ISRAEL JOURNAL OF
VETERINARY MEDICINE
SUPERFICIAL NECROLYTIC DERMATITIS IN A DOG. A CASE REPORT
AND REVIEW OF THE LITERATURE
Waner T.1*, Anug A.M.2, and Aizenberg I.3
1. Veterinary Clinic, 9 Meginay Hagalil Street, Rehovot 76200, Israel. wanertnt@shani.net
2. PathoVet, 137 Shikun Banim, Kfar Bilu, 76965, Israel.
3. Koret School of Veterinary Medicine, Hebrew University of Jerusalem, P.O. Box 12,
Rehovot 76100, Israel.
*Corresponding author:
Abstract:
This report describes a case of superficial necrolytic dermatitis (SND) in an
11-year old Schipperke female spayed dog. The report includes the clinical
presentation follow-up, clinical chemistry, histopathology and ultrasound
findings.
A diagnosis of SND was based on clinical presentation, clinical chemistry,
ultrasound examination and supported by the histological findings of
parakeratosis, acanthosis, basal cell hyperplasia and epidermal edema. The
dog also developed renal failure two months after initial presentation, a finding
that has not been reported previously.
A review of the literature is presented including comparative aspects of the
disease in cats, rhinocerus and humans.
Introduction:
Superficial necrolytic dermatitis (SND) is a rare and fatal disease of dogs
characterized by typical skin lesions
accompanied by hepatopathy, and uncommonly glucagonomas of the
pancreas (1). The condition is also known as hepatocutaneous syndrome,
metabolic epidermal necrosis and necrolytic migratory erythema. The
pathogenesis appears to be related to an underlying metabolic hepatic
dysfunction bringing about a cutaneous nutritional depravation, leading to
necrotizing skin disease (2). This condition is unusual in being one of the
relatively few skin conditions in which a diagnosis can be made from a skin
biopsy (2).
This report describes a case of SND in an 11-year old female spayed dog.
The report includes the clinical presentation, clinical chemistry and ultrasound
findings. A review of the literature is also presented.
Case Report:
An 11-year-old Schipperke female spayed dog was presented with a history of
erosive skin lesions on the lateral abdomen and thorax, polyuria, polydypsia
and weakness. It had a previous history of keratoconjunctivitis sicca that was
treated with cyclosporin eye ointment (Optimmune Ophthalmic Ointment,
Schering-Plough Animal Health, USA). Blood was collected for a complete
blood count (CBC) and clinical chemistry. At this stage treatment was initiated
and after one week with oral cephalexin monohydrate (Ceforal, Teva, Israel)
at 250mg PO BID an improvement in the condition of the skin was noted.
Clinical pathology findings at first presentation:
The clinical pathology findings are presented in Table 1. The complete blood
count (CBC) revealed a mild leukocytosis and neutrophilia without left shift.
The neutrophils were mature and often hypersegmented. The platelet count
was elevated. There was no apparent anemia in the smear, however marked
polychromasia and nucleated RBC’s were noted (<2% basophilic rubricytes
and metarubricytes).
Serum clinical chemistry findings included an increased activity of the liver
enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and
gamma-glutamyl transferase (GGT). Lactate dehydrogenase (LDH) activity
was also increased. Serum cholesterol levels were decreased whereas
triglycerides were increased. The serum albumin concentration was
decreased. Urea concentrations were elevated although serum creatinine
level was within the normal range. Electrolyte disturbances were detected:
serum chloride and potassium levels were increased whereas sodium levels
were decreased.
Further investigations:
A preliminary diagnosis of Cushing’s was suspected. A low dose
dexamethazone test was carried out but proved negative.
Three weeks later the condition deteriorated and the dog was presented with
severe crusted fissured erosive lesions on the head and muzzle (with
involvement of the mucocutaneous junction) (Figure 1). The footpads were
hyperkeratotic and the nails deformed. A skin biopsy was taken from the
muzzle area for histopathological assessment.
Histological description:
Biopsy of lesions from the facial area showed irregular epidermal hyperplasia
with moderate parakeratosis and extensive serocellular crusting (Figure 2).
Occasional areas of superficial epidermal edema (pallor) were evident (Figure
3). There was minimal basal cell hyperplasia and marked pigmentary
incontinence. There was a mild superficial dermal infiltrate of lymphocytes and
plasma cells. A diagnosis of superficial necrolytic dermatitis (SND) was made
based on the histological findings of parakeratosis, acanthosis, epidermal
pallor and mild basal cell hyperplasia. This diagnosis was supported by the
chemistry findings, which were indicative of ongoing liver pathology.
Ultrasound description and results:
After two months the condition of the dog had deteriorated. At this stage
abdominal ultrasound studies were carried out to evaluate the extent of the
liver pathology and assess whether the pancreas was also involved in the
pathogenesis of the condition. In addition blood was collected for a CBC and
clinical chemistry panel.
Ultrasound examination revealed pathological changes in the liver, spleen and
iliac lymph nodes. The liver (Figures 4) was enlarged with the presence of
multiple oval to round hypoechoic regions. The diameter of the hypoechoic
areas reached up to 17 mm. In the spleen (Figure 5) a 20 mm hyperechoic
area with a hypoechic center was detected. The iliac lymph nodes were mildly
enlarged. No peritoneal or pleural fluids were detected and both kidneys
appeared normal. No changes were detected in the pancreas.
Clinical pathology findings after two months from the first presentation:
The results of both the hematology and clinical chemistry findings are
presented in Table 1. Deterioration in both hematological and biochemical
parameters was evident. At this stage there was a moderate to severe anemia
(microcytic hypochromic). Examination of the blood smear showed marked
hypochromasia with the presence of rare ghost cells. The total white blood
cell count had risen to 31,720 leukocytes/μL; a neutrophilia (28,500
neutrophils/μL) was the origin of the increased leukocyte count. The
neutrophils were mature without left shift or toxicity, and the monocytes were
predominantly bland.
There was a marked increase (4-5 fold) in liver enzyme activities of ALP and
ALT as compared to the first examination. In this examination aspartate
aminotransferase (AST), which was not elevated in the first assay, was now
increased 3-fold above the upper limit of the normal range. GGT and LDH
activities remained increased at approximately the same level of the first
examination.
Serum creatinine was markedly increased along with the serum urea levels. A
further indication of kidney pathology was the marked increase in serum
phosphate levels. Chloride and potassium levels returned to within the normal
range while the sodium level remained decreased. The triglyceride
concentration was markedly decreased. Serum albumin levels remained low.
The dog was euthanized on the request of the owners who refused a postmortem examination.
Table 1: Hematology results at first presentation and at two months later
Differential leukocyte count
Table 2:
Biochemistry at first presentation and two months later
Figure 1: Dermal lesions three weeks after initial complaint: Severe crusted
fissured erosive lesions on the head, muzzle with involvement of the
mucocutaneous junction
e 2: Biopsy of lesion from the facial area
ng irregular epidermal hyperplasia with
ate hyperkeratotic parakeratosis (small
d arrow) and extensive serocellular crusting.
is minimal basal cell hyperplasia and
d pigmentary incontinence (arrow heads).
of superficial epidermal edema (pallor) are
t (large headed arrows)
Figure 3: Biopsy of a lesion from the facial area
showing details of superficial epidermal pallor
(arrows). There is a mild superficial dermal
infiltrate of lymphocytes and plasma cells. Note
the pigmentary incontinence (arrow heads).
Liver ultrasound: Note the presence of
Figure 5: Spleen ultrasound: Note the 20 mm
val to round hypoechoic regions (arrows). hyperechoic area with a hypoechic center
eter of the hypoechoic areas reached up to
Discussion and review of the literature:
Superficial necrolytic dermatitis (necrolytic migratory erythema or
hepatocutaneous syndrome) is an uncommon skin disorder associated with
an underlying systemic disease. The condition was first described in a human
patient with a pancreatic neoplasm in 1942 (3). In humans SND is seen most
commonly in patients with a glucagon-secreting pancreatic α-cell neoplasm
(4). In contrast, in dogs the majority of cases occur in association with
hepatopathy, and less commonly with a glucagon-secreting tumor (5).
The first canine case of SND,then termed canine diabetic dermatosis was
described in 1986 (6). The name canine diabetic dermatosis was used due to
the tendency of dogs for glucose intolerance and in some cases for the
development of diabetes mellitus.
The pathogenesis is probably related to nutritional deficiencies or metabolic
abnormalities caused by liver dysfunction.
Nutritional deficiencies that may be associated with this condition include zinc
deficiency, hypoaminoacidemia or decreased essential fatty acids. Profound
hypoaminoacidemia has been found to be a consistent feature of the disease
with up to 80% reduction in a number of amino acids (7). It has been
hypothesized that the contributing defect is a metabolic hepatopathy that
increases hepatic metabolism of amino acids (8).
Canine SND is primarily a disease of older dogs with a mean age of about 10
years. The typical age of onset of SND corresponds to the age range of the
dog described in this report, which was 11 years of age. There are indications
that there may be a higher incidence in small breeds (as in our case), and that
male dogs (the present case was a female) may be overrepresented (2). In
relation to this report, two cases in Schipperke breed have been previously
reported (1). Common presenting complaints other than dermatological
lesions include lethargy or anorexia, weight loss and difficulty or pain on
walking. In the case reported here the main presenting signs were weakness,
polyuria and polydypsia. Clinical pathology revealed a high urea level
probably due to mild dehydration. The cause of the polyuria and polydypsia is
not clear but may be due to the ongoing liver pathology (9).
The commonly reported sites of cutaneous lesions in the dog rank from
footpads, feet (haired skin), facial mucocutaneous junctions, distal limbs,
perineal and perianal area, nose and muzzle, elbows, ventral abdomen,
perivulva, pinna and oral cavity. In the case presented here, at first
presentation, lesions were present on the distal limbs and lateral abdomen.
Three weeks later the typical presentation of cutaneous lesions of the
mucocutaneous junctions of the face and muzzle were seen, with lesions of
the footpads and nails. The presentation of lesions on the mucocutaneous
junction of the face is reported in about 61% of cases (1).
Blood chemistry results were similar to the commonly reported clinical
laboratory findings for dogs with SND. Increased activity of serum ALP and
AST is very commonly reported, as in this report. Anemia and leukocytosis
have been reported to occur in about 43% of cases, and were also present in
this case albeit not on first presentation but two months later. At this stage
therewas a moderate to severe microcytic hypochromic anemia.
Hypoalbuminemia is reported to occur in only 29% of cases and was present
in this case. Diabetes mellitus and hyperglycemia, which is present in about
40% of cases, was not evident in this instance. Interestingly this dog also
developed subacute to acute renal failure two months after initial presentation
with markedly increased serum urea, creatinine and phosphate levels. Renal
failure is not usually associated with this SDN. The changes in the electrolyte
levels of sodium, potassium and chloride are not fully understood but are
probably related to the ongoing liver pathology and the developing kidney
failure.
Plasma glucagon concentrations were not carried out. The reliability of this
assay in dogs is considered by some to be to be questionable as elevations
have also been seen in cases that do not have pancreatic tumors (10). As no
definite conclusions can be drawn in this case regarding the presence or
absence of pancreatic neoplasia, it has been suggested that the condition be
described as SND-ND (SND-not conclusively determined) as apposed to
SND-GS (glucagonoma syndrome) or SND-HS (hepatocutaneous syndrome)
(1).
Ultrasonographic results in this study corresponded to those seen in previous
studies of dogs with SND (11), where a “Swisscheese appearance” of the liver
was evident. The nature of the ultrasound changes seen in the spleen and
iliac lymph nodes in this case is unclear due to the lack of further pathological
investigations.
The typical light microscopic finding is the classic “red, white and blue”
appearance with is pathognomonic for SDN. These pathognomonic lesions
may be focal. “Red” represents diffuse parakeratosis with crusting, ”white”
corresponds to epidermal pallor due to both hydropic swelling of keratinocytes
and spongiosis., and “blue” represents basal cell hyperplasia. Perivascular
superficial cellular infiltrates may be present in the dermis consisting of
neutrophils, macrophages, lymphocytes and plasma cells (12).
The clinical differential diagnosis should include pemphigus foliaceus, zinc
responsive dermatosis and generic dog food dermatosis. Pemphigus
foliaceus is a pustular dermatitis with involvement of the dorsal muzzle,
planum nasale, pinnae, periorbital skin, and footpads. Acantholytic cells are a
prominent histological feature(2). Zinc responsive dermatosis is predominantly
seen in Siberian huskies and Alaskan malamutes and is characterized by
crusting, scaling and alopecia around the eyes, mouth chin and ears (2).
Generic dog food dermatosis is an uncommon to rare syndrome seen due to
the feeding of poor quality food. The condition is seem most often in younger
dogs and the lesions are usually seen on the muzzle, mucocutaneous
junctions, pressure points, flexure surface and distal extremities(2).
In humans the condition is a cutaneous marker for pancreatic islet cell tumor
and is less commonly associated with hepatic cirrhosis. Besides, the condition
may be associated with chronic pancreatitis, Crohn’s disease, celiac sprue,
and malabsorption syndrome (1). There have been only a few reports of SND
in the cat that have been associated with a number of diverse
conditions including pancreatic carcinoma, thyroid amyloidosis and
hepatopathy and intestinal lymphoma (2). A high incidence of SND has been
reported in the black captive rhinoceros (Diceros bicornis). The remarkable
aspects of the disease in these animals include an incidence of about 50% in
the captive population, the mortality rate is only 57% (compared with dogs
which is estimated as high as 87%) and that only 23% of the cases in rhinos
are associated with liver disease without any cases of pancreatic neoplasia
(1).
In conclusion, this article presents a case of SND in an 11-year old
Schipperke female dog which was fairly typical for the disease. Distinguishing
features included symptoms of polyuria/ polydyspia and the development of
an atypical renal failure in a relatively short period of time. Renal failure
associated with SND has not been reported previously. This case represents
a diagnostic challenge in which clinical, clinical-pathological and
histopathological findings are combined with ultrasound results for the
diagnosis of this poorly understood metabolic disorder.
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