On your schedule today is an evaluation of a 7 year old labrador with a history of lameness and red, cracked footpads. Perhaps you’re wondering why we are discussing a dermatopathy on a NEUROLOGY TidBit Tuesday? Let’s dig deeper. On examination this patient has red, dry painful footpads and a few crusting erosions around the lip folds. You decide to run a routine biochemistry and find a mildly increased ALT, and low normal albumin. Those findings aren’t enough to diagnose a hepatopathy, which you know could be one cause of these dermatologic findings, so what is this? Then, you remember! This patient has been receiving phenobarbital for 6 years for suspected idiopathic epilepsy. Serum phenobarbital concentrations are 32 ug/ml (reference 15-40 ug/ml) on recent laboratory results.

It looks like you’ve stumbled upon a phenobarbital induced superficial necrolytic dermatitis (SND), which is a rare clinical adverse effect of phenobarbital. In a report by Dr. Phil March, and colleagues, at OSU (2004), 11 of 20 dogs with SND received phenobarbital. Of course, this means that other causes for SND are possible, but chronic phenobarbital administration should be one of the differentials for SND.

Clinical Key Points

Median age: 10 years
Median PB administration: 6 years

Classic SND distribution:

Footpads (100%)
Mucocutaneous junctions (nose, mouth, perianal, perivulvar)
Pressure points (elbows, hocks)

Pathophysiology

This paper was a retrospective study, so the authors were unable to fully determine the underlying etiology. However, according to other authors and 1 dog in this study, low amino acids are the smoking gun. The proposed mechanism is due to a severe (probably chronic) depletion of glutamine, proline, arginine, and alanine. Important: this is not a hepatotoxicity! These dogs have mild ALT elevation, typically normal albumin and zero to mild increase in bile acids. Dogs with a phenobarbital hepatotoxicity have marked elevations of ALT, bile acids and a low albumin. Furthermore, on liver biopsy there is evidence of cirrhosis and fibrosis. The dogs in this study did not have cirrhosis. Vacuolation and minimal fibrosis was noted. It is important to also note that we are not talking about ALP in this situation. ALP is induced by phenobarbital and is therefore expected to be elevated with therapeutic serum phenobarbital concentrations and thus is not a sign of hepatic disease.

Treatment

While not the focus of the paper, the authors suggested that any dog with SND on chronic phenobarbital with persistent mild increases in ALT and low-normal albumin should undergoing amino acid profiling and consider treatment. To treat, we should taper phenobarbital and consider amino acid supplementation. Six dogs in this study had phenobarbital discontinued prior to the onset of the dermatitis therefore simply discontinuing the drug may not be effective. Due to a lack of clinical improvement after stopping phenobarbital (no amino acid supplementation was started), most dogs were euthanized by 3 months.

Take away:

· Remember SND can be related to phenobarbital

· Biopsy the skin lesions to make the diagnosis, then taper phenobarbital and supplement amino acids.

· Prognosis is poor for return to function

Thanks for reading! The storms in Wisconsin have been intense over the last few weeks – stay safe and I hope we can work together soon!