A Challenging Clinical Case Holger Link, MD Liz Levine, M.D. PGY 2 Doernbecher Pediatric Pulmonary Program.

A Challenging Clinical Case

Holger Link, MD

Liz Levine, M.D. PGY 2Doernbecher Pediatric Pulmonary Program

Disclosures

None

HPI 16 yo teenage boy presented with worsening

wheezing, coughing, shortness of breath.

1 mo PTA:

Fever, coughing, dx with walking PNA, treated with Azithromycin for 5 days with some improvement

Cough gradually worsened with acute onset of SOB, wheezing.

In ED SpO2 82’%. Tx with Duoneb, Dexamethasone, and transferred to DCH PICU.

Further history:PMHx: Term infant, no hospitalizations prior to those

mentioned. No surgeries. No atopy or hx of asthma. 2 episodes of PNA 2 years ago, both tx as an outpatient. Fully vaccinated.

Fam Hx: No asthma, eczema, allergies. No other respiratory problems.

Social: Junior in HS, quite active usually, plays football. Smokes MJ “few times per month” over past 2 yrs, denies all other drug use, including tobacco. Has been sexually active in past, not in last 8-9 mo.

Travel: none out of Oregon in last 2 yearsAnimals/Exposures: Denies inhaled dust, smoke,

chemicals, no pets, birds, farm, or other animal exposureMeds: Albuterol MDI prnAllergies: NKA

PICU

Needing oygen, continuous nebs, mag sulfate, IV steroids, bronchodilators gradually weaned, transferred to floor after 2 days.

Pulm consult: recommended CT given unusual presentation for asthma.

**Had received 2 days of IV steroids at time of CT

CXR day of admission

Inspiratory chest CT

Inspiratory chest CT

Expiratory chest CT

Expiratory chest CT

Expiratory chest CT

Clinical course + tests CT initial read: significant amount of air trapping, GG

opacities and concern for a potential bronchiolitis obliterans w/cryptogenic pneumonia.

Workup: AFB neg, Legionella neg, HIV neg, Resp Viral panel neg, Hypersensitivity Pneumonitis panel neg, Mycoplasma pneumoniae IgM neg, IgG positive.

He improved from a respiratory standpoint.

PFT’s with FEV1 102% day of discharge

Discharged home with a tapering course of oral prednisone, albuterol prn and azithromycin.

CBC + Diff

After discharge:

Continued to improved while on tapering course of Prednisone, just about back to baseline

F/up in Pulm clinic 3 weeks later: doing well, excellent PFT's (FEV1 of 124%), and his azithromycin was discontinued

However…

After finishing course of steroids: increasing cough, using albuterol more often, no other cold-like sx. Also notes occasional night sweats, weight loss of 15-20 lbs over past few months.

Cough worsens, increasing SOB, wheezing, chest pain.

Re-admitted to hospital 2 months after initial PICU admission.

Physical exam VS: Temp 36.8 °C BP 112/69, HR 98, RR 24, SpO2 94% Wt

60.6 kg

Gen: awake, alert, NAD

HEENT, CV, Abd, Neuro: normal

Resp: Non-labored, no retractions or nasal flaring, currently on 0.5L. Chest shape is normal. Auscultation of lungs: slight tachypnea, prolonged expiration with wheezing (both insp and exp) in all lung fields.

Ext: WWP, no clubbing.

Skin: no rashes, several linear striae noted over lower back.

On admission: Initially required 2-5 L O2 via NC to maintain sat’s.

Albuterol every 2-4 hrs was helping some.

Labs:

WBC: 22.8 (Poly 20, lymph 12, mono 4, Eos 64%)

Lytes, LFT’s ,H/H, plt wnl

ESR 25, CRP <0.5

UDS: +Cannabinoids, all others negative

Imaging: CXR: airway thickening, hyperinflation

Pulmonology consult requested

CXR second admission

Bronchoscopy results + course Labs: IgE elevated at 867, rest of immunoglobulins wnl.

Bronchoscopy:

Mucosa: mild erythema

Secretions: thick whitish-yellowish secretions in bilateral airways. No blood.

Eosinophilia of 91% on BAL

Started on Solumedrol x 1 day, followed by Prednisone 60 mg daily

On discharge also started on ICS

BAL findings

BAL histology

Pulmonary Eosinophilic Syndromes

PrimaryAcute eosinophilic PNA

Chronic eosinophilic PNA

Churg-Strauss Syndrome

Hypereosinophilic syndrome

Eosinophilic granuloma

Secondary

Asthma

ABPA

Bronchocentric granulomatosis

Collagen vascular diseases

Drug/toxin reaction

Infection: parasite (Loeffler’s syndrome), helminthic, TB, coccidiodes, others

BOOP

Hypersensitivity pneumonitis

Malignancies

Chronic Eosinophilic Pneumonia Rare disorder of unclear etiology resulting in

insidious onset of respiratory symptoms accompanied by pulmonary consolidation and accumulation of large numbers of eosinophils in the lungs, blood and in BAL fluid.

Diagnosis

Based on history, imaging, eosinophilia

Proposed criteria:

1) Resp symptoms >2 weeks

2) Alveolar eosinophilia (>25%, esp >40%) or blood eosinophilia (>1000 eos/mm3)

3) Pulmonary infiltrates on CXR, usually peripheral

4) Exclusion of other causes of eosinophilic lung disease

Etiology Unknown initiating stimulus/insult results in

accumulation of eosinophils in the lungs

TH2 lymphocytes activatedIL-5, important role in recruiting eosinophils, and inhibiting their apoptosis.

Other chemokines involved: elevated TARC (thymus and activation regulated chemokine), eotaxin and RANTES act as other chemoattractants of eosinophils

Epidemiology:

Female nonsmokers, mean age of 45 yrs

Female/male ratio 2.1/1 in 1 review article

Age range 18 to 80 yrs in same article

Most patients do have asthma (52%), atopy in general 63-75%

Clinical Presentation: Gradual , subacute onset of symptoms which can

include:

Respiratory: cough (+/- productive), wheezing, SOB, chest pain

Systemic: low grade fevers, weight loss, night sweats, malaise

Acute respiratory failure, significant hypoxemia seen in acute eosinophilic pneumonia

Rarely, arthralgias, neuropathy, skin findings, GI sx reported

Physical findings

On exam, non specific findings

Expiratory wheezing in 50%

Occasionally inspiratory crackles

Labs Peripheral eosinophilia usually found first

90% patients had >30% eosinophils

Elevated inflammatory markers

Elevated IgE

PFT’s: inconsistent

1/3 no abnormality, 1/3 restrictive, 1/3 obstructive

BAL fluid: >25% eosinophils

Mean close to 60%

Normal <2%

Imaging: CXR

“Photographic negative of pulmonary edema” (though <25% with this finding)

Bilateral peripheral opacities, often in upper lobes

Infiltrates can range from ground-glass, migratory to dense consolidation

Imaging: CT

May help detect small ground glass opacities not seen on film

Study of high resolution CT scan in 81 patients, physicians unable to distinguish between CEP and bronchiolitis obliterans

Treatment:

Spontaneous remission in 10%

Oral corticosteroids: prednisone 0.3-1 mg/kg/day

Usually have dramatic response with cessation of symptoms

Marked decrease in peripheral eosinophilia (and BAL fluid)

Recommended course: gradual taper between 6-12 months, though some suggest trying 6-8 weeks

Prognosis:

>50% relapse, requiring prolonged courses of CS for months-years

Aside from potential for relapse after cessation of steroids, general prognosis is quite good with full resolution of symptoms and no long-term sequelae

Individual reports of pulmonary fibrosis

Rare cases have been associated with cutaneous T cell lymphoma, sarcoidosis, Churg-strauss

Final twist…

“Oil red O stain indicates a 95% positivity for lipid laden macrophages. There are numerous Charcot-Leyden eosinophilic crystals and a few scattered benign goblet cells suggestive of an asthma-like respiratory process.”

No hx of reflux, choking, GERD symptoms

After this obtained normal MBSS

Stool O&P obtained, but unable to be processed due to presence of barium

BAL histology

References: Alam, M. and N. Burki. Chronic eosinophilic pneumonia: a review.

Southern Medical Journal 2007, 100: 49-53.

Cakir, C. et al. Chronic eosinophilic pneumonia with mucous plugs in a child. Pediatric Pulmonology 2010, 45: 1040-1042.

Katz, U. and Y. Shoeneld. Pulmonary eosinophilia. Clinic Rev Allergy Immunol, 2008, 34:367-371.

Uptodate

Weschler, M. Pulmonary eosinophilic syndromes. Immonol Allergy Clin N Am, 2007, 27: 477-492.

Wubbel, C. et al. Chronic eosinophilic pneumonia: a case report and national survey. Chest 2003, 123; 1763-1766.