Bonus online case: Pulmonary coccidioidomycosis

The patient had been seen repeatedly for progressive dyspnea and a dry cough.


The patient

A 62-year-old man with a history of type 2 diabetes, hypertension, and stage 2 chronic kidney disease presented from a long-term acute care (LTAC) facility with worsening hypoxic respiratory failure. Three weeks earlier, the patient had presented to another hospital with progressive dyspnea and dry cough despite outpatient treatment with ciprofloxacin. He was afebrile but tachycardic with a new 3-L oxygen requirement, and labs were notable for leukocytosis (21.9 × 109 cells/L; reference range, 3.4 to 11 × 109 cells/L) with absolute eosinophilia. A chest X-ray demonstrated bilateral infiltrates consistent with multilobar pneumonia. He received ceftriaxone and doxycycline for community-acquired pneumonia (CAP), improved clinically within days, and was discharged to the LTAC with a persistent oxygen requirement of 2 L. Coccidioidomycosis serologies returned following discharge, and he was started on fluconazole, 200 mg/d.

A chest X-ray demonstrating bilateral pulmonary infiltrates consistent with multilobar pneumonia
A chest X-ray demonstrating bilateral pulmonary infiltrates consistent with multilobar pneumonia.

On the current admission, the patient was hypertensive with a blood pressure of 153/103 mm Hg, tachycardic (heart rate, 110 beats/min), febrile (temperature, 39.4 oC), and tachypneic (respiratory rate, 30 breaths/min) with oxygen saturation of 96% on a 60% fraction of inspired oxygen via bilevel positive airway pressure. He appeared in moderate distress with increased work of breathing. Pulmonary exam revealed bibasilar crackles with rhonchi and wheezing, and labs were notable for resolution of leukocytosis but persistent eosinophilia. A chest X-ray and chest CT showed multilobar consolidations consistent with severe pneumonia (Figure). Fluconazole was increased to 400 mg/d, and the patient was given broad-spectrum antibiotics for health care-associated pneumonia. Sputum culture was positive for coccidioides one week after admission, confirming the diagnosis.

One month later, the patient presented to the hospital again with a temperature of 39.4 oC and hypotension. Fluconazole was switched to posaconazole for refractory coccidioidomycosis with resultant resolution of fever. Follow-up imaging several months later showed improvement of pulmonary infiltrates.

The diagnosis

The patient was diagnosed with pulmonary coccidioidomycosis. Coccidioidomycosis is a fungal infection endemic to the southwestern United States and is caused by inhalation of Coccidioides spores. Cases can range from asymptomatic to severe with respiratory failure, sepsis, or disseminated infection requiring hospitalization. The infection can present similarly to bacterial or viral CAP, with symptoms such as fever, chills, and cough, making diagnosis difficult. However, patients may also experience night sweats, joint aches, muscle pains, and rash such as erythema nodosum or multiforme.

In endemic areas, 15% to 29% of all cases of CAP are due to primary coccidioidal pneumonia. Immunocompromised people and those with diabetes have increased risk of infection. This diagnosis should be considered in patients who do not respond to empiric antibacterial therapies for CAP. Diagnosis can be made with serologic enzyme immunoassay (IgM and IgG), immunodiffusion (IgM and IgG), or complement fixation (IgG). These tests become positive 7 to 21 days after exposure and often indicate recent or acute infection, as measurable anticoccidioidal antibodies decrease over time and become undetectable post-infection.

Enzyme immunoassay has the highest sensitivity of the three tests at 87%, which improves to 95% with subsequent and confirmatory testing. However, serologic testing may be falsely negative in early infection, and clinical suspicion remains key to accurate diagnosis. Peripheral eosinophilia, as was seen in our patient, occurs in up to 30% of cases and can assist with diagnosis.

Up to 95% of patients who develop symptoms of coccidioidomycosis infection have self-limited illness that resolves after several weeks and does not require treatment. Patients with mild, nondebilitating symptoms can be monitored closely as outpatients without antifungal medications, and serial serologic testing may be useful to monitor them for progressive disease. Patients who have debilitating illness, extensive pulmonary involvement, or diabetes or immunocompromise should be treated. At least 400 mg of oral fluconazole daily is the initial treatment of choice, and refractory infections can be treated with posaconazole.

Pearls

  • Coccidioidomycosis pneumonia should be considered in patients from the southwestern United States who have CAP that is prolonged or does not improve after antibiotic therapy.
  • Serologic testing with enzyme immunoassay, immunodiffusion, or complement fixation techniques may be false-negative in early infection but can be helpful.

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