Deep Fungal Infections

Chapter 40 Deep Fungal Infections

Amy M. Grooters

Deep “mycotic” infections are caused by a heterogeneous group of fungal and pseudofungal pathogens. Cutaneous and subcutaneous lesions may result from direct inoculation of an opportunistic fungal pathogen via trauma or may represent dermatologic manifestations of a systemic mycosis. Because the organisms that cause systemic mycoses typically exhibit unique morphologic features in tissue, the diagnosis of diseases such as blastomycosis, histoplasmosis, cryptococcosis, and coccidioidomycosis can often be made by histologic or cytologic identification of the pathogen in biopsy specimens or exudates (see Chapter 20). In contrast, specific identification of the less familiar opportunistic fungal pathogens that typically cause infection via wound contamination is not usually possible without culture. Despite this fact, opportunistic fungal pathogens can often be placed in a general category based on their morphologic features in tissue (such as pigmentation, hyphal diameter, and septation) and the inflammatory response that they induce. These categories include the following:

• Phaeohyphomycosis (pigmented hyphal forms)

• Hyalohyphomycosis (unpigmented hyphal forms)

• Eumycotic mycetoma (fibrosing granuloma with tissue grains containing pigmented or unpigmented fungal elements)

• Pythiosis, lagenidiosis, or zygomycosis (pyogranulomatous and eosinophilic inflammation associated with wide, infrequently septate, unpigmented hyphae)

A list of the pathogens discussed in this chapter and their categorization is found in Table 40-1.

Table 40-1 DEEP CUTANEOUS MYCOSES OF DOGS AND CATS

Disease	Causative Agents	Histologic/Cytologic Characteristics
Pythiosis	Pythium insidiosum	Pyogranulomatous and eosinophilic inflammation associated with broad (2–7 m), infrequently septate hyphae
Lagenidiosis	Lagenidium spp.	Pyogranulomatous and eosinophilic inflammation associated with broad (4–25 m), infrequently septate hyphae
Zygomycosis	Basidiobolus ranarum, Conidiobolus spp.	Pyogranulomatous and eosinophilic inflammation associated with broad (5–20 m), infrequently septate hyphae
Sporotrichosis	Sporothrix schenckii	Pyogranulomatous inflammation associated with round, oval, or cigar-shaped yeast forms, 5–9 m long, within macrophages or extracellular
Rhinosporidiosis	Rhinosporidium seeberi	Mixed inflammatory response associated with large (300 m) sporangia that contain many endospores; released endospores often visible in cytologic samples
Candidiasis	Candida albicans, other Candida spp.	Suppurative inflammation associated with numerous oval yeasts 2–6 m), pseudohyphae (chains of oval yeast cells), and true hyphae
Phaeohyphomycosis	Alternaria, Bipolaris, Cladophialophora (previously Cladosporium), Curvularia, Exophiala, Fonsecaea, Moniliella, Phialophora, Ramichloridium, and Scolecobasidium, among others	Pyogranulomatous inflammation associated with pigmented, irregularly septate hyphae or yeast-like cells that may be solitary or cluster in small groups or chains
Hyalohyphomycosis	Acremonium, Fusarium, Geotrichum, Paecilomyces, Pseudallescheria, and Scedosporium, among others	Pyogranulomatous inflammation associated with hyphal elements that have hyaline (transparent, non-pigmented) walls
Mycetoma (black grain)	Curvularia	Pyogranulomatous inflammation associated with pigmented tissue grains (which represent aggregates of fungal organisms)
Mycetoma (white grain)	Pseudallescheria boydii, Acremonium	Pyogranulomatous inflammation associated with non-pigmented tissue grains (which represent aggregates of fungal organisms)
Blastomycosis	Blastomyces dermatiditis	Suppurative to pyogranulomatous inflammation associated with large (8–15 m), spherical, thick-walled, broad-based budding yeasts
Cryptococcosis	Cryptococcus neoformans	Granulomatous inflammation (may be minimal) associated with pleomorphic, narrow-based budding yeasts (3–7 m) surrounded by a variably thick (1–30 m) polysaccharide capsule
Histoplasmosis	Histoplasma capsulatum	Granulomatous inflammation associated with intracellular, round to oval yeast cells (2–4 m) characterized by a basophilic center and clear halo
Coccidioidomycosis	Coccidioides immitis	Pyogranulomatous inflammation associated with large (20–200 m), round, thick-walled spherules that at maturity contain many small (2–5 m) endospores
Aspergillosis	Aspergillus terreus, A. deflectus, A. flavipes, A. fumigatus	Suppurative to granulomatous inflammation associated with multiple, non-pigmented, septate hyphae (3–6 m) with parallel walls and 45-degree angle branching

DIAGNOSTIC APPROACH FOR DEEP MYCOSES

Dogs and cats with deep fungal infections are typically presented with dermal or subcutaneous nodules (with or without ulceration) and/or draining tracts. In addition to fungal infection, differential diagnoses for such lesions include bacterial infections (e.g., actinomycosis, nocardiosis, mycobacteriosis, and furunculosis), protozoal infections (e.g., leishmaniasis), neoplastic lesions (e.g., cutaneous lymphoma, cutaneous histiocytosis, and disseminated histiocytic sarcoma), foreign body reaction, and sterile nodular dermatoses (e.g., sterile pyogranuloma syndrome and idiopathic panniculitis). Phaeohyphomycosis and melanoma should be suspected when lesions are visibly pigmented. The presence of granules or grains in exudate is suggestive of actinomycosis, nocardiosis, actinobacillosis, and eumycotic mycetoma.

Cytology

Cytologic examination is often the quickest and least expensive tool for either making a definitive diagnosis or categorizing diseases that cause nodules and draining tracts. Fine-needle aspirates of cutaneous nodules or enlarged lymph nodes, direct smears of exudate, or impression smears of ulcerated lesions often contain infectious organisms in animals with blastomycosis, cryptococcosis, histoplasmosis, or rhinosporidiosis and in cats with sporotrichosis. In other types of deep fungal infections, organisms are variably present in cytologic specimens.

Biopsy

Lesion biopsy for histopathology and culture should be pursued when a definitive diagnosis cannot be established cytologically. When possible, obtain multiple biopsies of representative lesions (including both draining and intact nodules) and include normal tissue at the margin of the biopsy sample.

Wedge biopsies are preferred to punch biopsies for the diagnosis of deep fungal infections.

In most cases, tissue biopsies should be submitted for bacterial (aerobic and anaerobic), mycobacterial, and fungal cultures and should be shipped at ambient temperature to arrive at the laboratory within 24 hours of collection. When unusual pathogens are suspected, it is helpful to contact the laboratory prior to collecting and shipping the samples. For additional information on diagnostic skin biopsy techniques, see Chapter 37.

Other Diagnostics

Additional diagnostic tests that may help further characterize deep fungal infections (and determine involvement of other organ systems) include a complete blood count, chemistry panel, urinalysis, and thoracic radiographs. Although serologic testing may help establish a diagnosis for some mycoses (such as cryptococcosis, blastomycosis, coccidioidomycosis, and pythiosis), in general, a diagnosis of deep fungal infection should not be based on serology results alone.

PYTHIOSIS

Pythiosis, lagenidiosis, and zygomycosis are caused by a taxonomically diverse group of pathogens but share similar clinical and histologic characteristics. Because of these similarities, they have previously been grouped under the now-obsolete term phycomycosis.

Etiology

Pythium insidiosum is an aquatic pathogen in the class oomycetes. Pythium species and other oomycetes differ from true fungi in producing motile, flagellate zoospores; having cell walls that contain cellulose and beta-glucan but not chitin; and having cell membranes that generally lack ergosterol.

• The infective stage of P. insidiosum is thought to be the biflagellate aquatic zoospore, which is released into warm water environments and likely causes infection by encysting in damaged skin or gastrointestinal (GI) mucosa.

• In the United States, pythiosis is most common in the Gulf Coast states but has been recognized in animals living in New Jersey, Virginia, Kentucky, Tennessee, southern Illinois, southern Indiana, Oklahoma, Missouri, and Kansas. Recently, a number of cases of GI pythiosis have been confirmed in dogs living in Arizona and northern California.

• Pythiosis occurs most often in young, large-breed, male dogs (especially outdoor working breeds such as Labrador retrievers). Affected dogs are most frequently presented to the veterinarian between October and March and often have a history of recurrent exposure to lakes or ponds.

• In cats, specific breed and sex predilections have not been observed in the few cases that have been reported to date. However, of 13 cats with cutaneous pythiosis diagnosed through my laboratory since 1999, 8 were less than 10 months old, with an age range of 4 months to 9 years.

Clinical Signs

The two forms of pythiosis are cutaneous and GI, depending on the route of infection. Both forms are rarely found concurrently in the same patient.

Cutaneous Pythiosis

Cutaneous pythiosis causes non-healing wounds and invasive masses that contain ulcerated nodules and draining tracts.

• Infected dogs often have solitary or multiple cutaneous or subcutaneous lesions involving the extremities, tail-head, ventral neck, perineum, or lateral thorax.

• In cats, lesions include subcutaneous masses in the inguinal, tail-head, or periorbital regions, draining nodular lesions or ulcerated lesions on the extremities, and nasopharyngeal lesions associated with retrobulbar masses.

Gastrointestinal Pythiosis

GI pythiosis in dogs is characterized by severe segmental thickening of the stomach, small intestine, colon, rectum, or, rarely, esophagus or pharyngeal region (see Chapter 69). The gastric outflow area, duodenum, and ileocolic junction are the most frequently affected portions of the GI tract, and it is not uncommon to find two or more segmental lesions in the same patient.

• Mesenteric lymphadenomegaly due to reactive hyperplasia is common.

• Involvement of the mesenteric root may form a single large, firm mass in the midabdomen.

• Extension of disease into mesenteric vessels may result in bowel ischemia, infarction, perforation, or acute hemoabdomen.

• Clinical signs associated with GI pythiosis include weight loss, vomiting, diarrhea, and/or hematochezia. Physical examination often reveals thin body condition and a palpable abdominal mass. Signs of systemic illness are usually absent unless intestinal obstruction or infarction occurs.

Diagnosis

Histopathology and Cytology

Pythiosis causes pyogranulomatous and eosinophilic inflammation associated with broad (mean, 4 μ; range, 2–7 μ), infrequently septate hyphae that are not well visualized on H&E-stained sections but are readily detected with a Gomori methenamine silver (GMS) stain. Because these same general features are associated with lagenidiosis and zygomycosis, a histologic diagnosis of pythiosis should be confirmed with culture, serology, polymerase chain reaction (PCR), or immunohistochemical staining of tissue sections with polyclonal antibodies specific for P. insidiosum.

• In animals with suspected cutaneous pythiosis, obtain wedge biopsies rather than punch biopsies to adequately reach infected tissues.

• Similarly, because inflammation in GI pythiosis centers on the submucosal and muscular layers rather than the mucosa and lamina propria, surgical biopsies are more likely to detect hyphae than are endoscopic biopsies. Therefore, consider pythiosis when endoscopic biopsies reveal eosinophilic or pyogranulomatous inflammation without identification of an etiologic agent.

• Cytologic examination of exudate associated with cutaneous pythiosis often reveals pyogranulomatous and eosinophilic inflammation but rarely reveals hyphae.

Culture

For best results, ship unrefrigerated tissue samples wrapped in a sterile, saline-moistened gauze sponge overnight at ambient temperature to a laboratory that has experience with the isolation of pathogenic oomycetes. Because P. insidiosum isolates rarely produce sexual reproductive structures in the laboratory, identification should be based on specific PCR amplification or ribosomal RNA gene sequencing whenever possible.

Serology

Detection of anti–P. insidiosum antibodies in canine serum using either enzyme-linked immunosorbent assay (ELISA) or immunoblot techniques has high sensitivity and specificity for the diagnosis of pythiosis.

• Although these techniques have only been evaluated in a small number of cats, they appear to have high diagnostic accuracy for feline pythiosis.

• In addition to providing a means for early, non-invasive diagnosis, the ELISA is also useful for monitoring response to therapy in affected patients. Recheck P. insidiosum serology 2 months after surgical resection of infected tissues or every 3 months in animals receiving medical therapy for non-resectable lesions.

• Veterinarians interested in submitting diagnostic samples for serology or culture from animals with suspected pythiosis, lagenidiosis, or zygomycosis should contact Dr. Grooters at 225-578-9600.

Tags: Saunders Manual of Small Animal Practice

Aug 27, 2016 | Posted by admin in SMALL ANIMAL | Comments Off

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