Diagnosis (see also Chapter 19 on IBD)
The first step when facing a dog or cat with a suspicion of PLE is to rule out other conditions associated with hypoalbuminemia such as renal loss (protein-losing nephropathy), lack of production (liver failure), third space loss (ascites or pleural effusion), or loss across the skin (burns).
Therefore, the workup should include a urinalysis, protein- to-creatinine ratio, liver function test (bile acids or ammonia), and a search for inflammatory fluid accumulation within the thorax and abdomen.Reported clinical signs include were diarrhea (91%), weight loss (74%), anorexia (56%) and lethargy (51%) (Lecoindre et al. 2010). In one study leukocytosis was detected in 20/29 dogs, whereof 14 had a high band count (Equilino et al. 2015). Serum biochemical analyses revealed that serum total protein, albumin, and total calcium concentrations were decreased in all 29 dogs (Equilino et al. 2015), whereas serum cobalamine concentrations were low in 75% of the dogs.
Serum concentration of C-reactive protein (CRP), an acute-phase reactant, can be useful as a prognostic marker in dogs with IBD (Jergens et al. 2003). However, in some studies in dogs (Allenspach et al. 2007; McCann et al. 2007), CRP concentration did not reflect the severity of IBD as assessed by use of the canine chronic enteropathy clinical activity index (CCECAI) or canine inflammatory bowel disease activity index (CIBDAI). A recent study (Equilino et al. 2015) showed that serum CRP concentration was high in most dogs with PLE and was significantly higher than in dogs with food- responsive diarrhea (FRD).
Alpha1-proteinase inhibitor (α1-PI) is present in plasma, interstitial fluid, and lymph, but is not usually found at high concentrations within the lumen of the gastrointestinal tract. Furthermore, α1-PI is resistant to proteolytic degradation and its molecular weight is similar to that of albumin.
Therefore, it can be used as a marker for intestinal protein loss (Murphy et al. 2003). A study in Yorkshire Terriers revealed an association between serum α1-PI concentrations less than the lower limit of the reference interval and cobalamine deficiency (Grutzner etal. 2013). This is suggestive of severe long-standing distal small intestinal disease, such as PLE, which has been reported frequently for this breed. In a recent study with PLE dogs secondary to IBD, serum α1-PI concentration was significantly lower in PLE than FRD and 50% of the dogs yielded α1-PI values below the lower end of the reference range (Equilino et al. 2015).The heterodimeric protein complex cal- protectin binds calcium and zinc, is expressed and released from infiltrating myelomono- cytic cells at sites of inflammation, and has the potential to differentiate between healthy dogs from those with inflammatory conditions, such as IBD (Heilmann, Suchodolski, and Steiner 2008). S100A12, a calcium-binding protein of the S100 superfamily that is mainly localized in granulocytes and mononuclear inflammatory cells appears to be a sensitive and specific biochemical marker of chronic gastrointestinal inflammation in humans. A test for S100A12 protein detection in serum and fecal samples from dogs has recently been developed and validated (Heilmann et al. 2011). Serum calprotectin and S100A12 concentrations were mostly elevated in dogs with PLE secondary to IBD (Equilino et al. 2015), but did not differ significantly between PLE and FRD.
Ultrasonographic findings in 29 dogs with PLE (Equilino et al. 2015) included stomach wall thickening in 5 dogs and abnormalities of the intestinal wall (stippling, striations, or loss of wall layering) in 26 dogs (segmental abnormalities in 14 dogs and generalized abnormalities in 12 dogs). The duodenum and jejunum were involved in almost all cases, whereas only 1 dog showed colonic changes on ultrasound. Abdominal effusion was present in 22 dogs (mild effusion in 16 dogs and moderate effusion in 6 dogs), and the mesentery was assessed as hyperechoic in 21 dogs. Abdominal lymph nodes were rarely enlarged.
Endoscopic and histopathology findings in 29 dogs with PLE (Equilino et al. 2015) showed evidence of gastric fibrosis (N= 17) and lymphocytic-plasmacytic gastritis (N = 16). Histopathology abnormalities in the duodenum were identified in all dogs: lymphocytic-plasmacytic inflammation (N = 29), lymphangiectasia (N = 21), eosinophilic inflammation (N = 9), and fibrosis (N = 9). There was no correlation found between severity of intestinal inflammation in histopathology and findings in abdominal ultrasound. Lecoindre et al. (2010) also found that most PLE cases where associated with moderate to severe inflammatory infiltrates (86%), associated with dilatation of intestinal crypts (71%) and lymphangiectasia (62%).