A challenging case: Glucagonoma-associated superficial necrolytic dermatitis in a dog

Although this skin disease is usually associated with hepatopathy, in this dog the lesions had a more uncommon cause.

1. An 8-year-old mixed-breed dog with inappetence, weight loss, and alopecia.
An 8-year-old 46.3-lb (21-kg) female spayed mixed-breed dog was referred to the Purdue University Veterinary Teaching Hospital for evaluation of lethargy, inappetence, weight loss, and alopecia of several months' duration (Figure 1).


2. Erythema, ulcers, and superficial excoriations on the dog's footpad.
At presentation, the dog was in poor body condition, with a score of 3/9. The dog's temperature and pulse and respiration rates were normal. The physical examination revealed erythema, ulcers, and superficial excoriations involving the footpads (Figure 2) and ventral interdigital areas, extending to the tarsus and carpus. Similar lesions were noted on the elbows, hocks (Figure 3), ears, and commissures of the mouth. No other abnormalities were identified on oral examination, abdominal palpation, or thoracic auscultation.

3. Erythema and crusty alopecia on the dog's dorsal paw, tarsus, hock, and stifle region.
Differential diagnoses considered at this point included various autoimmune, hypersensitivity, and paraneoplastic dermatitides; erythema multiforme; toxic epidermal necrolysis; various cutaneous neoplasms; canine distemper-associated hyperkeratosis; and nutritional disorders such as zinc deficiency.


4. A photomicrograph of a footpad biopsy showing parakeratotic hyperkeratosis, acanthosis, and superficial lymphohistiocytic dermatitis. Note the red upper layer of the stratum compactum (short arrow), the white middle layer of ballooning degeneration in the stratum spinosum (arrowhead), and the blue hyperplastic basal cell layer of the epidermis (long arrow) (hematoxylin-eosin stain, 100X).
Histologic examination of biopsy samples from the footpads and adjacent haired skin revealed severe, chronic, and regionally diffuse acanthosis with intracellular edema in the stratum spinosum, parakeratosis and crusting, and superficial lymphohistiocytic dermatitis, suggestive of superficial necrolytic dermatitis and glucagonoma-associated paraneoplastic syndrome (Figure 4). A radiographic examination revealed slightly decreased liver and cardiac silhouettes but no abdominal masses. An ultrasonographic examination did not reveal any space-occupying abdominal masses or abnormal hepatic echotexture.

Vital Stats
To explore possible causes of the superficial necrolytic dermatitis, such as hepatic deficiency or a pancreatic glucagonoma, fasting blood samples were submitted for a complete blood count (CBC), serum chemistry profile, and plasma glucagon concentration. A bile acid assay was also done. The CBC did not reveal any clinically relevant hematologic abnormalities, and the serum chemistry profile revealed only mildly decreased blood urea nitrogen (4 mg/dl; reference interval = 5 to 28 mg/dl) and creatinine (0.4 mg/dl; reference interval = 0.5 to 1.5 mg/dl) concentrations, attributed to the poor body condition score and associated reduced muscle mass. Hepatic enzyme activities and serum preprandial and postprandial bile acid concentrations were normal.

Urinalysis of a sample obtained by cystocentesis revealed hematuria and bacteriuria (2+ blood, 1+ bacteria, > 50 RBCs/hpf, and 5 WBCs/hpf), indicating bacterial cystitis. A urine bacterial culture was positive for Escherichia coli, with a wide spectrum of antibacterial sensitivity.

Plasma samples analyzed for glucagon concentration by using a human radioimmunoassay at The Ohio State University Medical Center revealed plasma glucagon concentrations greater than 1,700 ng/L (canine reference interval = 35 to 49 ng/L).1