Introduction

The majority of patients with common forms of periodontal disease

respond predictably well to conventional therapy, including oral hygiene
instruction, non-surgical debridement, surgery and supportive periodontal
maintenance. However, patients diagnosed with aggressive and some atypical
forms of periodontal diseases often don’t respond as predictably or as favourably
to conventional therapy. Fortunately, only a small percentage of patients with
periodontal disease are diagnosed with aggressive periodontitis. Patients who are
diagnosed with any type of periodontal disease that is refractory to treatment
present in small numbers as well. Even fewer patients are diagnosed with
necrotising ulcerative periodontitis. Each of these atypical disease entities possess
significant challenges for the clinician not only because they are infrequently
encountered but also because they may not respond favourably to conventional
periodontal therapy. Furthermore, the severe loss of periodontal support
associated with these cases leaves the clinician faced with uncertainty about
treatment outcomes and difficulty in making decisions about whether to save
compromised teeth or to extract them.

Aggressive periodontitis
Aggressive periodontitis, by definition, causes rapid destruction of the
periodontal attachment apparatus and the supporting alveolar bone. The
responsiveness of aggressive periodontitis to conventional periodontal treatment
is unpredictable, and the overall prognosis for these patients is poor than for
patients don’t respond “normally” to conventional methods and their disease
progress unusally fast, the logical question is whether there are problems
associated with an impaired host immune response that may contribute to such a
different disease and result in a limited response to the usual therapeutic
measures. Indeed defects in polymorphonuclear leucocytes (PMN, Neutrophil)
function have been identified in some patients with aggressive periodontitis.
Also, in a small number of cases, a systemic disease, such as neutropenia can be
identified. That clearly explains the unusual severity of the periodontal disease
for that individual. In most patients with aggressive periodontitis, however,
systemic diseases or disorders cannot be identified. Infact, the irony is that these
patients are typically quite healthy. Numerous attempts to examine
immunological profiles in patients with aggressive periodontitis have failed to
identify any specific etiological factors common to all patients.

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The prognosis for patients with aggressive periodontitis depends on
1. Whether the disease is generalised or localised
2. The degree of destruction present at the time of diagnosis
3. The ability to control future progression
Generalised aggressive periodontitis rarely undergoes spontaneous remission,
whereas localised forms of the disease have been known to arrest
spontaneously. These unexplained curtailment of disease progression has
sometimes been referred to as “Burnout” of the disease. It appears that cases of
localised aggressive periodontitis often have a limited period of rapid
periodontal attachment and alveolar bone loss, followed by a slower more
chronic phase of disease progression. Overall, patients with generalised
aggressive periodontitis tend to have a poorer prognosis because they typically
have more teeth affected by the disease and because the disease is less likely to
go spontaneously into remission compared to patients with localised forms of
aggressive periodontitis.

Therapeutic modalities
Early detection is critically important in the treatment of aggressive
periodontitis (generalised or localised) because preventing further destruction is
often more predictable than attempting to regenerate lost supporting tissues.
Therefore, at the initial diagnosis, it is helpful to obtain any previously taken
radiographs to assess the rate of progression of the disease.

One of the most important aspects of treatment success is to educate the patient
about the disease, including the causes and risk factors of the disease, and to
stress the importance of the patient’s role in the success of the treatment.
Essential therapeutic considerations for the clinician are to control the infection,
arrest disease progression, correct anatomic defects, replace missing teeth and
ultimately help the patient maintain the periodontal health with frequent
periodontal maintenance care. Educating family members is another important
factor because aggressive periodontitis is known to have family aggregation.
Thus family members, especially younger siblings of the patient diagnosed with
aggressive periodontitis should be examined for signs of disease, educated
about preventive measures, and monitored closely.

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Conventional periodontal therapy
Because aggressive periodontitis is primarily a bacterial infection, initial
treatment is comparable to treatment rendered for chronic periodontitis.
Conventional periodontal therapy for aggressive periodontitis consists of patient
education, oral hygiene improvement, scaling and root planning and regular
recall maintenance. It may or may not include periodontal flap surgery.
Unfortunately the response of aggressive periodontitis to conventional therapy
alone has been limited and unpredictable. Patients who are diagnosed with
aggressive periodontitis on early stage and who are able to enter therapy may
have a better outcome than those who are diagnosed at an advanced stage of
destruction. In general, the earlier the disease is diagnosed, the more
conservative is the therapy and the more predictable is the outcome.

Teeth with moderate to advanced periodontal attachment loss and bone loss
often have a poor prognosis and pose the most difficult challenge. Depending on
the condition of the remaining dentition, treatment of these teeth may have a
limited prospect for improvement an may even diminish the overall treatment
success for the patient. Clearly, some of these teeth should be extracted,
however, other teeth may be pivotal to the stability of that individual’s dentition
and thus it may be desirable to attempt treatment to maintain them. Treatment
options for teeth with deep periodontal pockets and bone loss may be non-
surgical or surgical. Surgery may be purely resective, regenerative or
combination of these approaches.

Surgical resective therapy

Resective periodontal surgery can be effective to reduce or eliminate
pocket depth in patients with aggressive periodontitis. However it may be
difficult to accomplish if adjacent teeth are unaffected, as often seen in cases of
localised aggressive periodontitis. If a significant height discrepancy exist
between the periodontal support of the affected tooth and adjacent unaffected
tooth, the gingival transition (following the bone) will often result in deep
probing pocket depth around the affected tooth despite surgical efforts. A less
than ideal outcome must be taken into consideration before deciding to treat
increased pocket depth surgery.

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It is important to realise the limitations of surgical therapy and to appreciate the
possible risk that surgical therapy may further compromise teeth that are mobile
because of the extensive loss of periodontal support. For example, in patients
with severe horizontal bone loss, surgical resective therapy may result in
increased tooth mobility that is difficult to manage and a non-surgical approach
may be indicated.

Regenerative therapy
The concept and application of periodontal regeneration has been
established in patients with chronic forms of periodontal disease. The use of
regenerative materials, including bone grafts, barrier membranes and wound
healing agents are well documented and often used. Intrabony defects,
particularly vertical defects with multiple osseous walls are often amenable to
regeneration with these techniques.

It is important to note that although the potential for regeneration in patients

with aggressive periodontitis appears to the good, expectations are limited for
patients with severe bone loss. This is especially true if the bone loss is
horizontal and if it has progressed to involve furcations.

Antimicrobial therapy
The presence of periodontal pathogens, specifically Aggregatibacter
actinomycetemcomitans, has been implied as the reason that aggressive
periodontitis doesn’t respond to conventional therapy alone. These pathogens
are known to remain in the tissues after therapy to re-infect the pocket. The use
of systemic antibiotics was thought to be necessary to eliminate pathogenic
bacteria from the tissues. Indeed several authors have reported success in the
treatment of aggressive periodontitis using antibiotics as adjuncts to standard
therapy.

There is compelling evidence that adjunctive antibiotic treatment frequently

results in more favourable clinical response than mechanical therapy alone.
Systemic antimicrobials in conjunction with scaling and root planning offer
benefits over scaling alone in terms of clinical attachment level, probing pocket
depth, and reduced risk of attachment loss. Patients with deeper, progressive

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pockets seems to benefit the most from systemic administration of adjunctive
antibiotics.

Genco and coworkers treated localised aggressive periodontitis with scaling and
root planing plus systemic administration of tetracycline (250mg, four times
daily for 14 days every 8 weeks). Measurements of vertical defects were made
at intervals of upto 18 months after the initiation of therapy. Bone loss stopped
and one third of the defects demonstrated an increase in bone level, whereas in
the control group, bone loss continued.

Liljenberg and Lindhe treated localised aggressive periodontitis with systemic

administration of tetracycline (250mg, four times daily for 2 weeks), modified
widman flaps, and periodic recall visits (one visit every month for 6 months,
then one visit every 3 months). The lesions healed more rapidly and more
completely than similar lesions in control patients. These investigators
reevaluated their results after 5 years and found that the treatment group
continued to demonstrate resolution of gingival inflammation, gain of clinical
attachment and refill of bone in angular defects.

Clearly numerous studies support the use of adjunctive tetracycline along with
mechanical debridement for the treatment of Aggregatibacter
actinomycetemcomitans-associated aggressive periodontitis. Given the possible
emergence of tetracycline-resistant A.actinomycetemcomitans, there is concern
that tetracycline may not be effective. In these cases the combination of
metronidazole and amoxicillin may be advantageous. The combination of these
two antibiotics with conventional periodontal therapy provides better disease
control and better clinical improvement in attachment levels in difficult to
manage periodontitis cases than similar periodontal therapy without antibiotics.
Similar effects were seen for a variety of antibiotic types. However a lack of
sufficient sample sizes among studies is difficult to offer specific
recommendations about which antibiotics were most effective.

Systemic tetracycline in treatment of aggressive periodontitis

Systemic tetracycline (250mg of tetracycline hydrochloride four times
daily for atleast 1 week) should be given in conjunctive with local mechanical
therapy. If surgery is indicated, systemic tetracycline should be prescribed and
the patient is instructed to begin taking the antibiotic approximately 1hr before
surgery. Doxycycline, 100mg/day, may be used instead of tetracycline.

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Chlorhexidine rinses should be prescribed and continued for several weeks to
enhance plaque control and facilitate healing.

The criteria for selection of antibiotics are not clear. Good clinical and
microbiological responses have been reported with several individual antibiotics
and antibiotic combinations. The optimal antibiotic or combinations for any
particular infections probably depends on the case. Choices must be made based
on patient-related and disease-related factors.

Antibiotic therapy for aggressive periodontitis

Associated microflora Antibiotics of choice

Gram positive organisms Amoxicillin-clavulanate potassium

(Augmentin)

Gram negative organisms Clindamycin

Non oral gram negative, facultative Ciprofloxacin

rods pseudomonas, staphylococci

Black pigmented bacteria and Metronidazole

spirochetes

Prevotella intermedia, Porphyromonas Tetracycline

gingivalis

Metronidazole-amoxicillin
Aggregatibacter Metronidazole-ciprofloxacin
actinomycetemcomitans Tetracycline

Porphyromonas gingivalis Azithromycin

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Microbial testing
Some investigators and clinicians advocate microbial testing to identify
the specific periodontal pathogens responsible for disease and to select an
appropriate antibiotic bases on sensitivity and resistance. There may be specific
cases in which bacterial identification and antibiotic sensitivity testing is
invaluable. For example, in localised aggressive periodontitis cases, tetracycline
resistant Actinobacillus species has been suspected. If antibiotic susceptibility
tests determine that tetracycline-resistant species exist as lesion, the clinician
may be consider another antibiotic or an antibiotic combination and
metronidazole.

Nonetheless, the use of microbial testing should be considered whenever a case

of aggressive periodontitis is not responding or if the destruction continues
despite good therapeutic efforts.

Local delivery
The use of local delivery to administer antibiotics offers a novel
approaches to the management of periodontal localised infections. The primary
advantage of local delivery is that smaller total dosages of topical agents can be
delivered inside the pocket, avoiding the side effects of systemic antibacterial
agents while increasing the exposure of the target microorganisms to higher
concentrations, and therefore more therapeutic levels of the medication. Local
delivery agents have been formulated in many different forms, including
solutions, gels, fibres, and chips.

Full mouth disinfection

Another approach to antimicrobial therapy in the control of infection
associated with periodontitis is the concept of full mouth disinfection. The
concept, described by Quirynan et al, consists of full mouth debridement
(removal of all plaque and calculus) completed in two appointments within a
24hr period. In addition to scaling and root planing, the tongue is brushed with
chlorhexidine gel (1%) for 1 minute, the mouth is rinsed with a chlorhexidine

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solution (0.2%) for 2 minutes, and periodontal pockets are irrigated with a
chlorhexidine solution (1%).

Host modulation
A normal approach in the treatment of aggressive periodontitis and
difficult to control forms of periodontal disease is the administration of agents
that modulate the host response. Several agents have been or evaluated to
modify the host response to disease.

Treatment planning and restorative considerations

In the patients with aggressive periodontitis, the approach to restorative
treatment should be chosen based on a single premise; extract severely
compromised teeth early and plan treatment accommodate future tooth loss. The
teeth with the best prognosis should be identified and considered when planning
the restorative treatment. The lower cuspids and first premolars are typically
more resistant to loss, probably because of the favourable anatomy ( i.e. single
roots, no furcations) and easier access for patient oral health. As a rule, an
extensive fixed prosthesis should be avoided, and removable partial dentures
should be planned in such a way as to allow for the addition of teeth.

When hopeless teeth are extracted, they need to be replaced. The desire to
replace missing teeth in a permanent manner without preparation of adjacent
teeth for a fixed partial denture motivated clinicians to attempt transplantations
of teeth from one side to another. Transplantation of developing third molars to
the sockets of hopeless first molars has been attempted to transplant teeth to
edentulous sites.

Use of dental implants

Initially, the use of dental implants was suggested and implemented with
much caution in patients with aggressive periodontitis because of an unfounded
fear of bone and implant loss. However, evidence to the contrary appears to
support the use of dental implants in patients treated for aggressive periodontal
disease. Thus, it is possible to consider the use of dental implants in the overall
treatment plan for patients with aggressive periodontitis.

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Clinical considerations
It is important to recognise that special consideration must be given to the
risk of occlusal overload of implants placed in a periodontally compromised
dentition. This is especially true only when only one or few implants are used to
replace a limited number of teeth with an implant supported fixed crown or
bridge in a patient with the majority of the remaining dentition being mobile.
The immobility of implants in a dentition that doesn’t have a stable vertical
occlusal stop may lead to implant overloaded.

Periodontal maintenance
When patients with aggressive periodontitis are transferred to
maintenance care, their periodontal conditions must be stable (i.e. no clinical
signs of disease and no periodontal pathogens). Each maintenance visit should
consist of a medical history review, an inquiry about any recent periodontal
problems, assessment risk of factors, a comprehensive periodontal and oral
examination, thorough root debridement, and prophylaxis, followed by a review
of oral hygiene instructions. If oral hygiene is not good, patients may benefit
most from a review of oral hygiene instructions and visualisation of plaque in
their own mouth before debridement and prophylaxis.

Frequent maintenance visits appear to be one of the most important factors in

the control of disease and the success of treatment in patients with aggressive
periodontitis.

A supportive periodontal maintenance program aimed at early detection and

treatment of sites that begin to lose attachment should be established. The
duration between these recall visits is usually short during the first period after
the patient’s completion of therapy, generally or longer than 3 months intervals.
Acute episodes of gingival inflammation can be detected and managed earlier
when the patient is on frequent monitoring cycle. Monitoring as frequently as
every 3 to 4 weeks may be necessary when the disease is thought to be active.
Fif signs of disease activity and progression persists despite therapeutics efforts
frequent visits and good patient compliance, microbial testing may be indicated.
The rate of disease progression may be faster in younger individuals, and
therefore the clinician should monitor such patients more frequently. Overtime
the recall maintenance interval can be adjusted (more or less often) to suit the

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patient’s level of oral hygiene and control of disease, as determined by each
examination.

Close collaboration among members of the treatment team, including the

periodontist, general dentist, dental hygienist and patient’s physician is required
for continuity of care and the patient motivation and encouragement. It is
important to monitor and observe the patient’s overall physical status as well,
because weight loss, depression and malaise has been reported in patients with
generalised aggressive periodontitis. Finally, there is constant need to reinforce
patient education about disease etiology and preserve practices (i.e. oral hygiene
and control of risk factors).

Periodontitis refractory to treatment

Although refractory periodontitis is not currently considered a separate
entity, patients who fail to respond to conventional therapy are considered to
have periodontitis that is “Refractory” to treatment. It is possible to characterise
any form of periodontal disease (eg: chronic periodontitis, aggressive
periodontitis) as refractory to treatment.

These cases are difficult to manage because the etiology behind their lack of
response to therapy is unknown. Initially because contributing factors may have
been overlooked, it is important to evaluate the adequacy of treatment attempts
thoroughly and to consider other possible etiologies before considering that a
case truly is refractory. A patient with periodontitis that is refractory to treatment
often doesn’t have any distinguishing clinical characteristics on initial
examination compared with cases of periodontitis that respond normally.
Therefore, the initial treatment would follow conventional therapeutic
modalities for periodontitis. After treatment is the patient has not responded as
expected, the clinician should rule out the following conditions

1. Inadequately treated periodontitis

Most forms of periodontitis can be treated effectively with currently
available modalities if they are performed properly. After treatment, if it is
determined that the patient has not responded, the clinician must evaluate
whether the therapy was adequately performed. Undetected or inaccessible
subgingival calculus may present in one or more areas. Retreatment may be
the best way to ensure that therapy was adequately performed. All root
surfaces must be meticulously inspected.

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 2. Poor plaque control
Plaque control is essential to the success of periodontal therapy. Patients
must understand the role of bacterial plaque in their disease process, and
they must comply with daily oral hygiene instructions. Thus, patient
compliance and the adequacy of their daily plaque control should be
assessed before concluding that a case of periodontitis is refractory to
treatment.

3. Endodontic infection
The presence of non-periodontal infections in the area can perpetuate
periodontal disease activity and prevent a normal healing response to
conventional periodontal therapy. Endodontic infection of teeth in the area
should be suspected and ruled out before concluding that a case is
refractory to treatment. The clinician should suspect an endodontic etiology
especially in those patients with localised recurrent disease.

A case may be considered refractory to treatment only when loss of periodontal

attachment and bone continues after well executed treatment in a patient with
good oral hygiene and no other infections or etiologic factors.

Clinicians are in quandary when presented with a patient who is not responding
to periodontal therapy. Therapeutic means must be broad in scope and thorough
to ensure that all aspects of the host response are addressed. At a minimum, a
frequent and intensive recall maintenance and home care program is necessary.
Mechanical debridement with scaling and root planning can reduce total
suprag54ingival and subgingival bacterial masses, but major periodontal
pathogens may persist. Surgical treatment may aid in providing access for
debridement and in elimination of bacterial pathogens. In addition, the
morphology of the gingival tissues should be modified to facilitate daily plaque
removal by the patient.

Systemic antibiotic therapy is administered to reinforce mechanical periodontal

treatment and support the host defence system in overcoming the infection by
subgingival pathogens that remain after conventional mechanical periodontal
therapy. Many antibiotics have been used according to the target microflora
with various degrees of success. For patients with refractory disease who failed
to respond to initial antibiotic therapy, subsequent treatment should include
microbial testing with bacterial identification and antimicrobial susceptibility.

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Cases of periodontitis (refractory) in which the associated microflora consists
primarily of gram positive microorganisms have been successfully treated with
amoxicillin-clavulanate potassium. Many efforts have been to establish the most
appropriate regimen of antibiotic therapy for these patients. Similar
antimicrobial regimens, consisting of 250mg of amoxicillin and 125mg of
clavulanate potassium, have been administered 3 times daily for 14 days, with
scaling and root planning, and produced a reduction in attachment loss for
atleast 12 months. A regimen of one capsule containing the same amount of
drug every six hours for 2 weeks, with intrasulcular full mouth lavage using a
10% povidone_iodine solution and chlorhexidine oral rinses twice daily,
resulted in a reduction in attachment loss that persisted at approximately 34
months. A regimen of 500mg of metronidazole 3 times daily for 7 days was
shown to be effective in treating periodontitis (refractory) in patients who were
culture positive for T.forsythia in the absence of A.actinomycetemcomitans.

Clindamycin is a potent antibiotic that penetrates well into gingival fluid,

although it is not usually effective against A.actinomycetemcomitans and
Eikenella corrodens. However, clindamycin has been effective in controlling the
extent and rate of diseases progression in refractory cases in patients who have a
microflora susceptible to this antibiotic. A regimen of clindamycin
hydrochloride, 150mg, 2 times daily for 7 days combined with scaling and root
planning reduced a decrease in the incidence of disease activity from an annual
rate of 8% to an annual rate of 0.5% of sites per patient. Clindamycin should be
prescribed with caution because of the potential for pseudomembranous colitis
from superinfections with Clostridium difficile. Patient should be warned and
advised to discontinue the antibiotic in symptoms of diarrhoea develop.

Azithromycin may be effective in periodontitis that is refractory to treatment,

especially in patients infected with P.gingivalis.

Combinations of antibiotic therapy may offer greater promise as adjunctive

treatment for the management of refractory periodontitis. The rationale is based
on the diversity of putative pathogens and no single antibiotic being bactericidal
for all known pathogens. Combination antibiotic therapy may help to broaden
the antimicrobial range of the therapeutic regimen beyond that attained by any
single antibiotic. Other advantages include lowering the dose of individual
antibiotics by exploiting possible synergy between two drugs against targeted
organisms. In addition, combination therapy may prevent or forestall the
emergence of bacterial resistance. Many combinations of antibiotics have
demonstrated significant improvement in the clinical aspects of the disease.
Examples of combinations include amoxicillin-clavulanate or metronidazole-
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amoxicillin for the treatment of A.actinomycetemcomitans associated
periodontitis; metronidazole-doxycycline for the prevention of recurrent
periodontitis; metronidazole-ciprofloxacin for the treatment of recurrent cases
containing a microflora associated with enteric rods and pseudomonads; and
amoxicillin doxycycline in the treatment of periodontitis associated with
A.actinomycetemcomitans and P.gingivalis.

Some cases of periodontitis that are refractory to treatment may not respond to a
given antibiotic regimen. When this occurs, the clinician should consider a
different antimicrobial therapy based on microbial susceptibility analysis. At
this point in the therapy, strong consideration should be given to consulting with
the patient’s physician for an evaluation of possible host immune system
deficiency or metabolic problem such as diabetes.

Necrotising ulcerative periodontitis

Necrotising ulcerative periodontitis (NUP) is a rare disease, especially in
developed countries. Often NUP is diagnosed in individuals with a
compromised host immune response. The incidence of NUP in specific
populations, such as patients who are positive Human Immune deficiency Virus
(HIV) infection or have Acquired Immuno Deficiency Syndrome (AIDS) has
been reported to be between 0% and 6%. These patients often have an
underlying predisposing systemic factor that renders them susceptible to NUP.
For this reason, patients presenting with NUP should be treated in consultation
with their physician.

The comprehensive medical evaluation and diagnosis of any condition that may
be contributing to an altered host immune response should be completed. It is
also important to rule out any haemotologic diseases (eg. Leukemia) before
initiating treatment of a case that has similar presentation to NUP.

Treatment can be initiated only after a thorough medical history and

examination to identify the existence of any systemic diseases. Treatment for
NUP includes local debridement of lesions with scaling and root planning,
lavage and instructions for good oral hygiene. It may be necessary to use local
anaesthesia during debridement because lesions are frequently painful. The use
of ultrasonic instrumentation with profuse irrigation may enhance debridement
and flushing of the deep lesions achieving good oral hygiene may be
challenging as well until the lesions and associated pain resolve.

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Antimicrobial adjuncts, such as chlorhexidine, added to the oral hygiene
regimen may be effective in contributing to the daily reduction of bacterial
loads. Patients frequently complaint of pain. The use of locally applied topical
antimicrobials and systemic antibiotics, as well as systemic analgesics, should
be used as indicated by signs and symptoms.

Patients with NUP often harbour bacteria, fungi, virus and other non-oral
microorganisms, complicating the selection of antimicrobial therapy.
Superinfection or overgrowth of fungi and viruses may be propagated by
antimicrobial therapy. Antifungal and/or antiviral agents can be considered
prophylactically against these infections or after they are diagnosed. Since oral
hygiene for these patients is complicated by the painful lesions, alternate
methods should be encouraged. In such patients, irrigation with diluted
cleansing and antimicrobial agents can be of some benefit.

Ultimately the successful treatment of NUP may depend on the reduction or

treatment of the systemic condition (Immune compromised) that predisposed
the individual to the disease. Evaluation and treatment of patients with known
systemic conditions, such as HIV infection, should be co-ordinated with the
patient’s physician.

Conclusion
Treatment of aggressive and atypical forms of periodontal disease is
challenging for clinicians because these forms are in frequently encountered can
manifest with more severe bone loss, and don’t respond as predictably or as
favourably to conventional therapy. Fortunately only a small percentage of
patients are diagnosed with these forms of periodontitis. This chapter discussed
therapies and rationale for management of these challenging cases.

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