GUIDELINE for Sporotrichosis
The rare opportunistic mycoses guidelines were first published in the J Feline Med Surg 2013; 15: 628-630; the present version has been authorised by Albert Lloret. The ABCD is grateful to Prof. Lluís Ferrer of the Foster Hospital for Small Animals, Cummings School of Veterinary Medicine, Tufts University, USA, who has graciously contributed to this article.
Synopsis
Sporotrichosis is an important subcutaneous fungal infection of humans and animals in some endemic tropical and subtropical areas. It is caused by the dimorphic saprophytic fungus Sporothrix schenckii, which is not a unique species but a complex containing at least four species. Amongst domestic animals, cats are the most frequently infected. The primary mode of transmission is traumatic inoculation of fungal conidia from plants and soil. Contact with infected cats is the major mode of transmission to humans, especially in endemic areas like Brazil, where a large epidemic has occurred in the last years. Most cat cases reported from Brazil are caused by Sporothrix brasiliensis.32
The prevalence of the disease varies markedly between regions. In Central and South America, it represents the most common deep mycosis. In Brazil it is endemic, and an important epidemic affecting humans, cats, and dogs was reported in Rio de Janeiro.2,5,11 More than 2000 feline cases have occurred over 7 years in just one institution, showing the magnitude of the epidemics and the difficulties to control it.33
Using histopathology and staining procedures, the organisms are readily visualised. Cats with few and well organized granulomas tend to have low numbers of fungal organisms in the lesions. Cats with poor general condition and large numbers of granulomas have the greatest numbers of fungal organisms.34
Most cases in cats are cutaneous, presenting as multiple ulcerated nodules in the skin and draining tracts. Lymphadenopathy, respiratory signs and systemic dissemination may also occur. Diagnosis is based on fungus detection by cytology and/or histology, and confirmation by culture. Treatment consists of systemic antifungal therapy during more than two months, with itraconazole as a first choice. Prognosis is good, if owner compliance is appropriate and adverse drug effects do not occur. Contact with infected cats carry a high zoonotic risk. Cat owners travelling to endemic areas should be warned and advised to keeping their cats indoors to prevent infection. Professionals handling cats with skin nodules and ulcers must don gloves when dealing with patients and diagnostic samples.
Agent properties
Sporotrichosis is a deep cutaneous mycosis caused by the dimorphic saprophytic fungus Sporothrix schenckii. Many mammalian species (including horses, camels, cattle, swine) can be affected, including the dog and cat; an infection of the latter was first reported in 1971.1
The fungus exists as a hyphal or mycelial form at environmental temperatures (below 37ºC) and as a yeast form at body temperature. Several subtypes have been recognised by using molecular techniques, but – in humans – these are not correlated with the various clinical pictures or with susceptibility to treatment.2 In cats, however, differences in virulence have been found between isolates from cats showing cutaneous forms versus disseminated forms.3
Epidemiology
Sporothrix schenkii is found worldwide in soil, wood, living plants and decaying plant material. Human infections are caused by traumatic inoculation of contaminated soil or organic material (sphagnum moss, hay bales, mould, plant thorns, wood splinters), especially in forestry workers, but also after contact with animals (fish spines, squirrel bites, armadillo scratches, draining lesions, scratches of infected cats or dogs).4 Many humans are thought to have been infected by cats – even by healthy ones that had been in contact with infected cats may pose a risk, as their oral samples have tested culture positive.5
Both human and animal disease is rare in Europe6, the USA7,8 and Japan9; cases have been described in particular areas (e.g. in the Apulia region, Italy, the South-eastern and South-western USA). In a recent retrospective study of 23 cases in various mammalian species in California, the cat was the most commonly affected (in 14 out of 23 cases).10 In Central and South America, however, it represents the most common deep mycosis. In Brazil it is endemic, and an important epidemic outbreak affecting humans, cats, and dogs was reported from Rio de Janeiro.2,5,11
The disease in cats is mainly reported in free-roaming intact males.12 Presumably, most infections occur when the fungus is inoculated into a wound caused by a bite or scratch from an infected cat. It can be isolated from claws13 and skin lesions, but also (importantly) from the nasal and oral cavities (Fig. 1).11
Fig. 1. Ulcerative lesions around the claw in a cat with sporotrichosis (Courtesy of Dr Larsson, São Paulo, Brazil)
Pathogenesis
Infection occurs through contact or skin puncture wounds at the inoculation site, and may diffuse by local propagation. Infection spreads via the regional lymphatic system, producing lymphangitis and lymphadenitis.4 On rare occasions, mainly in immunocompromised patients, the infection may disseminate systemically.
Fig. 2. Ulcerative crusted lesions in the facial area of a cat with sporotrichosis (Courtesy of Dr Larsson, São Paulo, Brazil)
Clinical presentation
Sporotrichosis has three clinical forms in cats: cutaneous, cutaneo-lymphatic and disseminated.
In the cutaneous form, there are multiple, ulcerated and crusted nodules, draining tracts and abscesses or cellulitis on the head (Fig. 2), limbs (Fig. 3, 4) and tail-base region, reflecting common areas of bites and scratches during fights. In some cases, these lesions may become necrotic, exposing underlying tissues.10,14 Although most cases of generalised cutaneous lesions arise from haematogenous spread, dissemination to e.g. the paws, limbs, ears may follow autoinoculation during grooming.4
Fig. 3. Multiple ulcerative crusted lesions on the forelimb of a cat with sporotrichosis (Courtesy of Dr Larsson, São Paulo, Brazil)
Lymphatic involvement may not be clinically evident, but can be demonstrated histologically, either in biopsies or after necropsy.10,14
Many organs may be affected in disseminated cases, the lungs and liver being preferred sites.10,15 Widespread cutaneous lesions typically arise from haematogenous dissemination after a primary respiratory infection. In these cases, the fungus can be cultured from blood.
Systemic signs are unspecific and include lethargy, anorexia and fever. Respiratory signs occur in about one third of cases, representing the most frequent non-cutaneous sign.14,16 Sneezing has been reported in infected cats in which the fungus was isolated from nasal mucosa.16
Fig. 4. Ulcerative lesions on the hind limb of a cat with sporotrichosis (Courtesy of Dr Larsson, Sao São Paulo, Brazil)
Some cats with disseminated disease have been found infected with feline immunodeficiency virus (FIV), but immunosuppression is not required for infection or clinical manifestation of the disease. Some FIV-positive cats affected with sporotrichosis have been treated, with complete resolution of the fungal lesions.14
Blood abnormalities (anaemia, leukocytosis, neutrophilia, hyperglobulinaemia and hypoalbuminemia) reported in cats with feline sporotrichosis are not specific, and consistent with a chronic inflammatory condition.14
Diagnosis
Although uncommon in Europe, sporotrichosis should be included in the differential diagnosis of nodular and/or ulcerative skin disease with draining tracts. This is particularly true for outdoor (fighting) cats, if a bacterial cause was initially suspected, but the response to antibiotic treatment was poor and/or the cat comes from an endemic area.
The fungus may be demonstrated by cytology and/or histology with confirmation by fungal culture.
Cytology
Smears from draining tracts and ulcers or fine needle aspiration from nodules or ulcers should always be performed. Stained samples (e.g. Romanowsky) should be examined carefully for yeast-like organisms. Special stains e.g. periodic acid-Schiff (PAS) may help to visualize and confirm the presence of fungi. Some authors report easy identification in exudates, at least in cats, while others have found it difficult.4,10 Good sensitivity (78,9%) of cytological examination as compared to culture has been recently reported in a study of 806 cats.17
Sporothrix schenkii (a 3 to 5 µm wide, 5 to 9 µm long, pleomorphic, round, oval or cigar-shape yeast) appears mainly intracellular, within macrophages and inflammatory cells, but may sometimes also be found extracellularly. Suspicious samples should be submitted for confirmatory fungal culture.
Fungal culture
Culture is the confirmatory test of choice.18 Only a few organisms may be present in the lesions, and exudate samples are best collected from the deep areas of the draining tracts/ulcers.4,17 Preferably, a piece of tissue should be submitted to the laboratory to avoid false negative results. Blood culture is recommended if the disseminated form is suspected.19 Sporothrix schenkii has also been cultured from nasal swabs and bronchoalveolar lavage in cats with respiratory signs.16
Histology
Histopathology is useful to diagnose sporotrichosis in cases with intact nodules. The histological pattern is similar to other fungal infections with a nodular to diffuse pyogranulomatous inflammatory reaction involving the dermis and subcutaneous tissues, sometimes extending into deeper tissues.10 The organisms, usually inside macrophages, may be numerous and readily visualised upon haematoxylin-eosin staining (Fig. 5); when they are scarce, special PAS staining is necessary to improve sensitivity.10
Fig. 5. Pyogranulomatous inflammatory reaction showing numerous sporothrix organisms within macrophages (Courtesy of Dr Larsson, São Paulo, Brazil)
Other tests
Recently, an ELISA for the detection of S. schenckii antibodies has been evaluated, showing good sensitivity and specificity (over 90%); it may serve as a screening tool for feline sporotrichosis.20 The PCR has been successfully used to identify Sporothrix schenkii in biopsy samples.21
Treatment
Prospective studies on the treatment of feline sporotrichosis do not exist, and all information stems from retrospective studies and case reports.
Itraconazole is the treatment of choice.10,18 Solutions (1.25 to 1.5 mg/kg q24h PO) seem to work better than itraconzale capsules (10 to 15 mg/kg q12-24h PO) due to their better bioavailability. Treatment should be continued one month beyond clinical cure, which means that the drug needs to be administered for more than two months. Itraconozale is potentially hepatotoxic; cat owners should be warned about clinical signs suggestive of hepatic disease, and monthly monitoring of serum liver enzymes is recommended.
A supersaturated solution of potassium iodide given orally is the treatment of choice for sporotrichosis in dogs; it has been also used in cats, where hepatotoxic effects are more likely to develop. However, a recent observational study in 48 cats treated with oral potassium iodide in capsules (variable doses from 2,5 mg/kg to 20 mg/kg every 24 hours) showed a success rate of 47,9%; also, less adverse effects compared to previous studies were seen, and this drug might serve as an alternative to itraconazole.22
Ketoconazole, commonly used in dogs as an alternative to potassium iodide, has also been used in cats, but adverse hepatic effects are more frequent compared to itraconazole.23
Recent reports have shown the efficacy of terbinafine (allylamine derivative) in people with sporotrichosis.24 As it showed good efficacy in vitro25, this drug might be an alternative for the treatment of cats that do not tolerate itraconazole, in cases that respond poorly, and/or if an azole resistance is suspected.
In a large retrospective study in Brazil, various regimens and combinations of antifungals, including itraconazole plus potassium iodide, itraconazole plus fluconazole, itraconazole plus terbinafine, and ketoconazole alone were examined. About one fifth of the cats was cured (68/347), in the others some clinical improvement was observed.15 In a recent retrospective study in California, most cats were successfully treated with itraconazole; in two cases treated with iodide derivatives and one disseminated disease case treated with fluconazole the infection was controlled.10
Successful intralaesional amphotericin B treatment was documented in a single case report, and recently in a series of 26 cats (in combination with itraconazole) to treat refractory skin disease.24,25
Concurrent bacterial infection, which is common, must be treated with an appropriate antibiotic for one to two months.4 Table 1 lists the treatment options for this infection.
| Drug | Dose and frequency | Comments |
|---|---|---|
| Itraconazole | 10 mg/kg q24h PO | Suggested treatment of choice; continue for 2 to 3 months or 1 month beyond clinical cure |
| Potassium iodide | Supersaturated solution 2.5 – 20 mg/kg q24h PO | Clinical adverse effects, mainly hepatotoxicity, may occur in many cats. Alternative to itraconazole in case of adverse effects or lack of efficacy |
| Terbinafine | 30 mg/cat q24h PO | May be used in combination with itraconazole. Consider in case of adverse effects or lack of efficacy of itraconazole |
| Fluconazole | 50 mg/cat q24h PO | Consider in cases of disseminated infections. May be used in combination with itraconazole. |
Table 1. Treatment options for Sporotrichosis
As a preventive measure, cats should be kept indoors in endemic areas to avoid contact with infected or carrier cats; this is especially important in immunocompromised animals (e.g. retrovirus-infected cats or those receiving immunosuppressive drugs). Owners moving to endemic areas, like Central and South America, should be warned about sporotrichosis, especially if cats will be allowed to have access to outdoors.
Prognosis
The prognosis is usually good, if treatment duration and owner compliance are adequate.10,14 However, it is poor in disseminated infections and/or if treatment is discontinued before the end of the recommended regime.14
Zoonotic risk
Close feline contacts are a potential source of zoonotic infection. In recent years, a growing number of human cases has been described, which occurred after contact with sick infected and healthy carrier cats in endemic countries like Brazil or India.28-30 A genuine epidemic of human sporotrichosis associated with transmission by cats had occurred in Brazil over last decade.31 Today, this route of human infection is considered significant, and more common than from vegetal or organic environmental sources. Cats are more efficient transmitters than other animals, presumably because larger amounts of the fungus are present in tissues, exudates and even faeces, and the infection may even be transmitted in the absence of penetrating skin lesions.7
Veterinarians and persons handling infected cats are at a high risk of acquiring the infection. It is recommended to always wear disposable gloves when handling cats with any kind of ulcerated, draining tract skin lesions, especially in areas where the infection is endemic.
Acknowledgement
ABCD Europe gratefully acknowledges the support of Boehringer Ingelheim (the founding sponsor of the ABCD).
References
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