A 45-year-old man comes to the emergency department due to 2 weeks of chest pain and cough. He has a history of advanced HIV and has taken his antiretroviral medications inconsistently over the past few months. Temperature is 38.1 C (100.6 F). Crackles are heard on pulmonary examination. CD4 cell count is 98/mm³. Chest x-ray reveals nodules and hilar lymphadenopathy. A bronchoscopy is performed. Mucicarmine staining of the patient's bronchoalveolar fluid shows budding yeast forms with thick capsules. Symptomatic infection with the organism causing this patient's condition most commonly manifests as which of the following?

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Budding yeasts with thick capsules are characteristic of Cryptococcus neoformans, which typically affects only immunocompromised patients (opportunistic pathogen). C neoformans is present in soil and pigeon droppings; it is transmitted by the respiratory route but not acquired via person-to-person contact. Inhaled yeast forms enter the lungs. In immunocompetent persons, they are cleared by macrophages and T cells. In individuals with an impaired cellular immune response, C neoformans can cause symptomatic disease, most commonly meningoencephalitis. Cryptococcal meningoencephalitis is typically seen in patients with HIV, sarcoidosis, or leukemia and in those on high-dose corticosteroid therapy. Headache, nausea, vomiting, and confusion are common symptoms. Diagnosis is made by examining cerebrospinal fluid (CSF) stained with India ink. The round budding yeasts have peripheral clearings or "halos," due to their thick polysaccharide capsules. Serologic testing (latex agglutination) is used to detect the C neoformans capsular antigen in CSF. Although lung infection occurs first, it is usually asymptomatic. In some patients, pulmonary cryptococcosis may manifest as cough with scant sputum production, dyspnea, or pleuritic chest pain; it can be diagnosed by microscopic examination of bronchopulmonary washings and lung tissue (red yeast on mucicarmine stain). C neoformans does not typically cause interstitial pneumonia (Choice B). Cutaneous cryptococcal disease (papules, pustules, nodules, ulcers) is rare (<10% of cases) (Choice F). (Choices A and D) Esophagitis in a patient with HIV is most commonly caused by Candida infection; it presents with odynophagia and is diagnosed by endoscopy with biopsy. Oral thrush due to Candida, which manifests as white oral plaques, is associated with diabetes mellitus, immunosuppression (eg, HIV), and treatment with antibiotics and corticosteroids. (Choice E) Mucormycosis classically affects the paranasal sinuses. Mucormycosis occurs in immunocompromised patients and is strongly associated with diabetes mellitus and diabetic ketoacidosis. Aspergillosis fumigatus is another fungus that may cause sinusitis. Educational objective: Meningoencephalitis is the most common presentation of Cryptococcus neoformans infection. It occurs in immunosuppressed patients and can be diagnosed by India ink staining of the cerebrospinal fluid. Cryptococcal pneumonia is diagnosed by mucicarmine staining of lung tissue and bronchoalveolar washings.

A 45-Year-Old Man Comes to the Emergency Department Due to 2