severe mixed cell colitis with
PAS-positive macrophages and ulceration
2: mild to moderate lymphoplasmocytic enteritis
The histological findings (PAS-positive macrophages) in context with the reported breed indicated a histiocytic and ulcerative colitis(HUC).This form of colitis develops especially in
boxer dogs and french bulldogs. Single cases are described forother breeds.A HUC is associated with an infection of certain strains of Escherichia coli. Clinical signs are weight loss, anorexia andpoor condition.A colitis with epithelial lesions and PAS-positive macrophages are typically found in histology.“
On the same day we started methilprednisolon 2 mg/kg/12h/i.v, ampicillin/sulbactam 15 mg/kg/8h/i.v, ceftriaxone 35 mg/kg/12h/i.v in addition to all other therapy.
On April 25, 2019 we only took complete blood count, which established increase of leukocytes and neutrophils, as well as deepening anemia. Clinically, the dog continued to have severe and watery diarrhea with tenesmus, most of which were mixed with blood. Robin began to lose weight progressively and refused to eat at his own will. He was fed by force, following a hypoallergenic diet of “Hill’s z/d cans” and “Royal Canin Hypoallergenic cans”. After a few days Robin felt better and started to eat dry hypoallergenic food.
On April 30, 2019 we took blood for a full blood count where the levels of leukocytes and neutrophils had dropped, but the levels of red blood cells were still low, so an ultrasound examination of the colon was carried out – the wall had begun to decrease in size
Robin’s condition was beginning to improve, the stools were getting better. After a few days, the patient was given home therapy (amoxicillin/clavulanic acid for 5 weeks, marbofloxacin for 6 weeks, prednisolone by scheme with start dose 3 mg/kg/12h/p.o for 7 weeks, b-complex liquit, legaphyton 200 tabl).
On May 09 2019 we took blood for a full blood count – the leukocytosis were even fewer, but still out of norm; the hematocrit, the hemoglobin and the number of red blood cells were still low. We sent another blood sample to Laboklin Germany for TLI (Tripsin-like-immunoreactivity) + Vit B12 + Folic Acid.
“Trypsin-like-Immunoreactivity (TLi) – CLA
Result 36.8 µg/l > 5
TLI values < 2.5µg/l are indicative for exocrine pancreas
With values of > 5.0 µg/l a EPI is most unlikely. 2.5 to 5.0 µg/l
is considered to be a questionable; a control measurement should be considered after 2 3 months time according to the clinical sings.
Reasons for questionable values are:
– acute phase of chronic pancreatitis
– sampling time within 12 hours post feeding
TLI values > 35 µg/l are indicative for pancreatitis. Renal
insufficiency can result in retention of TLI and thus falsely
elevated TLI resp.
Vitamin B12 Concentration – CLA
Vitamin B12 748 pg/ml 300-800
Folic Acid Concentration – CLA
folic acid 5.73 ng/ml 3.0-10.0”
The ultrasound study showed high-grade meteorism and reactive patch plaques. No increased mesenteric lymph nodes were detected. Clinically, diarrhea was accompanied by tenesmus and fresh blood.
Based on TLI levels, we included metronidazole 7,5 mg/kg/12h/p.o for 5 weeks.
On May 23, 2019 We took blood for a full blood count – the leukocytes and neutrophils were at baseline according to the reference values. However, the hematocrit, the hemoglobin and the red blood cells levels were still low. The condition of the patient had worsen after eating food from the rubbish bin. The ultrasound study showed high-grade meteorism and reactive patch plaques; the wall of the colon had begun to decrease in size; corrugation of the colon appeared. We placed an intravenous catheter and included fluid therapy NaCl 55 ml/h, antiemetics (famotidine and pantoprazole), vitamins (vit C, B- complex, arginine ,ornithine, citrulline), antioxidants (duphalyte, amynoplasmal), probiotics (Fortiflora and Pro-kolin paste), haemostatic drugs (Vit K1 and etamsylate), metronidazole, amoxicillin/clavulanic acid, enrofloxacin 5%. We chose to stop the prednisolone and try budesonide sachet in dose 2 mg/kg/24h/p.o. The dog continued to weaken progressively.
On May 30, 2019 we took blood for a biochemical profile, which showed the following results – elevated bilirubin, elevated ALT, AST, ALP, low creatinine. On the same day, we reduced the prednisolone (1 mg/kg/12h) to include ciclosporin. Clinically the dog continued to weaken and lose muscle mass progressive. The owners started adding veterinary ciclosporin liquit in dose 5 mg/kg/24h/p.o. Three hours after the intake of cyclosporine the dog’s condition deteriorated dramatically, began to vomit and defecate only fresh blood. Unfortunately, we hospitalized the dog again.
The condition of the colon was getting worse.
We started intravenous methylprednisolone again in combination with the rest of the therapy to stabilize the patient. He didn’t want to eat alone again.
On June 04 we took blood for a biochemical profile, which showed the following results – improvement in liver enzymes as well as in pancreatic lipase levels and normal creatinine. Two days later, Robin stopped vomiting and received the rest of the therapy. We fed him three times a day with hypoallergenic food (Royal Canin Hypoallegenic cans).
On June 08 the dog felt better; body temperature was in norm; Robin started to eat with appetite again. Diarrhea continued to be abundant and watery, accompanied by blood and tenesmus. We started budesonide, and stopped methylprednisolone.
Despite the applied complex therapy, diarrhea was unaffected. Defecation continued to be extremely frequent with blood and tenesmus. The patient continued to lose weight and muscle mass progressively. On 11 June Robin was discharged from the clinic with home therapy of budesonide and cyclosporine only. The owners had been offered euthanasia.
The wall of the column progressively hyperplasia.