JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
August 2022
I-F11

Signalment (JPC# 21474-1/2):  Age and breed unspecified dog

HISTORY:  This dog presented with multiple cutaneous scaly and alopecic foci.

HISTOPATHOLOGIC DESCRIPTION:  SLIDE A:  Haired skin: There is multifocal mild to moderate orthokeratotic hyperkeratosis and numerous dilated hair follicles filled with lamellations of keratin (follicular hyperkeratosis) and fragmented, degenerate hair shafts. There are occasional clusters of many 2-3µm, round, basophilic arthrospores embedded within keratin, within hair shafts (endothrix), and within follicles surrounding hair shafts (ectothrix); rarely there are poorly discernible hyphae within follicles. The epidermis is diffusely mildly hyperplastic with rete ridge formation, acanthosis, and occasional intracellular edema. Within the dermis there are rare lymphocytes, plasma cells, and neutrophils adjacent to dilated follicles. 

SLIDE B:  PAS reaction:  Follicular infundibula and hair shafts contain numerous 2-4 um diameter, PAS-positive arthrospores and few PAS positive, 5-6um diameter hyphae with thin, parallel walls; irregular septation; and rare, acute angle, dichotomous branching.

MORPHOLOGIC DIAGNOSIS:  Haired skin:  Epidermal and follicular hyperkeratosis, and hyperplasia, diffuse, mild, with intrafollicular arthrospores and rare fungal hyphae, breed not specified, canine.

ETIOLOGIC DIAGNOSIS:  Cutaneous dermatophytosis

CAUSE:  Microsporum, Trichophyton, or Epidermophyton spp.

CONDITION:  Dermatophytosis

SYNONYMS:  Ringworm

GENERAL DISCUSSION: 

• Worldwide distribution, highly contagious, zoonotic
• Superficial fungal infection caused by Microsporum, Trichophyton, and Epidermophyton fungi; typically confined to the keratin layers of the skin, hair, and claws of cats, dogs, cattle, horses, goats, pigs, sheep, and alpacas
• Species of dermatophytes are divided by host preference and natural habitat:
  • Geophilic ( gypseum) - Normal soil inhabitant, most common to infect dogs and cats
  • Zoophilic ( canis, M. equinum, T. equinum) - Live on animals, rarely in soil, occasionally infect humans
  • Sylvatic ( mentagrophytes, M. persicolor) - Zoophilic, live on rodents or hedgehogs
  • Anthropophilic ( tonsurans, T. rubrum) - Live on humans, do not survive in soil, reverse zoonosis is possible
• Incidence and prevalence varies with individual host factors and health status, climate, season, local environment, and natural reservoirs; predisposing factors include:
  • Host factors: young age, stress, poor nutrition, immunocompromised, chronically warm moist skin, comorbidities
  • Environmental factors: hot, humid weather, wet dark unsanitary conditions
  • Exposure to reservoirs: gypseum acquired from contaminated soil; M. canis acquired from cats; T. mentagrophytes acquired from rodents
• In healthy individuals, infection is self limiting and resolves within 2-3 months
  • Except in dogs with Trichophyton spp or persicolor infections may last up to 5 years without evidence of immunodeficiency

PATHOGENESIS: 

• Normal skin is inhospitable to fungal growth due to low moisture, normal resident flora, antifungal substances (e.g. sebum contains fungistatic fatty acids), and constant renewal of the stratum corneum
• Transmission via direct contact with infected animals or indirect contact with infected environment or fomites (e.g. contaminated brushes); hair fragments with arthrospores are highly infectious for up to 18 months
• Dermatophytes, with rare exceptions, only colonize cornified tissue (hair shafts, inner root sheath, stratum corneum, claws/nails) and do not invade living tissue
• Skin trauma (e.g. microabrasions, maceration) facilitates fungal invasion à dermatophytes hydrolyze surrounding keratin via keratinolytic/proteolytic enzymes, endoproteases, and exoproteases à penetrate hair shaft à grow downward until they reach the keratogenous zone (Adamson’s fringe) of the hair bulb (cannot infect viable tissue) à infection persists if downward growth of fungus is in equilibrium with keratin production and hairs become bittle/easily broken OR if not (e.g. hair enters telogen phase), fungus is sloughed and infection is cleared
• Can predispose to secondary bacterial infection

TYPICAL CLINICAL FINDINGS:

• Variable lesions and puritis (absent to severe); depends on the host-fungus interaction (e.g. well adapted canis in cats produces minimal inflammation vs less-adpated M. gypseum has prominent, inflamed lesions)
• Usually self-limiting in immunocompetent animals (weeks to months)

TYPICAL GROSS FINDINGS: 

• Classic lesions are expanding, circular, scaly, erythematous patches of alopecia or stubbled hairs +/- papules, pustules, furunculosis, crusting
• +/- rapidly developing, painful erythematous alopecic solitary nodules that may ulcerate and have draining tracts (kerion) on the face and forelimbs; secondary to severe furunculosis caused by gypseum or T. mentagrophytes
• +/- onychomycosis (infection of the claw) with misshapen, crumbly, easily broken claws that may slough
• Rarely subcutaneous nodules in Persian cats with canis (dermatophytic pseudomycetoma – see I-F12)
• May mimic autoimmune diseases (e.g. pemphigus erythematosus or foliaceus) in horses and dogs with Trichophyton spp infection

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Varied – histopathology is not as sensitive as culture for diagnosis; most useful with nodular forms such as kerion and pseudomycetoma
  • Biopsy should be taken from the outer border of the alopecic area where organisms are most likely; may need fungal stains (PAS, GMS) to demonstrate infection
• Dermatophytes are 2-7um septate hyphae with parallel walls to 2-4um chains of round to oval basophilic arthrospores in surface and follicular keratin, hair shafts, and outside of hairs (ectothrix) or within hairs (endothrix)
  • mentagrophytes and M. persicolor is only present in surface keratin (does not invade hair), so will be lost if the lesion is cleaned before biopsy
• Orthokeratotic to parakeratotic hyperkeratosis with variable acanthosis
• Inflammation variable, ranging from none to neutrophilic luminal folliculitis to furunculosis with discrete eosinophilic granulomas surrounding hair shafts at the base of follicles (trichogranuloma)
• Kerion: diffuse extensive furunculosis with pygranulomatous inflammation in the deep dermis
• May mimic autoimmune diseases (e.g. pemphigus erythematosus or foliaceus) in horses and dogs with lymphocytic lichenoid interface dermatitis with mural folliculitis, and subcorneal pustules containing neutrophils and acantholytic cells; however, fungal elements were demonstrable

ADDITIONAL DIAGNOSTIC TESTS: 

• Special histochemical stains: PAS, GMS, methenamine silver stain
• Fine needle aspirate of kerions and dermatophytic pseudomycetoma – pyogranulomatous inflammation with variable numbers of arthrospores
• Cytology of skin scrapings, touch impressions or hair plucks
  • Modified Wright stain: Squamous epithelial cells, neutrophilic inflammation, and oval to elongate basophilic 2-5um arthrospores with a thin, clear capsule
  • Plucked hairs treated with clearing agent (10% KOH): 2-4um arthrospores with a thin, clear capsule attached to or within hair shafts
• Dermatophyte test medium (DTM) – color based pH indicator
• Fungal culture for definitive diagnosis

DIFFERENTIAL DIAGNOSIS:

• Grossly indistinguishable from:
  • Demodicosis (I-P07)
  • Bacterial folliculitis
  • Seborrhea – tends to be more greasy scaling, but dermatophytes can present similarly
  • Pemphigus foliaceus/erythematous (I-M26)

COMPARATIVE PATHOLOGY: 

• Cats: Common in cats <1 year old (both domestic and wild); long haired cats (Persian and Himalayan) predisposed; M. canis most common and well adapted (minimally inflammatory) and cats serve as a reservoir for infection of other animals and humans; lesions highly variable on the face, pinnae, and paws, but usually has classic appearance; may look similar to eosinophilic plaques or feline acne; Persian cats can get atypical dermatophytosis with M. canis that results in nodules and “grains” in the deep dermis and subcutis (dermatophytic pseudomycetoma, I-F12)
• Dogs: Common in dogs <1 year old; caused by M. canis (most common), M. gypseum, T. mentagrophytes, E. floccosum, T. rubrum; localized to face, pinnae, paws, tail; circular patches of alopecia with variable papules, pustules, scaling/crust; certain breeds predisposed including Parson Russell Terrier (T. mentagrophytes), Yorkshire Terrier/Pekingese (M. canis)
• Horses: Common (“girth itch,” “tinea”); caused by T. equinum (most common), T. mentagrophytes, M. gypseum, and less often, T. verrucosum, M. canis; occurs in areas in contact with saddle and tack (face, neck, dorsolateral thorax, girth) or caudal aspect of the pastern (resembles “grease heel”); M. gypseum outbreaks have been associated with periods of high humidity and high prevalence of mosquitoes and stable flies; lesions start as tufted papules, but progress of typicaly scaly/crusted circular alopecic foci; variable pruritus
• Cattle: Common on the neck, head, pinnae, and pelvic area, especially in calves that are crowded or housed indoors during the fall and winter; verrucosum most frequent, less common isolates include T. mentagrophytes, T. equinum, M. gypseum, M. nanum, and M. canis; lesions range from tufted papules to circular areas of alopecia with variable crusting/scaling
• Goats: Common; verrucosum most frequent in lesions include alopecia, scaling, erythema and crust on the head, face, pinnae, neck, and legs
• Sheep: Uncommon; verrucosum affects the haired areas of the head, face, and pinnae (similar lesion as goat) vs M. canis/M. gypseum affect the wooled areas causing brown crusty, matted wool
• Pigs: Uncommon; nanum most frequent with lesions on the face, pinnae, and trunk with irregular, dark patches of fine brown scales or crusts (alopecia rare); less often, can get T. verrucosum (associated with housing with cattle), T. mentagrophytes, M. canis, and M. gypseum
• Black bear (J Vet Diagn Invest, 2022): Recent paper showed equinum caused generalized hyperkeratotic dermatitis, folliculitis, and furunculosis in young black bears
• Foxes: M. canis and T. mentagrophytes commonly cause focal or generalized alopecic dermatitis
• Red panda: M. gypseum is a common cause of skin disease with alopecia, crusting, and hyperkeratotic dermatitis during warm seasons on the tail, extremities, muzzle, and ears
• Non-human primates, including apes: Uncommon to rare; usually caninum, M. gypseum, T. rubrum, T. mentagrophytes, but many others reported; variable lesions
• Rodents (including Guinae pigs, rats, mice, hamsters): mentagrophytes, M. canis, M. gypseum; majority subclinically infected; high environmental temperatures and humidity predispose to laboratory outbreaks
• Reptiles: systemic infections by: canis in green iguana with nodular darkly pigmented skin lesions and granulomas in the liver, lung, and heart; T. mentagrophytes in green iguana with patchy darkened hyperkeratotic skin; Trichophyton spp in Tenerife lizards with ulcerative and heterophilic pustular dermatitis; T. cutaneum in green anoles with nucal hematomas
• Birds: Trichophyton spp and M. gypseum have been associated with skin or feather disease; complicated by fact that fungi may grow in heavy numbers on normal skin and heathers of healthy birds
• Rabbits: Uncommon due to T. mentagrophytes or M. canis

References: 

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th Ed. Ames, IA: Wiley Blackwell; 2016: 78-79, 146, 186, 234, 292-293.
2. Clothier KA, Watson KD, Mete A, et al. Generalized dermatophytosis caused by Trichophyton equinum in 8 juvenile black bears in California. J Vet Diagn Invest. 2022:34(2);279-283.
3. Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press; 2018: 512.
4. Fisher DJ. Cutaneous and subcutaneous lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and hematology of the dog and cat. 5th ed. St. Louis, MO: Elsevier; 2020: 79-81.
5. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press; 2018: 244-245.
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10. Raskin, RE, Conrado FO. Integumentary system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A color atlas and interpretation guide. 4th Ed. St. Louis, MO: Elsevier; 2023: 53-55.
11. Schmidt RE, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2^nd Ames, IA: John Wiley and Sons, Inc; 2015: 241.
12. Simmons J, Gibson S. Bacterial and Mycotic Diseases of Nonhuman Primates. In: Abee CR, Mansield K, Tardig S, Morris T, eds. Nonhuman Primates in Biomedical Research, Vol. 2: Diseases. 2^nd San Diego, CA: Academic Press; 2012: 150-151.
13. Terio KA, McAloose D, Mitchelle E. Felidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press; 2018: 278.
14. Welle, MM, Linder KE. The Integument. In: Zachary JF. Pathologic Basis of Veterinary Disease. 7^th St. Louis, MO: Elsevier; 2022:1174-1175.

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