Mucormycosis pathophysiology: Difference between revisions
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* Neutrophils play a major part in destroying fungal hyphae, once spores germinate. Macrophages and monocytes may also play part in host defense mechanisms against fungi causing mucormycosis (specifically alveolar macrophages prevent germination of spores).<ref name="pmid2490078">{{cite journal |vauthors=Waldorf AR |title=Pulmonary defense mechanisms against opportunistic fungal pathogens |journal=Immunol. Ser. |volume=47 |issue= |pages=243–71 |year=1989 |pmid=2490078 |doi= |url=}}</ref> Consequently, mucormycosis develops exclusively in immunocompromised patients who lack these defense mechanisms. Hyperglycemia, acidosis and corticosteroid treatment have also been known to hinder immunity (specifically the actions of phagocytic cells), which also puts patients with diabetes and DKA at an increased risk of acquiring mucormycosis.<ref name="pmid16020690">{{cite journal |vauthors=Spellberg B, Edwards J, Ibrahim A |title=Novel perspectives on mucormycosis: pathophysiology, presentation, and management |journal=Clin. Microbiol. Rev. |volume=18 |issue=3 |pages=556–69 |year=2005 |pmid=16020690 |pmc=1195964 |doi=10.1128/CMR.18.3.556-569.2005 |url=}}</ref> | * Neutrophils play a major part in destroying fungal hyphae, once spores germinate. Macrophages and monocytes may also play part in host defense mechanisms against fungi causing mucormycosis (specifically alveolar macrophages prevent germination of spores).<ref name="pmid2490078">{{cite journal |vauthors=Waldorf AR |title=Pulmonary defense mechanisms against opportunistic fungal pathogens |journal=Immunol. Ser. |volume=47 |issue= |pages=243–71 |year=1989 |pmid=2490078 |doi= |url=}}</ref> Consequently, mucormycosis develops exclusively in immunocompromised patients who lack these defense mechanisms. Hyperglycemia, acidosis and corticosteroid treatment have also been known to hinder immunity (specifically the actions of phagocytic cells), which also puts patients with diabetes and DKA at an increased risk of acquiring mucormycosis.<ref name="pmid16020690">{{cite journal |vauthors=Spellberg B, Edwards J, Ibrahim A |title=Novel perspectives on mucormycosis: pathophysiology, presentation, and management |journal=Clin. Microbiol. Rev. |volume=18 |issue=3 |pages=556–69 |year=2005 |pmid=16020690 |pmc=1195964 |doi=10.1128/CMR.18.3.556-569.2005 |url=}}</ref> | ||
* In order to cause disease, the agents of mucormycosis must acquire from the host sufficient iron for growth, must evade host phagocytic defense mechanisms, and must access vasculature to disseminate. | * In order to cause disease, the agents of mucormycosis must acquire from the host sufficient iron for growth, must evade host phagocytic defense mechanisms, and must access vasculature to disseminate. | ||
* In immounocompromised hosts (including diabetics), iron is released from sequestering proteins making it available to fungi for growth within the body.<ref name="pmid6816646">{{cite journal |vauthors=Artis WM, Fountain JA, Delcher HK, Jones HE |title=A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability |journal=Diabetes |volume=31 |issue=12 |pages=1109–14 |year=1982 |pmid=6816646 |doi= |url=}}</ref> This process alongwith a reduced number of neutrophils and phagocytes leads to fungal proliferation.<ref name="pmid8486769">{{cite journal |vauthors=Boelaert JR, de Locht M, Van Cutsem J, Kerrels V, Cantinieaux B, Verdonck A, Van Landuyt HW, Schneider YJ |title=Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies |journal=J. Clin. Invest. |volume=91 |issue=5 |pages=1979–86 |year=1993 |pmid=8486769 |pmc=288195 |doi=10.1172/JCI116419 |url=}}</ref> Damage to the endothelial cells by fungi causing mucormycosis leads to vascular invasion, subsequent dissemination and tissue necrosis. R. oryzae spores but not germlings (i.e., pregerminated spores) have the ability to attach themselves to subendothelial matrix proteins including laminin and type IV collagen.<ref name="pmid8738422">{{cite journal |vauthors=Bouchara JP, Oumeziane NA, Lissitzky JC, Larcher G, Tronchin G, Chabasse D |title=Attachment of spores of the human pathogenic fungus Rhizopus oryzae to extracellular matrix components |journal=Eur. J. Cell Biol. |volume=70 |issue=1 |pages=76–83 |year=1996 |pmid=8738422 |doi= |url=}}</ref> <ref name="pmid15664916">{{cite journal |vauthors=Ibrahim AS, Spellberg B, Avanessian V, Fu Y, Edwards JE |title=Rhizopus oryzae adheres to, is phagocytosed by, and damages endothelial cells in vitro |journal=Infect. Immun. |volume=73 |issue=2 |pages=778–83 |year=2005 |pmid=15664916 |pmc=547117 |doi=10.1128/IAI.73.2.778-783.2005 |url=}}</ref> | * In immounocompromised hosts (including diabetics), iron is released from sequestering proteins making it available to fungi for growth within the body.<ref name="pmid6816646">{{cite journal |vauthors=Artis WM, Fountain JA, Delcher HK, Jones HE |title=A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability |journal=Diabetes |volume=31 |issue=12 |pages=1109–14 |year=1982 |pmid=6816646 |doi= |url=}}</ref> Acidic conditions decrease the iron-binding capacity, suggesting that acidosis per se disrupts the capacity of transferrin to bind iron, probably by proton-mediated displacement of ferric iron from transferrin.<ref name="pmid18978530">{{cite journal |vauthors=Ibrahim AS, Spellberg B, Edwards J |title=Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment |journal=Curr. Opin. Infect. Dis. |volume=21 |issue=6 |pages=620–5 |year=2008 |pmid=18978530 |pmc=2773686 |doi=10.1097/QCO.0b013e3283165fd1 |url=}}</ref> This process alongwith a reduced number of neutrophils and phagocytes leads to fungal proliferation.<ref name="pmid8486769">{{cite journal |vauthors=Boelaert JR, de Locht M, Van Cutsem J, Kerrels V, Cantinieaux B, Verdonck A, Van Landuyt HW, Schneider YJ |title=Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies |journal=J. Clin. Invest. |volume=91 |issue=5 |pages=1979–86 |year=1993 |pmid=8486769 |pmc=288195 |doi=10.1172/JCI116419 |url=}}</ref> Damage to the endothelial cells by fungi causing mucormycosis leads to vascular invasion, subsequent dissemination and tissue necrosis. R. oryzae spores but not germlings (i.e., pregerminated spores) have the ability to attach themselves to subendothelial matrix proteins including laminin and type IV collagen.<ref name="pmid8738422">{{cite journal |vauthors=Bouchara JP, Oumeziane NA, Lissitzky JC, Larcher G, Tronchin G, Chabasse D |title=Attachment of spores of the human pathogenic fungus Rhizopus oryzae to extracellular matrix components |journal=Eur. J. Cell Biol. |volume=70 |issue=1 |pages=76–83 |year=1996 |pmid=8738422 |doi= |url=}}</ref> <ref name="pmid15664916">{{cite journal |vauthors=Ibrahim AS, Spellberg B, Avanessian V, Fu Y, Edwards JE |title=Rhizopus oryzae adheres to, is phagocytosed by, and damages endothelial cells in vitro |journal=Infect. Immun. |volume=73 |issue=2 |pages=778–83 |year=2005 |pmid=15664916 |pmc=547117 |doi=10.1128/IAI.73.2.778-783.2005 |url=}}</ref> | ||
Revision as of 16:48, 24 May 2017
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Mucormycosis Microchapters |
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Diagnosis |
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Treatment |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]
Overview
Pathophysiology
- Fungi of the order Mucorales (class Zygomycetes) are causes of mucormycosis, a life-threatening fungal infection affecting immunocompromised hosts in either developing or industrialized countries. [1] [2] [3]
- Species belonging to the family Mucoraceae are isolated more frequently from patients with mucormycosis.
- Among the Mucoraceae, Rhizopus oryzae (Rhizopus arrhizus) is by far the most common cause of infection. Increasing cases of mucormycosis have been also reported due to infection with Cunninghamella spp. Inhalation of Mucorales sporangiospores by immunocompromised patients leads to development of pulmonary mucormycosis and eventual hematogenous dissemination.
- The skin represents a major barrier to fungi causing the disease. The agents of mucormycosis are typically incapable of penetrating intact skin. However, burns, traumatic disruption of the skin, and persistent maceration of skin enables the organism to penetrate into deeper tissues and cause infection. traumatic implantation of contaminated soil or water. In addition, contaminated surgical dressings and nonsterile adhesive tape have been shown to be the source of primary cutaneous mucormycosis
- Neutrophils play a major part in destroying fungal hyphae, once spores germinate. Macrophages and monocytes may also play part in host defense mechanisms against fungi causing mucormycosis (specifically alveolar macrophages prevent germination of spores).[4] Consequently, mucormycosis develops exclusively in immunocompromised patients who lack these defense mechanisms. Hyperglycemia, acidosis and corticosteroid treatment have also been known to hinder immunity (specifically the actions of phagocytic cells), which also puts patients with diabetes and DKA at an increased risk of acquiring mucormycosis.[2]
- In order to cause disease, the agents of mucormycosis must acquire from the host sufficient iron for growth, must evade host phagocytic defense mechanisms, and must access vasculature to disseminate.
- In immounocompromised hosts (including diabetics), iron is released from sequestering proteins making it available to fungi for growth within the body.[5] Acidic conditions decrease the iron-binding capacity, suggesting that acidosis per se disrupts the capacity of transferrin to bind iron, probably by proton-mediated displacement of ferric iron from transferrin.[6] This process alongwith a reduced number of neutrophils and phagocytes leads to fungal proliferation.[7] Damage to the endothelial cells by fungi causing mucormycosis leads to vascular invasion, subsequent dissemination and tissue necrosis. R. oryzae spores but not germlings (i.e., pregerminated spores) have the ability to attach themselves to subendothelial matrix proteins including laminin and type IV collagen.[8] [9]
References
- ↑ Ribes JA, Vanover-Sams CL, Baker DJ (2000). "Zygomycetes in human disease". Clin. Microbiol. Rev. 13 (2): 236–301. PMC 100153. PMID 10756000.
- ↑ 2.0 2.1 Spellberg B, Edwards J, Ibrahim A (2005). "Novel perspectives on mucormycosis: pathophysiology, presentation, and management". Clin. Microbiol. Rev. 18 (3): 556–69. doi:10.1128/CMR.18.3.556-569.2005. PMC 1195964. PMID 16020690.
- ↑ Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, Sein M, Sein T, Chiou CC, Chu JH, Kontoyiannis DP, Walsh TJ (2005). "Epidemiology and outcome of zygomycosis: a review of 929 reported cases". Clin. Infect. Dis. 41 (5): 634–53. doi:10.1086/432579. PMID 16080086.
- ↑ Waldorf AR (1989). "Pulmonary defense mechanisms against opportunistic fungal pathogens". Immunol. Ser. 47: 243–71. PMID 2490078.
- ↑ Artis WM, Fountain JA, Delcher HK, Jones HE (1982). "A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability". Diabetes. 31 (12): 1109–14. PMID 6816646.
- ↑ Ibrahim AS, Spellberg B, Edwards J (2008). "Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment". Curr. Opin. Infect. Dis. 21 (6): 620–5. doi:10.1097/QCO.0b013e3283165fd1. PMC 2773686. PMID 18978530.
- ↑ Boelaert JR, de Locht M, Van Cutsem J, Kerrels V, Cantinieaux B, Verdonck A, Van Landuyt HW, Schneider YJ (1993). "Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies". J. Clin. Invest. 91 (5): 1979–86. doi:10.1172/JCI116419. PMC 288195. PMID 8486769.
- ↑ Bouchara JP, Oumeziane NA, Lissitzky JC, Larcher G, Tronchin G, Chabasse D (1996). "Attachment of spores of the human pathogenic fungus Rhizopus oryzae to extracellular matrix components". Eur. J. Cell Biol. 70 (1): 76–83. PMID 8738422.
- ↑ Ibrahim AS, Spellberg B, Avanessian V, Fu Y, Edwards JE (2005). "Rhizopus oryzae adheres to, is phagocytosed by, and damages endothelial cells in vitro". Infect. Immun. 73 (2): 778–83. doi:10.1128/IAI.73.2.778-783.2005. PMC 547117. PMID 15664916.