JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

October 2022

I-P02 

 

Signalment (JPC# 77P220): 14-year-old Hereford bull

 

HISTORY: Presented for a swollen left eyelid and a mass ventral to the left ear. There was corneal ulceration and edema with areas of alopecia on the ventral midline skin. The eyelid mass was consistent with squamous cell carcinoma and led to euthanasia. At necropsy, there were multiple areas of circular crusting alopecia along the ventral midline skin cranial to the prepuce.

 

MICROSCOPIC DESCRIPTION: Haired skin: Diffusely within the dermis, there is a moderate perivascular, periadnexal, and perifollicular inflammatory infiltrates composed of eosinophils and macrophages with fewer lymphocytes and plasma cells. This inflammation multifocally extends into, and occasionally effaces, adjacent follicular epithelium (mural folliculitis) and further into the lumen (luminal folliculitis) which are multifocally markedly ectatic up to 950µm in diameter and filled with abundant lamellations of keratin (follicular hyperkeratosis). Inflammation multifocally surrounds and separates hypereosinophilic collagenous dermal remnants (collagenolysis), and is occasionally admixed with eosinophilic cellular and karyorrhectic debris (lytic necrosis), eosinophilic fibrillar material (fibrin), and increased clear space (edema). Multifocally within cystically dilated hair follicles or surrounded by abundant previously described inflammation, there are few adult filarid nematodes that are up to 100µm in diameter with a 5µm thick smooth cuticle with rarely apparent lateral alae, polymyarian-coelomyarian musculature, lateral cords, a pseudocoelom, a thick-walled, relatively large intestine lined by uninucleate cuboidal cells, and reproductive organs including paired uteri containing microfilariae and eosinophilic discs (female), or testes (male). Inflammation extends into the superficial dermis where it admixes with numerous congested small-caliber blood vessels, occasionally arranged perpendicularly to reactive fibroblasts and fibrous connective tissue (granulation tissue). The overlying epidermis and follicular epithelium are characterized by one or more of the following changes: hyperplastic with acanthosis, forming long, interdigitating rete ridges; intracellular edema (hydropic degeneration) and intercellular edema forming prominent intercellular bridging (spongiosis); multifocally lifted and effaced by previously described inflammation admixed with neutrophils, abundant fibrin and edema, and a few acantholytic keratinocytes; separated by dilated foci of previously described inflammation admixed with necrotic cellular debris, edema, and small colonies of 1um deeply basophilic cocci (intracorneal pustules); or covered by either orthokeratotic and parakeratotic hyperkeratosis or a thick serocellular crust composed of keratin debris, necrotic debris, necrotic inflammatory cells, hemorrhage, eosinophilic fluid (serum), plant material, and a single, previously described, degenerating adult filarid nematode. Apocrine glands are diffusely moderately ectatic and lined by attenuated glandular epithelium. 

 

 

MORPHOLOGIC DIAGNOSIS: Haired skin: Dermatitis, perifollicular, periadnexal and perivascular, eosinophilic and histiocytic, diffuse, severe, with folliculitis, epidermal hyperplasia, hyperkeratosis, serocellular crusts, and few intrafollicular adult filarid nematodes, Hereford, bovine.

 

ETIOLOGIC DIAGNOSIS: Dermal stephanofilariasis

 

ETIOLOGY: Stephanofilaria stilesi

 

GENERAL:  

• Stephanofilaria stilesi uncommonly occurs in cattle in North America, causing cutaneous lesions affecting the abdominal skin near the midline, usually just cranial and caudal to the navel
• Order Rhabditida, Family Filariidae
• Five other geographically separated stephanofilarid species are found in Australia, Malaysia, India, and Russia; lesion location varies with species but all cause similar cutaneous lesions

 

LIFE CYCLE:

• The vector of S. stilesi is the horn fly, Haematobia irritans (H. irritans exigua in Australia); the fly ingests microfilaria when feeding on cutaneous lesions >  development in the fly > infective stage deposited into the skin by biting flies or onto cutaneous wounds in the case of non-biting vectors
• Female nematodes are viviparous (will see microfilariae in uterus, vs. genus Rhabditis in which ova are seen)

 

TYPICAL CLINICAL FINDINGS:  

• Lesions are mildly pruritic
• Disease occurs year round but is more severe in warm weather (West/Southwest US)

 

TYPICAL GROSS FINDINGS:  

• Lesions due to combination of fly bites of the vector, reaction to parasites in the dermis, and self-inflicted trauma
• Initial macroscopic lesions begin as small circular patches 1cm or less on the ventral midline but may also occur on the flank, udder, teats, face and neck; hairs are moist and erect, underlying epidermis is spotted with droplets of serum and small hemorrhages
• Lesions enlarge and coalesce to 25cm or more in diameter; hemorrhage develops along the periphery; older, central areas develop scabs or dry crusts
• Healing lesions are alopecic, lichenified plaques
• The parasites are very small, with males reaching 3 mm and females 8 mm in length

 

TYPICAL MICROSCOPIC FINDINGS:  

• Adult parasites are present within cystic diverticula off the base of hair follicles or in adjacent dermis, often just underneath the epidermis
• Microfilaria are free within the dermis, in dermal lymphatics, or enclosed within a vitelline membrane
• Parasites have lateral cords, lateral cuticular projections (alae), a distinctive thick intestine, and paired uteri containing microfilaria and eosinophilic discs
• Little dermal reaction to adults in cystic hair follicles or microfilariae; presence of adults within the dermis elicits eosinophilic and mononuclear inflammation
• Superficial and deep perivascular dermatitis with eosinophils and lymphocytes, secondary folliculitis, and furunculosis may also be present
• Epidermal hyperplasia with spongiosis, parakeratotic and orthokeratotic hyperkeratosis, and serocellular crusting
• +/- spongiform microabscesses with eosinophils and mononuclear cells (typically associated with arthropod ectoparasite bites)

 

ADDITIONAL DIAGNOSTIC TESTS:  

 

DIFFERENTIAL DIAGNOSIS:  

For histological findings:

• Pelodera strongyloides (I-P04): Rhabditid parasite, also found in follicles, or in dermis surrounded by pyogranulomatous and eosinophilic inflammation with perifollicular and perivascular eosinophilic and lymphoplasmacytic perifolliculitis and dermatitis; lesions typically on legs, feet, perineum, ventral trunk, and tail (areas that contact soil); uteri contain ova but not microfilaria; classic Rhabditid esophagus with corpus, isthmus and bulb regions; pruritis is variable and can be absent in cattle
• Onchocerca sp. (I-P01): Filarid; adults cause cutaneous lesions in cattle; not located in hair follicles; adult nematodes have very small intestine, hypodermis, and evenly spaced cuticular annulations; microfilaria in dermis are very large (200-300 µm long)

 

For gross findings:

• Pelodera strongyloides (I-P04): papules, erythema, excoriations, exudation, scaling, crusting, and alopecia 
• Dermatophytosis (Trichophyton verrucosum is most common) (I-F11)
• Mange (Chorioptes bovis): Mites on skin scraping
• Fly bite dermatitis
• Contact dermatitis
• Zinc-responsive dermatitis (I-M18)

 

COMPARATIVE PATHOLOGY:

• Other stephanofilarids:
  • S. dedoesi (Indonesia): Cattle, “cascado”, dermatitis on side of neck, dewlap, withers and around eyes
  • S. assamensis (India and Soviet Union): “Hump sore”, Zebu cattle, infective larvae deposited onto cutaneous wounds by nonbiting Musca conducens
  • S. kaeli (Malay peninsula): Cattle, leg dermatitis, infective larvae deposited onto cutaneous wounds by nonbiting Musca conducens; microfilariae may be found free or unhatched in surface exudate
  • S. zaheeri (Japan): Buffalo, ear dermatitis
  • S. okinawaensis (Japan): Cattle, teat and muzzle
  • S. kaeli, S. assamensis, S. dedoesi: Crusting dermatitis of face, neck, shoulders and feet in goats
  • S. dinniki: Crusty, dry raised areas of dermatitis of shoulder and ventral thorax in black rhinoceros and the rump in white rhinoceros; adults and microfilariae present in lesions; seasonal variation of infection with pruritus and erythema in the summer and resolution in the winter; crusts fall off and leave depigmented scars
  • S. boomkeri (Zaire): Severe dermatitis in pigs
• Other filarid parasites of skin:
  • Parafilaria spp.: Horse, cattle; subcutaneous, ruptured “blood nodules”
  • Elaeophora schneideri: Arterial worm found in sheep, goats, mule deer, black-tailed deer, white-tailed deer, bighorn sheep, moose, and elk; microfilariae are restricted to the skin and can cause severe, ulcerative to crusting facial skin lesions which can be necrotizing and proliferative, and complicated by secondary infection; differentiate from poxvirus infection; eosinophilic to granulomatous inflammation
  • Suifilaria suis: Pig
  • Onchocerca spp.: Dermatitis in free-ranging suidae in many countries
    • O. dewittei japonica: Japanese wild boars; adults encysted in fibrous subcutaneous nodules in distal limbs and fat bodies of the foot pad; microfilariae are found in the skin of ears, tail, back, and less frequently on the limbs
    • O. tacaokai: Infest skin of ears, neck, and back; no cutaneous nodules
    • O. ramachandrini: African warthogs; microfilariae in skin of neck, back, and feet; adults are coiled in subcutis of the distal limbs 
  • Dirofilaria repens (or Acanthocheilonema spp): Dog, cat; subcutaneous; associated with zoonotic subcutaneous nodules and ocular infections in humans; reported to cause mastitis in the dog
  • Dirofilaria spp.: Common in wild lagomorphs; D. uniformis in subcutis of trunk; D. scapiceps around tendons of the hock and stifle; transmitted by mosquitoes; microfilaria found in the blood 
  • Dirofilaria corynodes: Most prevalent filarial parasite in African Old World monkeys; subcutaneous tissues of the trunk and lower extremities; very little tissue reaction
  • Dirofilaria magnilarvatum and D. macacae: Asian Old World monkeys
  • Onchocerca volvulus: human parasite reported in gorillas; subcutaneous fibrous nodule; microfilariae remain in dermis rather than circulating in peripheral blood (unlike other filarids)
  • Mansonella streptocerca and M. rodhaini: Chimpanzees; microfilariae remain in dermis rather than circulating in peripheral blood (unlike other filarids)
  • Mansonella (Tetrapetalonema) spp: New World monkeys; subcutaneous tissues; very little, if any, inflammatory response
  • Pet and aviary birds: Adult and microfilarial filarids can be found in the subcutis; gross congestion or hemorrhage associated with adults; essentially no inflammation associated with microfilaria 
  • Nubian giraffes: Lesions progress from small, crusted nodules with eosinophilic and pyogranulomatous dermaitits and furunculosis to thick plaques and proliferative and fissured hyperkeratosis and acanthosis with dense dermal granulation tissue and severe eosinophilic and granulomatous dermatitis; dormant lesions appear as hairless plaques of hyperkeratosis with dermal scarring and residual inflammation; granulomas contain adult filarid nematodes, and myriad encysted microfilariae are present in the superficial dermis; novel filarids genetically and morphologically close in identity to the filarids Stephanofilaria spp. and Brugia malayi (Han, Vet Pathol 2022)

 

REFERENCES:

1. Barthold SW, Griffey SM, and Percy DH. Pathology of Laboratory Rodents and Rabbits. 4^th ed. Ames, IA: John Wiley & Sons, Inc; 2016: 301. 
2. Duncan M. Perissodactyls. In: Pathology of Wildlife and Zoo Animals. Ed: Terio KA, McAloose D, and St. Leger J. San Diego, CA: Elsevier; 2018: 450.
3. Gardiner CH, Poynton SL. Strongyles. In: An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology; 2006: 13-15, 36.
4. Han S, Dadone L, Ferguson S, et al. Giraffe skin disease: Clinicopathologic characterization of cutaneous filariasis in the critically endangered Nubian giraffe (Giraffa Camelopardalis Camelopardalis). Vet Pathol. 2022; 59(3): 467-475. 
5. Jones MEB, Gasper DJ, and Mitchell (nee Lane) E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Pathology of Wildlife and Zoo Animals. Ed: Terio KA, McAloose D, and St. Leger J. San Diego, CA: Elsevier; 2018: 138.
6. Keel MK, Terio KA, and McAloose D. Canidae, Ursidae, and Ailuridae. In: Pathology of Wildlife and Zoo Animals. Ed: Terio KA, McAloose D, and St. Leger J. San Diego, CA: Elsevier; 2018: 247.
7. Jimenez Martinez MA, Gasper DJ, Carmona Mucino MD, Terio, KA. In: Pathology of Wildlife and Zoo Animals. Ed: Terio KA, McAloose D, and St. Leger J. San Diego, CA: Elsevier; 2018: 221. 
8. Mauldin, EA and Peters-Kennedy, J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Ed. Maxie MG. Philadelphia, PA: Elsevier Saunders; 2016: 686-689.
9. Robinson WF and Robinson NA. Cardiovascular System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Ed. Maxie MG. Philadelphia, PA: Elsevier Saunders; 2016: 88.
10. Schmidt RE, Reavill DR, and Phalen DN. Pathology of Pet and Aviary Birds. 2^nd ed. Ames, IA: John Wiley & Sons, Inc; 2015: 240. 
11. Solano-Gallego L, Masserdotti C. Reprodutive System. In: Canine and Feline Cytology: A Color Atlas and Interpretation Guide. ^4th ed. Ed: Raskin RE, Meyer DJ, and Boes KM. St. Louis, MO: Elsevier; 2023: 443.
12. Strait K, Else JG, and Eberhard ML. Parasitic Disease of Nonhuman Primates. In: Nonhuman Primates in Biomedical Research. Vol 2: Diseases. 2^nd ed. Ed: Abee CR, Mansfield K, Tardif S, and Morris T. San Diego, CA: Elsevier; 2012: 240-243. 
13. Welle MM and Linder KE. The Integument. In: Pathologic Basis of Veterinary Disease. 7^th ed. Ed. Zachary JF. St. Louis, MO: Elsevier; 2022:1229. 

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