Clinical Case Challenge

A 9-year-old intact male Labrador retriever presented to Tufts Foster Hospital for Small Animals for further evaluation of history of painful gait, chronic atopic dermatitis/pododermatitis (for years) and the recent discovery of of increased liver enzymes (ALT =422 U/L, ALP= 377 U/L, AST =73 U/L) with a normal albumin and bilirubin. The dog had failed to respond to consecutive 3 week courses of clindamycin and cefpodoxime. On physical examination the dog was normal except for extreme difficulty in getting up and walked gingerly. He would not permit full examination of the feet, but a moist dermatitis and areas of ulceration were appreciated (Fig 2 A).

Fig 2

Fig 2. Hepatocutaneous syndrome in a dog. A. Gross appearance of feet with hyperkeratosis and ulceration. B. Ultrasound of liver showing typical ‘honeycomb’ pattern consisting of variable-sized hypoechoic regions surrounded by hyperechoic borders. B. Skin biopsy (H&E) with 1: Marked parakeratotic hyperkeratosis; 2: Vacuolar change in the upper levels of the epidermis; 3. Hyperplastic epidermis with acanthosis. Images A and C courtesy of Dr Lluis Ferrer and B from Dr. Dominique Penninck.

The scrotum was similarly involved. The finding of these skin lesions along with the increased liver enzymes without signs of hepatic functional failure (normal albumin and bilirubin, PT, PTT) suggested the possibility that the skin lesion may at this time be something different than a simple bacterial pododermatitis, and Dr. Lluis Ferrer, our dermatologist, agreed.  The Tufts team suspected hepatocutaneous syndrome (HCS). Ultrasound of the liver provided additional evidence to support our presumptive diagnosis, as the liver had the honeycomb pattern consisting of variable-sized hypoechoic regions surrounded by hyperechoic borders typically seen with HCS (Fig 2B). The histopathological correlate to this ultrasound appearance is the presence of multiple small, regenerative type nodules with fat/glycogen accumulation organized around fibrous bands of tissue with areas of parenchymal collapse. In order to obtain a definitive diagnosis of HCS, we obtained a skin biopsy and a plasma amino acid profile (UC Davis). The owner was reluctant to pursue a laparoscopic liver biopsy at this time.  Skin scrapes and scotch tape preparations of the skin were negative for Demodex and Malassezia. The skin biopsies showed the typical histopathologic changes consisting of marked parakeratotic epidermis with striking inter- and -intracellular edema from necrolysis in the upper epidermis, and hyperplastic basal cells, creating the red, white and blue lesion that is diagnostic for this disease (Fig 2C). The amino acid profile showed severe hypoaminoacidemia. The dog was treated with intravenous infusions of amino acid every three weeks for six months, and switched to a high quality protein diet supplemented with an amino acid powder.  Secondary infection was controlled with topical washes and antibiotic therapy for eight weeks. The dog has done extremely well and is alive and asymptomatic two years after diagnosis. He is being maintained on diet and oral AA supplements along with anti-oxidants (vitamin E) and hepatoprotectants (s-adenosylmethionine). Serum liver enzymes are mild to moderately elevated but hepatic function tests (albumin and bilirubin) are normal. Unlike many dogs with HCS that can be controlled, this dog has not gone on to develop diabetes mellitus.