A Map to CAP Mimics

Case Presentation

• 40F with a PMH of asthma who presented to the ED with dyspnea, cough, and subjective fevers 8 days after being discharged from an outside hospital on PO azithromycin for community-acquired pneumonia (CAP).

• At the other hospital, she was observed for 48 hours and received 2 doses of IV ceftriaxone (1g) and azithromycin (500mg).

• On this visit she is concerned due to worsening shortness of breath and blood streaks in her sputum. She also described a sensation of “tissue” falling from her nose into her mouth and throat.

• She notes that some mild progressive dyspnea began since visiting a friend in the Southeastern US six months prior.

• On physical exam, the patient appears anxious and tachypneic.

• Her vital signs are: RR 24, HR 90, BP 110/75, T 38.1°C, Pulse Ox 98% on 2L NC.

• Nasal mucosa appears excoriated and her nasal septum is perforated, which the patient reports is new since she was last examined.

• She has a regular rate and rhythm with no murmurs, rubs, or gallops.

• Expiratory wheezes and scattered rhonchi are appreciated on lung auscultation.

• No peripheral edema.

• PMH: asthma, for which she uses her daughter’s albuterol inhaler

• SH: smokes ½ ppd and drinks roughly four wine coolers a week. She smokes marijuana daily, but does not use any other substances. She works as a home health aide and lives with her four children.

• Her chest X-ray is below:

Clinical Questions

• What are non-infectious mimics of CAP that may be seen in the Emergency Department, and when they be considered?

Summary of the Evidence

• CAP is a well-known cause of visits to the Emergency Department: 2-4 million patients develop CAP yearly in the United States, leading to roughly a million hospitalizations and 60,000 deaths.(1)

• Less well known is that CAP misdiagnosed approximately 20 to 30% of the time.(1–4)

• Time from presentation in the ED to treatment with antibiotics has been used as a quality indicator, with the thought that early antibiotic administration decreases morbidity and mortality from sepsis. There is debate as to whether the use of time-to-antibiotics as a quality indicator has improved outcomes, and whether it has contributed to overdiagnosis of CAP—and thus overuse of antibiotics – in the ED.(5–8)

When should non-infectious mimics of pneumonia be on the differential?

There is no consensus as to when the signs and symptoms of treated CAP should resolve. However, the following rough timeline for improvement of signs and symptoms:(1,9,10)

• 2-3 days: Dyspnea, tachycardia, hypotension, fever, and hypoxia

• 2 weeks: Cough and fatigue

• 1 month: chest radiograph infiltrates

While there is no hard and fast rule as to when a patient is considered to have non-resolving pneumonia, if a patient visits or re-visits the Emergency Department after three or more days of CAP treatment, possible causes for non-response should be considered, including:

• Antibiotic resistance

• Unusual pathogens such as TB or fungi

• Complications of CAP such as abscess or empyema

• Host factors such as advanced age or comorbidities like diabetes, COPD, and CHF (1,9,10)

• Non-infectious etiologies of a CAP-like presentation

A chest CT can help clarify why a presumed CAP is not resolving, or resolving more slowly than would be expected.(3,10) It may, for example, suggest that the presumed CAP is indeed truly a CAP, but with an abscess or empyema leading to the lack of clinical improvement. Or it could suggest a non-infectious cause of the patient’s presentation.

Noninfectious mimics of community acquired pneumonia can be considered in four etiological categories: neoplastic, inflammatory, drug-induced, and vascular.

Neoplastic

• Especially small cell & non-small cell lung cancers, carcinoid, lymphoma

• A primary lung cancer may initially present very similarly to a CAP, and the infiltrate seen on imaging may be the neoplasm itself.

• Alternatively, a neoplasm may cause a non-resolving pneumonia through a post-obstructive process.(11)

• Consider:

• History of smoking

• Additional signs: weight loss (46-68% of patients with lung cancer at presentation), bone pain (20-21%), hoarseness (8-18%)(11)

Inflammatory

• Includes granulomatosis with polyangiitis, sarcoidosis, anti-GBM disease, lupus, cryptogenic organizing pneumonia

• Inflammatory processes can lead to a radiograph that looks similar to those seen in CAP. In addition, lupus and vasculitides such as granulomatosis can lead to diffuse alveolar hemorrhage which may appear similar to CAP on x-ray

• Consider:

• Personal or family history of autoimmune disease

• Hemoptysis, hematuria

• Extrapulmonary signs and symptoms: eye, ear, nose, throat, kidney, skin

Drug-induced

• Amiodarone, heroin; full list available at www.pneumotox.com

• Drug-induced pneumonitis, which may be confused with CAP symptomatically (fever, dyspnea, productive cough) and on imaging, usually occurs within weeks to months of first use.

• Consider:

• Initiation of new medications

• Use of non-prescribed drugs (check urine tox)

Vascular

• Pulmonary edema, pulmonary embolism

• Consider:

• Cardiac history and volume status

• Risk factors for PE (Wells Score). Although a PE cannot be diagnosed with x-ray, a wedge-shaped pleural infiltrate (a “Hampton hump”) may be seen with a PE on plain film.

Recommendations

• Initial assessment and treatment, as always in the Emergency Department, relies on the ABCs (Airway, Breathing, Circulation) to ensure adequate oxygenation, ventilation, and perfusion.

• Recall that radiographic evidence of pneumonia may take longer than clinical symptoms to improve, so guide further workup and therapy on the patient’s presentation and story rather than imaging.

• In patients with non-resolving or worsening clinical symptoms despite adequate antibiotic coverage and duration:

• Consider chest CT

• Consider non-infectious etiologies

• Consider admission for further workup as a full diagnostic workup may not be possible in the ED

Case Conclusion:

The clinical picture suggested a non-resolving pneumonia, and the patient was admitted for inpatient management and broadening of her antibiotic coverage. Given her clinical worsening, nasal involvement, and insidious onset of dyspnea, alternative diagnoses were also considered. Ultimately, however, other etiologies were ruled out during her hospitalization.

References

1. Long B, Long D, Koyfman A. Emergency Medicine Evaluation of Community-Acquired Pneumonia: History, Examination, Imaging and Laboratory Assessment, and Risk Scores. J Emerg Med. 2017;53(5):642-652. doi:10.1016/j.jemermed.2017.05.035.

2. Shariatzadeh M, Marrie TJ. Reasons for coming to hospital after treatment for community-acquired pneumonia on a ambulatory basis. Can Respir J. 2006;13(3):139-143.

3. Claessens YE, Debray MP, Tubach F, et al. Early chest computed tomography scan to assist diagnosis and guide treatment decision for suspected community-acquired pneumonia. Am J Respir Crit Care Med. 2015;192(8):974-982. doi:10.1164/rccm.201501-0017OC.

4. Daniel P, Bewick T, Welham S, McKeever TM, Lim WS. Adults miscoded and misdiagnosed as having pneumonia: Results from the British Thoracic Society pneumonia audit. Thorax. 2017;72(4):376-379. doi:10.1136/thoraxjnl-2016-209405.

5. Kanwar M, Brar N, Khatib R, Fakih MG. Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics: Side effects of the 4-h antibiotic administration rule. Chest. 2007;131(6):1865-1869. doi:10.1378/chest.07-0164.

6. Welker JA, Huston M, McCue JD. Antibiotic timing and errors in diagnosing pneumonia. Arch Intern Med. 2008;168(4):351-356. doi:10.1001/archinternmed.2007.84.

7. Pines JM, Isserman JA, Hinfey PB. The Measurement of Time to First Antibiotic Dose for Pneumonia in the Emergency Department: A White Paper and Position Statement Prepared for the American Academy of Emergency Medicine. J Emerg Med. 2009;37(3):335-340. doi:10.1016/j.jemermed.2009.06.127.

8. Sucov A et al. Time to first antibiotics for pneumonia is not associated with in-hospital mortality. J Emerg Med. 2013;45(1).

9. Black AD. Non-infectious mimics of community-acquired pneumonia. Pneumonia. 2016;8(1):2. doi:10.1186/s41479-016-0002-1.

10. Sialer S, Liapikou A, Torres A. What Is the Best Approach to the Nonresponding Patient with Community-Acquired Pneumonia? Infect Dis Clin North Am. 2013;27(1):189-203. doi:10.1016/j.idc.2012.11.009.

11. Long DA, Long B, Koyfman A. Clinical mimics: an emergency medicine focused review of pneumonia mimics. Intern Emerg Med. 2018;13(4):539-547. doi:10.1007/s11739-018-1840-z.