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Symptoms

Fever and Headache

Selby, Sarah Tolford, DO; Kaplan, Bonnie, MD

doi: 10.1097/01.EEM.0000550369.67201.ae
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Dr. Selby is an assistant professor of emergency medicine at the University of Colorado School of Medicine and the medical director of the forensic nursing program at University of Colorado Hospital in Aurora. Follow her on Twitter @DocSelbs. Dr. Kaplan is an assistant professor of emergency medicine at the University of Colorado School of Medicine in Aurora. Read her past columns at http://bit.ly/EMN-QuickConsult.

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A 35-year-old woman with a history of HIV (a CD4 count of 11 cells/mL and a self-reported high viral load a year earlier) presented to the ED with generalized headache three to four weeks after she was in a motor vehicle crash as the restrained driver.

The airbag deployed, but she didn't know if she had had a head strike. Her head CT at a different hospital had been negative. Since then, she had experienced increasing headache, photophobia, nausea, and neck and back pain. She had been seeing a chiropractor for the neck and back pain with minimal improvement. She noticed fever and chills the day before her presentation.

Her vitals included a temperature of 38°C, blood pressure of 125/90 mm Hg, pulse of 91 bpm, respiratory rate of 16 bpm, oxygen saturation of 99% on room air, and a weight of 56.7 kg. She was alert and oriented to person, place, and time. She was in no distress with no nuchal rigidity. Her sensation was intact, and she had normal finger-to-nose and reflexes and no pronator drift. She had no rashes or evidence of trauma. Her lungs were clear, and she was in no respiratory distress.

Consider the initial brain CT without contrast. What further diagnostic workup is needed? What does the patient likely have? What treatment should be started?

Find the diagnosis and case discussion on next page.

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Diagnosis: Cryptococcal Meningitis

Cryptococcal meningitis is an inflammation of the meninges and brain parenchyma caused most commonly by the fungus Cryptococcus neoformans, which is found in soil contaminated by bird droppings. C. neoformans infections are extremely rare in healthy individuals, but they are a major cause of illness in immunocompromised patients, especially those with HIV/AIDS and CD4 counts below 100 cells/mL. (Future Microbiol 2012;7[11]:1297.)

The incidence in 2014 was 223,100 cases worldwide per year and 181,100 annual global deaths. (Lancet Infect Dis 2017;17[8]:873; http://bit.ly/2yvZIIn.) Cryptococcal meningitis causes 15 percent of AIDS-related deaths globally.

Humans contract C. neoformans by inhaling spores or dried yeast cells that colonize the lung tissue. Cryptococci in the lungs can cause a pneumonia-like infection or disseminate to other body parts, usually the brain, where it causes cryptococcal meningitis. (Future Microbiol 2012;7[11]:1297.) Symptoms of cryptococcal meningitis usually develop slowly over a few weeks, and include subacute headache, neck pain, fever, nausea and vomiting, photophobia, and confusion. Classic meningism occurs in less than 20 percent of patients. (Postgrad Med J 2001;77[914]:769; http://bit.ly/2yvn1lR.) Altered mental state is associated with a higher mortality. (PLoS One 2013;8[3]:e60431; http://bit.ly/2ywMlrs.) Forty percent of patients will have ocular involvement with papilledema and uveitis with multifocal chorioretinitis. (Am J Ophthalmol 1993;116[6]:721.)

Diagnosis of cryptococcal meningitis requires a lumbar puncture and cerebrospinal fluid analysis. Typical CSF features include raised opening pressures reflecting elevated intracranial pressure, lymphocytic pleocytosis, and evidence of inflammation. (Clin Epidemiol 2014;6:169; http://bit.ly/2yxOdQJ.) CSF analysis in HIV-endemic populations, however, may be normal in 17 percent of patients. (Clin Infect Dis 1997;24[2]:131.) Cryptococcal antigen detection is used to detect asymptomatic, impending, or early cryptococcal infection in HIV-infected patients, but the gold standard for diagnosis is cultures, which usually grow after 36 hours. (Clin Epidemiol 2014;6:169; http://bit.ly/2yxOdQJ.)

Cryptococcal meningitis guidelines recommended by the Infectious Diseases Society of America and WHO consist of three phases: induction, consolidation, and maintenance. (Clin Infect Dis 2010;50[3]:291; http://bit.ly/2QJzKsz.) The induction phase involves treatment with intravenous amphotericin B and flucytosine for 14 days. Serial LPs are performed during induction to relieve elevated ICP and to monitor CSF cultures. Patients can be transitioned to the consolidation phase with oral fluconazole for eight weeks after 14 days of treatment or once the cultures show no growth. A low-dose oral fluconazole is used as prophylaxis in the maintenance phase to minimize the risk of cryptococcal meningitis relapse until the HIV is controlled by anti-retroviral therapy.

An LP was performed during this patient's workup in the ED, and she was started on empiric antibiotics for bacterial and viral meningitis given her CD4 count of 11 cells/mL. Her CSF cryptococcal antigen was reactive, and she had lymphocytic pleocytosis, so amphotericin B was started in consultation with infectious disease. The patient had a right lower lobe infiltrate on her chest x-ray and was treated with ceftriaxone (meningitis dosing) and doxycycline prior to receiving the CSF analysis results. She had no pulmonary symptoms of a pneumonia-like illness, so the infiltrate was thought to be community-acquired pneumonia rather than pulmonary C. neoformans infection, and she finished her course of doxycycline.

The patient was admitted for cryptococcal meningitis with amphotericin B and fluconazole (she had side effects with flucytosine) and had serial therapeutic LPs because of persistent headaches and continued high opening pressures with LPs. Her CSF cultures grew moderate Cryptococcus neoformans var. Grubii. She finished her pneumonia treatment, and was discharged on oral fluconazole for cryptococcal meningitis and TMP/SMX for Pneumocystis prophylaxis.

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