JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 1764737): Adult crossbred goat
HISTOPATHOLOGIC DESCRIPTION: Joint capsule: The synovial membrane is thickened up to 5 times normal and forms numerous wide papillary villar projections. Villi are hypertrophic and edematous and expanded by eosinophilic fibrillar to beaded material (fibrin), fibrous connective tissue and dense (rarely nodular) inflammatory infiltrates composed of many plasma cells and lymphocytes, fewer macrophages and rare multinucleated giant cells and neutrophils. Villi often have a superficial layer of hyalinized fibrin covering or just under to the synovium that is multifocally surrounded by a few fibroblasts and collagen (fibrosis). Multifocally, synovial lining cells are plump and pile up to four cells thick (hypertrophy and hyperplasia). Within the fibrous joint capsule, blood vessels are lined by hypertrophied endothelium and are surrounded by a few plasma cells and lymphocytes. There are scattered small hemorrhages and a small focus of mineralization in the joint capsule.
MORPHOLOGIC DIAGNOSIS: Joint capsule: Synovitis, proliferative and lymphoplasmacytic, diffuse, moderate, crossbreed goat, caprine.
ETIOLOGY: Caprine arthritis-encephalitis virus (CAEV); small ruminant lentivirus subgroup B
ETIOLOGIC DIAGNOSIS: Lentiviral synovitis
CONDITION: Caprine arthritis-encephalitis (CAE)
- Multisystemic lymphoproliferative disease in goats that causes persistent chronic inflammatory lesions in the CNS, lungs, joints, and mammary gland
- Arthritis often the major or only sign of infection
- Family Retroviridae, subfamily Lentivirinae
- Lentiviruses (nononcogenic retroviruses) cause diseases with long incubation periods, persistent infection (virus never eliminated) and progressive course
- Pathologic effects similar to the ovine progressive pneumonia/maedi-visna virus (lentivirus) in sheep
- Viral infection may involve 100% of a goat herd, with clinical signs in only 25%
- Goats develop 4 clinical syndromes that may occur concurrently: Arthritis, mastitis, encephalomyelitis, or interstitial pneumonia.
- Young goats (<4 months): Neurological disease with ascending paralysis and nonsuppurative leukoencephalomyelitis and often interstitial pneumonia
- Adults: Animals that survive the initial infection later develop chronic, nonsuppurative arthritis and synovitis (most common presentation), mastitis (usually subclinical), and chronic interstitial pneumonia (usually subclinical)
- Small ruminant lentiviruses (SRLVs; maedi-visna virus is SRLV subgroup A, and CAEV is SRLV subgroup B) have the following viral genes:
- pol – encodes reverse transcriptase and other enzymes
- gag – encodes for group-specific nucleocapsid & matrix glycoproteins; detected by antibody-based tests
- env – encodes for surface glycoprotein that mediates receptor binding and virus entry into cells; target for neutralizing antibody
- vif, rev, and tat – encodes for regulatory proteins
- Ovine progressive pneumonia/maedi-visna virus in sheep is a closely related lentivirus that shares similar pathologic effects
- Pulmonary, mammary, and nervous forms most common in sheep; nervous and articular forms more common in goats
- Recent report of outbreak of SRLV - CAEV like (subgroup B) with maedi-visna (SRLV subgroup A) genes in a specific region of the pol gene, causing an outbreak of arthritis in sheep
- May represent an adaption of caprine virus to sheep, maintaining the capacity to cause arthritis in sheep
- Immunosuppression is not a feature of small ruminant lentiviral infection
- Three methods of transmission (in order of importance):
- Ingestion of infective colostrum or milk
- Horizontal transmission via inhalation of nasal secretions
- In utero transmission rarely or never occurs; removing newborns prior to ingestion of colostrum from infected adults is effective means of eliminating virus from herd
- CAEV targets monocytes and macrophages
- Complete viral replication and assembly only occurs in mature macrophages; although virus may infect multiple cell types; infected monocytes do not produce virus and this allows virus to remain undetected for prolonged periods
- Infected macrophages disseminate to joints, lung, CNS and mammary gland
- Alteration of synovial vessel permeability and vascular injury to synovial-lined structures result in exudation of fibrin into the joint
- Infected macrophages produce viral protein and proinflammatory cytokines that results in lymphocyte recruitment (IL-16 expression increased; TNF alpha, IL-1 beta, IL-6, and IL-12 expression are all reduced)
- Chronic inflammation or recurrent infection because of immune response to CAEV in latently infected cells; abundant anti-viral non-neutralizing antibody forms immune complexes
- Bone marrow stromal cells represent a viral reservoir in asymptomatic animals
- Mechanisms of persistent infection / ineffective host defense:
- Chromosomal genome insertion: Viral genome is inserted into DNA of host cell; selectivity and specificity of tissues (lung, brain, mammary gland, and synovia) is determined by locations where macrophages are permissive to genome integration; for example Kupffer cells are not permissive to viral transcription and lesions do not develop in the liver
- Cells harbor virus in the latent state in which viral antigens are not produced in sufficient quantities for detection and destruction by the immune system
- Dysregulation of monocyte macrophage system and ineffective immune response
- Restricted gene expression suppresses viral RNA synthesis leading to minimal virus production
- Antigenic drift: Virus is thought to escape the immune system through somatic mutation of the envelope gene; therefore immune cells are presented with a new set of antigens after each round of virus production, and antibodies produced earlier fail to eliminate altered virus
TYPICAL CLINICAL FINDINGS:
- Most goats are asymptomatic
- Neurologic: Young goats (<4 months), hindlimb lameness, head tilt, tremors, and ataxia that progresses to paresis and paralysis of all limbs (motor spinal dysfunction without signs of cerebral disease)
- Arthritis and synovitis (“big knee”): Adults, hygroma (key feature) (unilateral or bilateral), lameness, joint effusion, weight loss, primarily carpal, stifle, and hock joints; often see bilateral carpal hygroma in goats; in some herds arthritis is the only clinical finding
- Mastitis: Adults, "hard udder", firm and swollen udder at parturition with agalactia or decreased milk production
- Pneumonia: Adults and kids, exertional dyspnea and coughing
TYPICAL GROSS FINDINGS:
- Neurologic: Asymmetric brown-pink swollen areas of necrosis and inflammation in the posterior brain and spinal cord (malacia)
- Arthritis and synovitis: Serosanguinous joint effusion, thickened joint capsule and tendon sheaths, fibrin attached to synovium or hard white grains of inspissated fibrin (“rice grains”), hygromas (flattened, cystic, subcutaneous distensions over the anterior carpus filled with serosanguinous fluid containing fibrinous or gelatinous masses); soft tissue mineralization; no communication with carpal joint or tendon sheaths
- Mastitis: Swollen, firm udder
- Pneumonia: Diffuse interstitial pneumonia most severe in caudal lobes; firm, gray-pink lungs with numerous 1-2 mm gray-white foci; tracheobronchial lymphadenopathy
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Neurologic: Nonsuppurative leukoencephalomyelitis in the posterior brain and spinal cord, perivascular cuffs of lymphocytes, macrophages (foci of mononuclear inflammation), and large reticulum cells; patchy foci of demyelination and malacia
- Arthritis and synovitis: Villous synovial hyperplasia, subsynovial lymphoplasmacytic inflammation, lymphoid follicle formation with germinal centers, hyperplasia of the surface synoviocytes, fibrosis, fibrin deposition, fibrillation and erosion of cartilage in severe cases
- Mastitis: Diffuse and nodular lymphocyte infiltrates in the periductal stroma, may result in obliteration of normal structure and necrosis
- Pneumonia: Chronic lymphocytic interstitial pneumonia, with type II pneumocyte hyperplasia, lymphoid hyperplasia and formation of lymphoid cuffs around vessels and airways; intra-alveolar eosinophilic proteinaceous fluid (surfactant) and expansion of alveolar septa
ADDITIONAL DIAGNOSTIC TESTS:
- ELISA; in situ hybridization
- Immunohistochemistry (p27 capsid protein)
- Serology: Agar gel immunodiffusion (AGID) using ovine progressive pneumonia virus antigen and ELISA tests
- Chlamydophila pecorum: Proliferative and fibrinous synovitis with lymphoplasmacytic infiltrates; similar to AEV; Chlamydophila organisms in synovial cells; Giemsa or Gimenez stains
- Septicemia-arthritis syndrome: Mycoplasma mycoides subspecies mycoides, large colony type and capricolum; severe fibrinopurulent polyarthritis, mastitis, lymphadenitis, splenitis, histiocytic meningitis, glomerulitis, renal tubular degeneration and liver necrosis
- Pyogenic bacteria: Usually purulent exudate and cartilage erosion; Staphylococcus , Streptococcus sp. and coliforms most commonly
- Erysipelothrix rhusiopathiae: causes fibrinous polyarthritis (acutely) and chronic villonodular synovitis (chronically); necrotizing vasculitis and fibrin thrombi in synovial arterioles; may be able to identify the bacteria (in walls of vessels or fibrin thrombi) using Gram stain (gram-positive)
- Lentiviruses are usually species-specific
- Maedi-visna virus (MVV/ovine progressive pneumonia/SRLV subgroup A) in sheep produces diseases very similar to CAEV (SRLV subgroup B) in goats
- Ovine progressive pneumonia virus (maedi-visna virus): Interstitial pneumonia, less alveolar edema, type II pneumocyte hyperplasia not prominent; MVV can infect goats
- Interspecies transmission of SRLVs possible; CAEV can infect sheep but does not always result in clinical disease; sheep can transmit CAEV to goats
- Can be transmitted from domestic goats to wild species, i.e. Rocky Mountain goats (Oreamnos americanus)
- Other lentiviruses: Equine infectious anemia; human, simian, bovine and feline immunodeficiency viruses; Jembrana disease in cattle
- Other causes of viral arthritis:
- Feline calicivirus: acute arthritis
- Feline foamy virus (syncytium-forming): chronic polyarthritis, most often young males
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