Intern Report 5.10

Case Presentation by Dr. Vit Kraushaar

A 38 year old African American female presents to the ED with a chief complaint of shortness of breath.  She began feeling ill 3 days ago with cough, myalgias, severe chills, fever and progressively worsening shortness of breath.  This morning she coughed up some blood streaked sputum, which prompted her to come to the emergency department.  The patient complains that her shortness of breath is associated with sharp, non-radiating midsternal chest tightness that is pleuritic in nature.  She informs you that several of her co-workers are also feeling ill, with one admitted to the ICU yesterday with a diagnosis of pneumonia.  The patient works at a coffee shop that you recall is located across the street from the local university’s newly constructed bioterrorism research lab.

ROS: Positive for fevers, chills, myalgias, nausea, cough/hemoptysis, and shortness of breath.

PMH: Hypertension.  Denies CAD, CHF, COPD, cancer.

PSH: None

Social Hx: Drinks alcohol rarely.  Denies tobacco or illicit drug use.

Medications:  amlodipine

Allergies: Seasonal allergies

Physical Exam:

General appearance:  Patient is ill-appearing, diaphoretic, and only able to speak in half-sentences because of dyspnea.

Vitals: BP 120/55, HR 115 bpm, RR 28, T 38.6, 97% O2 saturation on room air

Eyes: No scleral icterus or conjunctival pallor

HEENT: Mucous membranes are moist, no oropharyngeal swelling, erythema, or tonsillar exudates, no oral thrush

Neck:  Trachea midline. No nuchal rigidity, no jugular venous distension.

Heart: S1 and S2 were heard.  Tachycardic rate and regular rhythm.  No murmurs or gallops.

Lungs: Inspiratory rales and diminished breath sounds auscultated bilaterally.  No wheezing.

Abdomen: Soft, non-tender, no guarding.

Skin: No rashes or bruising noted

Neurologic: Alert and oriented with no motor or sensory deficits.

Labs:

CBC: Hb 15, Hct 46, WBC 11.5, Plt 130

Electrolytes: Na 134, K 3.5, Cl 96, CO2 26, BUN 18, Cr 0.8

Troponin: Negative x 1

Blood and sputum cultures are pending

EKG: Sinus tachycardia, 116 bpm.  PR, QRS, QTc intervals normal.  Normal axis, no LVH.  No ST-T changes.

Imaging:

Chest x-ray (see image below)

Formal read of the CT demonstrates “Mediastinal hemorrhagic lymphadenopathy (white arrowhead), with additional involvement of the paratracheal, subaortic, and azygoesophageal recess nodes. A high-density hemorrhagic pericardial effusion is also present.”

The patient continues to develop worsening respiratory distress and eventually she is intubated in the ED for acute respiratory failure.

As an astute ED physician, you think that there is a connection between this patient’s symptoms and the fact that she works across the street from a bioterrorism research facility, especially considering her reports of several sick coworkers.  Though you are still considering more common diagnoses on your differential, you consider that this patient may have been exposed to a bioterrorism agent.

1)     This patient’s history and clinical presentation is typical of inhalational exposure to which of the following possible bioterrorism agents?

  1. anthrax (Bacillus anthracis)
  2. Q fever (Coxiella burnetii)
  3. ricin toxin (from Ricinus communus)
  4. smallpox (Variola major)
  5. tularemia (rabbit fever) (Francisella tularensis)

2)     You call the hospital laboratory and state that you are concerned that your patient may have been exposed to a biologic weapons agent.  They send a blood sample to a state public health lab.  In the meantime, you request that they perform a peripheral blood smear on one of the blood samples that you sent to their lab.  They call you back in half an hour stating that the sample contained large gram positive bacilli.  Having tentatively confirmed your diagnosis (from question 1), which of the following antibiotics should you initiate?

  1. cefepime
  2. ceftriaxone
  3. ciprofloxacin
  4. gentamicin
  5. trimethoprim/sulfamethoxazole

3)     The patient was accompanied to the ED by one of her coworkers.  You are worried that he may have been exposed to the same bioterrorism agent.  He states that he generally feels fine, but he does have a skin lesion on his arm (see picture below).  The patient states that this lesion is painless.


What is the appropriate treatment?

a)     incision and drainage

b)     observation and follow-up

c)     oral antibiotics

d)     topical antibiotics

e)     topical steroids

 

Answers:

1)     Correct answer: A (Inhalational anthrax)

This case mimics a real life incident where anthrax spores were accidentally vented from a bioweapons facility in the town of Sverdlovsk, in the former Soviet Union in 1979.  This led to 77 cases of inhalational anthrax and many deaths, with many cases occurring in workers from a nearby factory.  The appearance of multiple cases of previously healthy patients who develop a rapidly fulminant pneumonia should raise the suspicion for a bioterrorism incident.  Inhalational anthrax has classically been described as following a two stage course.  In the first stage, symptoms are nonspecific and often flu-like (e.g. fever, dyspnea, cough, headache, vomiting, chills, weakness, abdominal pain, and chest pain).  This first stage can last from hours to days.  The second stage is marked by abrupt onset of high fever, dyspnea, diaphoresis, and shock.  Chest x-ray will show multiple abnormalities, most classically a widened mediastinum, but also including infiltrates and a pleural effusion.  CT Thorax will show enlarged hyperdense mediastinal and hilar lymph nodes.  Cyanosis and hypotension eventually develop, and death follows soon.  This second stage can occur within hours.  Mortality rate is estimated at between 50 – 90% for inhalational anthrax.   (Note: Pneumonic plague caused by Yersinia pestis can present very similarly to this case, with flu like symptoms progressing to respiratory failure, shock, and death within days.  Pneumonic plague, unlike inhalational anthrax, can be transmitted from person to person).   Ricin toxin inhalation would cause symptoms within hours of exposure, leading rapidly from flu like symptoms to respiratory distress and then shock and death.  Inhaled aerosolized F. tularensis, or C. burnetii could both cause initial flu-like symptoms progressing to pneumonia, though the course in both of these diseases would be slower, milder and less likely to be fatal than inhalational anthrax (especially for C. burnetii infection).  Neither ricin, tularemia, nor Q fever are associated with widened mediastinum on chest x-ray.  Variola major infection (Smallpox), starts off with a flu-like prodrome and then produces a characteristic pustular rash and is not consistent with this patient’s clinical picture.

2)     Correct answer: C (ciprofloxacin)

Anthrax is described as a large, gram positive bacilli that can be seen on a blood smear or CSF stain later on in the disease course.  Blood cultures should be drawn prior to antibiotic initiation, and will grow B. anthracis in 6-24 hours.  The recommended initial IV therapy for inhalational anthrax is ciprofloxacin, 400 mg Q12 hours or alternately doxycycline 100mg Q12 hours.   Naturally occurring B. anthracis have shown resistance to extended spectrum cephalosporins as well as TMP/SMX.

3)     Correct answer: C (oral antibiotics)

This picture shows the characteristic painless black eschar of cutaneous anthrax.  There were 11 cases of cutaneous anthrax following the 2001 anthrax mail attacks.  Cutaneous anthrax starts as a pruritic macule or papule, progresses to ulcer and vesicles, and finally leads to a black painless eschar with local edema.  Without treatment, cutaneous anthrax can progress to systemic disease with a mortality rate as high as 20%.  The appropriate treatment is oral ciprofloxacin or doxycycline.  Treatment does not alter the course of the eschar but does prevent the development of systemic disease.

 

 

Take Home Message:

–        ED physicians play an instrumental role in health surveillance in the event of a possible bioterrorism attack

–        Suspect inhalational anthrax in the presentation of multiple cases of a severe acute febrile illness progressing to pneumonia with a fulminant course in previously healthy individuals

–        Chest x-ray will commonly show a widened mediastinum and pleural effusions, and CT will show enlarged mediastinal and hilar lymph nodes

–        Large gram positive bacilli can be identified in blood smears and CSF gram stains, and in blood cultures in 6 – 24 hours

–        The initial IV antibiotics of choice are ciprofloxacin or doxycycline

–        Any case of inhalational anthrax should be regarded as a bioterrorism incident until proven otherwise.  Suspicions of anthrax infection should be reported immediately to local or state public health departments.


Anthrax (Bacillus anthracis)

 

Natural anthrax infections  – Natural cases of B. anthracis infection occur in herbivores that ingest the bacteria from the soil.  Human infection occurs mainly from exposure to infected animals, historically in goat hair mill workers and leather tanners.  No natural cases of inhalational anthrax have been reported in the U.S. since 1976 due to vaccination of livestock.

Anthrax as a weapon – Multiple countries including the U.S., former Soviet Union, and Japan historically investigated the use of anthrax as a biological weapon.  Unintentional release of anthrax from a Soviet bioweapons facility occurred in Sverdlovsk in the former Soviet Union in 1979 leading to many infections and deaths.  The Aum Shinrikyo cult, known better for releasing sarin nerve gas in a Tokyo subway station in the 1990s, attempted to disperse anthrax spores through Tokyo multiple times, but were unsuccessful.  In 2001, anthrax was used as a terror weapon through delivery of spores through U.S. mail to multiple locations, resulting in 22 anthrax cases, 11 cases of inhalational anthrax, and 5 deaths.

 

Pathogenesis

Humans can develop cutaneous, inhalational, and gastrointestinal anthrax.  In inhalational anthrax, spores are inhaled into the alveoli, where they are phagocytosed by macrophages and transported to the mediastinal lymph nodes.  There, the spores hatch into vegetative cells, which release cytotoxic factors leading to cell death, edema, and ultimately mediastinal hemorrhage and bloody pleural effusions.  In cutaneous anthrax, spores gain entry into the skin, often through abrasions or cuts.  The spores hatch and again the vegetative cells release cytotoxins leading to cell necrosis.  Gastrointestinal anthrax is mainly caused by ingestion of undercooked meat contaminated with vegetative B. anthracis, and is not generally associated with bioterrorism.

 

Clinical Manifestations

Inhalational anthrax classically has been described as following a two stage course.  In the first stage, symptoms are nonspecific and include fever, dyspnea, cough, headache, vomiting, chills, weakness, abdominal pain, and chest pain.  This first stage can last from hours to days.  The second stage is marked by abrupt onset of high fever, dyspnea, diaphoresis, and shock.  Mediastinal lymph node enlargement can be so severe that it leads to airway obstruction.  Cyanosis and hypotension eventually develop, and death follows soon.  This second stage can occur within hours.

Cutaneous anthrax starts as a pruritic macule or papule, progresses to ulcer and vesicles, and finally leads to a black painless eschar with local edema.  Without antibiotics, cutaneous anthrax can often lead to systemic disease with a mortality rate as high as 20%.

 

Lab/Microbiology

General lab tests – May show leukocytosis, hemoconcentration, and/or elevated transaminases.

Specific identification –    B. anthracis cells appear as large gram positive bacilli. They can be seen in blood smears and in CSF.  Blood cultures will grow B anthracis in all media in anywhere from 6 to 24 hours.  Suspected anthrax should be confirmed by a local or state public health laboratory.

Imaging

Chest x-ray: Multiple abnormalities are usually present, including mediastinal widening (secondary to mediastinal lymphadenopathy), pulmonary infiltrates, and pleural effusion

CT: Hyperdense hilar and mediastinal lymph nodes, edema, infiltrates, and pleural effusion

 

Treatment

Suspicion or confirmation of inhalational anthrax should lead to immediate notification of the local or state public health department, local or hospital epidemiologist, and local or state public health laboratories. It is important to treat suspected cases of inhalational anthrax even before there is laboratory confirmation.  It is also important to draw cultures before antibiotics are initiated.

The following tables show recommended treatments for inhalational anthrax in a contained casualty situation, as well as the treatment regimen for cutaneous anthrax.

Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, et al. Anthrax as a biological weapon 2002: updated recommendations for management. Jama. 2002;287:2236–2252.

Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, et al. Anthrax as a biological weapon 2002: updated recommendations for management. Jama. 2002;287:2236–2252.

Bibliography:

“CDC | Bioterrorism Agents/Diseases (by Category) | Emergency Preparedness & Response.” CDC Emergency Preparedness & Response Site. Centers for Disease Control and Prevention. Web. 13 Jan. 2012. <http://www.bt.cdc.gov/agent/agentlist-category.asp&gt;.

Cutaneous Anthrax picture was taken from: http://www.freeinfosociety.com/media.php?id=1298

Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, et al. Anthrax as a biological weapon 2002: updated recommendations for management. Jama. 2002;287:2236–2252.

Mina B, Dym JP, Kuepper F, Tso R, Arrastia C, et al. Fatal inhalational anthrax with unknown source of exposure in a 61-year old woman in New York City. JAMA. 2002;287:858–862.

 

 

One Response

  1. CDC recc for inhalational bioweapon exposures are for a poly drug regime:
    ciprofloxicin or doxycycline, plus 1 or 2 other drugs(rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenim, clindamycin, clarithromycin) with caution that naturally occuring beta-lactamase in native B. anthracis is relativly high, so the ‘cillins are not good initial choices.
    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5042a1.htm#tab1

    I’m not sure if the previous terroism events around 2001 were single strain or not. With a natural infection a single strain is thought to predominate. Sverdlovsk PCR has revealed at least 4 separate strains from autopsy samples. I have been unable to chase down the complete epidemiology but with a bioweappn unusual things can crop up like the published autopsy data, 42 cases, 9 female and no kids, out of 70 fatalities, interesting for a weapon. The other articles frequently list the fatalities as “70 people” without demografic identifiers.

    Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979.
    Abramova FA, Grinberg LM, Yampolskaya OV, Walker DH.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2291-4.

    Proc. Natl. Acad. Sci. USA
    Vol. 95, pp. 1224–1229, February 1998
    Microbiology

    As a bioweapon you will like see multiple strains with likely variations in antibiotic resistence across the various strains choosen for dispersal. Generally what is published seems to support the “Go Big or Go Home” or “Kill it all and let the ID Docs sort it out” philosophy

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