Chronic Invasive Aspergillosis with Fulminant Mucormycosis Sparing Palate in a Post-COVID-19 Patient - A Case Report : Annals of Maxillofacial Surgery

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Case Report – Infections

Chronic Invasive Aspergillosis with Fulminant Mucormycosis Sparing Palate in a Post-COVID-19 Patient - A Case Report

Ramani, Pratibha; Krishnan, Reshma Poothakulath,; Pandiar, Deepak; Benitha, J. Georgia; Ramalingam, Karthikeyan; Gheena, S.

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Annals of Maxillofacial Surgery: Jan–Jun 2022 - Volume 12 - Issue 1 - p 102-105
doi: 10.4103/ams.ams_296_21
  • Open

Abstract

INTRODUCTION

The pandemic COVID-19 continues to be a significant problem worldwide.[1] COVID-19 patients, especially immunocompromised or severely ill, have a higher probability of suffering from invasive fungal infections.[23] Recently, a more dangerous and potentially deadly infection, invasive fungal sinusitis, resulting from mucormycosis in post-COVID-19 patients has been observed.[4] The most common causes attributed to the rise of mucormycosis in COVID-19 patients are the excessive use of corticosteroids, uncontrolled diabetes, and long-term stays in the ICU.[5] We hereby report a case of chronic invasive aspergillosis with fulminant mucormycosis sparing palate in a post-COVID-19 patient. To the best of our knowledge, no case reports with invasive aspergillosis with fulminant mucormycosis in post-COVID patients have been reported in the literature.

CASE REPORT

A 41-year-old male reported pain and heaviness in the face for the past 20 days. He also complained of multiple swellings with pus discharge from the upper jaw and mobility of the upper teeth for the past 10 days. The patient had tested COVID-19 positive 20 days back and was hospitalised for the same for seven days. He noted facial swelling and blackish green nasal discharge within few days of being hospitalised. The patient was recently diagnosed with Type II diabetes mellitus (capillary blood glucose (CBG) – 317 mg/dl) and also gives a history of steroid administration for eight days during hospitalisation for COVID-19. On examination, swelling was present in relation to the left maxillary sinus [Figure 1a]. Multiple sinus openings were evident in relation to the attached gingiva of 13–23 region. The palatal mucosa appeared normal [Figure 1b]. No ulceration or pus discharge was evident on the palatal mucosa. Cone-beam computed tomography revealed osteolytic changes involving bilateral maxillary sinus with thinning of palate and haziness in the right and left maxillary sinus [Figure 1c]. Based on the patient history and clinical examination, a provisional diagnosis of mucormycosis was given. On histopathological examination, numerous tightly packed thin septate hyphae branching at acute angle along with many fruiting bodies (conidial heads) were evident [Figure 2a and b]. Several areas of broad aseptate hyphae branching at 90° and aseptate broad hyphae branching at obtuse angle were also present [Figure 2c and d]. There was also evidence of extensive areas of tissue necrosis and necrotic bone. Based upon the above histopathological findings, the diagnosis of chronic invasive aspergillosis with fulminant mucormycosis in a post-COVID-19 patient was reported. Since the lesion was spreading very rapidly, the patient was referred to an isolation facility for further management.

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Figure 1:
Photomicrograph showing (a) Multiple sinus openings in relation to attached gingiva of 13-23 region (black arrow) (b) Nasal discharge with apparently normal palatal mucosa (white arrow) (c) CBCT with osteolytic changes involving bilateral maxillary sinus with thinning of palate. CBCT: Cone-beam computed tomography
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Figure 2:
Photomicrograph showing (a) Aspergillus fruiting bodies dissipating spores, (b) Fruiting bodies (black arrow) with Mucor hyphae (yellow arrow), (c) Numerous broad aseptate hyphae, (d) Narrow septate hyphae (black arrow), broad aseptate hyphae (green arrow), broad tortuous Mucor hyphae (yellow hyphae), and hyphae showing branching (dark blue arrow)

DISCUSSION

Diabetes mellitus, immunosuppressive therapy, and systemic immune alterations of COVID-19 infection may lead to secondary infections.[6] Patients with COVID-19 show increased expression of inflammatory cytokines, and impaired cell-mediated immunity with decreased CD4- and CD8-positive T-helper cell counts, indicating susceptibility to fungal coinfections.[2] In the early stages, the infected tissue may appear normal, thereafter progressing to erythaema and subsequent development of black, necrotic eschars.[7] Over the past few months, our institute has seen a sudden rise in cases of invasive fungal infections, specifically mucormycosis in post-COVID-19 patients. A black necrotic intranasal or palatal eschar is highly suggestive of mucormycosis.[7] Majority of the cases of mucormycosis which are reported in the literature present with a palatal ulcer. Interestingly, our patient showed nasal discharge with swelling near the sinus region sparing the palate. Due to the COVID-19 infection, the clinical symptoms of mucormycosis seem to be varying. Aspergillosis usually affects the sinus mucosa with destruction of the nasal cavity, and adjacent structures such as orbit and brain.[8] Palatal mucosa is less commonly affected in aspergillosis when compared to mucormycosis. Aspergillosis could have been the first organism to cause disease in our patient, followed by mucormycosis. Mucor fungi could have followed the path of aspergillosis and hence sparing the palate. The presence of palatal ulcer should not be considered as the only clinical manifestation of mucormycosis and hence is important for the clinicians and pathologists to increase awareness of these varying degrees of clinical.

The finding of hyphal forms of Aspergillus is not very common in biopsies; detection of fruiting bodies of Aspergillus in histopathological section is a rare finding. The hyphal forms of Aspergillus can be confused with the hyphal forms of other fungi, but when fruiting bodies are present, diagnosis is possible at the histopathology level itself.[9] Fruiting bodies (conidia) of aspergilli develop from mycelia in areas of high oxygen tension or severe infections.[9] Our case showed chronic invasive aspergillosis along with mucormycosis. There are two possibilities for this occurrence, we could not ascertain whether aspergillosis was followed by mucormycosis and henceforth becoming a fulminant disease, or there was coexistence of these two infections together post-COVID. We have postulated few hypotheses for the coinfection of aspergillosis and mucormycosis in this case [Figure 3]:

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Figure 3:
Hypothesis for the coinfection of aspergillosis and mucormycosis

  1. Radiograph of this patient showed bilateral haziness suggestive of sinusitis? This leads to poorly drained sinus and blocked ostium. At this stage, patient would have inhaled asper followed by mucor spores leading to its coinfection
  2. Noninvasive aspergillosis such as aspergilloma could have led to invasive aspergillosis due to COVID infection and steroid therapy. During the course of steroid therapy, the patient could have encountered Mucor spores probably from the hospital (iatrogenic), which could be the reason for coinfection of mucormycosis and aspergillosis
  3. COVID-19, diabetes mellitus, and steroid therapy can lead to immune dysregulation, which could have led to invasive aspergillosis and tissue necrosis. At this stage, Mucor spores would have entered the sinus, as the ability of Mucor spores to cause infection depends upon mucosal barrier, environmental factors, and virulence of organism, and as the tissue of the nasal or sinus mucosa was already destroyed by the aspergillosis infection, there would have been an easy entry of these fungi, leading to a coinfection of aspergillosis and mucormycosis
  4. COVID-19 along with diabetes mellitus and corticosteroid therapy lead to a combined infection of chronic invasive aspergillosis and mucormycosis due to immune dysregulation.

While invasive aspergillosis and mucormycosis infections are often grouped together under the umbrella of invasive fungal sinusitis, studies have found very different clinical outcomes and treatment strategies between these two infections. Trief etal. reported that the treatment of mucormycosis and aspergillosis differs, amphotericin B is the preferred antifungal for mucormycosis, and when a diagnosis of invasive Aspergillus is made, amphotericin B is switched to voriconazole as this agent was demonstrated to be superior.[10] It is important to note that voriconazole does not have reliable activity against mucormycosis.[7] We recommend clinicians to systematically screen post-COVID-19 patients for fungal infections, especially in immunocompromised and severely ill patients.

CONCLUSION

Post-COVID-19 patients should receive fungal pathogen surveillance, including periodic cytology and culture to identify these fungal infections at the earliest and prevent subsequent comorbidity. Effort must be made to obtain accurate diagnosis including a tissue biopsy if required to confirm the diagnosis. Possibility of a concurrent infection with other fungal infections should also be kept in mind.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

REFERENCES

1. Garg D, Muthu V, Sehgal IS, Ramachandran R, Kaur H, Bhalla A, et al. Coronavirus disease (covid-19) associated mucormycosis (CAM):Case report and systematic review of literature Mycopathologia 2021 186 289 98
2. Song G, Liang G, Liu W Fungal co-infections associated with global COVID-19 pandemic:A clinical and diagnostic perspective from china Mycopathologia 2020 185 599 606
3. Pandiar D, Kumar NS, Anand R, Kamboj M, Narwal A, Shameena PM Does COVID 19 generate a milieu for propagation of mucormycosis?Med Hypotheses 2021 152 110613
4. Sharma S, Grover M, Bhargava S, Samdani S, Kataria T Post coronavirus disease mucormycosis:A deadly addition to the pandemic spectrum J Laryngol Otol 2021 135 442 7
5. Raut A, Huy NT Rising incidence of mucormycosis in patients with COVID-19:Another challenge for India amidst the second wave? Lancet Respir Med 2021 9 e77
6. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China:A descriptive study Lancet 2020 395 507 13
7. Munir N, Jones NS Rhinocerebral mucormycosis with orbital and intracranial extension:A case report and review of optimum management J Laryngol Otol 2007 121 192 5
8. Peral-Cagigal B, Redondo-González LM, Verrier-Hernández A Invasive maxillary sinus aspergillosis:A case report successfully treated with voriconazole and surgical debridement J Clin Exp Dent 2014 6 e448 51
9. Anila KR, Somanathan T, Mathews A, Jayasree K Fruiting bodies of aspergillus:An unusual finding in histopathology Lung India 2013 30 357 9
10. Trief D, Gray ST, Jakobiec FA, Durand ML, Fay A, Freitag SK, et al. Invasive fungal disease of the sinus and orbit:A comparison between mucormycosis and aspergillus Br J Ophthalmol 2016 100 184 8
Keywords:

Aspergillosis; coinfection; COVID-19; mucormycosis; mycoses

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