A 34-year-old man comes to the emergency department due to 2 weeks of slowly progressive global headache, malaise, and fevers. He has also had unintentional weight loss over the past several months. The patient has a history of injection drug use and was diagnosed with HIV 3 years ago. He has not been compliant with antiretroviral therapy. Temperature is 38.3 C (100.9 F). Examination shows white patches on the oropharyngeal mucosa and mild generalized lymphadenopathy. Brain imaging reveals no intracranial masses. India ink staining of cerebrospinal fluid demonstrates spherical yeast forms with thick capsules. Which of the following is the most likely site of primary infection in this patient?

Question

A 34-year-old man comes to the emergency department due to 2 weeks of slowly progressive global headache, malaise, and fevers.  He has also had unintentional weight loss over the past several months.  The patient has a history of injection drug use and was diagnosed with HIV 3 years ago.  He has not been compliant with antiretroviral therapy.  Temperature is 38.3 C (100.9 F).  Examination shows white patches on the oropharyngeal mucosa and mild generalized lymphadenopathy.  Brain imaging reveals no intracranial masses.  India ink staining of cerebrospinal fluid demonstrates spherical yeast forms with thick capsules.  Which of the following is the most likely site of primary infection in this patient?

Quizplus · Accepted Answer

11ec160b_387e_fbd0_9249_31dbf9b96334_MD0001_00 Cryptococcus neoformans is a low-virulence yeast with a thick polysaccharide capsule. The organism resides in soil contaminated by bird (eg, pigeon) droppings, and human exposure primarily occurs due to inhalation into the lungs. Alveolar macrophages ingest the yeast, travel to draining lymph nodes, and activate CD4 T-lymphocytes that subsequently promote granuloma formation and enhanced destruction of the pathogen within phagolysosomes. Although a minority of patients clear the organism, most individuals develop life-long latent infection, similar to tuberculosis; those who are severely immunocompromised (eg, AIDS with CD4 count <100/mm³) are at high risk for reactivation. Cryptococcal meningitis primarily occurs when C neoformans reactivates from a latent pulmonary focus, spreads through the circulation, and penetrates the endothelial cells of the cerebral capillaries. Replication within the CNS leads to slowly worsening headache, fever, and confusion. Visualization of the organism (ie, round/oval yeast with a thick capsule) on cerebrospinal fluid samples using India ink stain confirms the diagnosis. Polysaccharide antigen (cryptococcal antigen) testing can also be helpful. (Choice A) Ingestion of C neoformans in contaminated food can lead to infection. However, this route is much less common than inhalation into the lungs. (Choice C) Acute bacterial meningitis is caused primarily by pathogens (eg, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae) that colonize the nasopharynx. Manifestations of acute bacterial meningitis usually include the rapid onset fever, neck stiffness, and altered mental state. Cerebrospinal fluid Gram stain will be positive. (Choice D) Patients who have untreated AIDS often develop multiple opportunistic infections; the white patches on this patient's oral mucosa likely indicate oropharyngeal candidiasis. Superficial Candida infections rarely cause invasive disease. In addition, Candida does not have a thick polysaccharide capsule and is not seen on India ink stain. (Choice E) Skin bacteria (eg, Staphylococcus aureus, Streptococcus pyogenes) can cause systemic infection following skin breakdown. Systemic infection from skin fungus (eg, Candida) following skin breakdown is uncommon. This patient's encapsulated yeast on India ink stain indicates Cryptococcus, making inhalation the most likely route of infection. Educational objective: Cryptococcus neoformans is a yeast with a thick polysaccharide capsule that is found primarily in soil contaminated by bird droppings. Inhalation of the pathogen into the lungs leads to asymptomatic primary infection usually followed by life-long latent infection. However, immunocompromised (eg, advanced AIDS) patients are at high risk for reactivation with spread to the CNS. __________ References: Molecular mechanisms of cryptococcal meningitis. (http://www.ncbi.nlm.nih.gov/pubmed/22460646)

A 34-Year-Old Man Comes to the Emergency Department Due to 2