DOI: 10.1111/prd.
12325
REVIEW ARTICLE
Primer on etiology and treatment of progressive/severe
periodontitis: A systemic health perspective
Jørgen Slots
Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA
Correspondence
Jørgen Slots, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
Email: jslots@usc.edu
1 | I NTRO D U C TI O N
Periodontitis can lead to unsightly drifting of teeth and tooth loss
and has been linked to at least 50 systemic diseases and disabili-
ties.1 Severe periodontitis affects 8.9% of the US adult population2
3
and 11.2% of individuals worldwide and can constitute a major
therapeutic challenge. Localized severe periodontitis may be asso-
ciated with only moderate accumulation of dental plaque and un-
remarkable systemic risk factors. The classic example is localized
juvenile (aggressive) periodontitis, which commences at the onset
of puberty in otherwise healthy adolescents and is a short-lived,
highly destructive disease that usually burns out spontaneously.
Generalized severe periodontitis involves multiple teeth in a denti-
tion which may lead to partial or complete edentulism. The general-
ized type of severe periodontitis tends to occur in relatively young
individuals who exhibit high loads of periodontal pathogens and
major risk factors or serious systemic diseases such as medical syn-
dromes. Most types of adult periodontitis present with unknown
disease activity and microbiome, which can complicate prognosis
and treatment.
Treatment of periodontitis is important for dental reasons, but
the comorbidity between periodontitis and systemic diseases raises
periodontal treatment to a new level of importance. The possibility
that periodontitis contributes to cardiovascular disease,4 cancer,5
Alzheimer's disease,6 adverse pregnancy outcome,7 and various
8,9
other serious diseases provides a compelling argument for treating
10
periodontal patients of all income groups. Most individuals have a
limited health-care budget and cannot afford to disburse funds on
unproven or minimally efficient periodontal therapies. Conventional
(purely mechanical) periodontal surgical and nonsurgical treatments
can be expensive and pose a financial burden for many individu-
als11 but are unlikely to control active periodontitis and periodontal
focal infections.1 The cost issue is of special concern for low-income
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© 2020 John Wiley & Sons A/S.
Published by John Wiley & Sons Ltd
populations, who exhibit a particularly high prevalence of severe
periodontitis and have unmet treatment needs. 2 The realistic solu-
tion to the conundrum of severe disease and unaffordable treatment
is to create a high-quality low-cost periodontal therapy. Knowledge
of the etiology of periodontitis is key to developing an efficient and
affordable therapy.
2 | PATH O G E N I C IT Y O F PE R I O D O NTA L
H E R PE S V I RU S E S
Except for rare pathologies,12 periodontal diseases are infectious
illnesses involving several pathogenic agents and risk factors.
Progressive/severe periodontitis is closely linked to active herpesvi-
ruses, specific bacterial pathogens, and proinflammatory cytokines,
but herpesviruses constitute arguably the major pathogenic deter-
minants.1 Immunocompromised states, such as primary or acquired
immunodeficiency and immune-dysregulation syndromes, are im-
portant host risk factors for herpesvirus activation and morbidity,
including periodontitis. Herpesvirus infections can be primary, re-
activation, or reinfection, but the primary infection has the great-
est risk of inducing high viral loads and progressive periodontitis.
The host defense against herpesviruses involves cellular immunity,
especially effector memory CD8+ cytotoxic T cells, and proinflam-
matory cytokines, which secondarily may promote periodontitis and
systemic diseases.8 Herpesviruses establish lifelong latency in sen-
sory ganglia or inflammatory cells, but immunosuppression caused
by disease, medication, psychosocial stress, or advanced age can
trigger asymptomatic (seldom symptomatic) herpesvirus activation
and viral shedding.1
The human herpesvirus family includes 8 members, and herpes-
viruses are ubiquitous in all populations.1 However, marginal and
apical periodontitis may be the only body sites in generally healthy
Periodontology 2000. 2020;83:272–276.
SLOTS |
      273

subjects that exhibit longstanding inflammation containing substan-
tial quantities of latent and reactivated herpesviruses. Severe peri-
odontitis lesions usually harbor 2 or 3 species of herpesvirus, and
the periodontal herpesvirus total copy counts can exceed the total
bacterial cell counts.1 Herpes simplex virus-1,13 Epstein-Barr virus,14
15
and cytomegalovirus can replicate productively in oral/gingival
epithelial cells, and active herpesvirus infections have the potential
to impede humoral immunity and induce upgrowth of periodonto-
pathic bacteria.16 Major pathogenic bacteria, in turn, may reactivate
17
latent herpesviruses. The resulting pathogenic synergism between
herpesviruses and bacterial pathogens exacerbates periodontal
breakdown.18 Infectious virions of herpesviruses within inflamed
gingiva may also readily enter the systemic circulation, extravasate
10
into various tissues, and potentially produce nonoral diseases.
Herpesviruses can infect virtually every organ system in the human
body and have been implicated in most, if not all, of the systemic
diseases that have been associated with periodontitis.19 Whether
periodontal bacteria contribute to numerous systemic diseases has
still to be determined. Periodontopathic bacteria enter the circula-
tory system in relatively small amounts and are typically neutralized
within minutes by a powerful serum antibody response. 20 The ob-
served statistical association between periodontopathic bacteria
and systemic diseases may be due, at least in part, to periodontal
herpesviruses inducing bacterial overgrowth.17,21
3 | PE R I O D O NTA L TR E ATM E NT
The overarching goal of periodontics and the expectation of pa-
tients are to arrest and prevent periodontal breakdown. To ac-
complish such goals, periodontal therapy must markedly suppress
or eradicate herpesviruses and bacterial pathogens in periodontal
pockets and the adjacent gingiva, plus address safety and afford-
ability issues. Various studies have raised doubt regarding the ef-
ficacy of current treatments of severe periodontitis.1 As shown in
Table 1, purely mechanical treatments (periodontal surgery, scaling
and root planing) fail to prevent clinical attachment loss in a large
proportion of patients with severe periodontitis and, of great con-
cern, untreated and mechanically treated periodontitis sites seem
to exhibit similar rates of future attachment loss. One reason may
be that periodontal flap surgery focuses on calculus and bacteria on
root surfaces and ignores the raised flap which contains infectious
agents that pose a risk of repopulating the surgical site. It is not
surprising that mechanical therapy alone fails to arrest progressive
periodontitis, which harbors billions of herpesviruses and bacteria
in deep periodontal pockets and inflamed gingiva outside the reach
of mechanical instrumentation.1 The inability of purely mechanical
treatment to cure severe periodontal infections and stop progres-
sive periodontitis is a therapeutic issue that is too important to dis-
miss. Also, because periodontal therapy yields a significantly larger

TA B L E 1   Mechanical periodontal treatment of moderate/severe periodontitisa 

Study Periodontal treatment Periodontal outcome

Subgingival treatment
22
Ramfjord et al. Sites with CAL gain – sites with CAL loss
5-y study SRP alone 29.5%-14.8%
SPT every 3 mo SRP + pocket elimination surgery 18.5%-10.8%
7-12 mm pockets SRP + Widman flap surgery 22.6%-8.1%
SRP + subgingival curettage 32.7%-10.9%
Haffajee et al. 23
1-y study SRP alone 1.7% of sites gained CAL
0.8% of sites lost CAL
39% of patients lost CAL
Rams et al. 24
2.5-y study SRP + Widman flap surgery 2.4% of all posterior sites lost CAL
SRP every 3 mo 14.7% of angular bony sites lost CAL
l.8% of horizontal bony sites lost CAL
35.7% of patients lost CAL
No/minimal subgingival treatment
25
Lindhe et at.
6-y study No initial or subsequent periodontal treatment 0.2% of sites gained CAL
11.6% of sites lost CAL
Renvert et al. 26
5-y study Initial SRP + Widman flap surgery or initial SRP 19.0% of sites had distinct CAL gain
alone, but no subgingival treatment for 5 y 7.1% of sites had distinct CAL loss
Both types of initial therapy showed sites with CAL loss

Abbreviations: CAL, clinical attachment level; SPT, supportive periodontal therapy; SRP, scaling and root planing.
a
Studies by renowned researchers and clinicians.
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274       SLOTS

TA B L E 2   Efficient low-cost treatment of severe/active periodontitisa 

Time Treatment Purpose/comments

Day 0 Subgingival irrigation for 5 min
with 10% povidone-iodine
(undiluted [10%] Betadine®,
yielding 1% free iodine)
Day 0 Full-mouth gross scaling with
ultrasonic instrument
Day 0 Systemic valacyclovir (Valtrex®)
against herpesviruses
Day 0 0.1%-0.25% sodium
hypochlorite (freshly diluted
Regular Clorox© household
bleach) oral rinse for 30 s
twice weekly (patient
self-care)
Day 10 Follow-up scaling and root
planing
Day 10 Amoxicillin + metronidazole or
ciprofloxacin + metronidazole
against major
periodontopathic bacteria
Day 10 Patient self-care: instruction
in oral hygiene, including
oral rinsing with 0.1%-0.25%
sodium hypochlorite (freshly
diluted Regular Clorox®
household bleach) for 30 s
twice weekly
a
Modified from Slots and Slots1 and Slots.41
To reduce introduction of viruses and bacteria into the bloodstream during scaling. The povidone-
iodine is applied to the base of periodontal pockets of both scaled and unscaled sites using, for
example, a 3-mL endodontic syringe with a 23-gauge cannula having side ports and a blunt end. A
single course of subgingival povidone-iodine irrigation of the entire dentition takes about 1.5 min
and is performed 3 times for a total application time of 5 min
To reduce subgingival calculus and thus diminish gingival bleeding in order to facilitate detection of
calculus at day 10 (see below)
As herpesviruses trigger bacterial upgrowth, antiviral therapy is carried out first. Valacyclovir
(500 mg, twice daily for 10 d) aims to eliminate high loads of herpesviruses in deep periodontal
pockets and within inflamed gingiva. Herpesvirus chemotherapeutics are effective against
viruses in the lytic phase, which basically limits treatment with valacyclovir to disease-active
periodontitis. Valacyclovir may be substituted by acyclovir, which is less expensive.
Most common adverse events of valacyclovir: nausea, stomach pain, headache, dizziness
Sodium hypochlorite is highly effective in removing and preventing dental biofilm and gingival
inflammation (bleeding). Patient self-care includes freshly prepared sodium hypochlorite for
twice-weekly 30-s oral rinses. Sodium hypochlorite is readily available as household bleach, and
0.17% sodium hypochlorite can be obtained by adding one teaspoon (5 mL) of 8.25% Regular
Clorox© Bleach to a large glass (250 mL/8.5 oz) of water. Because sodium hypochlorite has
a non-discriminative action of killing, it does not induce pathogenic superinfections and may
even promote a healthier oral microbiota because of the rapid posttreatment repopulation of
indigenous/low-virulence bacteria relative to pathogenic species. Overuse or a high concentration
of sodium hypochlorite may produce brownish/black extrinsic tooth staining (which can be
removed by air-polishing with glycine or erythritol powder). No hypersensitivity reactions
Scaling and root planing only in sites with verified calculus or suspicion of calculus. Antiseptics and
antibiotics will remove periodontal pathogens in sites that have not been scaled
Amoxicillin + metronidazole (250 mg of each, 3 times daily for 8 d) for young and middle-aged
patients. Ciprofloxacin + metronidazole (500 mg of each, twice daily for 8 d) for older patients,
for patients allergic to penicillin, and for patients in developing countries who frequently harbor
subgingival enteric rods 40
Most common adverse events:
Amoxicillin: nausea, vomiting, diarrhea, stomach pain, vaginal itching or discharge, headache, rash,
swollen, black, or “hairy” tongue
Metronidazole: nausea, vomiting, loss of appetite, stomach pain, diarrhea, constipation, unpleasant
metallic taste, rash, itching, dizziness, vaginal itching or discharge, mouth sores
Ciprofloxacin: diarrhea, dizziness, drowsiness, headache, upset stomach, abdominal pain, nausea/
vomiting, blurred vision, anxiety, tendon rupture with exercise
Oral rinsing with sodium hypochlorite (used long-term) to reduce dental biofilm buildup and
prevent gingival inflammation

number of sites with clinical attachment level gain (of uncertain
clinical significance) than clinical attachment level loss (Table 1),
treatment outcome presented as the average of the total denti-
tional sites will hide deteriorating sites and create a false perception
of therapeutic success. Treatment proficiency ought to be deter-
mined by the ability to halt or avoid periodontal disease progression
in every single site of a dentition. Systematic reviews on periodontal
treatment usually employ therapeutic averages as study variables,
and those reviews must be interpreted with extra caution.
Increased insights into the etiopathogenesis of periodonti-
tis have led to the development of more efficient treatments.
The recognition of microbial specificity in severe periodontitis
supports the use of chemotherapeutic intervention by antibi-
otics. An important advantage of systemic antibiotics is their
ability to reach periodontal pathogens, especially herpesvi-
ruses, located within inflamed gingiva. 27 The periodontal ther-
apy described in Table 2 combines 3-4 modes of anti-infective
treatments, each of which is already used in periodontics and
has demonstrated significant efficacy and acceptable safety. In
patients with minimal calculus and gingival bleeding, the en-
tire therapy may be carried out in 1 treatment session, rather
than in 2, by administering valacyclovir and bacterial antibiotics
SLOTS
concomitantly.10 The proposed anti-infective therapy targets
28,29
periodontal herpesviruses (valacyclovir [acyclovir] ) and
periodontopathic bacteria (amoxicillin + metronidazole 30,31 or
ciprofloxacin + metronidazole 32,33 ) and employs common an-
tiseptics (povidone iodine, 34-36 sodium hypochlorite 37-39) plus
scaling. Controlled randomized prospective trials could confirm
the therapeutic effectiveness.
4 |  CO N C LU D I N G CO M M E NT S
Virtually all types of periodontal disease are infectious illnesses,
which can be resolved by anti-infective intervention. Periodontal
treatment varies according to disease severity and patient factors,
such as patient age, general health, and effectiveness of self-care.
Severe periodontitis has traditionally been difficult to control, but
microbiological and clinical research have transformed severe per-
iodontitis into a manageable and preventable disease.
The underlying concept of the periodontal therapy proposed
here is that active herpesviruses and specific pathogenic bacte-
ria constitute the main etiology of severe periodontitis.17,42 An
anti-infective treatment which markedly reduces or eradicates
these pathogens can halt progression of the disease, and patient
self-care with sodium hypochlorite oral rinsing can reduce the
risk of novel disease outbreaks or reactivation of a dormant peri-
odontitis. The additional theme of this article is treatment simpli-
fication to avoid therapies that are too complex and expensive to
serve the needs of low-income individuals. The suggested phar-
macotherapeutic treatment of severe periodontitis is efficacious,
affordable, reasonably well-tested, and can be readily imple-
mented in clinical practice and patient self-care. The treatment
may be employed as a standalone therapy or in conjunction with
conventional periodontal therapies. Inadequate antimicrobial
therapy, most notably purely mechanical treatment and subopti-
mal antibiotics and antiseptics, may not cure severe periodonti-
tis and prevent focal infections. Also, although periodontitis and
peri-implantitis show similar microbiomes, 43,44 the present treat-
ment proposal needs to be assessed against peri-implantitis.
To conclude, preserving a healthy periodontium is important for
both oral and systemic health reasons and ought to be a major public
health priority. The possibility that a relatively simple periodontal
treatment can lessen, or perhaps prevent, several systemic diseases
computes to a highly favorable cost-benefit ratio. Collaboration be-
tween dental and medical professionals to reduce the incidence and
severity of systemic diseases can provide exciting new opportunities
for both dentistry and medicine.45
REFERENCES
1. Slots J, Slots H. Periodontal herpesvirus morbidity and treatment.
Periodontol 2000. 2019;79(1):210-220.
2. Eke PI, Borgnakke WS, Genco RJ. Recent epidemiologic trends in
periodontitis in the USA. Periodontol 2000. 2020;82(1):257-267.
|
      275
3. Kassebaum NJ, Bernabe E, Dahiya M, Bhandari B, Murray CJ,
Marcenes W. Global burden of severe periodontitis in 1990–
2010: a systematic review and meta-regression. J Dent Res.
2014;93(11):1045-1053.
4. Schenkein HA, Papapanou PN, Genco R, Sanz M. Mechanisms un-
derlying the association between periodontitis and atherosclerotic
disease. Periodontol 2000. 2020;83(1):90-106.
5. Nwizu N, Wactawski-Wende J, Genco RJ. Periodontal disease and
cancer: epidemiologic studies and possible mechanisms. Periodontol
2000. 2020;83(1):213-233.
6. Kamer AR, Craig RG, Niederman R, Fortea J, de Leo MJ. Periodontal
disease as a possible cause for Alzheimer disease. Periodontol 2000,
2020;83(1):242-271.
7. Bobetsis YA, Graziani F, Gürsoy M, Madianos PN. Periodontal
disease and adverse pregnancy outcomes. Periodontol 2000
2020;83(1):154-174.
8. Falcao A, Bullón P. A review of the influence of periodontal treat-
ment in systemic diseases. Periodontol 2000. 2019;79(1):117-128.
9. Sabharwal A, Gomes-Filho IS, Stellrecht E, Scannapieco FA. Role
of periodontal therapy in management of common complex sys-
temic diseases and conditions: an update. Periodontol 2000.
2018;78(1):212-226.
10. Slots J. Focal infection of periodontal origin. Periodontol 2000.
2019;79(1):233-235.
11. Masood M, Sheiham A, Bernabé E. Household expenditure
for dental care in low and middle income countries. PLoS ONE.
2015;10(4):e0123075.
12. Porter S, Johnson NW, Fedele S. Challenges of the interface of
oral medicine and periodontology: some lessons for the future?
Periodontol 2000. 2019;80(1):225-228.
13. Visalli RJ, Courtney RJ, Meyers C. Infection and replication of her-
pes simplex virus type 1 in an organotypic epithelial culture system.
Virology. 1997;230(2):236-243.
14. Nawandar DM, Ohashi M, Djavadian R, et al. Differentiation-
dependent LMP1 expression is required for efficient lytic
Epstein-Barr virus reactivation in epithelial cells. J Virol
2017;91(8):e02438-16.
15. Weng C, Lee D, Gelbmann CB, et al. Human cytomegalovirus pro-
ductively replicates in vitro in undifferentiated oral epithelial cells. J
Virol. 2018;92(16):e00903-e00918.
16. Slots J. Periodontal herpesviruses: prevalence, pathogenicity, sys-
temic risk. Periodontol 2000. 2015;69(1):28-45.
17. Chen C, Feng P, Slots J. Herpesvirus-bacteria synergistic interac-
tion in periodontitis. Periodontol 2000 2020;82(1):42-64.
18. Slots J. Periodontics californiensis: focus on herpesviruses. J West
Soc Periodontol Abstr. 2018;66(4):104-106.
19. Pellett PE, Roizman B. The family Herpesviridae: a brief intro-
duction. In: Knipe DM, Howley PM, eds. Fields Virology, 5th edn.
Lippincott, Williams & Wilkins: Philadelphia, PA; 2007:2479-2499.
20. Pallasch TJ, Slots J. Antibiotic prophylaxis and the medically com-
promised patient. Periodontol 2000. 1996;10(1):107-138.
21. Slots J. Herpesviral–bacterial interactions in periodontal diseases.
Periodontol 2000. 2010;52(1):117-140.
22. Ramfjord SP, Caffesse RG, Morrison EC, et al. 4 modalities of
periodontal treatment compared over 5 years. J Clin Periodontol.
1987;14(8):445-452.
23. Haffajee AD, Torresyap G, Socransky SS. Clinical changes fol-
lowing four different periodontal therapies for the treat-
ment of chronic periodontitis: 1-year results. J Clin Periodontol.
2007;34(3):243-253.
24. Rams TE, Listgarten MA, Slots J. Radiographic alveolar bone
morphology and progressive periodontitis. J Periodontol.
2018;89(4):424-430.
 |
276       SLOTS
25. Lindhe J, Haffajee AD, Socransky SS. Progression of periodontal
disease in adult subjects in the absence of periodontal therapy. J
Clin Periodontol. 1983;10(4):433-442.
26. Renvert S, Nilvéus R, Dahlén G, Slots J, Egelberg J. 5-year follow up
of periodontal intraosseous defects treated by root planing or flap
surgery. J Clin Periodontol. 1990;17(6):356-363.
27. Kubar A, Saygun I, Özdemir A, Yapar M, Slots J. Real-time poly-
merase chain reaction quantification of human cytomegalovirus
and Epstein-Barr virus in periodontal pockets and the adjacent gin-
giva of periodontitis lesions. J Periodontal Res. 2005;40(2):97-104.
28. Sunde PT, Olsen I, Enersen M, Grinde B. Patient with severe peri-
odontitis and subgingival Epstein-Barr virus treated with antiviral
therapy. J Clin Virol. 2008;42(2):176-178.
29. Fu Y-W, Li X-X, Gong Y-Q, Xu H-Z. Valacyclovir as an adjunct to full-
mouth scaling and root planing of advanced chronic periodontitis: a
randomized clinical trial. Shanghai J Stomatol. 2014;23(1):103-106.
3 0. López NJ, Socransky SS, Da Silva I, Japlit MR, Haffajee AD. Effects
of metronidazole plus amoxicillin as the only therapy on the micro-
biological and clinical parameters of untreated chronic periodonti-
tis. J Clin Periodontol. 2006;33(9):648-660.
31. Winkel EG, Van Winkelhoff AJ, Timmerman MF, Van der Velden U,
Van der Weijden GA. Amoxicillin plus metronidazole in the treat-
ment of adult periodontitis patients. A double-blind placebo-con-
trolled study. J Clin Periodontol 2001;28(4):296-305.
32. Esfahanizadeh N, Khalilinejad S, Zonubi L. Clinical and microbi-
ological effects of systemic ciprofloxacin and metronidazole in
Aggregatibacter actinomycetemcomitans-associated periodontitis.
Afr J Pharm Pharmacol. 2014;8(16):433-437.
33. Tezel A, Yucel O, Orbak R, et al. The gingival crevicular fluid cipro-
floxacin level in subjects with gingivitis and periodontitis, and its ef-
fects on clinical parameters. J Periodontal Res. 2005;40(5):395-400.
3 4. Hoang T, Jorgensen MG, Keim RG, Pattison AM, Slots J. Povidone-
iodine as a periodontal pocket disinfectant. J Periodontal Res.
2003;38(3):311-317.
35. Perrella FA, da Silva Rovai E, de Marco AC, et al. Clinical and micro-
biological evaluation of povidone-iodine 10% as an adjunct to non-
surgical periodontal therapy in chronic periodontitis: a randomized
clinical trial. J Int Acad Periodontol. 2016;18(4):109-119.
36. Managutti A, Managutti SA, Patel J, Puthanakar NY. Evaluation of
post-surgical bacteremia with use of povidone-iodine and chlorhex-
idine during mandibular third molar surgery. J Maxillofac Oral Surg.
2017;16(4):485-490.
37. Shanker K, Suragimath G, Zope SA, Varma SA, Ashwinirani SR. A
case-control study to assess and compare the efficacy of 0.2% chlor-
hexidine and 0.25% sodium hypochlorite mouthwash in treatment
of chronic gingivitis. Asian J Pharm Clin Res. 2018;11(5):313-315.
38. Gonzalez S, Cohen CL, Galvάn M, Alonaizan FA, Rich SK, Slots J.
Gingival bleeding on probing: relationship to change in periodon-
tal pocket depth and effect of sodium hypochlorite oral rinse. J
Periodontal Res. 2015;50(3):397-402.
39. Califf KJ, Schwarzberg-Lipson K, Garg N, et al. Multi-omics analysis
of periodontal pocket microbial communities pre- and posttreat-
ment. mSystems. 2017;2(3):e00016-e00017.
4 0. Contreras A, Moreno SM, Jaramillo A, et al. Periodontal microbiol-
ogy in Latin America. Periodontol 2000. 2015;67(1):58-86.
41. Slots J. Low-cost periodontal therapy. Periodontol 2000.
2012;60(1):110-137.
42. Tonoyan L, Vincent-Bugnas S, Olivieri C-V, Doglio A. New viral facets
in oral diseases: The EBV paradox. Int J Mol Sci. 2019;20(23):5861.
43. Schwarz F, Derks J, Monje A, Wang HL. Peri-implantitis. J
Periodontol. 2018;89(Suppl 1):S267-S290.
4 4. Carinci F, Romanos GE, Scapoli L. Molecular tools for preventing
and improving diagnosis of peri-implant diseases. Periodontol 2000.
2019;81(1):41-47.
45. Slots J. Periodontitis: facts, fallacies and the future. Periodontol
2000. 2017;75(1):7-23.
How to cite this article: Slots J. Primer on etiology and
treatment of progressive/severe periodontitis: A systemic
health perspective. Periodontol 2000. 2020;83:272–276.
https://doi.org/10.1111/prd.12325