Invasive Skull Base Mucormycosis (eBook)

New Perspectives

Narayanan Janakiram, Sampath Prasad Rao (Herausgeber)

eBook Download: EPUB

2024 | 1. Auflage
326 Seiten
Thieme Medical Publishers (Verlag)
978-93-95390-35-4 (ISBN)

Infos

<p>COVID-associated mucormycosis (CAM) considered to be an 'endemic within a pandemic' affected the Indian subcontinent during the second wave of COVID-19 pandemic. This book deals with all the aspects of rhino-orbito-cerebral mucormycosis (ROCM) in its entirety, and it is unparalleled in the respect that it is wholly based on Dr. Narayanan Janakiram's clinical and surgical experience. This book contains in-depth details of surgical aspects of management of ROCM, and the authors stress on central skull base clearance in ROCM to ensure complete recovery of the patients. It describes a step-by-step approach to the management of ROCM, utilizing the unique staging system proposed by Dr. Janakiram. It gives clear-cut surgical approaches for each stage with the help of clinical scenarios and stresses on endoscopic approaches for all cases, except in advanced stages where combined approach is advised.</p> <p><strong>This book is authored by some of the pioneers in this subject, and has the following salient features:</strong></p> <ul> <li>Systematic organization of contents and wide coverage of each topic, from the basic surgeries to the most advanced in skull base surgery.</li> <li>Clinical coverage of all stages of ROCM with management as per the Janakiram staging for post- COVID-19 mucormycosis (JSPM) classification.</li> <li>Vivid illustrations and high-definition pictures and videos for in-depth explanation of surgical steps.</li> </ul> <p>This print book includes complimentary access to a digital copy on <a href='https://medone.thieme.com/'>https://medone.thieme.com</a>.</p> <p><strong>Publisher's Note: Products purchased from Third Party sellers are not guaranteed by the publisher for quality, authenticity, or access to any online entitlements included with the product</strong></p>

Textauszug

1

Mucormycosis in Pre-COVID-19 Era

Introduction

Pathogenesis

Risk Factors

Chapter 1

Mucormycosis in Pre-COVID-19 Era

Sampath Chandra Prasad Rao, Ananth Chintapalli, and Sunena Saju

Introduction

Zygomycetes class of fungi comprises of the order Mucorales and Entomophthorales. The Entomophthorales are rare cause of subcutaneous and new cutaneous infection known as entomophthoramycosis. The order Mucorales comprise of 55 genera with 261 species.

Not all 261 species cause human infection. Just a subset of this order, about 38 species, have been proved to cause infection in human being (Table 1.1).

Table 1.1 Current nomenclature of medically important mucoralean species according to updated taxonomy1

Current species names

Previous names/synonyms

Lichtheimia corymbifera

Absidia corymbifera, Mycocladus corymbifer

Lichtheimia ornata

Absidia ornata

Lichtheimia ramosa

Absidia ramosa, Mycocladus ramosus

Mucor ardhlaengiktus

Mucor ellipsoideus, Mucor circinelloides f. circinelloides

Mucor circinelloides

Rhizomucor regularior, Rhizomucor variabilis var. regularior

Mucor griseocyanus

Mucor circinelloides f. griseocyanus

Mucor irregularis

Rhizomucor variabilis

Mucor janssenii

Mucor circinelloides f. janssenii

Mucor lusitanicus

Mucor circinelloides f. lusitanicus

Rhizopus arrhizus (incl. var. delemar)

Rhizopus oryzae

Rhizopus microsporus

Rhizopus microsporus var. azygosporus, var. chinensis, var. oligosporus, var. rhizopodiformis, var. tuberosus

In 1876, Furbinger from Germany described fungal hyphae and few sporangia within hemorrhagic infarct in the lungs of a patient who died of cancer.2 This is considered the first ever documented case of mucormycosis. Arnold Paltauf in 1885 published the first case of disseminated mucormycosis coma which he named mycosis mucorina.3 In 1943, a case series of three fatal cases of advanced rhinocerebral mucormycosis in patients with diabetic ketoacidosis (DKA) were reported where typical findings like proptosis and ophthalmoplegia were described.4 It was only in 1955, after the development of amphotericin, the first cured case of mucormycosis was reported.5

Incidence of the disease went up from zero over the years and now is considered the third most common opportunistic fungal infection after candidiasis and aspergillosis.6 Increase in incidence of mucormycosis was documented well in literature but determination of exact incidence was a dilemma because population-based studies would vary in time period, population definition, and diagnostic parameters. Rising trend of mucormycosis in India is well documented in literature by various studies like by Chakrabarti et al. In their study, data from three consecutive studies from a single center reflected an incidence of 12.9 cases per year in the first decade, 35.6 cases per year over a period of 5 years, and 50 cases per year for 18 months.7–9 Similar rising trend was shown in a population-based study by Bitar et al in France between 1997 and 2006 and by Saegeman et al from Belgium in 2010.10,11 An alarming shift in mucormycosis cases from community acquired to nosocomial infection in susceptible host is also noted.12 Various studies like those by Mitchell et al and Verweij et al discuss the incidence of mucormycosis due to the use of contaminated wooden tongue depressor in preterm neonates and contaminated wooden applicator used to mix drugs in immunocompromised patients, respectively.13,14 A clear understanding of pathogenesis is important and inevitable in preventing and treating mucormycosis.

Pathogenesis

Pathogenesis of mucormycosis begins with inhalation or ingestion of sporangiospores, or inoculation of conidia via puncture wounds or trauma.15,16 The pathogenesis can be discussed under the following subheadings:

•Host defense mechanisms.

•Role of iron in pathogenesis.

•Fungal endothelial interactions.

Host Defense Mechanisms

Mucorales need to evade host defense mechanism, invade vascular system, and scavenge host immune system for growth and to cause disease.

In a normal healthy individual (host), primary defense mechanism against Mucorales includes:

•Specialized iron binding protein sequestering serum iron from organism.

•Endothelial cells which regulate vascular tone and permeability.

•Circulating mononuclear and polymorphonuclear (PMN) phagocytes which generate oxidative metabolites and cationic peptides (defensins).

•Neutrophils which on exposure to Mucorales upregulate expression of toll-like receptor 2 and rapidly induce NF-kB pathway related genes.17

Any condition resulting in imbalance of the above defense system can make an individual prone to mucormycosis like malignant hematological disease with or without stem cell transplantation, neutropenia, diabetes mellitus (DM) poorly controlled with or without DKA, iron overload, and major trauma.

Role of Iron in Pathogenesis

Iron plays a crucial role in the pathogenesis of mucormycosis. Mucorales have multiple pathways to acquire iron from the host. In the first mechanism, in patients with DKA or any state of systemic acidosis the available iron level in serum is high predisposing the individual to mucormycosis. This is because acidosis per se disrupts the capacity of transferrin to bind iron.

Second, an increased incidence of invasive mycosis is noted in patients with iron overload and patients on treatment with iron chelator deferoxamine. Fungi can obtain iron from the host with high affinity and permit low molecular weight iron chelator.18,19

Rhizopus species utilizes deferoxamine as a siderophore for acquiring iron from the host. A few species of Rhizopus can accumulate greater amounts of iron supplied by deferoxamine than Aspergillus fumigatus and Candida albicans.

There is a linear correlation between iron uptake by Rhizopus and its growth in serum.20 The latest iron chelators like deferiprone and deferasirox do not have siderophore activity. Fungi has high affinity iron permease which contain redundant surface reductases that reduce ferric into the soluble ferrous form. The protein complex comprising of a multicopper oxidase and ferrous permease captures the reduced ferrous iron.19

Rhizopus is also known to secrete rhizoferrin, a siderophore which supplies iron through an energy-dependent receptor-mediated process.21 Rhizoferrin lacks ability to take iron from serum, and the organism adapts to use of xenosiderophore like desferoxamine to obtain iron more efficiently. The third mechanism adopted by fungi to obtain iron is through the use of heme. The Rhizopus oryzae homologues of heme oxygenase enable it to obtain iron from lost hemoglobin which explains the angioinvasive nature of R. oryzae. High affinity iron permease gene (FTR1) in R. oryzae facilitates intracellular heme uptake by acting as cytoplasmic membrane permease, followed by heme oxygenase which degrade heme and release ferric iron. Sre A, a transcriptional regulator gene, and genes encoding for two ferritin orthologues for storage of iron, are other genes likely involved in the iron uptake mechanism of R. oryzae.22

Fungal Endothelial Interactions

R. oryzae strains adhere to type IV collagens and extracellular matrix laminin. Recently, GRP78 glucose regulated protein was identified to act as a receptor that mediates penetration through and damage of endothelial cells by Mucorales. GRP78 is also known as BiP/HSPAS member of HSP70 family in endoplasmic reticulum. It functions as a cellular chaperone protein, and recent studies report translocation of a fraction of GRP78 to cell surface.23

It is also interesting to find that along with elevated levels of glucose and iron, there is also enhanced expression of GRP78 surface protein which result in penetration through and damage of endothelial cells by Mucorales.

Other putative virulence factors are:

•Circulatory mononuclear and PMN lymphocytes are a major line of host defense which in presence of hyperglycemia and low pH is found to be dysfunctional.24 They have impaired chemotaxis and defective intracellular killing by both oxidative and nonoxidative24 mechanisms.

•In a study by Waldorf et al, they describe how critical it is for inhaled...

Produkt-Details

• Erscheint lt. Verlag: 10.1.2024
• Zusatzinfo: Beilage: Videos
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► HNO-Heilkunde
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Pneumologie
• Schlagworte: Endoscopic sinus surgery • Maxillectomy • Orbital exenteration • Rhinectomy • Surgical debridement
• ISBN-10: 93-95390-35-2 / 9395390352
• ISBN-13: 978-93-95390-35-4 / 9789395390354