Pulmonary eosinophilia (PE) can be found in very diverse pathological processes. Several medications have also been associated with this entity. Acetaminophen is a medication commonly used in multiple different drug formulations, many of which are available without a prescription. It has however been associated with pulmonary eosinophilia (eosinophilic pneumonia) in a few cases in Japan. We describe the case of a 68-year-old Caucasian female who presented with new persistent dry cough and dyspnea on exertion after she started using up to 4 grams of acetaminophen on a daily basis. Chest imaging revealed peripheral lower lung zone ground glass and reticular opacities, and increased eosinophils were present on bronchoalveolar lavage (BAL). The patient’s symptoms markedly improved upon acetaminophen cessation, and significantly decreased eosinophils were seen on repeat BAL. To our knowledge, this is the first case of likely acetaminophen-induced pulmonary eosinophilia reported outside Japan.
A 68-year-old Caucasian female presented with a 6-month history of new disabling nonproductive cough and exertional dyspnea (Medical Research Council dyspnea scale 2/5). She denied having any recent fevers, chills, or weight loss. The patient did not report new dermatologic complaints or arthralgias. She denied recent travel history. She had no history of smoking or drug use. She was retired, having previously worked in an office, and living in a well-kept home. Past medical history consisted of hypertension, idiopathic Raynaud’s phenomenon, and mechanical back pain. Her medications included hydrochlorothiazide, which she had been on for seven years, vitamin D, calcium carbonate, and magnesium. Also, she was using everyday a drug formulation (Genacol® maximum strength) containing acetaminophen, chlorpheniramine, dextromethorphan, and pseudoephedrine for persistent nasal congestion, which she started just prior to the onset of her respiratory complaints. She had in addition began taking acetaminophen for a few months, for nonspecific “body aches,” up to a total combined amount of 4 grams per day. She had received two different courses of antibiotics from her family physician for her new respiratory symptoms as well as a trial of inhaled ciclesonide without any improvement, before being seen in Respirology Clinic.
On physical examination, the patient looked well. Her blood pressure was 140/70 mm Hg, heart rate 76 beats per minute, and SpO2 97% on room air. Respiratory examination revealed the presence of fine bibasilar inspiratory crackles. She had no clubbing. The cardiovascular and abdominal examinations were unremarkable. A purple discoloration of the fingers and toes was present, in keeping with the patient’s known Raynaud’s phenomenon. The remainder of the examination was normal.
A chest radiograph showed increased bilateral lower lung interstitial markings (Figure
Posteroanterior and lateral chest X-ray revealing bilateral reticular infiltrates seen more significantly in the lower lung zones.
Chest computed tomography (CT) images showing lower lung zone predominant ground glass attenuation and reticulations present.
The complete blood cell count was normal: hemoglobin 141 gr/L, white blood cell count 8.1 × 109/L, eosinophils 0.1 × 109/L, and platelet count 232 × 109/L. Electrolytes, urinalysis, and renal and liver function tests were normal. Erythrocyte sedimentation rate and C-reactive protein were mildly elevated, at 28 mm/H and 5.4 mg/L, respectively. Antinuclear antibody level was weakly positive at 1 : 40, with a speckled pattern; the extractable nuclear antigens panel was negative. Complement levels, anti-double-stranded DNA, rheumatoid factor, anti-cyclic citrullinated protein antibody, cryoglobulins, perinuclear anti-neutrophil cytoplasmic antibodies (ANCA), and cytoplasmic ANCA were all either normal or negative. The patient was assessed by rheumatology; no evidence of a connective tissue disease was found.
Hydrochlorothiazide was stopped due to reported cases of drug-induced pneumonitis [
The patient was seen again in clinic after the bronchoscopy. A new literature search was performed and revealed a rare but previously described association between acetaminophen use and pulmonary eosinophilia [
Pulmonary eosinophilia, also called eosinophilic pneumonia or pulmonary infiltrates with eosinophilia, can be caused by drugs and toxins; it has also been described in autoimmune, infectious, and malignant processes or can be idiopathic [
Pulmonary eosinophilia can present with nonproductive cough, dyspnea, hypoxemia, fever, malaise, and weight loss. Peripheral blood eosinophilia is often seen but may be absent. Pulmonary function tests frequently show a restrictive pattern; concomitant airway obstruction is seen in some cases. CT findings of drug-induced PE almost always include areas of ground glass attenuation and airspace consolidation, with a lower lung or random zonal predominance. Also, pulmonary infiltrates tend to be more peripheral than central in distribution [
Acetaminophen is a very common medication used for its analgesic and antipyretic properties. It is also found in many formulations often available over the counter, which may contain antihistamines or cough suppressants. Patients are often prone to forgetting to mention acetaminophen use when seeing their physician given it is widely available. It has however been linked with the development of eosinophilic lung disease in five cases from Japan [
To our knowledge, this is the first case of likely acetaminophen-induced pulmonary eosinophilia reported outside Japan and is a reminder to consider common medications as a cause of drug-induced PE.
Learning objectives are as follows: To review the diagnosis and main conditions associated with pulmonary eosinophilia (PE). To recognize that common medications, including acetaminophen, have been linked with pulmonary eosinophilia.
What are the main conditions associated with pulmonary eosinophilia? How is drug-induced pulmonary eosinophilia diagnosed and treated?
None of the authors have conflict of interests to declare.
Drs. Saint-Pierre and Moran-Mendoza identified the case and both participated in writing this report.
The authors would like to thank Mrs. Geraldine MacDonald for her editorial help with the paper.