Superficial Necrolytic Dermatitis Research Articles

Short-term parenteral infusions with high-osmolality amino acid solutions can be safely administered through peripheral catheters in dogs treated for hypoaminoacidemia-related conditions.

To compare complications between central and peripheral administration of high-osmolarity (approx 700 to 1,000 mOsm/L) amino acid (± lipid) infusions. 18 client-owned dogs diagnosed with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome or superficial necrolytic dermatitis receiving parenteral amino acid ± lipid infusions. In this retrospective case series, medical records were reviewed for administration route (central vs peripheral), catheter details and infusion characteristics (product osmolarity, concurrent lipid administration, infusion volume, duration, and rate), and complications for each infusion. 18 dogs received 277 infusions (median, 8.5; range, 1 to 84). Effective infusion osmolarities were 683 mOsm/L in 22% of infusions, 791 mOsm/L in 8%, 802 mOsm/L in 2%, 837 mOsm/L in 45%, and 998 mOsm/L in 23% (65% peripheral, 35% central). Most (n = 230 [83%]) infusions were given peripherally. The osmolarities of solutions administered by each route (P = .53), the infusion rate indexed to body weight (P = .17), or the lipid infusion rates indexed to body weight (P = .89) did not differ. One dog suffered 2 complications in 63 infusions-1 mild, 1 severe-both occurring with peripheral infusions. Thus, the overall complication rate was 2 of 277 (0.9%) infusions. Short-term peripherally administered amino acid ± lipid infusions < 1,000 mOsm/L confer little risk compared to centrally administered infusions. Additional studies are needed to determine the safety of infusions with longer durations. Due to the relative ease of peripheral catheterization, clinicians should consider this route for medically managing aminoaciduric canine hypoaminoacidemic hepatopathy syndrome and superficial necrolytic dermatitis in dogs.

Treatment of Superficial Necrolytic Dermatitis with Copper Chelationina Dog with Copper-Associated Hepatitis.

A 7 yr old castrated male Cavalier King Charles spaniel presented for evaluation of liver enzyme elevations. Abdominal ultrasound revealed a small liver with mixed echogenicity, small hypoechoic nodules, and an irregular surface. Histologic examination and copper quantification of the liver obtained by laparoscopy diagnosed copper-associated hepatitis. One month later the dog developed hyperkeratosis of all four foot pads and ulcerations of feet, legs, and rectum. Punch biopsies confirmed superficial necrolytic dermatitis. After a total of 2 mo of chelation with no changes to medications, skin lesions began to improve, continuing over the following 6 wk to almost complete resolution. At this point the skin lesions returned and had minimal response to four amino acids infusions. The dog was switched from penicillamine to trientine. Zinc acetate was initiated 6 wk after the switch to trientine, and skin improvement was noted soon thereafter. At the time of death, skin lesions were improving and the dog was clinically comfortable. Copper-associated hepatitis should be considered as a possible etiology for superficial necrolytic dermatitis. Treatment of superficial necrolytic dermatitis is often unrewarding, and copper chelation, when copper-associated hepatitis has been confirmed, represents another therapeutic option.

Association of sterile neutrophilic dermatosis (Sweet-like syndrome) and superficial necrolytic dermatitis in a dog with acute myeloid leukaemia

A 1-year-old female dog is presented for acute hyperthermia and generalized erythematous papules, pustules and facial swelling. A sterile neutrophilic dermatosis resembling Sweet's syndrome (SND SS), successively followed by the development of a superficial necrolytic dermatitis associated with a multi-organ tumor infiltration due to acute myeloid leukaemia was diagnosed by skin biopsies and dermatopathological examinations. Une chienne d’un an est présentée pour hyperthermie aiguë et papules érythémateuses généralisées, pustules et œdème de la face. Une dermatose neutrophilique stérile ressemblant au syndrome de Sweet (SND SS), suivie successivement de l’évolution d’une dermatite nécrolytique superficielle associée à une infiltration tumorale multiorganique, due à une leucémie myéloïde aiguë, ont été diagnostiqués par des biopsies et des examens dermatopathologiques.

Treatment and outcomes of dogs with hepatocutaneous syndrome or hepatocutaneous-associated hepatopathy.

BackgroundSuperficial necrolytic dermatitis (SND) in dogs is a rare disorder most commonly associated with hepatocutaneous syndrome. Although often reported as fatal, sporadically reported long‐term remissions might be more common than previously believed and linked to treatment regimens.Hypothesis/ObjectivesEvaluate treatments and associated outcomes in dogs with hepatocutaneous‐associated hepatopathy (HCH) with or without SND, designated collectively aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES).AnimalsForty‐one dogs of various breeds and ages diagnosed with ACHES.MethodsRetrospective study. Electronic surveys, medical records (2014‐2019), and communication with veterinarians provided data. Three treatment categories were each dichotomized: IV amino acid (IV‐AA) infusions (≥2 vs <2), supplements including S‐adenosylmethionine (SAMe), arginine with ornithine, glutathione, lysine, proline, omega‐3 fatty acids, or zinc (≥3 vs <3), and diet type (home‐cooked vs commercial). Optimal treatment was defined as receiving ≥2 IV‐AA treatments, ≥3 nutritional supplements, and a home‐cooked diet.ResultsMost dogs (29/41, 71%) received IV‐AA infusions (23/29, ≥2 infusions). Twenty‐one dogs (51%) were fed commercial diets; 17/41 (41%) were fed home‐cooked diets. Most dogs received SAMe (32/41, 78%) and a median of 3 supplements. In 4 dogs, HCH remission occurred. Overall all‐cause median survival time (MST) was 359 days, and disease‐specific MST was 557 days (range, 1‐1783 days). Optimally treated dogs (n = 9) lived significantly longer (MST, >1783 days, P = .02) than variably treated dogs (MST, 214 days).Conclusions and Clinical ImportanceOptimized ACHES management can resolve SND and HCH and confer long‐term survival.

Clinical features and amino acid profiles of dogs with hepatocutaneous syndrome or hepatocutaneous-associated hepatopathy.

BackgroundSuperficial necrolytic dermatitis (SND), hepatocutaneous‐associated hepatopathy (HCH), aminoaciduria, and hypoaminoacidemia define hepatocutaneous syndrome (HCS) in dogs. Dogs without SND but that possess all other syndrome components are not well described.Hypothesis/objectivesTo define an inclusive syndrome, aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) for dogs with HCH or HCS. Compare clinical features, salient clinicopathologic variables, and plasma and urine amino acid (AA) profiles among ACHES cases by skin lesion status.AnimalsDogs of various breeds and ages diagnosed with ACHES (n = 41). A control (CON) cohort (n = 12) provided AA profile data.MethodsRetrospective case series. Available medical records of previously identified cases were reviewed for salient clinical features and clinical pathology data. Plasma and urine AA profiles were performed. Cutaneous lesion status was classified as none, mild, or fulminant.ResultsThirty cases (73%) developed SND at some time. Dogs with fulminant skin lesions at diagnosis (n = 22/41, 54%) had significantly lower hematocrit (P = .05) and mean corpuscular volume (P = .01) than dogs without SND. Principal component analysis of plasma AA profiles identified distinct clustering of CON from ACHES dogs, but not by skin lesion status. Plasma 1‐methylhistidine (<7 nmol/mL) and cystathionine (<7.5 nmol/mL) were robust ACHES biomarkers. Urine lysine (>344 nmol/mg creatinine) and methionine (>68 nmol/mg creatinine) also were useful ACHES biomarkers.Conclusions and Clinical ImportanceSpecific AA biomarkers provide additional diagnostic utility in ACHES. Data suggests that HCH is an early stage, and SND a later stage manifestation of ACHES.

Dermatite necrolítica superficial canina – revisão

Canine superficial necrolytic dermatitis (SND) is a progressive debilitating skin disorder commonly associated with liver abnormalities. It is an erosive skin disease with multifocal distribution, usually in the foot pads, mucocutaneous junctions and extremities of the limbs. The pathogenesis of SND in dogs is not known, and may be related to liver disease, mycotoxicosis and use of anticonvulsant drugs. SND manifests itself insidiously, especially in adult dogs, with no breed or gender predisposition. Therapy is supportive, improving the animal’s quality of life and survival time, with most animals dying within a few months of diagnosis, regardless of the proposed treatment.

Approach to the Diagnosis of Hepatocutaneous Syndrome in Dogs: A Retrospective Study and Literature Review.

Superficial necrolytic dermatitis (SND) is a rare and often fatal disease in dogs that has been associated with pancreatic neuroendocrine neoplasia (SND/EN) and hepatocutaneous syndrome (SND/HCS). Although various combinations of diagnostics have been used to differentiate these two causes of SND, there are currently no data on which combination would enable the most timely and noninvasive way to diagnose HCS. Medical records were reviewed retrospectively (2004-2018) for dogs with SND/HCS (n = 24) and SND/EN (n = 1). These data were compared with cases found by review of the literature of dogs with SND/HCS (n = 105) and SND/EN (n = 13). The most consistent findings with SND were dermatological lesions affecting paw pads or mucocutaneous junctions (143/143, 100%) and marked plasma hypoaminoacidemia (58/58, 100%). On ultrasound, a honeycomb liver was seen in 62/63 (98%) dogs with SND/HCS but none with SND/EN. Six out of 23 (26%) dogs in the retrospective study with SND/HCS had marked keratinocyte apoptosis, a finding that was associated with diabetes mellitus. This study suggests that in dogs with characteristic skin lesions, an amino acid profile permits a noninvasive diagnosis of SND. An abdominal ultrasound can then assist in the differentiation of SND/HCS and SND/EN.

Successful Long-Term Management of Canine Superficial Necrolytic Dermatitis With Amino Acid Infusions and Nutritionally Balanced Home-Made Diet Modification

A 10-year old, castrated male, Bichon Frise with a history of hyperadrenocorticism and intrahepatic portal vein hypoplasia was diagnosed with superficial necrolytic dermatitis (SND). The dog exhibited thick crusts on the chin, muzzle, prepuce, and paws. In addition, the dorsal surfaces of all paws were erythematous while the palmar/plantar surfaces were hyperkeratotic, hardened, and painful. The dog was treated with intravenous amino acid infusions (AAI), raw egg yolks, as well as zinc and omega-3 fatty acid oral supplements. The dog required AAI once every 2–3 weeks because this coincided with recrudescence of painful skin lesions. The dog was subsequently diagnosed with diabetes mellitus. A consult with the Nutrition Service was pursued 220 days after the original SND diagnosis because of concern for feeding raw eggs and for malnutrition since appetite was variable, muscle condition was reduced, and greater than 50% of ingested calories were from foods that were not nutritionally complete. There was also concern regarding the variability of the diet and the impact it would have on the management of diabetes mellitus. The diet was prepared by the dog owner according to a provided recipe and presented twice daily. The diet was rich in high quality protein and fat. All other treatments including medications, supplements, and bathing schedule remained unchanged at the time of diet modification. The dog was subclinical for SND associated clinical signs approximately 3 weeks after the diet modification, which also coincided with the last AAI. The AAI was postponed and was next administered 7 weeks later (i.e., 10 weeks from the previous infusion). The dog remained subclinical for SND related clinical signs and continued to receive AAI once every 10–12 weeks until he was euthanized 718 days later for complications related to severe multi-drug resistant, skin infections. In conclusion, this report highlights a novel role for nutritionally balanced home-made diets designed by a board-certified veterinary nutritionist could substantially increase time interval between AAI and outcome in dogs with SND.

Hepatocutaneous syndrome in Shih Tzus: 31 cases (1996-2014).

To characterize findings in Shih Tzus with progressive superficial necrolytic dermatitis and degenerative vacuolar hepatopathy consistent with hepatocutaneous syndrome. Retrospective case series. 31 Shih Tzus. Medical records were reviewed to obtain information on signalment, history, treatment, outcome, and results of clinicopathologic testing, abdominal ultrasonography, and histologic examination of skin and liver specimens. A pedigree analysis was performed. There were 16 males and 15 females. Median age at the time of diagnosis was 8 years (range, 5 to 14 years). Common clinical signs included lethargy, inappetence, weight loss, and lameness. Twenty-five dogs had cutaneous lesions consistent with hepatocutaneous syndrome; the remaining 6 initially only had hepatic abnormalities, but 3 of the 6 subsequently developed cutaneous lesions. Common clinicopathologic abnormalities included microcytosis (15/24 [63%] dogs) and high serum alkaline phosphatase activity (24/24 [100%] dogs). Hepatic ultrasonographic findings included a hyperechoic or heteroechoic appearance to the parenchyma with innumerable hypoechoic nodules. Histologic hepatic lesions consisted of degenerative vacuolar (glycogen and lipid) hepatopathy associated with minimally fibrotic to nonfibrotic, noninflammatory, proliferative nodules. Pedigree analysis confirmed a common ancestry in 12 of 18 dogs. Median survival time was 3 months (range, 1 to 36 months). Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. Clinical, clinicopathologic, ultrasonographic, and histologic abnormalities in affected Shih Tzus were similar to those previously reported for dogs of other breeds with HCS.

Superficial Necrolytic Dermatitis in a Dog With an Insulin-Producing Pancreatic Islet Cell Carcinoma

A 10-year-old dog presented with convulsive crisis and symmetrical hyperkeratotic cutaneous lesions affecting the abdomen, inguinal area, eyelids, muzzles, both pinnae, and all the paw pads. Hypoglycemia and hyperinsulinemia were the main biochemical findings. A mass 2cm in diameter was detected within the left pancreatic lobe by ultrasonography. It was surgically removed and histologically and immunohistochemically diagnosed as an insulin-producing pancreatic islet cell carcinoma. The animal was eventually euthanized due to lack of clinical improvement. At necropsy, metastatic nodules were observed in the pancreatic lymph nodes and liver. Histopathological findings of cutaneous lesions were highly suggestive of superficial necrolytic dermatitis and were interpreted as a paraneoplastic syndrome derived from the islet cell carcinoma. To the authors' knowledge, this is the first report of superficial necrolytic dermatitis associated with an insulin-producing pancreatic neuroendocrine carcinoma in dogs.

Necrolytic migratory erythema associated with a glucagon‐producing primary hepatic neuroendocrine carcinoma in a cat

In humans, necrolytic migratory erythema (NME) is a syndrome with a characteristic skin rash that is associated most often with a pancreatic glucagonoma and is recognized as part of the glucagonoma syndrome. In veterinary medicine, NME (also called as superficial necrolytic dermatitis, hepatocutaneous syndrome or metabolic epidermal necrosis) has been described in dogs in association with chronic liver diseases or, less frequently, glucagonoma, but NME associated with glucagonoma has not previously been reported in cats. A 6-year-old male neutered domestic short hair cat was diagnosed with NME associated with a glucagon-producing primary hepatic neuroendocrine carcinoma (hepatic carcinoid). The cat presented with a 2 week history of vomiting and anorexia, and a 5-cm-diameter liver mass was detected by abdominal ultrasound. The cat exhibited general weakness, crusted skin lesions and pain in all four limbs. It was euthanized 11 months after the initial presentation. Histopathological review of the paw pads revealed the classic 'red, white and blue' lesion composed of parakeratotic hyperkeratosis, epidermal hydropic change and hyperbasophilia of the deep epidermis. The liver mass was diagnosed as a neuroendocrine carcinoma (hepatic carcinoid). Neoplastic cells were strongly immunoreactive for glucagon. This is the first case report of NME associated with a glucagon-producing primary hepatic neuroendocrine carcinoma in a cat.

Successful treatment of canine necrolytic migratory erythema (superficial necrolytic dermatitis) due to metastatic glucagonoma with octreotide

Necrolytic migratory erythema (NME; also known as superficial necrolytic dermatitis) is a syndrome most often associated with certain chronic liver diseases or pancreatic glucagonomas. In humans with glucagonoma-associated NME, skin lesions usually respond to octreotide, a somatostatin analogue that inhibits glucagon release. In this report an 11-year-old golden retriever dog with pancreatic glucagonoma and metastasis to the regional lymph nodes, spleen and liver was diagnosed with NME. The dog exhibited erosions, ulcers and crusts on the paws, pressure points, muzzle, periocular area and prepuce. The dog was also anorexic and had difficulty walking. Because metastasis precluded surgery, treatment was initiated with subcutaneous octreotide (2 μg/kg twice daily). Skin lesions and systemic clinical signs improved markedly within 5 days. The dosage was increased to nearly 3 μg/kg twice daily and signs almost completely resolved within 10 days. Anorexia was the major adverse effect observed. During the following month, both dosage (1-3.7 μg/kg) and frequency (two to four times daily) of the octreotide injections were adjusted to permit control of clinical signs while maintaining adequate appetite. Temporary cessation of octreotide administration resulted in the rapid recurrence of skin lesions. Resuming injections led to improvement of clinical signs within 48 h. The dog was later euthanized because of progressive metastatic disease. In conclusion, subcutaneous octreotide injections were beneficial in this dog with glucagonoma-associated NME. This somatostatin analogue could be a valuable option to treat canine patients with non-resectable or relapsing pancreatic glucagonoma-associated NME.

Hypoaminoacidemia is not Associated with Ulcerative Lesions in Black Rhinoceroses, Diceros bicornis

Ulcerative oral and skin lesions have become an issue of concern for the health of the managed black rhinoceros (rhino) (Diceros bicornis) populations. Lesions exhibited by the black rhino are clinically similar to those observed in other species with superficial necrolytic dermatitis (SND). One biochemical alteration in dogs with SND is severe hypoaminoacidemia, and nearly all cases are fatal. The objective of this study was to determine if black rhinos with analogous lesions exhibit a similar hypoaminoacidemia. Amino acid concentrations were measured in monthly plasma samples collected for 1 yr from black rhinos with (n = 4) and without (n = 34) lesions clinically consistent with SND. The rhinos with skin and/or oral lesions were zoo born males, ages 2, 6, 17, and 23 yr, from four different facilities. Three rhinos recovered from skin (n = 2) and oral lesions (n = 1). However, the one male with both skin and oral lesions died with the disease. None of the affected black rhinos exhibited a decrease in any of the amino acids evaluated or for total amino acid concentrations (P > 0.05). Based on the absence of hypoaminoacidemia and the comparatively low mortality rate in rhinos with lesions, it appears that this syndrome is not entirely consistent with SND observed in other species. These data will be useful for future assessments of rhino nutritional status and other potential metabolic diseases.

Superficial necrolytic dermatitis in a dog associated with hyperplasia of pancreatic neuroendocrine cells

Superficial necrolytic dermatitis in a dog associated with hyperplasia of pancreatic neuroendocrine cells

Superficial necrolytic dermatitis

Companion AnimalVolume 14, Issue 2 p. 68-72 Superficial necrolytic dermatitis Stephen Shaw BVetMed PhD CertSAD MRCVS, Stephen Shaw BVetMed PhD CertSAD MRCVS Rutland House Referrals, Abbotsfield Road, St Helens, Merseyside. WA9 4HUSearch for more papers by this author Stephen Shaw BVetMed PhD CertSAD MRCVS, Stephen Shaw BVetMed PhD CertSAD MRCVS Rutland House Referrals, Abbotsfield Road, St Helens, Merseyside. WA9 4HUSearch for more papers by this author First published: 30 September 2010 https://doi.org/10.1111/j.2044-3862.2009.tb00332.xCitations: 1AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume14, Issue2March 2009Pages 68-72 RelatedInformation

Superficial necrolytic dermatitis associated with extrapancreatic glucagonoma in a dog

An 11-year-old Shih Tzu presented with crusting and erythema, mainly on the abdomen and the root of the tail. Based on histopathological findings, blood examinations and necropsy findings, the condition was diagnosed as superficial necrolytic dermatitis associated with a glucagon-secreting extrapancreatic neuroendocrine tumour. Gross necropsy revealed tumour invasion into the spleen, liver, adrenal glands and mesenteric lymph nodes. Immunohistochemical analysis of the neoplastic cells revealed that the tumour was a glucagonoma, consistent with earlier findings of persistent glucagonaemia and hypoaminoacidaemia.

A case of superficial suppurative necrolytic dermatitis of miniature schnauzers with identification of a causative agent using patch testing

A 9-year-old, castrated male, miniature schnauzer presented with malaise, anorexia, fever and severe inflammatory skin lesions on the dorsum, thighs and pinnae. The lesions developed 2 days after bathing with a commercial shampoo. Histopathological examination of skin samples revealed neutrophilic exocytosis, parakeratosis, epidermal hyperplasia and neutrophilic infiltration in the superficial dermis. Skin lesions resolved completely after 14 days of treatment with prednisolone and ofloxacin. Patch testing performed on the patient and a clinically healthy dog showed erythema at the site exposed to the culprit shampoo 48 h later only on the patient. Histopathological findings of the erythematous reaction were similar to those of the spontaneous skin lesions. Based on these findings, the dog was diagnosed with superficial suppurative necrolytic dermatitis of miniature schnauzers. The patch test results suggested that contact dermatitis to a commercial shampoo played a role in the pathogenesis of this disease.

Pathological Changes of the Skin and Liver in Three Cases of Canine Superficial Necrolytic Dermatitis

Canine superficial necrolytic dermatitis (SND) might be caused by nutritional deficiency mostly due to hepatopathy. However the associated hepatic lesions are varied among cases. Therefore, characterization of the concurrent hepatic lesions might be helpful to clarify the pathogenesis of canine SND. In this paper we described cutaneos and hepatic lesions in three cases of canine SND. The first case is an adult female Pomeranian dog. Grossly the liver showed characteristic diffuse nodular appearance. Microscopy revealed multifocal hydropic/glycogen degeneration of hepatocytes accompanying parenchymal collapse and regeneration of hepatocytes resulting in nodular accentuation of the liver. No significant fibrosis was observed. The diagnosis "vacuolar or glycogen hepatopathy" was preferable for the lesion. The second case is an 11-year-old, spayed female Maltese dog. The liver grossly showed nodular appearance as seen in the first case and was histopathologically diagnosed as vacuolar/fatty and hydropic/glycogen hepatopathy with moderate fibrosis and severe hemosiderosis. The third case is a 16-year-old castrated male mongrel dog. The hepatic lesion was diagnosed as hepatocellular carcinoma. All three cases had characteristic SND gross skin lesions such as erosion, scaling and crusting, and their histological findings of the skin biopsies were also consistent with those of SND. The paw pads were most intensely affected in all cases. Hypoalbuminemia and elevation with value of alkaline phosphatase were evidenced in all three cases. Hypoaminoacidemia was seen in the first and second cases. No elevation of glucagon value was observed in our cases. The hepatic lesions of the first and second cases might be of same hepatic disorder. The third case might be the first canine SND case associated with hepatoceller carcinoma.

Superficial necrolytic dermatitis associated with hepatic lipidosis in a red fox (Vulpes vulpes)

Superficial necrolytic dermatitis associated with hepatic lipidosis in a red fox (<i>Vulpes vulpes</i>)

Superficial Necrolytic Dermatitis in 11 Dogs with a History of Phenobarbital Administration (1995–2002)

The clinical records of 11 dogs with histologically confirmed superficial necrolytic dermatitis (SND) and a history of phenobarbital (PB) administration (SND/PB) were evaluated retrospectively (1995-2002). Historical, clinical, clinicopathologic, ultrasonographic, and pathologic findings were compared with those in dogs with SND without prior PB exposure (SND/No PB; n = 9) and with those dogs with PB-associated hepatotoxicity without skin disease (PB/hepatotoxicity). Dogs in the SND/PB group accounted for 44% of all histologically confirmed cases of SND that were evaluated at The Ohio State University Veterinary Teaching Hospital between 1995 and 2002. Median age of dogs in the SND/PB group was 10 years, and median duration of PB therapy was 6 years. Mean alanine aminotransferase (ALT) activity was 239 U/L, and median duration of abnormally high ALT activity was 6.25 months before SND diagnosis. Plasma amino acid concentrations measured in 1 dog were severely decreased. Ultrasonographic findings of hypoechoic nodules with hyperechoic borders corresponded to pathologic findings of nodular areas of normal hepatic tissue surrounded by zones of collapsed parenchyma with vacuolated hepatocytes. Clinical, clinicopathologic, ultrasonographic, and pathologic features of SND/PB and SND/No PB were similar. PB-associated cirrhosis and overt hepatic failure were not features of SND/PB. Different pathogenic mechanisms might induce SND in dogs. Chronic administration of PB requires further examination as a potential risk factor for the development of SND.