Candidiasis and cancer

ALSO KNOWN AS: Thrush, yeast infection, fungal infection

RELATED CONDITIONS: Fever, infections, and sepsis in cancer treatment

DEFINITION: Candida species are fungi that are part of humans' normal flora and are also major human pathogens. Candidiaasis is a disease caused by Candida species. As

Risk factors: Candida colonization increases after antibiotic (antibacterial) therapy, and the broader the spectrum of antibacterial treatment, the greater the growth. Cancer surgery, particularly if it involves the gastrointestinal (including oral) or female genital tract, can allow candida present in the normal flora of these areas to enter into the previously protected underlying tissues. Cancer chemotherapy can impair the immune system by decreasing the production of white blood cells in the bone marrow. When corticosteroids are used as part of cancer chemotherapy, both neutrophil and lymphocyte function is impaired. Radiation can damage mucous membranes and, in some cases, the bone marrow. Vascular catheters used to administer cancer chemotherapy and other drugs are frequently ports of entry for candida. Urinary and gastrointestinal catheters can also assist invading organisms. Leukemias, lymphomas, and bone marrow metastases can result in diminished numbers of the normally functioning neutrophils and lymphocytes essential to fight invading organisms.

Etiology and the disease process: Candida species are commensal organisms and are found as part of the normal human flora because of their ability to adhere to and persist on mucosal surfaces. Only when this natural balance is upset can these opportunistic pathogens cause disease. Candidal organisms possess several virulence factors. Production of hydrolytic enzymes (proteinases and lipases) can alter protective mucous membranes, allowing penetration into the tissues beneath. The cell wall of Candida species is made up of beta-glucans, mannoproteins, and chitins (carbohydrates). Different growth conditions can result in changes in cell wall components that drastically alter the morphology. Outside the body and on mucosal surfaces, Candida species exist as yeasts (round or oval, single-celled organisms). When tissues are invaded, the amount of cell-wall chitin is increased, and mycelia (long filaments) are formed rather than yeasts. This phenomenon is called dimorphism and may make the organism more challenging for the immune system. The formation of finger-like projections from yeast cells (pseudohyphae) seems important in penetration into host cells. These and other candida virulence factors are significant contributors to disease causation, but it is the impaired immune system of the host that usually tips the balance.

Incidence: Autopsies of leukemia patients reveal disseminated candidiasis involving major organs in 20 to 33 percent of cases. Bloodstream invasion has been documented in more than 10 percent of patients with leukemia and about 1 percent of patients with lymphoma. The incidence is lower in patients with solid tumors and in children. In 2014, the Centers for Disease Control and Prevention reported that invasive candidiasis is the fourth most common cause of hospital-acquired bloodstream infections in the United States and that oral candidiasis has been documented in nearly 20 percent of cancer patients.

Symptoms: Symptoms can vary, as many different areas of the body and organs can be infected. Oral discomfort, difficulty in swallowing, and associated pain may accompany oral and esophageal candidiasis. Abdominal discomfort can occur with stomach and intestinal ulcerations caused by candida in cancer patients. Vaginal discharge and itching are often associated with candida vaginitis. Endophthalmitis can cause blurred vision. Infected peripheral and central intravascular catheters may have minimal symptoms heralding the underlying suppurative thrombophlebitis. However, the most common symptom or sign of candidiasis is fever.

Screening and diagnosis: The diagnosis of candidiasis may be presumptively made by physical examination of the cancer patient. Examination of the skin and oral cavity for plaques, ulcers, and erythema may be revealing. Candida endophthalmitis, resulting from bloodstream infection, is strongly suspected when characteristic cotton-wool lesions are observed on ophthalmoscopic examination of the retina. A new heart murmur may result from candida endocarditis associated with vascular catheter infection. Rales and decreased breath sounds may be present during candida pneumonia. Intraluminal urine seen in indwelling urinary catheters is frequently cloudy with white fluffy debris when urinary candida infection occurs. Intravascular catheter sites may reveal erythema, induration, or purulent drainage, but these signs can be subtle or absent in neutropenic patients.

Endoscopic examination can be helpful with gastrointestinal candidiasis, particularly esophagitis. Computed tomography (CT) and magnetic resonance imaging (MRI) scans of the abdomen can demonstrate abscesses.

Blood tests for candida antigens, beta-glucan, and polymerase chain reaction (PCR) may provide a specific diagnosis. Microscopic examination of urine and tissue biopsies is also helpful. Culture of blood, urine, tissue biopsies, and the like provides specific diagnostic information, and the cultured Candida can be speciated and tested for susceptibility to antifungal agents.

Treatment and therapy: The relatively nontoxic azole and echinocandin antifungals are most often used to treat candidiasis. Amphotericin B has long been standard therapy for invasive candidiasis, but the comparatively high toxicities have limited its use in refractory or resistant cases. If candida has been cultured, then fungal susceptibilities can be used to guide therapy. It is important to begin therapy as early as possible to achieve the best outcome, and this mandates that therapy be commenced in high-risk cancer patients before the availability of diagnostic studies if candidiasis is suspected. Adjunctive measures are also important. Vascular, gastrointestinal, or urinary catheters should be removed if possible. Immune function must be optimized. Colony-stimulating factors can increase neutrophil numbers in neutropenic cancer patients.

Other treatment options include oral rinses containing antiseptic solutions or antifungal agents. A change in diet may also provide positive results. This can help eliminate foods that promote fungal groups. Dietary changes include replacing sugary, processed foods with those containing probiotics and nutrients that help the body's immune system. Those afflicted can also find assistance through support groups or mental health specialists or may elect to participate in a clinical trial.

Prognosis, prevention, and outcomes: Disseminated candidiasis with candidemia in cancer patients has a crude mortality rate of 70 to 75 percent with an excess mortality rate of about 40 percent. Without treatment survival rates are less than 5 percent.

Reducing risk factors is the best way to prevent infection. Removing catheters promptly, treating neutropenia, and using antibacterials only when absolutely necessary are all beneficial. Antifungal prophylaxis has been demonstrated to reduce the incidence of candidiasis in cancer patients with neutropenia and also in patients for whom treatment has included bone marrow or solid organ transplantation.

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