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CLINICAL AND DIAGNOSTIC APPROCHES TO THE
RHINOCEREBRAL MUCORMYCOSIS
PARW8
Introduction
• Mucormycosis is life-threatening infection caused by fungi belonging to the subphylum
Mucormycotina, order Mucorales .
• Furbinger described the first case in 1876 in Germany in patient lung who died of cancer
• In course of time, the case identification has increased and reported. Now in 2021, mucormycosis again
has come to the limelight, to some extent, because of its association with severe COVID-19 infection,
immunosuppressive therapies, and uncontrolled diabetes mellitus.
• Multiple variant of species are there, in that Rhizopus oryzae is the most commonly reported single
species . Other medically important Rhizopus species include Rhizopus rhizopodiformis and Rhizopus
microsporus. After genus Rhizopus, the genus Mucor and Lichtheimia is the most commonly
reported
Sample Footer Text 2
Clinical features
The infection is characterized by rapid tissue destruction, advancement across tissue planes
• Generally: Fever, and Malaise
• Sinus:
 Nasal congestion
 Dark blood-tinged rhinorrhea or epistaxis
 Sinus tenderness
• Orbital symptoms:
 Retro-orbital headache
 Advanced infection may present as facial or periorbital swelling and numbness, blurred vision,
lacrimation, chemosis, diplopia, proptosis, and loss of vision in the affected eye
 Infection also can extend to adjacent bone and ultimately to the base of the skull
 Orbital apex syndrome is an ominous complication of mucormycosis of the orbit
Sample Footer Text 3
• Cerebral involvment:
 Vision loss,
 Ophthalmoplegia,
 Corneal anesthesia
 facial anhidrosis may indicate cavernous sinus thrombosis
 Internal carotid artery thrombosis
 Contralateral hemiplegia
• Radiographic findings
 Opacification of the paranasal sinuses,
 Sinus fluid levels, sinus mucosal thickening
 Bone destruction
 Ill defined radiolucency , moth eaten appearance (Osteomyelitis)
Sample Footer Text 4
• Critical factors involved in mucormycosis are high iron and glucose level in blood,qualitative
and quantitative defects in phagocytosis
• The excessive glycosylation of proteins such as transferrin and ferritin, owing to poorly
controlled diabetes, results in decreased affinity of these proteins to bind iron, making that
important element available for Mucorales
• Similarly, lower blood pH due to ketoacidosis and other forms of acidosis compromises the
affinity of transferrin to bind iron.
• FTR1 iron permease gene responsible for iron utlisation in mucorales
Sample Footer Text 5
Pathogenesis
• Phagocytic defect
• In immunocompromised individual qualitative and quantitative defect in phagocytes
example
• Both hyperglycemia and acidosis are known to impair chemotaxis and the killing activity of
phagocytic cells against Mucorales by impairing oxidative and non oxidative mechanisms .
• Likewise, corticosteroids impair migration, ingestion and phagolysosome fusion in
human macrophages
• In mucormycosis diffuse necrosis caused by altered blood coagulation and thrombosis .
Sample Footer Text 6
Pathogenesis
Sample Footer Text 2/8/20XX 7
Inhalation of sporangiospores
Deposition on nasal turbinate , paranasal sinuses & cause
allergic sinusitis
CotH protein present on mucorales bind with GRP78 receptor
present on endothelium
Endothelial invasion of mucorales and endothelial damage
Sample Footer Text 2/8/20XX 8
Endothelial damage
Trypsin like protease Leukocytes elastase
Fibrin precipitation
Factor XIII activation
Thrombi formation
Thrombosis & necrosis
Diagnostic approaches
i. Direct microscopic examination
Cytology
Histopathological
ii. Culture methods
iii. Serology
iv. Molecular methods
Sample Footer Text 2/8/20XX 9
• Cytology
• KOH wet mounts with direct microscopy .
• KOH when supplemented with fluorescent brighteners
such as Blankophor and Calcofluor white,
enhance the visualization of the characteristic
fungal hyphae but requires a fluorescent microscope
Sample Footer Text 2/8/20XX 10
• Histopathology
• Angioinvasion and perineural invasion,
• Necrosis and thrombosis
• Neutrophillic and granulomatous inflammation
• Hyphae of the mucorales are broad (6 to 16 μm),
ribbon-like and irregularly shaped, non-septate
(coenocytic) or sparsely septate, with branches
often arising non-dichotomously in “right angles.”
Sample Footer Text 11
• Culture
• All Mucorales grow rapidly (3–5 days) on most fungal culture media, such as Sabouraud
agar and potato dextrose agar incubated at 25–30°C.
Sample Footer Text 2/8/20XX 12
• Serology
• Enzyme-linked immunosorbent assays (ELISA),
• Immunoblot assays(western blot)
• Limitation are poor specificity and sensitivity, cross-reactivity
with candida and aspergillus species or showed a lack of clinical validation.
• Molecular methods
• PCRs
• RFLP
• DNA sequencing can be used for identifying Internal transcribed spacer (ITS) reggion
Sample Footer Text 2/8/20XX 13
THANK YOU!!!!!
14

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rheino mucormycosis pathology

  • 1. CLINICAL AND DIAGNOSTIC APPROCHES TO THE RHINOCEREBRAL MUCORMYCOSIS PARW8
  • 2. Introduction • Mucormycosis is life-threatening infection caused by fungi belonging to the subphylum Mucormycotina, order Mucorales . • Furbinger described the first case in 1876 in Germany in patient lung who died of cancer • In course of time, the case identification has increased and reported. Now in 2021, mucormycosis again has come to the limelight, to some extent, because of its association with severe COVID-19 infection, immunosuppressive therapies, and uncontrolled diabetes mellitus. • Multiple variant of species are there, in that Rhizopus oryzae is the most commonly reported single species . Other medically important Rhizopus species include Rhizopus rhizopodiformis and Rhizopus microsporus. After genus Rhizopus, the genus Mucor and Lichtheimia is the most commonly reported Sample Footer Text 2
  • 3. Clinical features The infection is characterized by rapid tissue destruction, advancement across tissue planes • Generally: Fever, and Malaise • Sinus:  Nasal congestion  Dark blood-tinged rhinorrhea or epistaxis  Sinus tenderness • Orbital symptoms:  Retro-orbital headache  Advanced infection may present as facial or periorbital swelling and numbness, blurred vision, lacrimation, chemosis, diplopia, proptosis, and loss of vision in the affected eye  Infection also can extend to adjacent bone and ultimately to the base of the skull  Orbital apex syndrome is an ominous complication of mucormycosis of the orbit Sample Footer Text 3
  • 4. • Cerebral involvment:  Vision loss,  Ophthalmoplegia,  Corneal anesthesia  facial anhidrosis may indicate cavernous sinus thrombosis  Internal carotid artery thrombosis  Contralateral hemiplegia • Radiographic findings  Opacification of the paranasal sinuses,  Sinus fluid levels, sinus mucosal thickening  Bone destruction  Ill defined radiolucency , moth eaten appearance (Osteomyelitis) Sample Footer Text 4
  • 5. • Critical factors involved in mucormycosis are high iron and glucose level in blood,qualitative and quantitative defects in phagocytosis • The excessive glycosylation of proteins such as transferrin and ferritin, owing to poorly controlled diabetes, results in decreased affinity of these proteins to bind iron, making that important element available for Mucorales • Similarly, lower blood pH due to ketoacidosis and other forms of acidosis compromises the affinity of transferrin to bind iron. • FTR1 iron permease gene responsible for iron utlisation in mucorales Sample Footer Text 5 Pathogenesis
  • 6. • Phagocytic defect • In immunocompromised individual qualitative and quantitative defect in phagocytes example • Both hyperglycemia and acidosis are known to impair chemotaxis and the killing activity of phagocytic cells against Mucorales by impairing oxidative and non oxidative mechanisms . • Likewise, corticosteroids impair migration, ingestion and phagolysosome fusion in human macrophages • In mucormycosis diffuse necrosis caused by altered blood coagulation and thrombosis . Sample Footer Text 6
  • 7. Pathogenesis Sample Footer Text 2/8/20XX 7 Inhalation of sporangiospores Deposition on nasal turbinate , paranasal sinuses & cause allergic sinusitis CotH protein present on mucorales bind with GRP78 receptor present on endothelium Endothelial invasion of mucorales and endothelial damage
  • 8. Sample Footer Text 2/8/20XX 8 Endothelial damage Trypsin like protease Leukocytes elastase Fibrin precipitation Factor XIII activation Thrombi formation Thrombosis & necrosis
  • 9. Diagnostic approaches i. Direct microscopic examination Cytology Histopathological ii. Culture methods iii. Serology iv. Molecular methods Sample Footer Text 2/8/20XX 9
  • 10. • Cytology • KOH wet mounts with direct microscopy . • KOH when supplemented with fluorescent brighteners such as Blankophor and Calcofluor white, enhance the visualization of the characteristic fungal hyphae but requires a fluorescent microscope Sample Footer Text 2/8/20XX 10
  • 11. • Histopathology • Angioinvasion and perineural invasion, • Necrosis and thrombosis • Neutrophillic and granulomatous inflammation • Hyphae of the mucorales are broad (6 to 16 μm), ribbon-like and irregularly shaped, non-septate (coenocytic) or sparsely septate, with branches often arising non-dichotomously in “right angles.” Sample Footer Text 11
  • 12. • Culture • All Mucorales grow rapidly (3–5 days) on most fungal culture media, such as Sabouraud agar and potato dextrose agar incubated at 25–30°C. Sample Footer Text 2/8/20XX 12
  • 13. • Serology • Enzyme-linked immunosorbent assays (ELISA), • Immunoblot assays(western blot) • Limitation are poor specificity and sensitivity, cross-reactivity with candida and aspergillus species or showed a lack of clinical validation. • Molecular methods • PCRs • RFLP • DNA sequencing can be used for identifying Internal transcribed spacer (ITS) reggion Sample Footer Text 2/8/20XX 13