JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

October 2022

I-P03

 

Signalment (JPC# 4142619):  11 year old Friesian mare

 

HISTORY:  Mass removed from right front limb.

 

MICROSCOPIC DESCRIPTION: Haired skin, right front limb: Markedly infiltrating the dermis, elevating the diffusely ulcerated epidermis, and widely separating and surrounding scant remaining adnexa are multifocal to coalescing eosinophilic granulomas up to 1 mm in diameter which occasionally are centered on cross-sections of degenerate nematode larvae. The granulomas often contain a core of eosinophilic necrotic debris mixed with many degenerate eosinophils surrounded by epithelioid macrophages and occasional multinucleated giant cells (foreign body type) admixed with lymphocytes and plasma cells, further bounded by a layer of fibroblasts and fibrosis. The larval nematodes are up to 60µm in diameter with a 1-2 um thick cuticle with regularly spaced ridges and have variably preserved additional features including polymyarian-coelomyarian musculature and a digestive tract. Diffusely the surrounding dermis is infiltrated by numerous eosinophils and fewer lymphocytes and plasma cells, admixed with variably sized small caliber blood vessels that are lined by reactive endothelial cells and surrounded by abundant, perpendicularly oriented, hypertrophied fibroblasts (granulation tissue), all of which separate and surround collagen bundles, muscle fibers, and adnexa. Numerous collagen fibers are shrunken, hypereosinophilic, fragmented, or hyalinized and occasionally surrounded by degranulated eosinophils (flame figures).The epidermis is diffusely ulcerated with replacement by a serocellular crust composed of many degenerate inflammatory cells, fibrin, edema, and necrotic debris with superficial mixed bacterial colonies and plant material. 

 

MORPHOLOGIC DIAGNOSIS:  Haired skin, right front limb: Eosinophilic granulomas, multifocal to coalescing, marked, with nematode larvae and extensive epidermal ulceration, granulation tissue, and serocellular crust with superficial mixed bacterial colonies, Friesian, equine.

 

ETIOLOGY: Habronema muscae, Habronema majus, or Draschia megastoma

 

ETIOLOGIC DIAGNOSIS: Cutaneous habronemiasis

 

CONDITION: Summer sores

 

CONDITION SYNONYMS: Granular dermatitis, bursatti, esponja

 

 

 

 

GENERAL

• Cutaneous habronemiasis is the aberrant deposition of larvae of the spirurid nematodes Habronema muscae, Habronema majus (formerly H. microstoma), or Draschia megastoma at cutaneous or mucocutaneous sites
  1. It is a common disease of equids (horses, donkeys, and mules) causing ulcerative cutaneous and conjunctival granulomas 
  2. Habronemiasis can complicate other cutaneous or ulcerative wounds
• Cutaneous disease is usually seen in the summer and early autumn fall when flies are active; often regresses during the winter, hence the name “summer sores”
• Gastric habronemiasis is caused by adult worms in the stomach of horses and generally produces no clinical disturbances

 

PATHOGENESIS:

• Life cycle: 
  1. Adult nematodes are usually found in the stomach of horses 
     • Habronema muscae, H. majus: Attach to the fundic mucosa near the margo plicatus
     • Draschia megastoma (D-P08): Found in nodules (“brood pouches”) adjacent to the margo plicatus
  2. Eggs produced by adults in stomach nodules -> released into gastric lumen -> eggs passed in feces -> eggs ingested by fly larvae (maggots) (intermediate hosts) -> mature as fly larva matures
     • H. majus mainly uses Stomoxys calcitrans (stable fly)
     • H. muscae and D. megastoma uses Musca domestica (housefly)
  3. As an adult fly seeks moisture (e.g. from moist or traumatized tissue of a horse) Habronema larvae exit through fly’s proboscis and can invade tissue (unable to penetrate intact skin)
     • Fly bites from (Haematobia irritans) (horn fly), squamous cell carcinomas (especially penile), or pythiosis may predispose to Habronema infestation
  4. If Habronema larvae deposited near the horse’s mouth -> swallowed -> to stomach -> completes life cycle
• Horses with a hypersensitivity response to the larvae show disease

 

TYPICAL CLINICAL FINDINGS

• Proliferative, ulcerated lesions are located in moist, exposed body areas that attract flies; the most common sites are the medial canthus of the eye, the glans penis and prepuce, and any cutaneous wound
  1. Lesions also common on distal extremities (common site for lacerations)
• Cutaneous 
  1. Lesions consistently pruritic (mild to severe) during early infection leading to self-trauma/abrasion
  2. Ocular/periocular
     • Persistent conjunctivitis with ulcerated, proliferative nodules near the medial canthus; may cause profuse lacrimation; photophobia; chemosis
     • Conjunctival lesions may abrade the cornea and cause keratitis
  3. Male reproductive tissues:
     • Lesions may affect the penis (especially around the urethral meatus),  the preputial mucosa, and/or scrotum; raised nodular lesions may become large enough to cause paraphimosis
• Stomach
  1. Gastric habronemiasis is usually asymptomatic
• Other
  1. Occasionally Habronema or Draschia larvae may be found in the brain or in the lungs, where they may become encapsulated and mineralize
  2. Perforating gastric ulcers in horses resulting from Habronema spp. have reportedly led to adjacent splenic abscesses

 

TYPICAL GROSS FINDINGS

• Firm, proliferative nodular lesions with yellow caseous center +/- ulceration 
• Cutaneous 
  1. Single or multiple, ulcerated, red to brown, 5-15 cm (diameter) x 0.5-1.5 cm (deep) irregular to circular nodules with a friable surface that bleeds readily
     • Cut surface: Multiple small (1-5 mm) caseous to gritty yellow-white foci scattered throughout granulation tissue
  2. Ocular/periocular
     • Lesions smaller (<2 cm)
     • Lesions 2 to 3 cm below the medial canthus characteristic of lacrimal duct involvement
• Stomach
  1. Habronema spp found on gastric mucosa has have been associated with mild ulceration
  2. Draschia burrows into submucosa of the cardiac zone, especially along margo plicatus, and can produce large nodules (up to 5 cm wide)
     • Can lead to gastric abscessation or ulceration
  3. Adult worms are 1-2 cm in length

 

TYPICAL MICROSCOPIC FINDINGS

• Disease can depend on location that larvae deposited, but generally produces a nodular granulomatous reaction with abundant eosinophils
• Cutaneous
  1. Lesions are a combination of granulomatous inflammation, granulation tissue +/- ulceration, mineralization, viable or necrotic larvae (cutaneous) or worms (gastric)
  2. Multifocal coagulative necrosis with dense aggregates of degranulating eosinophils associated with larvae
  3. Larvae are only found in 50% of cases
     • Larvae have smooth, 1-2µm thick cuticle, coelomyarian-polymyarian musculature, prominent lateral chords, and a digestive tract lined by cuboidal, uninucleate cells
  4. Palisading granulomas with epithelioid macrophages and multinucleated giant cells, especially around foci containing necrotic larvae  
  5. Fibrous connective tissue diffusely infiltrated with large numbers of eosinophils with fewer mast cells, lymphocytes and plasma cells

 

ADDITIONAL DIAGNOSTIC TESTS

• History, clinical signs, location of lesions, presence of yellowish granules
• Biopsy: Method of choice to confirm diagnosis
• PCR may confirm disease, especially in the absence of visible larvae

 

DIFFERENTIAL DIAGNOSIS

• Habronemiasis may be superimposed over other conditions, especially those causing ulcers
• Gross lesions:
  1. Granulomas: Bacterial, fungal, foreign body
  2. Pythiosis (I-F02): Gomori’s methenamine silver stain demonstrates causative agent; kunkers are branching unlike granules seen with habronemiasis
  3. Botryomycosis (bacterial pseudomycetoma) (I-B02): Staphylococcus aureus; chronic granulomas - neck and pectoral region
  4. Exuberant granulation tissue (“proud flesh”)
  5. Squamous cell carcinoma (I-N04B)
  6. Equine sarcoid (I-N17)
  7. Equine hypertrophic gastritis is a focal lesion or more diffuse lesion associated with the nematodes Habronema spp. and Trichostrongylus axei, respectively
• Microscopic lesions (eosinophilic nodular dermatitis):
  1. Pythiosis (I-F02, Pythium insidiosum): Pale, 3-8 micron, irregular, branching hyphae with rare septa and non-parallel walls surrounded by eosinophilic and granulomatous inflammation
  2. Eosinophilic granuloma (I-M11C): Withers, back, and lateral neck; normal overlying hair coat and skin; eosinophilic granulomas
  3. Mast cell tumors (I-N21C): Nodules and/or sheets of well-differentiated mast cells often surrounding eosinophilic granulomas; can be difficult to distinguish as they may be primarily composed of eosinophils with few mast cells

 

COMPARATIVE PATHOLOGY:

• Cutaneous 
  1. Canine
     • Reported in a dog with similar lesions to horses
     • Housed in unsanitary conditions near heavily-parasitized pony pasture
  2. Camelid
     • Report of a nonhealing, severely pruritic, ulcerative fibrotic plaque at the medial canthus
• Gastric
  1. Habronema of other species are known parasites of birds (tropical birds, rhea) and rhinocerous
• Musca spp. (house fly) is implicated in the mechanical transmission of anthrax, mastitis, Habronema spp., and conjunctivitis in animals

 

REFERENCES

1. 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: 567.
2. Durham AC and Boes KM. Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022:876.
3. Foster RA. Male Genital System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016: 472, 508.
4. Foster RA, Premanandan C. Male Reproductive System. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022:1331.
5. Labelle P. The Eye. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022:1424.
6. 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: 666, 670, 685-6
7. Spagnoli ST, Belberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022:435, 461.
8. Terio K, McAloose, St. Leger J. Pathology of Wildlife and Zoo Animals. 1st ed. London, United Kingdom. Elsevier. 2018:222, 248, 451, 684, 820. 
9. Uzal FA, Plattner BL, Hostetter JM Alimentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016: 213, 217, 232-242.
10. 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. St. Louis, MO: Elsevier; 2016: 183.
11. Welle MW, Linder KE. The Integument. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022:1220.
12. Wilcock BP and Njaa BL. Special Senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016: 54, 204, 209.

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