Idiopathic chronic eosinophilic pneumonia presenting as diffuse alveolar haemorrhage

INTRODUCTION

Eosinophilic pneumonias are rare and characterized by accumulation of excess eosinophils in the interstitial and alveolar spaces. Diffuse alveolar haemorrhage (DAH) is an acute medical condition requiring prompt diagnosis with bronchoscopy and sequential bronchoalveolar lavage (BAL). Idiopathic chronic eosinophilic pneumonia (ICEP) can rarely present as DAH.

THE CASE

A 25-year-old male, soldier, presented to our chest centre with complaints of subacute, gradually progressive breathlessness with intermittent dry cough for 3 weeks. He had intermittent fever and episodes of haemoptysis without chest pain or weight loss. He also gave a history of allergic rhinitis, atopy, nocturnal cough, seasonal variation and trigger in the form of dust, smoke and gun powder. There was no family history of asthma. He was a vegetarian by diet and there was no history of any chronic drug intake. He denied any history of recent travel, sick contacts, joint pains, arthritis, Raynaud phenomenon or haematuria. He was a non-smoker and teetotaller with no known addictions or exposure to chemicals.

He had a pulse rate of 120/minute, respiratory rate of 35/minute and hypoxaemia (oxygen saturation 75% at room air). Blood pressure in the right arm, supine position was 120/80 mmHg. There were bilateral fine inspiratory crackles. Examination of the other systems was normal.

His haemoglobin was normal at 14 g/dl but the total leucocyte count was raised (21 300/cmm) with raised absolute eosinophil count (15 600/cmm). Peripheral blood smear showed marked eosinophilia. The C-reactive protein (CRP) (200 mg/L), lactate dehydrogenase (354 IU/L) and erythrocyte sedimentation rate (ESR) (60) levels were raised. The arterial blood gas (ABG) at room air showed respiratory alkalosis with type-1 respiratory failure (pH: 7.502, pCO₂ 25 mmHg, paO₂ 50 mmHg and bicarbonate –24.9 mmHg). All other metabolic and biochemical tests were normal. Sputum for Ziehl–Neelsen (ZN) stain and Mycobacterium tuberculosis polymerase chain reaction (PCR) were negative. The nasal and oropharyngeal swabs for influenza, Covid-19 and respiratory viral PCR panel were negative. His stool for ova and cyst was negative. The anti-nuclear antibody (ANA), cytoplasmic and perinuclear antineutrophilic cytoplasmic antibody (cANCA and pANCA), glomerular basement membrane antibodies and C3 and C4 complements were all negative. His chest X-ray showed bilateral multiple well-defined subpleural air space opacities (Fig. 1a). He underwent a high-resolution computed tomography of the chest which showed multifocal areas of consolidation with air bronchograms in both lungs with peripheral and upper lobe predominance which were surrounded by ground glass opacities (Fig. 1b). There were also multiple, discrete, variable sized mediastinal lymph nodes. He underwent a high-risk fiberoptic bronchoscopy through the oral route while he was oxygenated with high-flow nasal cannula which showed increasing bloody aliquots in serial BALs which were characteristic of DAH. The BAL Lieshman giemsa (LG) and Pap stains showed inflammatory cells which predominantly comprised eosinophils (85%; Fig. 2). The BAL ZN stain, potassium hydroxide mount and Gram stain were negative. He underwent 2D echocardiography which was normal. He was diagnosed as a case of idiopathic chronic eosinophilic pneumonia with DAH.

Close

FIG 1.

(a and b) High-resolution computed tomogram of chest showing multifocal areas of consolidation with air bronchograms in both lungs with peripheral and upper lobe predominance, which are surrounded by ground glass opacities (red arrows)

Export to PPT

Close

FIG 2.

Bronchoscopic lavage fluid LG stain showing inflammatory smear with increased eosinophil count (red arrow)

Export to PPT

In view of impending respiratory failure, the patient was managed with pulse steroids (Inj methylprednisolone 250 mg 6 hourly). There are no comprehensive guidelines for the dose and duration of steroids in such patients and we decided on the above given dose of steroids which was continued for 5 days. The dose was reduced to 1 mg/kg body weight and continued for 4 weeks. The patient showed response and started maintaining saturation on room air. He was continued on broad spectrum antibiotics and supportive management. The repeat imaging showed improvement and clearing of opacities (Fig. 3a and b). He had a pulmonary function test and his spirometry showed post-bronchodilator reversibility, raised fractional exhaled nitric oxide (FENO) levels and mild reduction in his diffusing capacity of the lung for carbon monoxide (DLCO) levels. He was started on dry powder inhalers consisting of long acting beta agonist (LABA) + inhaled corticosteroids (ICS) combination and oral antihistaminics. He was discharged on a tapering dose of steroids after 6 weeks and was asymptomatic.

Close

FIG 3.

(a and b) High-resolution computed tomogram of chest showing resolution of opacities

Export to PPT

DISCUSSION

ICEP is a rare group of pulmonary disorders which account for <2.5% of all patients with interstitial lung diseases. They are more common in females and non-smokers. ICEP generally affects patients in their fourth and fifth decades of life. These patients can have a history of atopy and allergic symptoms and they can have underlying asthma or are diagnosed with the same later in their life. ICEP has classically been described as subacute to chronic respiratory symptoms, alveolar and/or blood eosinophilia and peripheral opacities on chest imaging. Eosinophilic pneumonia is difficult to diagnose due to the lack of clarity of its pathogenesis. Exposure of alveolar macrophages to a foreign substance leading to type-1 hypersensitivity reaction has been the most commonly implicated mechanism. The diagnostic criteria are not well defined and includes:

1. Sub-acute respiratory symptoms of more than 2 weeks

2. Peripheral pulmonary infiltrates on chest imaging

3. Blood eosinophilia (>1000/cmm) and/or alveolar eosinophilia (BAL eosinophilia >40%)

4. Exclusion of all other causes of eosinophilia.

The symptoms lasting weeks to months include fever, cough with or without expectoration, breathlessness on exertion, weight loss, generalised malaise and night sweats. On auscultation, a wheeze may be heard. Respiratory failure is rare in ICEP and patients generally do not have extrapulmonary manifestations.¹

Serological studies include complete blood count, liver and renal function tests and urinalysis. ESR and CRP are generally raised. Patients can also have iron deficiency anaemia and thrombocytosis. The classical finding is eosinophilia (>1000/cmm). These patients also have features of atopy in the form of raised total immunoglobulin (Ig) E levels. The work up also includes ancillary tests to rule out other differential diagnoses such as allergic bronchopulmonary aspergillosis and eosinophilic granulomatosis with polyangiitis by doing a serum aspergillus specific IgG and ANCA levels.

Chest X-rays show bilateral peripheral parenchymal infiltrates which mimics the photographic negative of acute pulmonary oedema, although this is seen in only 25% of patients. High-resolution computed tomography of the chest shows bilateral, peripheral and non-segmental opacities with slight upper lobe predominanace.^1,2

Pulmonary function tests may show obstructive or restrictive patterns or may be normal. A number of these patients may have a history of asthma which requires a spirometry with pre- and post-bronchodilation. The diffusion test generally shows reduced carbon monoxide (CO) transfer factor and the CO transfer coefficient (KCO). The arterial blood gases usually demonstrate reduced paO₂.^1,2

DAH refers to bleeding in the alveoli. The underlying mechanism can be injury or inflammation of the arterioles, venules or alveolar septal (alveolar wall or interstitial) capillaries. The histopathological variants include pulmonary capillaritis, bland pulmonary haemorrhage and diffuse alveolar damage. The causes of DAH are numerous including infectious and non-infectious. The onset of DAH is generally acute, which includes history of cough, haemoptysis, fever and breathlessness but haemoptysis can be absent in one-third of patients. Clinical findings can be non-specific. The radiology shows diffuse bilateral ground glass or consolidative opacities. The ABG at room air shows hypoxia with reduction of alveolar–arterial oxygen gradient. Laboratory investigations are usually not confirmatory but there can be anaemia, thrombocytosis or thrombocytopenia and raised ESR levels. A fall in haemoglobin in these patients is a soft marker for DAH. Diagnostic confirmation requires flexible bronchoscopy with sequential BAL and, alveolar haemorrhage is confirmed when lavage aliquots are progressively more haemorrhagic. Haemosiderin-laden macrophages may be demonstrated by Prussian blue staining in the BAL fluid of patients with DAH. Pulmonary function tests may be difficult in these patients due to severity of the condition; however, characteristic findings include abnormal gas transfer in form of an increase in the DLCO (>100% of the predicted).

Our patient was a rare case of eosinophillic pneumonia that was implicated as a cause of DAH. There have been only six documented cases of eosinophilic pneumonia causing DAH. The pathogenesis is not clearly understood but can be due to invasion of the pulmonary basement membrane and vasculature by eosinophils, causing damage to the alveoli and alveoli basement membrane.^3–7