Interstitial Lung Disease or COVID-19? A Complex Pulmonary Differential Amid a Global Health Crisis

Pulmonary fibrosis of rheumatoid arthritis. Usual interstitial pneumonia (UIP). Very extensive honeycomb appearance of the lower lobes. Chest CT scan of a 70-year-old-male patient, axial section.
A case review demonstrates the challenges in differentiating interstitial lung disease from COVID-19 during the global pandemic.

Mrs B is an 81-year-old White female who presented in April 2020 with a worsening dry cough, fatigue, sinus congestion, myalgia, headache, and mild but progressive dyspnea over 10 days with nausea, decreased oral intake, and no reportable fever. She reported a recent hospitalization 1 month prior, in March 2020, for new onset atrial fibrillation requiring cardioversion. She had recently returned from winter travel to Florida, approximately 2 weeks prior to presentation.


The patient reported a past medical history significant for hypertension, hyperlipidemia, obstructive sleep apnea (OSA) requiring continuous positive airway pressure (CPAP), rheumatoid arthritis, histoplasmosis, and Sjögren syndrome. 

Mrs B initially noted dry mouth and an intermittent, non-productive, hacking cough beginning in her mid 40s. Chest radiography at that time noted an interstitial pattern of unknown etiology. Pulmonary function testing demonstrated a restrictive pattern. Serum autoantibodies including anti-Sjögren syndrome related antigen A (SSA), anti-Sjögren syndrome type B (SSB), and antinuclear antibodies (ANA) were repeatedly negative.

The patient experienced intermittent flares over the next 10 years but experienced no hospitalizations and had no need for supplemental oxygen. Approximately 15 years ago, a chest radiograph during a flare of pulmonary symptoms noted a lung nodule. Biopsy was positive for histoplasmosis within a background of interstitial lung disease (ILD), for which the patient was treated symptomatically.

A diagnosis of Sjögren syndrome was suspected clinically and ultimately secured at age 60 via a labial gland biopsy that noted focal lymphocytic sialadenitis. Mrs B was treated successfully with hydroxychloroquine for nearly 19 years, with significant improvement of pulmonary and related symptoms; however, she reported that the medication was discontinued in December 2019 due to drug related retinopathy ─ 4 months prior to presentation. 

Mrs B reported no significant surgical history. On presentation, her medications included olmesartan/hydrochlorothiazide (HCTZ), amlodipine, furosemide, rosuvastatin, apixaban, and gabapentin. She also noted seasonal allergies. The patient had a history of social smoking more than 60 years ago, and drank alcohol socially. She received her flu vaccination earlier in the season. She is a widow, lives alone, and travels to Florida regularly. Family history was non-contributory.

Physical Examination

Mrs B’s initial vital signs are as follows: temperature, 99.1 ℉; blood pressure, 189/108 mm Hg; heart rate, 72 beats per minute and regular; and respirations, 22 breaths per minute. Oxygen saturation was 93% on room air. Physical examination identified significant rheumatoid deformities of the hands. Mild expiratory wheezes bilaterally and a pleural rub at the left base were noted on lung auscultation. Neck, skin, cardiovascular, gastrointestinal, genitourinary, neurologic, and psychiatric areas were all normal. She had significant osteoporosis deformities.

Evaluation and Tests

Given Mrs B’s symptoms and history of ILD, histoplasmosis, Sjögren syndrome, and atrial fibrillation, blood work and imaging were obtained. Her white blood cells were 12.2 with normal lymphocytes; hemoglobin was 13.4 g/dL, and estimated glomerular filtration rate was 63 mL per minute (creatinine, 0.9 mg/dL). Liver function tests revealed an alkaline phosphatase of 135 IU/L, aspartate aminotransferase of 45 u/L, alanine aminotransferase of 38 IU/L, and normal bilirubin.

Her sedimentation rate was 26 mm/h (normal, 0-20 mm/h), high-sensitivity C-reactive protein was 1.87 mg/L (normal <7.4 mg/L), and Beta-2 microglobulin was 2.85 mcg/L (normal, 1.1-2.4 mcg/L). Induced sputum culture, serum mycoplasm antibody, pneumococcal antigen, and urine legionella antigen were all obtained and negative. In an effort to exclude congestive heart failure, a brain natriuretic peptide was measured and was normal (<100 pg/mL).

Available imaging included a recent chest radiograph performed at the time of her hospitalization for atrial fibrillation and a chest computed tomography (CT) scan obtained during the current evaluation (Figure).

Figure. Chest radiograph (left) and representative axial computed tomography (CT) image (right). These illustrate a left lower lobe retrocardiac opacity with interstitial markings on chest radiograph and a small infiltrate on axial CT images with mild bronchiolitis.


Mrs B’s differential diagnosis includes atypical infection, congestive heart failure, recurrence or reactivation of histoplasmosis, or exacerbation of her ILD secondary to recent discontinuation of her hydroxychloroquine for Sjögren syndrome. Given her risk factors, including recent hospitalization, travel, age, comorbidities, and symptoms, coronavirus disease 2019 (COVID-19) was also considered.

Clinical and radiographic data rule out other causes and support the diagnosis of an ILD flare, supported by imaging and a negative rapid influenza test and reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2. The patient was managed symptomatically with oral steroids and inhalers as an outpatient and recovered over the ensuing 10 days.

This article originally appeared on Clinical Advisor