JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
AUGUST 2022
I-B08

 

Signalment (JPC # 2643733):  10-day-old piglet.

HISTORY:  This piglet had rectangular, sharply demarcated, bright red to purplish skin lesions and dark red discoloration of the ears.

HISTOPATHOLOGIC DESCRIPTION:  Haired skin, subcutis, and panniculus carnosus:  Diffusely, vessels in the dermis, subcutis and panniculus carnosus exhibit one or more of the following changes: dilation with marked congestion; infiltration of the vessel wall by fibrin, necrotic debris, hemorrhage (fibrinoid or necrotizing vasculitis) and occasionally low numbers of lymphocytes, plasma cells and neutrophils; attenuation or loss of the endothelium; occlusion by fibrin thrombi; hypertrophied (reactive) endothelium; and vacuolation of the tunica media which is often lined by lamellations of fibrous connective tissue.  There is frequent perivascular hemorrhage, fibrin and edema, as well as occasional perivascular infiltrates of lymphocytes, plasma cells and neutrophils admixed with small amounts of necrotic debris.  There is a subepidermal band of hemorrhage and fibrin, which extends into the subcutis.  There is multifocal intracellular edema within the epidermis.  Apocrine glands are multifocally dilated.

Skeletal muscle: The underlying skeletal muscle exhibits similar vascular changes.  The epimysium, perimysium and endomysium are variably expanded by edema and hemorrhage. 

MORPHOLOGIC DIAGNOSIS:  1. Haired skin, subcutis and panniculus carnosus:  Necrotizing and fibrinoid vasculitis, acute, multifocal, moderate, with fibrin thrombi, hemorrhage and edema, breed unspecified, porcine.

2. Skeletal muscle: Necrotizing and fibrinoid vasculitis, acute, multifocal, moderate, with fibrin thrombi, hemorrhage and edema.

ETIOLOGIC DIAGNOSIS:  Cutaneous erysipelas

CAUSE:  Erysipelothrix rhusiopathiae

CONDITION:  Swine Erysipelas (SE)

SYNONYMS:  Diamond skin disease

GENERAL DISCUSSION:

• A gram-positive, non-spore forming, facultative anaerobic bacillus with a worldwide distribution; at least 28 known serotypes; can survive/grow in decaying material of animal origin; resistant to many disinfectants and is zoonotic.
• Outbreaks in pigs, lambs, birds, cetaceans, and sporadic disease in other domestic species
• Swine are the most important reservoir and are the principal source of infection for other pigs
  • Healthy swine harbor the organism for months in their tonsils or other lymphoid tissue, intestine, bone marrow and gallbladder
  • Swine from 2-12 months of age and pregnant sows are most susceptible
  • Three manifestations: Acute septicemic form (usually fatal), mild subacute form (also septicemic), chronic form (in some surviving animals)
  • Epidemics typically associated with septicemic form; but sporadic cases in endemic areas and can be associated with septicemia, polyarthritis or endocarditis
  • Vaccination helps prevent acute syndrome, but it may increase susceptibility to polyarthritis

PATHOGENESIS:

• Cutaneous and renal lesions: Septicemiaà bacterial embolization to the skin or glomeruli à systemic vasculitis and/or thrombosis → ischemia and infarction
• Cutaneous vasculitis in pigs is most associated with rhusiopathiae.
  • Cutaneous vasculitis → Cell lysis and infarction of skin
• Embolic nephritis: Spreads to the kidney because of bacteremia related to development of septic valvular endocarditis. The most common cause of embolic nephritis in swine is rhusiopathiae.
• Vegetative valvular endocarditis: Selective adherence to vascular endothelium of porcine heart valves, especially at base of chordae tendinae; immunologic cross reaction between rhusiopathiae antigens and valvular/myocardial antigens
  • Portions of vegetative lesions can travel as emboli to distant vessels/organs (bland= just thrombotic material; septic= thrombotic material and enmeshed bacteria)
• Mechanism of injury is cell lysis and infarction of skin secondary to cutaneous vasculitis.
• Transmission is primarily oral, with infection of palatine tonsils, GALT, or GI mucosa through ingestion of fomites and body fluids contaminated with the bacteria. Less commonly through skin abrasions, or bites of infected flies
  • Likely a commensal organism residing in the biofilm of mucosae of pharynx and tonsillar epithelia of healthy pigs. Environmental stressors allow the bacteria to replicate in sufficient numbers in some animals and become contagious to others.
• Grows and replicates in macrophage phagosomes/phagolysosomes, which isolates it from the immune system → spreads via leukocyte trafficking and infects additional macrophages.
• May have a tropism for vascular endothelium; cell lysis is due to direct infection by bacteria; bacterial neuraminidase may activate alternative complement pathway
• Virulence factors:
  • Neuraminidase activity may be involved with invasion of the mucus layer of the pharyngeal mucosa (removes sialic acid from glycoproteins/glycolipids/ polysaccharides expressed on target cells->exposing new receptors for bacterium); may also aid in attachment and invasion of endothelial cells leading to vasculitis, thrombosis, infarction, and DIC.
  • Capsular polysaccharides inhibit phagocytosis of bacterium by neutrophils (to a limited extent macrophages as well) and block oxidative burst and prevent killing of bacteria by molecules in lysosome
  • Surface proteins such as adhesins (thought to bind to macrophage and endothelial cell surface receptors), RspA/ RspB important in early biofilm formation
  • Invasins (hyaluronidase)-Spreading factor that damages extracellular matrix of connective tissues
  • Enzymes (superoxide dismutase & catalase)- block effect of respiratory burst and oxygen free radicals

TYPICAL CLINICAL FINDINGS:

• Acute/septicemic: Sudden onset of pyrexia, depression, lethargy, anorexia, lameness, abortion, blue-to-purple discoloration of the skin (abdomen, pinnae, and legs), diamond skin lesions, sudden death
• Subacute: Animals are asymptomatic or have less severe signs of mild fever, inappetence, and erythematous rhomboid urticarial skin lesions, often over belly, ears, tail, posterior thighs, and jowls (fewer lesions), infertility/mummies/small litters
• Chronic: May follow acute, subacute or subclinical disease; various degrees of lameness and joint enlargement; slow growth rate; and signs of cardiac insufficiency, especially after exertion; arthritis (+/- associated with earlier infection), necrosis and sloughing of the plaques →ulceration, distal extremities may slough.

TYPICAL GROSS FINDINGS:

• Acute/subacute:
  • Multifocal, well defined, red to purple square to rhomboidal (diamond; this is the shape of the vascular field) slightly raised skin lesions involving ears, ventral abdomen, and legs
  • Petechiae and ecchymoses of the epicardium, atrial myocardium, renal cortex, other serous membranes
  • Enlarged, congested liver & spleen
    • Can cause noncongested splenomegaly, called “meaty” spleen
  • Fibrinous polyarthritis; increased volume of synovial fluid, hyperemic synovial membrane (organisms may be isolated during acute phase)
• Chronic:
  • Chronic villonodular synovitis; thickened joint capsule with hyperemic and thick synovial membrane; deformed articular surface and cartilage erosion
  • Lesions in chronic erysipelas arthritis vary in severity.
  • Ankylosis & discospondylitis
  • Necrosis of tail, ears and rhomboidal lesions
  • Vegetative valvular (mitral valve most common) and mural endocarditis

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Acute/subacute:
  • Dermis/subcutis: Septic emboli lodged in small to medium sized arteries in deep dermis and panniculus; Dilated and congested vasculature with neutrophilic vasculitis, cutaneous necrosis,  microthrombi, bacterial emboli and infarction, accumulation of albuminous precipitates around blood vessels
    • Similar hyperemia, necrosis, vasculitis, neutrophilic infiltrates in brain, heart, kidneys, lungs, liver, spleen, synovial membranes
  • Characteristic renal lesion is focal fibrinoid necrosis of the glomerular capillary tufts with thrombi and intracapsular hemorrhage or small abscesses within the interstitium; bacterial colonies are occasionally found in the necrotic tufts (embolic nephritis)
  • Fibrinous polyarthritis +/- necrotizing vasculitis & fibrin thrombi in synovial arterioles
  • Long rod, free in interstitial areas and within vacuoles of inflammatory cells.
  • Alveolar septae- lymhpoplasmacytic infiltrates, microthrombi, and alveolar edema.
  • Corneal edema and panuveitis with fibrinoid vasculitis.
• Chronic:
  • Joint disease: Proliferative nonsuppurative fibrinous arthritis; hypertrophic synovial lining with villus hypertrophy to extensive villus hyperplasia; excess synovial fluid; hyperemic, mononuclear villous infiltration, including plasma cells; pannus formation and cartilage degeneration; diskospondylitis; vertebral osteomyelitis.
  • Vegetative valvular endocarditis: Thickened valves with granulation tissue, fibrin, connective tissue proliferation, bacterial colonies, necrosis

DIAGNOSIS: Gold standard is culture; IHC has been shown to be highly sensitive and specific in animals treated with antibiotics

 

DIFFERENTIAL DIAGNOSIS:

• Septicemia and sudden death:
  • Salmonella choleraesuis: Anorexia, septicemia, lethargy, pyrexia, diarrhea (gram-negative bacillus), blue-purple discoloration of skin on ears, ventral abdomen, snout, and tail.
  • Actinobacillus suis or Actinobacillus pleuropneumoniaea: Pyrexia, cyanosis, petechial hemorrhages, congestion & necrosis of feet, tail, ears. In adult pigs: pyrexia, respiratory signs, anorexia
  • Haemophilus parasuis (Glasser’s Disease): Sudden death
  • Streptococcus suis: Septicemia with cases of endocarditis and polyarthritis
  • Pasteurella multocida: Similar skin lesions
• Skin lesions:
  • Classical swine fever virus: Hyperemic skin and hemorrhages (abdomen, inner thighs, ears) or a purple cyanotic discoloration (snout, ears, and tail)
  • Porcine Dermatitis and Nephropathy Syndrome (PDNS): Characterized by necrotizing and neutrophilic vasculitis in skin and kidney; type III hypersensitivity reaction; often associated with porcine circovirus 2 (PCV2); other associated organisms include: PRRSV, Torque teno virus (arterivirus), Staphylococcus hyicus, Pasteurella multocida and Streptococcus suis
  • suis septicemia: See above.
  • Porcine Circovirus Associated Diseases (PCVD): Red-purple, osccasionally raised skin lesions starting in the hind and extending to the ventrum à whole body

COMPARATIVE PATHOLOGY:

• Lambs: Usually no history of contact with swine; thought to be percutaneous infection through the umbilicus, docking and castration wounds, shearing wounds, and cuts or abrasions acquired during dipping- May be confined to point of entry of bacteremia with localization to joints, rarely death by septicemia
  • Fibrinopurulent polyarthritis and osteomyelitis dominate in young lambs after docking or castration, and sometimes following umbilical infections. Mortality is low, consequence of severe lameness disproportionate to gross changes in affected feet.
    • Histologically, lymphocytes and plasma cells in synovium and neutrophils in synovial fluid.
  • Cutaneous infections following dipping area associated with contamination of non-bactericidal dips with E. rhusiopathiae.
    • Cutaneous lesions typically affect the fetlocks; hot, swollen pasterns with regional lymphadenitis
    • Histologically
      • Epidermis- superficial pustules
      • Dermis- perivascular edema, accumulation of neutrophils, and cellular thrombi within vessels → deep dermis- suppurative hidradenitis, necrotizing vasculitis, and vascular thrombosis
        • Similar changes occur in the sensory laminae of the foot → severe lameness
      • Glomerulonephritis
      • Occasional amyloidosis of spleen or liver
    • Avian Species
      • Turkey: Most common/severe avian species affected are turkeys: Especially susceptible to acute septicemia and sudden death; typically show signs of acute septicemic disease characterized by vascular damage/ thrombosis (cyanotic combs, petechial hemorrhages in muscle, pericardial fat, serous/mucus membranes), marked splenomegaly; with chronic disease- polyarthritis and vegetative valvular endocarditis; adult toms most commonly affected.
      • Penguin: rhusiopathiae caused an outbreak of illness and mortality in five Humboldt penguins. The likely cause of infection was contaminated fish.
      • Seabirds: rhusiopathiae was detected in island seabirds of New Zealand indicating that they are possible reservoirs and may be the source of spill over to other special on the islands.
      • Consider rhusiopathiae in all avian species when acute septicemia is suspected as the cause of mortality. Mortality can occur in the absence of other clinical signs.
    • Cetaceans:
      • Acute fatal septicemia- sudden death with ascites and mottled livers
        • Histologically- moderate multifocal necrotizing lymphadenitis and hepatitis with hepatic capsular edema
      • Mild form- clear rhomboid shaped patch of skin discoloration and ulcerative dermatitis, inappetence, inflammatory leukogram
    • Dogs: Rhusiopathiae can cause endocarditis in dogs. There is one case of erysipeloid in the dog.
    • Wild boar: Lesions in wild boars are similar to those in porcine erysipelas. Boars may also be an important vector for infection of commercial swine herds.
    • Nonhuman primates: Two reports documented erysipelothrix in nonhuman primates that caused septicemia and death.
    • Muskoxen: In free ranging muskoxen rhusiopathiae has been associated with widespread mortalities. Authors utilized a case study of coinfection to propose that skin affected by orf virus lesions is more susceptible to E. rhusiopathiae and subsequent septicemia and death.
    • Goats: rhusiopathiae was isolated from a 5 day old kid found dead on a farm that experienced a 70% mortality rate during one kidding season. Gross findings were focally extensive hemorrhage along the remnants of the urachus and umbilical arteries and the apex of the urinary bladder. E. rusiopathiae was observed in tissues from the lung, heart, liver, skeletal muscle, kidney, and thymus.

 

REFERENCES:

1. Bobrek K, Gaweł A. Erysipelas Outbreaks in Flocks of Geese in Poland—Biochemical and Genetic Analyses of the Isolates. Avian Diseases. 2015;59(3):436-439.
2. Brogden, Kim A. Cytopathology of Pathogenic Prokaryotes. In: Cheville NF, ed. Ultrastructural Pathology: The Comparative Cellular Basis of Disease. 2^nd Ames, IA; 2009: 447.
3. Craig LE, Kittmer 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: 102, 149-150.
4. Crespo R, Franca MS, Fenton H, Shivaprasad HL. Galliformes and Columbiformes. In: Terio KA, McAloose D, St. Leger J. ed. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 762.
5. Ersdal C, Jørgensen HJ, Lie KI. Acute and chronic Erysipelothrix rhusiopathiae infection in lambs. Vet Pathol. 2015; 52(4): 635-643.
6. Fulton RM. Bacterial Disease. In: Boulianne M. ed. Avian Disease Manual. 7^th Jacksonville, FL: Omnipress; 2013: 94.
7. Gal A, Castillo-Alcala F. Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels. In: Zachary JF eds. Pathologic Basis of Veterinary Disease. 7th ed. Louis, MO; 2022: 689-690.
8. Gerber PF, Macleod A, Opriessnig T. Erysipelothrix rhusiopathiae serotype 15 associated with recurring pig erysipelas outbreaks. Veterinary Record. 2018;182(22):635-635.
9. Jayasinghe M, Midwinter A, Roe W, et al. Seabirds as possible reservoirs of Erysipelothrix rhusiopathiae on islands used for conservation translocations in New Zealand. Journal of Wildlife Disease. 2021; 57(3): 534-542.
10. Jimenez Martinez MA, Gasper DJ, del Carmen Carmona Mucino M, Terio KA. Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J. ed. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 216-217.
11. Mauldin EA, Peters-Kennedy J. Integumentary System. In: Maxie MG ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016: 612, 645.
12. Opriessnig T, Wood RL. Erysipelas. In: Straw BE, Zimmerman JJ, et al. eds. Diseases of Swine. 10th ed. Ames, IA: Blackwell Publishing; 2012: 750-759.
13. Palm HA, Thirumalapura NR, Boger LA, Ringler SR. An unusual outbreak of erysipelas on a goat farm in Pennsylvania. Journal of Veterinary Diagnostic Investigation. 2022; 34(2); 268-272.
14. 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: 30-31, 167.
15. Silva AP, Cooper G, Blakey J, et al. Retrospective summary of Erysipelothrix rhusiopathiae diagnosed in avian special in California (2000-19). Avian Diseases. 2020; 64(4); 499-506.
16. Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF eds. Pathologic Basis of Veterinary Disease. 7th ed. Louis, MO; 2022: 182, 235-236.
17. Sula MM, Lane LV. The Urinary System. In: Zachary JF eds. Pathologic Basis of Veterinary Disease. 7th ed. Louis, MO; 2022: 733, 719, 749-750.
18. Leger J, Raverty S, Mena A. Cetacea. In: Terio KA, McAloose D, St. Leger J. ed. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 555-556.
19. Tomaselli M, Ytrehus B, Opriessnig T, et al. Contagious ecthyma dermatitis as a portal of entry for Erysipelothrix rhusiopathiae in Muskoxen (Ovibos moschatus) of the Canadian arctic. Journal of Wildlife Diseases. 2022; 58(1); 228-231.
20. Welle MM, Linder KE. The Integument. In: Zachary JF eds. Pathologic Basis of Veterinary Disease. 7th ed. Louis, MO; 2022: 1231.
21. Xie S, Hsu CD, Tan BZY, et al. Erysipelothrix Septicaemia and Hepatitis in Colony of Humboldt Penguins (Spheniscus humboldti). Journal of Comparative Pathology. 2019; 172; 5-10.

Click the slide to view.

---