Protein-losing enteropathy (PLE) is frequently caused by intestinal lymphangiectasia following lymphocytic-plasmacytic enteritis. Immunosuppressive medications, such as prednisolone and azathioprine, are often used to treat PLE. Achieving and maintaining remission with these drugs alone, however, can be difficult. In this case study, a 9-year-old female pug with a 1-month history of diarrhea was confirmed to have PLE secondary to lymphocytic-plasmacytic enteritis. She was initially treated with ampicillin (20 mg/kg SC Q 12 H), prednisolone (1 mg/kg SC Q 12 H ), and metronidazole (12.5 mg/kg PO Q 12 H). However, total protein and albumin levels remained low and additional treatment with cyclosporine (5 mg/kg PO Q 12 H) was initiated on day 4. Supplementation with cobalamin (50 µg/kg SC once weekly) began on day 6 when cobalamin levels were found to be low (97 pg/ml). By day 8, protein and albumin levels were found to be decreasing even further, and methotrexate (MTX) was substituted for the cyclosporine at a dose of 0.6 mg/kg IM. The following day, protein and albumin levels began to increase and normalized within 1 week. Diarrhea also improved at the same time. MTX was then administered 5 times at 7-day intervals up until the 37th day, at which point the azathioprine was expected to become effective (azathioprine can take as long as 3 to 4 weeks to achieve clinical effectiveness). No side effects from the MTX were noted. Prednisolone was then gradually decreased, and complete remission was maintained at a low dose of prednisolone (0.3 mg/kg PO Q 48 H) and azathioprine (2 mg/kg PO Q 48 H) after the 59th day. Cobalamin levels were also noted to have normalized within 6 weeks of MTX treatment and cobalamin supplementation. The authors of the study conclude that MTX could become a treatment of choice for PLE.
COMMENTARY: PLE can be frustrating to treat. Sometimes, the underlying cause cannot be found, or if it is, cannot be treated effectively. In this case, the patient did not respond to cyclosporine as expected. Thus, the authors chose to replace it with MTX based on MTX's effectiveness in human cases of inflammatory bowel disease and autoimmune diseases, such as rheumatoid arthritis. MTX is an antimetabolite (folic acid inhibitor) with immunosuppressive and antiinflammatory activity. Its use in veterinary medicine has been limited to cancer treatment; however, this article presents an intriguing possibility for future clinical use. Further studies investigating this drug's mode of action, ideal dose for PLE (the dose used in this study was based on chemotherapy protocols), safety, and efficacy may prove to be worthwhile.
A case of protein-losing enteropathy treated with methotrexate in a dog. Yuki M, Sugimoto N, Takahashi K, et al. J VET MED SCI 68:397-399, 2006.