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109  Fungal Infections  993

                 In contrast to cats, dogs often develop widespread   Because false‐positive latex agglutination titers of up to
  VetBooks.ir    dissemination with neurologic involvement. They may   1:200 have been detected in cats, attempts to confirm
               also  present  with  signs  relating  to  gastrointestinal  or
                                                                  infection using other diagnostic tests are recommended
               pancreatic involvement. Cryptococcal rhinosinusitis
               may be subclinical in dogs or may result in sneezing and   in animals that have titers <1:200. For dogs and cats sus­
                                                                  pected to have cryptococcal meningoencephalomyelitis
               mucopurulent nasal discharge. Cutaneous involvement   that have negative serum antigen titers, CSF should be
               is uncommon but, as in the cat, may be a marker for dis­  submitted for cytologic examination, antigen titers, and
               seminated disease. Other clinical signs that are occasion­  fungal culture.
               ally present in dogs include peripheral lymphadenomegaly
               or lameness (due to osteomyelitis or arthritis).
                                                                  Therapy
                                                                  Some dogs and cats with cryptococcosis, especially
               Diagnosis
                                                                  those with lesions restricted to the skin, can be treated
               Thoracic radiographs in dogs and cats with cryptococ­  successfully with azole antifungal drug monotherapy.
               cosis are often normal, although interstitial to alveolar   Fluconazole is a reasonable initial choice, because of its
               infiltrates or small nodular lesions may be present.   good penetration of the brain and eye. Generally, cats
               Occasionally, pulmonary  nodules,  tracheobronchial   improve within 1–2 weeks of starting therapy. Treatment
               lymphadenopathy, mediastinal masses, or pleural effu­  should be continued until there is complete lesion
               sion are found.                                      resolution and the cryptococcal antigen titer becomes
                 Definitive diagnosis of cryptococcosis is based on eval­  negative. This typically takes 2–12 months, although
               uation of representative tissue specimens or body fluids   longer periods of therapy may be required. For recovered
               (including cerebrospinal fluid) with cytology, culture,   animals that achieve an antigen titer of 0, the titer can be
               and occasionally histopathology (Figure 109.4), with or   monitored every 3–6 months, so that relapse is diag­
               without serologic detection of cryptococcal antigen.  nosed early. Some cats (especially those in California
                 Latex agglutination assays for detection of cryptococ­  infected with molecular type VGIII) fail to respond com­
               cal polysaccharide capsular antigen are widely used in   pletely to treatment, antigen titers persist at high levels,
               veterinary patients and are very (>85%) sensitive and   and relapse occurs after an initial treatment response. In
               specific, although false‐negative and false‐positive   some of these cats, prognosis is guarded and treatment
               results can occur. ELISAs are also available. Serum anti­  with other azoles or combination therapy with ampho­
               gen testing provides a rapid diagnosis when organisms   tericin B may be necessary.
               cannot be visualized or cultured, and may prove advan­  For  cats with  CNS  cryptococcosis  or  those  that  fail
               tageous when CSF collection is unacceptably risky. Even   to  respond to azole antifungal drugs, a combination
               a titer as low as 1:2 can indicate cryptococcal infection.   of amphotericin B and 5‐flucytosine (250 mg PO q8h) or
                                                                  amphotericin B and fluconazole is recommended. Dogs
                                                                  with disseminated disease or CNS involvement should
                                                                  be treated initially with amphotericin B and fluconazole,
                                                                  because those treated with flucytosine often develop
                                                                  cutaneous necrosis 1–2 weeks after starting therapy.
                                                                  Treatment with 5‐flucytosine and amphotericin B is con­
                                                                  tinued for 2–4 weeks or until azotemia develops, after
                                                                  which treatment is continued with an azole. Anecdotally,
                                                                  administration of terbinafine to some dogs and cats that
                                                                  have failed azole or amphotericin B treatment has led to
                                                                  clinical improvement.


                                                                  Prognosis
                                                                  In studies from Australia, approximately 75% of cats with
                                                                  cryptococcosis were treated successfully. In one study,
                                                                  the median survival time of cats with CNS cryptococco­
                                                                  sis was only 13 days (0–4050 days), but outcomes were
                                                                  more favorable if cats survived at least three days after
               Figure 109.4  Histopathology showing large numbers of
               Cryptococcus organisms within the meninges of a 3‐year‐old   diagnosis. The prognosis is guarded for dogs, with suc­
               domestic short‐hair that died of disseminated cryptococcosis.  cess rates that range from 30% to 55%. The median survival
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