Maciej Guzera^1,2 DVM PhD DipECVCP MRCVS

Dorota Pomorska-Handwerker^2,3 DVM PhD

Cynthia de Vries^1,4, DVM, MSc, DipECVP

¹ Laboklin, Bad Kissingen, Germany

² Laboklin Polska, Warsaw, Poland

³ Lubelska Poliklinika Weterynaryjna, Lublin, Poland

⁴ Laboklin N.V., Hoensbroek, the Netherlands

SIGNALMENT

Dog, 8 years old, male, Hovawart.

HISTORY

A dog presented to the veterinarian with a 3-month history of polydipsia and polyuria. A more recent finding was the presence of skin lesions in the caudal part of the body which did not respond to a week-long course of antibiotics. The owner also reported that the dog was apathic and had a decreased appetite.

PHYSICAL EXAMINATION

On initial clinical examination bilateral palm-sized extensive alopecia around the iliac region was evident. The hairs were easy to epilate with most hairs being in the telogen phase on trichogram examination. The epidermis showed multifocally extensive erosion and ulceration and was partly covered with exudate and crusts (Fig. 1A and B). After trimming the hair, it became obvious that the lesions described spread all over the back of the animal. The physical examination was otherwise unremarkable.

INVESTIGATION

Haematology and biochemistry

EDTA and serum samples were sent to the laboratory as part of routine diagnostic work-up. Complete blood count was unremarkable. Biochemistry revealed a moderate increase in ALP (961 IU/L, reference interval, RI: 0-212 IU/L), GGT (47 IU/L, RI: 0-10 IU/L) and a mild elevation of ALT (227 IU/L, RI: 0-88 IU/L) and lipase DGGR (220 IU/L, RI: 25-125 IU/L). Renal parameters and electrolytes were within limits.

Thyroid function

Total T4 was mildly decreased (1.1 µg/dL, RI: 1.3-4.5 µg/dL). TSH concentration was within limits (0.3 ng/mL, RI: <0.60 ng/mL).

Cytology

Fine-needle aspiration (FNA) cytology of the skin lesions was performed (Fig. 2A and B). Aspirated material appeared white and gritty. Impression smears were taken from the exudative erosions exposed after removal of crusts (Fig. 3A and B).

INTERPRETATION OF RESULTS

Haematology and biochemistry

Moderately elevated ALP could have reflected the presence of endocrinopathy / hyperadrenocorticism. Hepatobiliary disease (e.g. steroid hepatopathy) was also a likely consideration given a moderate increase in GGT and a mild increase in ALT. Other primary and secondary causes of cholestasis and hepatocellular damage could not have been totally ruled out. There was no history of toxin exposure.

Mild elevation of lipase was likely secondary to the action of endogenous glucocorticoids. Although the clinical symptoms were not suggestive of acute pancreatitis, disease damaging pancreatic acinar cells (e.g. chronic pancreatitis) could not have been totally ruled out. Other unlikely causes of raised lipase included intestinal disease and decreased renal function.

Thyroid function

An increase in TSH which is usually diagnostic for hypothyroidism was not observed. Low total T4 with normal TSH likely manifested the presence of nonthyroidal illness / euthyroid sick syndrome (e.g. in the course of hyperadrenocorticism). What is also worth noting, the dog was not receiving any medications which could lower T4 levels (e.g. exogenous glucocorticoids or anticonvulsants). As TSH concentration will be within limits in a proportion of dogs with hypothyroidism checking free T4 would allow better evaluation of the thyroid status.

Cytology

FNA cytology of the skin lesion showed the presence of dark grey granular crystalline material of variable size and irregular shape. After addition of immersion oil, this material changed colour to pale pink-yellow. Moderate numbers of macrophages and occasional nondegenerated neutrophils were also observed. This cytological picture was most consistent with deposition of calcium in the skin. Moderate mixed inflammatory infiltration was also identified. Confirmatory stain for calcium (e.g. von Kossa or Alizarin red S) was not done.

Impression smear cytology of exudate from the skin lesion identified high numbers of neutrophils (some degenerated), low numbers of macrophages and occasional plasma cells and lymphocytes (mostly small). This indicated the presence of neutrophilic inflammation. Although bacteria were not visualized, infection was still a likely consideration. Antibiotic therapy could have decreased the sensitivity of cytology in detecting bacterial organisms.

In conclusion, the main differential diagnosis for these skin lesions was calcinosis cutis with secondary inflammation and possible infection. Accumulation of calcium was most likely secondary to hyperadrenocorticism. Metastatic calcification was ruled out based on normal calcium and phosphate levels (calcium phosphate product was below 70 mg²/dL²). There was no history of glucocorticoid treatment or calcium injections. Skin lesions were widespread and did not appear to be associated with previous trauma.

Histopathology would be necessary to fully characterize the skin lesions.

Summary

The clinical picture was most compatible with hyperadrenocorticism but further diagnostic tests were required to confirm this. Less likely differential diagnoses included liver, pancreatic and gastrointestinal disorders. Hypothyroidism was unlikely but could not have been totally ruled out.

FURTHER TESTS

Adrenal function

ACTH stimulation was performed – pre-ACTH (basal) cortisol was 113 ng/mL and post-ACTH cortisol was >500 ng/mL. An exaggerated response to ACTH (post ACTH >217 ng/mL) confirmed the suspicion of hyperadrenocorticism.

Low-dose dexamethasone suppression test would be another consideration for diagnosis of hyperadrenocorticism – more sensitive but less specific than ACTH stimulation test.

Thyroid function

Free T4 was measured. Normal concentration (9.6 pmol/L, RI: 7.7-47.6 pmol/L) ruled out hypothyroidism and confirmed the presence of euthyroid sick syndrome.

Imaging

Abdominal ultrasound was performed and showed moderate enlargement of both adrenal glands with no discrete mass present. An enlarged, hyperechogenic liver was observed. A pituitary-depended hyperadrenocorticism (PDH) was suspected based on the imaging findings.

Histology

Two punch biopsies of 0.6 cm in diameter were fixed in 10% buffered formalin, embedded in paraffin according to standard procedures and routinely stained with haematoxylin and eosin (H&E) for histopathological examination. The dermis was characterized by a multifocal basophilic appearance of collagen fibres due to variable mineralization, confirming the diagnosis of calcinosis cutis (Fig. 4). The collagen fibres were fragmented and surrounded by low to moderate numbers of macrophages, with to a lesser extent lymphocytes, plasma cells and rare neutrophils. Secondary epidermal changes included diffuse moderate epidermal acanthosis, marked orthokeratotic hyperkeratosis and focal epidermal erosion. Tortuous hair follicles in telogen phase and moderate infundibular hyperkeratosis were confirmed as well. Crusts and significant neutrophilic infiltration were not observed in histology. This could be explained by loss of crusts during processing of the sample and different sampling sites for cytology and histology.