JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM 

November 2023

U-B09

 

Signalment (AFIP #1946321): 3-year-old crossbred sow

 

HISTORY: An outbreak of disease occurred on a large swine breeding facility. Symptoms common to a majority of the sick animals were anorexia, high fever, cyanosis and abortion.  

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Multifocally glomerular tuft and interstitial capillaries contain brightly eosinophilic, hyalinized fibrin thrombi. Mild edema and fibrin accumulation are present within the tunica adventitia and perivascular tissues of arcuate and intralobular arteries as well as hypertrophy of vascular endothelium. Multifocally, the interstitium contains a few small aggregates of lymphocytes, plasma cells, macrophages, and occasional neutrophils. Multifocally tubular epithelial cells exhibit one or more of the following changes: flattening and attenuation; increased cytoplasmic volume and vacuolation (degeneration); shrunken cells with bright eosinophilic cytoplasm, angular margins and dense to pyknotic nuclei (necrosis); sloughing of epithelium into tubular lumina, and accumulation of few erythrocytes and small amounts of flocculant eosinophilic debris. There are moderate multifocal autolytic changes. 

 

MORPHOLOGIC DIAGNOSIS: Kidney, glomerular and interstitial capillaries: Fibrin thrombi, acute, multifocal, moderate with lymphoplasmacytic and neutrophilic interstitial nephritis, perivascular edema, and mild tubular degeneration and necrosis, crossbred pig, porcine. 

 

ETIOLOGIC DIAGNOSIS: Renal erysipelas

 

CAUSE: Erysipelothrix rhusiopathiae 

 

CONDITION: Swine erysipelas; “diamond skin disease”

 

GENERAL DISCUSSION:  

• Ubiquitous gram-positive, facultative anaerobic bacillus that is both a commensal and pathogen in wide range of vertebrates  
• Swine are the most important reservoir of the organism  

• Approximately 30-50% of healthy swine harbor the organism in their tonsils or other lymphoid tissue, and shed the organism in urine, saliva, vomitus, and feces 
• Pigs are the principal source for infection of other pigs despite persistence of organism within the environment

• Most common bacterial cause of embolic nephritis in pigs
• Swine 2-12 months old and pregnant sows are most susceptible; skin lesions may occur in pigs up to 3 years of age
• Disease manifestations include: septicemia (acute), cutaneous lesions (acute), polyarthritis (chronic), endocarditis (chronic), discospondylitis and septic emboli in the CNS

• In epidemics, septicemia is the predominant form. Endemic populations see chronic forms and vaccination may enhance susceptibility to polyarthritis.

 

PATHOGENESIS:  

• Pigs encounter the organism via ingestion, contamination of cutaneous wounds, or bites of infected flies; E. rhusiopathiae is also a commensal and stress or other conditions may precipitate disease 
• Neuraminidase: Virulence factor that helps invade the mucus layer of the pharynx by removing sialic acid from host cells possibly exposing receptors for the bacteria, to include endothelial cells (and involvement with subsequent vasculitis)
• Other virulence factors include capsular polysaccharides (antiphagocytic properties; blocks effects ox oxidative burst), surface proteins (surface protective antigens; also play a role in biofilm formation), invasins (e.g. hyaluronidase to help invade tissues), and superoxide dismutase and catalase (enhance survival by blocking respiratory burst effects) 
• Acute systemic erysipelas: Invades through tonsils or GALT > infects and replicates in macrophages > travel to regional lymph nodes and infect additional macrophages > bacteremia > endothelial swelling of capillaries & venules > bacteria can invade endothelial cells > fibrinoid necrosis > fibrin thrombi > ischemia & infarction > organ/tissue necrosis  
• Chronic erysipelas: Bacterial neuraminidase may activate the alternative complement pathway > complement-derived chemotactic messengers > injury to capillary beds; this may contribute to vegetative valvular endocarditis and arthritis that occurs in the chronic septicemic form of the disease 

    

TYPICAL CLINICAL FINDINGS:

• Acute erysipelas:  
  • Sudden onset, sometimes sudden death in one or more animals in the herd
  • High fever (104-108 degrees F)
  • Fibrinous polyarthritis
  • Painful joints with a stiff, stilted gait and/or reluctance to move
  • Erythematous rhomboid urticarial skin lesions, often over abdomen, ears, tail, posterior thighs and jowls
  • Abortions
• Chronic erysipelas:  
  • Arthritis is common; varying degree of severity; diskospondylitis
  • Slow growth rate
  • Signs of cardiac insufficiency, especially after exertion

 

TYPICAL GROSS FINDINGS: 

• Cutaneous vasculitis with dermal infarcts
  • Characteristic erythematous cutaneous lesions are rhomboid (diamond-shaped), slightly raised, light pink to dark purple, and vary in number;  the skin lesions may be necrotic and eventually peel off 
• Edematous and congested lungs 
• Petechiae and ecchymoses of the epicardium, atrial myocardium, and renal cortex 
  • Multifocal regions of pinpoint hemorrhage in renal cortex (in glomeruli), OR multifocal tan-white foci of infiltrate in interstitium
• Enlarged spleen 
• Congested to hemorrhagic lymph nodes  
• Chronic villonodular synovitis 
  • Joints (most commonly hock, stifle, elbow, and carpal): excessive serosanguinous synovial fluid, variably hyperemic and proliferative synovial membrane, fibrous synovial “tags” that project into the joint cavity, and synovitis and articular cartilage destruction leading to ankylosis  
• Vegetative valvular (mitral valve most common) and mural endocarditis   

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Capillaries & venules in skin, heart, kidney, lung, liver, CNS, skeletal muscle and synovium may have swollen endothelial cells with adherent monocytes, fibrin thrombi and bacteria often arranged side by side in a radial fashion near the surface of the thrombi  
  • Small foci of encephalitis common in pigs with valvular endocarditis, in addition to renal lesions
• Perivascular lymphocytes and macrophages predominate, with fewer neutrophils as acute lesions become subacute
• Circulatory stasis may cause focal necrosis in affected tissues  
• Lung: Acute interstitial pneumonia
• +/- Glomerular hemorrhage and inflammation and rare tubular necrosis  
• Joints: Mononuclear infiltrate, proliferative synovitis, cartilage erosion, and osteitis  
• Valvular granulation tissue with fibrin and masses of bacteria
• In skin: Dermal congestion, neutrophilic vasculitis, cutaneous necrosis, and suppurative hidradenitis.

 

ADDITIONAL DIAGNOSTIC TESTS:

• Gram stain
• Culture
• Serology
• PCR
• PTAH- highlights thrombi purple/blue

 

DIFFERENTIAL DIAGNOSIS:

• For “Turkey egg kidney”:
  • Hog Cholera (Pestivirus) – Splenic infarction, if present, is pathognomonic
  • Salmonella choleraesuis – Paratyphoid nodules in the liver
  • African Swine Fever (“Asfarviridae”) – Splenomegaly
  • Porcine dermatitis and nephropathy syndrome – Severe necrotizing and leucocytoclastic (presence of neutrophils with nuclear fragments) vasculitis; red to purple macules and papules that often coalesce forming irregular patches and plaques over perineum and lower limbs
  • Septicemia due to other bacteria such as Streptococcus spp.,Actinobacillus spp, or Haemophilus (Glaeserella) parasuis
• For cutaneous lesions:
  • Dermatosis vegetans; porcine juvenile pustular and psoriasiform dermatitis; swine pox

 

COMPARATIVE PATHOLOGY:

• Sheep: Percutaneous infection via umbilicus, docking/shearing/castration wounds; no history of contact with swine (often acquired via contaminated non-bactericidal dips); bacteremia/septicemia with fibrinopurulent polyarthritis & osteomyelitis in lambs usually around the fetlocks; necrotizing glomerulonephritis and amyloid deposits in liver and spleen in chronic cases, as well as necrosis of Purkinje cells in brain
• Turkeys: Important disease in turkeys; acute septicemia most common – vascular damage with thrombosis (snood commonly affected; petechial hemorrhages in muscle, pericardial fat, serous/mucus membranes); chronic form – polyarthritis and endocarditis; older toms most commonly infected
• Wild boar: Uncommon; lesions similar to domesticated swine 
• Calves: Rare arthritis (tibiotarsal, stifle, and carpal) and encephalomeningitis
• Lab animals (rats): Fibrinopurulent polyarthritis, myocarditis, and endocarditis
• Chickens: Enteritis, salpingitis and peritonitis (manifest as decrease in egg production), petechiation of pericardial and abdominal fat, splenomegaly and hepatomegaly with multifocal areas of necrosis. 
• Goats: Typically are resistant to infection, but may succumb if exposed to large amounts of the organism (e.g. if co-housed with swine and/or poultry – see JVDI  Palm et al 2022)
• Cetaceans: Cutaneous vasculitis (“Diamond Back”) or peracute to subacute septicemia
• Dogs: Case report of erythematous/purpuric macules and lethargy/fever mirroring porcine presentation of the disease (Marshall et. al, Vet. Derm.; 2019)
• Penguins: Case report of an outbreak among captive Humboldt Penguins causing septicemia and hepatitis; fish may be a possible source of infection
• Fish: Reports of disease among eel, barramundi; may affect a wider group of teleosts
• Pribilof arctic foxes: Shaggy, lame fox syndrome (suspected)

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016: 141.

2. Chang RK, Pomaranski EK, Giray C et al.. spaB-positive Erysipelothrix rhusiopathiae, a novel teleost pathogen isolated from cultured barramundi. J Vet Diagn Invest. 2023 Nov 2. doi: 10.1177/10406387231209035. Epub ahead of print.

3.  Cianciolo RE, Mohr, FC.   Urinary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed.  St Louis, MO: Elsevier; 2016: 433.

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: 149-151.

5.  Crespo R, Franca MS, Fenton H, et al.  Galliformes and Columbiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 756..

6.  Ersdal C, Jørgensen HJ,  and Lie K-I.  Acute and Chronic Erysipelothrix rhusiopathiae Infection in Lambs.  Vet Pathol.  2015; 52(4): 635-643.

7. Eriksson H.  Erysipelas. In: Swayne DE ed. Diseases of Poultry. Vol. 2.  14^th ed. Hoboken, NJ: Wiley; 2020: 1010-1018. 

8. Gal A, 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; 2022:643-698.

9. Gerber PF, Macleod A, Opriessnig T. Erysipelothrix rhusiopathiae serotype 15 associated with recurring pig erysipelas outbreaks. Vet Record. 2018; 182(22): 635-635.

10. Fulton, RM. Bacterial diseases.  Boulianne M. Avian disease manual. 8th ed; 2019. Jacksonville, FL: OmniPress. 82-84.

11. Marshall KR, Walton SA, Boyd M, et al. Erysipeloid lesions caused by Erysipelothrix rhusiopathiae in a dog: clinical and histopathological findings, molecular diagnosis and treatment. Vet Dermatol. 2019;30: 434-e134.

12.  Martinez MAJ, Gasper DJ, Mucino MCC, et al.  Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 216-7.

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14. Miller LM, Gal A. Cardiovascular system and lymphatic vessels. In Zachary JF, ed. Pathologic Basis of Veterinary Disease.  6th ed. St. Louis, MO:  Elsevier; 2017: 608.

15. Opriessnig T, Coutinho TA.  Erysipelas. In: Zimmerman JJ et al eds.  Diseases of Swine. 11^th Ed. Hoboken, NJ: Wiley; 2019: 835-843. 

16. Palm HA, Thirumalapura NR, Boger LA, Ringler SR. An unusual outbreak of erysipelas on a goat farm in Pennsylvania. J Vet Diagn Invest. 2022;34(2):268-272. 

17. 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:  30-32.

18.  Shimoji Y, Bito M, Shiraiwa K, et al. Disassociation of Spa type and serovar of an Erysipelothrix rhusiopathiae serovar 6 strain isolated from a diseased pig. J Vet Diagn Invest. 2019;31(3):488-91.

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20. Spraker TR, White PA.  Shaggy lame fox syndrome in Pribilof island arctic foxes (Alopex lagopus pribilofensis), Alaska.  Vet Pathol.  2017: 54(2): 258-268.

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25. Xie S, Hsu CD, Tan BZY, et al. Erysipelothrix septicaemia and hepatitis in a colony of Humboldt penguins (Spheniscus humboldti). J Comp Pathol. 2019;172: 5-10.

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