Susan E. Shaw, BVSc (Hons), BSc, DACVIM, DECVIM, FACVSc, MRCVS
It is not uncommon in cats for percutaneous injury to introduce deep infections that progress to form poorly healing wounds, draining tracts, cutaneous nodules and /or ulceration. Greater global movement of animals, climate change and improved methods of detection have meant that more unusual fungal, bacterial and protozoal infections are being increasingly diagnosed world-wide.
A. SUBCUTANEOUS AND DEEP FUNGAL INFECTIONS
Deep dermal and subcutaneous fungal infection with M. canis caused by dermatophytes is reported almost exclusively in Persians. Because of the strong breed predisposition, selective immunodeficiency to the organism may play a role. Infection probably begins with follicular colonisation followed by deeper implantation from bites or self-trauma. Multiple or solitary, firm, nodules with or without tracts draining seropurulent material with granules are present. The syndrome is usually associated with concurrent generalised cutaneous dermatophytosis and hairs from unaffected areas are often positive on Woods' lamp and culture. Systemic signs are uncommon although lymphadenopathy may occur. Concurrent FeLV /FIV status requires evaluation. Definitive diagnosis involves recognition of the breed predisposition, histopathology with PAS/silver and fungal culture from a biopsy sample. Surgical removal is recommended in combination with itraconazole (7-10mg/kg SID) for 4-6 weeks. However, prognosis for cure is poor and recurrence is probable.
Opportunistic subcutaneous fungal infections
A syndrome of ulcerated poorly healing nodules in the "fight and bite" sites mimicking cryptococcosis with or without nasal cavity involvement, is now recognised. Species of opportunist fungi including Aspergillus, Alternaria, Penicillium, have been isolated. Cryptococcal antigen titres are negative. Saprophytes fungi can also be involved in the syndrome of eumycotic mycetoma. The major identifying sign is the presence of granules or grains in discharge from lesions. Extension of infection to involve subcutaneous tissue may occur.
Phaeohyphomycosis is another uncommon fungal syndrome. The fungi concerned (D.reschlera, Curvularia, Phialophora, Cladosporium ) are marked by their dark pigment. Diagnosis requires cytology with special staining of discharge, histopathology with special staining and culture. Therapy is problematic. The biological behaviour of these organisms varies as does their susceptibility to antifungal therapy. There may be partial response to triazoles (itraconazole 7-10mg/kg SID)but recurrence is common and surgical debulking in combination with IV amphotericin B (0.5mg/kg q48/72hrs cumulative dose to 4-8mg/kg) may be the only curative approach. Liposomalised amphoteracin B may allow up to 2mg/kg per dose to be used without nephrotoxicity.
The prevalence of cryptococcal infection is unknown but it is considered a ubiquitous pathogen with a world-wide distribution. Cryptococcus neoformans (var neoformans, var gattei), is a dimorphic fungus which is an inhabitant of decaying vegetation and soil. The route of entry is usually by inhalation of mycelia and colonisation of the respiratory tract particularly the nasal cavity in the cat. However, percutaneous infection has been reported in other species. Cutaneous manifestations include multiple subcutaneous nodules with ulceration of the head, bridge of nose and periocular regions. Clinical signs are referable to nasal granulomata, local involvement of bone, and ocular involvement (uveitis, optic neuritis, retinal detachment). Neurological signs are dependent on the site of granuloma formation and regional lymphadenopathy is common. Demonstration of encapsulated yeast in cytology specimens or in PAS stained biopsy specimens are quick and usually definitive diagnostic tests. The organism can be cultured from tissue and exudate. Serological detection of capsular antigen is validated in the cat. Therapy may involve surgical debulking of the lesion in combination with oral fluconazole (10-15mg/kg SID/BID), oral itraconazole (7-10mg/kg SID) for 4-6 weeks, and/or IV amphotericin B treatment as for subcutaneous fungal infections. The prognosis is guarded to good for C.n.var. neoformans but poorer for C.n.var. gattei.
The dimorphic fungus Sporothrix schenkii is an inhabitant of soil and decaying vegetation. Infection occurs via contaminated wounds. Sporotrichosis is recognised as a major pathogen of people and transmission by bite or scratch wounds from infected cats is reported. Early lesions may mimic catfight wounds and are distributed on the head, limbs and base of tail. As the disease progresses, nodule formation with multiple draining sinuses occurs. Cavitating ulcers may develop which expose subcutis, muscle and bone. Infection usually remains localised in the cat but spread along afferent lymphatics may produce disseminated disease. Spread may also occur following licking and grooming of the lesions. Sporothrix organisms are easily identified on impression smears of draining exudate. Histologically, pyogranulomas are associated with large numbers of intracellular yeast organisms with classic morphology and PAS staining is positive. Culture is definitive but care is required because of the zoonotic implications. Treatment recommended is oral fluconazole (10-15mg/kg Sid/BID) or itraconazole (7-10mg/kg SID) for 6 weeks.
B. MYCOBACTERIAL INFECTIONS
Feline cutaneous tuberculosis
Infection with Mycobacterium microti and M. avium intracellulare is associated with cutaneous disease in exposed cats. M. microti (vole TB) infection is thought to be contracted via fight or bite wounds from a sylvatic reservoir but the source of M. avium intracellulare is rarely determined. Extension of the ulcerated lesions to involve subcutaneous tissue, muscle and bone, and generalised signs may occur. Regional lymphadenopathy is common but macroscopic pulmonary lymph node lesions are not. M. microti has relatively low zoonotic potential but M. avium intracellulare is associated with tuberculosis in humans. Cats may be infected orally or by inhalation with Mycobacterium bovis and M. tuberculosis with resultant systemic involvement. The skin may be secondarily involved. Definitive diagnosis requires culture, PCR and species identification from a biopsy samples (skin and/or lymph node). Cytology and histopathology with Zeil Neelsen (ZN) staining alone, are not pathognomonic. Consideration of the zoonotic risk should precede any therapeutic attempt. Treatment may only suppress clinical signs and life-long therapy may be necessary. Surgical excision of small lesions may be considered with double or triple chemotherapy. Combinations of oral enrofloxacin (0.5mg/kg SID), clarithromycin (5-10 BID) and rifampicin (10-20mg/kg SID or BID) are usually recommended.
Because of difficulty in culture, infection with M. lepraemurium is largely assumed. Rodents are the postulated reservoir and contaminated soil inoculation may play a role. Animals in cooler geographic areas of country appear predisposed but this may reflect the sylvatic reservoir. There is no known zoonotic potential. Two syndromes have been reported. The first is associated with M. lepraemurium, occurs in young cats, is associated with rapid progression of multiple ulcerated nodules with a "tuberculoid" pathology. The second is associated with a novel species of mycobacteria, occurs in older cats and is associated with slowly progressive, single discrete nodules with a "lepromatous" pathology. Regional lymphadenopathy and systemic disease is not common but more likely with the first syndrome. Cytology and histopathology with ZN staining combined with PCR are the diagnostic tests of choice.
Treatment of choice is surgical removal but spontaneous regression may occur. There has been some suggestion that oral clofazimine (8mg/kg SID) for 6-8 weeks is useful for treatment but that has not been our experience. The prognosis is good and there is no zoonotic potential.
Opportunist mycobacterial disease
This syndrome is caused by saprophytic usually non-pathogenic organisms which are found in soil, water, decaying vegetation. Mycobacterium chelonei, M. fortuitum, M. smegmatis and M. phlei have been implicated in causing this syndrome although slower growing species are now being recognised. They cause disease by contamination of cutaneous wounds and are particularly pathogenic if inoculated into adipose tissue. Entry through the gastrointestinal tract is rare. The disease is more common in tropical and semi-tropical areas of the world. No causes of immunosuppression have been found in affected cats. The clinical signs are referable to severe panniculitis. Multiple draining tracts and nodules occur with a punctate "salt and pepper" shaker appearance. Coalescence produces large areas of ulcerated non-healing tissue. The inguinal fat pads, flanks and tail base are predisposed sites but any area may be affected if it is prone to injury and has sufficient subcutaneous fat. Although systemic spread is rare fever, anorexia, reluctance to move may be seen. Primary pulmonary infection with M. fortuitum and disseminated infection with M. smegmatis have been reported and may have arisen from non-cutaneous routes of entry. On histopathology, a pyogranulomatous panniculitis is seen and should automatically warrant a search for mycobacteria. These organisms are difficult to detect in routine acid fast stained sections but the use of modified Fite's or rapid ZN methods increase sensitivity. Culture of a biopsy specimen on Lowenstein Jensen media is the diagnostic test of choice.
Antibiotic therapy in combination with radical surgical debulking is recommended. There is a difference in antibiotic sensitivity between species of opportunist mycobacteria; M. fortuitum and smegmatis are sensitive to the fluquinolones, M. chelonae is sensitive to clarithromycin (See above for dose rates). Antibiotic therapy should be continued for at least 812 weeks. The prognosis is guarded.
C. ACTINOMYCES INFECTION
This is an uncommon bacterial infection causing pyogranulomatous dermatitis. Disease in the cat is primarily attributable to Actinomyces spp which are non-acid fast, micro-aerophilic or anaerobic, filamentous branching rods. The organisms are common in the gastrointestinal tract and oral cavity of cats. Once introduced, infection may extend to produce osteomyelitis and infection of body cavities. Epidural and disseminated forms have been reported. Cutaneous signs are characterised by cellulitis, multiple draining sinus tracts and abscesses. "Sulphur granules" are seen in the exudate. The organism can be identified using cytology from the exudate of a draining sinus tract but more usefully, from an impression smear of sulphur granules. Nocardia infection has a similar pathogenesis and may produce disseminated or pleural disease as well as cutaneous signs. Confirmation of both diseases requires culture. The organisms are difficult to culture due to anaerobic/microaerophilic requirements. Histopathology with special stains (PAS) is required but culture of granules from discharge provides the best confirmation. Therapy and management includes the use of penicillin/potentiated sulphonamide combinations for 8-10 weeks and surgical exploration for a foreign body.
D. RHODOCOCCUS INFECTION
This is an uncommon cause of "poorly healing wounds" and pyogranulomatous dermatitis in cats caused by the intracellular bacterium Rhodococcus equi. The source of infection is likely to be contaminated soil or faeces introduced by cutaneous damage. Affected cats may develop cellulitis, abscess formation, lymphadenitis and pyogranulomatous dermatitis usually of the extremities. Secondary development of multiple organ abscessation and pneumonia may occur. Although no direct transmission to humans from cats has been reported, Rhodococcus is a human pathogen and as such, it is considered a zoonotic infection. Culture from a biopsy specimen is diagnostic. Biopsy followed by special staining with PAS is supportive. The prognosis with rapid recognition and diagnosis is good particularly if there is no systemic involvement. Doxycycline 5mg/kg twice daily for several weeks is recommended.