Intestinal crypt lesions associated with protein-losing enteropathy in the dog

Six dogs were diagnosed with protein losing enteropathy (PLE). There was no evidence of inappropriate inflammatory infiltrates or lymphangiectasia in multiple mucosal biopsies of the small intestine of 4 of the dogs. The 5th and 6th dogs had obvious lymphangiectasia and a moderate infiltrate of inflammatory cells in the intestinal mucosa. All 6 dogs had a large number of dilated intestinal crypts that were filled with mucus, sloughed epithelial cells, and/or inflammatory cells. Whether PLE occurs in these dogs because of protein lost from the dilated crypts into the intestinal lumen or whether the dilated crypts are a mucosal reaction due to another undetermined lesion that is responsible for alimentary tract protein loss is unknown. However, when large numbers of dilated intestinal crypts are present, they appear to be associated with PLE even if there are no other remarkable lesions in the intestinal mucosa.     

Protein-losing enteropathy in a dog with lymphangiectasia,lymphoplasmacytic enteritis and pancreatic exocrine insufficiency

This is a report of seven-year-old male Akita mixed dog, with protein-losing enteropathy (PLE). He had a history of chronic vomiting and diarrhea with anorexia/hyporexia. Previously he suffered acute abdomen about eight months prior to this visit. Our dog showed uncommon combination of diseases that could cause PLE since it was affected by inflammatory bowel disease (IBD), intestinal lymphangiectasia (IL), and exocrine pancreatic insufficiency (EPI). The dog had most of the abnormalities found in IL, as well as hypoalbuminemia, hyperglobulinemia, lymphopenia, hypocalcemia, and hypercholesterolemia. During endoscopy exam, we found changes characteristic of IL such as irregular small white spots. We took biopsies from stomach, duodenum, and cecum. These biopsies showed infiltration by lymphocytes and plasmatic cells in the lamina propria also, the duodenal biopsies showed moderate dilation of the lymphatic vessels. The patient had 2.1?µg/mL of TLI, this result was compatible with EPI. We assume that the first pathology in this animal was IBD, which caused chronic pancreatitis (CP) that in turn progressed to EPI. It is also possible that IL was secondary to IBD. We have reported for the first time the correlation of IBD and EPI in dogs. This should change our approach to treating chronic diarrhea in dogs. Therefore, we propose that dogs diagnosed with EPI should also be subjected to endoscopy and intestinal biopsy. Similarly, to rule out secondary EPI, TLI should be measured routinely in dogs with IBD.     

Focal Intestinal Lipogranulomatous Lymphangitis in 6 Dogs (2008–2011)

Background

Lipogranulomatous lymphangitis is inflammation of the intestinal lymphatic vessels and surrounding tissues caused by chronic leakage of lipid‐laden chyle. Grossly, lipogranulomas are typically disseminated small masses on the serosa and surrounding lymphatic vessels and consist of epithelioid macrophages, multinucleated giant cells, and cholesterol. Lipogranulomatous lymphangitis is occasionally seen in patients with lymphangiectasia and protein‐losing enteropathy (PLE).

Objectives

To characterize the historical features, clinical signs, treatment, histopathology, and outcome of dogs with focal lipogranulomatous lymphangitis.

Animals

Six dogs with ultrasonographic evidence of focal, regional small intestinal masses, often with involvement of the adjacent mesentery, and a diagnosis of focal lipogranulomatous lymphangitis based on histopathology of biopsied masses.

Results

The median age of dogs was 6.9 years (range 3–10 years). All dogs had total protein, globulin, and albumin concentrations within the reference range at initial presentation and had intestinal masses identified on abdominal ultrasound examination. Histopathologic evaluation of lesions identified severe mural and mesenteric lipogranulomatous lymphangitis. Lymphangiectasia was noted in 5 cases and only in sections within the mass‐like lesion; tissue without lipogranulomas had minimal lymphangiectasia, suggesting a localized phenomenon. Postoperative outcomes ranged from remission of clinical signs with no subsequent treatment for 10–12 months in 2 dogs, postoperative management with medical and nutritional management in 3 dogs, and no outcome for 1 case.

Conclusions and Clinical Importance

This case series describes a unique mass‐like manifestation of intestinal lipogranulomatous lymphangitis and should be considered as a possible differential diagnosis in dogs with an intestinal mass.     

Evaluation of the degree and distribution of lymphangiectasia in full-thickness canine small intestinal specimens diagnosed with lymphoplasmacytic enteritis and granulomatous lymphangitis

Intestinal lymphangiectasia (IL) is often observed in dogs with chronic small intestinal diseases. Hypoplasia of the lymphatic vessel due to decreased lymphangiogenesis, which has been suggested in human idiopathic IL, may contribute to the pathogenesis of canine IL. This study aimed to evaluate the diameter and number of lymphatic vessels in full-thickness small intestinal specimens of dogs with IL. Immunohistochemical labeling of lymphatic endothelial cell markers was performed on retrospectively retrieved full-thickness small intestinal specimens. Sixteen dogs with histologically confirmed IL were included, of which 10 had lymphoplasmacytic enteritis (LPE), and six had granulomatous lymphangitis (GL). Nine dogs that died from non-gastrointestinal disorders and with little or no abnormalities in the small intestine were used as controls. Lymphatic vessel diameters in dogs with IL were significantly increased in all layers of the small intestine, including the villus lacteal, lamina propria, submucosa, muscularis, and mesentery, compared with controls (all P<0.01). There was no significant difference in the lymphatic vessel diameters between dogs with LPE and GL (all P>0.05). There was no significant difference in the number of lymphatic vessels between dogs with IL and the controls in all layers of the small intestine (all P>0.05). This study demonstrated that IL was observed in all layers of the small intestine, including the submucosa, muscularis, and mesentery, independent of the underlying disease. Factors other than reduced lymphatic vessels would contribute to the pathogenesis of IL in dogs.     

Familial protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers: 222 cases (1983-1997)

Records and pedigrees of Soft Coated Wheaten Terriers (SCWT) with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) were studied retrospectively. Criteria for inclusion were defined based on analysis of blood (panhypoproteinemia for PLE, hypoalbuminemia for PLN) and urine (proteinuria for PLN) and histopathologic examination of tissue. Two hundred twenty-two affected dogs (female:male ratio = 1.6, P < .001) were clinically identified. Dogs were diagnosed with PLE earlier (P < .005; mean +/- SD age: 4.7+/-2.6 years, n = 76) than with PLN (6.3+/-2.0 years, n = 84) or with both diseases (5.9+/-2.2 years, n = 62). Clinical signs included vomiting, diarrhea, weight loss, pleural and peritoneal effusions, and less commonly thromboembolic disease. Dogs with PLE generally had panhypoproteinemia and hypocholesterolemia; intestinal lesions included inflammatory bowel disease, dilated lymphatics, and lipogranulomatous lymphangitis. Dogs with PLN generally had hypoalbuminemia, proteinuria, hypercholesterolemia, and azotemia; renal lesions typically showed chronic glomerulonephritis/glomerulosclerosis, and less commonly endstage renal disease. Dogs with combined PLE/PLN had intermediate mean values (P < .001) for serum total protein, albumin, globulin, and cholesterol but had a higher mean urine protein:creatinine ratio than did PLN dogs (P < .05); intestinal and renal lesions in these dogs were similar to those in the other groups. Two dogs had incidental mild renal dysplasia. Pedigree analysis from 188 dogs demonstrated a common male ancestor, although the mode of inheritance is unknown. Both PLE and PLN are common diseases in this small breed population. The prognosis is poor. Compared with previously reported intestinal and renal diseases in dogs, a new, distinctive familial predisposition for both PLE and PLN has been recognized in the SCWT breed.     

Protein-losing enteropathies.

GI protein loss can result from a heterogeneous group of diseases, including lymphangiectasia, IBD, neoplasia, ulceration, intussusception, and histoplasmosis. PLE should be suspected in any hypoalbuminemic patient with no evidence of exudative protein loss, proteinuria, or HI. A minimum laboratory database for the suspected PLE patient should include a complete blood cell count, a biochemical and electrolyte profile, urinalysis (+/- urine protein:cretinine ratio), and pre- and postprandial bile acid determinations. Fecal alpha 1-PI concentrations may be used to confirm the presence of GI protein loss in cases with concurrent renal or hepatic disease. Because PLE is a syndrome and not a specific disease, the most effective therapy must be directed at the underlying cause. Multiple high-quality endoscopic biopsies are sufficient to diagnose most patients with PLE, although full-thickness biopsies are required in some cases. Patients with PLE are often clinically "fragile," and careful symptomatic therapy must be integrated with dietary and medical management strategies in most cases.     

Lymphoedema — a problem of gigantic proportions

Extract

Lymphoedema (LO) is the accumulation of protein-rich interstitial fluid caused by failure of normal lymphatic drainage. Human lymphoedema is classified as primary (congenital hereditary or idiopathic, praecox or tarda forms) or secondary (complication of surgery or radiotherapy, such as that for breast cancer, as well as bancroftian filariasis, cellulitis and lymphangitis amongst others). Primary LO may be due to lymphatic aplasia, hypoplasia, dyspla-sia, lymphangiectasia, or aplasia or hypoplasia of draining lymph nodes. Approximately one in thirty people worldwide has LO.     

EFFECTS OF CORN OIL ADMINISTERED ORALLY ON CONSPICUITY OF ULTRASONOGRAPHIC SMALL INTESTINAL LESIONS IN DOGS WITH LYMPHANGIECTASIA

Lymphangiectasia is one of the causes of protein‐losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full‐thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P < 0.05) and were best identified in dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal.     

White spots on the mucosal surface of the duodenum in dogs with lymphocytic plasmacytic enteritis

Distended lacteals, described as expanded white villi in duodenum, are strongly indicative of primary intestinal lymphangiectasia. In the present study, we evaluated the significance of white spots present in the duodenal mucosa of dogs with lymphocytic plasmacytic enteritis (LPE). Fifty dogs with LPE were included in this study, and white spots were detected in the duodenal mucosa in 22 dogs during endoscopy. Hypoproteinemia was more frequent in dogs with white spots than in dogs without spots (p = 0.02). Serum protein and albumin concentration were significantly lower in LPE dogs with white spots (p = 0.038) compared to LPE dogs without white spots (p = 0.039). There was a significant correlation between white spots density and lymphatic dilatation histological scores (p = 0.023; ρ = 0.481). These results suggest that the presence of white spots in the duodenal mucosa of dogs is not a finding exclusive for intestinal lymphangiectasia. Low serum protein and albumin concentrations together with lymphatic dilatation seem to be related to the presence of white spots in the duodenal mucosa of LPE dogs.     

Prognostic value of small intestinal dilatation in dogs with protein-losing enteropathy

To date, little is known about the prognostic significance of ultrasonographic findings in dogs with protein-losing enteropathy (PLE). The aim of this retrospective study was to examine the prognostic value of ultrasonographic findings in dogs with PLE. A total of 26 dogs with PLE were included: 20 dogs with chronic enteropathy and 6 dogs with gastrointestinal lymphoma. The presence of small intestinal dilatation was associated with shorter survival time in dogs with PLE (P=0.003). The presence of hyperechoic intestinal mucosal striations was associated with longer survival time in dogs with PLE (P=0.0085). The results of the current study indicate that the presence of small intestinal dilatation might be associated with poor prognosis in dogs with PLE.     

Primary intestinal lymphangiectasia in three dogs: a morphological and immunopathological investigation

Morphological and immunological findings of three dogs with primary lymphangiectasia are described and compared with three normal dogs. Scanning electron microscopy showed distended and fused intestinal villi in dogs with intestinal lymphangiectasia, and morphometric evaluation revealed deeper crypts in the small intestine of dogs with intestinal lymphangiectasia. Although plasma cells of all classes were diminished in the cranial parts of the small intestine, there was an absolute and relative increase of immunoglobulin G-containing plasma cells in the caudal small intestine in dogs with intestinal lymphangiectasia.     

Immune cell populations within the duodenal mucosa of dogs with enteropathies

The mucosal immune system may play a critical role in the pathogenesis of small intestinal enteropathies. The aim of the current study was to assess mucosal immune cell populations in dogs with inflammatory bowel disease (IBD), idiopathic antibiotic-responsive diarrhea (ARD), and adverse reactions to food (FR). Endoscopic biopsies were performed of the duodenum of dogs with these conditions and from a group of dogs without enteric disease. Additional control samples were collected after death from other dogs that did not have evidence of enteric disease. Immunohistochemistry and computer-aided morphometry were used to assess the distribution of immune cell subsets in both lamina propria and intestinal epithelium. Compared with controls, dogs with ARD had increased numbers of lamina propria immunoglobulin (Ig) A- plasma cells and CD4+ cells. More marked alterations were noted in dogs with IBD, with significant increases in lamina propria IgG+ plasma cells, T cells (CD3+), CD4+ cells, macrophages, and neutrophils, but with reduced mast cell numbers. Increased intraepithelial CD3+ T cells were also present in the dogs with IBD, compared with controls. However, lamina propria and epithelial populations were unaltered in dogs with FR when compared with controls. The altered mucosal immune cell populations observed in dogs with ARD or IBD may reflect an underlying immunologic pathogenesis in these disorders.     

Retrospective study on the diagnostic value of full-thickness biopsies from the stomach and intestines of dogs with chronic gastrointestinal disease symptoms

An evaluation of histologic findings in full-thickness biopsies from the gastrointestinal tract (GIT) from 64 dogs with chronic GIT disease symptoms was performed. In the majority of cases (38/64; 59%), intestinal lymphangiectasia and mucosal edema of unknown etiology were present. In 10 dogs (16%) an eosinophilic colitis, either alone or together with gastritis and/or enteritis, was found. In 5 dogs (8%) lymphocytic-plasmacytic enteritis or enterocolitis was diagnosed. Five dogs (8%) had an intestinal T-cell lymphoma. Samples from the remaining cases were histologically normal or did not allow for a final diagnosis. In contrast to reports about findings in endoscopic biopsies (which often are of varying quality or inadequate for diagnosis), in the majority of cases of this study, examination of full-thickness biopsies from the GIT allowed us to make a definitive histopathologic diagnosis. Furthermore, the study revealed that transmural biopsies are very helpful for diagnosing lymphoma.     

Clinical, clinicopathologic, radiographic, and ultrasonographic characteristics of intestinal lymphangiectasia in dogs: 17 cases (1996-1998)

OBJECTIVE: To characterize the clinical, clinicopathologic, and imaging findings in dogs with intestinal lymphangiectasia and to compare the histologic grade of lymphangiectasia with clinicopathologic and imaging abnormalities. DESIGN: Retrospective study. ANIMALS: 17 dogs with a histologic diagnosis of intestinal lymphangiectasia. PROCEDURE: Medical records of dogs with a histologic diagnosis of intestinal lymphangiectasia were reviewed for signalment, history, clinical signs, results of exploratory laparotomy, and clinicopathologic, radiographic, ultrasonographic, and histologic findings. RESULTS: Mean age of dogs was 8.3 years; the most common clinical signs were diarrhea, anorexia, lethargy, vomiting, and weight loss. Abnormal physical examination findings included dehydration, ascites, and signs of pain on palpation of the abdomen. The most notable clinicopathologic findings were low serum ionized calcium concentration and hypoalbuminemia. Abdominal ultrasonography was performed in 12 dogs and revealed intestinal abnormalities in 8 dogs and peritoneal effusion in 7 dogs. Exploratory laparotomy revealed abnormalities in 9 of 16 dogs including thickened small intestine, dilated lacteals, lymphadenopathy, and adhesions. On histologic examination of the small intestine, concurrent inflammation was observed in 15 of 17 dogs, crypt ectasia in 5 of 17, and lipogranulomas in 2 of 17. CONCLUSIONS AND CLINICAL RELEVANCE: Intestinal lymphangiectasia in dogs appears to be a heterogeneous disorder characterized by various degrees of panhypoproteinemia, hypocholesterolemia, lymphocytopenia, and imaging abnormalities. In most dogs, the severity of hypoalbuminemia appears to offer the best correlation with severity of histologic lesions of lymphangiectasia. Imaging abnormalities are common in dogs with intestinal lymphangiectasia but are not specific enough to differentiate this disorder from other gastrointestinal disorders, nor are they predictive of histologic severity.     

Ultrasonographic evaluation of the thickness of the small intestinal wall in dogs with inflammatory bowel disease

OBJECTIVES: To establish whether the intestinal wall thickness, as measured ultrasonographically, is significantly increased in dogs with inflammatory bowel disease (IBD). The results would provide the information necessary to decide whether measurement of ultrasonographic wall thickness can predict IBD in dogs. METHODS: The intestinal wall thickness of 75 dogs with idiopathic IBD, as measured by ultrasonography, was compared with recently published normal values. IBD was either confirmed histologically (n = 54) or suspected (n = 21). In all cases there was a positive response to immunosuppressive treatment. RESULTS: A positive association between intestinal wall thickness in dogs and either the histological diagnosis or the response to treatment was not found. Ultrasonographic intestinal wall measurements do not appear to be able to establish a diagnosis of intestinal inflammation and may result in a false negative diagnosis in cases of IBD. CLINICAL SIGNIFICANCE: The same 'grey zone' of between 4 and 6 mm used in humans can be used in the canine duodenum to distinguish the normal range, reserving the term 'abnormal' for an intestinal measurement greater than 6 mm in the duodenum and greater than 4.7 mm in the jejunum.     

Protein-losing enteropathy in dogs is associated with decreased fecal proteolytic activity

Background: Measurement of proteolytic activity in feces is a traditional method for the diagnosis of exocrine pancreatic insufficiency (EPI). A drawback of this method is the occurrence of falsely low results that may lead to a false‐positive diagnosis of EPI. We hypothesized that intestinal loss of serum proteinase inhibitors in protein‐losing enteropathy (PLE) may inhibit fecal proteolytic activity and be a potential source of false low results. Objective: The objective of this study was to determine the effect of PLE on fecal proteolytic activity in dogs. Methods: Fecal proteolytic activity was measured using a radial diffusion casein digestion assay in 12 samples from 4 clinically healthy control dogs and 30 samples from 16 dogs with PLE. Gastrointestinal protein loss was assessed using an ELISA to determine fecal canine α₁‐proteinase inhibitor concentration. The relationship between the concentration of canine α₁‐proteinase inhibitor in the feces and the diameter cleared in the casein digestion assay was determined. The mean clearing diameter was compared between control dogs and dogs with PLE. Results: A significant negative correlation was observed between fecal canine α₁‐proteinase inhibitor concentration and casein clearing diameter (P < .001, Pearson r=—.6317, r 2 =.3999). Mean clearing diameter was significantly lower in dogs with PLE than in control dogs (12.63 vs 16.83 mm, P < .001, two‐tailed Student's t‐test). Conclusion: Increased fecal loss of α₁‐proteinase inhibitor in dogs with PLE is associated with a significant decrease in fecal proteolytic activity and may result in a false positive diagnosis of EPI.     

Possible causal association of idiopathic inflammatory bowel disease with thrombocytopenia in the dog

Extraintestinal manifestations of inflammatory bowel disease (IBD) are commonly observed in humans but are poorly documented in companion animals. Thrombocytopenia is an uncommon but well-documented extraintestinal hematological abnormality in humans; however, there are no previous reports of IBD and concurrent thrombocytopenia in the veterinary literature. Seven dogs having idiopathic IBD and concurrent thrombocytopenia were identified and evaluated retrospectively (this represents an incidence of 2.5% in the authors' IBD population). Obvious known causes for thrombocytopenia were eliminated by diagnostic testing as deemed appropriate by the clinician of record. Thrombocytopenia resolved with treatment for the IBD in some but not all patients. This is similar to reports in humans. Thrombocytopenia typically appears to be subclinical, and the severity does not correlate with the degree of intestinal inflammation defined histopathologically. However, quantitative platelet counts should be monitored during IBD therapy, as additional immunosuppression may be required to treat thrombocytopenia, despite resolution of gastrointestinal signs. It is speculated that thrombocytopenia may be causally associated with canine IBD, possibly secondary to immune stimulation from lumenal bacterial antigens, altered immunological regulation, or both.     

A scoring index for disease activity in canine inflammatory bowel disease

The clinical course of inflammatory bowel disease (IBD) in dogs is characterized by spontaneous exacerbations and remissions, which makes assessment of disease burden difficult. The objectives of this study were to develop a scoring system for evaluation of canine IBD activity and to validate this scoring method by correlating it to objective laboratory and histologic indices of intestinal inflammation. Fifty-eight dogs with IBD were evaluated prospectively and compared to 9 disease-free control dogs. Clinical disease activity was quantified by a simple scoring system, the canine IBD activity index (CIBDAI), and compared to serum concentrations of C-reactive protein (CRP), haptoglobin (HAP), alpha-acid glycoprotein (AGP), and serum amyloid A (SAA), as well as histology scores derived from endoscopic biopsy specimens. Forty-six dogs were available for a reevaluation of the CIBDAI, CRP HAP, and AGP, and 34 dogs had repeat analysis of SAA performed after medical therapy. Serum concentrations of CRP were significantly (P < .02) increased in dogs with CIBDAI scores > or = 5 (mild disease activity or greater) compared to controls. Among IBD dogs, the CIBDAI showed good correlation (r = 0.82, P < .0001) to both histology and HAP scores, but CRP also was a strong co-correlate of disease activity. The IBD dogs showed significantly (P < .0001) decreased CIBDAI and CRP values but significantly (P < .0001) increased HAP concentrations after medical therapy compared to pretreatment values. We conclude that the CIBDAI is a reliable measure of inflammatory activity in canine IBD and that CRP is suitable for laboratory evaluation of the effect of therapy in these patients.     

Comparison of Oral Prednisone and Prednisone Combined with Metronidazole for Induction Therapy of Canine Inflammatory Bowel Disease: A Randomized‐Controlled Trial

Background: Although prednisone and metronidazole are commonly used to treat canine inflammatory bowel disease (IBD), no randomized‐controlled trials have been performed. Hypothesis: Combination drug therapy with prednisone and metronidazole will be more effective than prednisone alone for treatment of canine IBD. Reduction in disease severity will be accompanied by decreased canine IBD activity index (CIBDAI) scores and serum C‐reactive protein (CRP) concentrations. Animals: Fifty‐four pet dogs diagnosed with IBD of varying severity. Methods: Dogs were randomized to receive oral prednisone (1 mg/kg; n = 25) or prednisone and metronidazole (10 mg/kg; n = 29) twice daily for 21 days. Clinical (CIBDAI) scores and serum CRP were determined at diagnosis and after 21 days of drug therapy. The primary efficacy measure was remission at 21 days, defined as a 75% or greater reduction in baseline CIBDAI score. Results: Differences between treatments in the rate of remission (both exceeding 80%) or the magnitude of its change over time were not observed. CRP concentrations in prednisone‐treated dogs were increased because of many dogs having active disease. Both treatments reduced CRP in comparison with pretreatment concentrations. An interaction between CIBDAI and CRP was identified in 42 of 54 dogs (78%), whereas 8 of 54 dogs (15%) showed disagreement between these indices. Conclusions and Clinical Importance: Prednisone is as effective as combined treatment with prednisone and metronidazole for induction therapy of canine IBD. CRP may be normal or increased in dogs with IBD and may be useful in assessing the response of individual dogs to treatment along with changes in the CIBDAI.