Remission of Histiocytic Ulcerative Colitis in Boxer Dogs Correlates with Eradication of Invasive Intramucosal Escherichia coli

Background: Historically, histiocytic ulcerative (HUC) (or granulomatous) colitis of Boxer dogs was considered an idiopathic immune-mediated disease with a poor prognosis. Recent reports of dramatic responses to enrofloxacin and the discovery of invasive Escherichia coli within the colonic mucosa of affected Boxer dogs support an infectious etiology.
Hypothesis: Invasive E. coli is associated with colonic inflammation in Boxer dogs with HUC, and eradication of intramucosal E. coli correlates with clinical and histologic remission.
Animals: Seven Boxer dogs with HUC.
Methods: Prospective case series. Colonic biopsies were obtained at initial evaluation in 7 dogs, and in 5 dogs after treatment with enrofloxacin. Biopsies were evaluated by standardized histopathology, and fluorescence in situ hybridization (FISH) with probes to eubacteria and E. coli .
Results: Intramucosal E. coli was present in colonic biopsies of 7/7 Boxers with HUC. Clinical response was noted in all dogs within 2 weeks of enrofloxacin (7±3.06 mg/kg q24 h, for 9.5±3.98 weeks) and was sustained in 6 dogs (median disease-free interval to date of 47 months, range 17–62). FISH was negative for E. coli in 4/5 dogs after enrofloxacin. E. coli resistant to enrofloxacin were present in the FISH-positive dog that relapsed.
Conclusions and Clinical Relevance: The correlation between clinical remission and the eradication of mucosally invasive E. coli during treatment with enrofloxacin supports the causal involvement of E. coli in the development of HUC in susceptible Boxer dogs. A poor response to enrofloxacin treatment might be due to colonization with enrofloxacin-resistant E. coli .     

Histiocytic ulcerative colitis in a French bulldog

A 9-month-old French bulldog was referred for signs of chronic large bowel diarrhea. The dog had an increased frequency of defecation, tenesmus and hematochezia. Flexible colonoscopy showed hyperemia, irregularities and ulcerations with multifocal hemorrhages in the mucosa from the descending colon to the proximal rectum. Multiple colonic biopsies were characterized by infiltrations of PAS positive histiocytes in the lamina propria. A diagnosis of histiocytic ulcerative colitis (HUC) was made, and the animal showed only minimal improvement, although it was treated with nutritional and medical therapies. This is the second case of HUC in French bulldog, a breed which has ancestral relations to Boxer dogs.     

HISTIOCYTIC ULCERATIVE COLITIS IN A BOXER DOG

SUMMARY: A 2-year-old male Boxer dog had passed loose faeces mixed with fresh blood and mucus for 8 months. Tenesmus after defaecation was a feature. Colitis was diagnosed from the proctoscopic appearance of the recto-colonic mucosa and confirmed from a biopsy. The disorder proved unresponsive to sulphasalazine therapy, but oral chloramphenicol, betamethasone and prednisolone enemas administered over a 6-week period produced a satisfactory clinical improvement, which persisted for a further 3 weeks without treatment. However, follow-up proctoscopy showed only a marginal improvement in the appearance of the mucosa and appeared to exacerbate further bloody diarrhoea, which persisted. The dog was destroyed and histiocytic ulcerative colitis confirmed at autopsy.     

Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs

Canine histiocytic ulcerative colitis (HUC) is characterized by colonic inflammation with predominantly periodic acid-Schiff (PAS)-positive macrophages. The inflammation results in colonic thickening, ulcerations, and distortion of normal glandular architecture. Resultant clinical signs consist of chronic large bowel diarrhea, tenesmus, and marked weight loss, and the disease frequently results in euthanasia. Conventional therapy consists of some combination of prednisone, azathioprine, sulfasalazine, and metronidazole. Nine dogs (8 Boxers and 1 English Bulldog) with histologic confirmation of HUC were treated with antibiotic therapy (either with enrofloxacin alone or in combination with metronidazole and amoxicillin). Clinical signs, physical examination findings, laboratory abnormalities, and the histologic severity of the disease were evaluated. Four of the 9 dogs had been treated previously with conventional therapy and had failed to respond favorably; then, these dogs were placed on antibiotic therapy (enrofloxacin, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3) and had resolution of clinical signs within 3-12 days. Five dogs were treated solely with antibiotic therapy (enrofloxacin, n = 1; enrofloxacin and metronidazole, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3), and clinical signs resolved in 2-7 days. Repeated biopsy specimens were obtained from 5 dogs after treatment, and all showed marked histologic improvement. The increase in body weight after treatment was statistically significant (P = .01). Three dogs currently are not on any treatment and have had resolution of clinical signs for up to 14 months. These observations suggest that an infectious agent responsive to antibiotics plays an integral role in the clinical manifestation of canine HUC, and they support the use of antibiotics in its treatment.     

Canine histiocytic ulcerative colitis

Objective To assess prevalence, breed predilection, response to therapy and prognosis of canine histiocytic ulcerative colitis (CHUC).
Design A retrospective study of cases of CHUC seen at Sydney University Veterinary Teaching Hospital (SUVTH) over a 20-year period (1975 -1994).
Procedure Case records of all dogs in which colitis was suspected were reviewed. Dogs were diagnosed with CHUC based on colonorectal biopsy and histopathological examination.
Results CHUC was diagnosed in 8 of 57 dogs presented for colitis. All affected dogs were Boxers and six were female. Dogs with milder clinical signs showed moderately good response to therapy. Four dogs were still alive 1 to 7 years after diagnosis. Three dogs were euthanased, one for reasons other than CHUC, and one was lost to follow-up.
Conclusions Young boxer dogs with relatively mild signs of CHUC may respond moderately well to medical and dietary therapy with fair prognosis. Euthanasia early in the course of the disease may be unwarranted. Prevalence may be increasing within the SUVTH referral population.     

Histiocytic ulcerative colitis in a French Bulldog

A case of histiocytic ulcerative colitis (granulomatous colitis) in a one–year–old female French Bulldog is described. Until now this disease has been described only in the Boxer breed.
The dog had an increased frequency of defaecation and the faeces contained blood and mucus. Colonoscopy showed some irregularities and a few haemorrhages in the mucosa of the caudal part of the colon. At a distance of approximately 25 cm from the anus there was a stricture caused by rigidity of the colon wall. Radiographic examination revealed marked shortening of the colon. There was also narrowing of the midpoint of the descending colon in some radiographs, but the colon appeared to be fully distensible when filled with barium. Histologically, periodic acid–Schiff (PAS)–positive staining histiocytes were found in biopsy and autopsy specimens from the colon.     

Attempts to produce granulomatous colitis in Boxer dogs with a mycoplasma.

Four of six Boxer dogs with granulomatous colitis had mycoplasmas in the colon and three in the draining lymph node as well. One isolate identical with Mycoplasma strain HRC-689 was inoculated into the colon of five Boxer dogs at eight weeks of age; four controls were inoculated with medium. Animals were killed at two week intervals and examined. The mycoplasma strain produced changes of the colon characterized by lymphocytic infiltration of mucosa, lymphocytic submucosal perivasculitis, and enlargement of colonic lymphoid nodules but granulomatous colitis did not occur. The experimental dogs developed antibodies, and dogs from a kennel with a high prevalence of colitis cases had high antibody titers against strain HRC-689.     

The histological appearance of large intestinal biopsies in dogs with clinical signs of large bowel disease.

Colonic and rectal forceps and excision biopsies of 355 dogs with clinical signs of large bowel disease were investigated. Five percent of the forceps biopsies were unsuitable for examination; all excision biopsies were of good quality. Forceps biopsies were obtained from one to eight sites, up to 60 cm cranial from the anus, while excision biopsies, mostly from tumors, were from the rectoanal region. Slight to severe colitis and/or proctitis was found in 192 dogs (54%). A single type of colitis was seen in 160 dogs; in 53 cases the lesions were local, in 107 cases multiple. A combination of different types of colitis was found in 32 dogs. Atrophic colitis, diffuse colitis and canine histiocytic ulcerative colitis were the most prominent findings, followed by ulcerative, superficial and eosinophilic colitis. Follicular, hypertrophic and aspecific granulomatous colitis were found in only a few cases. Tumors were diagnosed in 57 dogs (16%). Of these tumors 50 were of epithelial and seven were of mesenchymal origin. A high percentage (61%) of the epithelial tumors consisted of adenomas of the rectoanal region. In ten other dogs (3%) a differential diagnosis of lymphosarcoma or colitis had to be made. Colitis and colorectal tumors were more prevalent in Boxers, German Shepherds, Poodles, Great Danes and Spaniels. In the Boxers simple chronic colitis, as well as canine histiocytic ulcerative colitis were more frequently found, the latter especially in females. Other biopsy findings were edema, crypt cysts, hemorrhages, an increased number of intraepithelial lymphocytes and an increased or decreased number of goblet cells.     

Histiocytic ulcerative colitis in boxer dogs in the UK

Histiocytic ulcerative colitis is an uncommon cause of canine large bowel diarrhoea that is generally refractory to standard treatment for idiopathic colitis. It is characterised pathologically by mucosal ulceration with a mixed inflammatory cell infiltrate, in which periodic acid-Schiff positive histiocytes are a dominant feature. The disease is well recognised in young boxer dogs in the USA, Australasia and mainland Europe. This paper reports the occurrence of seven cases of histiocytic ulcerative colitis seen recently in the UK, along with the clinical signs, histopathology, treatment and post mortem findings.     

醋酸诱导犬急性溃疡性结肠炎模型的建立

试验旨在探索醋酸诱导犬急性溃疡性结肠炎（ulcerative colitis，UC）的方法，建立稳定的犬急性UC模型。选取16只健康犬，随机分成对照组和3个不同浓度醋酸组，每组4只。注射犬眠宝麻醉后，醋酸组分别灌注4%、7%和10%的2 mL/kg醋酸，对照组无需麻醉，直肠灌注相应剂量无菌生理盐水；用药后第1、3、7 天观察各组排便情况，并用电子内窥镜观察试验犬结肠黏膜的损伤程度；于第7 天牺牲试验犬，切取病变结肠做组织切片检查。结果显示，灌注4%醋酸的犬均出现短暂的稀便，病理切片观察只有轻微炎性细胞浸润；灌注10%醋酸的犬，炎症反应过于强烈导致肠穿孔和死亡；灌注7%醋酸的犬，粪便性状及结肠内窥镜检查均显示明显的结肠炎症状，3 d后出现溃疡灶，7 d后可见溃疡灶脱落，组织学检查发现溃疡灶周围有明显的炎性细胞浸润，随着时间的推移炎性细胞浸润明显减少，成纤维细胞增生。以上结果表明，直肠灌注7%醋酸能成功稳定诱导犬急性UC。     

The ultrastructure of macrophages in granulomatous colitis of Boxer dogs.

Thirteen cases of granulomatous colitis of Boxer dogs were studied by electron microscopy to define the contents of macrophages and to seek infectious agents. Macrophages were of three types. The most numerous were distended with residual bodies composed of membranes and parallel pairs of membranes, many arranged in circular patterns. A second common form had heterogeneous cytoplasm distended with phagosomes containing numerous small granular spheres of various sizes and electron densities. The least common were "young" macrophages containing phagocytic vacuoles. Rare macrophages in four of 13 dogs contained bacteria. Macrophages in five of the dogs contained abundant coccoid, coccobacillary of lobulated granular structures, 100-500 nm in diameter, resembling chlamydia. Transition from phagocytic particle to phagosome to residual body was apparent. Granulomatous colitis of Boxer dogs is probably caused by a lipid-rich, ribosome-rich, coccoid to coccobacillary organism that possesses a cell membrane and sometimes a nucleoid, and ranges from 100 to 500 nm in size.     

Antimicrobial Resistance Impacts Clinical Outcome of Granulomatous Colitis in Boxer Dogs

Background: Escherichia coli have recently been identified within the colonic mucosa of Boxer dogs with granulomatous colitis (GC). Eradication of invasive E. coli is associated with clinical and histological remission. Objectives: To determine antimicrobial susceptibility profiles of E. coli strains from GC and healthy dogs, and the association of antimicrobial resistance with clinical outcome. Animals: Fourteen Boxer dogs with GC and 17 healthy pet dogs. Methods: Prospective study: E. coli was cultured from GC biopsies and rectal mucosal swabs of healthy dogs. Individual strains were selected by phylogroup and overall genotype, determined by triplex‐ and random amplified polymorphic DNA‐polymerase chain reaction respectively. Antimicrobial susceptibility was determined by broth microdilution minimal inhibitory concentration. Results: Culture yielded 23 E. coli strains from GC (1–3/dog, median 2) and 34 strains from healthy (1–3/dog, median 2). E. coli phylogroups were similar (P= .18) in GC (5A, 7B1, 5B2, 6D) and healthy (2A, 10B1, 15B2, 7D). Resistance to ampicillin, amoxicillin‐clavulanate, cefoxitin, tetracycline, trimethoprim‐sulfa (TMS), ciprofloxacin, and chloramphenicol was greater (P < .05) in GC (21–64%) than healthy (0–24%). Enrofloxacin resistant E. coli were isolated from 6/14 GC versus 0/17 healthy (P= .004). Of the enrofloxacin resistant cases, 4/6 were also resistant to macrophage‐penetrating antimicrobials such as chloramphenicol, rifampicin, and TMS. Enrofloxacin treatment before definitive diagnosis was associated with antimicrobial resistance (P < .01) and poor clinical outcome (P < .01). Conclusions and Clinical Importance: Antimicrobial resistance is common among GC‐associated E. coli and impacts clinical response. Antimicrobial therapy should be guided by mucosal culture and antimicrobial susceptibility testing rather than empirical wisdom.     

Histiocytic ulcerative colitis in a boxer. A case report

A case of canine histiocytic ulcerative colitis, a disease of boxers, is here described. It appears that this disease has not been previously reported in Scandinavia. The diagnosis was established at necropsy of a 5-month-old boxer, which had shown bloody diarrhoea since the age of four weeks. Treatment with antibiotics had only given a temporary remission of the condition. Macroscopical findings included thickening of the wall of the descending colon and rectum, multiple ulcers in the rectocolonic mucosa and marked enlargement of the colonic lymph nodes. Microscopically the lesions were characterized by large accumulations of PAS-positive histiocytes, mixed with cells of the plasma cell type, in the mucosa and submucosa of the rectum and descending colon and in the colonic lymph nodes. The importance of using proctocolonoscopy and colon biopsy for the clinical diagnosis of this condition is stressed.     

活菌制剂“妈咪爱”中枯草杆菌的分离与应用

通过对枯草杆菌的分离、鉴定以及在临床上的应用,探究其对溃疡性结肠炎的疗效。结果显示,枯草杆菌经灌肠治疗后,小鼠溃疡性结肠炎的厌食、乏力、倦怠等症状消失,结肠功能恢复正常。与常规药物治疗比较,枯草杆菌培养液更有效。该结果表明,枯草杆菌不仅能够调节结肠的生理功能,而且能治疗溃疡性结肠炎。     

Feline histiocytic colitis. A case report with electron microscopy.

A 5-year-old cat with clinical colitis had histiocytic inflammation of colonic mucosa. Light and electron microscopy demonstrated bacilli, 0.7 x 3.0 micrometers, in various stages of degradation within macrophage cytoplasm. The disease is similar to histiocytic granulomatous bowel disease of other species. The cat responded to long-term treatment with antibiotics.     

Temporal Variability of Ventricular Arrhythmias in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is prevalent in the Boxer. There is little information on the temporal variability of ventricular arrhythmias within affected dogs.
Objective: To evaluate ambulatory electrocardiograms (AECG) from Boxers with ARVC for hourly variation in premature ventricular complexes (PVC) and heart rate (HR).
Animals: One hundred and sixty-two Boxer dogs with ARVC.
Methods: Retrospective, observational study of 1,181 AECGs collected from Boxer dogs at The Ohio State University from 1997 to 2004 was evaluated. The proportion of depolarizations that were PVCs was compared across each hour of the day, during six 4-hour periods of day, to the time after AECG application, and to the maximum and minimum HR.
Results: A lower proportion of PVCs was noted during early morning (midnight to 0400 hours) as compared with the morning (0800–1200 hours) and late (1600–2000 hours) afternoon ( P = .012). There was no increase in PVC proportion in the 1st hour after AECG application as compared with all other hours of the day ( P = .06). There was poor correlation between maximum (ρ= 0.19) and minimum (ρ= 0.12) HR and PVC proportion.
Conclusions and Clinical Importance: The likelihood of PVC occurrence in Boxer dogs with ARVC was relatively constant throughout the day, although slightly greater during the hours of 0800–1200 and 1600–2000. A biologically important correlation with HR was not apparent. The role of autonomic activity in the modulation of electrical instability in the Boxer with ARVC requires further study.     

Chronic regional intestinal inflammatory disease: A trans-species slow infection?

Crohn’s disease and ulcerative colitis in humans and paratuberculosis in domestic and wild ruminants can be defined as chronic regional intestinal inflammatory diseases (CRIID). This review is a literature overview on these diseases in humans, non-human primates, dogs, cats, rabbits, equids and ruminants with a focus on pathological and microbiological features aimed identifying common characteristics that could lead to a unified pathological classification for a better understanding of their mechanisms and causes. The result is a framework of inflammatory forms throughout the different species indicative of common mechanisms of the slow infection type characterized by a time course varying from weeks to months or even years, and where the inflammatory component would be more prominent in the intestinal interphase between host and environment and be morphologically characterized by an infiltrate ranging from lymphoplasmacytic to histiocytic. This should provide new insights for causation demonstration and therapeutic approaches in human IBD.     

Nodular dermatofibrosis and cystic renal disease in three mixed-breed dogs and a Boxer dog

Three mixed-breed dogs and a Boxer dog with nodular dermatofibrosis are described. The three mixed breed dogs had concurrent renal epithelial cysts ( n  = 2) or renal cystadenomas ( n  = 1); these lesions were visualized antemortem on ultrasonographic examination. One of these dogs was a 7-year-old Labrador Retriever-Gordon Setter mixed breed which survived 5 years after diagnosis, and was euthanized for unrelated causes. The Boxer dog had renal cystic adenomatous hyperplasia and renal cystadenocarcinomas which were not visualized on ultrasonographic examination but were diagnosed at necropsy.     

Ciprofloxacin as a representative of disk diffusion in vitro susceptibility of enrofloxacin for bacterial organisms from the middle-ear tissue of dogs with end-stage otitis externa

The purposes of this study were to determine whether ciprofloxacin disk diffusion susceptibility test (DDT) results could be used to assess the in vitro susceptibility of otic bacterial organisms to enrofloxacin and to determine the effect of concurrent enrofloxacin administration on the DDT results for enrofloxacin and ciprofloxacin. Thirty dogs with end-stage otitis externa undergoing unilateral total ear canal ablation were enrolled. The dogs were randomized to one of four enrofloxacin-treatment groups or to the control group. Each dog in the treatment groups received two intravenous doses of enrofloxacin prior to surgical removal of the middle-ear tissue while the control group did not receive any enrofloxacin. One dog was excluded from the study as no middle-ear tissue was removed during surgery. Twenty-four dogs were in the enrofloxacin-treatment groups and five dogs were in the control group. In 12 of 29 dogs (41.4%), 14 of 82 (17.1%) of bacteria had discrepancies in DDT results for enrofloxacin and ciprofloxacin. Discrepancies between the control group and treatment groups were not significantly different even though the percentage of discrepancies for the combined treatment group was 19.4% compared to 6.7% for the control group. In this study, ciprofloxacin DDT results were not an accurate indicator of the in vitro susceptibility of enrofloxacin for bacteria isolated from the middle-ear tissue of dogs with end-stage otitis.     

Hyperinsulinism in the dog due to pancreatic islet-cell tumour: a report on three cases

Hypoglycaemia due to hyperinsulinism caused by an islet-cell tumour, in three male Boxer dogs aged 9, 81/2 and 81/2 years respectively, is described.
The clinical signs, the laboratory findings and the histological picture of the tumour of the pancreas which led to the diagnosis are discussed. The plasma immunoreactive insulin level (IRI), after 24-hours fasting, or after stimulation by glucose, was elevated in only one case, but the 'amended insulin-glucose ratio' was clearly increased in the other two cases, compared with normal dogs.