Fig. 6.61 A-C. Cryptococcosis. A Cryptococcus neoformans cells with a thick capsule and spiculation (arrow). B A nodule skin lesion and an ulcerating subcutaneous "tumor.". Although the patient had no neurological symptoms, the fungus was found in the cerebrospinal fluid. C Subcutaneous tumefaction as the sole manifestation of cryptococcosis.

Fig. 6.62 A-G. Pulmonary cryptococcosis. A Multiple pulmonary subpleural nodules seen at autopsy. B A cut section of the lung showing that there are confluent nodules in the lung parenchyma. C A solitary pulmonary lesion, well circumscribed but not encapsulated. A granuloma due to Cryptococcus neoformans, a primary infection, most of which are undetected. D, E PA and lateral radiographs of the chest of a 22-year-old male complaining of fever: his neck was stiff and he was slightly disorientated. There is a large solitary mass in the basal segment of the left lower lobe, close to the pleura. The outline is irregular, especially anteriorly (better seen on the lateral view). The differential diagnosis includes tuberculosis or other lung granulomas or pneumonia. F A surgical specimen shows the lobu lated, irregular contour of a large cryptococcal granuloma. AFIP 1239772. G Multiple fungal cells with macrophages and giant cells. Mucicarmine, x200. (A, B, G from Bittencourt and Londero 1995; C specimen contributed by Drs. D. Rulon, Ohio and D. H. Connor)

Clinical Characteristics

Candidiasis is seldom a disease of healthy people, though candida vulvovaginitis may occur in healthy women and oral thrush may be found in apparently normal newborn infants. Cutaneous candidiasis appears on damaged skin but also in moist, hot surfaces such as the creases and folds in the axilla or inguinal regions, or under heavy breasts. Infections are common in the extremes of age, premature infants, and the elderly.

The status of the immune system is the most significant factor in the natural history of the disease. Those most at risk are immunocompromised, because of AIDS, diabetes, leukemia, or chronic ill health or malnourishment. Other patients will have been on prolonged antibiotic, steroid, or cytotoxic therapy: some have had a prior bacterial infection. Drug addicts are heavily at risk of intravenous selfinoculation. Sickle cell disease has been associated with candidiasis. There are no occupations with particular risk, apart from tea tasting.

Candida spp. are invasive, which accounts for hematogenous spread. Pulmonary candidiasis causes pneumonia, usually bilateral and particularly at the lung bases. There are no characteristic clinical signs or symptoms.

Gastrointestinal candidiasis may be completely asymptomatic or cause retrosternal pain. Esophagoscopy may show white mucosal plaques along the whole length of the esophagus, particularly the distal third. In between the plaques, the esophageal mucosa is edematous and red. As the infection progresses, the esophagus may ulcerate, the ulcers being lined with a shaggy, gray base: bleeding is common. In severe infections swallowing is affected and perforation may occur. There are quite often complicating concomitant infections, particularly in AIDS patients.

In the stomach, candidiasis causes superficial gastric erosion and the symptome are those of gastritis. Ulceration may develop in the small intestine and colon. The lesions may be extensive, and invade blood vessels, spreading to the liver, spleen, and gallbladder (perhaps spreading directly also). Candidal peritonitis more commonly follows contaminated dialysis, causing abdominal pain, tenderness, and a low-grade fever. Candidal peritonitis can also follow abdominal surgery. Pancreatic abscesses have been reported.

Candidiasis of the urinary bladder usually follows catheterization, but hematogenous spread can occur, with the kidneys, ureters, and bladder being infected. Candida infection may occur whenever the bladder does not empty properly, particularly in a neurogenic bladder, and following pelvic irradiation. Clinically, these infections are often asymptomatic but may precipitate complete urinary obstruction. When there is pyuria, it is probably due to a secondary infection or underlying bladder disease rather than to candidiasis. In the kidney, Candida pyelitis also follows obstruction or surgical interference, including ureteric catheterization. Renal papillary necrosis following such infection is another cause of renal pelvic and ureteric obstruction. Urine cultures can be used as evidence of Candida dissemination, but must be interpreted carefully because they may be falsely positive or negative.

Candidiasis is a common cause of septicemia, particularly in long-stay hospital patients with numerous catheters and heavy antibiotic therapy. Scattered candidal skin lesions may develop when there is fungemia, even when it is difficult to isolate Candida spp. from the blood. When disseminated, the site of clinical infection depends on many factors, but particularly on tissue damage from previous surgery, radiotherapy, the passage of calculi, or catheterization. When the liver and spleen are infected, the patient will have a low-grade fever, upper quadrant abdominal pain, hepatomegaly, splenomegaly, and, sometimes, jaundice. Liver function tests may become abnormal. Biopsy or autopsy will show multiple small abscesses throughout the liver and/or spleen: their centers may be necrotic, with hyphae, pseudohyphae, and yeasts growing in them.

Candidal septicemia often causes acute and subacute endocarditis, particularly if there is a valvular abnormality or previous surgery. Intravenous or pulmonary artery catheters are a common source of infection. Candida spp. can usually be grown from blood which is taken from these patients. Retinal infections can result from candidemia.

Badly damaged joints, e. g., from rheumatoid arthritis or following joint replacement, may become infected by Candida spp., usually by hematogenous spread, but occasionally directly at the time of surgery. Bone infection may be by direct or hematogenous spread; the lumbar vertebrae seem to be the most commonly affected.
Candidal meningitis afflicts neonates, particularly those of low birth weight. Adults may develop candidal cerebral abscesses, but most cerebral candidal infections follow surgery or trauma to the head.

The clinical findings in candidiasis have been summarized by Rippon (Table 6.4).