Equine Mycotic Diseases PDF

**EQUINE MYCOTIC DISEASES** **(Presented by: Althea Joy T. Rapista)** ***Aspecific Invasive Mycoses*** Opportunistic fungi are most commonly seen in immunocompromised hosts, affecting predominantly the skin and the respiratory tract, especially the guttural pouches, and rarely other systems, such...

**EQUINE MYCOTIC DISEASES** **(Presented by: Althea Joy T. Rapista)** ***Aspecific Invasive Mycoses*** Opportunistic fungi are most commonly seen in immunocompromised hosts, affecting predominantly the skin and the respiratory tract, especially the guttural pouches, and rarely other systems, such as the digestive tract. Of importance, guttural pouch mycosis can lead to fatal haemorrhage. In addition, a wide variety of dermatophytes have been isolated from animals, but a few zoophilic species are responsible for the majority of cases: *Microsporum canis, Trichophyton mentagrophytes, Trichophyton equinum,* and *Trichophyton verrucosum,* as also the geophilic species *Microsporum gypseum,* with *T. equinum* being the most prevalent. Equine dermatophytosis ("ringworm") has public health significance. **ASPERGILLOSIS (Guttural Pouch Mycosis)** Aspergillosis is a fungal infection caused by several Aspergillus species. It is primarily a respiratory infection that may become generalized. Aspergillosis is found worldwide and in almost all domestic animals as well as in many wild animals; however, the susceptibility to fungal infections varies among species. [Aetiology] - *Aspergillus* species are globally ubiquitous saprophytes found in a variety of ecological niches. - Among them *A. funigatus* is the most prevalent and is largely responsible for the increased incidence of invasive aspergillosis in the immunocompromised patient population. - Among the equine mycoses, dermatophytosis, cryptococcosis, and aspergillosis are of particular concern due to their worldwide diffusion and, for some of them, zoonotic potential. - *A. fumigatus* is also the major organism found in the guttural pouch (auditory tube diverticulum) of horses affected with mycosis besides *A. versicolor, A. nidulans,* and *A. niger.* - In addition, a mycetoma is a chronic, proliferative lesion of cutaneous/subcutaneous tissue characterized by draining tracts and granules in the discharge caused by actinomycetes or filamentous fungi (eumycotic mycetoma) [Epidemiology] - *Emericella nidulans* from bedding materials in the equine environment has also been associated with guttural pouch mycosis [Pathophysiology] - Invasive mycoses pose a major diagnostic and therapeutic challenge. - Many fungal pathogens occur almost exclusively in opportunistic settings, such as in the immunocompromised host. [Incubation Period] - Mycotic lesions were observed in normal horses 2-4 days, following experimentally infection by endoscopy-guided intrapouch inoculation of A. fumigatus culture and preceded by administration of corticosteroids. - Spontaneous regression was observed within 15-28 days, and no clinical signs were noticed associated with this experimental infection of the guttural pouches [Clinical Presentation] - The presenting signs of guttural pouch mycosis were, in order of frequency, epistaxis at rest, nasal catarrh, pharyngeal paralysis, ipsilateral laryngeal, hemiplegia, swelling of the submandibular/parotid region, extension of the head and neck, and dyspnea; cases that presented with pharyngeal paralysis were usually fatal. [Differential Diagnosis] - Horses with diseases of the GI tract result in mucosal compromise, and horses with clinical signs of respiratory tract disease, particularly if the horse is unresponsive to treatment with antimicrobial agents, should be considered at high risk of having pulmonary aspergillosis. - The differential diagnosis includes causes of (unilateral) epistaxis without fever, such as trauma, e.g. haemorrhage into the guttural pouch associated with rupture of the longus capitis muscle, and progressive ethmoidal haematoma [Diagnosis] - Diagnosis is based on the clinical manifestation, supported by laboratory methods such as antigen detection and/or molecular assays to detect fungal nucleic acids or protein profiles. - In addition, the isolation and identification of the fungus allows the determination of its susceptibility to antifungal drugs. - A pan-dermatophyte nested-PCR assay was developed using a novel primer pair targeting the translation elongation factor 1-α sequences for direct detection and identification of most veterinary relevant dermatophytes and was positive in 90% of samples, followed by direct microscopy (86%) and culture (75%). - In addition, real-time polymerase chain reaction, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOFMS), and nano-electrospray ionization mass spectrometry (nano-ESI-MS) might be considered as well regarding diagnosis of mycotic infections - Guttural pouch mycosis can be visualized by means of endoscopy [Pathology] - Microscopic examination is necessary to identify the intralesional fungal organisms. Typically, fungi-induced inflammations are suppurative and histiocytic or granulomatous, with epithelioid and/or multinucleated macrophages; lymphoplasmacellular infiltrates are variable. - In many cases, fungi induce tissue necrosis, and fungal angioinvasion may be present in various systemic infections - Cleistothecia and/or Hulle cells have been observed in guttural pouch mycosis [Management/Treatment] - Antifungal susceptibility testing may be considered as part of the diagnostic process, which is of relevance for the management of the infection - Treatment of horses with guttural pouch mycosis is initially supportive, aimed at possible haemorrhagic shock. - Specific treatment options include veterinary treatment involving local administration of various antifungal preparations via a specifically designed catheter and/or the oral administration of benzimidazole drugs; inserting a transarterial coil into the internal carotid, external carotid, and maxillary arteries, which is effective in occluding the arteries and in inducing regression of the mycotic lesions without adjunctive medical treatment and ligation of the internal carotid artery on the cardiac side of the lesion, also an effective means of reducing the chance of fatal epistaxis in cases of guttural pouch mycosis - Equine keratomycosis might require medical management alone or surgical intervention to improve either using globe-sparing procedures or enucleation. - Dermatophytosis is usually self-limiting, but topical fungicidal administration might be considered. Furthermore, an inactivated vaccine against "ringworm" is available. **EQUINE EPIZOOTIC LYMPHAGINITIS/HISTOPLASMOSIS/PSEUDOFARCY** Overview Equine epizootic lymphaginitis (EL) (also called equine histoplasmosis or pseudofarcy) is a relatively common infectious disease of horses and other equids in certain parts of the world, and histoplasmosis is the most common endemic mycosis causing human infection. The disease is characterized by a cord-like appearance of the subcutaneous lymphatic and cutaneous pyogranulomas, the discharge from which contains spherical or pear-shaped bodies of the causal agent, *Histoplasma capsulatum* var. *farciminosusm* Etiology *H. capsulatum* var. *farciminosum* is a dimorphic fungus. Genetically distinct geographical populations or phylogenetic species should be recognized, with phylogeny suggesting that the radiation of *Histoplasma* started between 3 and 13 million years ago in Latin America Pathophysiology Similar to the other fungi in this category, initial exposure to *H. capsulatum* is by way of the respiratory tract, but once inhaled into the alveoli, the organism readily spreads in macrophages throughout the reticuloendothelial system. Furthermore, the pathogen disseminates via the lymphatic vessels, producing nodules with a characteristic corded appearance Incubation period In one study of EL, two horses were experimentally infected. Following injection into the pre-scapular and pre-femoral lymph nodes, with scarification of the skin of the left hindlimb, conjunctiva of the right eye, and the nasal membrane of the right nostril, nodular lesions of EL appeared during the fourth week of infection at all sites in the horse infected with the yeast form, whereas lesions only appeared in the lymph nodes and skin scratches of the horse infected with the mycelial form after 3 months. Both forms were recovered from the lesions of infected horses. Clinical Presentation Four disease presentations have been described, although combinations of these may occur within the same host. The cutaneous form is characterized by pyogranulomatous nodules occurring on any part of the body. The other forms of the disease are ocular (keratitis), respiratory, and asymptomatic carriers. Newborn foals died from severe granulomatous pneumonia within a few days of birth, and a weanling Thoroughbred developed granulomatous pneumonia and lymphadenitis at 5 months of age. EL also caused granulomatous placentitis and abortion in the 7^th^-10th months of gestation. Clinical signs in a 2-year-old Trakehner filly with pulmonary histoplasmosis included weight loss, intermittent fever, dyspnea, and depression. Abdominal histoplasmosis was reported in Thoroughbred mares. Of note, the organism can be found in apparently healthy horses. Differential diagnosis Differentials include glanders/cutaneous farcy, ulcerative lymphangitis associated with *Corynebacterium pseudotuberculosis* and *Mannheimia hemolytica*, sportothricosis, strangles, *Rhodococcus equi* (associated with skin penetration by *Strongyloides westeri*), melioidosis, and botryomycosis. Diagnosis The diagnosis is historically based on clinical signs, a positive reaction to the skin hypersensitivity (histofarcin) test, combined with demonstration of typical organisms in stained smears of aspirated pus from unruptured nodules, culture, and tissue sections. Serological tests have been described, such as an iFAT. The concentration of histofarcin that caused an optimum skin hypersensitivity reaction was 0.2-0.4 mg/ml in a 0.1 ml dose, and this was attained 24-48 hour postinjection. The sensitivity and specificity of the histofarcin test were 90% and 69% in disease-endemic districts. On the other hand, specificity was 100% in disease-free districts. Positive and negative predictive values of the histofarcin test were 78% and 86%, respectively. However, a large proportion (31%) of "false positives" was recorded in endemic districts, which could be due to the pre-clinical stage of the disease. Pathology Cutaneous lesions begin as papules or nodules that later ulcerate into crateriform lesions. In the lung and other tissues, multiple granulomas or pyogranulomas are found. The fungal yeast form is abundantly found intralesionally and in exudates. Freely present or within macrophages, the yeast-like fungus is round to ovoid and measures 2-3 µm in diameter. Abdominal histoplasmosis in a 4-year-old female Thoroughbred racehorse suffering from acute peritonitis was considered secondary to granulomas formed in the duodenum, lung, liver, and abdominal lymph nodes primarily caused by *Yersinia enterocolitica.* Management/Treatment Preference should be given to eradication, although amphotericin B is the drug of choice for the treatment of clinical cases. A 5-week regimen of amphotericin B administered intravenously to a 2-year-old Trakehner fully with pulmonary histoplasmosis resulted in clinical recovery and return of the animal to normal activity. An attenuated vaccine and a killed formalized vaccine are available and can be used in endemic areas to control the disease. Public health significance Most infections in humans are ascribed to *Histoplasma capsulatum var. capsulatum,* while HCF is an equine pathogen. Histoplasmosis is the most common endemic mycosis-causing human infection. Large ourbreaks have been ascribed to histoplasmosis, but most infections are sporadic. Improvements in diagnostic tests have made it feasible to establish a diagnosis of histoplasmosis more quickly, thus allowing appropriate antifungal therapy to be started promptly. Classical histoplasmosis caused by *H. capsulatum* var. *capsulatum* and African histoplasmosis caused by *capsulatum* var *duboisii* are both endemic in Africa. *H. capsulatum* var. *capsulatum* is known to occur naturally in caves inhabited by bats. Outbreaks of histoplasmosis have been reported in cave explorers. Surveys of histoplasmin skin sensitivity carried out in Africa have shown the rate of positive reactors to be 0-28%. **EQUINE PHYTIOSIS** Overview *Phytium insidiosum* is an oomycete, a fungus-like organism which may cause opportunistic infections in horses and in several other animal species, including humans. The disease pythiosis, also known as oomycosis or "swamp cancer", is characterized by granulomatous inflammatory lesions and has a worldwide distribution, although equine pythiosis is usually limited to (sub)tropical moist conditions. Response to treatment and prognosis may be poor. Synonyms - Swamp fever - Florida horse leeches - Gulf coast fungus - Phycomycosis Etiology Oomycetes are filamentous, fungus-like, eukaryotic microorganisms that reproduce both sexually. Oomycetes or water moulds include saprophytic species associated with crop diseases and include pathogenic species, such as *P. insidiosum*, associated with opportunistic infections in animals and humans. *P. insidiosum* prevails in warm, moist conditions as branching mycelium that produces infectious motile biflagellate zoospores with adhere to skin and develop into tissue-invading hyphae. The hyphae, also called pseudo-hyphae, measure approximately 2-8 µm in diameter. Infected horses may play a role in the oomycete life cycle and survival during drought, since new sporangia sprout from hyphae within necrotic tissue concrements, called kunker, when these concrements are expelled from ulcerated cutaneous granulomas into wet environments. Epidemiology Pythiosis is a relatively rare disease that may occur worldwide. Most reports concern horses, and few donkeys and mules, especially in South America. Direct contact with stagnant warm waters, such as swamps and ponds, and drinking water basins containing zoospores is the usual source of infection. Horses bathing and grazing in flooded areas is considered a major risk factor. The highest incidence was noted after the rainy season. Gravidity in mares was considered as permissive factor of infection and disease. No predisposition for age, breed, or sex of horses is reported. Pythiosis is not known to be contagious amongst horses. Pathophysiology The anatomical location of infection usually determines the site of inflammation, since dissemination seldomly occurs. Cutaneous and nasal lesions result from contact with bathing or drinking water harbouring infections zoospores. Skin wounds, also caused by biting or stinging insects, may serve as port d'entrée. Skin with darker coat colour preferred by blood-feeding insects was found to be affected more frequently. Additionally, ulcerated sarcoids may favour infection. Although invasion of hairs and hair follicle in absence of skin wounds has been suggested as route of infection also. Keratinophilic zoospores invade skin, hairs, or mucous membranes and develop into tissue invading hyphae that produce proteases and incite a necrotising inflammation. The resulting ulcerative granulomas may be painful and/or pruritic and promote itching, self-mutilation, and lameness. Loss of blood and proteins through wound exudation may result in hypoproteinaemia and anaemia. Intestinal pythiosis was reported to cause stenosis and colic. Incubation period The exact incubation period of pythiosis has not been established in horses, although 15--30 days was estimated following the onset of rainy seasons. In general, pythiosis is a chronic disease, but the development rate of inflammatory lesions may show rapid progression. Clinical presentation Equine pythiosis is characterised by severe progressive granulomatous inflammatory lesions. They are commonly observed in the skin and subcutis of limbs, chest and abdomen, inguinal areas, and less common on the face and shoulders. Lesions are mostly unifocal but may be multifocally present. A predisposition for skin areas with darker coat colour was reported. The skin lesions show nodular proliferation, often with ulcerations and serosanguinous exudation and foul odour. Secondary bacterial infections are common. From the centres of the granulomas, typical horse-specific yellow-white coral-like concrements, called kunkers or leeches, may be expelled. Other manifestations include lymphonodular, osseous, nasal, pulmonary, and intestinal forms of equine pythiosis. The clinical course concerns mostly a chronic debilitating disease up to 24 months, with reported signs of fever, anaemia, serosanguinous discharge, pain, pruritis, auto-mutilation, lameness, lymphadenopathy, stenosis and colic, weight loss or emaciation. Individual mortality may be high, as euthanasia may be indicated in advanced disease with poor prognosis. Reported spontaneous death of horses occurred between 3 and 7 months after lesions appeared, although shorter clinical courses were reported in presence of comorbidities. Differential Diagnosis The differential diagnosis should include other infectious causes of granuloma formation, such as cutaneous eumycotic mycetomas, and intestinal or pulmonary granulomas (aspergillosis, mycobacteriosis), and nasal granulomas (rhinosporidiosis). Furthermore, exuberant granulation tissue (proud flesh), cutaneous habronemiasis, eosinophilic granuloma, sarcoid, and squamous cell carcinoma should be considered. Infections with opportunistic saprophytic fungi Conidiobolus coronatus and Basidiobolus ranarum (zygomycosis or entomophthoromycosis, or most specific conidiobolomycosis and basidiobolomycosis), have been reported, causing similar necrogranulomatous inflammations like pythiosis. C. coronatus especially infects the caudal nasal cavity and trachea, whereas B. ranarum especially infects the trunk, head, and neck of the horse. Like pythiosis, zygomycosis is more common in tropical and subtropical climates, and diagnostic differentiation (by immunohistochemistry, culture, and/or genetic sequencing) is of significance since Conidiobolus sp. and Basidiobolus sp., being true fungi, are susceptible to antifungal medication in contrast to oomycetes Diagnosis A clinical tentative diagnosis can be made by demonstration of the pathognomonic horse-specific kunkers from fistulating skin wounds that may be encountered in bandages. Confirmation on formalinfixed kunkers or tissue samples relies on P. insidiosum-- specific immunohistochemistry. Classical culture identification of pythiosis may prove laborious and time-consuming. As early diagnosis and intervention may improve prognosis, faster serologic tests are important and include specific antibody demonstration by immunodiffusion (ID), indirect ELISA, and immunochromatographic tests (ICT). Preference might be given to molecular diagnosis based on DNA extraction from infected tissue with PCR-based assays and internal transcribed spacer (ITS) sequence analysis Pathology Macroscopically, the cutaneous lesions consist of unifocal or multifocal relatively large (4--50 cm in diameter) rounded firm granulomatous nodules that may be ulcerated and fistulated and may exude serosanguinous fluid and kunkers. These kunkers are specific for equine pythiosis and develop within the granulomas by repeated eosinophilic degranulation on a necrotic tissue core containing invading hyphae. They are hard, coral-like yellow-white concrements of different sizes ranging from few millimetres to several centimetres. Dissemination is rare, and other primary granulomatous inflammations are reported less often in the nasal cavity, lungs, bones, and intestines of horses Microscopic lesions are characterised by inflammatory foci with central necrosis and abundant intralesional hyphae (kunkers) surrounded by abundant degranulating and intact eosinophilic granulocytes.Additional inflammatory infiltrates spread outwards, consisting of macrophages, neutrophilic granulocytes, lymphocytes, and plasma cells, with peripheral fibrosis usually present. The hyphae are pausi-septate, nonparallel, relatively thickwalled of 2--8 μm in diameter with infrequent branching, which require silver stains like Grocott to enhance discernibility. Management/Treatement In general, therapy includes radical surgery to remove all infected tissue. Although recurrence may be common, complete excision of cutaneous granulomas combined with antibiotic treatment may be curative. Since P. insidiosum is not a true fungus, response to most antifungal medication is poor. More promising therapies, such as immunotherapy and intravenous distal regional perfusion with amphotericin B in 10% dimethylsulfoxide solution, were reported. If delicate anatomical locations (nasal conchae, lungs, intestines, bones) or dissemination prohibits curative excision, the disease usually progresses to mortality. In general, prevention of infection involves avoiding wading and grazing in stagnant waters, although this may prove unfeasible in extensively farmed horses. Public Health Significance Pythiosis is not known to be contagious amongst animals or humans and not known to cause zoonotic transmissions (horse-to-human or human-to-horse). Like in horses, individual human infections may result from exposure to water harbouring infectious zoospores. In addition, immunocompromised humans with comorbidities have an increased risk of disease **CANDIDIASIS** Overview Candida spp. are opportunistic fungal pathogens that can cause a variety of localized and systemic infections in neonatal and adult horses that have been immunocompromised for any reason. Synonyms Thrush Epidemiology Genetics and breed predisposition - Horses with genetic conditions leading to immune compromise (eg, severe combined immunodeficiency of Arabians) are at increased risk. Risk factors - Prolonged broad-spectrum antibiotic therapy - Disruption of cutaneous or mucosal barriers by burns, surgery, cytotoxic agents, or trauma - Any immune deficiency or immunosuppression produced by genetic defects, disease states such as sepsis, or administration of drugs such as glucocorticoids - Low birth weight, premature foals - Long-term placement of indwelling IV or urinary catheters or endotracheal tubes - Prolonged parenteral nutrition Contagion and Zoonosis - Although humans may develop a variety of infections from Candida spp., infection acquired from handling affected horses is probably unlikely unless the person is immunocompromised. Associated conditions and disorders - Any other condition associated with immune deficiency Clinical Presentation Disease forms/subtypes - Oral candidiasis or thrush - Systemic candidiasis with variable organ localization - Endometritis History, chief complaint - History and chief complaint vary depending on the risk factors present, the reason for immunocompromise, and the site of infection. Physical exam findings - Physical examination findings vary depending on the risk factors present, the reason for immunocompromise, and the site of infection. - Oral candidiasis (thrush) manifests as white plaques on the oral mucosa and tongue. - Systemic candidiasis may present with nonspecific signs of fever or with signs related to the site of infection of the infection (eg, arthritis, meningitis, omphalophlebitis, pneumonia). - Mares with uterine candidiasis may present with vaginal discharge or failure to conceive. Etiology and Pathophysiology - Candida is acquired as part of the normal flora as neonates pass through the birth canal. - It colonizes the mucosal and mucocutaneous surfaces of the gastrointestinal, respiratory, and genitourinary tracts. - Under most circumstances, overgrowth of Candida spp. is inhibited by normal microflora. - Opportunistic infections occur when immune defenses are altered by disease or various interventional strategies. - Mucocutaneous forms such as thrush are often related to defects in cellmediated immunity; systemic spread is more likely to be associated with neutropenia. Diagnosis Differential diagnosis - Other bacterial or fungal infection Initial database - Complete blood count and serum biochemical profile to assess systemic health and identify possible sites of infection or reasons for immunocompromise - Cytologic evaluation or culture of appropriate clinical samples (eg, blood, synovial fluid, cerebrospinal fluid, scrapings from mucosal surfaces) Treatment Therapeutic goals - Eliminate infection. - Resolve underlying reasons for immunodeficiency. Acute general treatment - Treat any underlying diseases and discontinue administration of immune suppressive medications. - Antifungal therapy with fluconazole as a loading dose of 8 mg/kg PO followed by 4 mg/kg q12--24h - Resistant strains may be treated with itraconazole at 3--6 mg/kg PO. - Intrauterine infections (endometritis) may be treated with large-volume uterine flush followed by intrauterine infusion of nystatin (0.5--2.5 million units), clotrimazole (500--700 mg), fluconazole (100 mg), or miconazole (200 mg) in a small volume of solution. - Supportive care should be provided as appropriate depending on the site of infection and underlying disease processes. Prognosis and outcome - Prognosis is guarded because many cases are complicated by serious underlying immunosuppressive conditions. **COCCIDIOIDOMYCOSIS (Valley Fever)** Overview A systemic fungal infection of equids and other mammals that may result in pneumonia, osteomyelitis, mastitis, abortion, or superficial or internal abscessation. Epidemiology Contagion and zoonosis - Horses and humans acquire disease by inhalation of arthroconidia or rarely through the skin. - Horse-to-horse and horse-to-human transmission is very rare. However, there is one report of a veterinarian developing fatal disease after attending the necropsy of a horse with disseminated coccidioidomycosis Geography and seasonality - Indigenous to the southwestern and western United States and areas of Mexico, Central America, and South America between 40 degrees south latitude and 40 degrees north latitude - Areas with significant problems often have hot, dry summers with relatively mild winters and moderate rainfall. - Cases are most common in late summer and fall. Clinical presentation Disease forms/subtypes - Respiratory disease is common because infection is usually acquired by inhalation. - Systemic dissemination may occur, leading to disease in a variety of locations. - Cutaneous inoculation may cause localized subcutaneous infection. History, chief complaint - Fever, weight loss - Signs reflecting an internal site of infection - Respiratory tract infection: Increased respiratory rate, cough, dyspnea - Osteomyelitis: Pain, lameness, neurologic signs - Abdominal infection: Colic - Subcutaneous infection: Abscess, chronic draining tracts - Respiratory tract: Abortion, placentitis Physical exam findings - Vary to reflect the site of infection Etiology and Pathophysiology - Coccidioides immitis is a diphasic, pleomorphic mold and fungus. - The saprobic phase is found in nature and in culture. - Hyphae differentiate into chains of arthroconidia (spores). - Mammalian infection occurs by inhalation of arthroconidia. - Inside the host, arthroconidia transform to spherules, which release endospores to form more spherules. - Spherules and endospores induce a neutrophil and macrophage response with development of suppurativegranulomatous lesions. - Growth elicits host antibody response to chitinase enzyme that is released as spherules mature and release endospores. Diagnosis - History - Clinical signs - Physical exam - Radiographs -- taken of lungs, showing multiple small nodular lesions - Histopathology - Fungal culture of lesioned tissues, lavage fluid or exudates - Serology tests for antibodies Differential diagnosis - Respiratory infection - Bacterial pneumonia, pleuropneumonia - Other fungal pneumonias - Pulmonary abscess - Interstitial pneumonia - Pulmonary nodular fibrosis (equine herpesvirus-5) - Systemic infection - Abdominal abscess - Strangles (Streptococcus equi subsp. equi) - Pigeon fever (Corynebacterium pseudotuberculosis) - Other bacterial or fungal forms of osteomyelitis - Abortion secondary to bacterial or fungal endometritis, nocardioform infection, leptospirosis - Cutaneous infection - Subcutaneous bacterial or fungal abscesses - Sporotrichosis - Corynebacterium pseudotuberculosis Treatment Therapeutic goals - Eliminate infection through a combination of surgical and medical therapy. Acute general treatment - Surgical removal of lesions if possible - Preferred antifungal therapy may be fluconazole (10 mg/kg PO loading dose followed by 5 mg/kg PO q24h). - Alternative antifungal medications include amphotericin B, ketoconazole, itraconazole, and voriconazole. Chronic treatment - Antifungal therapy may be required for months or years. Possible complications - Amphotericin B is nephrotoxic and irritating when administered IV and should be used with caution. Recommended monitoring - Increasing serum antibody titer generally indicates worsening disease. Prognosis and outcome - Guarded prognosis; successful treatment may require considerable time and expense - Horses with higher titers may have a poorer prognosis. **SPOROTRICHOSIS (ROSE HANDLER'S DISEASE)** Overview Chronic, slowly invasive subcutaneous mycosis caused by the yeast form Sporothrix schenckii. The disease generally manifests as cutaneolymphatic pyogranulomatous inflammation. Epidemiology Risk factors - Wound contaminated with soil and organic debris. - Immunosuppression (eg, corticosteroids administration) is likely to increase the risk of disease development, progression, and/or recurrence. Contagion and zoonosis - Although zoonotic potential exists, there are no reports of transmission from an infected horse, presumably because tissues from infected horses have fewer numbers of organisms compared with tissues from infected cats. Associated conditions and disorders - Sporadic infection affecting a number of susceptible hosts, including horses, mules, cattle, dogs, cats, rats, mice, domestic fowl, and humans. - Similar to horses, the most common form of sporotrichosis in humans is cutaneolymphatic. - In dogs, the most common forms are cutaneous and cutaneolymphatic; in cats, the disseminated form occurs in addition to the other two. Clinical presentation Disease forms/subtypes - Cutaneolymphatic form: Most common form in horses - Cutaneous form: Less common - Visceral or disseminated form: Extremely rare in horses History, chief complaint - Insidious onset - Puncture wound (often lower limb) that may have gone unnoticed - Development of limb edema associated with nodular and ulcerated cutaneous lesions Etiology and Pathophysiology - Sporothrix schenckii is an ubiquitous dimorphic fungi. - Mycelial form found naturally in soil, decaying vegetation, sphagnum moss, wood, and tree bark - Yeast form in tissues - Infection is acquired from wound contamination with soil and organic debris from puncture by plant thorns or wood splinters - The mycelial form is inoculated into tissues. The fungus changes to the yeast form and slowly proliferates, extending along the lymphatic vessels and causing them to become thick and corded. - Multiplication of the organism is associated with pyogranulomatous inflammation (although organisms are rarely seen inside neutrophils and macrophages in exudates of horses), leading to the formation of nodules associated with enlargement of lymphatic vessels. Nodules become ulcerated, resulting in a small amount of drainage of thick, red-brown to yellowish exudates or serosanguinous fluid. - Most lesions develop on distal extremities and rarely affect the upper parts of the body, such as upper forelimb, chest, shoulder, hip, and perineum. - Infection rarely spreads to regional lymph nodes. - Dissemination through lymphatics into other organs is extremely rare in horses. Diagnosis Differential diagnosis - Ulcerative lymphangitis caused by Corynebacterium pseudotuberculosis - Sporadic bacterial lymphangitis/ cellulitis caused by Streptococcus spp., Staphylococcus spp., Pseudomonas aeruginosa, Rhodococcus equi - Other causes: Foreign body, trauma, insect/arthropod bite - Cutaneous glanders by Burkholderia (Pseudomonas) mallei (exotic to United States; reportable) - Epizootic lymphangitis by Histoplasma farciminosum (exotic to United States; reportable) - Pythiosis: Pythium insidiosum (ulcerated granuloma) - Cutaneous habronemiasis (ulcerated granuloma) - Neoplasia: Sarcoid, squamous cell carcinoma (ulcerated granuloma) Initial database - No consistent abnormal findings on complete blood count or serum biochemistry are reported. - Cytologic evaluation of exudates reveals pyogranulomatous inflammation; the organism is unlikely to be seen in exudates from horses. Advanced or confirmatory testing - Demonstration of the organism by: - Fungal culture of macerated tissue samples or exudate (best tissue specimens are from biopsy rather than exudate) - Histopathologic evaluation of biopsy specimen - Diffuse to nodular pyogranulomatous dermatitis, multinucleated giant cells are common; fungal elements are nearly impossible to find - Direct fluorescent antibody test aids in the identification of fungal forms. Treatment Therapeutic goals - Clear the fungal infection and ensure regression of lesion(s) Acute and chronic general treatment - Iodides are effective and not too expensive; iodide should be administered daily for at least 1 month after complete regression of lesions. - Organic iodides: More efficacious than inorganic iodides - Ethylene diamine dihydroiodide (EDDI) administered as a feed additive at a dosage of 20 to 40 mg of the powdered form per kilogram of body weight (which corresponds to 1--2 mg of active ingredient per kilogram) q12-- 24h; this dose may be reduced to half after the first week. - Inorganic iodides - Sodium iodide: - Dosage of 20 to 44 mg/kg/day as 20% IV solution given slowly for 2 to 10 days, then orally at the same daily dose for the remainder of the treatment - Dosage of 20 to 40 mg/kg/day as 20% IV solution given intravenously slowly for 7 to 10 days - Dosage of 67 mg/kg as 20% IV solution given intravenously slowly twice weekly - Potassium iodide: Dose of 20 to 40 mg of the powdered form per kilogram of body weight per day orally (mixed with molasses and given by syringe or given with a small amount of feed or grain) - Anecdotal reports of signs of iodism occurring during the first several days as the body adjusts to the medication have prompted some clinicians to initiate therapy with inorganic iodides at a lower dosage for the first few days and then increase to the recommended dosage. - The affected limb can be cleaned with povidone-iodine and hydrotherapy applied. - Treatment with itraconazole is an alternative in cases refractory to iodides, pregnancy, or relapse after apparent cure. - Treatment should be administered q24h for at least 1 month after complete regression of lesions; overall poor bioavailability (requires acid pH for dissolution; therefore absorption is highly variable). - Oral solution licensed for use in humans has a higher and less variable solubility than capsules - Dosage for horses 5 mg/kg PO q24h. Drug interactions - Itraconazole inhibits P-450 enzymes; thus there are multiple drug-drug interactions. Possible complications - Premature discontinuation of therapy leading to relapse - Signs of iodism can develop - Lacrimation, salivation, scaling and alopecia, coughing, serous discharge, anorexia, depression, fever, nervousness, cardiovascular abnormalities, and abortion - If iodism develops, treatment should be discontinued for 7 days, then reinstituted at a lower dose (eg, three quarters of the dosage at which iodism was noted) Recommended monitoring - Revaluate every 2 to 3 weeks for clinical signs and side effects associated with treatment. - If itraconazole is used, monitoring of liver enzymes is recommended (although no adverse effects have been reported in horses). - Baseline biochemical profile should be performed to evaluate liver enzymes before administration of itraconazole. Prognosis and outcome - Prognosis is fair to good Pearls and considerations Comments - Corticosteroids and other immunosuppressive drugs are contraindicated during and after apparent clinical cure. - Corticosteroids can result in relapse of clinical sporotrichosis as long as 4 to 6 months after apparent clinical resolution. - Considering the zoonotic potential, precautions must be taken when handling horses or samples from horses suspected of sporotrichosis. - Use gloves, thoroughly clean hands, wrists, and arms with chlorhexidine or povidone-iodide. Client education - Emphasize the zoonotic potential of sporotrichosis and ensure that precautions are taken when handling a horse and suspected samples. **ZYGOMYCOSIS (Basidiobolomycosis, Conidiobolomycosis)** Overview Deep, progressive, and rapidly invasive subcutaneous mycosis caused by fungi belonging to the class Zygomycetes (includes Entomophthorales and Mucorales) Synonyms - Phycomycosis, entomophthoromycosis, conodiobolosis, rhinophycomycosis, basidiobolosis, mucormycosis Clinical presentation Disease forms/subtypes - Entomophthoromycosis - Conodiobolosis: Ulcerative granulomas on mucosa - Basidiobolosis: Ulcerative cutaneous granulomas - Mucormycosis: Ulcerated cutaneous granulomas History, chief complaint - Insidious onset of cutaneous granulomas, potentially fast-growing lesions. - Nasal granulomas can go unnoticed, and the only clinical signs might be red-tinged nasal discharge and dyspnea. Physical exam findings - Basidiobolus infects the lateral aspects of the head, neck, trunk, and body - Lesions are usually single and large, nodular eroded to ulcerative granulomas associated with moderate to severe pruritus and oozing of serosanguineous discharge. - Moderate to severe pruritus - If excised, tissue has a thickened fibrotic dermis (pink) and might contain small, scattered areas of red surrounding a white to yellow central core ("leeches") smaller than those seen with pythiosis. - Conidiobolus affects almost exclusively the mucosa of the nares, nasal passages, and possibly the mouth and nasopharynx. - Serosanguinous nasal discharge - Single or multiple ulcerative pyogranulomas may lead to mechanical blockage of the airway, resulting in dyspnea. - If on the external nares: Lesions appear similar to basidiobolus infection. - If in nasal passages and nasopharynx: Firm nodules covered by edematous, focally ulcerated mucosa. - Mucormycosis: Single or multiple ulcerated cutaneous granulomas of the limbs, muzzle, and lips Etiology and Pathophysiology - Zygomycetes are ubiquitous saprophytic fungi in soil and decaying vegetation and may be present as part of the normal flora of skin and haircoat of horses. - Infection may be caused by several related fungal species belonging to two orders under the class Zygomycetes, phylum Zygomycota: - Entomophthorales (includes genera Conidiobolus and Basidiobolus) - Mucorales (includes genera Rhizopus, Mucor, Absidia, and Mortierella) - Infections are thought to develop secondary to wound inoculations. - After inoculation, the fungi develop in the dermis, resulting in a pyogranulomatous inflammation. Diagnosis Differential diagnosis - Exuberant granulation tissue - Cutaneous habronemiasis - Foreign body granuloma - Pythiosis - Bacterial pseudomycetoma or botryomycosis (limb, lips, head, mammary area, scrotum) - Cutaneous actinomycosis (generally head and neck) - Cutaneous nocardiosis (generally distal limb) - Phaeohyphomycoses and eumycotic mycetomas - Ulcerated neoplasia such as squamous cell carcinoma - Neoplasia such as sarcoid, squamous cell carcinoma (ulcerated granulomas), and possibly cutaneous lymphoma, melanoma (generally not ulcerated) Initial database - Abnormalities in the complete blood count and biochemistry profile are not reported. Advanced or confirmatory testing - Cytologic evaluation of aspirate or direct smear: Pyogranulomatous to granulomatous inflammation with numerous eosinophils. - Definitive diagnosis requires demonstration of the organism by histopathology evaluation or fungal culture of biopsy specimen - Thickened fibrotic dermis with diffuse to nodular, pyogranulomatous to granulomatous inflammation containing numerous eosinophils. - Scattered areas with a central core of necrotic tissue, which often contains hyphal forms (poorly or occasionally septated) surrounded by eosinophilic infiltrate of the Splendore-Hoeppli phenomenon; hyphae are often poorly stained and may appear as clear spaces. - Tissue sections stained with Giemsa reveal large, branching occasionally septate, 4- to 20-µm, hyphae. - Immunohistochemistry of histologic sections allows identification of the organism - Biopsy specimen for culture (in Sabouraud dextrose agar) should not be macerated. - A serum agar gel immunoprecipitation test is useful for the diagnosis of conidiobolomycosis. Treatment Therapeutic goals - Attempt to reduce fungal burden via both medical and surgical management. - Treatment should be instituted as soon as possible. Acute and chronic general treatment - Surgical excision should be performed if possible. Surgical excision should be followed by chemotherapy. - Drug therapy depends on the causative agent. - Entomophthoromycosis - Iodides are effective and not too expensive; iodide should be administered daily for at least 1 month after complete regression of lesions - Organic iodides: More efficacious than inorganic iodides. Ethylene diamine dihydroiodide (EDDI) administered as a feed additive at a dosage of 1 to 2 mg/kg q12-- 24h for 7 days; then reduce to 0.5 to 1.0 mg/kg q24h for the remainder of the treatment - Inorganic iodides - Sodium iodide: Dose of 10 to 40 mg/kg/d as a 20% solution given IV slowly; the length of treatment varies: 2 to 5 days and then orally for the remainder of the treatment. - Potassium iodide: Dose of 20 to 40 mg/kg/d PO mixed with molasses and given by syringe or given with a small amount of feed or grain. - Anecdotal reports of signs of iodism occurring during the first several days as the body adjusts to the medication have prompted some clinicians to initiate therapy with inorganic iodides at lower doses for the first few days and then increase to the recommended dose - Azoles can be attempted in cases refractory to iodides, pregnancy, or relapse after apparent cure; treatment should be administered daily for at least 1 month after complete regression of lesions. - Itraconazole: Overall poor bioavailability (requires acid pH for dissolution; therefore, absorption is highly variable). - Oral solution licensed for use in humans has higher and less variable solubility than capsules - Dosage for horses: 5 mg/kg q24h. - Fluconazole: Successfully used to treat zygomycosis in pregnant mares. Recommended dosage: Loading dose of 14 mg/kg PO followed by 5 mg/kg q24h. - Mucormycosis - Iodides are not effective against Mucorales (Rhizopus, Mucor, Absidia). - Amphotericin B given systemically after surgical excision must be dissolved in 5% dextrose and water. - The initial dose should be low and gradually increased. The initial daily dose is 0.3 mg/kg, and every third day, the dose is increased by 0.1 mg/kg until a maximum dose of 0.8 to 0.9 mg/ kg/d is reached. - Treatment is continued daily or every other day for a total of 30 days. [Reference] Taboada, Joseph. 2019. *Fungal Infections (Mycoses) in Horses.* June. Accessed August 21, 2024. https://www.msdvetmanual.com/horse-owners/infectious-diseases-of-horses/fungal-infections-mycoses-in-horses. van der Kolk, J.H., and E.J.B. 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