Signs and Their Pathogenesis

Disruption of normal barriers is necessary to allow Candida spp. to invade the host. Concurrent use of broad-spectrum antibiotics suppresses the normal bacterial flora and allows Candida to proliferate, which increases the risk that organisms will be introduced into tissues. Candida can adhere to a variety of tissue components such as epithelial and endothelial cells, fibronectin, and thrombi, as well as other bacteria and inanimate objects such as catheters.²³ The yeasts can also form biofilms on medical devices and produce a huge variety of hydrolytic enzymes. Within tissues, neutrophils are a key defense against Candida.²⁴ Candida blastospores are phagocytized and destroyed by neutrophils. Mononuclear cells play a less important role. Reactive oxygen species, hydrolytic enzymes, and antimicrobial peptides contribute to the intracellular destruction of blastospores by neutrophils. Thus, any condition that impairs neutrophil numbers or function, such as neutropenia or diabetes mellitus, predisposes dogs and cats to candidiasis. A large number of other cytokines, complement, dendritic cells, and lymphocytes are also involved in the immune response to Candida.²⁴ The formation of hyphae by Candida promotes tissue invasion, which may be followed by life-threatening fungemia and dissemination to multiple organs. This ability of Candida to change its morphology (“morphologic dimorphism”) is thought to be an important virulence factor.

Lower urinary tract candidiasis may be subclinical or associated with dysuria, stranguria, and/or hematuria. Systemic signs of pyrexia, lethargy, inappetence, and weight loss have also been described in affected dogs and cats,⁶ but these signs may result from the presence of other predisposing diseases. Ascending infections may lead to development of Candida pyelonephritis.

Cutaneous candidiasis may manifest as erythema, scaling, alopecia, erosions, and crusting, often where disruption of cutaneous or mucocutaneous regions has occurred (such as a previous surgical site or a feeding tube or cystotomy stoma). Persistent disease in the face of systemic or topical treatment with broad-spectrum antibiotics should raise suspicion for candidiasis. Dogs with Candida otitis externa often have a history of chronic bacterial otitis externa that has been treated aggressively with systemic or topical antibacterials.

Overgrowth of Candida in the gastrointestinal tract may occur in animals that are immunosuppressed or treated with glucocorticoids and/or broad-spectrum antibacterial drugs. In some cases, invasion of the mucosa into the lamina propria or deeper tissues occurs (e.g., intestinal candidiasis). Intestinal candidiasis is occasionally identified at necropsy in puppies that die after treatment for parvoviral enteritis and may be a reason for persistent vomiting, diarrhea, and death despite aggressive fluid and antibacterial drug therapy.¹⁴ Candida spp. may also contribute to ulcerative glossitis in puppies with parvovirus infection (Figure 67-1).

Candida peritonitis can follow intestinal surgery, treatment with broad-spectrum antibacterial drugs, and subsequent enterotomy site dehiscence.4,5 Mixed infections with Candida and intestinal flora may develop. Affected dogs are febrile, have abdominal pain, and may have other gastrointestinal signs such as vomiting and diarrhea.

Disseminated candidiasis results from hematogenous spread of Candida from intestinal, urinary, or possibly corneal or cutaneous sites.12,15,25A diagnosis of disseminated candidiasis should be considered whenever Candida infections are identified in the eye, skin, or urinary tract of an animal that has (or subsequently develops) severe systemic illness. Clinical signs of disseminated candidiasis in dogs include fever, inappetence, anorexia, weight loss, and a variety of other clinical signs that reflect underlying immunosuppressive disease processes and specific organs involved. The latter can include the pancreas, liver, mesentery, spleen, kidneys, heart, lungs, lymph nodes, and, less often, the bone, intestinal tract, eyes, meninges, thyroid, and/or prostate gland.^{3,12,15,17,20,25–28} Ocular signs in animals with disseminated disease include keratitis and corneal ulceration, uveitis, chorioretinitis, and endophthalmitis.^11,12,28 Candida keratitis may also occur as a localized process, sometimes secondary to aggressive treatment of corneal ulceration secondary to other disease processes with topical broad-spectrum antibacterial drugs. Thromboembolic disease may complicate disseminated infections. Pulmonary thromboembolism may result in respiratory distress and death.^3,11

Laboratory Abnormalities

Laboratory abnormalities in dogs and cats with candidiasis result from the underlying disease process (such as diabetes mellitus or systemic neoplastic disease) as well as the location and severity of the fungal infection. Laboratory abnormalities in dogs or cats with Candida UTIs may be absent, or there may be evidence of renal failure with azotemia and isosthenuria. Grossly, urine may contain flocculent white debris. Urinalysis may reveal proteinuria, pyuria, and, in some cases, hematuria and/or Candida fungal elements (see Case Example). Dogs and cats with disseminated candidiasis or Candida peritonitis frequently have had nonregenerative anemia and mild to marked neutrophilia with bandemia and toxic neutrophil changes (in contrast to other deep mycoses, where hematologic abnormalities are often mild or absent). Lymphopenia may be present as a result of underlying immunosuppressive illness or drug therapy. Some dogs are thrombocytopenic and have coagulation abnormalities consistent with disseminated intravascular coagulation.³ Findings on the serum biochemistry panel in dogs with disseminated candidiasis are variable and nonspecific but may include metabolic acidosis, moderate to severe hypoalbuminemia, and increased liver enzyme activities.