Fig. 6.57 A-F Paracoccidioidomycosis of the alimentary tract. A, B Barium contrast studies showing nodular thickening of the duodenum and proximal jejunum. The normal mucosal pattern has been lost. C More extensive jejunal and ileal involvement, with diffuse thickening and loss of the normal mucosal pattern. There are some sections with marked narrowing and thickening of the mucosa, and some small pseudodiverticuli have developed. D Loops of jejunum and upper ileum in which the normal pattern has disappeared: some segments are dilated and others narrowed. The lower ileum is still normal. E Diffuse narrowing of the entire cecum and the ascending colon, as far as the hepatic flexure. The mucosal pattern has been replaced with nodulation. The terminal ileum and transverse colon appear normal. F Severe localized stenosis of the upper rectum, with nodular mucosa above and below it. All these patients are adult males.

Meningeal infection is very common and causes thickening of the subarachnoid meninges, especially at the base of the brain and over the cerebellum. There may be a mucoid exudate: the fungi will be seen in the cerebrospinal fluid or may be cultured from it. In those who are severely immunodeficient, the fungal masses in the leptomeninges may be large enough to displace the brain, while in other patients there may be meningeal adhesions. The diagnosis can be confirmed by finding cryptococcal polysaccharide antigen in the cerebrospinal fluid, using latex agglutination. This is a very sensitive test, reliable in over 90% of patients with cerebral infections.

Clinical Characteristics

There are three ways in which cryptococcosis presents clinically. Meningitis (or meningo-encephalitis) ist the most common, pulmonary infection is almost as frequent but may be undetected, and there may be hematogenous dissemination to various sites, including bone, prostate and the eyes.

As already noted, the patient's susceptibility is increased by the preexistence (or coexistence) of Hodgkin's disease or other reticulosis, leukemia, sarcoidosis when treated with steroids, diabetes, immunosuppressive drugs, or AIDS. Rarely, apparently healthy patients with no detectable immunodeficiency develop cryptococcal meningitis, but why this should happen to these individuals and not to thousands of others who are exposed to the organism is an unsolved problem.

Primary pulmonary infections are often undetected and subclinical infections are common: many pigeon handlers have positive serological evidence for cryptococcosis and are quite unaware of having had any infection. There may be a vague history of illness during childhood, clinically thought at the time to be an upper respiratory virus or bronchitis. Small cryptococcomas may be found on chest imaging or autopsy without having been clinically suspected. Such cryptococcomas are either small nodules close to the pleura or solitary circumscribed lesions in the lung parenchyma (Fig. 6.62). Those with clinical symptoms complain of cough, sputum, pain in the chest, loss of weight, and fever. There may be hemoptysis and night sweats, a clinical spectrum varying from influenza to tuberculosis. When the patient is immunocompromised there may be reactivation of a previously unknown focus or a new infection. Even immunocompromised patients may be asymptomatic or have nonspecific chest symptoms, such as cough and shortness of breath. These may persist a long time and often slowly worsen. However, in the majority of immunocompromised patients there is an acute, rapidly progressing pulmonary infection, with pleural effusions and disseminated disease. Many of the symptoms are caused by the large fungal masses and when these rupture into a bronchus, the sputum will be copious and gelatinous.

Many immunocompromised patients go on to have meningeal symptoms, complaining of headache, vomiting, and a stiff neck: this may be followed by raised intracranial pressure, coma, and death. The cerebrospinal fluid will contain monocytes and the initial diagnosis may be tuberculous meningitis (Fig.6.63). In other patients, the onset of CNS cryptococcosis is insidious and it is only later that focal neurological signs appear. Clinically a solid intracranial cryptococcoma mimics a cerebral tumor. Cutaneous cryptococcosis may present as ulcers, granulomas, nodules, or spreading cellulitis (Fig. 6.61 B, C). Both cutaneous and meningeal cryptococcosis are features of immunodeficiency and dissemination: approximately half of the patients with skin infection will progress to meningitis, even if they have previously been without clinical signs.

Cryptococcal bone infection is usually painful: the skull and the vetebrae are common sites, but there may be infection anywhere in the skeleton. Most bone and cutaneous lesions are multiple. Lesions in the liver, spleen, and kidneys are also part of disseminated disease in patients who are severely immunocompromised. In patients with AIDS, other clinical presentations have been of arthritis, peritonitis, and myocarditis. Without treatment, disseminated or meningeal cryptococcosis is eventually fatal.