Medical Mystery of the Week

      Because of the COVID19 pandemic, you are practicing telemedicine. You interview a 44-year-old woman who has a 10-year history of aplastic anemia. She was admitted to another hospital one month previously for evaluation of three weeks of persistent fever. A thorough workup, which included a chest x-ray and blood cultures, did not reveal the source of her fever and she was discharged. She now presents with persistent fever and a 10-days history of an expanding purple-colored lesion on her left arm. She notes that her temperature spikes as high as 38 degrees celsius and is often associated with shaking chills. With the exception of her fever, the arm lesion, and conjunctival pallor, her physical examination is reported as being unremarkable.
      Her CBC reveals a normochromic normocytic anemia and a leukopenia with a granulocyte count of 400 cells/cumm. Her metabolic panel is normal, and routine blood cultures are negative.
      Her chest x-ray and a photo of her arm lesion are shown below.
      What is your diagnosis, what lab test(s) would you order to confirm you suspicions, and what treatment, if any, do you recommend?

DIAGNOSIS: Disseminated mucormycosis. Mucor and rhizopus are zygomycetes known for their propensity to invade vessels (angioinvasion) and/or sinuses of neutropenic and Type I diabetic hosts causing infarction and syndromes such as rhinocerebral zygomycosis. These organisms are ubiquitous and seen, for example, as causes of bread mold, culture contamination, and, on occassion, surgical wound infection.  
      The source of the dissemination in the presented case was her lungs. Although her chest x-ray was free of infiltrates, a ventilation profusion scan showed multiple wedge-shaped areas of non-profusion, findings characteristic of infarction (see left lower photo, above).
      The patient was placed on optimal doses of intravenous amphotericin B. She showed clinical improvement (some abrogation of fever) but on her 10th day of hospitalization she became septic with klebsiella and expired.  At postmortem, the infarcted areas in her lungs were confirmed to be the result of angioinvasion with mucor (see right lower photo, above). A biopsy of the periphery of her skin lesion also showed angioinvasion with mucor. This fungus belongs to the order mucorales, and is best visualized with silver methenamine stains as seen in the above micrograph. In contrast to aspergillus, mucor has broad-based mycelia that branch obliquely.
      Aspergillosis, candidiasis, fusariosis, mucormycosis, cryptococcosis, and trichosporonosis are the most important infections reported in transplant patients, in neutropenic hosts and in type I diabetics.
      The mortality of pulmonary mucormycosis has fallen from 72.1% before year 2000 to 49.8% during the years 2010-2020. The improved mortality is the result of a combined medical-surgical approach to treatment using combinations of antifungal agents and surgical extirpation of pulmonary lesions (this would not be feasible in the presented case). In the absence of sugical removal of infected foci antifungal treatment is rarely curative.
      Amphotericin B, extended-spectrum azoles, and echinocandins are the drugs used to treat mucomycosis. Unfortunately, there is increasing resistance to all of these choices emphasizing the need to develop new antifungal agents. 
      In suseptible hosts, major steps should be taken to avoid their exposure to these fungi, including the use of air filters and negative room air pressures. With regard to aspergilli and zygomycetes, the old addage that an ounce of prevention is worth a pound of cure could not ring more true.