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DOI: 10.1111/vde.12247
Background Canine sterile nodular panniculitis (SNP) is an inflammatory disease of the panniculus that is typically managed with immunomodulatory or immunosuppressive treatments. It has been reported to be a cutaneous marker of an underlying systemic disease.
Hypothesis/Objectives To assess the presence or absence of concurrent systemic diseases associated with
canine SNP and to document breed predispositions.
Animals Thirty nine dogs presented to a veterinary teaching hospital from 1990 to 2012 which met inclusion
criteria.
Methods Inclusion in this retrospective study required a diagnosis of SNP via histopathological analysis and
negative special stains for infectious organisms. Breed distributions of affected dogs were compared to all other
dogs examined at this hospital during the study period. Correlations between the histological pattern of panniculitis and the histological presence of dermatitis, clinical presentation of lesions, dog breed and therapeutic outcomes were assessed.
Results Australian shepherd dogs, Brittany spaniels, Dalmatians, Pomeranians and Chihuahuas were significantly over-represented, but correlations between inflammatory patterns of panniculitis and other histological
and clinical factors were not identified. Based on the information available in medical records, 32 dogs (82.1%)
had no concurrent systemic diseases identified. Four dogs had concurrent polyarthritis, which may be related to
SNP through unknown mechanisms.
Conclusions/Clinical Importance This study identified several novel breed predilections for SNP; it failed to
find any clear correlations with associated systemic diseases other than polyarthritis. The histological inflammatory pattern of SNP does not predict therapeutic outcome.
Introduction
Panniculitis is a disease in which subcutaneous fat (panniculus adiposus) becomes inflamed. Gross lesions
resulting from inflammation of this tissue can be single or
multiple, and may be focal or generalized in their distribution.1 Lesions often present as deep nodules with or without clinically observed draining tracts, fistulae and ulcers.
These lesions can be confused with deep pyoderma,
cutaneous neoplasia or a cutaneous cyst.1,2 Infectious
aetiologies for panniculitis include bacterial, fungal, viral,
parasitic and protozoal organisms. Noninfectious aetiologies include foreign body reactions, post-vaccination/injection reactions, thermal burns, trauma, vitamin E
deficiency, pancreatic disease, immune-mediated disease and idiopathic sterile nodular panniculitis (SNP).1,3
The diagnosis of SNP is made after infectious or other
noninfectious causes have been ruled out. Ideally, diagnostic tests for SNP include histopathological analysis of
full-thickness skin biopsy samples with special stains to
rule out aetiological agents, and bacterial, fungal and
mycobacterial cultures of deep tissues. Cytological examination of fine needle aspirate samples is considered to
be insufficient because results are often inconsistent with
the histopathological findings.1
The current standard treatment for SNP involves
immunosuppression with oral glucocorticoids, with or
without adjunctive therapies such as oral ciclosporin and/
or a combination of a tetracycline antibiotic with niacinamide.1,4 The pathogenesis of SNP is poorly understood, although previous studies and case reports have
proposed that it should be considered a cutaneous marker of systemic diseases, including, but not limited to,
pancreatic and hepatic disease.1,512
The aims of this retrospective study were to evaluate
case records for evidence of concurrent systemic
451
Contreary et al.
Table 1. Historical Information, presence of concurrent disease and laboratory diagnostic tests
Dog number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
Febrile
Reported
anorexia
Y
Y
Reported
lethargy
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
UA
SBP
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
CBC
Y
Y
Y
Y
Y
Y
Y
Y
Y
AUS
AXR
TXR
Y
Y
Diagnosed
concurrent
disease
IMPA
SD
SD
Y
IMPA
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
IMPA
Y
Y
Y
DM
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
IMPA
CBC, complete blood count; SBP, serum biochemistry profile; UA, urinalysis; AUS, abdominal ultrasound; AXR, abdominal radiographs; TXR,
thoracic radiographs; Y, test performed; IMPA, immune-mediated polyarthritis; SD, seizure disorder; DM, diabetes mellitus.
452
Histopathology
Evaluation of H&E stained sections was carried out for the pattern of
inflammation, the predominant cell type(s) present, and the presence
and extent of concurrent dermatitis. The patterns of subcutaneous
inflammation were categorized as: (i) septal; (ii) nodular; (iii) diffuse;
(iv) intralobular; or (v) a combination of different patterns. Involvement of the dermis was categorized as either: (i) superficial; (ii) middermal; or (iii) deep dermal.
Statistical analysis
Breed distributions were compared between dogs with SNP and the
remainder of the canine hospital population seen at the VMTH-UCD
from 1990 to 2012 using an exact chi-square test of homogeneity.
Specific breeds with more than one case of panniculitis that con-
Negative
special
stains
Negative
bacterial
culture
Negative
fungal
culture
Negative
mycobacterial
culture
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
Y
Y
Y
Y
Y
y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
P*
TNP
P*
Y
Y
Y
Y
TNP
Y
Y
TNP
Y
Y
Y
P*
Y
Y
Y
Y
TNP
TNP
P*
Y
P*
TNP
Y
P*
TNP
Y
Y
TNP
Y
Y
TNP
Y
Y
Y
Y
TNP
TNP
TNP
TNP
Y
Y
Y
Y
TNP
Y
Y
TNP
Y
Y
Y
Y
Y
TNP
Y
TNP
TNP
TNP
Y
TNP
TNP
TNP
TNP
TNP
TNP
TNP
Y
TNP
Y
Y
TNP
TNP
Y
Y
Y
TNP
TNP
TNP
Y
TNP
TNP
TNP
TNP
TNP
TNP
Y
TNP
TNP
TNP
TNP
Y
TNP
TNP
Y
TNP
TNP
TNP
TNP
TNP
Y
TNP
TNP
TNP
TNP
TNP
TNP
TNP
TNP
TNP
TNP
TNP
TNP
TNP
TNP
tributed to overall significant differences were identified using breedspecific contributions to the chi-square statistic that were significant
(P < 0.05). Significant results are reported as observed to expected
(O:E) ratios the number of dogs belonging to a particular breed with
panniculitis relative to the number of dogs expected with panniculitis
based on the total hospital distribution of dog breeds seen.
Results
Medical record review
Signalment: Thirty nine dogs met inclusion criteria, of
which eight (20.5%) were Australian shepherd dogs, four
each (10.3%) were Chihuahuas, Labrador retrievers or
mixed breed dogs, and two each (5%) were Rottweilers,
Dalmatians, Pomeranians or Brittany spaniels. One dog
represented each of the following breeds: pug, Cardigan
Welsh corgi, American cocker spaniel, Jack Russell terrier, dachshund, Chesapeake Bay retriever, golden retriever, Airedale terrier, toy poodle, boxer and beagle.
Nineteen (48.7%) of the dogs were spayed females, 15
(38.5%) were castrated males, two (5.1%) were intact
females and three (7.7%) were intact males. The mean
age at presentation was 6.5 yr (range 113 yr).
A total of 131,281 dogs were admitted to the VMTHUCD between 1990 and 2012. There was a significant difference in the breed distribution between dogs with SNP
and the overall hospital population (P < 0.0001). Compared to the expected distribution, the following breeds
were significantly overrepresented with diagnoses of
SNP: Australian shepherd dogs (n = 8; O:E = 13.3), Brittany spaniels (n = 2; O:E = 6.7), Dalmatians (n = 2; O:
E = 6.7), Pomeranians (n = 2; O:E = 6.7) and Chihuahuas
(n = 4; O:E = 5.0).
History and physical examination findings
Mean duration of lesions prior to initial presentation to the
VMTH-UCD was 3 months (range 0.2512 months). Nine
dogs had been treated previously with systemic corticosteroids, one dog had been treated with a systemic antihistamine (diphenhydramine), 12 dogs had been treated
with one systemic antibiotic and 19 dogs had been treated with more than one systemic antibiotic. The dosages
of corticosteroids administered previously were not
recorded in the majority of these cases.
Locations of lesions according to body region were
trunk (30), neck (9), face/head (7), shoulder (6), limb (4)
and hip (2). A solitary lesion was present in 6 of 39 dogs
(15.4%); the remaining 33 dogs had multiple lesions (Figure 1). The most commonly affected areas were the
trunk (30 of 39 dogs; 76.9%) and the neck (9 of 39 dogs;
23.1%). The most common skin lesions were dermal or
subcutaneous nodules, documented in 35 of 39 dogs
(89.7%). The nodules were draining at the time of initial
presentation in 13 dogs and two dogs had ulcerated nodules. The remaining four dogs presented with ulcers (1 of
39), haemorrhagic bullae (1 of 39), crusts and alopecia (1
of 39) and a plaque (1 of 39).
Eight dogs (20.5%) were pyrexic at the time of diagnosis (mean 40C; range 39.645C). In all cases, these
dogs temperatures were within normal limits during subsequent visits. Six dogs (15.4%) were reported to be
anorexic at the time of diagnosis and four dogs (10.3%)
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Contreary et al.
were noted to be lethargic by their owners. All dogs presenting with clinical signs of systemic illness (fever, anorexia or lethargy) had a CBC, SBP and AUS performed
with unremarkable findings. These results are summarized in Table 1. In all dogs, clinical signs of systemic illness quickly resolved after SNP treatment was instituted.
No dog in this study presented with vomiting, diarrhoea,
weight loss/gain, auscultable heart murmur or palpable
hepatomegaly.
Clinicopathologic findings
Results for complete blood counts were available for 28
of 39 dogs (71.8%) and revealed a nonregenerative, normocytic, normochromic anaemia in 12 of 28 (median
haematocrit: 31%; mean 28.3 2.8%; range 24.5
39.2%; normal 4055%), and a leukocytosis with a
mature neutrophilia in 9 of 28 dogs (median: 19.7 9 103/
lL; mean 27.1 9 103/lL 12,499.44 9 103/lL; range
1648.8x103/lL; normal 310.5 9 103/lL). Other abnormalities noted included monocytosis in five dogs and lymphopenia in three dogs.
Urinalysis results were available in 28 of 39 dogs
(71.8%); none had significant proteinuria. Serum biochemistry panels were available for review from 25 of 39
dogs (64.1%). Alkaline phosphatase values were elevated
in 13 of 25, (median 238.0 IU/L; mean 374.9 IU/
L 227.14 IU/L; range 173773 IU/L; normal 21170 IU/
L), aspartate aminotransferase values were elevated in 6
of 25 (median: 79 IU/L; mean: 81 IU/L 12.09 IU/L;
range 6899 IU/L; normal 1942 IU/L) and alanine aminotransferase values were elevated in 2 of 25 dogs (median:
140.5 IU/L; mean: 141 IU/L 14.85 IU/L; range 130
151 IU/L; normal 1970 IU/L). One dog had elevations of
all three enzymes; an AUS at the time of diagnosis did not
indicate evidence of hepatic disease. Five dogs had elevations in two of these enzymes; four of which had AUS
performed at the time of diagnosis. There was no evidence of hepatic or pancreatic disease in three of these
four dogs, whereas the fourth had ultrasonographic
changes interpreted to be consistent with a steroid hepatopathy. This dog had not received corticosteroids
according to the medical record, but due to the retrospective nature of the study, the possibility of corticosteroid
use cannot not be excluded entirely. This dog had skin
lesions present for 1 week prior to presentation and neither repeated AUS nor cortisol function tests were performed. However, the dog developed no clinical signs of
systemic disease during the follow-up period of
16 months.
Concurrent diseases
Four dogs (10.3%) were diagnosed with concurrent polyarthritis via arthrocentesis; in all four cases the signs of
polyarthritis developed within days of the skin lesions.
One of the four dogs was pyrexic at the time of diagnosis.
All dogs had clinical signs referable to joint disease; two
of the four with shifting leg lameness, one nonweight
bearing on the left hind limb and one with joint effusion of
the left tarsus.
Other concurrent systemic disease identified in the
study group included one dog with a 13-month history of
well-controlled diabetes mellitus prior to development of
SNP and two dogs with long-standing histories (3 and
6 yr) of seizure disorders that had been well-managed
with potassium bromide. These conditions were not
thought to be related to the SNP. The remaining 32 dogs
(82.1%) had no identifiable evidence of concurrent systemic disease based on available clinical findings or
results of diagnostic tests recorded in the medical
records (see below), either at the time of their initial presentation, or during the follow-up period available for
evaluation.
Imaging studies
Abdominal ultrasound was performed at the time of diagnosis in 20 of 39 (51.3%) of the dogs in this study. As
mentioned above, one had evidence of a mild steroid
hepatopathy. All other ultrasonographic examinations
were within normal limits. Abdominal radiographs were
performed in three other dogs (7.7%) and were within
normal limits. Thoracic radiographs were performed in 23
of 39 dogs (60.0%) and were also within normal limits.
Overall, 13 dogs had CBC, SBP, UA and AUS performed
to evaluate for concurrent diseases and an additional two
dogs had these tests with the exception of an UA.
454
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Contreary et al.
Discussion
Follow-up
Follow-up ranged from 0 to 2490 days (mean 251 days).
There was no available follow-up after initial diagnosis for
nine dogs (23.1%). Of the 30 dogs for which follow-up
information was available, one died within 2 months as
noted above. Of the remaining 29 dogs, 21 (72.4%)
achieved clinical remission of SNP, defined as complete
absence of any skin lesions. One dog was able to achieve
remission without treatment 2 weeks after diagnosis and
was followed for two additional weeks; the other 20
456
dogs that did have identifiable concurrent systemic disease, only four (10.2%) showed evidence of a concurrent inflammatory disease in another location
(polyarthritis with associated lameness or joint effusion). Three dogs had histories of long-standing diseases that were well-managed at the time of SNP
development (either diabetes mellitus or a seizure disorder), and were not thought to be related to the development of SNP. The two dogs with a long-standing
seizure disorder were managed with potassium bromide (KBr). A prior case report has linked KBr to panniculitis in two dogs.16 However, both dogs in the
present study continued to receive KBr along with
immunosuppressive therapy for SNP and both showed
improvement of their clinical signs. Therefore, an
adverse reaction to KBr was considered unlikely but
could not be ruled out.
Neither the histological pattern of inflammation, the
types of inflammatory cells present nor involvement of
the dermis, correlated with locations of the lesions, specific breeds and presence of draining tracts or presence/absence of concurrent systemic diseases. Nodular
inflammatory aggregates were the most common inflammatory pattern (35%) seen in this study, followed by septal, diffuse and intralobular patterns. Neutrophils and
histiocytes predominated in most lesions, but differences
seen in cellular infiltrates likely change over time and
could result from inherent differences in locations where
skin biopsies were taken. Moreover, involvement of the
dermis was not necessarily associated with formation of
draining tracts and draining tracts were seen without evidence of extensive dermatitis.
Oral immunosuppressive/immunomodulatory medical
management is required in most cases of SNP and in this
study there was no correlation between time to remission and the initial medications prescribed. Only one case
for which follow-up was available resolved without treatment. A combination of a corticosteroid and nonsteroidal
immunosuppressive/immunomodulatory medication(s)
was the most successful method of treatment. This combination was necessary for 85% of the dogs that
achieved remission, with the other 15% achieving remission with corticosteroid therapy alone. Relapse was
noted in five dogs after treatment was either discontinued or tapered, which supports prior reports of the need
for long-term or even lifelong treatment in some dogs.16
Due to the retrospective nature of this study follow-up
was not available in all dogs, but from available data only
two dogs maintained remission after all medications were
discontinued.
Adverse effects of medications were primarily limited
to corticosteroid-induced polyuria, polydipsia and polyphagia. Two dogs experienced either leukopenia or thrombocytopenia while receiving azathioprine, which highlighted
the importance of monitoring CBCs while administering
azathioprine. One dog developed nocardiosis while
receiving 0.5 mg/kg prednisolone twice daily and 500 mg
of both tetracycline and niacinamide thrice daily. Whether
this was acquired during therapy as an effect of immunosuppression is unknown.
In conclusion, this study reports new breed predispositions for SNP and shows that the disease often occurs
457
Contreary et al.
References
1. Miller WH Jr, Griffin DE, Campbell KL. Miscellaneous skin diseases. In: Muller and Kirks Small Animal Dermatology, 7th edition. St. Louis, MO: Elsevier Health 2013; 701704.
2. Yamagishi C, Momoi Y, Kobayahi T et al. A retrospective study
and gene analysis of canine sterile panniculitis. J Vet Med Sci
2007; 69: 915924.
3. Scott DW, Anderson WI. Panniculitis in dogs and cats: a retrospective analysis of 78 cases. J Am Anim Hosp Assoc 1988; 24:
551559.
4. Kim H, Kang M, Kim J. Sterile panniculitis in dogs: new diagnostic findings and alternative treatments. Vet Dermatol 2011; 22:
352359.
5. OKell AL, Inteeworn N, Diaz SF et al. Canine sterile nodular panniculitis: a retrospective study of 14 cases. J Vet Intern Med
2010; 24: 278284.
6. Moreau PM, Fiske RA, Lees GE et al. Disseminated necrotizing
panniculitis and pancreatic nodular hyperplasia in a dog. J Am
Vet Med Assoc 1982; 180: 422425.
7. Gear RNA, Bacon NJ, Langley-Hobbs S et al. Panniculitis,
polyarthritis, and osteomyelitis associated with pancreatic
neoplasia in two dogs. J Small Anim Pract 2006; 47: 400
404.
Supporting Information
Additional Supporting Information may be found in the
online version of this article.
Table S1. Breed and histopathological analysis.
Table S2. Treatment, remission and relapse.
sume
Re
rile canine (SNP) est une maladie inflammatoire de lhypoderme qui
Contexte La panniculite nodulaire ste
re par des immunomodulateurs ou des immunosuppresseurs. Elle a e
te
de
crite comme un marqueur
se ge
de maladie syste
mique sous-jacente.
cutane
ses/Objectifs De
terminer la pre
sence ou labsence dune maladie syste
mique concourante
Hypothe
e a la SNP canine et documenter les pre
dispositions raciales.
associe
sente
s a un ho
^pital ve
te
rinaire denseignement de 1990
Sujets Trente et un chiens pre
a 2012 remplissant les conditions dinclusion.
thodes Linclusion dans cette e
tude re
trospective ne
cessitait le diagnostic de SNP par histopatholoMe
gie et des colorations speciales negatives pour les organismes infectieux. Les distributions de race des
te
compare
es a tous les autres chiens examine
s au sein de lho
^pital au cours de la pe
richiens atteints ont e
tude. Les corre
lations entre les patrons histopathologiques de la panniculite et la pre
sence hisode de
sentation clinique des le
sions, la race des chiens et la re
ponse au traitement
tologique de dermatite, la pre
te
e
value
es.
ont e
sultats Les bergers australiens, dalmatiens, e
pagneuls bretons, loulous de Pome
ranie et chihuahuas
Re
taient significativement plus repre
sente
s mais la corre
lation entre les patrons inflammatoires de pannie
te
identifie
. A partir des informations disponculite et autre facteurs histologiques et cliniques nont pas e
dicaux, 32 chiens (82.1%) navaient pas de maladie syste
mique identifie
e.
ibles dans les dossiers me
^tre relie
e
canismes inconQuatre chiens avaient une polyarthrite concurrente pouvant e
a la SNP via des me
nus.
tude identifie plusieurs nouvelles pre
dilections raciales pour
Conclusions et importance clinque Cette e
lation claire na pu e
^tre identifie
e avec des maladies syste
miques autres que la polla SNP; aucune corre
dire une re
ponse the
rapeuyarthrite. Le patron inflammatoire histologique de la SNP ne permet pas de pre
tique.
Resumen
n la paniculitis este
ril nodular canina (SNP) es una enfermedad inflamatoria del panculo que
Introduccio
tpicamente se maneja con tratamientos inmunomoduladores o inmunosupresores. Se ha indicado que
mica subyacente.
puede ser un marcador cutaneo de enfermedad siste
458
(SNP)
/ SNP
1990201239
SNP
32(82.1%)4
SNP
/ SNP
SNP
e104
Contreary et al.
(SNP),
,
/ SNP,,
19902012,39,
SNP,
,,
,
,,
,32(82.1%)
,SNP
,SNP;,
SNP
e105