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An unusual case of pneumonia

BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e5272 (Published 09 August 2012) Cite this as: BMJ 2012;345:e5272
  1. Andrew W Barritt, neurology registrar,
  2. Mark B Jackson, consultant respiratory physician
  1. 1Department of Respiratory Medicine, Royal Sussex County Hospital, Brighton BN2 5BE, UK
  1. Correspondence to: A W Barritt awb{at}doctors.org.uk

A 28 year old woman presented with a one week history of increasing shortness of breath on exertion, which was associated with a dry cough and mild pain on the right side of the lateral chest wall. She had also felt feverish and experienced night sweats for three days. Her medical history included mild asthma for five years, which was well controlled on twice daily inhaled beclometasone, and a caesarean section three months before. Her postoperative recovery was uneventful. She was an ex-smoker, rarely drank alcohol, and denied any illicit drug use. In addition, her only recent foreign travel was a trip to France six months ago.

On examination, she was fully alert and oriented but was febrile (38.2°C), with a peripheral oxygen saturation of 95% on room air. On auscultation she had right sided lower zone lung crackles but no wheeze. The lymph nodes were not palpable. Her blood pressure was 96/60 mm Hg and her pulse was 84 beats/min. Initial blood tests showed haemoglobin 127 g/L (reference range 115-165) and the total white cell count 9.3×109/L (4.0-11.0), with an eosinophil count of 2.3×109/L (0.0-0.4). C reactive protein and erythrocyte sedimentation rate were raised at 172 mg/L (<5) and 102 mm in the first hour (0-15), respectively. Renal and liver function tests were normal and HIV serology was negative. A plain posterior-anterior radiograph is shown in fig 1.

Questions

  • 1 What does the chest radiograph show?

  • 2 What is the differential diagnosis?

  • 3 Which further investigations would you perform?

Answers

1 What does the chest radiograph show?

Short answer

The radiograph shows bilateral, particularly right sided, peripheral air space consolidation. Consolidation is also seen posteriorly and peripherally in the right lower zone, below the level of the right hilum. The cardiac outline is normal and no pleural effusion or pneumothorax is seen.

Long answer

The plain radiograph shows bilateral, particularly right sided, consolidation (fig 2) which is peripheral and, therefore, not restricted to a lobar distribution. The cardiac outline is normal and there is no evidence of pleural effusion or pneumothorax on either side. Lung nodules, cavitation, effusions, bronchiectasis, and fibrotic change—abnormalities sometimes associated with eosinophilic lung disease—are absent.

Figure2

Fig 2 Plain posterior-anterior radiograph showing bilateral, particularly right sided, peripheral air space consolidation (C)

2 What is the differential diagnosis?

Short answer

Given the clinical history, eosinophilia, and radiographical changes, the diagnosis is probably one of the pulmonary eosinophilia syndromes.

Long answer

A raised eosinophil count can be associated with a variety of conditions such as inflammatory states, drug reactions, and infections, and it can even herald haematological cancer.1 When the lungs are affected, however, the list focuses on pulmonary eosinophilic syndromes, which can be classified as having identified and non-identified causes.2 3 Identified causes include inhaled fungal allergens (such as Aspergillus fumigatus and Candida albicans), helminth infections (with Ascaris lumbricoides, Strongyloides stercoralis, and filariasis), drugs (penicillins, sulfonamides, tetracyclines, and non-steroidal drugs), and even radiation.2 3 A thorough travel history is therefore essential, along with a detailed drug history. Non-identified causes are Churg-Strauss syndrome (granulomatous vasculitis of small and medium sized vessels), the multisystem hypereosinophilic syndrome, and idiopathic pulmonary eosinophilia, which can be classed as acute or chronic, depending on the clinical presentation.2 3

3 Which further investigations would you perform?

Short answer

Further tests include antineutrophil cytoplasmic antibody (ANCA) serology, total IgE values, testing for A fumigatus (skin prick tests or specific IgE), and stool microscopy and culture. High resolution computed tomography of the thorax provides more detail than plain radiography, and flexible bronchoscopy with bronchoalveolar lavage can confirm whether the infiltrate is eosinophilic and provide samples for microscopy and culture. Lung function testing may also be useful because several causes of pulmonary eosinophilia are associated with asthma and airflow obstruction.

Long answer

If pulmonary eosinophilia is suspected on the basis of the history, full blood count, and chest radiograph, further tests are performed to identify an underlying cause, the idiopathic pulmonary eosinophilias being diagnoses of exclusion.

High resolution computed tomography of the thorax may show a spectrum of characteristic patterns, from ground glass interstitial change through to consolidation.2 In chronic idiopathic pulmonary eosinophilia these opacities are bilateral, peripheral, and predominantly in the upper zones, and, as in this case, the chest radiograph may have the typical “reverse batwings” appearance (or the inverse of pulmonary oedema).3 A computed tomogram of the thorax also showed the mainly peripheral consolidation, with prominent air bronchograms favouring the upper lobes (fig 3).

Figure3

Fig 3 Computed tomogram of the thorax showing mainly peripheral consolidation, with prominent air bronchograms favouring the upper lobes (C)

Bronchoalveolar lavage is performed to confirm a raised eosinophil count in the bronchial fluid and help exclude infection, ideally before treatment is started. In the idiopathic pulmonary eosinophilias, the eosinophil count in the fluid is usually more than 25% of the total white cell count, but in the slowly progressive chronic idiopathic pulmonary eosinophilia, the proportion of eosinophils can be in excess of 40%.2 3 Lung biopsy is now rarely performed, being reserved for ambiguous diagnoses. Bronchoalveolar lavage fluid may also be useful for culturing a causative fungal pathogen, but it is crucial to prove a true immune hypersensitivity reaction as opposed to colonisation. Allergic bronchopulmonary aspergillosis is perhaps the most widely recognised of these conditions and could present in a similar manner to this case, but hypersensitivity to other fungal spores such as Candida spp and Coccidioides immitis can also cause pulmonary eosinophilia and may require a different treatment approach.4 5 Tests for A fumigatus specific IgE should therefore be performed. Culture and microscopy of stool are also recommended, particularly if a travel history implicates a tropical parasitic infection.

Signs indicating involvement of organs other than the lung—particularly the skin, heart, or nervous system—raise the possibility of Churg-Strauss syndrome or hypereosinophilic syndrome, which can affect patients in their fourth and fifth decades.2 Hypereosinophilic syndrome is seen mostly in men and involves insidious eosinophilic infiltration of the viscera with hepatosplenomegaly, myocardial and pulmonary fibrosis, and congestive heart failure.2 Echocardiography is, therefore, indicated if there is evidence of extrapulmonary disease. Churg-Strauss syndrome is a granulomatous, often necrotising, vasculitis of medium sized vessels that affects both sexes equally. Typically, patients have a history of asthma and allergic rhinitis. Total IgE values tend to be raised, and perinuclear ANCA serology is positive in roughly half of patients. Full blown Churg-Strauss syndrome may not be apparent on first presentation and may manifest only after a period of observation. Lung function tests are appropriate in all patients with a suspected pulmonary eosinophilic syndrome, given that asthma and airflow obstruction are associated with Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, and chronic idiopathic pulmonary eosinophilia.

Treatment of pulmonary eosinophilia depends on the cause. Exposure to precipitating factors, such as drugs, should be avoided. Parasitic infections are managed with specific drugs, Churg-Strauss syndrome with immunosuppressive agents, and hypereosinophilic syndrome with chemotherapy. Oral corticosteroid, starting at a dose of 0.3-1.0 mg per kg each day, is recommended for idiopathic pulmonary eosinophilia and exacerbations of allergic bronchopulmonary aspergillosis.

Patient outcome

Given our patient’s history and findings on physical examination, she was started on 40 mg prednisolone once daily, to which she responded rapidly. Bronchoscopy 24 hours later showed a relatively low proportion of eosinophils (5% of white blood cells rather than >25% in bronchoalveolar lavage fluid), probably because steroids cause apoptosis of eosinophils within hours. All cultures and serological investigations were negative. Given that no cause was identified, she was diagnosed as having idiopathic pulmonary eosinophilia, for which her symptoms of breathlessness, cough, fever, chest pain, and inspiratory crackles are characteristic.2 3 However, although she is in the typical age range for acute idiopathic pulmonary eosinophilia, this condition is almost excluded on the basis that it is usually seen in patients without asthma and presents with severe respiratory compromise and hypoxaemia.3 In addition, the peripheral blood eosinophil count is usually normal in acute forms of pulmonary eosinophilia,6 although high counts have been recorded when pulmonary eosinophilia is caused by pharmacotherapy.7 The radiographic changes, peak peripheral eosinophil count, and the lack of severe hypoxaemia support an ultimate diagnosis of chronic idiopathic pulmonary eosinophilia, even though this condition often manifests in patients over the age of 40 years after several weeks of symptoms.3

On review two weeks later her symptoms had resolved and a repeat chest radiograph had returned to normal, along with her serum eosinophil count (zero). The steroid dose was gradually reduced over a few months without recurrent symptoms or an increase in her eosinophil count. Relapse while reducing the steroid dose, however, is well described, particularly in acute idiopathic pulmonary eosinophilia,2 3 and long term vigilance is needed in these patients.

Notes

Cite this as: BMJ 2012;345:e5272

Footnotes

  • Competing interests: Both authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; MBJ has received fees from Boehringer, Allen and Hanburys, and MSD for occasional lectures outside this submitted work; MBJ has attended the European Society Annual Congress four times in the past 10 years as a guest of Boehringer, Allen and Hanburys, and MSD, who provided accommodation and registration fees; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References

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