Introduction
Chronic eosinophilic pneumonia (CEP) is an idiopathic disease rarely
reported in children1,2. It typically occurs in
non-smoking, middle age females and the diagnosis requires exclusion of
systemic or primary eosinophilic lung diseases1,2. The
triad of pulmonary symptoms (usually for >2 weeks),
abnormal chest radiographic findings and eosinophilia in the blood
and/or pulmonary tissue in the absence of an alternative etiology is
highly suggestive of CEP. Patients may present with cough (90-93%)
dyspnea (50-90%), fever (77-87%), night sweats (23%), weight loss
(57-75%), rhinitis or sinusitis (6-24%), chest pain (8-16%),
hemoptysis (8-10%), and weakness/fatigue1,2. An
asthma phenotype is present in roughly a third to 3/4 of patients.
Bilateral peripheral consolidative infiltrates are seen on chest
radiograph (CXR) with computed tomography (CT) showing peripheral
airspace disease and reactive hilar adenopathy1,2.
Peripheral eosinophilia is almost universal with cell counts routinely
higher than 1000/mm3 and more than half of patients
also have an elevated IgE2. Eosinophilia on the
bronchoalveolar lavage (BAL) ranges from 12 to 95% with a mean of
58%2.
The triad of pulmonary symptoms, radiographic findings and eosinophilia
in CEP typically respond to prednisone within a few
days2. Initial doses range from 0.5 to 1mg/kg/day and
may be tapered after clinical/radiographic improvement. Duration of
therapy depends on the response and is highly variable, with a mean of
19 months but a range of 0.5 to 96 months1. Relapse is
common, occurring in up 50% of patients2.
While the pathogenesis of CEP is not fully understood, the underlying
mechanism undoubtedly involves eosinophils and likely shares
inflammatory pathways with asthma, which is why it may be amenable to
treatment with novel biologic therapies approved for asthma. Although
there are case reports of patients with CEP who were treated with either
omalizumab or mepolizumab, there are no reports of treatment with
dupilumab3. However, there is a report of a patient
possibly experiencing CEP as a consequence of
dupilumab4.
Case Report
An 11-year-old, previously healthy, African American female presented
with fever, cough, dyspnea, chest pain and decreased appetite of 3
months duration. Her past medical history was significant for pneumonia
three months prior that failed to resolve with antibiotics. She was
subsequently prescribed albuterol and treated as an outpatient with a
working diagnosis of asthma. Her symptoms persisted and she was
ultimately hospitalized with chronic pneumonia of unclear etiology. Her
family and social histories were unremarkable. She strongly denied
vaping or inhalant abuse. Her physical exam was remarkable for bilateral
coarse crackles, signs of respiratory distress and reproducible chest
pain. Her CXR showed bilateral consolidative opacities and her CT
demonstrated bilateral lymphadenopathy and multilobar consolidation (see
Figures 1 &2). Her initial lab work was remarkable for a white blood
cell count of 10,000/µL (3.84-9.84/µL) with 10% (0-4%) peripheral
eosinophilia, erythrocyte sedimentation rate of 103 mm/hr (0-15mm/hr),
and C reactive protein of 7mg/dL (0.00-0.50mg/dL). She was treated with
14 days of antibiotics without clinical improvement. During the course
of follow up her FEV1 declined > 35% and she developed a
severe persistent asthma phenotype. She was evaluated for tuberculosis,
allergic bronchopulmonary aspergillosis, helminth infection,
eosinophilic granulomatosis with polyangitis, sarcoidosis, and
immunodeficiency however her work up was negative. She underwent
bronchoscopy, which demonstrated significant bilateral lower airway
casts that were 93% eosinophilic. She was treated with high dose
prednisone for 4 weeks and improved for a few months, however her
symptoms returned. She continued oral prednisone intermittently for
approximately 22 months without improvement and was deemed refractory to
therapy. Repeat imaging during that time demonstrated persistent
opacities and she developed bronchiectasis. Repeat bronchoscopies
revealed return of mucoid impactions. Throughout her course, she
continued to have eosinophilia in the blood (ranging from 0.4 to 13%)
and on BAL (ranging from 9-93%).
She was then treated with pulse methylprednisolone and daily
cyclosporine in an attempt to gain clinical remission which resulted in
modest improvement of symptoms. She continued daily cyclosporine with
the addition of dupilumab every 2 weeks for 6 months. Following the
addition of dupilumab significant clinical and radiographic improvement
were noted within 2 weeks. Her cyclosporine was subsequently weaned
without recurrence of symptoms and she remains symptom free with marked
improvement in her Chest X-ray findings for over 12 months on
subcutaneous dupilumab injections q 2 weeks.