Mucormycosis in covid 19 patients; Is it worrisome?
13 June 2021
What is mucormycosis :
Mucormycosis, commonly called black fungus, is a rare but serious fungal infection associated with order Mucorales, many different organisms can cause this infection like mucor spp, licthemia spp, rhizomucor spp, but the main causative organism for Mucormycosis in India is Rhizopus spp and not the mucor species (which is always misconceived). Lichthemia spp is not found in India yet, but it’s the most common organism in Spain.
Clinical presentation
Essentially it's sinusitis-like symptoms, therefore there is a chance of misinterpreting this disease as sinusitis. Therefore any people with covid, or recently recovered patients or patients with DM, corticosteroid therapy if presents with nasal blockage or blood-tinged nasal discharge should be monitored thoroughly to rule out Mucormycosis.
Common symptoms are
Ø Nasal blockage
Ø Headache
Ø Pain in the eye
Other symptoms include pain and redness around the eyes and/or nose, fever, headache, coughing, shortness of breath, bloody vomits, and altered mental status. Warning signs can include toothache, loosening of teeth, blurred or double vision, diplopia, swelling of the eye, and adnexa with pain.
Further, it can spread to the orbital areas which are called the rhino orbital Mucor mycosis causing open-sided facial pain and swelling in the orbit, Tenderness, and pain.
It then moves towards the maxilla causing toothache, loosening teeth, the discomfort of chewing, but if it spreads to the upper portion (cranial cavity) then it's more dangerous called Rhino-cerebral Mucormycosis. Nasal cavity and sinusitis are manageable however, the fatality increases if it spreads from orbit to the cranial cavity of the brain.
Why is it called as black fungus?
It is called black fungus because it's highly necrotizing, cheeks may get necrosed and may become black. It can produce Black discharge from the skin around the eye, nose. Endoscopic findings would show black tissues.
Route of infection:
In immunocompromised patients, due to the inhalation of sporangiospores, these infections can develop.
In diabetic patients; it could be rhino orbital disease that would be more prevalent
Risk factors :
Risk factors are :
Ø Neutropenia
Ø HSCT
Ø Immunocompromised
Ø High cytokines IL6
Ø High ferritin
Ø Uncontrolled diabetes
Ø High CT score (ventilation support)
Ø Immunomodulators eg: Toclizumab
Ø High dose of corticosteroids
Ø lymphopenia
Ø Covid 19 Patients with uncontrolled diabetes , Diabetic ketoacidosis and with high dose of corticosteroids or immune modulators and using an oxygen delivery system
Precautions
📷 Undergo weekly nasal endoscopy
📷 Sterilise before nasal endoscopy
📷 Then think about rhinoscopy by next week
📷 But in India it’s not easy to make a weekly endoscopy but at least make a follow up
Beyond box
Immune competent patients might also develop this infection as they are more prone to cutaneous and soft tissue. Mucormycosis which usually occurs after skin disruption like Roads traffic accidents, burns, therefore continuous monitoring should be made for those patients who present with skin swelling, necrosis, abscess, or eschar formation.
Pathogenesis:
Diabetes results in
Polymorphonucelar dysfunction or neutrophil dysfunction resulting into
Decreased chemotaxis and reduced intracellular killing which further leads to
Decreased immunity
2)Diabetic ketoacidosis is associated with
More free iron in serum,so this
Mucorales takes this free iron which is essentially required for their growth
Thus making it more virulent.
3)steroids causes
Decreased immunity as well as an increased chances of hyperglycaemia
4)steroid induced mucormycosis
Why is it considered so dangerous?
It is angio-invasive, therefore It can invade into vessels and block this vessel as they block these vessels, it can cause ischemia which leads to necrosis which when prolonged causes black discharge thus called black fungus.
Diagnosis :
1)Biopsy endoscopic or CT-guided
Histopathology staining; PAS,GMS
Findings:non-septate ,pauci septate ,ribbon like hyphae,vessel occlusion (hyphal morphology in mucor mycosis can resemble like that of aspergillosis lesions , but there is a difference as mucormycosis is 6-16 micro metre wide and branched irregularly )there fore the chanceds of misinterpretation can be a factor )
CT: Halo sign,a ring of grond glass opacity surrounding a nodular infiltrate ,that represents a region of ischemia
Reverse halo sign-inversed halo or atoll sign, an area of ground glass opacity surrounded by a ring of consolidation
2)Culture -cottony white or greyish black colonies, followed by susceptibility testing
3)Lab findings
4)Microscopy: Acute lesions-haemorrhagic infarction ,neutrophil infiltration, Angio-invasion, peri-neural invasion
Chronic lesions -giant cells, Pio granulomatous inflammation, hyphae covered eosinophilic material splendore -hoeppli phenomena
Management :
v Control diabetes
v Stop steroids or taper to a lower dose or a proper pharmacological intervention
v Liposomal amphotericin B- less than 5mg/kg/day
Ø >5mg /kg/day-10m mg/kg/day in orbital cavity involvement
Ø >10 mg /kg/day in cranial (but not in nephrotoxic not in renal failure pts or for prolonged use)
Drawback: expensive
Benefit: penetrates more, toxicity less
If amphotericin can’t be used:
v IV /Delayed release tablets of Posaconazole
v IV Isavuconazole (both are suitable for prolonged treatment)
Surgical debridement
o FESS -functional endoscopic sinus surgery
o Orbital exenteration
o Orbital decompression
Limitations
Newer drug evidence is still pending
Existing antifungals are Expensive.
Conclusion
Patients most vulnerable to mucormycosis are those who have been treated with steroids and other drugs for Covid 19 to reduce inflammation. Efforts are underway to collect data for large studies. One. should remember that it is a rare disease. However, some groups of people are more vulnerable than others. It is treated with antifungals, or surgery. It is of utmost importance to control diabetes, reduce steroid use, and discontinue immunomodulating drugs if possible or after proper interventions with multidisciplinary team. To maintain adequate systemic hydration, the treatment includes infusion of normal saline (IV) before infusion of amphotericin B and antifungal therapy, for at least 4-6 weeks. Experts in the task force have stressed the need to control hyperglycaemia, and monitor blood glucose level after discharge following Covid-19 treatment.
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