Treatment of a Myasthenic Dog with Mycophenolate Mofetil

Abstract

A ten-year-old, male castrated Springer Spaniel was presented for dysphagia, ptyalism, and regurgitation. Evidence of megaesophagus and mild aspiration pneumonia were apparent on thoracic radiographs. A diagnosis of focal acquired myasthenia gravis was suspected and subsequently confirmed with a positive serum acetylcholine (ACh) receptor antibody concentration (3.87 nM/L). A gastrostomy tube was placed shortly after presentation; food and drugs (including azathioprine) were administered through the tube. After transient improvement, the dog suddenly deteriorated clinically, experiencing frequent episodes of regurgitation and developing severe aspiration pneumonia. Mycophenolate mofetil (MMF), a novel immunosuppressive drug with relative specificity for lymphocytes, was instituted every twelve hours via the gastrostomy tube. Within four days of beginning MMF therapy, both clinical evidence of pharyngeal/esophageal dysfunction and radiographic evidence of megaesophagus had resolved. Initially, clinical side-effects of combined MMF/AZA administration were not apparent, but the patient experienced several vomiting episodes during the third week of treatment. The vomiting resolved after decreasing the dose of both drugs. The patient made a full recovery, and a one-month follow-up ACh receptor antibody concentration was normal ( 0.26 nM/L). After one month of combination therapy, the patient was weaned off of AZA and maintained on MMF as the sole immunosuppressive drug. The dog was subsequently weaned off of MMF on two occasions. Mycophenolate mofetil was reinstituted after the first discontinuation due to the development of profound appendicular muscle weakness two days after stopping MMF; the weakness resolved within 24 hours of reinstituting MMF. A positive ACh receptor antibody concentration (0.89 nM/L) after the second MMF weaning prompted the second reinstitution of MMF. Two months following this second MMF reinstitution, the dog was again serologically negative (0.51 nM/L) for myasthenia gravis. At the time of last followup, the dog remained in clinical remission eight months after initial presentation. The use of MMF to treat acquired myasthenia gravis in dogs has not been reported previously. The literature concerning MMF and its potential use in treating patients with autoimmune diseases is discussed.

Treatment of five haemodynamically stable dogs with immune‐mediated thrombocytopenia using mycophenolate mofetil as single agent

“…The most common adverse reactions associated with MMF administration in dogs with naturally occurring immune‐mediated diseases are weight loss, GI upset and mild allergic reactions during parenteral administration (Dewey et al , Lange et al ). In this case series, GI side effects due to MMF therapy were common, which is consistent with previous studies (Dewey et al , Banyard & Hassett , Broaddus et al , Yuki et al , Abelson et al , Dewey et al , Ginel et al , Wang et al , West & Hart ).…”

Myasthenia gravis in dogs with an emphasis on treatment and critical care management

“…All 3 animals were seropositive for AChR antibodies; this was the first report in dogs successfully demonstrating the use of MMF in treatment of severe generalized MG 30 . In another case report, a 10‐year‐old male castrated Springer Spaniel diagnosed with focal MG (seropositive for AChR antibodies) initially improved with azathioprine but deteriorated shortly after 86 . MMF was orally instituted in addition to azathioprine resulting in dramatic improvement 86 .…”

“…30 All 3 animals were seropositive for AChR antibodies; this was the first report in dogs successfully demonstrating the use of MMF in treatment of severe generalized MG. 30 In another case report, a 10-year-old male castrated Springer Spaniel diagnosed with focal MG (seropositive for AChR antibodies) initially improved with azathioprine but deteriorated shortly after. 86 MMF was orally instituted in addition to azathioprine resulting in dramatic improvement. 86 However, in a recent retrospective cohort study of 27 dogs with serologically confirmed acquired MG that were treated with a combination of MMF and pyridostigmine compared with those treated with pyridostigmine alone did not show any beneficial therapeutic effect of MMF over the long term.…”

“…86 MMF was orally instituted in addition to azathioprine resulting in dramatic improvement. 86 However, in a recent retrospective cohort study of 27 dogs with serologically confirmed acquired MG that were treated with a combination of MMF and pyridostigmine compared with those treated with pyridostigmine alone did not show any beneficial therapeutic effect of MMF over the long term. 64 There have been a number of studies on the use of MMF in human medicine.…”

Myasthenia gravis

“…Mycophenolate mofetil (MM) has been used in the treatment of focal MG (Dewey et al, 2000). It is an immunosuppressive agent developed and originally used to prevent acute rejection of solid-organ transplantation.…”