key: cord-0735164-loadx5r6 authors: Chugh, Ankita; Pandey, Akhilesh Kumar; Goyal, Amit; Soni, Kapil; Jain, Vidhi; Thirunavukkarasu, Balamurugan; Vedant, Deepak; Kumar, Deepak; Kumar, Pravin title: Atypical presentations of Fungal Osteomyelitis during post COVID-19 outbreak – Case series date: 2022-04-04 journal: J Oral Maxillofac Surg Med Pathol DOI: 10.1016/j.ajoms.2022.03.007 sha: 8854089eb7642708d17528f71aea32132a48b528 doc_id: 735164 cord_uid: loadx5r6 INTRODUCTION: Mucormycosis and Aspergillosis are opportunistic fungal infections causing significant morbidity and mortality. Post the outbreak of COVID-19, these fungal osteomyelitis have seen a global rise with few atypical presentations noted. CASE REPORT: Current case series reports three such atypical presentations of fungal osteomyelitis including mandibular fungal osteomyelitis in two patients, fungal osteomyelitis mimicking space infection in a middle aged male, and suspected mixed fungal osteomyelitis involving maxillary sinus. Aggressive surgical debridement was indicated along with institution of antifungal therapy (Liposomal Amphotericin B, and Posaconazole). The fungal osteomyelitis was successfully treated with surgical and medical management with no recurrence. DISCUSSION: The injudicious use of corticosteroids in COVID-19 patients along with their immunocompromised status increases their susceptibility to opportunistic fungal osteomyelitis. Prompt and aggressive surgical intervention along with antifungal therapy is important after diagnosing fungal osteomyelitis, as a delay could increase the mortality rate considerably. The outbreak of the global pandemic COVID-19 since March 2020 has engendered breeding grounds for many opportunistic bacterial and fungal infections such as Mucormycosis and Aspergillosis. Mucormycosis is caused by an ubiquitous fungal pathogen which belongs to the phylum Zygomycota, family Mucoraceae, with Rhizopus being the most common genera. Paltauf in 1885 first documented the case of upper airway mucormycosis [1] . This aggressive saprophytic fungal infection, aptly described as a 'phoenix' has been on a global rise since the pandemic began [2] [3] . The prevalence of the coronavirus associated mucormycosis (CAM) was 0.27% among the hospitalized COVID-19 patients, and by July 2021 the CAM cases reached around 40,000 in India [4] . Having a male predisposition (78.9%), mucormycosis commonly involves the nose and sinuses (88.9%) followed by rhino-orbital involvement (56.7%) and then rhino-orbitocerebral (22.2%) with a significant rise in mortality rates in these cases. The mucorales gain access to the nose and paranasal sinuses via inhaled spores, causing high morbidity and mortality and in absence of prompt and urgent intervention. They gain access to the cavernous sinus through reterograde infection, and the brain parenchyma through cribriform plate, orbital apex or orbital vessels [5] . Metabolic states such as diabetes mellitus and diabetic ketoacidosis (DKA) lead to an hypoxic acidic environment which is the key necessity for mucorales spread, owing to the presence of ketone reductase enzymes, which makes such acidic environment suitable for their growth.(or helps them thrive in such acidic environment) . The rampant use of corticosteroids to combat COVID-19 infection, has significantly contributed to the prevailing immunosuppression (neutropenia) found in these patients. Factors such as long term J o u r n a l P r e -p r o o f hospitalization, prolonged invasive or non-invasive ventilation due to hypoxia, poor hygiene status (prolonged wearing of old unclean mask), hematological malignancies, solid organ or haematopoetic cell transplantation, chemotherapeutic drugs and iron chelating agents such as deferoxamine [6] , have surfaced as the highest risk association with mucormycosis. Debridement of left maxillary sinus was done via Caldwell-luc approach (Fig. 5) . The maxillary sinus lining sent for histopathological analysis (Fig. 6.A,B) and KOH mount confirmed the presence of mucormycosis infection (Fig. 7.) . Patient was started on Injection Liposomal Amphotericin B 200mg in 500 ml D5 with 6 HIR and discharged on Posaconazole. A 35 year old male reported to emergency room of tertiary care hospital with pain in upper left back teeth region since 1 month. Multiple sinuses with pus discharge was associated with maxillary left labial gingiva, along with mobility of dentoalveolar complex (Fig. 8.) . The Even the slightest suspicion of mucormycosis warrants immediate evaluation and intervention, as the fatality rate is seen as high as 90% in intracranial involvement [16] and a delay of 3-6 days in initiating aggressive intervention could raise the thirty days mortality rate from 35% to 66% [17] . After establishing the aforesaid diagnosis, aggressive surgical debridement should commence along with the administration of first line Antifungals [18] viz. Posaconazole IV as induction therapy [10] (300mg BD loading dose at day 1 followed by 300mg OD) or Posaconazole oral as step down therapy (300mg BD loading dose at day 1 followed by 300mg OD) and Voriconazole (6mg/kg q 12hr on day 1 followed by 4mg/kg q12hr from day 2) for aspergillosis till clinical/radiological resolution of the disease. According to Code Mucor, Posaconazole oral is used as step down therapy for 3-6 months [4] . It's safety and efficacy was studied in Rhino-orbito-cerebral Mucormycosis patients of South India, the study reported no morbidity and disease clearance in about 66.6% of patients [9] . In the literature only 15 cases of isolated mandibular mucormycosis have been documented [19] . True invasive pathogens must be confirmed by consistent visualization on direct microscopy and fungal culture, both from sinuses as well as from deep tissue (intra-operative) biopsies. The usual route of dissemination involves inhalation of spores, invasion through extraction socket wounds, or breached cutaneous surfaces. The mortality rate of aspergillosis is 30% even after instituting antifungal therapy, and is as high as 85% in pediatric immunocompromised patients [21] . In developing country like ours this sudden outbreak was faced with scarcity of adequate antifungal therapy. Amphotericin which is advocated as the first line therapy could not be administered to all patients or in adequate doses. Prioritization for amphotericin based on extent of involvement of the disease was followed. Amphotericin was reserved for intracranial, orbital extension or mixed invasive fungal infection. Posaconazole which a second line therapy was used commonly in less extensive cases due to its better availability. Early surgical management was considered the best method to improve prognosis in this situation of lack of logistic issues with pharmacotherapy dependence. However to our surprise even Posaconazole along with adequate surgical debridement controlled the disease considerably well. In the present case series we have documented three atypical presentations of mucormycosis, mandibular fungal osteomyelitis, fungal osteomyelitis mimicking space infection, and suspected mixed fungal osteomyelitis. J o u r n a l P r e -p r o o f All these cases are rare presentations, and very little literature evidence has been documented so far. No funding was received for this study. Not required Written patient consent was obtained to publish the clinical photographs The authors report no declarations of interest. 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