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Basics ⬇

Outline

BASICS

Definition!!navigator!!

SC fungal infections are generally secondary to wound inoculations, have invaded the viable tissues of the skin, and are subdivided into the following categories:

  • Phaeohyphomycoses and eumycotic mycetomas—nodular, slowly extensive mycoses due to dematiaceous pigmented fungi (melanin pigments). With mycetomas, the lesions contain fungal grains that can be either pigmented or nonpigmented and the disease is rarely invasive
  • Sporotrichosis—slowly extensive SC infection due to the yeast phase of Sporothrix schenckii; slowly invasive
  • Oomycosis—pythiosis: SC and extensive infection due to Pythium insidiosum, rapidly invasive (not true fungi)
  • Zygomycoses—deep, rapidly invasive infections from 2 orders in the Zygomycetes class (Entomophthorales and Mucorales), rapidly invasive

Pathophysiology!!navigator!!

  • Phaeohyphomycoses and eumycotic mycetomas—most dematiaceous fungi exist on soil and plants. After inoculating a wound, the fungus induces chronic inflammation
  • Sporotrichosis—infection from wounds. The mold form is normally present in soil, plants, wood, and water. After inoculation, the fungus changes to a yeast phase that slowly proliferates and extends to lymphatic vessels and lymph nodes
  • Pythiosis—P. insidiosum develops on aquatic plants. Motile spores in water are attracted by damaged skin tissue and germinate on the surface of the skin. SC invasion results in proliferative necrotic extensive lesions
  • Zygomycoses—after inoculation, the fungi develop in the dermis, resulting in a pyogranulomatous inflammation with tropism for blood vessels

Systems Affected!!navigator!!

  • Skin—all
  • Phaeohyphomycoses and eumycotic mycetomas—regional lymphatic
  • Sporotrichosis—regional lymphatic
  • Pythiosis—secondarily systemic
  • Zygomycoses—occasionally rhinofacial, nasopharyngeal

Incidence/Prevalence!!navigator!!

  • Dependent on geographic distribution
  • Phaeohyphomycoses—rare in USA. Eumycotic mycetomas—most commonly reported fungus in the USA being Pseudallescheria boydii; account for approximately 9.5% of cases of equine non-neoplastic nodular lesions submitted for histopathology in the Pacific northwest of the USA
  • Sporotrichosis—worldwide and areas of high humidity and mild temperatures
  • Pythiosis—most cases are seen during the summer and fall. The environmental factors of water, decaying vegetation, and temperatures between 30°C and 40°C are the most influential factors governing the occurrence
  • Zygomycoses—found in soil and decaying vegetation. Cases occur throughout the year

Geographic Distribution!!navigator!!

  • Eumycotic mycetomas—found most frequently near the Tropic of Cancer, including Africa, North, South, and Central America, India, and southern Asia, and less commonly in the USA and Europe
  • Sporotrichosis—most common in warm countries, endemic in Spain and Italy
  • Pythiosis—in tropical and subtropical areas of the world (e.g. Thailand, Japan, Indonesia, Burma, New Guinea, Colombia, Costa Rica, Brazil, and Australia). In the USA, cases are mainly seen in the Gulf Coast region and other southern states; however, it has also been documented in Oklahoma, Arkansas, Missouri, Kentucky, Tennessee, North and South Carolina, Virginia, New Jersey, and southern Indiana
  • Zygomycoses—Rhizopus, Mucor, Absidia (Mucorales) have a worldwide distribution. The 2 major species of Entomophthorales are Basidiobolus ranarum (Americas, Australia, Asia, and tropical Africa) and Conidiobolus coronatus (tropical Africa and southeast Asia). In the USA, states along the Gulf of Mexico

Signalment!!navigator!!

  • Cutaneous granulomas most common in young (mean age 6 ± 4.2 years), with no breed or sex bias
  • Pythiosis—commonly affected horses have had prolonged contact with water in lakes, ponds, swamps, and flooded areas. The horse is the most susceptible species

Signs!!navigator!!

Phaeohyphomycosis

  • Firm, single or multiple well-circumscribed dermal nodules (1–10 cm) on the face and legs but can be widely scattered
  • Lesions initially haired but become alopecic, eroded, ulcerated, and drain
  • Papular satellites possible
  • Grossly pigmented, nonpruritic, and nonpainful

Eumycotic Mycetomas

  • SC lesions occur anywhere; however, single or multiple nodules on the head including lips and ears and neck are the most common involved sites
  • As lesions progress, they become firm, alopecic, ulcerative plaques or nodules that may drain serous, purulent, or hemorrhagic discharge that may contain black or white grains. Average size 7 mm
  • On the cut surface, suppurative exudate contains generally brown to black (rarely white to yellow) tissue grains (1–2 mm in size)
  • Mycetomas discharge tissue grains in contrast to phaeohyphomycoses, which do not

Sporotrichosis

  • Cutaneolymphatic form most common. Firm dermal to SC nodules (1–5 cm) common on the distal extremity but can be found on the chest, proximal foreleg, shoulder, and perineal region
  • Nodules linearly disposed along lymphatics and lymph nodes draining the area of the lesion
  • Lymphangitis with enlarged thickened “corded” vessels
  • Possible secondary fistulation with hemorrhagic rust to brown thin seropurulent fluid
  • Usually nonpruritic, nonpainful
  • Primary cutaneous form occurs but is uncommon

Pythiosis

  • Disease affects ventral part of the body including the legs, chest, and ventrum. Occasionally nasal
  • Progressive development of cutaneous or SC nodular tumor-like, ulcerative lesion; thick, sticky material exudes from the wound
  • Rapidly enlarging; may reach 50 cm in diameter
  • Pruritus frequent, sometimes intense
  • Visible hard, gritty, yellowish to gray coral-like masses named “kunkers” (rice grain to several centimeters) which are composed of fungal hyphae, host exudates, and protein
  • Possible extension (bones, joints, lungs, digestive tract)

Zygomycoses

  • Basidiobolus infects the lateral aspects of the head, neck, and body; lesions are usually single nodular eroded to ulcerative granulomas that may demonstrate moderate to severe pruritus
  • Fistulous tracts discharge a serosanguineous exudate from the lesions, which are frequently traumatized and can contain small, gritty, yellow-white coral-shaped bodies (0.7–1.7 mm)
  • Conidiobolus affects almost exclusively the mucosa of the nose and mouth
  • Ulcerative firm, single or multiple to coalescing lesions that may have a cobblestone appearance and may cause mechanical blockage, resulting in dyspnea and nasal discharge
  • Vascular invasion and hematogenous spread more common with mucormycosis than entomophthoromycosis

Causes!!navigator!!

  • Phaeohyphomycoses—Drechslera spinferum, Alternaria alternata, Exserohilum rostratum, Cladosporium spp.
  • Eumycotic mycetomas—Curvularia spp., Madurella (black grained mycetomas), Scedosporium/Pseudallescheria complex, Phialophora, and Aspergillus versicolor (white grained mycetomas), Alternaria spp.
  • Sporotrichosis—Sporothrix schenckii complex
  • Pythiosis—P. insidiosum
  • Zygomycoses—2 orders:
  • Mucorales (genera include Rhizopus, Mucor spp., Absidia, and Mortierella)
  • Entomophthorales (genera include Conidiobolus spp. and Basidiobolus)

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Phaeohyphomycoses and eumycotic mycetomas—neoplasia (sarcoid, squamous cell carcinoma, cutaneous lymphoma, melanoma), granulomas (foreign bodies, eosinophilic, bacterial), sporotrichosis, insect bite reactions, histoplasmosis, and molluscum contagiosum
  • Sporotrichosis—cutaneous habronemiasis, foreign body and infectious granulomas, sarcoids, neoplasia, ulcerative, and histoplasmosis
  • Pythiosis and zygomycoses—as for sporotrichosis and extreme granulation tissue

CBC/Biochemistry/Urinalysis!!navigator!!

Pythiosis—anemia and hypoproteinemia.

Other Laboratory Tests!!navigator!!

  • Sporotrichosis—mold phase growth at 27°C or yeast growth on blood agar CO2 enriched at 37°C
  • Direct fluorescent antibody tests on biopsy specimen are performed at specialized laboratories like the Centers for Disease Control and Prevention, Atlanta, GA
  • PCR from skin biopsy for identification of chitin synthase 1 gene
  • Pythiosis—serology (ELISA, Western blot) and molecular tests (PCR) conducted by Pan American Veterinary Labs, Hutto, TX (www.pavlab.com): accurate and rapid diagnosis

Diagnostic Procedures!!navigator!!

  • Definitive diagnosis for all SC mycoses is by demonstration of the organism via cytologic examination of exudate, culture of tissue or exudates, and/or histopathology
  • Pythiosis—tissue samples should be submitted via overnight shipping at room temperature. Procedures for determination of the agent include: (1) wet mount examination in 10% KOH followed by culturing, (2) detection of anti-P. insidiosum antibodies using serological assays, and (3) detection of DNA of the agent in the infected tissue by PCR and sequencing

Pathologic Findings!!navigator!!

  • Phaeohyphomycoses and eumycotic mycetomas—granuloma with central core of cellular debris and neutrophils surrounded by lymphocytes and epithelioid macrophages, organisms with septate and branched hyphae, thick walled, pigmented, or not hyphae or yeast-like elements (organized in grains in mycetomas)
  • Sporotrichosis—special stains are required (periodic acid–Schiff or GMS) as yeast are difficult to detect. Typically elongated yeasts in a granulomatous reaction with multinucleated giant cells
  • Pythiosis—pyogranulomatous dermatitis and panniculitis with eosinophils. Wide and irregular hyphae (special stains), frequently surrounded by eosinophilic Splendore–Hoeppli reaction and kunkers
  • Zygomycoses—in excised tissues, a thickened fibrotic dermis has scattered, red to creamy white areas with a central core of necrotic tissue, which often contains hyphal forms surrounded by eosinophilic infiltrate of the Splendore–Hoeppli phenomenon. Tissue sections stained with GMS reveal large, branching, sometimes septate, 4–20 µm hyphae

Treatment ⬆ ⬇

Outline

TREATMENT

Aims!!navigator!!

Attempt to reduce fungal burden via both medical and surgical management.

Appropriate Health Care!!navigator!!

  • The treatment of choice is aggressive surgical excision of all infected tissue (at least 2–3 cm of apparent healthy margins)
  • Chronic disease may not allow complete surgical excision
  • Medical management may reduce nonresectable lesions to the point that they become resectable

Client Education!!navigator!!

  • All SC dermatomycoses carry a fair to guarded prognosis if complete surgical excision cannot be achieved
  • Treatment duration is a least 3 weeks but often much longer
  • Treatment is expensive

Surgical Considerations!!navigator!!

  • Wide surgical excision should be performed for all SC mycoses
  • Phaeohyphomycoses—the only effective treatment
  • Eumycotic mycetomas—recurrence is common if incomplete excision
  • Sporotrichosis—effective in limiting the disease
  • Pythiosis—only possible in early cases
  • Zygomycoses—early removal effective

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Phaeohyphomycoses—fluconazole loading dose of 14 mg/kg given once followed by 5 mg/kg PO every 24 h concurrently with inorganic potassium iodide at 10–15 g every 24 h (for horses), 5–10 g every 24 h for ponies for 30 days or 1 month beyond clinical cure
  • Sporotrichosis—ethylene diamine dihydroiodide, drug of choice administered as a feed additive at a dosage of 1–2 mg/kg every 12–24 h × 1 week; then reduce to 0.5–1.0 mg/kg every 24 h for the remainder of the treatment. Continue treatment at least 1 month past clinical cure
  • Alternative systemic antimycotic therapy; sodium iodine therapy (125 mL of 20% solution IV slowly for 3 days) then 30 g/horse daily IM injection for 30 days
  • Zygomycoses and pythiosis—amphotericin B given systemically after surgical excision must be dissolved in 5% dextrose and water. Initial daily dose is 0.3 mg/kg. Every third day the dose is increased by 0.1 mg/kg until a maximum dose of 0.8–0.9 mg/kg/day is reached. Lesions of the extremities should receive surgical excision of exuberant granulation tissue followed by IV regional limb profusion of 50 mg amphotericin B (10 mL) in a 10% solution of medical grade dimethylsulfoxide (6 mL) and lactated Ringer's solution (44 mL)

Contraindications!!navigator!!

Use of azoles in horses with compromised hepatic function warrants careful monitoring of liver function during treatment or avoiding use of the drug if further hepatic compromise is considered to have serious clinical consequences.

Precautions!!navigator!!

  • Tolerance to iodides is variable and some horses show signs of iodism. Stop treatment for at least 1 week; then reinstitute at 75% of dosage responsible for toxic signs
  • Baseline biochemical profile should be performed to evaluate liver enzymes before administration of azoles
  • Ketoconazole is not recommended in the horse due to poor bioavailability

Alternative Drugs!!navigator!!

Pythiosis—immunotherapy with USDA licensed P. insidiosum vaccine has been reported to be effective in control or resolution of the disease in > 85% of affected horses. Can be combined with concurrent therapies.

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Reevaluate every 2–3 weeks for clinical signs and side effects associated with treatments
  • Pythiosis—ELISA serology can be used to monitor response to therapy; serology should be checked 2–3 months after surgery or every 3 months during medical therapy

Possible Complications!!navigator!!

  • Phaeohyphomycoses and eumycotic mycetomas—osteomyelitits, arthritis, myositis
  • Pythiosis—acute abdomen and death from gastrointestinal thrombosis and perforation

Expected Course and Prognosis!!navigator!!

  • Unresponsive to therapy—not unexpected; consider alternative treatment or combined treatment regimens (supersaturated potassium iodide, amphotericin B, and itraconazole)
  • Phaeohyphomycoses—wide surgical excision may be curative; horses with multiple lesions may heal spontaneously within 3 months after the diagnosis
  • Eumycotic mycetomas—some response to aggressive surgical removal of affected nodules, but recurrence is common. May stay localized for years and not invade muscle or bone
  • Pythiosis—prognosis varies with treatment response
  • Zygomycoses—chronic lesions have a poorer prognosis

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Zoonotic Potential!!navigator!!

Sporotrichosis—humans are susceptible to sporotrichosis; however, there are no reports of transmission from an infected horse.

Pregnancy/Fertility/Breeding!!navigator!!

  • Systemic iodides may cause abortion
  • Azoles antifungals are tetratogenic and should not be used in pregnant mares

Synonyms!!navigator!!

  • Phaeohyphomycoses and mycetomas—chromomycosis, pseudomycetoma (dermatophytic mycetoma)
  • Pythiosis—swamp cancer, phycomycosis, hyphomycosis, Florida horse leeches
  • Zygomycoses—mucormycosis, entomophoromycosis, basidiobolomycosis, and conidiobolomycosis

Abbreviations!!navigator!!

  • ELISA = enzyme-linked immunosorbent assay
  • GMS = Gömöri methenamine silver stain
  • PCR = polymerase chain reaction
  • USDA = United States Department of Agriculture

Suggested Reading ⬆ ⬇

Renata GS, Cravalho MB, Freitas SH, et al. Evaluation of intravenous regional perfusion with amphotericin B and dimethylsulfoxide to treat horses for pythiosis of a limb. BMC Vet Res 2015;11:152.

Author(s) ⬆ ⬇

Author: Gwendolen Lorch

Consulting Editor: Gwendolen Lorch

Acknowledgment: The author/editor acknowledges the prior contribution of Patrick Bourdeau.

Additional Further Reading ⬆

Click here for Additional Further Reading