A 53 year old man with a history of substance abuse initially presented to an emergency room with complaints of progressive dyspnea. He was diagnosed with an acute exacerbation of chronic obstructive pulmonary disease (COPD) and discharged home. With worsening dyspnea, dry cough, and weight loss, he was hospitalized and started on levofloxacin along with corticosteroids. Due to a history of high risk behaviour, an HIV test was obtained which returned positive. Given the patient's hypoxia and demonstration of diffuse ground glass opacities on computed tomography (CT) of the chest [Fig. 1], a clinical diagnosis of PCP was made, and the patient was switched to intravenous (IV) trimethoprim-sulfamethoxazole (TMP-SMX) and corticosteroids. He remained in the hospital for about 3 weeks, continuing to require supplemental oxygen as well as non-invasive ventilation in the form of BiPAP (Bilevel Positive Airway Pressure). This prompted transfer to our institution, a tertiary care university hospital, for a possible need for an open lung biopsy.
Upon presentation at our institution, he had no fever or hemodynamic instability. He appeared to be in moderate respiratory distress requiring BiPAP support. He had diffuse, coarse crackles on lung auscultation bilaterally. The rest of his examination was unremarkable except for the presence of skin tattoos and oral thrush.
He reported a 37-pack-year smoking history and denied any alcohol abuse. He denied international travel or known exposure to anyone with tuberculosis. He reported that he had sex with men and prior history of IV methamphetamine use. He denied any known exposure to chemicals or toxic fumes.
Differential diagnoses in this case included atypical infections such as Mycoplasma, Legionella, mycobacteria such as Mycobacterium avium complex (MAC), Mycobacterium tuberculosis, fungal etiology such as Cryptococcus or Histoplasma, and viral pneumonia including CMV, adenovirus, respiratory syncytial virus, or influenza virus. Drug-resistant Pneumocystis was also possible given the non-response to treatment. Non-infectious causes such as acute eosinophilic pneumonia, acute interstitial pneumonia, cryptogenic organizing pneumonia as well as immune reconstitution syndrome were possibilities. Considering the patient's immunocompromised status, infectious causes were, however, more likely.
A complete blood count revealed a normal white count of 6500/mm3 (normal: 4000-10,000/mm3). Hemoglobin was 10.5 g/dL (normal: 13.0-16.5 g/dL) with a normal platelet count. Chemistry panel showed normal renal and hepatic function with a low albumin of 2.9 g/dL (normal: 3.5-5.0 g/dL). Arterial blood gases (ABG) analyses showed a PaO2 of 64.7 mmHg on supplemental oxygen. HIV RNA PCR showed a viral load of 194,901 copies/mL. His CD4 count was 44 cells/mm3 with CD4% of 8.5%.
1,3-beta-d-glucan assay was strongly positive with a value >500 pg/mL (>80 pg/mL is considered positive). Routine blood cultures showed no growth at 5 days, fungal and AFB (acid fast bacilli) blood cultures also remained negative. Urinary Histoplasma antigen and serum Cryptococcal antigen were both negative. Serum rapid plasma reagin (RPR) was non-reactive.
A repeat CT scan of the chest showed progression of bilateral ground glass opacities with development of mild interlobular septal thickening resulting in a characteristic "crazy-paving" pattern [Fig. 2].
On day 3 of admission, he underwent a bronchoscopy and bronchoalveolar lavage (BAL). BAL Gram stain and culture showed no organisms. BAL fungal and AFB stains along with cultures remained no growth. BAL galactomannan was negative. BAL cytology showed enlarged cells with a large intranuclear inclusion surrounded by a halo, creating an "owl's eye" appearance which is characteristic for Cytomegalovirus. Also present were alveolar casts which stained weakly with Gomori methenamine silver (GMS) and revealed structures morphologically consistent with Pneumocystis organisms [Fig. 3].
Plasma CMV DNA PCR was also positive with 17,424 copies/mL.