AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

HEMOLYMPHATIC SYSTEM

April 2015

H-V10

 

SIGNALMENT (AFIP Accession # 2286727): 9-year-old male Appaloosa

 

HISTORY: This horse presented with anorexia, ataxia, behavioral changes, and photosensitivity.

 

HISTOPATHOLOGIC DESCRIPTION: Liver: Diffusely, portal areas are moderately infiltrated by lymphocytes and plasma cells that extend into and expand the sinusoids and multifocally infiltrate the capsule. Hepatocytes are multifocally separated, individualized and lost and replaced by the infiltrate. Moderate numbers of Kupffer cells and macrophages scattered throughout the sinusoids or in portal areas contain intracytoplasmic, fragmented erythrocytes (erythrophagocytosis) or yellow-brown, granular cytoplasmic pigment (hemosiderin).  There are multifocal areas of hemorrhage, especially subcapsular, where red blood cells surround and individualize hepatocytes. Multifocally, bile canaliculi are distended with green-brown, globular material (bile stasis).

 

MORPHOLOGIC DIAGNOSIS: Liver: Hepatitis, lymphoplasmacytic, portal, diffuse, moderate, with erythrophagocytosis, hemosiderosis, and mild hepatocellular necrosis and loss, Appaloosa, equine.

 

ETIOLOGIC DIAGNOSIS: Lentiviral hepatitis

 

CAUSE: Equine infectious anemia virus (EIAV), equine lentivirus

 

CONDITION: Equine infectious anemia

 

SYNONYMS: Swamp fever

 

GENERAL DISCUSSION:

·         Arthropod-borne virus in the Lentivirinae subfamily of Retroviridae (RNA virus); infects cells of the monocyte-macrophage system

·         Causes disease in all species of equidae (horses, mules, and donkeys)

·         Mechanical transmission through the transfer of contaminated blood or blood products by biting insects or contaminated needles; transmission also transplacental, or by insemination with contaminated semen

·         Viral replication does not occur in insect vectors (mechanical); vectors include the biting fly (Stomoxys calcitrans), horse flies (Tabanus spp.), and mosquitoes (Anopheles spp., Culex spp.)

·         Infection is lifelong with a cyclic viremia; asymptomatic to acutely fatal

·         Worldwide distribution; outbreaks usually in the summer in wet, marshy areas ("swamp fever")

·         Virus causes anemia by immune-mediated hemolysis and decreased erythropoiesis

 

PATHOGENESIS:

·         Mechanism of injury is inflammation and proliferation of the monocyte-macrophage and lymphocytic systems

·         Infection of blood monocytes (without viral replication) > monocytes disseminate virus to tissues throughout body without host immune detection > differentiation of monocytes to macrophages as they enter tissue > activation of viral replication > high levels of virus in macrophage-rich tissues (liver, spleen) > proinflammatory chemokine/cytokine production by macrophages recruits additional leukocytes, resulting in splenomegaly/lymphadenomegaly > Infected tissue macrophages in various tissues continue to release viral antigen (reservoir)

·         Acute intracellular hemolysis > immune proliferation > hematopoetic exhaustion also contributes to anemia

·         Hemolytic anemia

·         Immune-mediated erythrocyte destruction (phagocytosis or complement lysis): Circulating viral antigen adsorbed to erythrocyte membranes (act as haptens) > antibody and C3 bind to the antigen > extravascular hemolysis via macrophage recognition of complement or haptens/ intravascular hemolysis due to type II hypersensitivity response in acute phase (Ab-viral hapten complex on red cell membrane activates complement cascade); “innocent bystander” destruction of erythrocytes

·         Anemia also due to direct suppression of early-stage erythroid cells by virus

·         Immune-mediated thrombocytopenia – platelets destroyed by similar mechanism or are activated and then bound by fibrinogen and phagocytosed

·         Virus does not kill cells > reason why CID foals without functional B and T cells infected with EIAV do not develop widespread inflammatory lesions

·         Viral envelope glycoproteins gp90, gp45 and p26 bind to equine lentivirus receptor-1 in cell membranes on monocytes/macrophages

·         Recurrence in chronic EIA is due to antigenic variance of surface glycoproteins

 

TYPICAL CLINICAL FINDINGS:

·         Acute: High fever (up to 108oF), depression, anorexia, weakness, ataxia, weight loss, dependent edema, petechiae (ventral tongue, ocular and vulvar mucosa) due to thrombocytopenia, anemia, icterus (pre-hepatic)

·         Chronic: Recurring 1-2 week cycles of fever, emaciation, weakness, ventral edema, serous atrophy of fat with bilirubin staining, anemia, and thrombocytopenia; lasts 8 to 12 months with decreasing frequency and severity of disease until asymptomatic infection; asymptomatic carriers may suffer relapse

 

CLINICAL PATHOLOGY:

·         Anemia – PCV 14-20%

·         Acute – macrocytosis, anisocytosis, poikilocytosis (abnormally shaped RBCs)

·         Regenerative anemia without reticulocytes (not found in horses)

·         Chronic – normochromic, normocytic, nonregenerative

·         Sideroleukocytes – circulating monocytes with phagocytized erythrocytes and hemosiderin; indicate intracellular hemolytic anemia; highly suggestive of EIAV

·         Bone marrow:

·         Acute – hypercellular with erythroid shift

·         Chronic – reduced cellularity with dyserythropoiesis; macrophage and plasma cell proliferation

·         Thrombocytopenia

·         Decreased serum albumin/globulin ratio with normal total protein

·         Hyperbilirubinemia – unconjugated (indirect)

·         CSF – elevated protein and leukocytes; xanthochromic

 

TYPICAL GROSS FINDINGS:

·         Bone marrow: The increase of reddening (hyperplasia of the hematopoietic marrow) is directly proportional to disease duration

·         Dark red and yellow, focal hemorrhagic infarcts within the proximal and distal segments of the medullary cavity and along the subendosteal surface of the diaphysis

·         Icterus, widespread hemorrhagic foci, subcutaneous edema, pallor, and renal petechiae (capsule, cortex, and medulla)

·         Spleen, lymph nodes: Splenomegaly and lymphadenomegaly with capsular hemorrhages, and abundant lymphoid follicles that bulge from the cut surface

·         Liver: Enlarged, dark, and turgid with capsular hemorrhage

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·         Lesions most prominent in the heart, lungs, liver, spleen, kidney, bone marrow, and lymph nodes; severity is dependent on the chronicity of infection

·         Acute:

·         Hemosiderosis in major organs; prominent lymphoid hyperplasia

·         Ischemic necrosis of the heart, liver, and kidneys with perivascular and interstitial lymphocytic infiltration

·         Bone marrow: Hypercellular with productive synchronous erythroid hyperplasia and reduction in mature granulocytes (eosinophils are prominent)

·         Chronic:

·         Monocyte/macrophage hyperplasia with hemosiderosis; myocardial fiber atrophy; lymphoid involution and atrophy

·         Liver: Periportal lymphocytic infiltrates, atrophic cords with sinusoidal dilation, Kupffer cell hyperplasia, hemosiderosis, hemorrhage and hepatocellular necrosis in acute phase

·         Spleen: Large follicles but hypocellular with sharp distinction between follicular center and mantle and marginal zones and sinusoidal congestion ("bull's eye" appearance)

·         Kidney: Immune complex glomerulonephritis; IgG and C3 in mesangium and basement membranes

·         Bone marrow: Erythroid hyperplasia replaces adipose tissue; large macrophages containing hemosiderin, erythrocytes, or rubricytes; dyserythropoiesis with binucleate interphase rubricytes

·         CNS: Granulomatous ependymitis and choroid plexitis; inflammation surface related (central canal, ventricular system and leptomeninges) and most prominent in spinal cord

·         Heart:  Myocyte fiber atrophy

 

ADDITIONAL DIAGNOSTIC TESTS: 

·         Agar-gel immunodiffusion test – AGID (Coggins test), detects anti-EIAV antibody; gold standard

·         Western blot, ELISA, PCR

 

DIFFERENTIAL DIAGNOSIS:

For anemia in the horse:

·         Purpura hemorrhagica

·         Equine granulocytic ehrlichiosis (Anaplasma phagocytophilum)

·         Babesiosis

·         Equine viral arteritis (Arterivirus)

·         Red maple leaf toxicosis

·         Neonatal isoerythrolysis

·         Immune-mediated hemolytic anemia; idiopathic thrombocytopenia

·         Gastric ulcers

·         Parasitism (external or internal)

·         Leptospirosis

 

COMPARATIVE PATHOLOGY:

Lentiviruses:

Immunosuppressive (virus replicates in macrophages & lymphocytes)

·         Human immunodeficiency virus (HIV); feline immunodeficiency virus (FIV); simian immunodeficiency virus (SIV)

·         Bovine immunodeficiency virus (BIV); Jembrana Disease (JD) – cattle (mild, transient immunosuppression)

 

Immunostimulatory (virus replicates in macrophages)

·         Caprine arthritis-encephalitis virus (CAEV) – goats

·         Ovine progressive pneumonia virus (Maedi-visna virus) – sheep

·         Equine infectious anemia virus (EIAV) – horses

 

References:

1.  Campbell RSF, Robinson WF. The comparative pathology of lentiviruses. J Comp Path. 1998;119:333-395.

2.  Cullinane A, et al. Diagnosis of equine infectious anaemia during the 2006 outbreak in Ireland. Vet Rec. 2007;161(2):647-652.

3.  Radostits OM, Gay CC, Hinchcliff KW, Constable PD. Veterinary Medicine; a Textbook of the Diseases of Cattle, Horses, Sheep, Pigs and Goats. 10th ed. Philadelphia, PA: Saunders Elsevier; 2007:1173-7.

4.  Valli VEO. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 5th ed. Vol 3, Philadelphia, PA: Saunders Elsevier; 2007:235-239.

5.  Zachary JF. Mechanisms of microbial infections: In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Mosby Elsevier; 2012:221-2.

 

Cline 2015


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