Fungal diseases

7 Fungal diseases

A considerable range of infectious actinomycetes and fungi are recognized as potential causes of disease of the skin and internal organs in many species and in all cases they offer significant diagnostic and therapeutic challenges to the clinician. The causative organisms involved and the treatment options in the two broad groups of fungal pathogens are also very different. Fungal skin infections in horses range from some very common superficial disorders such as dermatophytosis (ringworm) caused by almost ubiquitous Trichophyton and Microsporum fungi, to the exotic and difficult disorders related to secondary wound infections such as pythiosis (‘Florida leeches’) due to Pythium spp., and conidiobolomycosis (black-grained mycetoma) caused by cutaneous and subcutaneous infection with Conidiobolus coronata. There is an increasing awareness, too, of the role of fungal skin infections on and within the skin. Some result in diffuse or localized areas of dermatitis while in more benign situations such as the temperate European climate some result in nodular fungal granuloma.

Classification of the fungal dermatological infections in other species is usually based on the location of the infection. This system is also applicable to equine mycotic disease (Table 7.1). Three broad groups of fungal skin disease can be identified:

1. Superficial mycoses are those in which the pathogen is confined to the stratum corneum (and does not affect hairs). As might be expected, there is little or no tissue reaction or inflammation and as result they tend to be rather benign. Some of the conditions are viewed as facultative pathogens, or even commensals, rather than primary pathogens and in either case there can be secondary seborrhoeic changes that result in excessive scale and flake on the skin surface. There is usually little immunological or cellular response associated with the organisms and no obvious seroconversion. A good example of this is Malassezia spp. infection, which has recently been recognized as a potentially significant skin infection in horses.

2. Cutaneous mycoses affect all keratinized tissue including hair, horn and skin, although most of the pathogens are confined to the non-living layers of the skin and the appendages. The organisms are capable of causing significant destruction of keratinized tissue and there are usually immunological responses in the host that result in obvious lesions and seroconversion with variable protective properties.

3. Subcutaneous/deep mycoses constitute a heterogeneous group of fungal diseases that are more deep-seated. They involve subcutaneous tissues, possibly in addition to the dermal/epidermal involvement. Whilst most of these remain localized (e.g. Alternaria alternate), some do spread insidiously to contiguous tissues, e.g. Basidiobolus haptosporus and Conidiobolus coronatus infections. Some spread via lymphatic vessels occurs, e.g. histoplasmosis (epizootic lymphangitis) due to H. farciminosum and sporotrichosis due to Sporothrix schenckii. There may be difficulties with diagnosis and treatment in this group of diseases. Seroconversion may take place but seldom seems to result in an effective protective process. Most of the conditions are chronic and progressive.

Table 7.1 The main fungal and actinomycete infections of the skin of the horse

The deep mycoses are necessarily much more serious in most cases but are fortunately geographically restricted. Although some of the diseases are sporadic others occur in epidemics or are enzootic. For the most part, however, apart from the major disease epizootics, deep fungal infections are rare or very rare in horses.

Generally the clinical signs of cutaneous mycoses (both deep and superficial) are not pathognomonic in that they may closely resemble those elicited by other microorganisms and some other non-infectious pathological states. For example, some early dermatophytosis cases can closely resemble urticaria and even some forms of pemphigus. Epizootic lymphangitis can be easily mistaken for glanders (and vice versa). In places where the diseases are common, some conditions can be quickly recognized by veterinarians through a combination of historical, clinical and environmental/epidemiological findings. For example, pythiosis is singularly rare outside the southern states of the USA but within the region itself it is well recognized and usually rapidly diagnosed, and black grained mycetoma is a rare but recognized condition in the northern parts of Australia.

There are also some incidental and secondary fungal infections. Therefore, a definitive diagnosis is often dependent on the clear and unequivocal detection of a known pathogenic organism.

Apart from the superficial dermatophytosis (ringworm) disorders, in which culture and direct microscopic examination of hair shafts and skin scrapings are diagnostic in most cases, the best definitive and practical procedure is biopsy and in some cases histological demonstration of the definitive organism. This also has some difficulty because the juvenile or early forms of some of the deeper mycoses are not ‘typical’. New methods of immunohistochemistry involving immunofluorescence and PCR can be used in some cases.

Trichophytosis

Profile

Cutaneous mycosis (ringworm) due to Trichophyton spp. is a very common, highly contagious disease which affects horses of all ages. Younger horses are naturally less resistant and take longer to recover than older ones. Transmission is by direct or indirect contact with a source of infection.

The most common species are Trichophyton equinum var. equinum (TEvE), T. equinum var. autotrophicum (TEvA), and less commonly T. verrucosum (most often from direct or indirect contact with infected cattle) and T. mentagrophytes (most often derived from contact with infected rodents and cats) (Pascoe 1979, 1984). T. equinum var. equinum tends to be the predominate species in the northern hemisphere while T. equinum var. autotrophicum tends to dominate in the southern hemisphere and the Antipodes.

The spores are highly resistant to environmental destruction and may persist in stables and on tack, etc. for many years. Most cases occur in winter months when horses are closely grouped and groomed heavily using shared or unhygienic tack, harness, clothing and equipment. Wet, warm weather has also been associated with outbreaks but sunshine is a significant inhibitor of the fungi in general. The distribution of lesions in some cases suggests that biting flies may be a significant vector.

Infection relies upon the presence of active (live) spores and mechanical skin abrasion (even if very mild) and this is the reason for most lesions developing on girths and saddle and jockey boot friction areas. The spores become vegetative in the damaged stratum corneum and the fungal hyphae penetrate the anagen hair follicles. In Trichophyton species infection, the hyphae invade the hair shafts and relatively few spores are produced within the hair shafts (endothrix spores). As the fungal hyphae penetrate downwards towards the hair bulb, keratolytic enzymes are produced. These enhance and facilitate further penetration. Damage to the anagen hair shaft occurs so that the outer portion is shed; the fungus may be expelled with it. In order for the fungus to thrive the hair has to be actively growing and so as soon as the hairs enter the telogen stage the fungus cannot easily survive. At this stage the highly resistant spores are produced and may be shed into the environment with the hair shaft. Most cases resolve spontaneously as a result of hair shedding in telogen phase or as a result of hair breakage or following an immuno-excitatory inflammatory folliculitis; this can be a result of local hypersensitivity responses to the secretions of the fungus. In some cases the complex of secretory and induced inflammatory products results in a more florid inflammation – often with some mild irritation to the horse. Following infection, lesions are visible at around 7–21 days depending largely on the immune status of the horse. Reinfection of a single hair follicle and its hair shaft does not occur until the hair re-enters its anagen phase. If immunity is strong at this stage, the infection is unlikely to re-establish. Clinically the lesions may expand and continue to spread across the horse for some 2–4 months depending on the stage of hair growth and the extent of immunity. Immunity to Trichophyon spp. fungi is short-lived; there are some common antigens and so reinfestation with another Trichophyton species is less likely. However, there does not appear to be any significant correlation between circulating antibody concentrations and the extent of resistance to reinfection. The natural antifungal effects of healthy untraumatized skin seem to be at least as important in the overall resistance to the disease. Repeated degreasing shampoos are probably not helpful because sebum has a significant protective property.

Immunocompromised horses (such as those on steroid treatment or clinical cases of pituitary pars intermedia dysfunction (PPID/Cushing’s disease)) are liable to recurrent, severe and often overwhelming infections.

The positive identification of the species involved (in all dermatophytosis cases) provides useful information on the likely source of infection. The treatment is unlikely to vary but as immunity is generally poor, avoidance of reinfection may depend on a combination of avoiding the source of the infection (where this can be achieved) and sterilization of the environmental challenges arising as a result of spore contamination of buildings, tack harness, rugs, etc.

Note

Although most species of dermatophyte are in theory at least transmissible to humans, this appears to be much less common with the specific equine species. The bovine and pet species of dermatophyte can infect horses and then the infectivity to humans may be greater than with the equine species. Human disease does nevertheless occur and it is always useful to enquire about any human skin disease and if anything is recognized, the person must be referred to a medical practitioner (carrying a note of the suspicion for the animal). Therefore it is important to establish the species involved in an outbreak so that proper measures can be taken to control it amongst the horses and limit the associated human risks.

Key points: Trichophytosis

1. Very common cutaneous mycosis due to Trichophyton spp. dermatophytes. Worldwide distribution. Spores are highly resistant so repeated infections occur in stables/yards. The fungus requires epidermal damage to gain entry and remains inside the hair follicle and on the hair shafts. The sites of infection reflect areas of superficial skin trauma such as tack and harness contact points. Generalized infection can follow simply from grooming with infected brushes or transferring the fungus to fresh sites on the same horse. The spores can survive for many years.

2. Early clinical signs are erect hairs, some local swelling/ oedema with mild exudate in a few cases. As all hairs are involved within a local area, complete shedding of hair occurs and lesions are easily and completely epilated leaving a silvery exposed epidermis. Abrasions from jockeys’ boots and girths are common sites for infection.

3. Diagnosis is relatively simple clinically but differential culture is important for control measures. Biopsy can be helpful.

4. Treatment involves isolation of affected horses and careful hygiene to prevent spread between horses and to humans. Topical antifungal washes are effective and oral griseofulvin can be given; it should not be given to pregnant mares. Envi-ronmental control is also important to limit the risks of spread so fungicidal disinfectants are used as sprays and washes for tack and harness, etc.

5. Control by vaccination is possible in some countries but early recognition and isolation of cases, and stable and personal hygiene are by far the best ways to prevent its spread. Individualized tack, harness and rugs, etc. are essential, especially in stables with a history of dermatophyte infection. When handling any case of dermatophytosis, gloves should always be worn.

The earliest lesions appear as erect hairs in circular areas of 5–20 mm diameter (Fig. 7.1). There is often a degree of localized inflammation resulting in a thickening of the skin within the infected area; this can be urticarial in nature and there may be some exudate, which dampens the site. By day 7–10 post-infection hair can easily be plucked from the site (Fig. 7.2), leaving a silvery, slightly reddened circular area of exposed epidermis (Fig. 7.3). Hair loss also occurs naturally but this is less abrupt and so the lesions may not be obvious until 14–21 days. One of the cardinal signs is the ease with which the hair is removed – this is because most (probably all) hairs are affected within the lesion (Fig. 7.4).

Figure 7.1 Ringworm. Early lesions of Trichophyton equinum var. equinum infection in the girth area (attributed to a contaminated girth some 5–7 days previously).

Figure 7.2 Ringworm. Removal of the hair in a mat at 10 days after natural infection with Trichophyton equinum var. equinum.

Figure 7.3 Ringworm. The typical silvery, slightly scaly appearance of a lesion due to Trichophyton equinum var. autotrophicum infection. The hair loss in this case occurred naturally and infection was considered to have arisen some 14 days previously.

Figure 7.4 (A) This 5-year-old Warmblood had a very subtle, slightly pruritic raised lesion with elevated hairs on his nose (arrow). (B) By 7 days later a more typical ringworm lesion had developed and several smaller, slightly later lesions were developing on the muzzle.

The infected areas expand centrifugally and may lose the circular appearance, becoming diffuse and ill-defined.

Girth and shoulder/chest wall areas are common sites owing to infection from contaminated girths, riding boots, etc. (Fig. 7.5). Generalized infections are also common, particularly in younger horses (Fig. 7.6).

Figure 7.5 (A) Diffuse infection with Trichophyton equinum var. autotrophicum in the girth and chest wall areas due to infection from contaminated girths and riding boots. (B) The worst affected areas are in the regions where skin rubbing by the tack occurs the most.

Figure 7.6 Ringworm. Generalized infection with Trichophyton equinum var. autotrophicum in a 6-month-old Warmblood foal.

Different species of Trichophyton such as T. verrucosum and T. mentagrophytes, which are respectively usually derived from infected cattle and rodents, show some differences in the type of lesion (Fig. 7.7 and Fig. CD7 • 1A–D) .

Figure 7.7 Trichophyton verrucosum infection derived from infected cattle. The cattle and the horse fed from the same metal hay rack. Note the generally verrucose nature of the lesions (A) and the mildly inflamed, hairless, shiny skin surface that is exposed when a scab is lifted off (B). The severity and extent of the condition was noticeably worse in the region where the head collar made contact with the skin. The owner of this horse was also affected on her arms and neck.

Lesions are pruritic only in the early stages of infection; however, the horse can be irritable if lesions are ‘picked’ with a fingernail (when performing this test, due hygiene precautions must be taken for self-protection). This response persists even 5–10 days after treatment if the lesion is still infected and is a useful aid to diagnosis when the hair has been shed and scale and crust are still present on the lesion.

The healing lesions are usually markedly alopecic, smooth and silvery in colour. There may be secondary infection under the shedding scab with accumulation of purulent material.

Differential diagnosis

• Microsporum infection: this is a similar condition epidemiologically and clinically but tends to involve only a proportion of the hairs in an infected area; plucking of the hair is therefore more difficult and is sometimes resented.

• Dermatophilosis (Dermatophilus congolensis): characteristic bacteria and epidemiology; tends to infect the back and lower limb legions mostly and lesions are more purulent.

• Culicoides allergy/hypersensitivity (sweet itch): severe localized pruritus mainly centred on the mane, tail and in some cases the ventral abdomen, associated with seasonal exposure to Culicoides spp. in particular.

• Insect bites: defined localized swellings associated with oedema and a central haemorrhagic spot.

• Mite or louse infestation: obvious parasites and more pruritus; localized to limbs and head and tail; no defined lesions usually present.

• Pemphigus foliaceus: this can be very similar clinically and even histologically and it may require special stains to identify the fungal elements.

• Sarcoidosis: generalized exfoliative seborrhoeic disease with little similarity; some generalized forms of trichophytosis can be similar but they tend to self-cure and mycology and skin scrapings are diagnostic.

• Granulomatous enteritis syndrome: systemic involvement with prominent scaling.

• Alopecia areata: similar circular areas but with characteristic absence of any inflammatory responses and sterile cultures; characteristic histology.

• Anhidrosis: single cases affected with typical history of a move to a warm climate; affected cases may develop secondary trichophytosis due to impaired local immunity.

• Actinic dermatitis: restricted to white regions, particularly on the nose, face and distal limb regions.

• Mercurial poisoning: history of applications.

• Wound/exudate/lacrimal scalding: history and obvious clinical evidence; may be secondarily affected with trichophytosis due to skin damage.

Diagnostic confirmation

• Characteristic clinical signs and history of contact with infected horses (or other species).

• Hair plucking from the margins of fresh lesions (Fig. 7.8) can be examined microscopically (possibly after clearing with chlorolactophenol or 10% potassium hydroxide solution). Hyphae and relatively few large endothrix spores will be seen.

• Staining with lactophenol cotton blue can assist the recognition of the hyphae.

• Infected hairs do not fluoresce under ultraviolet light.

• Culture of hairs plucked from the margins of lesions on Sabouraud’s fungal medium. Medium with added phenol red provides an early indicator of dermatophytosis. Culture permits easy identification of the typical macroconidia.

• Skin biopsy is usually diagnostic of dermatophytosis but does not help to establish the species concerned (upon suspicion the pathologists should be informed so that special stains can be used to confirm the hyphae and spores).

Figure 7.8 Hair plucking being taken from one of many circular alopecic, scaling lesions on a pony mare. Note that gloves are worn when handling the case and that hairs are plucked using artery forceps from the margin of the lesion.

Note

It is not easy to be certain of the species of fungus involved without culture. Cultures of hair plucking on commercially prepared Sabouraud’s agar at 25°C show characteristic colonies and change in colour of medium. The species can be confirmed from the colony and conidial spore characteristics.

For Trichophyton equinum vitamin enrichment is important and this can be achieved by the addition of two drops of injectable vitamin B complex to the medium.

Treatment

Most cases will resolve spontaneously after 6–12 weeks (particularly if the horses are in sunshine) (Pascoe 1973a). Treatments do not shorten the course but may limit the spread of infection and limit the extent of environmental contamination. Subsequent immunity can last for an extended period but some cases can re-emerge following partial elimination from hair follicles.

Treatment is directed at the use of fungicidal treatment of the horse and sporicidal treatment of the environment. The infected areas should be clipped (taking care to disinfect the clippers at regular intervals and particularly thoroughly after each horse). All horses in contact should be considered for treatment at the same time and access to sunlight should be encouraged. The horse(s) may be washed with a fungicidal wash such as enilconazole or natamycin. Proprietary washes of these compounds are widely available. A 2% miconazole–2% chlorhexidine shampoo applied twice weekly has been shown to be effective in reducing the infectivity and so limiting an outbreak (Paterson 1997). Some tertiary amine surgical scrub solutions have a strong antifungal (but limited sporicidal) effect. Spot treatment of lesions (with the above solutions or miconazole) is probably not very useful in the horse in view of the rapid spread across the horse.

Individual lesions and the immediate surrounding hair may also be scrubbed for 1–2 minutes daily for 7–10 days with one of the following treatments:

• 10% povidone-iodine solution

• 2.5% lime sulphur in water

• 10% thiabendazole in water

• 2.5–10% tincture of iodine (painted on, not scrubbed)

• 0.3% Halamid

• tertiary amine disinfectant scrub solution.

Oral griseofulvin may be administered daily for 15–60 days (Hiddleston 1970) but the results of this alone are very variable. There are no reports of its efficacy and many specialists consider that it is of no material help. In any case, it probably does not reduce the infectivity of the spores and fungus-laden hairs. It should therefore not be used alone except perhaps in grazing horses. The drug is teratogenic and must not be used in pregnant mares.