Sporotrichosis in cats

Abstract

Overview:

Sporotrichosis is an important subcutaneous fungal infection of humans and animals in some endemic tropical and subtropical areas. Among domestic species, cats are the most frequently infected.

Infection:

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 past decade.

Disease signs:

Most cases in cats are cutaneous, presenting as multiple ulcerated nodules and draining tracts in the skin. Lymphadenopathy, respiratory signs and systemic dissemination may also occur.

Diagnosis:

Diagnosis is based on fungal detection by cytology and/or histology, and confirmation by culture.

Treatment:

Treatment consists of at least 2 months’ systemic antifungal therapy, with itraconazole as the first-choice agent. The prognosis is favourable provided there is good owner compliance and adverse drug effects do not occur.

Prevention:

Contact with infected cats carries a high zoonotic risk. Cat owners travelling to endemic areas should be warned and advised to keep their cats indoors to prevent infection. Professionals must wear gloves when handling cats with skin nodules and ulcers and dealing with diagnostic samples.

Agent properties

Sporotrichosis is a deep cutaneous mycosis caused by the dimorphic saprophytic fungus Sporothrix schenckii (a 3–5 µm wide, 5–9 µm long, pleomorphic, round, oval or cigar-shape yeast). Many mammalian species – including horses, camels, cattle and swine, as well as dogs and cats – can be infected. Feline infection 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 using molecular techniques, but – in humans – these are not correlated with the various clinical pictures or responses to treatment. ² In cats, however, differences in virulence have been found between isolates from individuals showing cutaneous forms versus disseminated forms. ³

Epidemiology

S schenckii 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, and draining lesions and scratches of infected cats or dogs). ⁴ Many humans are thought to have been infected by cats – even healthy cats that have 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 Europe, ⁶ the USA^7,8 and Japan; ⁹ cases have been described in particular areas (eg, in the Apulia region in Italy, and southeastern and southwestern USA). In a recent retrospective study of 23 cases in various mammalian species in California, the cat was the most commonly affected (14 out of the 23 cases). ¹⁰ In Central and South America, however, sporotrichosis represents the most common deep mycosis. In Brazil it is endemic, and an important epidemic outbreak affecting humans, cats and dogs has been 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 bite or scratch wound from an infected cat. The fungus can be isolated from claws ¹³ and skin lesions (Figure 1), but also, importantly, from the nasal and oral cavities. ¹¹

Figure 1

Ulcerative lesions around the claw in a cat with sporotrichosis. Courtesy of Dr Larsson, Săo Paulo, Brazil

Pathogenesis

Infection occurs through contact or skin puncture wounds at the inoculation site, and there may be 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.

Clinical presentation

Sporotrichosis has three clinical forms in cats: cutaneous, cutaneolymphatic and disseminated.

In the cutaneous form, there are multiple, ulcerated and crusted nodules, draining tracts and abscesses or cellulitis on the head (Figure 2), limbs (Figures 3 and 4) and tail-base region, reflecting common areas for 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 (eg, to the paws, limbs and ears) may follow autoinoculation during grooming. ⁴

Figure 2

Ulcerative crusted facial lesions in a cat with sporotrichosis. Courtesy of Dr Larsson, Săo Paulo, Brazil

Figure 3

Multiple ulcerative crusted lesions on the forelimb of a cat with sporotrichosis. Courtesy of Dr Larsson, Săo Paulo, Brazil

Figure 4

Ulcerative lesions on the hind limb of a cat with sporotrichosis. Courtesy of Dr Larsson, Săo Paulo, Brazil

Lymphatic involvement may not be clinically evident, but can be demonstrated histologically, either in biopsies or necropsy samples.^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 non-specific 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

Some cats with disseminated disease have been found to be 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 hypoalbuminaemia) reported in cats with feline sporotrichosis are non-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 aspirates from nodules or ulcers should always be obtained. Stained samples (eg, Romanowsky) should be examined carefully for yeast-like organisms. Special stains (eg, periodic acid-Schiff [PAS]) may help to visualise and confirm the presence of fungi. Some authors report easy identification in exudates from cats, while others have found this difficult.^4,10 Good sensitivity (78.9%) of cytological examination as compared with culture has recently been reported in a study of 806 cats [EBM grade III]. ¹⁷

S schenckii appears to be mainly intracellular, residing 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 S schenckii has also been cultured from nasal swabs and bronchoalveolar lavage samples in cats with respiratory signs. ¹⁶

Histology

Histopathology is useful for the diagnosis of sporotrichosis in cases with intact nodules. The histological pattern is similar to that seen in other fungal infections, with a nodular to diffuse pyogranulomatous inflammatory reaction involving the dermis and subcutaneous tissues, and sometimes extending into deeper tissues. ¹⁰ The organisms, which are usually inside macrophages, may be numerous and readily visualised upon haematoxylin-eosin staining (Figure 5); when they are scarce, special PAS staining is necessary to improve sensitivity. ¹⁰

Figure 5

Pyogranulomatous inflammatory reaction showing numerous Sporothrix organisms within macrophages Courtesy of Dr Larsson, Săo 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 [EBM grade I]. ²⁰ The PCR has been successfully used to identify S schenckii 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 (Table 1) [EBM grade III].^10,18 Treatment should be continued 1 month beyond clinical cure, which means that the drug needs to be administered for more than 2 months. Itraconazole is potentially hepatotoxic; cat owners should be warned about clinical signs suggestive of hepatic disease, and monthly monitoring of serum liver enzymes is recommended.

Table 1

Treatment of sporotrichosis

Drug	Dose and frequency	Comments
Itraconazole	10 mg/kg q24h PO	Suggested treatment of choice; continue for 2–3 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 if adverse effects or lack of efficacy to itraconazole
Terbinafine	30 mg/cat q24h PO	May be used in combination with itraconazole Consider if adverse effects or lack of efficacy to itraconazole
Fluconazole	50 mg/cat q24h PO	Consider if disseminated infection May be used in combination with itraconazole

A supersaturated solution of potassium iodide given orally is the treatment of choice for sporotrichosis in dogs; it has also been 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 2.5–20 mg/kg q24h) showed a success rate of 47.9%; also, fewer adverse effects compared with previous studies were seen, and this drug might serve as an alternative to itraconazole [EBM grade III]. 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 with itraconazole. ²³

Recent reports have demonstrated the efficacy of terbinafine (allylamine derivative) in people with sporotrichosis. ²⁴ As it showed good efficacy in vitro, ²⁵ 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 [EBM grade IV].

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 were cured (68/347); in the others some clinical improvement was observed. ¹⁵ In a retrospective study in California, most cats were successfully treated with itraconazole; in two cases treated with iodide derivatives and one case of disseminated disease treated with fluconazole the infection was controlled [EBM grade III]. ¹⁰

Successful intralesional amphotericin B treatment was documented in a single case report, and in a series of 26 cats (in combination with itraconazole) to treat refractory skin disease [EBM grade III].^26,27

Concurrent bacterial infection, which is common, must be treated with an appropriate antibiotic for 1–2 months. ⁴

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 regimen. ¹⁴

Prevention

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 (eg, 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.