JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1176745): Age and gender unspecified Sprague-Dawley rat
HISTORY: Incidental finding
HISTOPATHOLOGIC DESCRIPTION: Small intestine and mesentery: Diffusely, mesenteric arteries are tortuous with lumina variably narrowed by markedly thickened walls which are expanded by reactive fibroblasts within the tunica media, collagen, numerous small caliber blood vessels, and clear space (edema) and which are transmurally infiltrated by numerous viable and degenerate neutrophils, fewer macrophages, lymphocytes, plasma cells, rare multinucleate giant cells, eosinophils, and necrotic debris (necrotizing vasculitis). The internal elastic lamina is discontinuous and the tunica intima is markedly expanded by thick bands of deeply eosinophilic hyalinized fibrin admixed with cellular and karyorrhectic debris (fibrinoid necrosis) between the hypertrophied reactive endothelium and the internal elastic lamina. Arterial lumina are rarely occluded by organizing fibrin thrombi. Inflammatory cells and fibroblasts extend into the tunic adventitia, disrupt elastic fibers of the external elastic membrane, and extend into surrounding connective tissue, which contains many small caliber blood vessels and edema. Multifocally, there is moderate atrophy of mesenteric fat with increased numbers of spindle to stellate cells (fibroblasts), edema and numerous small caliber blood vessels (granulation tissue).
MORPHOLOGIC DIAGNOSIS: Arteries, mesenteric: Arteritis, proliferative, fibrinoid and necrotizing, chronic-active, diffuse, severe, Sprague-Dawley rat, rodent.
CONDITION: Polyarteritis nodosa
SYNONYMS: Panarteritis; periarteritis nodosa; systemic necrotizing vasculitis
- “Polyarteritis nodosa” applies to a mixed group of arteritides, which occur sporadically in all species of domestic animals, based upon classic polyarteritis nodosa in humans, in which small and medium-sized arteries undergo severe necrotizing inflammation, often in a sharply segmental (nodose) pattern, and with a predilection for branching points; arterioles, capillaries, and venules not involved
- Chronic progressive degenerative disease that most often occurs in aging rats, with higher incidence in males
- In rats, occurs most often in the muscular medium-sized arteries of the mesentery, pancreas, pancreaticoduodenal artery, and testis, but also seen in hepatic, coronary, uterine, cerebral, adrenal, and renal arteries; spares the pulmonary circulation, large arteries and glomeruli
- Most often in Sprague-Dawley and spontaneously hypertensive (SHR) strains, and rats in late stage chronic nephropathy
- Thought to be an immunologically mediated disease (type III hypersensitivity)
- Antigen:antibody complexes form in bloodstream (Ag > Ab) with immune complex deposition in arterial walls
- Inflammation and/or activation of complement
- Recruitment of WBCs results in tissue damage due to release of lysosomal enzymes, and generation of toxic free radicals
- Fibrinoid necrosis and arteritis
TYPICAL CLINICAL FINDINGS:
- Often no clinical signs in rats
TYPICAL GROSS FINDINGS:
- Thick, tortuous, gray to red, hard, medium-sized muscular arteries
- Spares pulmonary arteries, large arteries, and glomeruli
- Focal hemorrhage
- May have aneurysmal dilatations
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Fibrinoid necrosis with neutrophilic and mononuclear infiltration of the intima and media
- With chronicity, transmural fibrosis and inflammation
- Mural thrombosis is common; chronic lesions may exhibit recanalization
- Narrowing or occlusion of the vascular lumen may occur
- Drug-induced vascular lesions can mimic the spontaneous disease
- Numerous entities can cause arteritis in domestic animals (vasculitis):
- Metazoan parasites: Strongylus vulgaris, Dirofilaria immitis, Schistosoma spp., Elaeophora schneideri, Onchocerca armillatus, Angiostrongylus spp.
- Viruses: Equine viral arteritis (arterivirus, Arteriviridae), equine herpesvirus-1 (brain), bovine viral diarrhea and border disease (pestivirus, Flaviviridae), classical swine fever (pestivirus, Flaviviridae), African swine fever (Asfarviridae), malignant catarrhal fever (alcelaphine herpesvirus-1 or ovine herpesvirus-2; Gammaherpesviridae)
- Bacterial diseases: Salmonella, Erysipelothrix, beta-hemolytic Streptococcus, Rickettsia rickettsii
- Fungi: Aspergillus, Zygomycetes
- Idiopathic necrotizing polyarteritis (idiopathic canine polyarteritis, juvenile polyarteritis syndrome, “beagle pain syndrome”):
- Clinical signs: Recurrent fever, hyperesthesia, severe pain on manipulation of the neck, cervical rigidity, hunched body posture, and anorexia; some affected dogs asymptomatic
- Small to medium sized muscular arteries of heart, cranial mediastinum, cervical spinal meninges, epididymis, thymus
- Intimal and medial fibrosis, rupture of elastic laminae, perivasculitis, thrombi, aneurysms; splenic, renal and hepatic amyloidosis
- Usually acute, but can be chronic (affecting all layers of vascular tunic)
- Mice: Polyarteritis is common in mice that are prone to autoimmune disease, including MRL and NZB mice; may affect vessels of tongue, head, pancreas, bladder, heart, kidneys, uterus, testes, gastrointestinal tract; may include vestibular syndrome in mice
- Recently described in sheep with similar presentation as in other species; however, lesions similar to polyarteritis nodosa, or idiopathic systemic necrotizing vasculitis, are reported in sheep clinically susceptible to ovine herpesvirus-2 (OvHV-2; malignant catarrhal fever) (Vet Pathol., 2019)
- Recent report in a young cat (J Comp Pathol., 2019); lesions consistent with polyarteritis nodosa, affecting small, medium and large vessels of heart, kidneys, small and large intestine, mesentery, liver and thyroid, with multifocal, meningeal vasculitis associated with focal infarction of the frontal lobe and necrotizing polyneuropathy; central and peripheral nervous system lesions are new finding in cats
- Göttingen minipigs: Occasionally observed background change in preclinical toxicology studies; most commonly reported in cardiac and extracardiac vessels, vagina, oviduct, rectum, epididymis, spinal cord, pancreas, urinary bladder, kidneys and stomach (Toxicol Pathol., 2018)
- Lambs: Recent report (J Vet Diagn Invest., 2017) of systemic necrotizing polyarteritis in three unrelated lambs; lesions involved small intestine, abomasum, mesentery, kidney, heart with concurrent lymphocytic enteritis
- Raccoons: There has been a report of spontaneous idiopathic arteritis of the testicular artery in raccoons, closely resembling polyarteritis nodosa; however, none of the arteries were completely occluded or showed fibrinoid necrosis of the media of affected vessels
- Human classic polyarteritis nodosa affects young adults, often with renal involvement; 30% of cases are associated with hepatitis B antigen
- Dincer Z, Piccicuto V, Walker UJ, Mahl A, McKeag S. Spontaneous and drug-induced arteritis/polyarteritis in the Göttingen minipig-review. Toxicol Pathol. 2018; 46(2):121-130.
- Ferreras MC, Benavides J, Fuertes M, et al. Pathological features of systemic necrotizing vasculitis (polyarteritis nodosa) in sheep. J Comp Pathol. 2013;149:74-81.
- Hamir AN, Palmer M, Li H, Staska J, Rogers DG. Spontaneous idiopathic arteritis of the testicular artery in raccoons (Procyon lotor). Vet Pathol. 2009;46:1129-1132.
- Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:70-71.
- Miller LM, Gal A. Cardiovascular system and lymphatic vessels. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:614-615.
- Mitchell RN. Blood vessels. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Philadelphia, PA: Elsevier Saunders Co; 2016:509-510.
- Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. 4th ed., Ames, IA: John Wiley & Sons Inc; 2016:99,156.
- Pesavento PA, Dange RB, Ferreras MC, et al. Systemic necrotizing vasculitis in sheep is associated with ovine herpesvirus 2. Vet Pathol. 2019;56(1):87-92.
- Salvadori C, Vezzosi T, Marchetti V, Cantile C. Polyarteritis nodosa in a cat with involvement of the central and peripheral nervous systems. J Comp Pathol. 2019;167:6-11.
- Wessels M, Strugnell B, Woodger N, Peat M, La Rocca SA, Dastjerdi A. Systemic necrotizing polyarteritis in three weaned lambs from one flock. J Vet Diagn Invest. 2017;29(5):733-737.