Neutropenic Fever

Kelly Wepking, MS4Contributions by Paul Lewis, MD and Palmi Shah, MD

June 2013

• CC: “I had a fever of 102.4, and my doc told me to come in.”

• HPI: 47-year-old male presents to the emergency room with 1 day history of high fever (Tmax 102.4 F). + for fatigue, frontal headache, and nasal congestion; 2 weeks s/p 3rd cycle of consolidation chemo with HiDAC. Induction chemo was complicated by fever and mucositis. Consolidation chemo was complicated by gingivitis/periodontitis

• PMH: AML, M5 (monocytic variant, dx 1/21/13 via BMBx), history of dental infections

Clinical History: MR 6368330

2

3

• PSH: R Rotator Cuff repair, R ankle ORIF

• Allergies: cats and seasonal hay fever

• Rx: S/p induction and 3 cycles consolidation chemo

• SocHx: Smokes 1/2ppd X 30 years. ETOH 3-4 drinks/mo;

Denies illicits; Married, 1 son

• ROS: + for fatigue; Denies cough, chills, nausea, vomiting

or diarrhea; denies hematuria or dysuria

Clinical History: MR 6368330

Vitals: Tmax 102.4FBP 128/84 HR 120 Temp:100 °F RR 18

SpO2 96 %General: No apparent distress, awake, alertHEENT: normocephalic, MMM, no erythema/exudates in

oropharynx, PERRLA, EOMI NECK: Supple, symmetrical, trachea midlineCV: RRR, Normal S1,S2; No S3 or S4, no murmur, rubs, bruits,

pulses equal bilaterally LUNGS: No increased WOB, good air exchange, CTAB, no crackles

or wheezing ABDOMEN: +BS, soft, round, ND, NT, no masses or HSMMUSCULOSKELETAL: No redness, warmth, or swelling of the

joints, full ROM, strength 5/5 BL

Physical Exam

4

MUSCULOSKELETAL: No redness, warmth, or swelling of the joints, full ROM, strength 5/5 BL

NEUROLOGIC: CN II-XII grossly intact, FTN, HTS, sensory intact BACK: No skin lesions, erythema or scars; Spinous processes and

paraspinous muscles NT; No CVA tendernessSKIN: : No erythema or lesionsACCESS: R chest wall triple lumen Hickman, site C/D/I, no

erythema, drainage, or edema LABS:• CBC with Diff:

• UA: Rare G+ and RBC; Negative for nitrites, leukocyte esterase

and ketones

Physical Exam

3.4 23

139 105 14

0.77

8.330

240.29 127

• Bacterial Pneumonia• Fungal Infection (mucormycosis, aspergillosis, histoplasma)• Sinusitis• Catheter Site Infection• UTI

DDx Neutropenic Fever

6

Diagnostic Plan– CXR– UA, Ucx, BCx, and Catheter Cx – Chest Noncontrast CT Scan– ID consult

• Histoplasma Antigen• Cryptococcal Antigen

Treatment Plan– Transfusion goals: Hgb>8, Platelets

>20; – Give 1 unit PRBCs 1 unit Platelets, – Empiric Antibiotic and Fungal

Coverage given neutropenic state:– Zosyn, diflucan, acyclovir– KCL

Upright, Frontal PA Chest Radiograph

*

5283027

Upright, Frontal PA Chest Radiograph; Anterior Ribs Removed

*

5283027

Upright, Lateral Chest Radiograph

*

5283027

Axial, non-contrast chest CT5283727

Axial, non-contrast chest CT

5283727

Axial, non-contrast chest CT

5283727

Axial, non-contrast chest CT 5283727

*

Axial, non-contrast chest CT 5283727

Axial, non-contrast chest CT

*

5283727

*

Coronal Non-contrast CT5283727

Coronal Non-contrast CT5283727

Coronal Non-contrast CT5283727

Coronal Non-contrast CT5283727

5283727Coronal Non-contrast CT

*

CT non-contrast Sagittal

5283727

*

CT non-contrast Sagittal5283727

CT non-contrast Sagittal

*

• Multifocal Bacterial Pneumonia• Fungal Infection (mucormycosis, aspergillosis, histoplasma)• Neoplasm (Bronchogenic Carcinoma)• Pulmonary Emboli/Infarct• Septic Emboli

Radiographic DDx

24

Treatment Plan– Voriconazole to cover aspergillus– Continue Zosyn to cover possible

sinusitis

Radiographic Features:• multiple pulmonary nodules (40%) • nodules have a characteristic halo of ground glass

appearance – represents pulmonary hemorrhage

• peribronchial opacities, focal areas of consolidation• within 2 weeks, 50% of nodules undergo cavitation,

which results in the air crescent sign– Air crescent sign indicates the recovery phase (increased

granulocytic response) – Also seen in TB, actinomycosis, mucormycosis, septic

emboli, and tumors – Do not confuse the air crescent sign with the Monod sign

• clinical hx helps to differentiate 25

INVASIVE ASPERGILLOSIS

Clinical Features:• high mortality (70-90%) and occurs mainly in severely

immunocompromised patients (CMT, leukemia)• infection starts with endobronchial fungal

proliferation and then leads to vascular invasion with thrombosis and infarction of lung – "angioinvasive infection"

• additional sites of infection (in 30%) are brain, liver, kidney, GI tract

• Treatment with systemic and or intracavitary administration of voriconazole or amphotericin

INVASIVE ASPERGILLOSIS

26

Be sure to differentiate the various conditions related to Aspergillus

Each is associated with a specific immune status and radiographic findings

Patient history is critical!

27

Type of Reaction Disease Examples

Angioinvasive Aspergillosis Serious, often fatal disease, that affects immunocompromised patients

Aspergilloma Most common form; noninvasive; involves formation in preexisting cavities

Allergic Bronchopulmonary Aspergillosis (ABPA)

Caused by a hypersensitivity reaction; most commonly occurs in patients with asthma

Chronic necrotizing aspergillosis (semi-invasive)

Chronic, cavitary pneumonic illness; often in patients with preexisting lung disease (e.g. COPD)

http://www.learningradiology.com/archives2012/COW%20525-ABPA/abpacorrect.html

28

Types of Pulmonary Aspergillosis

Allergic Bronchopulmonary Aspergillosis (ABPA)

Radiographic Findings:• Fleeting pulmonary alveolar

opacities*• Central upper lobe saccular

bronchiectasis (Hallmark) • Mucus plugging (“finger in glove”)• Bronchial wall thickening • Chronic disease may progress to

pulmonary fibrosis predominantly in upper lobe

• Cavitation found in 10% of casesClinical Findings:• Complex hypersensitivity reaction

(type 1) to aspergillus• Often Comorbid with asthma and CF• Hypersensitivity causes

bronchospasm and bronchial wall damage

• Elevated aspergillus-specific IgE, elevated precipitating IgG vs aspergillus, peripheral eosinophilia, positive skin test

• Tx: Prednisonehttp://www.learningradiology.com/archives2012/COW%20525-ABPA/abpacorrect.html

Aspergilloma

Radiographic Findings:• Focal intracavitary mass (3-

6cm)• Upper lobes, solitary• Small area of consolidation

around cavity• Adjacent pleural

thickening• Fungus ball moves with

position changes

Clinically:• preexisting structural

disease (cavitary/bulla from TB, end-stage sarcoid, emphysema

• “fungus ball” • Tx: resection or

amphotericin in cavityMonod sign = air surrounding aspergilloma –

mimics cavitation seen with invasive aspergillosis

DDx:TBNeoplasmCavitary hemorrhage

Outcome

•The patient received voriconazole for angioinvasive aspergillosis.•Zosyn was given for prior dental infections and to cover bacterial infections given patient’s neutropenic state.•Eventually recovered despite the poor prognosis for angioinvasive aspergillosis.•continuing treatment for AML.

Questions?

Outcome

32

THANK YOU!