JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
September 2022
I-M33

Signalment (JPC #2839300):  5-month-old male castrated crossbred Sus scrofa (domestic swine)

HISTORY:  This animal was one of two affected in a group of 1000.

HISTOPATHOLOGIC DESCRIPTION:  Haired skin and subcutis:  Multifocally, small to medium sized arteries within the superficial dermis and to a lesser extent within the deeper dermis and subcutis are characterized by transmural infiltration of vessel walls by moderate numbers of viable and necrotic neutrophils with occasional eosinophils and macrophages, eosinophilic cellular and karyorrhectic debris (necrosis), hemorrhage, fibrin, and edema (necrotizing leukocytoclastic vasculitis). The inflammatory infiltrate and fibrin often extend into the surrounding dermis and subcutis. There is perivascular and periadnexal edema. There is multifocal full-thickness infarction of the overlying epidermis and associated hair follicles characterized by retention of cellular architecture with loss of differential staining and pyknotic nuclei (coagulative necrosis). There is mild epidermal hyperplasia with anastomosing rete ridges, acanthosis, and mild orthokeratotic hyperkeratosis with occasional intracorneal clusters of necrotic neutrophils and cellular debris (intracorneal pustule).  Apocrine glands are moderately ectatic.

Kidney:  There is diffuse, global necrotizing and neutrophilic glomerulitis characterized by glomerular tufts with replacement by numerous viable and degenerate neutrophils, necrotic debris, and abundant fibrin that extends into and fills Bowman's space; there are frequent fibrin thrombi within glomerular capillaries. Occasionally, there is periglomerular hemorrhage and multifocally the parietal and visceral epithelium of Bowman’s capsule is fused (synechia). There is necrotizing vasculitis of the arcuate vessels with associated hemorrhage, fibrin, and mild perivascular edema. Neutrophils, lymphocytes, and macrophages expand the interstitium, separating and surrounding tubules. Multifocally, tubules are mildly ectatic, often lined by attenuated epithelium, and often filled with an eosinophilic homogenous fluid (proteinosis), occasional cellular debris (cellular casts), or rarely, degenerate neutrophils. Tubular epithelial cells are swollen and contain numerous, variably sized amphophilic vacuoles (degeneration).

MORPHOLOGIC DIAGNOSES:  1. Haired skin and subcutis: Vasculitis, necrotizing, leukocytoclastic, acute, multifocal, severe, with epidermal infarcts, crossbred swine, porcine.

2. Kidney: Glomerulitis and vasculitis, fibrinonecrotizing, neutrophilic, acute, diffuse, severe, with fibrin thrombi, tubular degeneration, proteinosis, and cellular casts.

CONDITION:  Porcine dermatitis and nephropathy syndrome (PDNS)

GENERAL DISCUSSION:

• Necrotizing and neutrophilic systemic vasculitis affecting primarily the skin and kidneys in feeder pigs
• General characterization of vasculitis based on leukocyte type:
  • Neutrophilic vasculitis - can be leukocytoclastic (with neutrophil karyorrhexis producing a “nuclear dust” in the vessel wall) or not; can mature into a lymphocytic vasculitis
    • Examples: hypersensitivity reactions (e.g. equine purpura hemorrhagica, urticarial vasculitis), septicemia (e.g. salmonellosis, diamond skin disease), direct vascular infection (e.g. Rocky mountain spotted fever), fungal and some viral infections (e.g. PDNS), autoimmune disease (e.g. SLE, drug-reactions, Shar Pei fever syndrome)
  • Lymphocytic vasculitis – uncommon
    • Examples: dermatomyositis, vaccine-induced panniculitis/vasculitis, malignant catarrhal fever
  • Eosinophilic vasculitis – rare
    • Examples: arthropod injury, drug or vaccine reactions, horses with vascular oomycete or fungal infections, feline herpesvirus-1 infections
  • Granulomatous vasculitis – exceedingly rare
    • Examples: Bartonella , mycobacterial or fungal infections

PATHOGENESIS:

• Unknown; thought to be immune mediated type III hypersensitivity (deposition of immune complex in vessel walls)
  • Studies suggest association with porcine circovirus 2 (PCV-2) or porcine circovirus 3 (PCV-3) infection and/or the antibody response to these viruses; affected pigs have high serum antibody titers for PCV-2 and PCV-2/PCV-3 nucleic acids present in the skin lesions
  • However experimental infection with PCV-2 does not produce these lesions (PCV-3 can); co-infection with other viruses (e.g. swine torque teno sus virus [TTSuV or TTV], multiple PCV types) may be required
• Vasculitis is primary lesion

TYPICAL CLINICAL FINDINGS:

• Incidence is low (<1%), but epizootics can occur with 10-20% of pigs affected; mortality is high (80-90%)
• Mildly affected pigs only have skin lesions and usually eventually recover
• Severely affected pigs also develop systemic signs including anorexia, depression, hyperthermia, stiff gait reluctance to move, weight loss, dyspnea or tachypnea, and severe subcutaneous edema

TYPICAL GROSS FINDINGS:

• Skin (acute): Round to irregular, red to purple (hemorrhagic) macules and papules on the ears, limbs, abdomen, thorax, and perineum that occasionally coalesce into large, irregular patches and thin plaques
• Skin (chronic): Lesions develop dark crusts and fade, sometimes scaring
• Kidneys: Bilaterally enlarged, edematous, and pale with petechial hemorrhages

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Cutaneous lesions: Necrotizing neutrophilic (or leukocytoclastic) vasculitis of small to medium arteries/arterioles in the dermis and panniculus  
• Accompanied by hemorrhage, edema, fibrin deposition, thrombosis and infarction
• Lesions in other organs:
• Leukocytoclastic vasculitis in renal pelvis and synovium
• Glomerulonephritis with exudation in tuft, cellular crescent formation and interstitial nephritis

ADDITIONAL DIAGNOSTIC TESTS:

• Clinical signs are strongly suggestive but not pathognomonic; diagnosis often made based on gross and microscopic post-mortem examination
• Immune complex deposition identified in vessel walls and glomeruli

DIFFERENTIAL DIAGNOSIS:

• Erysipelothrix rhusiopathiae (I-B08): most common cause of cutaneous vasculitis in pigs; diamond shaped lesions
• Classical or African swine fever (H-V05, H-V06) – hyperemic, hemorrhagic skin or purple cyanotic discoloration
• Septicemia (e.g. Actinobacillus suis, A. pleuropneumoniae, Haemophilus parasuis, Staphylococcus hyicus, Pasteurella multocida, Streptococcus suis, Salmonella choleraesuis, E. coli) – may cause petechial hemorrhages
• PRRSV (P-V25) – may cause skin hemorrhage
• Vitamin E and selenium imbalance- microangiopathy

COMPARATIVE PATHOLOGY:

• PCV-2 has been associated with multiple syndromes in pigs included postweaning multisystemic wasting disease (PMWS) or PCV2-systemic disease (PCV2-SD), PCV2-associated pneumonia, PCV2-associated enteritis, PDNS, PCV2-associated reproductive failure, and PCV2-associated cerebellar vasculitis; these now go by the collective name of porcine circovirus-associated disease (PCVAD)
• Dogs: Cutaneous and renal glomerular vasculopathy (CRGV) or “Alabama rot” in Greyhounds; idiopathic; characterized by a thrombotic microangiopathy and fibrinioid vascular necrosis causing multifocal erythematous, edematous and/or ulcerated skin lesions, thrombocytopenia, and oligoanuric acute kidney injury with numerous fibrin thrombi within glomeruli
• Horses: leukoclastic vasculitis can be seen with purpura hemorrhagica (secondary to IgA and streptococcal M protein depositing in vessels walls) and pastern leukoclastic vasculitis (unknown cause; possibly related to sun exposure, drugs, plant toxins, or allergens; erythematous, exudative, crusting lesions develop on white-haired areas of the distal limbs, usually hind)

REFERENCES:

1. Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, Pennsylvania: Elsevier; 2016:412.
2. 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: 626.
3. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, Pennsylvania: Elsevier; 2016:612.
4. Robinson WF, Robinson NA. Cardiovascular System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, Pennsylvania: Elsevier; 2016:(3)69-70.
5. Sula MJ, Lane LV. The Urinary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 750.
6. Valli VEO, Kiupel M, Bienzle D. Hematopoietic System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, Pennsylvania: Elsevier; 2016:(3)210.
7. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 1141, 1232, 1255.

Click the slide to view.

---