REVIEW ARTICLE

James L. Gutmann, Vivian Manjarrés Focal infection: historical perspective intertwined with realistic contemporary thought

KEY WORDS dental infection, focal infection, social media, systemic disease and infection

ABSTRACT Historically the idea of possible links between dental infections and systemic diseases, as expressed by the medical profession, impacted clinical dentistry and millions of patients well over 100 years ago. However, a small core of dental professionals strove to retain teeth by scientifically refuting the concepts of focal infection and elective localisation; and slowly the conflagrations of these theories began to be reduced to but a few smoking embers. However, over the years these embers have continued to smoulder, and this once-thought-dead controversy has been revived, fanned by the winds of questionable science, charlatanism and the use of social media platforms to misinform both the profession and the public. This presentation will highlight a brief history of this dilemma, along with current thought from a realistic perspective.

Introduction: identifying the issue whole. The question at hand is root canal treat- ment or the need to have Controversies have existed in dentistry for dec- and its impact on the physical wellbeing of the ades. Some come and go, some occasionally raise patient … with the issue being somewhat reflective their biased head, while others linger ad nauseam. of the great bird in Greek mythology, the Phoenix Often these controversies are based on empiri- bird that dies in a show of flames and combus- cal beliefs or ‘stretches of the imagination’, so tion only to arise again from its ashes. Today the to speak, while others may have something of a Phoenix bird of has again arisen and scientific basis but may also have been exagger- threatens, through its tangled web of media and ated in an attempt to prove a point or promote or ill-educated purveyors of snake oil, to promote even condemn a product, technique, procedure tooth removal as opposed to retention through the or treatment. Since the late 1800s dentistry has use of contemporary endodontic procedures. In been caught in a series of controversies, especially fact, this newly arisen bird has even gone one step as it has related to the dentist’s role relative to the further in an attempt to link root canal proced- ’s role in the overall health of the patient. ures to the incidence of cancer in specific popula- One such issue, which began in the late 1800s is tions1. The film entitled ‘Root Cause’, claiming that beginning again to raise its tentacles of challenge root canals cause cancer, was originally shown on and confusion for both professionals and patients. NetFlix in early 2019; it has since been removed Presently this issue has begun, and not for the first due to the rejection of the ill-based concepts by time, to use social media and the film industry to many associations and agencies globally2-5. Often, further its cause and to reach the populace as a the self-proclaimed gurus of this controversy have

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never really undergone a reflective introspective of own experience they include not only pyorrhoea the origin of this controversy, or the very scientific alveolaris, but stomatitis and gingivitis of every basis of its flaws … or maybe its truths. Therefore, degree of severity- ‘erythematosa’, ‘pustulosa’, let’s examine the historical basis of what has been ‘ulcerosa’, ‘gangraenosa’, and, indeed every other referred to as the ‘’ and then form of trouble, dental and oral, producible by focus on contemporary perspectives. septic infection for which an appropriate adjective can be found. The list, moreover, includes in my experience others for which a suitable qualifying The historical roots of adjective cannot so readily be found, and which I the controversy may describe as ‘foul septic toothplate’ stomatitis, ‘bridge’ stomatitis, and ‘gold cap’ stomatitis; this In the late 1800s the issue of the human mouth as latter group, I venture to think, considerably on the a focus of infection, not only within the oral cavity, increase in this era of conservative dentistry and but also systemically was identified by Willoughby high professional mechanical skill”10. His medical D. Miller in 1888 and again in 18916,7. Miller’s perspective on this issue was enhanced in his text purpose was to “call attention to the various dis- entitled ‘Oral ’ in 190111 with subsequent eases, both local and general, which have been discussions on oral sepsis as a cause of disease in found to result from the action of microorganisms relation to general medicine in 190412. which have collected in the mouth, and to the vari- Ultimately it was Dr. Hunter’s message that ous channels through which these microorganisms he delivered in a speech at the McGill Faculty of or their waste products may obtain entrance to Medicine in Montreal on 3 October 1910, and parts of the body adjacent to or remote from the which was later published in both Lancet13 and mouth”. Previously, articles had been published Dental Cosmos14 that was the conflagration that in Germany, the United Kingdom, France and the set the concept of ‘focal infection’ ablaze; how- USA. Even prior to that, however, ancient medicine ever, this terminology has been purported to origi- had identified this potential relationship8 with the nate from Dr. Frank Billings15. first reference to this relationship being recorded in Dr. Hunter became famous for many of his dia- 1845 by John Harris in the dental literature9. tribes on sepsis, such as “Figuratively, if not actu- In 1900, in the British Medical Journal, Dr. Wil- ally, he sees in flaming characters written above liam Hunter commented that “the whole subject the doors of his wards, and the operation thea- of oral sepsis as a cause of disease has been one of tres, the words ‘Abandon Sepsis, all ye who enter special interest to me for many years; that I have here’.” And even if this escapes his notice, the dealt with it at some length in published papers janitor who guards the door is there to remind you, during the past year and a-half; and that the more “Put on thy shoes, for the place on which thou I study it the more impressed I am, at once with enterest is antiseptic ground”13,14. He ranked sep- its importance, and with the extraordinary neglect sis in medicine as “the most prevalent and potent with which it is treated alike by and infective disease in the body”; “focusing on the surgeons”10. He goes on to say: “I have to point movement of staphylococcal and streptococcal out that for every case of gastric or other affec- organisms throughout the body, compromising tion traceable to pyorrhea alveolaris a hundred specific regions or organ systems”. When applying cases equally well marked are daily to be found these principles to oral medicine, the physician was associated with other dental and oral conditions immune to the potential disease processes occur- of sepsis. In short, I deprecate this subject of oral ring in the oral cavity, regarding it as “matter of sepsis and its effects being brought under discus- teeth and dentistry”, with which he cannot deal16. sion, in connection with any one pathological Hunter referred to these oral conditions as “oral condition of the mouth. The list of such condi- sepsis”, a topic he had lectured on in years prior to tions might be increased almost indefinitely. In my his 1910 indictment13.

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Moreover, Hunter focused both on teeth and of focal infection and elective localisation. They felt on supporting structures as being the seats of sep- that bacteria had a predisposition to lodge in specific sis: “It is in poor patients that these septic condi- areas, causing a disease process remote from the ori- tions are most common. They have had ‘no care’ ginal site of infection16. However, as early as 1917, of their mouths; their fate is the relatively happier Meyer criticised the culturing of extracted teeth as a one of having their septic roots lying exposed in all diagnostic technique and called attention to the pos- their nakedness surrounded with tartar, overgrown sibility of culturing normal mouth organisms which it may be by foul, septic fungating gums. This sep- contaminated the tooth during extraction22. Gross- sis is relatively open and above-board; it stares one man indicated that it was disconcerting, but true, in the face when it is looked for”13,14. that practically every investigation dealing with the Throughout this time frame Hunter showed pulpless tooth with this approach to bacterial sam- great respect for the mechanical skills of the den- pling, made prior to 1936 was invalid16,23. tist, while at the same time he voiced his contempt The theories of focal infection and elective for the lack of awareness of the seat of oral sep- localisation, when coupled, were to have a devas- sis, citing it as surgical malpractice16. “No one has tating effect on the dental profession, as not only probably more reason than I have had to admire pulpless teeth, but also teeth with any possibility of the sheer ingenuity and mechanical skill constantly chronic inflammation or infection, along with the displayed by the dental surgeon. And no one has surrounding periodontium, were considered as the had more reason to appreciate the ghastly trag- primary source of systemic disease16. edies of oral sepsis, which his misplaced ingenuity Throughout the first half of the 20th century, so often carries in its train. Gold fillings, gold caps, teeth and the seat of potential focal infection they gold bridges, gold crowns, fixed dentures, built in, represented have been implicated in multiple dis- on, and around diseased teeth, form a veritable ease processes throughout the body, such as eye mausoleum of gold over a mass of sepsis to which disease, arthritis, tonsillitis, stomach ulcers, chol- there is no parallel in the whole realm of medicine ecystitis, myositis, diabetes, and many nondescript or surgery. The whole constitutes a perfect gold unexplained vague systemic conditions24-31. This trap of sepsis of which the patient is proud, and stance on focal infection and its impact on systemic which no persuasion will induce him to part with; disease continued to be fostered by Dr. Weston for has it not cost him much money, and has he A. Price with the publication of his two-volume not been proud to have his black roots elegantly research exposé ‘Dental Infections – Oral and Sys- covered with beaten gold, although no ingenuity temic’32 and ‘Dental Infections and Degenerative in the world can incorporate the gold edge of the Diseases’33 published in 1923. Price’s publications cap or crown with the underlying surfaces of the only fuelled the concept of focal infection and root beneath the edges of the gums. There is no resulted in a frightening era of tooth extraction rank of society free from the fatal effects on health for both the treatment of systemic disease and a of this surgical malpractice”13,14. prophylactic measure against future disease state. In 1911, Dr. Frank Billings defined focal infec- Ironically, Price’s scientifically invalid concepts are tion as “a circumscribed area of tissue infected also permeating contemporary thinking to a great with pathogenic organisms”17. He recommended extent among certain populations. the removal of all foci of infection and the improvement in patient immunity by absolute rest and improvement of the general and individual The rejection of the pervading hygiene. He felt that “these measures alone will concept stop further progress of the disease and usually entire recovery will take place”15. The criticism of septic dentistry and demand for During this time, Rosenow18-21 and Billings15,17 tooth extraction was vehemently rejected by the were rapidly clarifying and espousing the concept Editors of ‘Dental Cosmos’ in 193034.

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“The castigation of septic dentistry by Hunter by the vital tissues”36, and this was deemed as and the almost immediate demand of the medical analogous to what occurred in pulpless teeth16. profession for relief from this supposedly newly Therefore, root canal systems required a hermetic discovered source of bodily ills, which focused itself seal37 to prevent the irritation and inflammation upon the pulpless tooth, and the willing submission of the periradicular tissues and possible spread of of the dental profession to what was apparently the disease. Furthermore, the materials used to fill the quickest and easiest mode of affording such relief, root canal or apical foramen could not irritate the namely, removal of the suspected teeth, proved to tissues, and caution was expressed as to the use of be a most serious impediment toward the logical many materials in root surgery, especially copper solution of the problem. The combination of the amalgam that was used in root-end fillings. How- physician, the radiographer and the exodontist for ever, in the hands of good clinicians, these mater- the moment completely overshadowed the efforts ials worked extremely well and, in the process, of that conservative group who were making enabled the retention of many teeth for years, long efforts to perfect a technique which would make before Price’s challenges existed38. While the need the pulpless tooth an efficient and harmless unit of to prevent localised tissue irritation was valid, the the masticatory apparatus. And today we are not hollow tube theory, as promulgated by Rickert and yet fully awakened from the nightmare of ruthless Dixon36 was effectively disproven in the 1960s. tooth destruction which has shaken the very foun- While focal infection was not dead, its tenets were dations of dental practice ... The ready accession to being slowly disassembled, and its impact was the demands of the medical profession apparently eroding over the years. satisfied their requirements for the moment from the standpoint of removal of a possible source of evil, but it did not satisfy the legitimate demands of The American Medical Association 34 the patient for an efficient masticatory organ” . (AMA) takes a stance on focal Price’s research was determined to be invalid infection in so many respects, as it did not include proper control populations but did include the use of In 1952, an affirmation of the position taken by excessive, uncontrolled doses of bacteria to prove the ADA one year earlier appeared in an Editorial in his hypotheses. Price’s research was ultimately dis- the Journal of the American Medical Association39: credited over the next 20 to 30 years and in 1951 “After exerting a tremendous influence on the the American Dental Association (ADA), through practice of medicine for a generation, the theory of its official vehicle, its journal, took an extraordi- focal infection in the past 10 to 15 years has fallen nary step in publishing a special edition reviewing in part into disfavour”39. While the observations the scientific literature and shifting the standard of by many that supported this position were damn- dental practice to one of tooth retention, especially ing of this theory, “none of them actually disproves in the presence of a tooth with a non-vital pulp, the theory that some foci of infection can, in the whenever possible16,35. presence of predisposing or accessory factors, pro- As with any controversial issue, other perspec- duce some systemic diseases”39. Furthermore, the tives then arose from the conflagrations of focal AMA indicated that: infection that focused on the issue of root canal “... many patients with diseases presumably procedures, such as the ‘hollow tube’ theory. In caused by foci of infection have not been relieved 1931, Rickert and Dixon36 demonstrated ‘halos of of their symptoms by removal of the foci. Many irritation’ around the open ends of implanted plati- patients with these same systemic diseases have no num and steel hypodermic needles36. For them evident focus of infection, and also foci of infection this finding “gave rather convincing evidence are, according to statistical studies, as common that the circulatory elements diffusing out of the in apparently healthy persons as those with dis- openings of these tubes were not well tolerated ease ... the indiscriminate removal of all suspected

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or potential foci from a person without complaints by DeStefano et al43 that reported that patients is to be condemned”16,39. with periodontitis had a 24% increase risk of coro- Regardless of the position of the ADA and nary heart disease43. The stage was now set for AMA, there existed professionals who would con- an attack on the provision of root canal proced- tinue to espouse one or more aspects of the focal ures, relative to necrotic, infected pulps, periapical infection theory when a diagnosis could not be abscesses and the inability to fully disinfect the made, or successful treatment achieved. Sadly, root canal system. Ironically this resistance came many professionals today who have failed to learn from a charter member of the AAE, Dr. George A. from the lessons of history, have chosen to espouse Meinig, who attacked the provision of root canal this theory in spite of more current scientific and procedures in his publication ‘Root Canal Cover- valid evidence16. Often the attempt to use science up’44. Meinig, in quoting the tenets of Weston A. for their position is based on archaic facts or mis- Price wrote “the reams of scientific data published conceptions, as correlations of dental treatment and subsequently buried years ago regarding the procedures are erroneously tied together with the exhaustive 25-year root canal research programme incidences of systemic disease1. conducted by Weston A. Price, DDA, FACS, and The quality and success of both nonsurgical and a group of working under the auspices surgical endodontic procedures in dental practice of the ADA’s research institute ... with ... the pur- over the years began to take hold prior to the pos- pose to alert readers to the possible ill health side itions taken by the ADA and AMA. In the early effects that were discovered to result from infected 1950s with the founding of the Philadelphia Root teeth, , and other oral tissues”44. A new era Canal Study Club in 193940, in an era that was had begun in the relationship of oral and systemic seeing the wholesale extraction of teeth, based disease that affected both the periodontal and on the theory of focal infection, this one timely endodontic communities, and which captured the and fortuitous occurrence was the genesis for a attention of dentistry as a whole. national association of dentists interested in root In surveying the US National Library of Medi- canal therapy – the American Association of Endo- cine (www.pubmed.gov), National Institutes of dontists (AAE). Health, using the phrase ‘relationship of oral and systemic disease’, 88 references were identified from 1947 to 1989. Overall, 1433 articles have Focal infection and root canal been published to 1 March 2019, addressing the procedures in the late 1900s possible relationships that had been promulgated more than 100 years ago. For 30 years, from 1950 to 1980, little interest Today, systemic diseases that have some level was shown in the relationship between oral health of association with oral infections, in particular and systemic health. The provision of root canal inflammatory , include: cardio- procedures grew exponentially with the approval vascular disease, coronary heart disease including of Endodontics by the ADA, as a specialty of den- atherosclerosis and myocardial infarction, stroke, tistry in 196341, which was coupled with a rapid infective , bacterial pneumonia, infant commencement of advanced specialty education low birth weight, diabetes mellitus, psoriasis, rheu- programs in the USA. Concomitantly, there was matoid arthritis, some cancers45-48; and following also a focus on the management of a wide range root canal procedures49, and chronic apical peri- of periodontal disease states with enhanced pro- odontitis50,51, that appear to associate indepen- cedures, both surgically and non-surgically. How- dently with coronary artery disease and in particu- ever, at the end of the decade in 1989, Matilla et lar with acute coronary syndrome52. In a recent al42 addressed the association of oral health and systematic review that addressed any relationship acute myocardial infarction42. This relationship between pulp/periapical infections and systemic was highlighted further in 1993, with a publication disease, potential correlations have been identified

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with , chronic liver disease, the periapical lesions were associated with the diabetes mellitus, some blood disorders and bone systemic inflammatory burden and cardiovascu- mineral density53,54. However, limited links exist lar risk determined by hsCRP, which supported a that identify a meaningful relationship of systemic mechanistic link for cardiovascular diseases (CVD) diseases and the provision of properly performed in young adults60. root canal procedures55,56. At the same time it Messing et al58 addressed the relationship of is possible that patients who have incomplete or periapical lesions their potential association with poorly treated root canals may have a higher risk of cardiovascular disease (CVD) using epidemiologi- cardiovascular challenges57. However, within the cal and genetic approaches. They found signifi- published literature, there is some confusion in this cant associations existed between ‘endodontic regard, as some authors use the terms ‘endodontic pathology’ and various CVDs and CVD related pathology’ as being a risk factor58, or ‘endodontic risk factors, particularly hypertension58. Exploring infection’ as a risk factor59, terms that are non- a different oral to systemic relationship, Tavares specific in nature, as opposed to identifying the et al61, using a rat animal model, explored the issues of concern, with the former as being: influence of (PP) in a rat • an improperly managed root canal system model of a metabolic syndrome induced by 10% including missed canals fructose supplementation. Specifically, they inves- • a mishap-filled root canal procedure, includ- tigated the cross talk between systemic inflamma- ing perforations, apical alterations, or broken tory changes and intestinal dysbiosis, and their cor- instruments relation with PP outcomes. They found evidence • a persistent, symptom-free or symptomatic that PP is able to alter systemic parameters related periapical lesion to metabolic syndrome, by showing that PP per se • a misdiagnosis and inability of the clinician to leads to intestinal leptinaemia and dysbiosis. identify the source of the problem, especially in One of the most commonly investigated bac- multi-rooted teeth, and so forth. terial species relative to pulpal and periapical pathosis is Enterococcus faecalis, which is often Or with the latter as being: used or investigated in studies due to its invasive, • failure to remove truly infected tissue and bac- virulent, pathosis-inducing and fastidious proper- teria from the intricacies of the anatomical ties62. While its presence in initial pulpal infection is complexities minimal, it does maintain a strong presence in root • failure to remove recalcitrant biofilms canal-treated teeth with persistent lesions and in • failure to use proper asepsis during the pro- recalcitrant biofilms, both intra and extraradicular cedures in nature63-65. As a gram-positive microorganism, • having a communication apically with a peri- E. faecalis has properties that support the persis- odontal infection tence and potential spread of infection in the oral • failure to deal with the issue of coronal leakage, cavity and beyond. and so forth. In light of this perspective, and the capabilities of E. faecalis, another similar organism that is also Recently, an investigation by Garrido et al60 aimed found beyond the confines of the oral cavity in to assess whether periapical lesions were associ- various states of disease66 and in periapical peri- ated with inflammatory serum markers of cardio- odontitis, has been receiving significant attention vascular risk, especially high sensitivity C-reactive in its potential role in systemic disease, that being protein (hsCRP), in young adults. In that cross- Fusobacterium nucleatum67. This organism is con- sectional study, individuals with periapical lesions sidered to be a periodontopathic bacteria, which of pulpal origin and a clinical diagnosis of asymp- has also been identified in necrotic pulps, periapical tomatic apical periodontitis, and controls aged periodontitis and is associated with biofilms68,69. between 18 and 40 years, were included. Overall, Therefore, its persistence in the apical portion

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of the root canal70, in both dentinal tubules and its emerging stages, however, the reader should highly irregular anatomical variabilities, may very understand fully that there are no confirmed well lead to both the persistence and spread of links that connect a specific root canal procedure, infectious processes, especially in teeth that have or persistent periapical pathosis, with the social not received the highest level of shaping, clean- media’s implication to the prevalence of cancer or ing/disinfection and obturation. F. nucleatum also other debilitating systemic disease. possesses similar virulence factors to E. faecalis that include adhesiveness and invasiveness, which are essential for colonisation, dissemination and References evasion of host responses71. Under these circum- 1. Root Cause. https://www.imdb.com/title/tt7851798/. stances, the potential for a secondary periapical Accessed 8 February 2019. periodontitis is enhanced70, along with both the 2. Response to Netflix documentary: Root Cause. https:// failure of the root canal procedure and the poten- www.dentistry.ucla.edu/news/response-netflix-documen- tary-root-cause. Accessed 20 June 2019. tial for the interplay among a wide range of species 3. Article on Netflix documentary: Root Cause. https:// that foster periodontitis72, including F. nucleatum, www.dentistryiq.com/articles/2019/02/netflix-s-root- cause-is-dumb-but-is-it-also-dangerous.html. Accessed E. faecalis, and Porphyromonas gingivalis in fur- 15 February 2019. thering the potential for the spread of disease well 4. Review on Netflix documentary: Root Cause. https:// www.todaysrdh.com/root-cause-netflix-documentary- beyond the confines of the periradicular tissues. lets-review-the-science/. Accessed 15 February 2019. In this respect, F. nucleatum has been implicated 5. Do root canals cause cancer? https://perioimplantadvi- sory.com. Accessed 15 February 2019. 71 in a wide range of systemic diseases . Due to its 6. Miller WH. Gangrenous tooth-pulps as centers of infec- ubiquitous nature, F. nucleatum has been identi- tion. Dent Cosmos 1888:30:213–214. 7. Miller WD. The human mouth as a focus of infection. fied as playing a role in colorectal cancer in two Dent Cosmos 1891;33:689–713. recent studies by promoting the development of 8. Weinberger BW. An introduction to the history of dentis- colorectal neoplasms73 through its induction of try, vol 1. St. Louis, CV Mosby, 1948. 9. Harris J. Dissertation on toothache. Am J Dent Sci 1845– Wnt/`-catenin modulator annexin A173,74. 1846;6:60–110. These findings have basically labelled F. nucle- 10. Hunter W. Oral sepsis as a cause of disease. Brit Med J 1900;1:215–216. atum as a cancer facilitator74. From a dental and 11. Hunter W. Oral sepsis. London: Cassell and Company, endodontic viewpoint, in particular, these types 1901. 12. Hunter W. 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James L. Gutmann DDS, Cert Endo, Vivian Manjarrés, DDS, Cert Endo, PhD, FICD, FACD, FADI, FAAHD, FAAHD FDSRCSEd Assistant Professor of Endodontics, Professor, Chair and Postgraduate Nova Southeastern University College of Program Director, Department of Endo- Dental Medicine, Davie, Florida, USA dontics, Nova Southeastern University, College of Dental Medicine, Davie, FL, USA

James L. Gutmann

Correspondence to: Dr James L. Gutmann, Department of Endodontics, Nova Southeastern University, College of Dental Medicine, 3200 South University Dr., Davie, USA. E-mail: [email protected]

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