Mucormycosis

Mucormycosis - Facts in brief

1. MUCORMYCOSIS Dr. Ashwin Menon

2. Introduction Mucormycosis is an invasive fungal infection (IFI ) first described by Paulltauf A in 1885. Mucormycosis are the group of invasive infection caused by filamentous fungi of the Mucoraceae family. Mucormycosis also known as Zygomycosis is an opportunistic fungal infection with a fulminant course and high Mortality rate. Rhizopus  species are the most common causative organisms. The Rhinocerbral variant of Mucormycosis involves facial,orbital,paranasal sinus and cerebral regions.

3. Prevalence & incidence of Mucormycosis Ress et al reported an annual incidence rate of 1.7 cases per million people in the united states. Biter et al reported an average annual incidence rate of 0.9 per million people in France. The Rhinocerbral accounting for 30-50% of all cases of Mucormyscosis Overall Mucormycosis Prevalence of 0.14 cases per 1000 population in India. A Meta analysis of all the zygomycosis cases reported from India, Diwakar et al. describe an overall prevalence of ROC (58%), Cutaneous (14%), Pulmonary (6%), Disseminated(7%), Gastrointestinal (7%) and Isolated renal(7%).

4. The annual incidence of mucormycosis reported from different case series in India It is difficult to determine the exact incidence and prevalence of mucormycosis in the Indian population. The computational-model-based method estimated a prevalence of 14 cases per 100,000 individuals in India

5. Based on the Clinical presentation and particular site of involvement six manifestations of the disease can be described: Rhino cerebral (ROC), Pulmonary Cutaneous Gastrointestinal Disseminated Localized infection Different types of Mucormycosis

6. Different types of Mucormycosis A. MALLIS, S.N. MASTRONIKOLIS Rhinocerebral mucormycosis : an update, 2010; 14: 987-992

7. Common Causative Organisms Mucormycosis -causing species are the filamentous fungi of mucoraceae family of the order mucorales,subphylum Mucormycotina .   Mucor Cunninghamella Apophysomyces Absidia Saksenaea , Rhizomucor , and other species. A. MALLIS, S.N. MASTRONIKOLIS Rhinocerebral mucormycosis : an update, 2010; 14: 987-992

8. Pathophysiology OF MUCORMYCOSIS

9. Risk factors for Mucormycosis A. MALLIS, S.N. MASTRONIKOLIS Rhinocerebral mucormycosis : an update, 2010; 14: 987-992

10. Risk factors for Mucormycosis

11. Mucormycosis in Covid-19 Spores germinate in hypoxia, acidosis & hyperglycemic state Increased use of voriconazole Increased use of broad spectrum antibiotics Deferoxamine Endothelial damage Spores get attached High flow oxygen Mucosal injury

12. Doubtful associations Increased use of Zinc Industrial oxygen usage Impure humidifiers Inappropriate mask usage

13. Mortality Rates Mucormycosis carries a mortality rate of 50-85%. Cutaneous disease carries the lowest mortality rate (15%). The mortality rate associated with rhino cerebral disease is 50-70%. Pulmonary and gastrointestinal (GI) diseases carry an even higher mortality rate, because these forms are typically diagnosed late in the disease course. Disseminated disease carries a mortality rate that approaches 100%.

14. Red flag signs U/L Nasal block U/L Headache Nasal discharge Foul smell Redness of the eyes Lid edema Retro orbital pain

15. Clinical Presentation Eye Redness Edema Drooping Proptosis Retroorbital pain Diplopia

16. Clinical Presentation Face Facial edema Numbness Nose U/L Nasal block Dryness Increased crust formation Black eschar Anosmia/ foul smell

17. Clinical Presentation Oral cavity Blackish discoloration Numbness of teeth Loosening of teeth

18. Warning signs Reappearance of fever Headache associated with nausea & vomiting Altered sensorium Unresponsive patient with DKA whose mental state not improving with normal electrolytes ---- Mucormycosis

19. Clinical stages

20. Differential Diagnosis Bacterial orbital cellulitis Cavernous sinus thrombosis Rapidly growing orbital tumor Aspergillosis Fusariosis Tuberculosis

21. Diagnosis Timely diagnosis is paramount in cases of Mucormycosis. DNE CECT (PNS) / MRI (with Gadolinium) For pulmonary disease, a bronchoalveolar lavage (BAL), biopsy, or both may assist in the diagnosis. For cutaneous disease, a skin biopsy for pathology and culture should be obtained.

22. Investigations CBC with ESR CRP FBS,PPBS LFT RFT with SE S.Fe , S.Ferritin , IBC Viral markers

23. Investigations Biopsy HPE FUNGAL SMEAR FUNGAL CULTURE HPE 10% Formalin Fungal culture Saline

24. Diagnosis of Rhino cerebral Mucormycosis . Walsh, M. Gamaletsou , M. Mcginnis , R. Hayden, D. Kontoyiannis /

25. Mucor on Sabouraud dextrose agar

26. Typical mucorales hyphae on grocott methenamine-silver staining

27. Therapeutic goals for Mucormycosis

28. Management Correction of Predisposing Factors Surgical Debridement Systemic Antifungal Agents

29. Management Correction of Predisposing Factors Tapering or discontinuation of corticosteroids is advised Neutropenia should be rapidly corrected by initiation of granulocyte colony stimulating factors (G-CSF) as well as discontinuation of chemotherapeutic agents responsible for marrow suppression

30. Management Surgical Debridement Early, aggressive and repeated surgical excision of necrotic craniofacial tissues is the cornerstone of successful management. Repeated removal of necrotic tissue, extensive, disfiguring debridement of the sinuses and enucleation of orbit may be required to prevent dissemination to critical structures.

31. Anti Fungal Therapy Liposomal and lipid complex amphotericin B Dose - 5 mg/kg/day and 7.5-10mg/kg/day (CNS) Amphotericin B deoxycholate Dose - 1-1.5 mg/kg/d Isavuconazole Dose – 200mg TDS for 2 days followed by 200mg OD Posaconazole Dose – 300mg BD for 1 day followed by 300mg OD After 3-6weeks of Amph B – 3-6 months of Consolidation therapy

32. Adjunctive Treatments Hyperbaric oxygen therapy Deferasirox Immune augmentation strategies – granulocyte macrophage colony-stimulating factor, interferon

33. References 1. Hora JF. Primary aspergillosis of the paranasal sinuses and associated areas. Laryngoscope. 1965;75:768–73. 2. Chakrabarti A, Sharma SC, Chander J. Epidemiology and pathogenesis of paranasal sinus mycoses. Otolaryngol Head Neck Surg. 1992;107:745–50. 3. Hussain S, Salahuddin N, Ahmad I, Jooma R. Rhinocerebral invasive mycosis: occurrence in immunocompetent individuals. Eur J Radiol . 1995;20:151–5. 4. Veress B, Malik OA, Tayeb AA, El Daoud S, El Mahgoub S, El Hassan AM. Further observations on the primary paranasal Aspergillus granuloma in Sudan. Am J Trop Med Hyg . 1973;22:765–72. 5. Gillespie MB, O’Malley Jr BW, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in immunocompromised host. Arch Otolaryngol Head Neck Surg. 1998;124(5): 520–6. 6. Demuri GP, Wald ER. Sinusitis. In: Mandell GL, Benett JE, Dolin R, editors. Principles and practice of infectious diseases, vol. 2. 7th ed. Philadelphia: Elsevier Churchill Livingstone; 2010. p. 842.

34. Thank you