Typical MUE Treatment

Piper celebrating completing 4 of 6 GME chemotherapy treatments

MUE is a fast moving progressive disease that requires aggressive treatment to achieve remission.

According to the scientific literature, up to 90% may make it to remission, but the speed at which your dog or cat must be treated cannot be stressed enough. Delays in starting treatment can be deadly.

As soon as the presumptive diagnosis of MUE is made, treatment must begin.

Your veterinarian will need to use high dose, long term, immunosuppression (typically using prednisone) with the addition of chemotherapy (best outcome) and/or additional immunosupressive agents.

The tapering of prednisone must be very slow. This is the single biggest mistake made by veterinarians who are inexperienced in treatment.

If seizures are present, anti-seizure medication will be needed to control the seizures.

You may also need support for the gastrointestinal system (nausea/vomiting/diarrhea) and liver support.

The common GME treatment options are below with more information about each including side effects.

Immune Suppression with Corticosteroids

Immune suppression with high dose corticosteroids, primarily prednisone, must initally be used at immunosuppressive doses. 

Once the GME progresion is controlled, the dose of prednisone is maintained at high levels and then very slowly lowered (titered) down to achieve the minimum dose required to control the disease until eventually being tapered off.

Titering too quickly is the single biggest mistake veterinarians who are not used to treating GME make, which results in relapse. 

In Piper's case, she started high does immunosupressive prednisone on March 14, 2017.  After stopping disease progression and seizures, she was maintained on high dose for approximately 6 months before she was slowly titered down. Her last does of prednisone (low dose) was May 26, 2018.

  • Dogs weighing less than 5 kgs are dosed as 5 kg dogs
  • Dogs weighing 5 to 10 kgs are dosed as 10 kg dogs
  • Dogs weighing over 35 kg are dosed as 35 kg dogs

Common Side Effects of GME Treatment

The most common side effects from GME treatment are nausea and vomiting and elevated liver enzymes. 

Your veterinarian should prescribe Zofran to help control the nausea and over the counter Pepsid to help control stomach acid. 

Other antiemetics may be prescribed if Zofran is not effective.

In Piper's case, she had to stay at the hospital on IV Zofran after her first chemotherapy treatment until she was stabilized enough to come home after having severe nausea and vomiting.

After completing treatment we worked to get her liver enzymes lowered. 

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Response to prednisolone is variable and results are much better if additional medications such as chemotherapy and/or additional immunesuppression are added.

Your veterinarian will add one or more of the following treatments:

Low Dose Chemotherapy Agents

Chemotherapy has the highest success rate of achieving remission and you shouldn't be afraid of it.

In general, animals respond very well to low dose chemotherapy and side effects are more from prednisone than the chemotherapy. 

Given the low dose, your dog will not lose their hair/fur but you will need to wear gloves when cleaning up urine/vomit within days after the treatment.

Low dose chemotherapy drugs must be administered through IV over 4-6 hours.

  • Cytarabine (Cytosine arabinoside): Has been shown to be the most effective. Adverse effects, beyond nausea and vomiting, are not common, but in very rare occurances, it can cause myelosuppression - a condition in the bone marrow that results in fewer red blood cells, white blood cells, and platlets. Bloodwork will be needed to monitor how your dog is responding and Cytarabine may be terminated if cell counts are too low.

  • Lomustine (CCNU): Used to treat brain tumors and lymphosarcoma, it has been shown to be effective in addition to or replacement for prednisone immune suppression in prednisone resistant cases, or for cases that relapse off of prednisone or when prednisone adverse effects are too severe.

    It can cause a severe decrease in the number of blood cells in the bone marrow which may cause certain symptoms and may increase the risk of a life threatening infection or bleeding. Must be monitored very closely for fever and signs of infection; unusual bleeding or bruising, bloody or black, tarry stools; bloody vomit; or vomiting blood or brown material that resembles coffee grounds.

  • Procarbazine: Used to primarily treat lymphosarcoma. Side effects include bone marrow suppression and gastrointestinal side effects such as pancreatitis and inflammation and bleeding of the stomach and intestines called hemorrhagic gastroenteritis (HGE). HGE is very serious and can qiuckly be life threatening.

Anti-Seizure Medication (if presents with seizures)

An anticonvulsants will need to be used if your dog or cat has seizures. The three most common and their side effects are listed below.

Levetiracetam (Keppra): Generally well-tolerated, with minimal side effects, such as mild sedation or gastrointestinal upset. It is preferred over other anticonfulsants due to showing less long term side effects than others. 

Gabapentin: Side effects may include sedation, dizziness, loss of coordination, and gastrointestinal upset. With prolonged use, some individuals may develop tolerance to the effects of gabapentin, requiring higher doses to achieve the same therapeutic effect. In rare cases, dependence or withdrawal symptoms may occur upon discontinuation. Incidence of liver complications are low. 

Phenobarbital: Side effects include ncreased thirst and urination, weight gain, sedation, liver damage, and potential long-term effects on liver function.

Immune Suppression

If there are significant side effects to prednisone it may be reduced in dose or terminated and another immunosuppressive drug will need to be used.

  • Leflunomide (Arava): A drug developed to manage rheumatoid arthritis, this newer and more expensive drug is being used as a possible alternative to cortocosteroid use for dogs/cats that do not tolerate the side effects of prednisone. It can cause liver damage.

  • Cyclosporine (microemulsified): Can be used in place of, or more often combined with, prednisone, leflunomide, cytarabine or lomustine to achieve maximum immunosuppression. Most common side effect is vomiting and/or diarrhea. 

  • Azathioprine: Was found to have some effectiveness but is generally less effective and more toxic than leflunomide in most cases. The adverse effects of azathioprine include bone marrow suppression, hepatotoxicosis, and acute pancreatitis. These side effects can rapidly be life threatening which is why it is often used only if the other 2 immunosuppressive drugs are not effective to achieve remission.

Gastrointestinal Support

Treatment for GME can be very hard on the gastrointestinal system (usually from the high dose prednisone).

Your dog or cat may need one or all of these medications to manage symptoms.

Piper had to take all 3 at the start of treatment and was able to remove all but Pepsid after lowering her dose of prednisone but she stayed on Pepsid until completing Prednisone.

  • Pepsid: Consult with your veterinarian on dosage but it is generally best taken first thing in the morning on an empty stomach.

  • Zofran: Used to treat nausea and vomiting. 

  • Omeprazole: Used to treat certain stomach and esophagus problems (such as acid reflux, ulcers). It works by decreasing the amount of acid in the stomach.

  • Cerenia: Used to help with nausea and vomiting (not as effective as Zofran in our experience).

Liver Support

Elevated liver enzymes is very common. You can use these separately or together at the same time (depending on the ALT levels and your need to lower them): 

  • Denamarin: A supplement containing the antioxidant Silybin used to improve your pet's liver function by increasing liver glutathione levels.

  • Adored Beast Liver Tonic: Helps support, detox, and repair liver, kidney, pancreas, and gallbladder function. Made with herbal ingredients such as dandelion root, milk thistle, barberry, and vegetable glycerine.

For more information on the treatment of GME, MUE, MUO, etc. please see the paper written by Dr. Sisson (2012). While an older paper, it does contain some valuable information.

Long Term Prednisone Use

As dog moms who are very holisticlly focused, the thought of putting Piper on steroids for such a long period of time was terrifying.

Unfortnutaely, given the seriousnes of GME, without aggressive treatment, your dog or cat will not survive. It is that simple.

The most common immunosupressive used to achieve remission is prednisone, and it is not uncommon to have side effects.

Report side effects to your veterinary neurologist so they can continue to monitor with bloodwork and help you manage side effects as needed.

Prednisone alone or in combination therapy may cause the following:
  • Panting
  • Frequent urination 
  • Extreme thirst
  • Exteme hunger
  • Urinating in the house or urinary incontence (should check to make sure there isn't a urinary tract infection)
  • Weight loss (at the start of treatment due to muscle wasting from high dose prednisone).  Piper got very scrawny and bony until the prednisone dosage was reduced, then she gained weight!
  • Weight gain (after dosage is lowered from the initial starting dose)
  • Vomiting 
  • Diarrhea
  • Gastrointestinal ulcers or perforation of the gastrointestinal lining
  • Liver damage (which can be life threatening)
  • Urinary tract infections (UTIs)
  • Skin infections
  • Lethargy 
  • Depression
  • Aggressiveness
  • Muscle atrophy / weakness (muscle wasting)
  • High blood pressure
  • Hair loss
  • Skin lumps called calcinosis cutis
  • Disruption of the endocrine system
Your dog or cat may need to be on medication to help control nausea/vomiting during treatment which can be tapered down over time.