Acute eosinophilic pneumonia

Abstract

We report the case of an 18-year-old woman who presented to an outside hospital in respiratory distress and was found to have pulmonary eosinophilia. She remained profoundly hypoxaemic despite maximal ventilatory strategies and underwent cannulation for veno-venous extra corporeal membrane oxygenation (ECMO). The respiratory failure improved with time, using corticosteroids, and the veno-venous ECMO helped in stabilisation of the patient in the setting of profound hypoxaemia.

Background

Acute eosinophilic pneumonia is a rare but potentially curable cause of respiratory failure that should be in the differential diagnosis for acute respiratory distress syndrome. Treatment with corticosteroids results in a rapid and dramatic positive response without recurrence. In this case, we emphasise the importance of utilising veno-venous extra corporeal membrane oxygenation (VV-ECMO) to support patients during the early stages of the disease, thereby stabilising the patients while treatment with corticosteroids takes effect.

Case presentation

We report the case of an 18-year-old woman who presented to an outside hospital in respiratory distress. According to the patient, she had exertional dyspnoea for the preceding 2 days that was associated with non-productive cough. Pertinent positives were a low grade fever, nausea, vomiting and non-bloody diarrhoea for 2 days prior to presentation. Review of systems was otherwise negative. She had a history of allergy to wasps and used her epinephrine auto-injector without significant improvement in her dyspnoea. She reported close contact with a raccoon that she had adopted 2 weeks earlier.

The patient's medical history was significant for dilation and curettage of a molar pregnancy 6 months prior to presentation. She had recovered uneventfully after the procedure. She regularly used vaporised nicotine, and 1 week prior to presentation smoked cigarettes for the first time. She denied any alcohol or drug use. On presentation at the outside hospital she was febrile (102°F), tachycardic (190/min) and tachypnoeic with peripheral oxygen saturation in the 70s. Based on the clinical situation, she was immediately emergently intubated for refractory hypoxaemia. Despite heavy sedation, paralytics and bi-level mechanical ventilation, she had significant refractory hypoxaemia with PaO₂/FiO₂ ratios in the mid-40s. Our ambulatory ECMO team was consulted for refractory hypoxaemia despite maximal ventilatory strategies, and the patient was emergently placed on VV-ECMO for immediate stabilisation and transferred to our facility, for a higher level of care.

Investigations

The patient's laboratory investigations revealed a normal basic metabolic panel and a complete blood count significant for peripheral eosinophilia. At the outside hospital, her white cell count had been elevated at 41 k/mm³, with >80% segmented neutrophils and >5% eosinophils (absolute 2.2 k/mm³). Bronchoalveolar lavage (BAL) had shown >25% eosinophils. After the transfer to our hospital, which was within 6 h of her presentation to the outside hospital, her white cell count had fallen to 21.8 k/cm³, with 80% segmented neutrophils and 12% eosinophils (absolute 2.6 k/mm³). Her absolute eosinophil count rose and reached a maximum of 2.9 k/cm³. Her liver function tests were unremarkable. Antineutrophil cytoplasmic antibody test was negative. Coccidoides titres and Strongyloides testing were also negative. Chest X-ray revealed complete opacification of the bilateral lung fields (figure 1). Chest CT showed extensive pulmonary disease in lung fields, septal thickening and nodular and alveolar infiltrates.

Figure 1.

Chest X-rays. (A) CXR on admission, day 1: diffuse confluent lung disease, consistent with ARDS, pulmonary oedema or other airspace process. (B) CXR on day 13: bilateral infrahilar opacities have continued to improve. ARDS, acute respiratory distress syndrome.

Differential diagnosis

Lung diseases that present with pulmonary eosinophilia share characteristic traits, which include peripheral blood eosinophilia, lung tissue eosinophilia and increased eosinophils in the BAL fluid; all of which are traits that were present in our patient.

The major causes of pulmonary eosinophilia include:

1. Drug-induced and toxin-induced eosinophilic lung diseases

2. Helminthic and fungal infection-related eosinophilic lung diseases

3. Acute eosinophilic pneumonia

4. Chronic eosinophilic pneumonia

5. Eosinophilic granulomatosis with polyangitis

6. Idiopathic hyper eosinophilic syndrome

7. Neoplasms

8. Non-helminthic infections

Treatment

A thorough review of the history indicated that the patient was exposed to cigarette smoking, which is a known precipitant of idiopathic acute eosinophilic pneumonia. Exposure to a raccoon was also deemed to be a risk factor, although previously unreported. The absence of any helminths in the BAL along with negative serological titres suggested that helminthic-related eosinophilic lung disease was lower on the differential diagnosis. Idiopathic acute eosinophilic pneumonia or an eosinophilic reaction to raccoon exposure seemed to be the most plausible mechanism for the febrile illness leading to severe respiratory failure that was otherwise unexplained. Eosinophilic granulomatosis with polyangiitis (EGPA) was in the differential diagnosis but the patient did not have any other features of EGPA (such as asthma, migratory or transient pulmonary opacities, mononeuropathy, or paranasal sinus abnormality). She was evaluated by the haematology service for potential hypereosinophilic syndrome, given the extent of peripheral eosinophilia at presentation. There was no other evidence of end-organ damage to any other tissues other than those of the respiratory system.

Owing to her instability on maximum ventilator support, the patient required ECMO placement prior to transportation to our hospital. A dual-lumen Avalon cannula was placed in the right internal jugular vein and VV-ECMO was initiated at 3.5–4.0 L flow. She was started on anticoagulation and brought to our hospital by helicopter on our mobile ECMO unit. On arrival at our facility, her ventilatory requirements improved significantly on VV-ECMO and we were able to provide lung rest ventilation.

She underwent fibre optic bronchoscopy and transbronchial biopsy to evaluate the aetiology of the acute lung injury. The airways appeared normal and a BAL revealed elevated white cell count at 2825/mm³ with 80% eosinophils (figure 2). The biopsy showed acute lung damage with eosinophils in the alveolar space and alveolar wall, perivascular eosinophils and degranulation (figure 3).

Figure 2.

Initial BAL. Low power H&E staining of bronchoalveolar lavage fluid revealing eosinophilia. BAL, bronchoalveolar lavage.

Figure 3.

BAL at 7 days. Low power H&E staining of bronchoalveolar lavage fluid revealing eosinophilia resolved after steroid therapy. BAL, bronchoalveolar lavage.

Based on the BAL, transbronchial biopsy and the clinical course, the patient was diagnosed with acute respiratory distress syndrome with pulmonary eosinophilia. She underwent evaluation for parasitic diseases and a thorough history of all drug exposures was reviewed again. Relevant rheumatological studies were sent and these were negative. She was started on high-dose corticosteroids for presumed acute eosinophilic pneumonia within 2 h after transfer to our facility, after which significant improvement was noted clinically and radiographically within a week after presentation. By the end of the first week, a repeat bronchoscopy revealed a significant decrease in the patient's white cell count (260/mm³) with 10% eosinophils (figure 1).

Outcome and follow-up

The patient was de-cannulated from VV-ECMO on day 6 after cannulation and extubated on day 11 after intubation. Her eosinophil count normalised 8 days after hospitalisation. She was monitored on a step-down unit and sent home on tapering doses of steroids after 18 days of hospitalisation. She returned for follow-up in clinic, with no significant limitation.

Discussion

Acute eosinophilic pneumonia is an acute febrile illness resulting in life-threatening respiratory failure. It has been speculated that acute eosinophilic pneumonia is idiopathic in most patients. It may be triggered by drugs, inhaled substances, tobacco smoke or infections. A significant proportion of patients have engaged in outdoor activities such as cave exploration, wood pile moving, motor car racing or working in dusty conditions,¹ prior to onset. A higher proportion of patients have allergic diatheses, suggesting that it is likely to occur in atopic individuals.² The key features in diagnosis are respiratory impairment, diffuse pulmonary infiltrates on the chest X-ray and BAL, and lung biopsy eosinophilia.³ Normally, eosinophils are found in very few numbers (<2%) in the BAL. However, in eosinophilic lung diseases, there are >25% eosinophils (2–25% are found in non-specific conditions).⁴ Lung biopsy shows marked infiltration of eosinophils in the interstitial and alveolar spaces.⁵ High-resolution CT at the peak of the disease reveals peripheral ground glass opacities and diffuse bilateral reticular densities, with septal thickening and pleural effusions.^{5 6} Helminths may or may not be seen in the BAL, and presence of eosinophils is a more sensitive marker for eosinophilic lung diseases. Clinical history, BAL fluid analysis and progression of the disease should be taken into account as differential diagnoses are narrowed and other possibilities eliminated.^{7 8} Given rapidly progressive hypoxaemic respiratory failure that does not respond to conventional treatments, an algorithm for management of hypoxaemic respiratory failure should be followed so patients are appropriately considered for extra corporeal life support for immediate stabilisation.^{9 10}

Learning points.

• Acute eosinophilic pneumonia should always be considered in patients who present with acute respiratory distress syndrome.

• It could be misdiagnosed, and bronchoalveolar lavage fluid is always indicated for further diagnosis.

• Patients are usually young and otherwise healthy.

• When patients present with refractory hypoxaemic respiratory failure despite maximal ventilatory strategies, veno-venous extra corporeal membrane oxygenation should be considered.