Medical Mystery of the Week

      You have recieved your COVID19 immunizations and are assigned to the Emergency Room.
      You examine a critically ill man who has just flown in from Africa. His illness is characterized by the sudden onset of fever, rigors, followed in several hours by a cough - initially nonproductive, but rapidly becoming watery and then bloody. The cough is associated with progressive dyspnea and chest discomfort. He is too ill to provide an epidemiologic history. Your examination reveals a pulse rate of 120 beats/min, a blood pressure of 90/40 mm Hg, a respiratory rate of 30 breaths/minute, and a temperature of 38.2°C. Lung examination reveals bilateral patchy areas of bronchial breath sounds and inspiratory crackles.  You obtain a chest x-ray (Panel A) and collect a sputum sample. A picture of one of his hands is shown in Panel B.
       What is your diagnosis, what test(s) do you advise to substantiate your suspicions, and what treatment, if any, do you advise? What precautions do you want to take during and after your examination of the patient?
DIAGNOSIS:  Primary pneumonic plague with intravascular dissemination.
      Yersinia pestis is a highly lethal Gram-negative bacterium that causes bubonic, septicemic, pneumonic, meningitic, and phayngeal plague. Inhalation of respiratory droplets contaminated with Y. pestis results in primary pneumonic plague, a rapidly progressing pneumonia that is nearly 100% fatal without antibiotic treatment.
      Y. pestis is endemic on every continent except Antartica and Australia, with most cases occurring on the African continent. In the United States the disease is endemic to States west of the Rockies. Y. pestis is recognized as a potential bioweapon by the World Health Organization.
      Y. pestis evolved from Yersinia pseudotuberculosis about 5700-6000 years ago eventually obtaining the ability to be transmitted by fleas and to cause three historical pandemics (Justinian, Black Death, 3rd pandemic [not named]).
      First line drugs used to treat pneumonic and septicemic plague include fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), aminoglycosides (gentamicin), tetracyclines and streptomycin; treatment should include drugs of two distinct classes.  For pharyngeal and bubonic plague, doxycycline  should be included along with a fluoroquinolone. For meningitis, dual treatment with chloramphenicol and levofloxacin or moxifloxacin is indicated. In all cases, treatment should be continued for 10-14 days depending on the patient's response. Unfortunately, antibiotic resistant strains of Y. pestis have emerged in endemic foci, emphasizing the need for in vitro sensitivity testing.
      Persons with significant exposure to plague (i.e., sustained exposure to a coughing patient ≤ 6 feet away and absence of personal protective equipment [PPE]); lab exposure; handling of infected carcasses) should be placed on doxycycline prophylaxis. Patients infected with Y. pestis should be admitted to an isolation room where all personelle wear PPE (mask, eye protection, face shield, gown and gloves) (see Panel E below for Justinian plague PPE).

Panel A. The patient's chest x-ray

The x-ray shows a large area of consolidation in the left mid-lung field and early apical cavitation in the right lung. There is evidence of mediastinal widening due to lymphatic spread of Y. pestis.

Panel B. Photo of the patient's hand

The patient had Y. pestis bacteremia with disseminated intravascular coagulation resulting in acral gangrene (left). Y. pestis is a Gram-negative bipolar coccobacillus shown here in a buffy coat examination of the patient's peripheral blood (right).

Panel C.

Schematic of the pre-inflammatory and inflammatory phases of Y. pestis pneumonia.

Panel D. 

Schematic of the laboratory diagnosis of Y. pestis infection.

Panel E.

Personal protective equipment worn by a doctor during the Justinian plague. 

Bonus Question: What is your diagnosis?

Answer: Sister Mary Joseph's nodule. These nodules occupy the umbilicus (which should always be palpated during the abdominal examination); they are composed of metastic deposits from an intraabdominal organ or from an ovary. Diagnosis is made by performing a fine needle aspirate of the nodule.

Citations:
      The schematics shown above were obtained from: Crane, S.D.; Banerjee, S. K., Eichelberger, K.R.; Kurten, R.C.; Goldman, W.E.; Pechous, R.D. The Yersinial pestis GTPase BipA promotes pathogenesis of primary pneumonic plague. 2021. Infect. Immun. 89:e00673-20.
      Information about the treatment of the plague was obtained from: Treatment and prophylaxis of plague: recommendations for naturally acquired infection and bioterrorism response.  2021. MMWR, 70(3).