Comparative pathophysiology and management of protein‐losing enteropathy

Abstract

Protein‐losing enteropathy, or PLE, is not a disease but a syndrome that develops in numerous disease states of differing etiologies and often involving the lymphatic system, such as lymphangiectasia and lymphangitis in dogs. The pathophysiology of lymphatic disease is incompletely understood, and the disease is challenging to manage. Understanding of PLE mechanisms requires knowledge of lymphatic system structure and function, which are reviewed here. The mechanisms of enteric protein loss in PLE are identical in dogs and people, irrespective of the underlying cause. In people, PLE is usually associated with primary intestinal lymphangiectasia, suspected to arise from genetic susceptibility, or “idiopathic” lymphatic vascular obstruction. In dogs, PLE is most often a feature of inflammatory bowel disease (IBD), and less frequently intestinal lymphangiectasia, although it is not proven which process is the true driving defect. In cats, PLE is relatively rare. Review of the veterinary literature (1977‐2018) reveals that PLE was life‐ending in 54.2% of dogs compared to published disease‐associated deaths in IBD of <20%, implying that PLE is not merely a continuum of IBD spectrum pathophysiology. In people, diet is the cornerstone of management, whereas dogs are often treated with immunosuppression for causes of PLE including lymphangiectasia, lymphangitis, and crypt disease. Currently, however, there is no scientific, extrapolated, or evidence‐based support for an autoimmune or immune‐mediated mechanism. Moreover, people with PLE have disease‐associated loss of immune function, including lymphopenia, severe CD4+ T‐cell depletion, and negative vaccinal titers. Comparison of PLE in people and dogs is undertaken here, and theories in treatment of PLE are presented.

Clinical characteristics of dogs with food‐responsive protein‐losing enteropathy

“…Because the FR‐PLE group had significantly lower CIBDAI and CCECAI scores than those found in the IR/NR‐PLE group, the longer survival time of the FR‐PLE group may be attributed to the severity of the disease, which has been shown to be associated with prognosis in dogs with PLE . In addition, other factors, such as body weight, BUN, ALB, and PARR could be associated with survival time . Therefore, further study is needed to evaluate the effect of ULFD itself on the prognosis of dogs with PLE.…”

“…A fat‐restricted diet, especially homemade ultralow‐fat diet (ULFD), has been recommended for dogs with primary IL for many years, and it has been believed to decrease intestinal lymphatic pressure by decreasing fat absorption from intestinal mucosa . The fat content of an ULFD made from chicken breast and white potato is 0.35 g/100 kcal, whereas that of a conventional low‐fat dry diet is approximately 2 g/100 kcal . A study showed that dogs with IL refractory to prednisolone or dependent on high‐dose prednisolone exhibited improvements in total protein and albumin concentrations and clinical signs after an ULFD were introduced .…”

Ki‐67/CD3 ratio in the diagnosis of chronic inflammatory enteropathy in dogs

“…The CIE group included 1 dog with PLE. This fact must be interpreted with caution because PLE is not a single disease but a syndrome that develops in different diseases of different etiologies such as lymphatic obstruction, increased vascular permeability because of cytokines, or mucosal inflammation as in IBD (primarily caused by severe lymphoplasmatic enteritis) . Another limitation was that not all areas were always available for every patient because of the nature of biopsy samples and cutting techniques.…”

Diagnostic features, treatment, and outcome of dogs with inflammatory protein‐losing enteropathy

“…Other negative prognostic indicators include clinical abnormalities such as chronic vomiting, low body weight, failure to normalize CIBDAI or CCECAI, laboratory abnormalities (eg, decreased or increased blood urea nitrogen concentration), high endoscopic scores, and duodenal inflammation . Elevations in serum C‐reactive protein concentration and decreases in 25(OH) vitamin D serum concentration also have prognostic value …”

“…However, diagnostic imaging findings have not been evaluated for their prognostic value. Endoscopy and histopathology scores are inconsistent predictors of diagnosis and prognosis of PLE …”