Relapsing pulmonary infiltrates, severe asthma, and eosinophilia with systemic manifestations





History of present illness


A 68-year-old Caucasian woman arrived at the emergency department (ED) due to a severe cough with sputum, breathlessness, and wheezing. The symptoms had started 4 weeks earlier, and the general practitioner had given her an oral antibiotic (amoxicillin/clavulanic acid 750/250 mg every 8 hours) and mucolytic (carbocisteine 2.7 g every 24 hours) for 10 days. She was also suggested to use bronchodilators (salbutamol and ipratropium) and glucocorticoids (beclomethasone) through a nebulizer in addition to the medications she usually took for asthma. Despite such treatment, the patient had poor improvement of the symptoms.


Past medical history


The patient was a nonsmoker housewife with no history of exposure to noxious substances. She reported no adverse drug reactions. At the age of 55, she was diagnosed with type 2 bronchial asthma (blood eosinophilia and increased fractional exhaled nitric oxide [FeNO]) requiring long-term therapy with medium dose of inhaled corticosteroids (ICS-) associated with long-acting β 2 -agonist (LABA): beclomethasone/formoterol 100/6 μg, two inhalations at morning and two in the evening.


No allergen sensitization was found.


At the age of 65, she was hospitalized due to pneumonia and asthma exacerbation. In this circumstance, chest radiograph and computed tomography (CT) scan showed large bilateral opacities ( Fig 10.1 ; Fig 10.2 ), and the patient received both antibiotic and systemic corticosteroid therapy. Notwithstanding the complete radiological resolution of pneumonia, she experienced poor asthma control and two acute exacerbations requiring oral corticosteroids (OCS-) over the next 6 months.




Fig 10.1


Chest radiograph performed when the patient had pneumonia at age 65. Posteroanterior (A) and lateral (B) views show multiple bilateral opacities.



Fig 10.2


Axial CT scan of the chest performed when the patient had pneumonia at age 65. Images on the lung window setting (A–F) show multiple bilateral hyperdensities in all the lung lobes, with greater involvement of the left side.


Thus, the patient was successively placed on progressively major therapy including high-dose ICS/LABA (beclomethasone/formoterol 200/6 μg, two inhalations in the morning and two in the evening), long-acting muscarinic antagonist (LAMA: tiotropium 2.5 μg, two inhalations every 24 hours), and anti–interleukin-5 (IL-5) biological therapy for severe eosinophilic asthma: mepolizumab 100 mg subcutaneous once every 28 days.


The patient also had arterial hypertension, gastroesophageal reflux disease (GERD), and glaucoma. Mild obstructive sleep apnea (apnea-hypopnea index [AHI] 14 without nocturnal desaturation) was diagnosed a few years earlier, but only positional therapy was undertaken (lateral recumbency).


Her home medication list also included omeprazole 20 mg and valsartan 80 mg in the morning, Travoprost 40 μg/mL 1 drop in each eye in the evening. She frequently took topical decongestants for nasal obstruction and nonsteroidal anti-inflammatory drugs (NSAIDs) due to both headache and pain in the four limbs with distal paresthesia.


Physical examination and early clinical findings


Upon arrival at the ED, the patient was dyspneic and tachycardic (heart rate 105 beats/min), had a low-grade fever (body temperature 37.5°C [99.5°F]), and low oxygen saturation (SpO 2 88% at rest while breathing in ambient air). Arterial blood gas analyses revealed acute partial respiratory failure (pH 7.44, pCO 2 36.9 mmHg, pO 2 58.4 mmHg, HCO 3 22 mmol/L). The respiratory rate was 24 breaths/min, and arterial pressure was 135/80 mmHg.


On auscultation, the breath sounds were slightly reduced and wheezing was present in the middle and lower fields.


Blood tests showed mild leukocytosis (white blood cell [WBC] count 11,420 cells/mm 3 ) with relative eosinophilia (eosinophils 983 cells/mm 3 , 8.6%), increase in the indices of inflammation (C-reactive protein [CRP] 183 mg/L, normal values <10 mg/L; erythrocyte sedimentation rate [ESR] 56 mm/h, normal values <10 mm/h), no anemia (Hb 13.8 g/dL), normal brain-type natriuretic peptide (proBNP 320 pg/mL; normal values <400 pg/mL), and normal kidney and liver functions.


Due to an increased D-dimer (976 ng/mL), chest CT-angiography was done. This excluded pulmonary embolism and detected bilateral opacities in the upper lobes ( Fig 10.3 ).




Fig 10.3


Axial CT scan of the chest (lung window setting) performed at the ED. Hyperdensities were present in the upper lobes, while the remaining lobes were spared.


Low-flow oxygen supplement (2 L/m by nasal cannula) was able to grant good SpO 2 .


ED doctors gave a bolus of methylprednisolone 40 mg and started intravenous antibiotic therapy (ceftazidime 1 g 3 times daily). The patient was admitted to the pulmonology guard.




Clinical course


The patient underwent bronchoscopy with BAL in the left upper lobe, then she was placed on methylprednisolone 20 mg intravenously every 12 hours and oral acetylcysteine 600 mg daily. Ceftazidime intravenous was continued, as well as her usual home therapy that included bronchodilators and a proton pump inhibitor. The total amount of BAL fluid recovered was 47 mL (39.2% of saline instilled): 9 mL in the first aliquot and 38 mL in the remaining aliquots. Total cellularity of BAL fluid was 1,483,000 cells/mL, and cell differential count revealed a marked eosinophilia (eosinophils 74%, alveolar macrophages 18%, neutrophils 1%, lymphocytes 7%; CD4:CD8 ratio 0.9). No eggs, larvae, or adult parasites were found on microscopy of the BAL fluid, and no organisms grew on the culture. The polymerase chain reaction for the detection of Mycobacterium tuberculosis was negative.




The patient’s clinical condition progressively improved. After 5 days of hospitalization, she no longer needed supplemental oxygen, while blood tests showed a clear reduction in eosinophils and inflammation indices: WBC 10,650/mm 3 with eosinophils 576/mm 3 (5.4%), CRP 16.2 mg/L, and ESR 21 mm/h. The anti-neutrophil cytoplasmic antibody (ANCA) essay was negative. Serum total IgE was 98.2 IU/mL (normal range for adults <200 IU/mL). The corticosteroid was switched to oral administration at a lower dosage (prednisone 35 mg daily).


After 10 days of treatment, parenchymal opacities were no longer recognizable on the chest radiograph, and inflammatory indices were negative. The patient was much better; the antibiotic was stopped, and the oral prednisone was gradually tapered. Given the current and previous extensive use of corticosteroids, she underwent dual-energy x-ray absorptiometry (DXA) to measure bone mineral density (BMD). This revealed osteoporosis in the femoral neck and lumbar spine (T-score –2.7 and –2.5, respectively). A 25-hydroxyvitamin D deficiency was also highlighted (14 ng/mL, normal range 20–40 ng/mL).


Recommended therapy and further indications


The patient was discharged with the diagnosis of idiopathic chronic eosinophilic pneumonia (ICEP). She was prescribed oral prednisone 25 mg daily, to be reduced by 5 mg every 4 weeks. Oral cholecalciferol (5,000 IU weekly for 6 weeks) and oral bisphosphonate (once-weekly alendronate 70 mg) were added to the therapy. A continuation of the diagnostic process for suspected EGPA was scheduled on an outpatient basis.


The patient underwent several further investigations. An esophagogastroduodenoscopy (EGD) with biopsy of the esophageal mucosa showed eosinophilic esophagitis (eosinophilic infiltration of the esophageal epithelium).


The parasitological examination of the stool was negative.


A CT scan of the sinuses ( Fig 10.4 ) revealed diffuse mucous thickenings in the paranasal cavities due to chronic inflammation. There was also turbinate hypertrophy without nasal polyps.


Jun 29, 2024 | Posted by in RESPIRATORY | Comments Off on Relapsing pulmonary infiltrates, severe asthma, and eosinophilia with systemic manifestations

Full access? Get Clinical Tree

Get Clinical Tree app for offline access