Polyarteritis nodosa in a captive common wooly monkey (Lagothrix lagotricha) associated with intestinal necrosis, peritonitis, and sepsis.

Polyarteritis nodosa is an idiopathic necrotizing vasculitis that affects small to medium-sized arteries. We describe a case of polyarteritis nodosa in a captive common wooly monkey (Lagothrix lagotricha) associated with transmural intestinal necrosis and secondary peritonitis. This condition must be considered for differential diagnosis of segmental arteritis in neotropical primates.

Cerebral Ovine Herpesvirus 2 Infection of Cattle Is Associated With a Variable Neuropathological Phenotype.

Cross-species infection with ovine herpesvirus 2 (OvHV-2) in cattle causes malignant catarrhal fever (MCF). MCF may involve the central nervous system (CNS) with necrotizing arteritis and/or vasculitis described to be unique to MCF and discriminatory compared to other viral CNS infections. However, a systematic histopathological characterization of the neural form of MCF in cattle is lacking. We examined medulla oblongata (n = 9) or the entire brain (n = 9) of 18 cattle in which OvHV-2 was identified by quantitative polymerase chain reaction (qPCR), in order to pinpoint potential variations in neuropathology. In 2/18 animals (11%) no lesions were identified, while 16/18 cattle (89%) had brain lesions of varying severity. Presence and quantities of OvHV-2 nucleic acid were determined by in situ hybridization and qPCR, respectively, and were related to the severity of lesions. Fifteen of 18 animals (83%) showed vasculitis, which was mainly of the lymphohistiocytic type, while pathognomonic necrotizing arteritis was only rarely present. Neuroparenchymal lesions included gliosis and/or neuronal changes in 7/16 brains with lesions (44%). The number of CD3+ lymphocytes was highest in animals with simultaneous vascular and neuroparenchymal lesions and high viral genome load. In one animal, OvHV-2 was exclusively observed in CD3+ lymphocytes but not in neurons or microglia. In conclusion, the neuropathological phenotype of bovine MCF in the brain was variable. In some cases, lesions mimicked neurotropic viral encephalitis, while pathognomonic necrotizing arteritis was not a consistent feature of neural MCF. Therefore, molecular detection of OvHV-2 is warranted in the presence of nonsuppurative encephalitis and in the absence of necrotizing arteritis.

Aberrant Mesenteric Migration of Spirocerca lupi Larvae Causing Necrotizing Eosinophilic Arteritis, Thrombosis, and Intestinal Infarction in Dogs.

This report presents a novel canine condition in 32 dogs in which aberrant migration of Spirocerca lupi larvae through mesenteric arteries, instead of gastric arteries, led to small or large intestinal infarction. This form of spirocercosis was first recognized in Israel in 2013 and is currently ongoing. Typical clinical signs were anorexia and weakness of 3 to 4 days and, less frequently, vomiting and diarrhea, followed by collapse, bloody diarrhea, and severe vomiting. Exploratory laparotomy showed 1 or more infarcted and often perforated intestinal segments in all cases. Microscopically, there was intestinal mucosal to transmural coagulative necrosis and mesenteric multifocal necrotizing eosinophilic arteritis, thrombosis, hemorrhage, and early fibroplasia. Third-stage S. lupi larvae were identified by morphologic features in 9 of 32 (28%) cases, and the species was confirmed by polymerase chain reaction in 4 cases. Nearly 50% of the dogs had been receiving prophylactic therapy, which did not prevent this form of spirocercosis.

Polyarteritis Nodosa in a Cat with Involvement of the Central and Peripheral Nervous Systems.

An 18-month-old neutered male domestic shorthair cat was referred with a history of pyrexia, polyuria and polydypsia, and transient episodes of bilateral hindlimb paralysis. Cardiac evaluation revealed severe systemic hypertension and severe concentric hypertrophy of the left ventricle. One month later the cat had a new episode of hindlimb paralysis with recurrent seizures, and died in status epilepticus. At necropsy examination, the coronary arteries, arcuate renal arteries and common iliac arteries showed marked thickening with nodules segmentally located along the vessels and consequent narrowing of the lumina. Histologically, acute and chronic inflammatory infiltration of the vascular walls was associated with necrosis of the muscular layer. Lesions were consistent with polyarteritis nodosa and involved the small, medium and large arteries of the heart, kidneys, small and large intestine, mesentery, liver and thyroid. Multifocal meningeal vasculitis associated with focal infarction of the frontal lobe and necrotizing vascular polyneuropathy were detected. Involvement of the central and peripheral nervous systems in polyarteritis nodosa is a novel finding in cats.

Systemic Necrotizing Vasculitis in Sheep Is Associated With Ovine Herpesvirus 2.

Ovine herpesvirus 2 (OvHV-2) is one of the gammaherpesviruses in the genus Macavirus that can cause malignant catarrhal fever (MCF) in ungulates. Sheep are the adapted host for OvHV-2 and it is generally assumed that infection is not associated with disease in this species. However, cases of "polyarteritis nodosa" or idiopathic systemic necrotizing vasculitis reported in sheep are similar to vascular lesions in clinically susceptible species with MCF. Using a recently developed in situ hybridization (ISH) method, we were able to identify OvHV-2 nucleic acids within lesions and correlate the viral distribution with systemic necrotizing vasculitis in 9 sheep, including both naturally and experimentally OvHV-2-infected animals. ISH, combined with polymerase chain reaction and histology, identify OvHV-2 as the likely agent responsible for sporadic, MCF-like vascular disease in sheep.

Systemic necrotizing polyarteritis in three weaned lambs from one flock.

Systemic necrotizing polyarteritis was diagnosed in three 7-11-mo-old lambs from the same flock. Aneurysmal dilation and rupture of the gastroduodenal artery in 1 lamb resulted in fatal hemorrhage. All lambs had severe necrotizing vasculitis involving the small intestine, abomasum, mesentery, kidney, and heart with concurrent lymphocytic enteritis. Immunohistochemistry for T- and B-lymphocytes and macrophages found a T-cell- and macrophage-dominant transmural vascular infiltrate and T-cell-associated enteritis. PCR analysis for pestivirus failed to identify infection in 1 lamb, and more extensive viral microarray techniques applied to the second and third lamb failed to detect viral nucleic acid. The identification of 3 cases within 1 flock raises the possibility of a common etiology; however, no cause was established. A genetic etiology was not considered likely as not all of the lambs were related. The presence of concurrent T-lymphocyte-associated enteritis raises the possibility of an immune-mediated disease process linking the vasculitis and enteric lesions.

Hemorrhage in the central canal of the cervical spinal cord in a coonhound diagnosed with canine juvenile polyarteritis (steroid responsive meningitis-arteritis).

Patchy meningeal and parenchymal contrast enhancement of the spinal cord with multifocal central canal dilations was noted in a computed tomography myelogram of the cervical spine of a 6-month-old intact female coonhound with a confirmed diagnosis of canine juvenile polyarteritis and associated hemorrhage within the central canal.

Hémorragie dans le canal central de la moelle épinière cervicale d'un coonhound avec un diagnostic de polyarthrite juvénile canine (méningite-artérite réactive aux stéroïdes). Une augmentation du contraste méningé et parenchymenteux en foyers de la moelle épinière avec des dilatations multifocales du canal central a été notée dans un myélogramme réalisé par tomodensitométrie de la moelle épinière d'une chienne coonhound intacte âgée de 6 mois avec un diagnostic confirmé de polyarthrite juvénile canine et une hémorragie connexe dans le canal central.(Traduit par Isabelle Vallières).

Pathological features of systemic necrotizing vasculitis (polyarteritis nodosa) in sheep.

Polyarteritis nodosa (PAN) is a systemic vasculitis of unknown aetiology affecting small- and medium-sized arteries of multiple organ systems without involvement of pulmonary arteries. This report describes four cases of PAN in sheep from different flocks. Three of these animals displayed clinical signs of locomotor disturbance. Gross necropsy findings included bilateral nodular thickening of vessels together with thromboses and aneurysms at several locations. Microscopically, small- to medium-sized arteries of the kidneys, ovary, uterus and skin were consistently involved and other locations were affected less frequently. Arteries within the lung were normal in all animals. Vascular lesions were characterized by focal fibrinoid necrosis, rupture of the internal elastic lamina and transmural infiltration of mononuclear inflammatory cells, extending into the perivascular tissue. In the kidney, many arteries showed narrowing or occlusion of the lumen and marked fibrosis. The distribution of arterial lesions was segmental, showing alternation of affected and microscopically normal areas. Immunohistochemical studies did not identify immune complex deposition. The inflammatory infiltrates were composed of T lymphocytes and macrophages, suggesting that a cell-mediated immune response may be involved in the pathogenesis of this disease.

Cerebral extension of steroid-responsive meningitis arteritis in a boxer.

A comatose 30-month-old, entire male boxer was presented because of an acute history of a cluster of three to four seizures. Neurological examination suggested a diffuse to multifocal intracranial lesion. Magnetic resonance tomography revealed symmetrical multifocal to diffuse changes of the cerebral grey matter and ependymal lining with sediment in the lateral ventricles. Haematological examination revealed leucocytosis with neutrophilia. Cerebrospinal fluid examination revealed high protein concentration and polymorphonuclear pleocytosis. Despite antiepileptic treatment, therapy against increased intracranial pressure and antibiosis, the dog's condition continued to deteriorate and he was euthanased. Pathological examination revealed fibrinosuppurative meningo-ependymitis and necrotising arteritis throughout the brain. In addition, chronic inflammation and arterial stenosis was found in the spinal meninges. No infectious agent was found. A diagnosis of steroid-responsive meningitis arteritis was made. The massive extension into the meninges and ventricular system of the forebrain has not been described previously in dogs with steroid-responsive meningitis arteritis and should be considered in the differential diagnosis when an intracranial suppurative infection is suspected.

High incidence of polyarteritis nodosa in the brains of culled sows.

A total of 307 brains of purebred sows obtained from an abattoir were retrospectively examined. These sows were culled with reasons of reproductive failure, urogenital infections, or locomotor problems. The most common macroscopic lesions were cavitations or lacunae in the basal nuclei (9.1%, 28/307) and coarse and thickened leptomeninges with marked vessels (3.9%, 12/307). The most frequent microscopic lesion was polyarteritis nodosa (21.2%, 65/307), which was found in all 40 brains with the above-mentioned gross lesions and in all 25 brains with microscopic cerebral infarcts or cavitations. The affected arteries of polyarteritis nodosa were distributed primarily in the cerebral leptomeninges, basal nuclei, and internal and external capsules. Histopathologically, a characteristic change of the affected arteries was transmural fibrinoid necrosis with severe infiltration of mixed inflammatory cells; narrowing or occlusion of the lumen. The inflammatory cells were chiefly composed of lymphocytes, macrophages, and plasma cells, with a few eosinophils and occasional multinucleated giant cells. Polyarteritis nodosa was found at a high percentage in the brains from culled sows. It may result in cerebral ischemia, infarcts, and hemorrhage, and possibly play a role in the necessity for culling due to locomotor problems.

Idiopathic canine polyarteritis in control beagle dogs from toxicity studies.

It is sometimes difficult to assess the relevance of polyarteritis with treatment-related lesions in dog toxicity studies, as number of dogs used in a toxicity study is small and the lesions are similar to those seen in spontaneous diseases. This report is intended to establish a general profile of idiopathic canine polyarteritis in beagle dogs. Data from a total of 40 dog studies including 4-, 13- or 52- weeks studies conducted between 1990 and 2003 at Huntingdon Life Sciences, UK, were collected and analysed. There was no death by this disease and also no prominent clinical signs related to this disease. Histologically, males tended to develop polyarteritis more frequently than in females and epididymis is the most probable tissues, followed by thymus and heart. Dogs in two studies showed higher incidences of these lesions, whereas animals in the other studies did not exhibited, suggesting that genetic predilection plays an important role in this disease.

Polyarteritis nodosa in a cynomolgus macaque (Macaca fascicularis).

Polyarteritis nodosa (PAN) is an idiopathic necrotizing vasculitis affecting small- to medium-sized arteries. The disease is well recognized in humans, and PAN-like syndromes have been described in a number of other species. This report describes a case of PAN in a 6-year-old male cynomolgus macaque. The animal had necrotizing arteritis affecting vessels in the kidney, small intestine, colon, heart, spleen, mesentery, urinary bladder, and pancreas. The lesions were segmental in distribution and of varying severity and stage of development. A transmural mixed inflammatory cell infiltrate was present, often accompanied by fibrinoid necrosis of the tunica media and loss of the internal elastic lamina. Immunohistochemical staining showed that many of the infiltrating cells were T lymphocytes and histiocytes, suggesting a cell-mediated component to the pathogenesis.

Intradural vasculitis and hemorrhage in full sibling Welsh springer spaniels.

Two, full sibling, Welsh springer spaniel presented at 8 and 18 mo of age with rapidly progressive ataxia, recumbency, and pyrexia. The spinal cord contained extensive subdural hemorrhage and, in 1 dog, suppurative and necrotizing arteritis in the dura. The findings suggest a familial form of canine juvenile polyarteritis syndrome.

Differentiating spontaneous from drug-induced vascular injury in the dog.

When vascular injury is observed in dogs used in preclinical toxicology studies, careful evaluation of the lesions is warranted, especially when differentiating drug-induced vascular changes from spontaneous findings, such as idiopathic canine polyarteritis. The clinical signs as well as the nature and distribution of lesions can often be distinguishing, as is the case with vasoactive drugs, including vasodilators and/or positive inotropes (hydralazine, minoxidil, endothelin receptor antagonists, and phosphodiesterase III inhibitors). For most types of vasodilator-induced vascular injury, the lesion is often restricted to coronary arteries, whereas in idiopathic canine polyarteritis, arterial lesions not only involve coronary arteries, but also medium to small arteries of other organs. In addition, the nature of the changes in vessels yields important clues. Medial and adventitial hemorrhage is generally associated with vasodilator-induced arterial lesion, whereas hemorrhage is generally absent in idiopathic polyarteritis. Although idiopathic canine polyarteritis can generally be differentiated from vasoactive-induced vascular injury in dogs, there are increasing incidences of this type of polyarteritis in dogs receiving any 1 of a number of unrelated classes of compounds, suggestive of an exacerbation of the spontaneous disease. Therefore, in order to differentiate drug-induced injury from idiopathic canine polyarteritis, it is critical that examination of the vascular pathology be conducted with good understanding of clinical, pharmacological, and mechanistic data associated with the drug.

Restriction fragment length polymorphism of the T-cell receptor beta-chain gene in dogs.

Since T-cells and the T-cell receptor (TCR) play a pivotal role in the response of the immune system, they are a target for pathogenesis studies in immune mediated diseases and have been used to generate markers for T-cell dependent diseases in humans and dogs. TCR rearrangement is generated at the genomic DNA level and can be analyzed by Southern blotting techniques. In the present study this method to detect rearrangement of the TCR beta chain in the dog was critically examined. To search for restriction fragment length differences due to either inherited polymorphism or in diseases with suspected superantigen influence (X-linked severe combined immune deficiency and canine juvenile polyarteritis syndrome) 13 dog families of three different breeds were examined. In addition primary spleen cell cultures, stimulated with either phytohemagglutinin A (PHA) or staphylococcus enterotoxin A (SEA) and B (SEB) were studied. The germline digest pattern of the enzymes Pst I, Sst I, Bgl II, Eco RI and Eco RV were identical in all dogs examined with the exception of one dog with canine juvenile polyarteritis syndrome. In this dog an additional band was found in the Bgl II and Eco RV digestion suggestive of specific TCR rearrangement. Bam HI digestion revealed restriction fragment length polymorphisms (RFLPs) showing Mendelian inheritance. After digestion of the genomic DNA extracted from PHA, SEA or SEB stimulated spleen cells and Southern blot analysis, no differences in fragment patterns between the unstimulated cells and the stimulated cells could be detected. An important point to consider before a specific pattern variation between dogs is classified to be a marker for a specific disease or is used in pathogenesis studies, is the possibility of an inherited RFLP, especially after Bam HI digestion. In such studies the combined examination of the parents and the offspring must be recommended.

Pathologic features of naturally occurring juvenile polyarteritis in beagle dogs.

Eighteen young Beagle dogs (eight males and 10 females), ages 6-40 months, with canine juvenile polyarteritis syndrome (CJPS), a naturally occurring vasculitis and perivasculitis of unknown etiology, were necropsied, and their tissues were examined by histopathologic and histochemical methods. The condition is characterized by recurring episodes of an acute onset of fever (> 40 C) and neck pain that persist for 3-7 days. The major histopathologic alterations were a systemic vasculitis and perivasculitis. During the febrile, painful period of CJPS, the vascular lesions ranged from a histiocytic-lymphocytic periarterial infiltration to transmural arterial inflammation with concomitant fibrinoid necrosis and vascular thrombosis. Massive periarterial accumulations of inflammatory cells were common and often extended into adjacent tissues. The small- to medium-sized muscular arteries of the heart, cranial mediastinum, and cervical spinal meninges were consistently involved. Vasculitis occasionally occurred in other organ systems. The vascular lesions in dogs examined during clinically normal periods consisted of intimal and medial fibrosis, ruptured elastic laminae, and mild perivasculitis; these lesions were probably related to previous episodes of vasculitis. Eight dogs that had experienced repeated acute episodes also developed splenic, hepatic, and renal amyloidosis. The clinical signs, laboratory abnormalities, and the vascular lesions suggest that the condition may be immune-system mediated. CJPS may serve as a naturally occurring animal model of human immune-system-mediated vasculitides such as polyarteritis nodosa, infantile polyarteritis, and Kawasaki disease.