History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include immunosuppression; exposure to disturbed soil, chicken guano, or bat caves; neutropenia; impaired phagocytic function; and neurosurgery. Infants and neonates are also at increased risk.

progressive headache

Typically presents with headache that progresses over several weeks.

severe headache

Suggests raised intracranial pressure.

Common finding of cryptococcal meningitis, where raised intracranial pressure probably occurs due to impaired reabsorption of cerebrospinal fluid at the arachnoid villi.

meningismus

Nuchal rigidity, photophobia, and headache.

symptoms of hydrocephalus (impaired cognitive function, confusion, coordination and gait disturbances, and urinary incontinence)

Classical signs of hydrocephalus.

Hydrocephalus is a common early presentation and complication of coccidioidal meningitis.

behavioural or personality change

Due to meningoencephalitis.

reduced visual acuity and papilloedema

Signs of raised intracranial pressure.

Suggestive of cryptococcal meningitis in the appropriate clinical context.

Other diagnostic factors

common

nausea or vomiting

Early feature of meningitis.

fever

Early feature of meningitis.

reduced conscious level

Common and poor prognostic marker in HIV-associated cryptococcal meningitis.[91]

cranial nerve palsies

Fungal meningitis commonly affects the basilar meninges and can injure cranial nerves.

uncommon

seizures

Inflammation of the meninges can cause seizures.

weight loss

Symptom of disseminated infection.

mouth ulcers

Symptom of disseminated infection.

focal neurological signs

Secondary to cerebral infarction. Coccidioidal infection causes arteritis of small- to mid-sized blood vessels.

lymphadenopathy, hepatosplenomegaly

Patients with histoplasmal meningitis may demonstrate these signs as a complication of disseminated progressive histoplasmosis.

dyspnoea

Cough and dyspnoea are associated with pulmonary cryptococcal involvement.

Neonates with candidal meningitis present with respiratory distress.

papular umbilicated skin lesions

Occasionally seen in cryptococcal meningitis.

retinal defects

Retinal involvement may be apparent in central nervous system candidal infection.

nasal or palatal eschar

A specific sign in the later stages of mucormycosis infection is necrotic eschar on the skin, palate, or nasal turbinates.

Risk factors

strong

HIV infection

The progressive loss of CD4+ helper cells in HIV-infected patients correlates with an increasing risk of cryptococcal meningitis. Most patients with cryptococcal meningitis have a CD4 count <100 cells/microlitre, and usually <50 cells/microlitre.[58]

corticosteroid use

The second most important risk factor for the development of cryptococcal meningitis. Solid-organ transplant recipients and patients with connective tissue diseases (e.g., sarcoid, or reticuloendothelial malignancies) who take prednisone doses of >10-20 mg/day have an increased risk of developing cryptococcal meningitis.

Cryptococcal meningitis in an immunocompetent adult after corticosteroid treatment for COVID-19 has been reported.[59]

underlying chronic disease (e.g., malignancy, organ failure, autoimmune disease, organ transplant)

In patients with non-HIV-associated cryptococcal meningitis, predisposing factors have been identified as organ transplant, chronic organ failure (liver, lung, kidney), malignancy, rheumatological disease, and sarcoidosis, irrespective of corticosteroid use.[60][61] In approximately 20% of cases of non-HIV-associated cryptococcal meningitis, no underlying cause for the development of cryptococcal meningitis is found.

exposure to disturbed soil, chicken guano, or bat caves

Histoplasmosis occurs infrequently in individuals living outside endemic areas. Risk factors for acquisition of histoplasmosis include: exposure to disturbed soil, chicken guano, or bat caves. It is important to elicit these risk factors in patients who have travelled to endemic areas.

impaired cell-mediated immunity

Patients presenting with progressive disseminated histoplasmosis and progressive disseminated coccidioidomycosis often have impaired cell-mediated immunity secondary to, for example, HIV/AIDS, transplantation, malignancy, corticosteroid use, tumour necrosis factor antagonist use, or congenital T-cell deficiencies.

Filipinos and African Americans

Filipinos and African Americans have a significantly increased risk of severe disease and dissemination.[64][65][66] However, the overall incidence of coccidioidomycosis is similar in different ethnic groups.

neutropenia or impaired phagocytic function

Neutropenia is a major risk factor for invasive candidiasis, including candidal meningitis. Defective neutrophil function (e.g., in chronic granulomatous disease) also increases the risk of invasive candidiasis. Candida meningitis may occur in patients with AIDS, but usually only when additional risk factors such as neutropenia are present.[67]

neurosurgery

Candidal meningitis is the most common fungal meningitis following central nervous system shunt or ventriculostomy placement.[68]

infants and neonates

Infants exposed to Histoplasma capsulatum are at increased risk of severe, life-threatening infection.

Candida albicans is a relatively common cause of meningitis in premature infants or infants younger than 1 month. Candidaemia in adults is less commonly associated with meningitis.

weak

residing in or visiting northern Australia, Papua New Guinea, or Vancouver Island, Canada

Patients with or without overt immunosuppression, living in or visiting certain areas, especially northern Australia and Papua New Guinea, and more recently Vancouver Island, Canada, may be at risk of Cryptococcus gattii infection.[12][13][62][63]

central vascular catheters

Patients with intravascular catheters are at increased risk for the development of candidaemia.

sinonasal disease

Chronic sinusitis or mastoiditis may be the primary source of fungal meningitis.

antibacterial usage

Prolonged therapy with broad-spectrum antimicrobials increases the risk of heavy candidal colonisation and invasive infection.

prior surgery

Surgical manipulation of a mucosal site colonised with Candida (i.e., gastrointestinal tract surgery) increases the risk of candidaemia.

hyperalimentation

Intravenous hyperalimentation increases the risk of candidaemia.

intravenous drug use

Intravenous drug users are at risk of chronic neutrophilic meningitis caused by Candida albicans.[69]

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