A 38-year-old man presents to the emergency department with nasal congestion, blurry vision, and diplopia. His nasal congestion started about 1 week ago and he noticed the blurry vision this morning when he struggled to read the words on his television screen. His medical history is significant for IV drug use, HIV (CD4: 47/mm^3), hypertension, hyperlipidemia, diabetes mellitus, and seasonal allergies. His home medications include hydrochlorothiazide, atorvastatin, metformin, cetirizine, darunavir, tenofovir, and emtricitabine. He denies recent IV drug use. His temperature is 100.8°F (38.2°C), blood pressure is 127/85 mmHg, pulse is 78/min, and respirations are 12/min. He has injected conjunctiva and rhinorrhea. His cranial nerves are intact, and his motor and sensory neurologic exam is normal. A MRI of the brain is performed and can be seen in Figure A. Which of the following is the most appropriate next step in management?
Empiric treatment with pyrimethamine-sulfadiazine
Lumbar puncture
Brain biopsy
Empiric treatment with dexamethasone
Empiric treatment with pyrimethamine-sulfadiazine
This patient with a past medical history of immunosuppression due to HIV (CD4 < 100/mm^3), new focal neurologic findings, and ring-enhancing lesions on head MRI should be treated empirically with pyrimethamine-sulfadiazine for 10-14 days.

The differential diagnosis for ring-enhancing lesions in patients with HIV is determined by the degree of immunosuppression. For patients with CD4 counts > 200/mm^3, the most likely diagnoses include primary brain tumors and metastases. In patients with CD4 counts < 200/mm^3, the differential includes toxoplasma encephalitis, primary CNS lymphoma, progressive multifocal leukoencephalopathy (PML), and other infections. Patients with CD4 counts < 100/mm^3 should have empiric treatment for toxoplasma encephalitis with pyrimethamine-sulfadiazine with follow-up head imaging after 10-14 days. If the patient fails to improve clinically or the size of the lesion does not change, the next step would be a biopsy of the lesion.

Robert-Gangneux and Darde present a review of toxoplasmosis diagnosis and treatment. They discuss how the incidence of these infections has increased dramatically since the advent of organ transplantation and HIV. They recommend increasing vigilance and prophylaxis for this disease.

Figure/Illustration A is an MRI of the brain that demonstrates a ring-enhancing lesion (red circle) in the right occipital lobe. This lesion is likely causing the patient's visual complaints and is consistent with toxoplasmosis.

Incorrect Answers:
Answer A: Brain biopsy should be performed if the patient has no response clinically or on follow-up head imaging to empiric treatment with pyrimethamine-sulfadiazine for 10-14 days. Biopsy in these cases may reveal a CNS lymphoma or other neoplastic process.

Answer C: Empiric treatment with dexamethasone is indicated for patients with substantial mass effect on imaging and severely depressed mental status, neither of which is present in this patient.

Answer D: Lumbar puncture is contraindicated in patients with focal neurologic findings due to the risk of transtentorial herniation. Lumbar puncture would be indicated in the diagnosis of meningitis which presents with fever, headache, photophobies, and meningeal signs.

Answer E: There is no role for serology for anti-John Cunningham (JC) virus antibodies in the workup of ring-enhancing lesions. If it were safe to perform a lumbar puncture (if the patient had no focal findings and no evidence of mass effect on head imaging), it would be reasonable to perform PCR of the CSF for JC virus.

Bullet Summary:
For patients with a past medical history of HIV with CD4 <100 cells/µL, focal neurologic findings, and ring-enhancing lesions on head imaging, the next step in management is empiric treatment for toxoplasma encephalitis with pyrimethamine-sulfadiazine for 10-14 days.