JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
April 2022
M-V02

Signalment (JPC# 1764737): Adult crossbred goat

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Joint capsule: The synovial membrane is thickened up to 5 times normal and forms numerous wide papillary villar projections.  Hypertrophic villi are 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)

 

GENERAL DISCUSSION:

• Lentiviruses are a group of single stranded, non-oncogenic RNA viruses in genus Lentivirus in the Retroviridae family; cause diseases with long incubation periods (lentus; Latin for “slow”), persistent infection (virus never eliminated), and progressive course
• Caprine arthritis and encephalitis virus (CAEV) is one of several small ruminant lentiviruses (SRLVs); closely related to maedi-visna virus (MVV, N-V13) and ovine progressive pneumonia virus (OPPV, P-V17)
  • SRLVs previously thought to be species specific between sheep and goats but now considered to represent a genetic continuum that may infect either species; 5 genotypes (A-E); genotypes A-C known to cross species barrier; maedi-visna virus is SRLV subgroup A and is principal cause of disease in sheep whereas CAEV is SRLV subgroup B is the most pathogenic genotype for goats
• 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
• 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)
• Viral genes include:
• 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
• Pulmonary, mammary, and nervous forms most common in sheep; nervous and articular forms more common in goats
• Immunosuppression is not a feature of small ruminant lentiviral infection

 

PATHOGENESIS:

• Three methods of transmission (in order of importance):
  1. Ingestion of infective colostrum or milk
  2. Horizontal transmission via inhalation of nasal secretions
  3. 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
• Exposed mucosa à infection of local macrophages à trafficking to local lymphoid tissues (MALT) à virus released via exostosis or cellular lysis with infection of naïve macrophages à trafficking to regional lymph nodes followed by systematic distribution to all organ systems, including bone marrow à infection of immature monocyte precursor cells (reservoirs for distribution)à infected monocytes migrate via circulatory system to tissues (e.g. joints, lung, CNS, and mammary tissue) where they mature into tissue macrophages à Infected macrophages produce viral protein and proinflammatory cytokines resulting in lymphocyte recruitment (IL-8 and IL-16 expression increased; TNF alpha, IL-1 beta, IL-6, and IL-12 expression are all reduced) àinduction of chronic inflammation à vascular injury to synovial structures with exudation of plasma proteins into synovial fluid à synovial villi become undergo hypertrophy with synoviocyte hyperplasia
• SRLVs target 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
• 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
• 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
• 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)
• Mastitis: Hard, indurated udder and reduced milk production (agalactia)
• Pneumonia: Adults and kids, increased respiratory rate and dyspnea (especially during exertion)

 

TYPICAL GROSS FINDINGS:

• 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
• CNS (N-V13): Asymmetric brown-pink swollen areas of necrosis and inflammation in the posterior brain and spinal cord (malacia)
• Mammary gland: Reduced milk yield; progressive atrophy and induration of glands; mastitis (“hardbag”)
• Lung (P-V17):
• Goat: Diffuse or multifocal pale firm lesions throughout lung; firm, dense, rubbery, and enlarged lungs, stippled with small, white foci, bulge on cut surface, airway may contain mucus; caudal lung lobes most severely affected
• Sheep: Remarkably heavy, pale gray or tan, and have a diffusely firm or rubbery texture with rib imprints; failure to collapse when the chest is opened; cut surfaces bulge but are not edematous or exudative

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• 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
• CNS (N-V13): 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
• Mammary gland: Massive infiltration of lymphocytes and plasma cells into ductal and acinar interstitia; degeneration, necrosis, and loss of acini and ducts; mastitis is often a subclinical lesion, but not a presenting complaint
• Lung (P-V17):
  • Goats: Chronic interstitial pneumonia with expansion of alveolar septa by lymphocytes, macrophages, and plasma cells; formation of cuffs of lymphoid cells around blood vessels and airways; type II pneumocyte hyperplasia; and alveoli filled with abundant dense eosinophilic proteinaceous material (surfactant)
  • Sheep: Interstitial pneumonia with prominent perivascular and peribronchial/peribronchiolar lymphoid nodules with germinal centers are characteristic of Maedi; marked smooth muscle hypertrophy of terminal bronchioles and alveoli and mild interstitial fibrosis; type II pneumocyte hyperplasia is NOT a feature in OPP (in contrast with CAEV)

 

ADDITIONAL DIAGNOSTIC TESTS:

• AGID (agar gel immunodiffusion) or ELISA (serology for screening flocks; false negative and false positive may occur)
• In situ hybridization
• Immunohistochemistry (p27, gp130 viral protein)
• PCR

 

DIFFERENTIAL DIAGNOSIS:

• Chlamydophila pecorum: Proliferative and fibrinous synovitis with lymphoplasmacytic infiltrates; 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: Fibrinous polyarthritis (acute) and chronic villonodular synovitis (chronic); 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)

 

COMPARATIVE PATHOLOGY:

SRLV in other species:

• Interspecies transmission of SRLVs possible; CAEV can infect sheep but does not always result in clinical disease; sheep can transmit CAEV to goats (reservoir)
• Maedi-visna virus (MVV/ovine progressive pneumonia/SRLV subgroup A) in sheep produces disease very similar to CAEV (SRLV subgroup B) in goats
• SRLV can be transmitted from domestic goats to wild species, i.e. Rocky Mountain goats (Oreamnos americanus)

 

Lentiviruses in other species (lentiviruses are usually species-specific):

Equine infectious anemia virus  (EIAV)	Horse (H-V10)
Human immunodeficiency virus (HIV)	Human
Bovine immunodeficiency virus (BIV)	Cattle
Jembrana disease (JD)	Cattle
Feline immunodeficiency virus (FIV)	Cat
Simian immunodeficiency virus (SIV)	Nonhuman primate (N-V14, P-V19)

 

Other causes of viral arthritis:

• Feline calicivirus: Acute arthritis
• Feline foamy virus (syncytium-forming): Chronic polyarthritis; young males most often affected

 

REFERENCES:

1. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:378-379.
2. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:558-560.
3. Constable PD, Hinchcliff KW, Done SH, Grunberg W. Veterinary Medicine: A Textbook of the Diseases of Cattle, Sheep, Pigs, Goats, and Horses. 11th ed. St. Louis, MO: Elsevier; 2017:1253-1256.
4. Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:154-155.
5. Czopowicz M, Szaluś-Jordanow O, Moroz A, et al. Use of two commercial caprine arthritis-encephalitis immunoenzymatic assays for screening of arthritic goats. J Vet Diagn Invest. 2018;30(1):36-41.
6. Gayo E, Polledo L, Balseiro A, et al. Inflammatory lesion patterns in target organs of Visna/Maedi in sheep and their significance in the pathogenesis and diagnosis of the infection. J Comp Pathol. 2018;159:49-56.
7. Highland MA. Small ruminant Lentiviruses: strain variation, viral tropism, and host genetics influence pathogenesis. Vet Pathol. 2017;54(3):353-354.
8. Lopez, A, Martinson SA. Respiratory system, thoracic cavities, mediastinum, and pleurae. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:620-621.
9. Miller AD, Porter BF. Nervous system. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:970.
10. Nardelli S, Bettini A, Capello K, Bertoni G, Tavella A. Eradication of caprine arthritis encephalitis virus in the goat population of South Tyrol, Italy: analysis of the tailing phenomenon during the 2016-2017 campaign. J Vet Diagn Invest. 2020;32(4):589-593.
11. Pérez M, Biescas E, Reina R, et al. Small Ruminant Lentivirus–Induced Vet Pathol. 2015;52(1):132–139.
12. Pinczowski P, Sanjosé L, Gimeno M, et al. Small Ruminant Lentiviruses in Vet Pathol. 2017;54:413–424.
13. Stanton JB, Zachary JF. Mechanisms of microbial infections. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St Louis, MO: Elsevier; 2022:255.

 

Click the slide to view.

---