Practitioners in the emergency room, primary care settings, and specialty clinics who provide services to patients with various forms of ILD must often distinguish respiratory symptoms associated with pre-existing conditions from those attributable to possible acute COVID-19 infection (Table). Unfortunately, many of the signs and symptoms overlap. Moreover, fear of infection with COVID-19 — particularly among the elderly and those with pre-existing and predisposing comorbidities — may drive patients to seek medical evaluation more acutely.
Table. Comparison Between Interstitial Lung Disease (ILD) and COVID-19 Infection
|ILD||COVID – 19|
|Causes||Interstitial pneumonia; hypersensitivity pneumonitis; systemic autoimmune diseases (eg, lupus, rheumatoid arthritis, scleroderma, Sjögren syndrome, sarcoidosis); medications (eg, chemotherapy, statins); idiopathic pulmonary fibrosis||SARS-CoV-2|
|Symptoms||Shortness of breath; nonproductive, dry, hacking cough; tiredness and weakness; poor appetite and progressive weight loss; mild chest pain||Fever and chills, cough (dry early in disease), malaise, sore throat, rhinorrhea, myalgia, loss of appetite and/or sense of smell, diarrhea|
|Timing||Chronic, but may flare. If infectious, it may be more acute||2 to 14 days after exposure|
|Lab Evaluation||Complete blood count, basic metabolic panel, and liver function tests.||Complete blood count, basic metabolic panel, liver function tests, and coagulation evaluation|
|Lab Findings||Depending on suspected etiology, findings may include serum antibodies, urinalysis, angiotensin converting enzyme levels, C-reactive protein, sedimentation rate, and Beta-2 microglobulin levels||Findings may include lymphopenia (common), anemia, prolonged prothrombin time and D-dimer, lactate dehydrogenase ≥250 U/L (seen in >40%), procalcitonin ≥0.5 ng/mL (seen in 5%), and elevated inflammatory markers|
|Radiographic Findings||Chest radiograph demonstrates linear, reticular, and or nodular opacities, while chest CT demonstrates ground-glass opacity, interlobular septal thickening, intralobular interstitial thickening, reticular infiltrates, and honeycombing||Chest radiograph findings vary from normal to consolidation. Chest CT presents ground-glass opacification that evolves into consolidation. Lower lobe involvement predominates; peripheral lung involvement is most common, and pleural effusions and lymphadenopathy are typically absent|
|Evaluation||Pulse oximetry and pulmonary function tests. Depending on suspected etiology, this may include bronchoscopy and lavage or lung biopsy||Pulse oximetry, targeted history to identify risk factors (eg, travel or exposure), isolation and notification, RT-PCR assay for detecting SARS-CoV-2. Use appropriate PPE|
|Treatment||Successful management depends upon establishing an accurate and specific diagnosis. Depending on suspected etiology, this may include targeted therapy based on diagnosis (eg, corticosteroid/cytotoxic, or antimalarial drugs), supplemental oxygen as needed, inhaled therapies, smoking cessation, vaccinations, weight reduction, lung transplantation, and best supportive care||Supportive care depending on severity, antibiotics if pneumonia is present, systemic steroids, antivirals (eg, remdesivir), antimalarials, and clinical trials|
Mrs B felt very uneasy about the possibility that her symptoms may be related to the early onset of COVID-19, given the epidemiology and high reported death rates in octogenarians. She noted that her age, hypertension, recent hospitalization, travel history, pre-existing lung conditions, and possibly the use of an angiotensin receptor blocker (ARB) put her at a high risk of severe respiratory consequences if she were to contract the SARS-CoV-2 virus. Additionally, the patient discontinued hydroxychloroquine 4 months prior due to retinopathy, which had helped manage her ILD and Sjögren syndrome symptoms for many years. Mrs B. felt that this may potentially have mitigated her risk of contracting COVID-19, given reports of use of another similar medication, chloroquine, in infected individuals.1
Differential Diagnosis of Interstitial Lung Disease
ILD is characterized by the presence of inflammation and altered lung interstitium. Over 100 forms of ILD have been described and are differentiated from each another using clinical, radiologic, and pathologic findings.2 The histopathologic changes in the lungs of patients with ILD can vary, and diagnoses fall into multiple categories such as idiopathic interstitial pneumonia, connective-tissue-disease-associated ILD, hypersensitivity pneumonitis, iatrogenic fibrosis (drug-induced ILD), eosinophilic ILD, occupational lung disease, inherited disorders, and primary disorders.2
Since various forms of ILD have similar clinical presentations, establishing a clear diagnosis is required to guide subsequent management. Evaluation must include a careful history and physical examination looking for associated signs and symptoms, targeted laboratory analyses, chest imaging, and — when necessary — invasive diagnostic procedures including bronchoscopy and lung biopsy.
Once an accurate and confident diagnosis is made, treatment can be tailored to the underlying condition. Key to management is providing education and devising a care plan with both the patient and their caregivers, as many forms of ILD will progress and limit quality of life. Disease-specific monitoring for prognostication and treatment decisions are critical, as are pulmonary rehabilitation and supplemental oxygen as needed.
Many patients will have associated comorbidities; these must be identified and treated concurrently (eg, hypertension, anemia, anxiety, reflux, and sleep disorders). Lung transplantation may ultimately be required for progressive or refractory ILD, which is now the leading indication for lung transplantation in the United States, surpassing chronic obstructive pulmonary disease.2 The 5-year survival rate following lung transplantation for most forms of ILD is 53%.3
Pulmonary Manifestations in Sjögren Syndrome
Sjögren syndrome is a progressive autoimmune disease primarily affecting women that is caused by inflammatory lymphocytic infiltrate of exocrine glands. Symptoms include dry mouth and eyes, parotid swelling, profound fatigue, widespread musculoskeletal pain, and polyarthritis.4
Lung manifestations of Sjögren syndrome vary and can include both airway abnormalities and ILD, which may be present in 43% to 75% of patients based on radiographic studies.4 Pulmonary symptoms may be present in up to 20% of afflicted patients.4 Lymphoproliferation and autoimmune destruction of lung tissue may cause elevation in Beta-2 microglobulin,4 as seen in Mrs B.
Clinical manifestations are often nonspecific and can include dyspnea (62%), cough (54%), sputum production (14%), chest pain (11%), and/or fever (7%).4 Nearly three-fourths of patients have positive anti-Ro/SSA serum antibodies.4 Sjögren syndrome is associated with multiple forms of pulmonary involvement including airway disease, ILD, cystic lung disease, pulmonary lymphoma, and lymphocytic interstitial pneumonitis. The prognosis of Sjögren syndrome lung disease varies by the type of pulmonary involvement. Cystic lesions are usually associated with good survival and fewer complications compared with ILD.