Original Article Chronic subdural hematoma Singh et

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secretions from outer one-third of the external auditory canal ... forms a physiological barrier between the external environment and deeper part ... sweat glands.
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Vol 15 | April-June 2018 | Issue 2 | Pages 49-120

Original Article

Review Article

Original Article

Chronic subdural hematoma

Chondrocalcinosis

Drug sensitivity of urinary Candida sp in neurosciences ICU

Singh et al

Gupta et al

Rath et al

Review Article

Antimicrobial Properties of Human Cerumen Santosh Kumar Swain, Mahesh Chandra Sahu1, Priyanka Debta2, Manash Ranjan Baisakh3 Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University (Deemed to be), 1Medical Research Laboratories, IMS and SUM Hospital, Siksha “O” Anusandhan University (Deemed to be), 2Department of Oral Pathology and Microbiology, IDS and SUM Hospital, Siksha “O” Anusandhan University (Deemed to be), 3Department of Pathology, Apollo Hospital, Bhubaneswar, Odisha, India

Abstract In daily clinical practice, clinicians and otolaryngologists often confront with cerumen or earwax. Cerumen is formed by sebaceous glands and ceruminous glands at the outer one‑third of the human external auditory canal and creates an acidic coat which aids in the prevention of infections of the external auditory canal. The cerumen forms a physiological barrier between the external environment and deeper part of the ear. The chemical composition of the cerumen has been thought to be of antibacterial and antifungal properties, although it is under controversy. Other than antibacterial and antifungal activities, it also protects the eardrum by acting as a physical barrier. Cerumen cleaning is not advisable unless it is causing symptoms such as otalgia or hearing loss. A large percentage of people believe in self‑cleaning of the ear canal with different objects, which is really harmful, so they should be counseled against the habit of self‑cleaning of the external auditory canal. Keywords: Antibacterial, antifungal, antimicrobial effect, cerumen

Introduction Cerumen or earwax formation at the ear canal is a normal physiologic process. Cerumen or earwax is formed by sebaceous glands, ceruminous glands, and apocrine glands, which are present at the outer one‑third of the human external auditory canal and creates an acidic coat which aids in the prevention of infections of the external auditory canal.[1] The function of the cerumen to prevent the ear canal against the invasion of microorganisms has long been a subject of controversy. Lack of earwax may cause infection as it serves antimicrobial property by physiological protection of ear canal, creating a low pH and inhospitable atmosphere for pathogens and creating antimicrobial substance such as lysozyme, so its absence leads to ear canal‑susceptible infections.[2] Earwax or cerumen is a naturally occurring substance in the external auditory canal which cleans, protects, and lubricates the ear canal. Cerumen or earwax is a common cause for conductive hearing loss and sometimes presents with tinnitus, irritation, otalgia, and vertigo.[3] In most of the cases, there are no symptoms at all. Cerumen is formed from glandular secretions from outer one‑third of the external auditory canal and exfoliated squamous epithelium, which migrate out of the ear canal due to jaw movement.[4] Impacted wax occurs due to the failure of self‑cleaning mechanism in the ear canal. The Access this article online Quick Response Code:

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function of the cerumen/earwax against the microorganisms invading the ear has long been a subject of controversy. The cerumen in the external auditory canal does not require removal unless it causes any problem. This review article reviews the antibacterial and antifungal properties of the cerumen and its clinical utility. This review article presents a baseline from where further prospective trials can be designed and help as a spur for further research in this commonly encountered clinical entity where not many studies are done.

Methodology For searching the published article, we conducted an electronic search of the Medline, SCOPUS, and PubMed databases. The search term in the database included earwax, cerumen, and antimicrobial property. The abstracts of the published article are identified by this search method and other articles were identified manually from the citations. This review article reviews the antibacterial and antifungal properties of the cerumen and its clinical utility. This review article presents a Address for correspondence: Prof. Santosh Kumar Swain, Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University (Deemed to be), Kalinga Nagar, Bhubaneswar ‑ 751 003, Odisha, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected]

DOI: 10.4103/am.am_69_18

© 2018 Apollo Medicine | Published by Wolters Kluwer - Medknow

How to cite this article: Swain SK, Sahu MC, Debta P, Baisakh MR. Antimicrobial properties of human cerumen. Apollo Med 2018;15:197-200.

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baseline from where further prospective trials can be designed and help as a spur for further research in this commonly encountered clinical entity where not many studies are done.

Antimicrobial Properties of the Cerumen

Figure 1: Brownish wax extracted from the ear canal

Cerumen is a hydrophobic protective barrier in the external auditory canal. It shields the skin of the ear canal from water damage, trauma, foreign bodies, and infections. Cerumen also lubricates and cleans the ear canal, traps dusts, and repels water for entering inside the canal.[10] Cerumen also protects the middle ear against bacteria and fungus.[11] Hence, cerumen plays an important role biologically and clinically for host defense although it is relatively weak. Cerumen or earwax creates an acidic barrier in the external auditory canal which prevents infection.[1] There are many contradictory reports on the antibacterial activity of cerumen. The antibacterial nature of cerumen is based on the consideration that the high nutrients of cerumen which enable bacteria and fungi to grow, which is against the antibacterial property of the cerumen.[12] However, some hold a view that cerumen contains antimicrobial property which prevents infections at the external ear.[13] Cerumen is slightly acidic in nature, which discourages the growth of bacteria and fungus in the moist and dark environment of the external auditory canal. It is almost impossible to avoid infection at the ear canal without the presence of cerumen.[14]  An enzyme called lysozyme present in the cerumen, so without presence of earwax make the ear canal vulnerable for infection. It is expected that if cerumen provides immunity, its composition should alter in response to infection and exposure to bacteria and should induce antibacterial components of the cerumen at the ear canal. However, in otitis externa, cerumen does not provide antibacterial polyunsaturated fatty acids than without any infection at the external auditory canal.[15] Cerumen inhibits the growth of bacteria and fungi at various concentrations. Few studies demonstrated the antibacterial and antifungal properties which show its protective role toward the external auditory canal. One study also proved the antibacterial property of earwax in some mammals.[16] One study shows the mycobacterial effect of earwax, which is consistent with our study.[5] The human earwax shows more antibacterial property in comparison to the antifungal property and this may be due to some protective mechanism of the fungus, leading to lower inhibition of fungal growth as compared to bacteria. In one study, authors demonstrated the bactericidal properties of earwax on Pseudomonas aeruginosa.[5] Some other studies reported that cerumen has no bactericidal effect on P. aeruginosa.[17] Cerumen inhibits the growth of Escherichia coli, which is consistent with other study,[18] whereas one study shown insignificant bactericidal effect and stated that E. coli is not a normal commensal bacterium in the external auditory canal and so may not be considered by the immune system of the ear canal.[17] Human cerumen has antibacterial and antifungal properties against common bacteria and fungi as done in a study, which was in the following order: E. coli > P. aeruginosa > Staphylococcus aureus > Candida albicans.[13] As cerumen is secreted in the external auditory canal, it often does not come in contact with bacteria in middle‑ear infection. Immunohistochemical studies of cerumen show that antibody‑mediated immune reactions rather that

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Composition of the Cerumen Cerumen or earwax [Figure 1] is a mixture of desquamated keratinocyte from the outer part of the external auditory canal and secretions from sebaceous glands along with apocrine sweat glands. It creates a gray‑brown‑to‑grayish‑black‑colored tick substance and deposited at the external auditory canal. Glandular secretions coming from the hair follicles of the external auditory canal also mix with the cerumen and make it a sticky substance which is known as cerumen.[5] Cerumen is present in 10% of all the pediatric age group and up to 57% of the older persons.[6] Cerumen or earwax is a yellow‑brownish waxy substance and protects the skin of the ear canal from water and infection. It prevents infection by trapping the microorganisms, sweat, dirts, dead skin cells, oil, and hair. The outer ear canal is lined with hairs called cilia which push the offending particle toward the ear opening where the wax can be washed off. There are two different forms of the human cerumen and these are dry and wet which are often associated with race and decided by two autosomal alleles. The wet earwax is light or dark brown and sticky in nature, possessing high concentration of lipid and pigment granules. The dry allele is most often seen in mongoloid people of Asia and in American Indians, whereas the wet variety is common in Caucasian and Negro populations. Cerumen consists of amino acids, neurostearic acid, cerotic acid, triglyceride, cholesterol, hexone bases, lysozyme, immunoglobulin, glycopeptides, copper, and others.[7] The dry earwax is gray or tan and brittle and possesses less lipid and pigment granules. Dry wax contains approximately 20% lipid in comparison to 50% in the wet wax.[8] Cerumen or earwax is formed from a combination of glandular secretion of the lateral one‑third of the external auditory canal and exfoliated squamous epithelium, which migrates of the external auditory canal by self‑cleaning mechanism during jaw movement.[9]

Swain, et al.: Antimicrobial properties of human cerumen

earwax protect the ear canal from infective microorganisms. The epidermis and dermis of the skin lining the external auditory canal contain ceruminous and sebaceous glands as well as piliary follicles which are capable of activating local immunity by immunoglobulin (Ig) A and IgG.[19] However, it needs more studies to confirm the nature of host defense in this anatomical location. There are many controversial reports in medical literature explained on the basis of culture media, methodology, and virulence of microorganisms. Microorganisms such as S. aureus, P. aeruginosa, and C. albicans are common microorganisms that cause otitis externa, whereas their presence in cerumen in the external auditory canal reduces the chance of infection.[5]

Antibacterial Properties of the Cerumen There is little known about the chemical composition of the human cerumen and its antimicrobial role. Several proteins are found in the cerumen such as antimicrobial peptides of human beta defensin (hBD) 1‑3, lactoferrin, LL‑37, bactericidal permeability‑increasing (BPI), hSLPI, and HNP1‑3. All have some role to prevent bacteria and fungi those causing infections at the external auditory canal. If this local defense system gets disturbed, infections of ear canal occur.[20] These proteins are described below.

Antimicrobial peptides

There is little known about the chemical composition of the human cerumen regarding the antimicrobial peptides. Different antimicrobial peptides from cerumen are hBD1‑3, lactoferrin, LL‑37, BPI, hSLPI, and HNP1‑3. The antibacterial peptides in cerumen prevent bacteria and fungi from causing infections in the ear canal.[20]

Human beta defensins

The hBD is named after beta sheet structure which is stabilized by intramolecular disulfide bonds. It has strong antimicrobial property on Gram‑negative bacteria.[21] hBD2 has a strong antimicrobial effect on E.  coli, P. aeruginosa, and C. albicans, whereas a weak effect on S. aureus. hBD3 induced by tumor necrosis factor‑alpha attaches with P. aeruginosa or S. aureus, for example, keratinocytes.[22] hBD3 has antimicrobial properties against S. aureus including methicillin‑resistant S. aureus, Streptococcus pyogenes, P. aeruginosa, E. coli, Haemophilus influenzae, C. albicans, and vancomycin‑resistant Enterococcus faecium.[23]

Human LL‑37

Human LL‑37 (LL‑37) is a 37‑aminoacid long C terminus which has active antimicrobial component of the human cathelicidin antimicrobial peptide 18 (Hcap‑18).  This protein is expressed on leukocytes like neutrophils, monocytes, B‑cells and T‑cells), epithelial cells like skin, respiratory tract and gastrointestinal tract which is secreted into the wound and surface fluid.[24] It has antibacterial activity against Gram‑positive and Gram‑negative bacteria. LL‑37 also plays a role in angiogenesis, cancer development, and neutralization Apollo Medicine  ¦  Volume 15 ¦ Issue 4 ¦ October-December 2018

of bacterial lipopolysaccharide and chemotactic for monocytes, neutrophils, and CD4 T‑lymphocytes.[25]

Human lactoferrin

Human lactoferrin can be seen in saliva, tears, milk, nasal mucosa, neutrophils, and granulocytes.[26] The antibacterial spectrum of human lactoferrin includes Streptococcus mutans, Vibrio cholera, E. coli, Actinobacillus actinomycetemcomitans, Enterobacteriaceae, Legionella pneumophila, C. albicans, and P. aeruginosa.[20]

Human secretory leukoprotease inhibitor

Human secretory leukoprotease inhibitor (hSLPI) is a heavy protein particle expressed on macrophages, epithelial cells, and neutrophils. It has antimicrobial properties against Gram‑positive and Gram‑negative bacteria at the N‑terminal domain of the protein. hSLPI blocks the viral DNA synthesis and inhibits human deficiency virus.[27]

Human bactericidal permeability‑increasing protein

This is a single‑chain cationic protein which is divided by proteolysis into two segments with antibiotic‑ and endotoxin‑neutralizing functions in the N‑terminal segment.[28] BPI is mainly seen in the granules of neutrophils, dermal fibroblasts, and excretory lacrimal gland and often selective to the Gram‑negative bacteria.[29] It has significant protective effect in meningococcal infection.[30] Cerumen has a protective antimicrobial potency, and cleaning the ear canal by rinsing with water leads to a complete elimination of the cerumen, which leads to alteration of the physiological pH. This explains why otitis externa occur after cleaning the ear canal with water. Removal of the earwax or cerumen manually by a hook and leaving some wax in the ear canal would maintain the physiological antimicrobial potency of the ear canal.

Conclusion Variable results have been obtained from different authors regarding the antimicrobial nature of the cerumen. However, most of the authors strongly believe in the antimicrobial nature of the cerumen which does inhibit the microbial growth. Cerumen of the human has both bactericidal and fungicidal properties. Apart from being a physical barrier of cerumen in the ear canal, it also acts as a protective agent against bacteria and fungi. This may provide prevention or eradication of the infections of the external ear such as otitis externa. Hence, routine wax removal from the ear canal should be discouraged unless it is impacted leading to hearing loss or earache. An extensive study should be done to reveal the bactericidal and fungicidal roles of cerumen or earwax. The different outcome among documented literatures may be due to the fact that earwax from different persons varies in it composition and contents of inhibitory factors due to the different genetic profile of the patients. Finally, since different levels of health‑care providers are involved in managing patients with cerumen or earwax impaction, they should have awareness about the antibacterial property of the cerumen. 199

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1. Campos A, Arias A, Betancor L, Rodríguez C, Hernández AM, López Aguado D, et al. Study of common aerobic flora of human cerumen. J Laryngol Otol 1998;112:613‑6. 2. Bojrab DI, Bruderly T, Abdulrazzak Y. Otitis externa. Otolaryngol Clin North Am 1996;29:761‑82. 3. Aung T, Mulley GP. Removal of ear wax. BMJ 2002;325:27. 4. Roland PS, Smith TL, Schwartz SR, Rosenfeld RM, Ballachanda B, Earll JM, et al. Clinical practice guideline: Cerumen impaction. Otolaryngol Head Neck Surg 2008;139:S1‑S21. 5. Lum CL, Jeyanthi S, Prepageran N, Vadivelu J, Raman R. Antibacterial and antifungal properties of human cerumen. J Laryngol Otol 2009;123:375‑8. 6. Roeser RJ, Ballachanda BB. Physiology, pathophysiology, and anthropology/epidemiology of human earcanal secretions. J Am Acad Audiol 1997;8:391‑400. 7. Yassin A, Mostafa MA, Moawad MK. Cerumen and its micro‑chemical analysis. J Laryngol Otol 1966;80:933‑8. 8. Tomita H, Yamada K, Ghadami M, Ogura T, Yanai Y, Nakatomi K, et al. Mapping of the wet/dry earwax locus to the pericentromeric region of chromosome 16. Lancet 2002;359:2000‑2. 9. Saxby C, Williams R, Hickey S. Finding the most effective cerumenolytic. J Laryngol Otol 2013;127:1067‑70. 10. Shapiro J, Clarke C. Earwax woes. Harv Health Lett 2002;27:8. 11. Lindsey D. It’s time to stop washing out ears! Am J Emerg Med 1991;9:297. 12. Campos A, Betancor L, Arias A, Rodríguez C, Hernández AM, López Aguado D, et al. Influence of human wet cerumen on the growth of common and pathogenic bacteria of the ear. J Laryngol Otol 2000;114:925‑9. 13. Gupta S, Singh R, Kosaraju K, Bairy I, Ramaswamy B. A study of antibacterial and antifungal properties of human cerumen. Indian Journal of Otology 2012;18:189. 14. Hyslop NE Jr. Ear wax and host defense. N Engl J Med 1971;284:1099‑100. 15. Osborne JE, Baty JD. Do patients with otitis externa produce biochemically different cerumen? Clin Otolaryngol Allied Sci 1990;15:59‑61. 16. Martinez Devesa P, Willis CM, Capper JW. External auditory canal pH in chronic otitis externa. Clinical Otolaryngology & Allied Sciences

2003;28:320-4. 17. Pata YS, Ozturk C, Akbas Y, Gorur K, Unal M, Ozcan C. Has cerumen a protective role in recurrent external otitis? Am J Otolaryngol 2003;24:209‑12. 18. Stone M, Fulghum RS. Bactericidal activity of wet cerumen. Ann Otol Rhinol Laryngol 1984;93:183‑6. 19. Sirigu P, Perra MT, Ferreli C, Maxia C, Turno F. Local immune response in the skin of the external auditory meatus: An immunohistochemical study. Microsc Res Tech 1997;38:329‑34. 20. Schwaab M, Gurr A, Neumann A, Dazert S, Minovi A. Human antimicrobial proteins in ear wax. Eur J Clin Microbiol Infect Dis 2011;30:997‑1004. 21. Schneider JJ, Unholzer A, Schaller M, Schäfer‑Korting M, Korting HC. Human defensins. J Mol Med (Berl) 2005;83:587‑95. 22. Harder J, Bartels J, Christophers E, Schroder JM. Isolation and characterization of human beta ‑defensin‑3, a novel human inducible peptide antibiotic. J Biol Chem 2001;276:5707‑13. 23. Sørensen OE, Cowland JB, Theilgaard‑Mönch K, Liu L, Ganz T, Borregaard N, et al. Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J Immunol 2003;170:5583‑9. 24. Wang Y, Walter G, Herting E, Agerberth B, Johansson J. Antibacterial activities of the cathelicidins prophenin (residues 62 to 79) and LL‑37 in the presence of a lung surfactant preparation. Antimicrob Agents Chemother 2004;48:2097‑100. 25. von Haussen J, Koczulla R, Shaykhiev R, Herr C, Pinkenburg O, Reimer D, et al. The host defence peptide LL‑37/hCAP‑18 is a growth factor for lung cancer cells. Lung Cancer 2008;59:12‑23. 26. Stenfors LE, Bye HM, Räisänen S. Immunocytochemical localization of lysozyme and lactoferrin attached to surface bacteria of the palatine tonsils during infectious mononucleosis. J Laryngol Otol 2002;116:264‑8. 27. Wahl SM, McNeely TB, Janoff EN, Shugars D, Worley P, Tucker C, et al. Secretory leukocyte protease inhibitor  (SLPI) in mucosal fluids inhibits HIV‑I. Oral Dis 1997;3 Suppl 1:S64‑9. 28. Reichel PH, Seemann C, Csernok E, Schröder JM, Müller A, Gross WL, et al. Bactericidal/permeability‑increasing protein is expressed by human dermal fibroblasts and upregulated by interleukin 4. Clin Diagn Lab Immunol 2003;10:473‑5. 29. Peuravuori H, Aho VV, Aho HJ, Collan Y, Saari KM. Bactericidal/permeability‑increasing protein in lacrimal gland and in tears of healthy subjects. Graefes Arch Clin Exp Ophthalmol 2006;244:143‑8. 30. von der Möhlen MA, Kimmings AN, Wedel NI, Mevissen ML, Jansen J, Friedmann N, et al. Inhibition of endotoxin‑induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/ permeability‑increasing protein. J Infect Dis 1995;172:144‑51.

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References