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Abstract
Eosinophilic lung diseases are a rare group of lung disorders with multiple known and unknown aetiologies and the diagnosis is often challenging. We present a case of a young man who was admitted with pneumonia due to methicillin-sensitive Staphylococcus aureus and was discharged on antibiotics. He presented to the emergency department approximately 2 weeks after discharge with high-grade fever, cough and shortness of breath associated with serum and bronchoalveolar lavage eosinophilia. He was then treated with steroids with complete resolution of disease process.
- pneumonia (infectious disease)
- pneumonia (respiratory medicine)
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Background
Eosinophilic lung diseases consist of a broad range of diseases with a number of aetiologies. Some of the known aetiologies include drug reactions, parasitic infections, allergic bronchopulmonary aspergillosis and eosinophilic vasculitis.1 Rare fungal and viral aetiologies have also been reported in the literature to cause eosinophilia and eosinophilic lung diseases.2–5 To the best of our knowledge bacterial infections have not been reported to cause eosinophilic lung disease. We present a case of a young man who was initially managed in hospital with methicillin-sensitive Staphylococcus aureus (MSSA) pneumonia. He later presented with worsening symptoms and lung infiltrates on chest X-ray with serum and bronchoalveolar lavage (BAL) eosinophilia.
Case presentation
A 24-year-old man with no known prior comorbidities came to the emergency room with complaints of high-grade fever, shortness of breath and cough productive of mucopurulent sputum for 3 days. He did not report any weight loss or night sweats. There was no history of chronic lung disease or any allergies. He was unmarried with no history of high-risk behaviour. He was a current smoker with 3 pack-year history of smoking; however, there was no history of use of alcohol or other substance abuse. There was no history of electronic cigarette consumption. On examination, his blood pressure was 135/90 mm Hg, heart rate was 90 beats per minute, respiratory rate was 24 breaths per minute and he was afebrile. He was maintaining saturations above 95% on room air. Chest examination revealed bilateral mid-zone crepitations. The rest of the systemic examination was normal.
Laboratory work-up on first admission revealed haemoglobin of 136 g/L, white cell count of 9.7×109/L with 83% neutrophils, 7% lymphocytes and 9% eosinophils (normal: 0.3–7.4), and platelet count of 327×109/L. Erythrocyte sedimentation rate was 2 mm/first hour (normal 0–15). Chest X-ray showed bilateral alveolar infiltrates predominantly in the mid and lower zones sparing the apices and the periphery (figure 1). Serum electrolytes and renal function were normal. Serum procalcitonin was 0.039 ng/mL and serum HIV was non-reactive. Nasal swab for H1N1 influenza virus was negative. Sputum for acid fast bacilli (AFB) smear and culture with Gene XPERT/MTB-RIF were also negative. Sputum cultures showed growth of MSSA. However, blood cultures were negative.
Chest X-ray on first admission showing bilateral alveolar infiltrates predominantly in the middle and lower zones sparing the apices and the periphery. PA, posteroanterior.
He was treated with intravenous ceftriaxone and oral azithromycin for the initial 2 days. His condition improved and he became afebrile. Antibiotic was switched to oral cefpodoxime and he was discharged home.
He presented to the emergency room on the 17th day of discharge with high-grade fever, worsening cough and shortness of breath. These symptoms started after 1 week of discharge but worsened over the last 4–5 days. On examination his blood pressure was 128/83 mm Hg, heart rate was 97 beats per minute, respiratory rate was 31 breaths per minute and he was febrile with a temperature of 39°C. He was maintaining oxygen saturations at 98% with 2 L of supplemental oxygen. His chest examination revealed bilateral basal crepitations.
Investigations
Complete blood count showed increased peripheral eosinophils of 39.4% (normal: 0.3–7.4). The trend of complete blood count is shown in table 1. The peripheral eosinophil count was gradually increasing on serial complete blood count. Stool for ova and parasites was negative. Serum antineutrophil cytoplasmic antibodies (c-ANCA and p-ANCA) was also within normal limits. Serum IgE level was 361.3 IU/mL (normal: <158). Arterial blood gas measurements performed on room air revealed pH of 7.39, partial pressure of carbon dioxide in arterial blood (PCO2) of 38 mm Hg, partial pressure of oxygen in arterial blood (PaO2) of 68 mm Hg, serum bicarbonate (HCO3) of 25 mmol/L and oxygen saturation of 91%. Chest X-ray showed bilateral alveolar infiltrates predominantly involving the peripheral lung fields (figure 2). High resonance CT scan showed patchy areas of ground-glass opacities in bilateral lungs predominantly in the basal region with interlobular septal thickening. It also showed randomly distributed nodules in both lungs, more confluent in the lung bases (figure 3). Bronchoscopy with BAL was done. All cultures including galactomannan in BAL were negative. The differential cell count in BAL showed 42% neutrophils, 30% lymphocytes and 28% eosinophils.
Trend of complete blood count
Chest X-ray done on the second admission showing bilateral alveolar infiltrates predominantly involving the peripheral lung fields. PA, posteroanterior.
High resonance CT scan showing patchy areas of ground-glass opacities in bilateral lungs predominantly in the basal region with interlobular septal thickening and randomly distributed nodules in both lungs, more confluent in the lung bases.
Differential diagnosis
The two top differential diagnoses in this case were drug-induced eosinophilic pneumonia and postinfectious eosinophilic pneumonia. Drug-induced eosinophilic pneumonia was suspected as he received cephalosporins (ceftriaxone and cefpodoxime) and azithromycin. This diagnosis was less likely because even after the suspected medications were withdrawn, the patient’s symptoms continued to deteriorate, peripheral eosinophilia worsened and chest X-ray showed new infiltrates. Post-MSSA eosinophilic pneumonia was the most likely diagnosis because the peripheral eosinophil counts were raised even during the first admission before initiation of the antimicrobials. As the patient improved clinically after antibiotics, other possible respiratory viruses were not investigated and therefore bacterial superinfection after an initial viral infection cannot be entirely excluded.
Treatment
The patient was started on intravenous piperacillin/tazobactam and vancomycin. There was mild clinical improvement; however, the peripheral eosinophilia continued to deteriorate gradually, as shown in table 1, and there was no radiological improvement. The patient was started on systemic steroids at a dose of 0.5 mg/kg and remarkable clinical and radiological improvements were seen after 2 days of steroid therapy.
Outcome and follow-up
The patient’s condition improved remarkably and hence he was discharged on a tapering dose of steroids. He was followed up in the clinic after 2 weeks, where his steroids were gradually tapered. Repeat chest X-ray on follow-up showed complete resolution of infiltrates.
Discussion
Eosinophilic lung diseases are a rare group of heterogeneous lung diseases which are characterised by abnormally increased eosinophils in the airways and the lung parenchyma.6 The defining characteristics of pulmonary eosinophilia include peripheral blood eosinophilia with abnormalities on chest imaging, increased eosinophils in BAL fluid and lung tissue eosinophilia on lung biopsy.7 8 Major unknown causes include simple pulmonary eosinophilia, acute eosinophilic pneumonia, chronic eosinophilic pneumonia and idiopathic hypereosinophilic syndrome, and some known causes include allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis, parasitic infections, drug reactions and eosinophilic vasculitis.1
Many infections are known to cause eosinophilic pneumonia. Fungal infections such as coccidioidomycosis have been reported in the literature to cause eosinophilia.2 3 Pulmonary mucormycosis has shown relation with peripheral blood and pulmonary eosinophilia.4 Disseminated cryptococcal infection is also associated with peripheral blood and pulmonary eosinophilia.9–11 Helminths and retroviruses such as human T-lymphotropic virus human T-lymphotropic virus (HTLV-II and HIV-1) can also be associated with eosinophilia.5
Many drugs have been known to cause eosinophilic lung diseases. Majority of them are antimicrobials and non-steroidal anti-inflammatory drugs.12 Mesalazine has been implicated to cause eosinophilic pneumonia.13 Administration of ibuprofen and acetaminophen has also shown to cause hypoxaemia with pulmonary infiltrates and BAL eosinophils.14 Penicillins can lead to pulmonary infiltration with eosinophilia, with piperacillin/tazobactam specifically causing acute eosinophilic pneumonia.15 16 Cephalosporins have been documented to cause maculopapular rash, anaphylaxis, acute interstitial nephritis and urticaria.17
A case report described a patient who had acquired MSSA pneumonia and was treated with vancomycin, after which he developed eosinophilia. Interestingly, the sequela in this case report is actually opposite our case.18 An explanation as to why our patient developed eosinophilia can be attributed to the ability of S. aureus to directly induce eosinophil activation via platelet-activating factor receptor (PAFR). The platelet-activating factor (PAF) is an inflammatory mediator and eosinophils are expressed by PAFR. PAF can result from eosinophilic degranulation to superoxide production, enhanced adhesion and chemotaxis.19 S. aureus can bind to PAFR mimicking endogenous PAF. Eosinophils can also be directly activated via S. aureus and can use PAFR to kill the bacteria, releasing proinflammatory mediators. However, the exact relation between eosinophils and S. aureus is incompletely understood and has been defined in atopic dermatitis but not in pulmonary eosinophilia.20 Another possible mechanism, as described in a study, is the interaction of S. aureus with eosinophils via CD48, a Glycosylphosphatidylinositol (GPI) anchored receptor that leads to activation of eosinophils.21 However, objective evidence of the mechanism of S. aureus causing eosinophilia is yet to be established.
Patient’s perspective
I could not understand the cause of such illness for which I had to be hospitalized twice. I was up and about with no history of any illnesses previously hence it was a shocking experience for me. The good thing is that now I am well and I hope I do not need to go to the hospital again.
Learning points
Eosinophilic lung disease should be suspected when there are fleeting/migratory infiltrates on imaging.
The aetiology of eosinophilic lung diseases is broad and includes drug reactions, parasitic infections, vasculitis, and viral and fungal infections.
For physicians, thorough history and investigation should be of primary importance to identify the cause.
In rare instances, Staphylococcus aureus can cause eosinophilic lung disease and hence one should be aware of all the possible causes of eosinophilic lung diseases so as to timely diagnose and manage the patients.
References
Footnotes
Contributors SMZ: literature search, manuscript writing, reviewed and edited the manuscript. MZHH: literature search, manuscript writing. ABSZ: conceived the idea, reviewed and edited the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.