Treatment of juvenile periodontitis with microbiologically modulated periodontal therapy (Keyes technique).

Antimicrobial therapeutic strategies widely referred to as the Keyes Technique were directed at suppression of the periodontopathic microflora of 7 juvenile periodontitis patients who were treated and followed for at least 22 months. Following collection of baseline clinical and microbiological parameters, the patients received meticulous scaling and root planing of all teeth with concomitant irrigation to probing depth of saturated inorganic salt solutions and 1% chloramine-T. The patients were recalled at approximately 2to 3-month intervals for maintenance care which was modulated by clinical parameters and phase-contrast microscopic findings. Six patients received at least 2 courses of systemic tetracycline (1 gin/day for 14 days) during the study. Patient home treatments included daily application of a sodium bicarbonate/3% hydrogen peroxide paste, and inorganic salt irrigations. Clinical reevaluations made an average of 29.6 months posttreatment showed statistically significant (p(.01) decreases in bleeding on probing in all patients. Significant decreases in probing depth, and gains in clinical attachment levels also were found in all patients, particularly in advanced sites initially 4-6 mm and >-7 mm in probing depth. Among sites with initial attachment loss >-5 mm, 25.8% experienced a >-3 mm gain in clinical attachment level from baseline with therapy. Significant decreases in motile organisms and crevicular polymorphonuclear leukocytes present in the subgingival plaque of the patients also occurred with the antimicrobial therapy employed. These findings demonstrate that juvenile periodontitis patients can be treated successfully and maintained on a long-term basis without periodontal surgery when appropriate antimicrobial therapy is directed at the subgingival periodontopathic microbiota. A wide variety of therapeutic approaches have been used to manage juvenile periodontitis (JP) patients, even though the exact nature of its etiology has been understood poorly until recently. Almost all of these approaches have employed clinical periodontal parameters alone to guide therapy diagnostically, and determine its success or failure. 1-6 Most also have placed emphasis in treatment on mechanical control of bacteriologically undefined dental plaque, and surgical correction of anatomic and morphologic defects associated with JP disease progression (i.e., infrabony pockets, inflamed gingival tissues). 1-6 Antimicrobial therapy targeted at specific diseaseassociated bacterial species in the subgingival plaque microbiota also has been suggested for treatment of jp.7,s This rationale was applied initially to the treatment of adult periodontitis lesions, and has been referred to widely as the Keyes Technique, 9 or microbiologically modulated periodontal therapy. 1°13 As a therapeutic strategy for the control of specific plaque infections ~4,15 associated with human periodontal diseases, it incorporates microbiological evaluations of the subgingival flora, such as with phasecontrast microscopy, into diagnostic decision-making and patient management. 16-21 Additionally, chemical antimicrobial agents are utilized in both office therapy and patient home treatment procedures as adjuncts to mechanical plaque removal techniques, such as root planing, flossing, and toothbrushing. ~6-21 The concept of directing therapeutic measures at specific microbial pathogens in JP has been supported by recent cultural studies of subgingival plaque from PEDIATRIC DENTISTRY: December 1985/Vol. 7 No. 4 259 JP subjects. These studies repeatedly have associated elevated numbers of certain species of gram-negative rods with localized JP sites, especially Haemophilus (formerly Actinobacillus) actinomycetemcomitans (Ha). 23-25 Further, Ha has been shown to elaborate a number of potential virulence factors (e.g., leukotoxin, collagenase, immunoglobulin proteases, fibroblast growth inhibitors, and bone resorption factors), which may be important in the pathogenesis of ]p.26 Some morphologic studies with phase-contrast, darkfield, and transmission electron microscopy also have revealed large numbers of spirochetes and motile rods in localized JP subgingival plaque. 7"8"21"27-31 Consistent with these findings, elevated serum titers of antibodies specific to antigenic determinants of Treponema species also have been reported in individuals with localized jp.32,33 However, there is evidence that not all localized JP patients harbor high proportions of motile bacteria in their subgingival microflora, 4"23’34"35 and the exact role of these organisms in JP is not well understood. The purpose of the present investigation was to determine whether the principles of microbiologically modulated perioclontal therapy (Keyes Technique)7,s, lo-13, 16-20 could be applied successfully to the long-term clinca[ management of JP. Methods and Materials This longitudinal therapeutic investigation was conducted within the clinical research facilities of the National Institute of Dental Research (NIDR), of the National Institutes of Health (NIH) in Bethesda, Maryland. The patients studied were selected from persons referred to the NIDR dental clinic for periodontal disease treatment. Seven untreated patients younger than 22 years of age with idiopathic JP, as defined by Baer, 36 were treated and followed for at least 22 months posttreatment (Table 1). Five of the JP patients were classified as having localized cases (first molars, incisors, and additional teeth equaling <14 total teeth), and 2 patients had generalized cases (->14 total teeth involved), based on the number affected teeth. 37 The 5 females and 2 males in the study had a mean age of 18 years (range = 12-21 years), and 193 teeth on initial examination. The follow-up clinical observations on the patients ranged from 22 to 39 months posttreatment, with a mean of 29.6 months. All patients were in good general health and presented with radiographic evidence of >50% bone loss associated with the permanent first molars and incisors (Fig 1), and clinical attachment loss of ->7 at these sites. Comprehensive medical and dental histories were obtained, with particular emphasis on any renal disorders, hypertension, sodium intake restrictions, or previous allergic reactions to tetracycline antibiotics. All patients underwent complete physical and hematological examinations (including CBC, SMA12, and urinalysis) conducted by the NIH Clinical Center medical staff to exclude the presence of any contributing systemic medical disorders. None of the subjects had any systemic disorders reported to be associated with periodontal manifestations in adolescents, such as diabetes mellitus, sarcoidosis, Down’s syndrome, cyclic neutropenia, agranulocytosis, Papillon-Lef~vre syndrome, of Ch6diak-Higashi syndrome. In vitro evaluations of neutrophil and monocyte functions were unavailable at the start of these studies, and were not determined for the patients followed. None of the patients had received any type of periodontal prophylaxis or systemic antibiotic therapy during the previous 6-month period. Diagnostic Procedures Clinical Examinations Clinical parameters for all teeth were assessed independently by a single NIDR staff periodontist (author WEW) who was unaware of the patient’s course of therapy (single-blind evaluation). Periodontal probing depths and clinical attachment levels were measured to the nearest mm at interproximal and buccal surfaces of all teeth with a calibrated probe, as described by Philstrom et al. 38 The degree of gingival inflammation for each tooth was determined by scoring the amount of bleeding seen after gentle probing to the "bottom" of the gingival sulcus. A sulcular bleeding score was assigned as follows:.0 = no bleeding, 1 = spot bleeding point only, 2 = bleeding along the gingival margin. Microbiological Examinations At each patient appointment, the composition of the subgingival plaque was monitored with phasecontrast microscopy at chairside to assess the effectiveness of the therapeutic measures. No cultural or immunologic monitoring was conducted as part .of this study. Enumeration of disease-associated morphotypes in subgingival plaque samples with phase-contrast microscopy followed procedures previously described, 7"16-21 and included counts of spirochetes, brush formations, motile rods (large-, medium-, and small-sized), oral protozoa (i.e., Entamoeba gingivalis, Trichomonas tenax), .and accumulated crevicular polymorphonuclear leukocytes. Briefly, subgingival plaque was removed carefully from periodontal sites with a sterile curette, placed 260 TREATMENT OF JUVENILE PERIODONTITIS: Rams et al. FIG 1. Typical molar/incisor angular defects associated with untreated JP lesions. into 0.02 ml of sterile water on a microscopic slide, coverslipped, and examined immediately at 400x and 600x with a high quality, phase-contrast microscope. The highest scoring fields for each of the bacterial and cellular morphotypes then were recorded. Based on previous research,-patients with periodontal pockets harboring ^ 125/highest scoring fields of either spirochetes, mediumor large-sized motile rods (spinning, 2 x 3-9 |xm), or crevicular polymorphonuclear leukocytes were considered in this study to have elevated numbers of disease-associated morphotypes. Small, highly motile coccobacilli (0.10.2 u,m in diameter), which exhibited a circular "darting" motion, were not considered to be disease-associated in this study, since previous reports have found this plaque morphotype predominantly in healthy periodontal sites.Multiple (^ 2) periodontal sites in each patient were monitored microbiologically as a supplement to clinical periodontal parameters. Advanced periodontal pockets and furcations in particular were monitored closely throughout the posttreatment observation periods, since the possibility of a disease-associated flora remaining in subgingival sites after the completion of treatment is known to increase significantly with residual probing depth.As these sites came into microbiological control, samples from additional surfaces less severely involved in each quadrant were evaluated to confirm suppression of the disease-associated morphotypes. However, microbiological data reported in the results section is limited to levels of disease-associated morphotypes in periodontal sites presenting at recall appointments with the worst clinical conditions (i.e., gingival inflammation) in each patient, and/or surfaces having the greatest residual probing depth or furcation involvement. For some patients, additional microbiological observations were collected for several months after the last posttreatment clinical evaluations were made. Therapeutic Procedures Professional Office Therapy All teeth were subjected to meticulous subgingival scaling and root planing until a smooth, hard root surface was detected clinically. Chemical antimicrobial agents actively were delivered subgingivally and maintained in periodontal pockets throughout these procedures. Between instrumentation of different root surfaces, instruments were disinfected routinely by passage through antiseptic solutions, such as 1% chloramine-T (sodium para-toluene sulfonchloramide), or 3% hydrogen peroxide saturated with sodium chloride. All periodontal pockets were irrigated professionally to probing depth before, during, and after mechanical instrumentation with chemical antimicrobial agents. Chloramine-T (1%) was used for this purpose, along with a saturated inorganic salt solution consisting of sodium bicarbonate (NaHCO3) or sodium chloride (NaCl). To facilitate rapid subgingival drug delivery to probing depth, especially into advanced sites (^ 7 mm) and furcations, oral irrigation devices were modified with foot-activated on/off switches, and equipped with monojet irrigation tips having 23or 25-gauge blunt needle or cannula extensions 10 mm long, as described elsewhere. The extended tip was advanced like a periodontal probe to probing depth and into furcations to maximize contact and exposure of subgingival plaque bacteria to the antiseptic agents during the mechanical debridement sessions. Approximately 4-6 hr were required for initial mechanical instrumentation and professionally applied PEDIATRIC DENTISTRY: December 1985/Vol. 7 No. 4 261 subgingival chemotherapy. No surgical flaps or osseous recontouring procedures were employed. All carious lesions and defective restorations were restored or replaced as needed. Patient Home Treatment Procedures All patients were instructed in sulcular toothbrushing and flossing. As previously described, 7"8 patients also were directed to apply daily a saturated inorganic salt solution (i..e., 2 tablespoons of NaHCO3 or NaC1 dissolved into 112 fl oz warm water) with an oral irrigation device (unmodified) at a moderate-to-high pressure setting. This was then to be followed by application of a sodium bicarbonate/3% hydrogen peroxide paste or slurry to the dentogingival surfaces via toothbrushing, flossing, interdental brushes, and rubber cone stimulators (#600a). Instruction and reinforcement was emphasized to encourage the patients to deliver the antimicrobia! chemicals as deeply as possible into the sulcus/pocket spaces during the self-applied treatments. All of the patients were capable of completing this home treatment regimen in approximately 10-15 min. At each recall appointment, patients viewed phasecontrast microscopic projections showing the bacteriologic composition of their subgingival plaque on equipment previously described. 7 This served as a feedback mechanism aiding in patient education, motivation, and compliance with prescribed home treatment procedures. The microscopic analysis also aided the treating clinician in assessing the self-care ability of patients to deliver antimicrobials into the targeted treatment sites. Modulation of Therapy The antimicrobial effects of the professional and home treatment procedures were monitored by (1) clinical examinations for evidence of changes in gingival inflammation and periodontal attachment level, and (2) phase-contrast microscopy to determine whether a satisfactory elimination of the initial periodontopathic subgingival flora had been obtained. Levels of motile bacteria and accumulated crevicular polymorphonuclear leukocytes in subgingival plaque samples were used in this study as "indicator" morphotypes to assess the presence of a disease-associated subgingival flora, and to identify patients at increased risk of destructive disease activity. Patients suffering additional clinical deterioration and/or identified as remaining with elevated numbers of disease-associated morphotypes in their subgingival flora after repeated use of the locally applied chemomechanical procedures described above, were #600 -John O. Butler Co: Chicago, IL. placed on a short-term course of systemic tetracycline HCI therapy (1 grn/day for 14 days). As previously stated, patients with periodontal sites harboring ~ 125/highest scoring fields of either spirochetes, mediumto large-sized motile rods (spinning, 2 x 3-9 + ~m), or crevicular leukocytes were considered in this study to have elevated numbers of disease-associated morphotypes. The effects of adjunctive antibiotic therapy on motile bacteria and crevicular leukocyte levels were checked, by examining new subgingival plaque samples with phase-contrast microscopy at the end of the 14-day drug course. Periodontal recall therapy was carried out a.t approximately 2-3 month intervals, and included reinforcement of patient home treatment procedures, mechanical instrumentation of all tooth surfaces, and subgingival irrigations to probing depth of all sites with chemical antimicrobial agents. Additional systemic tetracycline therapy as described above was prescribed if further clinical deterioration appeared and/or persistent reinfection of the subgingival microflora with high levels (~ 125/highest scoring fields) of motile bacteria or accumulated crevicular leukocytes were seen with phase-contrast microscopic monitoring.