JPC SYSTEMIC PATHOLOGY
HEMOLYMPHATIC SYSTEM
April 2024
H-V06
Signalment (JPC #690455): Pig, age, breed, and sex unspecified
HISTORY: This is one of a group of pigs inoculated with an infectious agent. At necropsy, there were numerous petechial hemorrhages over the serosal surfaces of many organs.
HISTOPATHOLOGIC DESCRIPTION: Spleen: There is multifocal vasculitis characterized by hypertrophy, degeneration, and/or necrosis of the endothelium and expansion of the tunica media by brightly eosinophilic, hyalinized fibrin, edema, and minimal necrotic debris (fibrinoid necrosis). In more severely affected vessels there is complete loss of vessel architecture with replacement by fibrin, edema, hemorrhage, and necrotic debris. Vessel lumina are occasionally occluded by fibrin thrombi. Affected vessels are surrounded by variably sized, well-demarcated, up to 4 mm areas of coagulative necrosis (infarcts) admixed with lytic necrosis, fibrin, edema, and hemorrhage which fill and expand red pulp vascular spaces. There is diffuse lymphoid depletion of the white pulp characterized by a marked decrease in size and number of periarteriolar lymphatic sheaths and lymphoid follicles, and remaining follicles lack discernable germinal centers, mantle zones, and marginal zones. The capsule is diffusely lined by hypertrophied (reactive) mesothelial cells, and fibrous papillary projections multifocally extend from the capsule. There is minimal focal hemorrhage in the perisplenic adipose tissue.
MORPHOLOGIC DIAGNOSES: Spleen: Vasculitis, fibrinonecrotizing, multifocal, marked, with necrosis (infarcts) and diffuse lymphoid depletion, breed not specified, porcine.
ETIOLOGIC DIAGNOSIS: Pestiviral splenic infarcts
CAUSE: Classical swine fever virus (porcine pestivirus)
SYNONYMS: Classical swine fever (CSF), hog cholera, Schweinepest, peste du porc, pesti svina
GENERAL DISCUSSION:
- CSF is an acute hemorrhagic disease characterized by disseminated intravascular coagulation, thrombocytopenia, and immunosuppression
- CSFV is a member of the genus Pestivirus, family Flaviviridae and is an enveloped, single stranded RNA virus
- Pigs and wild boars are the only natural hosts; wild pigs can serve as source of infection for domestic pigs
PATHOGENESIS:
- Mechanism of injury is widespread necrosis of endothelial cells and hematopoietic cells.
- Virus is shed in urine, oronasal and lacrimal secretions, and feces
- Transmitted primarily through direct contact between swine (ingestion and/or inhalation); less often, indirect contact with fomites, mechanical vectors, and/or aerosol; feeding virus-containing garbage; also transmitted transplacentally
- Direct contact > infection of epithelial cells of tonsillar crypts > spread to regional lymph nodes > replication > mononuclear cell and leukocyte-associated viremia > day 3 or 4 post-infection, virus invades endothelial and epithelial cells (tonsil, pharyngeal mucosa, gastrointestinal tract, gallbladder, pancreas, uterus, and salivary, adrenal, and thyroid glands) > endothelial cell necrosis > thrombocytopenia, DIC, thrombosis, infarction, and hemorrhage
- Macrophage spread of virus to lymphatic tissue and bone marrow > infection of lymphocytes and hematopoietic cells > impairment of immune response and platelet production > secondary infection and thrombocytopenia
- Monocyte/macrophages are the main target cells; TNF alpha, and to a lesser extent IL-6 and IL-1 alpha produced by these macrophages, appear to be involved in the pathogenesis of lymphopenia and thrombocytopenia
- E(rns) and E2 envelope glycoproteins are involved in binding to mucosal epithelium and macrophages
- Secondary bacterial or concurrent viral disease may alter severity and course of disease
- Infection of pregnant sows results in congenital CSFV infection or fetal death
TYPICAL CLINICAL FINDINGS:
- High virulence infections:
- Peracute: Sudden death
- Acute: Most common, death in 10-20 days
- Severe depression, anorexia, pyrexia, purulent tonsillitis and conjunctivitis, leukopenia, constipation initially, followed by diarrhea
- Nervous signs: Circling, incoordination, tremors, convulsions, posterior paralysis
- Terminally: Cutaneous cyanosis of ears, tail, ventral abdomen, hindquarters
- Low virulence infections:
- Chronic: Death in 1-3 months; depression, pyrexia, anorexia, leukopenia followed by clinical improvement, then terminal exacerbation of disease
- Transplacental infection:
- Stillborn piglets: Subcutaneous edema, ascites, hydrothorax, head and limb malformations, cerebellar hypoplasia, hypomyelogenesis
- If born alive, weak pigs die shortly after birth
- Some pigs may be born healthy and are persistently infected with late onset of disease: Gradual depression and anorexia, pyrexia, conjunctivitis, dermatitis, locomotion abnormalities, death in 2-11 months
TYPICAL GROSS FINDINGS:
- Peracute disease - No gross lesions
- Acute – Most common lesions are hemorrhage in the kidneys with ecchymoses (“turkey egg kidney”) and lymph nodes with diffuse edema and hemorrhage in sinusoids creating a “marbled” appearance; infarcts along margins of spleen; suppurative and necrotizing tonsillitis; hydropericardium, hydrothorax, and hydroperitoneum
- Chronic - Button ulcers of cecum and colon, splenic infarction, rib calcification
- In utero infections- Thymic atrophy, lymph node edema, cerebellar hypoplasia
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Acute: Widespread endothelial cell degeneration, necrosis, hemorrhage, and infarction; encephalitis with perivascular cuffing, focal necrosis, microgliosis; progressive lymphoid depletion; necrosis of intestinal mucosa
- Chronic: Glomerulonephritis (immune-mediated mesangioproliferative), calcification of cartilaginous cells of ribs
- Nonpurulent meningoencephalitis
- In utero: Widespread lymphoid depletion and thymic atrophy; hypomyelination
ADDITIONAL DIAGNOSTIC TESTS:
- Direct fluorescent antibody on frozen tissue (tonsil, spleen, kidney, distal ileum)
- Virus neutralization
- Virus isolation
- Centrifugal microfluidic disk (Yuan, J Vet Diagn Invest. 2019)
DIFFERENTIAL DIAGNOSIS:
- African swine fever (H-V05)
- High-pathogenic porcine reproductive and respiratory syndrome (P-V25)
- Swine erysipelas (I-B08, U-B09)
- Septicemic salmonellosis
- Dermatitis and nephropathy syndrome (I-M33)
For gross lesions:
Spleen:
- African swine fever (Asfarviridae)
- Acute: Hyperemia with splenomegaly
- Subacute: Partial hyperemia with splenomegaly or focal infarct
- Erysipelothrix rhusiopathiae- in acute infection the spleen may be enlarged and red, and in chronic infection there may be large infarcts in the spleen
- Porcine reproductive and respiratory syndrome – scattered infarcts or white spots on the surface
Kidney: (turkey egg kidney)
- Erysipelothrix rhusiopathiae – Thrombus formation
- African swine fever – Vascular endothelial damage and fibrinoid arterial changes
- Salmonella Choleraesuis – Septicemia, endothelial damage from endotoxin
- Porcine circovirus type 2 (I-M33) – Porcine dermatitis and nephropathy syndrome (PDNS); glomerulonephritis
Tonsils and Lymphoid Tissue:
- Suid herpes virus 1 (Pseudorabies, N-V07) – Necrosis of the palatine tonsils
- African swine fever virus – Lymphatic necrosis and hemorrhage
- Salmonella Choleraesuis – Septicemia, endothelial damage from endotoxin
- Porcine reproductive and respiratory syndrome virus (PRRS) – Lymphoid hyperplasia and necrosis
For similar clinical signs and cutaneous lesions:
- Salmonella Choleraesuis -induced septicemia – Ear, foot, tail and ventral abdomen cutaneous cyanosis, splenomegaly, swollen lymph nodes, sudden death
- Streptococcus suis-induced septicemia – Dyspnea, cyanosis, pyrexia, meningitis, arthritis, pneumonia, sudden death
- Acute Erysipelothrix rhusiopathiae – Pyrexia, cutaneous cyanosis, widespread hemorrhages, sudden death
- Haemophilus parasuis – Pyrexia, anorexia, pain, swollen joints, lameness, tremors, incoordination, cyanosis, recumbency
- Suid herpes virus 1 – Pyrexia, listlessness, anorexia, trembling, incoordination, ataxia, seizures, posterior paralysis
- Mycoplasma (Eperythrozoon) suis – Pyrexia, cyanosis of ear margins
COMPARATIVE PATHOLOGY:
Other pestiviruses
- Bovine pestivirus (Bovine virus diarrhea virus)
- Acute systemic disease with severe diarrhea, oral lesions, gastrointestinal hemorrhage, interdigital erosions, vasculitis
- Chronic mucosal disease with severe lymphoid depletion and vasculitis, progression to diarrhea, anorexia, death
- In utero infection - Cerebellar hypoplasia
- Border disease virus (hairy shaker lamb)
- Affects sheep and goats
- Virus is very closely related to BVD virus
- Congenital infection results in stillborn lambs or birth of weak lambs with abnormal hair coats, abnormal body conformation, clonic rhythmic tremors, and unthriftiness
REFERENCES:
- Gal A. and Castillo-Alcala, F. Cardiovascular system, Pericardial Cavity, and lymphatic vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:691.
- Kirkland PD, Potier ML, Vannier P, Finlaison D. Pestiviruses. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW, eds., Disease of Swine. 10th ed., Ames, IA: Blackwell Publishing; 2012:539-546.
- Martinez MAJ, Gasper D, Mucino MCC, Terio K. Suidae and Tayassuidae. In: Pathology of Wildlife and Zoo Animals. London, United Kingdom: Academic press, 2018: 216.
- Sánchez-Vizcaíno JM, Mur L, Gomez-Villamandos JC, Carrasco L. An update on the epidemiology and pathology of African swine fever. J Comp Pathol. 2015;152(1):9-21.
- Stanton, JB and Zachary, JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:261-262.
- Valli VEO, Kiupel M, Bienzle D. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:178-181.
- Yuan X, Jizhou Lv, Lin X, et al. Multiplex detection of six swine viruses on an integrated centrifugal disk using loop-mediated isothermal amplification. J Vet Diagn Invest. 2019;31(3):415-425.
