JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
AUGUST 2022
I-B07

 

Signalment (JPC# 2155783):  Female rabbit (Oryctolagus cuniculus)

 

HISTORY:  Genital lesion

 

HISTOPATHOLOGIC DESCRIPTION: Mucocutaneous junction, vulva (2 sections): Diffusely the epidermis is hyperplastic, thickened up to 3 times normal, characterized by acanthosis, anastomosing rete ridges, intercellular clear spaces with prominent intercellular bridging (spongiosis), and intracellular edema.  There are multifocal erosions and ulcerations with replacement by a serocellular crust composed of necrotic cellular and karyorrhectic debris admixed with serum, numerous degenerate heterophils, lymphocytes, and variably sized colonies of 2 um diameter basophilic cocci.  Within the adjacent epithelium there is ortho- and rare parakeratotic hyperkeratosis.  The superficial dermis is infiltrated by moderate numbers of macrophages, heterophils, and fewer lymphocytes and plasma cells that surround adnexa and blood vessels, transmigrate the epidermis and follicular epithelium (exocytosis), and infiltrate follicular walls and lumens (folliculitis).  Hair follicles are multifocally dilated and filled with lamellations of keratin.  Multifocally within the superficial dermis there is hemorrhage, fibrin, and increased clear spaces and ectatic lymphatics (edema). The inflammation extends into the deep dermis and panniculus carnosus muscle, surrounding, separating, and individualizing skeletal myocytes which are often shrunken and hypereosinophilic (atrophy).

 

MORPHOLOGIC DIAGNOSIS:  Mucocutaneous junction (vulva):  Dermatitis and folliculitis, suppurative and lymphoplasmacytic, diffuse, moderate, with epidermal hyperplasia, orthokeratosis, ulceration, and superficial mixed bacteria, breed not specified, lagomorph.

 

ETIOLOGIC DIAGNOSIS: Cutaneous treponemiasis

 

CAUSE: Treponema paraluiscuniculi (formerly T. cuniculi)

 

CONDITION:  Rabbit syphilis

 

SYNONYMS:  Venereal spirochetosis, vent disease, treponematosis

 

GENERAL DISCUSSION:

• Rabbit syphilis is an uncommon, self-limiting disease that results in perineal (see R-B09) and facial lesions
• Gram-negative, filamentous, microaerophilic, spirochete, 0.1-0.2 um wide by 6-15 um long with tapered ends
• Genus Treponema includes both pathogenic species and nonpathogenic species; nonpathogens are part of the normal flora in the oral cavity
• Prevalence is less than 10% in enzootically infected colonies
• Effect on fertility rates has not been determined

 

PATHOGENESIS:

• Spread by direct or venereal contact
• Horizontal transmission during breeding is the primary route of exposure
• Transmission via extragenital contact and vertical transmission during birth and nursing are possible, but infrequent
• There is no evidence of intra-uterine transmission
• The organism proliferates locally after penetrating damaged or intact epithelium
• There is a long 3-6 week incubation period; takes 8-12 weeks for seroconversion
• Susceptibility increases with age; young rabbits are relatively resistant
• Prevalence increases with parity and length of time in breeding program
• Bucks are often asymptomatic carriers and can spread disease to multiple does
• Asymptomatic carriers occur, with recrudescence when under stress
• Infection may increase susceptibility to other infections

 

TYPICAL CLINICAL FINDINGS:

• Lesions can be painful, resulting in decreased breeding activity
• Colony epidemics can result in metritis, retained placentas, neonatal deaths, and decreased conception rates

 

TYPICAL GROSS FINDINGS:

• Initial lesions are on the perineum and genitalia: Edema, erythema, and papules at mucocutaneous junctions (vulva, prepuce, and anal region)
• Lesions progress to ulcerations and crusting
• Autoinfection results in similar lesions on the chin, lips, nostrils, eyelids, muzzles, and periorbital region
• Bucks can have small star-shaped scars on their scrotum

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Epidermal hyperplasia, necrosis, acanthosis, erosions, and ulcerations, with infiltration by plasma cells, macrophages, and heterophils
• Infection is usually confined to the epithelium
• Prominent periadnexal infiltration with lymphocytes, macrophages, heterophils, and plasma cells
• Regional lymph node hyperplasia
• No visceral involvement
• Gram-negative, filamentous, microaerophilic, spirochete, 0.1-0.2 um wide by 6-15 um long with tapered ends best demonstrated by Warthin-Starry and Steiner’s silver stain

 

ADDITIONAL DIAGNOSTIC TESTS:

• Definitive diagnosis is by demonstration of spirochetes in typical lesions
• The most reliable diagnostic test is using skin scrapings to make wet mounts and dark field examination; the spirochetes have a characteristic "corkscrew" movement in wet mounts
• Scrapings stained with Giemsa stain can be used
• Warthin-Starry and Steiner’s silver stains sometimes demonstrate organisms
• Microhemagglutination assay
• Plasma reagent antibody test
• Fluorescent treponemal antigen test
• The organism shares antigenic cross-reactivity with pallidum (human syphilis), so screening tests developed for human syphilis will detect rabbit syphilis

 

DIFFERENTIAL DIAGNOSIS:

• Dermatitis: Pasteurella multocida: Snuffles, conjunctivitis, and genital tract infections
• Dermatophytosis: Trichophyton mentagrophytes most commonly; head and ears
• Acariasis: Psoroptes cuniculi (ear mites); Notoedres cati, and Sarcoptes scabiei (dermatitis of the face, nose, lips, and external genitalia)
• Myxomatosis: Leporipoxvirus; mucopurulent conjunctivitis
• Traumatic lesions

 

COMPARATIVE PATHOLOGY:

• NOT zoonotic
• Very similar to Treponema pallidum (human syphilis)
  • Treponema pallidum associated with genital ulceration in wild baboons
• Treponema pallidum pertenue associated with disfiguring destructive facial lesions in wild western lowland gorillas
• Sheep: Contagious ovine digital dermatitis (CODD) is a cause of severe lameness resulting in extensive solar ulceration with or without exophytic papilliform hyperkeratosis grossly and chronic lymphoplasmacytic, suppurative and ulcerative pododermatitis histologically
• Detection of Treponema phagedenis–like antibodies in serum and bulk milk from cows with and without digital dermatitis (Frossling, JVDI 2018)
• Treponeme-Associated Hoof Disease of Free-Ranging Elk (Cervus elaphus) in Southwestern Washington State, USA
  • Debilitating and progressive condition, shares similarities to bovine digital dermatitis and contagious ovine digital dermatitis
• Pigs: Ear necrosis (“necrotic ear syndrome”, “ulcerative spirochetosis of the ear”), affecting the lower to entire ear margin of 6-9 week old piglets, is thought to be caused by a Treponema bacterium
• Horses: Often associated with proliferative pododermatitis (“canker”), a chronic hyperplasia of the horn-producing tissue on the sole, mainly the frog region

 

REFERENCES: 

1. Barthold SW, Griffey SM, Percy DH. Rabbit. In: Pathology of Laboratory Rodents and Rabbits, 4th ed., Ames, IA: John Wiley & Sons, Inc.; 2016:287.
2. DeLong D, Manning P. Bacterial diseases. In: Manning PJ, Ringler DH, Newcomer CE, eds. The Biology of the Laboratory Rabbit. 2nd ed. San Diego, CA: Academic Press; 1994:151-154.
3. Frössling J, Rosander, A, et al. Detection of Treponema phagedenis–like antibodies in serum and bulk milk from cows with and without digital dermatitis. J Vet Diagn Invest. 2018;30(1): 86–92.
4. Hans S, Mansfield KG, et al. Treponeme-Associated Hoof Disease of Free-Ranging Elk ( Cervus elaphus) in Southwestern Washington State, USA. Vet Pathol. 2019;56(1):118-132.
5. Howerth EW, Nemeth NM, Ryser-Begiorgis MP. Cervidae. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 165.
6. Klaphake E, Paul-Murphy J. Disorders of the reproductive and urinary systems. In: Quesenberry KE, Carpenter JW, eds. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery, 3rd ed., St. Louis, MO: Saunders; 2012:222-223.
7. Matz-Rensing K, Lowenstine LJ. New World and Old World Monkeys. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 360.
8. Mauldin EA, Peters-Kennedy J. Integumentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol. 1. Louis, MO: Elsevier; 2016: 643-645.
9. Njaa BL. The ear. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. Louis, MO: Elsevier; 2022: 1373-1374.
10. Welle MM, Linder KE. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. Louis, MO: Elsevier; 2022: 1219-1220.

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