Carlos Eduardo Larsson
Full professor of Internal Medicine-FMVz/USP, Av. Prof. Dr. Orlando Marques de Paiva
São Paulo, Brasil
Among the subcutaneous and systemic mycosis (European blastomycosis or torulosis) is the most frequently diagnosed in cats. Ajello (1970) classified the disease as "sleeping disease", hidden on the iceberg of medical mycology. However, after a short period of time this concept drastically changed because this infection became an awake giant7 given the increasing use of immunosuppressive therapy in organ transplantation. Moreover, after the AIDS arrival the occurrence as well as the severity itself of the human cryptococcosis increased considerably.
CAUSE AND PATHOGENESIS
The causative agent is a capsulated saprophytic ubiquitous yeast that belong to the Basidiomycotina subdivision, species Cryptococcus neoformans, with two varieties neoformans and gattii. The former is cosmopolite found in temperate climate regions, frequently isolated from bird feces. On other hand, the variety gatii frequently found in tropical areas has been isolated mainly from vegetable tissues12. Currently there are four serotypes differentiated according to the external capsule's polysaccharides component. This capsule is the main virulence factor2. The encapsulated agents are not phagocytosed because are electronegativity charged determining a electrostatic rejection between the yeast and the host defense cells that are isoeletric13.
The well characterized four infective serotypes (A, B, C, D) were identified during the fifties and the sixties. The serotype A is the most common all over the world; the D is rare in the EUA although frequent in Italy and Spain. The serotypes A and D are the most commonly isolated from animal lesions and bird feces in the USA as well in Brazil2,14.
Several question regarding the infections pathways unanswered to date. Probably the agent inhalation is the most feasible. However in some reported cases the initial lesions developed in areas such as the clawbeds2,3,8. Nasal or pulmonary is not the most common. In the respiratory tract the agent grows with a massive capsular glycoprotein release in the blood stream. The capsule interferes greatly with antigen presentation determining the subsequent immune response and thus the agent elimination. The yeast disseminate to the CNS through the hematogenous pathway and may also reach it from the nasal cavity by contiguity (through cribriform plates)6. The disease establishment and diffusion in the host, show a narrow relationship with the all mediated immunity.
In human medicine, a search for immunosuppression causes is always performed for instance in cryptococcal meningitis patients since that human beings have a solid natural resistance to the Cryptococcus. Usually the immunosuppressive causes are secondary or tertiary to lymphoreticular neoplasias, glucocorticosteroid therapy and also sarcoidosis and HIV infections. In veterinary medicine a search for immunosuppression the cryptococcal infections has been aggravated or accelerated by the abusive and sometimes incorrect use of corticosteroids.
It has been speculated that FeLV and FIV infection may play a role as a predisposing factor to the cryptococcosis in diseased cats. However reports from north american, australian and brazilian authors could not confirm such hypothesis, meaning that the prevalence of FIV/FeLV infections in cats with cryptococcosis is similar to those from the general feline population what is also true regarding the disease prognosis2,4,10,15.
According to LARSSON8 (2000) the immunodeficiency factors in canine cryptococcosis cases has been infrequently (less than 10% of the cases).
Although the cryptococcosis affects several animal species (domestic and wild), dogs and cats are more susceptible to the disease showing characteristic clinical signs.
The feline are the most affected by the cryptococcal infection as well as by the disease itself. The Brazil may be the only country in which the number of feline cryptococcosis cases surpasses the sporotrichosis cases.
Both of the varieties (C. neoformans var neoforman and gattii) has been isolated in cats. In Brazil2 the disease is more frequent in cats older than 4 years (62%), mean age of 63 months, males (75%), pure breed animals, especially Siamese cats (60%). However with the exception of this breed, also reported by MALIK et al10 (1992), in the USA there is no sex or age susceptibility6.
The canine cryptococcosis in seen in adult animals from one to seven years of age and among these four years old or younger animals are over represented.
There is no sexual predisposition although some breeds seen to be more susceptible such as Doberman pinscher, Great Dane and Cocker Spaniels8,9.
Clinical signs or lesions found in canine and feline cryptococcosis6 are listed in Table 1.
Generally the diagnosis is established with relative easiness, especially in cats. Besides the symptoms / clinical signs and the findings of physical, dermatologic, neurologic and ophthalmologic examinations, it requires some complementary exams2,6,11,14. Among these and considering the most utilized are the fungal culture, histopathology and serology.
The cytologic exam represents a quick method to demonstrate the agent from fistular, erosions, ulcerations, CSF and aqueous humor materials. The New Methylene blue, Gram and India (Nankin) stains are also utilized. The agent cannot be visualized by this method in approximately 25% of cases and thus a negative result in the cytologic exam does not rule out the cryptococcosis diagnosis.
The serologic tests are used to capsular antigen detection through latex agglutination test or a ELISA test with polyclonal antibodies capture and monoclonal detection, being the former (LAT) the most utilized one. It's not rare to find false negative results in patients with localized skin lesions.
The fugal isolation represents the method of choice due to the effortless agent isolation from tissues fragments, exudate material, urine, CSF and synovial fluid. It is used agar Sabouraud dextrose media, sometimes with antibiotics, with the exception of cyclo heximide (actidione). Thus, one should pay attention to not include this impeditive substance in the yeast culture media, in order to avoid false negative results. The culture plates are maintained under 25° and 37° C degrees evaluating the growth in a period ranging from 2 to 42 days, depending on the amount of inoculum. Morphometry, growth temperature (37° C), urea hydrolysis, assimilation tests response and even virulence determination in mouse are features used to the fungal identification.
The histopathologic exam is made from skin biopsy fragments (incisionals or excisionals) stained by HE, PAS, GMS, Masson Fontana and mainly by Mayer´s mucicarmine. This later is the definitive stain of choice, because the cryptococcal capsule appears a rose-red colour and the organism appears pink in a blue background.
1. Ajello, L. The medical mycological iceberg. Proceedings International Symposium on Mycoses, 1970. Pan Amer. Healthy Org., Washington, DC, USA.
2. Chiesa, S.C. Criptococose felina: aspectos clínico-epidemiológicos. São Paulo (Brasil), 1998. 94 p. Dissertação (Mestrado). Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo.
3. Diamond, R.D. Cryptococcus neoformans. In: MANDELL, G.L.; DOUGLAS, R.G.; BENNETT, J.E. (eds): Principles and Practice of Infections Diseases. New York, John Wiley & Sons, p. 1460-8, 1985.
4. Flatland, B.; Greene, R.T.; Lappin, M.R. Clinical and serologic evaluation of cat with cryptococcosis. JAVMA., v. 209, p. 1110-13, 1996.
5. GROOTERS, A.M. Systemic mycoses with dermatologic manifestations. In: AAVD/ACVD Meeting , 17th, New Orleans/USA. Proceedings, 2002. p. 73-77.
6. Jacobs, G.J.; Greene, C.E.; Medleau, L. Criptococosis felina y canina. WALTHAM FOCUS, v. 8, n. 4, p. 21-7, 1998.
7. Kaufman, L.; Blumer, S. Cryptococcosis: the awakening giant. In: The black and white yeasts. International Health Organization Science Publishing 356, Washington, DC: 1978, Proceedings, p. 176-84.
8. Larsson, C.E. Criptococose. In: Simpósio Brasileiro Sobre Micoses Animais, Porto Alegre (Brasil). Anais, 2000. p. 72-7.
9. Malik, R.; Dill-Macky, E.; Martin, P. Cryptococcosis in dogs: a retrospective study of 20 consecutive cases. J. Med. Vet. Mycology, v.33, p. 291-7, 1995.
10. Malik, R.; Wigney, D.I.; Muir, D.B. Cryptococcosis in cats: clinical and mycological assessment of 29 cases and evaluation of treatment using orally - administered fluconazole. J. Med. Vet. Mycology, v. 30, p. 133-44, 1992.
11. Medleau, L.; Barsanti, J.A. Cryptococcosis. In: GREENE, C.E. (ed). Infectious diseases of dogs and cats. Philadelphia, W.B. Saunders, 1990. p. 687-95.
12. Montenegro Netto, H. Ocorrência das variedades de Cryptococcus neoformans na Cidade de São Paulo (Brasil): isolamento em fezes de pombo e em bosques de eucalipto. São Paulo (Brasil), 1998. 89 p. Tese (Doutorado). Instituto de Ciências Biomédicas da Universidade de São Paulo.
13. Nosanchuk, J.D.; Casedevall, A. Cellular charge of Cryptococcus neoformans: contributions from capsular polyssacaride, melanin and monoclonal antibody binding. Infection and Immunity, v. 65, p. 1836--41, 1997.
14. Scott, D.W.; Miller Jr., W.H.; Griffin, C.E. In: Muller & Kirk´S Small Animal Dermatology. 6 ed., Philadelphia, Saunders, p. 375-400, 2001.
15. Walker, C.; Malik, R.; Canfield, P.J. Analysis of leucocytes and lymphocyte subsets in cats with naturally occurring cryptococcosis but differing feline immunodeficience virus status. Aust. vet. J., v. 72, p. 93-7, 1995.
Carlos Eduardo Larsson