Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (488 page)

   Esophageal: Esophageal candidiasis is an AIDS-defining illness in patients with HIV infection. Patients may have oropharyngeal candidiasis. Odynophagia and retrosternal pain are common complaints. White plaques are seen by endoscopic examination, the scrapings of which show budding yeast with pseudohyphae.

   Skin and nails: Superficial infection may occur, typically in intertriginous or other warm, moist areas. Infection presents with erythema, pruritus, and characteristic rash.
Candida albicans
and
C. parapsilosis
are the most common causes of onychomycosis of the fingers and may be associated with paronychia. Congenital candidiasis may present in neonates as a generalized erythematous desquamating rash. Chronic mucocutaneous candidiasis is uncommon but may occur in patients with congenital autoimmune syndromes or other defects in cell-mediated immunity. Conditions commonly misdiagnosed as cutaneous candidiasis include psoriasis, chronic nail trauma, squamous carcinoma of the nail bed, “yellow-nail syndrome,” or other conditions that should be considered and ruled out as appropriate. In skin and nail involvement in children, congenital hypoparathyroidism and Addison disease should be ruled out.

   Candidemia: Invasive candidiasis is most commonly caused by hematogenous spread of endogenous
Candida
in immunocompromised patients, often associated with a break in the integrity of the mucosal barrier of the bowel or indwelling central venous catheter. Symptoms may be variable, ranging from low fever and malaise to a full-blown sepsis syndrome. The incidence of candidemia is increasing as a result of HIV infection and other acquired immunodeficiency diseases, increasing use and potency of immunosuppressive therapies, intensive care interventions, increased survival of premature infants, increased use of chronic IV nutrition, and other factors.
Candida albicans
is the most common isolate, but other
Candida
species are playing an increasing role in candidemia, resulting in an increased rate of resistance to antifungal agents in candidemic patients.
Candida
species play a significant role in the etiology of nosocomial bloodstream infections, causing up to 10% of these infections. Candidemia has a high attributable mortality. Cofactors contributing to poor outcome include older age, disseminated candidiasis, and severe and persistent neutropenia.

   Pneumonia: Though
Candida
species are commonly isolated from cultures of lower respiratory samples, they are usually contaminants; primary
Candida
pneumonia is extremely rare, even in intubated patients. Secondary
Candida
pneumonia occurs rarely in candidemic patients, but diagnosis may require invasive techniques and histopathologic confirmation.

   Cardiovascular: Endocarditis, myocarditis, or pericarditis may occur.
Candida
is responsible for <5% of cases of endocarditis, but
C. albicans
is responsible for >50% of the cases of fungal endocarditis. Risk factors include presence of prosthetic valves, IV drug abuse, major surgery, preexisting valve disease, and chronic placement of deep IV catheters or pacemakers. The presentation of
Candida
endocarditis cannot be distinguished from bacterial endocarditis on the basis of clinical presentation alone. Patients with
Candida
endocarditis are at high risk for embolization; the brain, eye, kidney, liver, skin, and spleen are common sites.

   CNS: Infections are uncommon but may arise as secondary infections in candidemic patients or as complication of neurosurgery or chronic ventricular shunting. The clinical presentation is not distinctive.

   Ocular: Chorioretinitis or endophthalmitis is usually caused by hematogenous spread and may be the first sign of invasive candidiasis. Keratitis and some cases of chorioretinitis or endophthalmitis are caused by trauma or surgery. Patients present with pain and loss of visual acuity. Ophthalmologic examination is recommended for all patients with candidemia. Characteristic findings are confirmed by culture.

   Bone and joint: Infections may be due to direct trauma, joint injection or surgery, or secondary to hematogenous seeding. These infections may present many months after the infectious incident; onset is often gradual and subtle. The vertebrae are most commonly affected in the elderly, whereas infection of the long bones is most common in children. Diagnosis is established by isolation of
Candida
from specimens collected from the bone or joint.

   Abdominal:
Candida
species, as common components of the endogenous GI microflora, may be isolated in almost any infectious process of the abdomen. Specific
Candida
peritonitis may be seen in patients undergoing chronic peritoneal dialysis.
Candida
infection is a fairly common complication in patients recovering from acute pancreatitis from other causes. Hepatosplenic candidiasis may complicate resolution of neutropenia in patients on chemotherapeutic regimens for hematologic malignancies. The liver and spleen may have been seeded during a recognized or unrecognized episode of candidemia, although there is the possibility that
Candida
was introduced by the portal vasculature. Patients present with fever, nausea, vomiting, anorexia, and right upper quadrant pain. Discrete microabscesses form in the liver and spleen, which may be detected by a variety of imaging techniques.