Aalbæk, Bent

McEvoy, Fintan

Spodsberg, Eva-Maria Hohneck

English

Copenhagen University Research Information System

u n i ve r s i t y  o f  co pe n h ag e n  Københavns UniversitetFeline disseminated cryptococcosisSpodsberg, Eva-Maria Hohneck; Aalbæk, Bent; McEvoy, FintanPublished in:Dansk VeterinaertidsskriftPublication date:2012Document versionEarly version, also known as pre-printCitation for published version (APA):Spodsberg, E-M. H., Aalbæk, B., & McEvoy, F. (2012). Feline disseminated cryptococcosis: a case report.Dansk Veterinaertidsskrift, 95(13), 26-29.Download date: 03. Feb. 202026      DVT 13 2012ORIGINALARTIKELIntroductionCryptococcosis is an opportunistic syste-mic fungal infection and occurs worldwide, caused by several Cryptococcus (C.) spe-cies, which are saprophytic, round, basidi-omycetous yeasts with C. neoformans most commonly causing disease (1, 2, 3). Infection occurs in the environment through e.g. pigeon droppings and soil rich in vegetable matter primarily via inhalation through the respiratory system. Cryptococcal basidiospores are consid-ered the main infectious particles due to their small size of 2-3 µm, compared to vegetative, encapsulated cells (4, 5). In the desiccated state, the Cryptococcus organ-ism may be no larger than 1 µm and may survive up to 2 years (2). In infected tissue, and often when cultured, the organism is a variable-sized yeast (3.5 to 7 µm) with a large heteropolysaccharide capsule (1 to 30 µm) (2). The majority of yeasts settle out in the nasal cavity or nasopharynx, where they can produce disease or result in animals becoming asymptomatic carriers of the organism (2).Feline disseminated cryptococcosisA case reportSPodSBerg, e.h.1*, aalBæK, B.2, mCeVoy, F.J. 11UniVerSity hoSPital For ComPanion animalS, dePartment oF Veterinary CliniCal and animal   SCienCeS, FaCUlty oF health and mediCal SCienCeS, UniVerSity oF CoPenhagen, denmarK2dePartment oF Veterinary diSeaSe Biology, FaCUlty oF health and mediCal SCienCeS, UniVerSity oF CoPenhagen, denmarK*CorreSPonding aUthorSummary Disseminated cryptococcosis was diagnosed in a cat presenting with severe dyspnoea and multiple cutaneous nodules based on cytology, serology and culture. A 3.5 years old male, castrated, domestic shorthaired cat presented with an acute history of progressive dyspnoea, tachypnoea and anorexia and a history of chro-nic continuous stridor, stertor and recurrent cutaneous masses.Nasal and thoracic radiographs showed an increased opacity in the nasal cavity, a diffuse pulmonary infiltrate and a suspected cranial mediastinal mass. Thoracic ultrasound confir-med the presence of several cranial mediastinal masses. Fine needle aspiration of the cutane-ous and mediastinal masses revealed the pre-sence of encapsulated yeast cells. Culture con-firmed infection with Cryptococcus neoformans. Latex Cryptococcus agglutination antigen test was highly positive with a titer of  >1:8192. The cat was treated with fluconazole for 15 months until the titer was below detec-table levels. Sammendrag En kat med svær dyspnø og multiple kutane masser blev diagnosticeret med dissemineret cryptococcose på basis af cytologiske og serologiske undersøgelser samt mykologisk dyrkning.En 3,5 år gammel, kastreret hankat blev præsenteret med akut, progressiv dyspnø, tachypnø og anorexi. Katten havde haft kro-nisk stridor og stertor og tilbagevendende kutane masser. Røntgenbilleder fra næse og thorax viste en øget opklaring i næsehulen, en diffus pulmonær infiltrering og en mistænkt kranial mediastinal masse. Den sonografiske undersøgelse af thorax bekræftede forekom-sten af flere kraniale mediastinale masser. Fin-nålsaspiration af de kutane og mediastinale masser viste kapseldannende gærceller. Myko-logisk dyrkning bekræftede infektion med Cryptococcus neoformans. Latex Cryptococcus Agglutination Antigen Test var kraftigt positiv med en titer på >1:8192. Katten blev behandlet med fluconazole i 15 måneder indtil titeren fandtes negativ.Dissemination can occur by either direct extension or hematogenous spread (by macrophages), to the skin, lungs, eyes, or central nervous system (CNS) (2, 4, 6). Direct extension from the nasal cavity through the cribriform plate to the CNS or to the paranasal soft tissues and skin is common (2). Cell-mediated immune response results in granuloma formation (2). Direct implantation into skin wounds may also occur. Cryptococcosis is a spo-radic infection, but is considered the most common systemic fungal infection in cats worldwide (3). Exposure to outdoor envi-ronments is significantly associated with the disease (7, 8, 9). While cryptococcosis in people is most often associated with immunosuppression, the organism appears to be a primary pathogen of immunocom-petent cats and dogs (2). An association with feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infections in cats has been reported, and prolonged glucocorticoid treatment has been impli-cated as a predisposing factor in both cats and dogs (2). However, cryptococcosis is DVT 13 2012      27 not more common in cats with retroviral infections (7, 8, 10, 11). Diagnostic options of cryptococcosis include cytologic examination, capsular antigen detection, and culture. Cytological finding in aspi-rates of encapsulated yeast cells is sugges-tive. Capsular antigen can be demon-strated by Latex Cryptococcus Agglutination Test (LCAAT) (12). Aetiolog-ical diagnosis is obtained by culture and mycological characterisation of the isolate.Case HistoryA 3.5 years old male castrated, domestic shorthaired cat presented to the University Hospital for Companion Animals at the University of Copenhagen with a 5-days history of progressing dyspnoea, tachyp-nea and anorexia. The cat was born and raised in California, USA and was imported to Denmark one year previously. It had a history of long-standing respiratory symp-toms, described as continuous stridor and stertor and occasionally dyspnoea, and recurrent cutaneous masses, some of which had been surgically removed. There was no history of nasal discharge and cough was only occasionally observed. The cat had been kept indoors for the past year, but had been an outdoor cat prior to that. It was current on vaccinations, but it had not been wormed for the last year. It had been treated with amoxicillin/clavula-nic acid (12.5 mg/kg q12h per os) without response for the previous three days. Physical examination confirmed tachy-pnoea (respiratory rate 50 breaths/min-ute) with an increased inspiratory and expiratory effort. Auscultation of the lungs was difficult due to pronounced stridor and stertor. Mucous membranes were pale pink with a capillary refill time of two sec-onds. The cat had multiple cutaneous, indolent, mobile, firm masses of varying size with a raised, smooth surface, dis-persed over the whole body.The initial therapeutic approach was aimed at addressing the respiratory dis-tress with oxygen supplementation. After the initial stabilization, blood was collected for complete blood count (CBC), serum biochemistry, acid-base chemistry (venous blood sample) and Idexx SNAP® FIV/FeLV Combo Test. CBC and biochemistry did not show any abnormalities except for a mild stress-induced hyperglycemia. Acid-base chemistry did not show any abnormalities either, but as venous blood was used, blood oxygenation could not be assessed. Lactate was in the reference range. FIV and FELV tests were negative. Nasal and thoracic radiographs showed an increased opacity in the nasal cavity and a diffuse pulmonary infiltrate with a broncho-interstitial pattern and a sus-pected cranial mediastinal mass (Figure 1). Thoracic ultrasound confirmed the pres-ence of several cranial mediastinal masses (Figure 2). Fine needle aspirates (FNA) of all cutaneous masses were performed and revealed a yellowish gelatinous content. On cytology encapsulated yeast cells were observed (Figure 3). On day 2, fine needle aspirates of the cranial mediastinal masses and a computed Figure 3. Cytology from multiple cutaneous lesions and mediastinal masses. There is a massive appe-arance of circular cryptococcal cells of varying size surrounded by a large capsule. There is an infiltrate of activated highly vacuolized macrophages, sho-wing active phagocytosis. Background material consists of a basophilic lightly granulated material, compatible with proteinaceous material. Figure 1. Thoracic radiograph of the cat: detail of thoracic radiograph, latero-lateral projection. Dif-fuse pulmonary infiltrate with a broncho-intersti-tial pattern is visible.Figure 2. Ultrasonography of the thorax of the cat. There are three approximately 1.5 cm in diameter roughly spherical masses in the cranial mediasti-numtomography (CT) of the nasal cavity and thorax were performed under general anaesthesia. Recovery from anaesthesia was uneventful. In fine needle aspirates of the mediastinal masses encapsulated yeast cells identical to those from the cutaneous masses were demonstrated (Figure 3). Computed tomography revealed soft tis-sue masses in the nasal cavity and frontal sinus, nasal turbinate destruction and deviation of the nasal septum, soft tissue nodules distributed throughout the lungs and lung consolidation in the ventral lung field (Figure 4).  Aspirated material from a cutaneous nodule was cultured on Sab-ouraud dextrose agar (CM0041, Oxoid, Basingstoke, Hampshire, England). After incubation at 30° for 7 days, growth was observed of grey-white, mucoid colonies consisting of budding yeast cells with cap-sule formation (Figure 5).  A subculture was identified as Cryptococcus neoformans by using the API 20C AUX kit (BioMerieux, 3 B: Mediastinal mass.3 A: Skin. >28      DVT 13 2012Marcy-l’Etoile, France) according to the manufacturer’s instructions. Latex Crypto-coccus agglutination antigen test (LCAAT), performed on blood serum at Athens Uni-versity, Georgia, USA, was highly positive with a titer of >1:8192. Treatment with the antifungal flucon-azole (10mg/kg q12h PO) was initiated on day 2 based on the cytological findings. The cat continued to be stable on cage rest and did not require further oxygen supple-mentation. It was bright, alert and respon-sive, started eating, and was discharged after five days with instructions to ensure a quiet, non-stressful environment and reduced physical activity. Follow-up examinations were performed on day 30, 90 and 150. Blood samples for biochemistry profile and LCAAT titer were obtained to monitor progress of treatment and liver parameters, as increased liver enzyme activity and hepatic toxicity are known as rare side-effects of fluconazole treatment. Liver parameters were within reference range and LCAAT titers were unchanged on all follow-up visits. No clini-cal side effects to medication were observed. On day 30, the cat was bright, alert and responsive. The cutaneous nod-ules were unchanged. On day 90, all nod-ules had disappeared except for one which had decreased in size. On day 150, the last nodule had completely disappeared. The cat’s activity level had markedly increased and the only clinical signs were stridor and stertor. Thoracic radiographs were obtained which did not show improvement compared to previous findings. After mov-ing back to the USA, LCAAT titer was tested 15 months after treatment start with levels below detection limit. Flucon-azole treatment was discontinued. DiscussionThis presentation of a young cat with chronic respiratory symptoms and cutane-ous nodules due to disseminated crypto-coccosis represents a rare case in Denmark, though the disease is described to have worldwide significance. In all likelihood, the infection had been acquired during the cat’s stay in California, USA, as it had a history of long-standing respiratory signs. Regarding the cat’s history, systemic mycoses were important differential diag-noses due to a high prevalence in certain regions in the USA. All findings including the history of long-standing continuous upper respiratory tract noise and chronic recurrent cutaneous nodules could be explained by chronic disseminated crypto-coccosis with intranasal, intrathoracic and cutaneous involvement.The severe findings on radiography and CT indicated irreversible chronic intranasal changes and marked pulmonary pathology with intrathoracic granulomata which might prevent full recovery, so that ongo-ing respiratory sounds and decreased lung capacity would be expected. The presence of CNS disease caused by cryptococcosis is the major factor described to influence outcome in cats (13). In our case, the cat did not show any signs of CNS involve-ment, but as imaging studies of those regions were not performed, this could not be definitely ruled out. Our patient had a LCAAT titer >1:8192 which correlated pos-itively with the disseminated distribution of the disease, as patients with dissemi-nated skin and/or lymph node involve-ment have significantly higher titers (12). Although the prognosis of cryptococcosis should be considered as guarded, a major-ity of cats can be expected to be cured, but treatment is protracted and expensive (13). We initiated treatment with flucon-azole, an azole antifungal, which is described to be very effective in the treat-ment of feline cryptococcosis, including cases with advanced, longstanding, or dis-seminated disease (2, 13, 14). Further-more, this drug can be given orally. Side effects in cats can be inappetence and, rarely, increased liver enzyme activity and hepatic toxicity (14). On follow-up visits, liver enzyme activity and LCAAT titers were measured to monitor progress, evaluate prognosis, and guide cessation of treat-ment (2, 12, 15, 16). The cat responded well to treatment and no side effects were observed. Antifungal therapy was contin-ued until the LCAAT titer declined to an undetectable level after 15 months of con-tinued therapy. This was a significantly longer treatment period than described in a previous study where the median dura-tion of treatment with fluconazole in cats Figure 4. CT nasal cavity and thorax (2 mm slice thickness). A: Nasal cavity: soft tissue filling bilaterally in the nasal cavity and in the left frontal sinus, bilateral nasal turbinate destruction and deviation of the nasal septum. B: Thorax: soft tissues nodules distributed throughout the lungs and significant consolida-tion of the lungs in the ventral lung field. Figure 5. Culture on Sabouraud dextrose agar of isolate from aspirated material from a cutaneous nodule, incubated at for 30°C for 6 days, showing mucoid, grey-white colonies.ORIGINALARTIKELDVT 13 2012      29 with less severe cryptococcosis was 4 months with a range of 1 to 8 months (13). Due to the advanced disease progression in our patient, a longer treatment period was expected. Despite clinical improve-ment, resolution of the cutaneous masses and a finally undetectable LCAAT titer, a full recovery with resolution of all respira-tory symptoms seems unlikely due to the severe intranasal anatomical changes. This case report emphasises that it is important to consider cryptococcosis in Reference1.     Bovers, M., Hagen F., and Boekhout T. Diversity of the Cryptococcus neofor-mans-Cryptococcus gattii species complex. Rev.Iberoam.Micol. 2008. 25:4-12.2.     Taboada, J. and Grooters A.M. 2011. Cryptococcosis, In: S. J. Ettinger and E. C. Feldman (eds.), Textbook of Veterinary Inter-nal Medicine. 7. ed. W.B.Saunders Company, Philadelphia. 3.     Lester, S. J., Malik R., Bartlett K.H., and Duncan C.G. Cryptococcosis: update and emergence of Cryptococcus gattii. Vet.Clin.Pathol. 2011. 40:4-17.4.     Giles, S. S., Dagenais T.R., Botts M.R., Keller N.P., and Hull C.M. Elucida-ting the pathogenesis of spores from the human fungal pathogen Cryptococcus neo-formans. 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Feline disseminated cryptococcosis:a case report

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Feline disseminated cryptococcosis:a case report

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