A 52-year-old male diabetic presents with a week-long history of fever, headache, confusion, facial nerve palsy with pain and a black, purulent nasal discharge. He is referred to ICU for his deteriorating level of consciousness.

Give the most likely diagnosis.   (20% marks)

List four predisposing factors.    (10% marks)

List the specific management of this condition.         (40% marks)

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College Answer

a) 

  • Rhinocerebral mucormycosis or fungal sinus infection with cerebral spread.

b)                                                                   

  • HIV/AIDs Diabetes
  • Cancer – lymphoma
  • Renal failure
  • Organ transplantation
  • Long term steroid or immunosuppressive therapy
  • Cirrhosis
  • Deferoxamine therapy
  • Iron overload
  • Burns

c)

  • Investigation with MRI or CT to determine the extent of the spread. 
  • Blood culture and biopsy to obtain tissue for fungal culture +/- Surgical debridement if amenable
  • Amphotericin B
  • Possibly hyperbaric oxygen therapy.

Discussion

a) "Give the most likely diagnosis" for 20% of the mark really only gives enough time for two words. Fortunately, you only need one: mucor. Not much else presents as encephalitis/meningitis "and a black, purulent nasal discharge".

Having said this, "mucor mimics" do exist. Firstly, it could be another Zygomycete (Branscomb, 2002, lists Rhizopus, Absidia,  Saksenaea and Cunninghamella). Secondly, it could be a bacterial infection causing necrotising fasciitis,  or it could be the black eschar of an airway burn, or the patient might have recently had a nasogastric tube which had produced a nasty intranasal pressure area with necrosis. But these are not especially plausible. 

b) List four predisposing factors is worth only 10% of the marks, but these are reasonably easy to earn. The college have already given you one, by volunteering a history of diabetes. Mucor likes to extend along blood vessels, and even more so when the vessels are full of sugar. In total, Branscomb (2002) lists the following nine predisposing factors:

  • Acidosis
  • Uncontrolled diabetes mellitus
  • Leukemia
  • Lymphoma
  • AIDS
  • Severe malnourishment
  • Severe burns
  • Cytotoxic therapy
  • Immune suppression from corticosteroid use

In addition to this, the college also add

  • Renal failure
  • Cirrhosis
  • Deferoxamine therapy
  • Iron overload

c), "List the specific management of this condition" calls for some additional thinking, as it is worth 40%. Interestingly, the college had listed imaging and cultures in this section, even though those (undoubtedly important) elements are investigations which don't themselves manage anything. Still, if one is expected to list the investigations, they would be:

  • Investigations of the underlying predisposing factors
    • HbA1c
    • FBC to look for neutropenia
    • HIV test
  • Imaging and endoscopy:
    • MRI or CT  of the head and sinuses
    • CT venogram to look for involvement of the cavernous sinus
    • Nasendoscopy to look for necrotic tissue from which a sample can be taken
  • Microbiology
    • Tissue culture is gold standard. Mucor in blood is rather difficult to find as - even if it is in there - it tends to be outcompeted by bacteria on standard blood culture media, and special cultures are required (Sabouraud’s dextrose agar or brain-heart infusion agar).
    • The most sensitive investigation would be histological section of a sizeable chunk, as the hyphae are aseptate and rather fragile (i.e. they may not survive a scraping sample). Histology will demonstrate characteristic fungal elements and arterial invasion with necrosis.

Craig et al (2019) give an excellent overview of management options, classifying them in the following manner: 

  • Surgical
    • Extensive debridement, "until bleeding is seen"
    • This typically results in disfigurement
    • The patient needs to be agreeable to that possibility, particularly where the orbit is involved 
  • Antifungal therapy
  • Reversal of predisposing condition
    • Control of the diabetes
    • Transfusion of ranulocytes or GM-CSF if neutropenic
    • Antiretroviral therapy if AIDS

References

Craig, John R. "Updates in management of acute invasive fungal rhinosinusitis." Current opinion in otolaryngology & head and neck surgery 27.1 (2019): 29-36.

Branscomb, Robert. "An overview of mucormycosis." Laboratory Medicine 33.6 (2002): 453-455.

Tragiannidis, A., and A. H. Groll. "Hyperbaric oxygen therapy and other adjunctive treatments for zygomycosis." Clinical Microbiology and Infection 15 (2009): 82-86.