Hepatocyte growth factor exhibits anti-fibrotic effects in an in vitro model of nifedipine-induced gingival overgrowth.

PURPOSE: The aim of this study was to establish an in vitro model of nifedipine-induced gingival overgrowth and characterize the anti-fibrotic effect of hepatocyte growth factor (HGF) using this model. METHODS: Human gingival fibroblasts were cultured-treated with 0.1, 1, or 10 µg/mL nifedipine or 10 ng/mL IL-1ß + 0.1, 1, or 10 µg/mL nifedipine (0.1N, 1N, 10N, IL + 0.1N, IL + 1N, IL + 10N). Cell proliferation and levels of type I collagen, TGF-ß1, CCN2/CTGF, and α-SMA were measured 48 h after the simultaneous addition of 10 and 50 ng/mL HGF (10 and 50HGF) along with IL-1ß and nifedipine. Type I collagen was measured after administration of anti-HGF neutralizing antibody. RESULTS: Significant increases in type I collagen, TGF-ß1, and CCN2/CTGF were observed after treatment in the 1N and IL + 0.1N groups. Levels of type I collagen and CCN2/CTGF differed significantly between the IL + 0.1N group and the IL + 0.1N + 50HGF group. Production of type I collagen increased significantly following addition of anti-HGF antibody. CONCLUSION: This study demonstrated the establishment of an in vitro model of nifedipine-induced gingival overgrowth by showing increased collagen levels. Experiments using this model suggested that HGF exerts anti-fibrotic effects.

Lamotrigine-Induced Gingival Enlargement: An Older Problem Due to a Newer Drug - A Rare Case Report.

INTRODUCTION: Gingival enlargement (GE) due to anti-epileptic drugs (AEDs) shows a high prevalence rate. However, lamotrigine, a newer AED, has not shown to induce GE. The present case report describes a rare case of GE in a patient with epilepsy under lamotrigine therapy for the past 3 years. CASE PRESENTATION: In this report, successful management of lamotrigine-influenced GE in a 24-year-old patient with epilepsy by gingivectomy followed by stringent oral hygiene protocol is presented. CONCLUSION: The present case report suggests that, even this newer AED can cause GE and the oral hygiene status of the patients could be an important triggering factor.

Antioxidants protect against gingival overgrowth induced by cyclosporine A.

OBJECTIVE: We investigated the importance of reactive oxygen species (ROS) on developing gingival overgrowth (GO) and then introduced the antioxidant strategy to prevent, or even reduce GO. BACKGROUND: Gingival overgrowth is a common side effect of the patients receiving cyclosporine A (CsA), an immune suppressant. Although it has been broadly investigated, the exact pathogenesis of the induced GO is still uncertain. METHODS: We cultured human primary gingival fibroblasts and used animal model of GO to investigate the ameliorative effects of antioxidants on CsA-induced GO. To examine the CsA-induced oxidative stress, associated genes and protein expression, and the overgrown gingiva of rats by using immunocytochemistry, confocal laser scanning microscopy, real-time PCR, ELISA, gelatin zymography, gingival morphological, and immunohistochemical analysis. RESULTS: We found for the first time that ROS was responsible for the CsA-induced oxidative stress and TGF-ß1 expression in human primary gingival fibroblasts, as well as the GO of rats. The antioxidants (oxidative scavenger of vitamin E and an antioxidative enzyme inducer of hemin) ameliorated CsA-induced pathological and morphological alterations of GO without affected the CsA-suppressed il-2 expression in rats. CsA-induced oxidative stress, HO-1, TGF-ß1, and type II EMT were also rescued by antioxidants treatment. CONCLUSIONS: We concluded that CsA repetitively stimulating the production of ROS is the cause of CsA-GO which is ameliorated by treating antioxidants, including vitamin E and sulforaphane. Furthermore, the immunosuppressive effect of CsA is not interfered by antioxidant treatments in rats. This finding may thus help the clinician devise better prevention strategies in patients susceptible to GO.

Gingival overgrowth induced by anticonvulsant drugs: A cross-sectional study on epileptic patients.

OBJECTIVE: Our aim was to estimate the prevalence of gingival overgrowth (hyperplasia) and to determine whether active molecules affect the severity of overgrowth in a group of epileptic patients. BACKGROUND: The effects of phenytoin on oral health have been explored in different studies, yet little information is available on other antiepileptic drugs. METHODS: Data were collected from 213 subjects of both sexes, from 5 to 80 years. Patients taking the same antiepileptic therapy for at least 1 year and meeting the inclusion criteria of the study (n = 162) were subjected to measurement of gingival overgrowth according to the modified Harris and Ewalt classification and O'Leary's plaque control record (OLR). Descriptive statistics were calculated. Data were analyzed using Pearson's r correlation coefficient and chi-square test. Significance level was set at 5%. RESULTS: The active drugs lamotrigine, oxcarbazepine, and phenobarbital were significantly associated with gingival overgrowth in 61%, 71%, and 53% of cases, respectively, and phenytoin, valproic acid, and carbamazepine in 50%, 44%, and 32% of cases, respectively. CONCLUSION: Different antiepileptic molecules may be related to gingival overgrowth. In addition to phenytoin, also lamotrigine, oxcarbazepine, and phenobarbital were associated with increased prevalence of gingival overgrowth. In the management of epileptic patients, dentists should take into account different drugs as possible causes for gingival overgrowth and warn for possible alternatives.

Management of Cyclosporine-Influenced Gingival Enlargement With Azithromycin.

INTRODUCTION: Management of drug-influenced gingival enlargement is challenging, and surgery is most often indicated. However, because of a unique mechanism of action, azithromycin helps in the management of gingival enlargement caused by cyclosporine. An incidental observation of the effect of azithromycin in the cyclosporine-influenced gingival enlargement by physicians in 1995 led to series of basic investigations and clinical trials confirming this observation and providing a non-surgical treatment modality. CASE PRESENTATION: In this report, successful management of cyclosporine-influenced gingival enlargement in a 39-year-old renal transplant patient with the use of azithromycin without any surgical intervention is presented. CONCLUSION: Use of azithromycin for managing cyclosporine-influenced gingival enlargement is a useful alternative or adjunct to surgical management. It is hoped that this report will raise further awareness of this non-surgical modality in patients taking cyclosporine.

Amlodipine-induced gingival enlargement: A case report.

Gingival enlargements (GEs) can be caused by local, systemic diseases or drugs. Three molecules can be responsible of GEs: ciclosporin, phenytoin and calcium channel blockers (CCBs). We report the case of a 56-year-old male treated by Amlodipine, a CCB, for hypertension for many years and who recently developed a severe GE affecting both mandibular and maxillary arches inducing dental malposition. The histological examination showed non-specific inflammation with a predominance of lymphocytes. Amlodipine was suspected and suspended in agreement with his physician. One month later, the enlargement significantly reduced but GE was so severe and dental malposition so marked that all the teeth but the canines were extracted. No recurrence was noted one year later. This exceptional case should encourage every practitioner to be vigilant with patient treated with CCBs and their potential side effects and consequences.

Gingival leukemic infiltration as the first manifestation of acute myeloid leukemia.

Leukemic infiltration of the gingival tissue associated or not with gingival enlargement may be the first manifestation of acute leukemia, despite being rarely reported in the literature. A 10-year-old female patient presented with a 1-month history of an asymptomatic, firm, and pinkish-red generalized gingival overgrowth. There was no bone resorption. Incisional biopsy of the gingival tissue was performed, with histopathological examination revealing a diffuse and hypercellular infiltration of monocytoid cells. The patient was referred to a hematologist and underwent a bone marrow biopsy, which led to a conclusive diagnosis of acute myeloid leukemia. The patient was treated with chemotherapy and we observed regression of gingival enlargement after 4 weeks from the initial therapy.

4PBA strongly attenuates endoplasmic reticulum stress, fibrosis, and mitochondrial apoptosis markers in cyclosporine treated human gingival fibroblasts.

Cyclosporine induces overgrowth of human gingiva. Previously we have shown (i) cyclosporine-inducing ER stress in human gingival fibroblasts (HGF), (ii) increased matrix protein expression, and (iii) interference with mitochondrial pro- and anti-apoptotic factors. This study was undertaken to assess the effects of melatonin (an antioxidant), 4PBA (an ER stress inhibitor), and simvastatin on the expression of ER Stress markers as well as on matrix and mitochondrial markers. HGF incubated with cyclosporine, or without melatonin/4PBA/statin. After 24 hr of incubation, mRNA expression of ER stress markers (GRP78, CHOP, XBP1, and XBPs) and matrix protein markers (like α-SMA, VEGF, TGF-ß, CTGF), and mitochondrial apoptosis markers estimated and compared with housekeeping gene GAPDH. Compared to the control cyclosporine significantly augmented ER Stress and matrix proteins, which decreased significantly with the use of melatonin, 4PBA, and simvastatin. The mitochondrial proapoptotic molecule cyclophilin D, as well as Bcl2 expression also decreased after PBA treatment, paralleling an increase in cytochrome c expression. The effect of 4PBA was much more pronounced than the influence of other two. In conclusion, 4PBA could be a viable therapeutic option for drug-induced gingival overgrowth.

La toxina botulínica como adyuvante en el tratamiento de la sonrisa gingival / Botulinum toxin as an adjuvant in the treatment of gummy smile

RESUMEN: La búsqueda de la excelencia estética es un objetivo importante de la odontología. La sonrisa gingival es una de las principales quejas estéticas, ya que perjudica la autoestima y las relaciones sociales del paciente. Nuevas técnicas como la aplicación de la toxina botulínica (TB) pueden tornarse una opción terapéutica más conservadora, y ayudar a disminuir las proporciones de las intervenciones quirúrgicas resectivas. El propósito de este trabajo es describir la aplicación de la TB como adyuvante de la cirugía gingival resectiva, a través del reporte de un caso clínico de discrepancia dentogingival y sonrisa gingival. Con la cirugía resectiva el equilibrio dentogingival fue mejorado, y la aplicación de TB tipo A causó la dehiscencia uniforme del labio superior, devolviendo la armonía facial. La TB es un complemento útil y conservador en la mejora estética de la sonrisa, y puede aumentar los resultados de la cirugía gingival resectiva.

ABSTRACT: The search for aesthetic excellence is an important goal in dentistry. The gummy smile is one of the main aesthetic complaints as it can affect self-esteem, and prejudice the patients' social relationships. New techniques, such as the application of botulinum toxin (BT) may become a more conservative treatment option and help to reduce the proportions of resective surgery. The purpose of this paper is to describe the application of BT, used as an adjuvant to gingival resection surgery, using a case report of a dento-gingival discrepancy and gummy smile. The resection surgery improved the dento-gingival equilibrium and the application of BT led to a uniform dehiscence of the upper lip, and facial harmony. BT is a useful and conservative adjuvant in the aesthetic enhancement of the smile, and can improve the outcomes of gingival resection surgery.

Tanshinone IIA treatment alleviated the rat gingival connective tissue overgrowth induced by cyclosporine A.

BACKGROUND AND OBJECTIVE: The use of cyclosporine A induces fibrous enlargement of the gingival connective tissue. Existing treatment modalities, although effective, do not necessarily prevent the recurrence of the lesion. Emerging evidence indicates that tanshinone IIA (Tan IIA) could effectively attenuate a variety of fibrotic diseases. The present research aims to assess whether Tan IIA can effectively alleviate the gingival fibrous overgrowth induced by cyclosporine A. MATERIAL AND METHODS: Forty-five Wistar rats were divided into the no-treatment control group, cyclosporine A-treated group and the group treated with a combination of cyclosporine A and Tan IIA. Paraffin-embedded sections of mandibular first molar regions were selected for hematoxylin and eosin staining, Masson's trichrome staining, picro-sirius red staining and immunohistochemistry analyses of transforming growth factor-ß1 (TGF-ß1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-1 (MMP-1). The gingival connective tissue area was measured and numbers of the TGF-ß1-, TIMP-1- and MMP-1-positive cells were counted. The analysis of variance for factorial designs for testing the overall differences and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. RESULTS: Cyclosporine A treatment led to overgrowth of gingival connective tissue in rats. In the cyclosporine A-treated rats, the expression of TGF-ß1 and TIMP-1 was significantly upregulated, whereas expression of the MMP-1 was downregulated, along with thicker and denser collagen fibers. In rats treated with a combination of cyclosporine A and Tan IIA, the cyclosporine A-induced changes were alleviated. CONCLUSIONS: Cyclosporine A enhanced gingival fibrous overgrowth via upregulation of the TGF-ß1 and TIMP-1 expression, and downregulation of MMP-1 expression. Tan IIA can effectively prevent cyclosporine A-induced gingival fibrous overgrowth in rats by downregulating TGF-ß1 and TIMP-1 expression, and upregulating MMP-1 expression.

Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18α-glycyrrhetinic acid inhibits human gingival fibroblast growth.

BACKGROUND AND PURPOSE: This investigation aimed to establish the basis of a pharmacotherapy for nifedipine-induced gingival overgrowth. Gingival overgrowth has been attributed to the enhanced growth of gingival fibroblasts. In this study, we investigated the effects of 18-α-glycyrrhetinic acid (18α-GA) on growth, the cell cycle, and apoptosis and on the regulators of these processes in gingival fibroblasts isolated from patients who presented with nifedipine-induced gingival overgrowth. EXPERIMENTAL APPROACH: Gingival fibroblasts were cultured in medium containing 1% FBS with/without 10 µM 18α-GA for 24 or 48 h, and the cell number, cell cycle phase distribution, relative DNA content, apoptotic cell number and morphological characteristics of the cells undergoing apoptosis were measured together with the levels of proteins that regulate these processes and the level of caspase activity. KEY RESULTS: 18α-GA significantly decreased cell numbers and significantly increased the percentage of cells in the sub-G1 and G0 /G1 phases of the cell cycle and the number of apoptotic cells. Nuclear condensation and fragmentation of cells into small apoptotic bodies appeared in the fibroblasts treated with 18α-GA. In addition, 18α-GA significantly decreased the protein levels of cyclins A and D1, CDKs 2 and 6, phosphorylated Rb (ser(780) and ser(807/811)), Bcl-xL and Bcl-2 and increased the protein levels of p27, cytosolic cytochrome c, pro-caspase-3, and cleaved caspase-3 and the activities of caspases 3 and 9. CONCLUSIONS AND IMPLICATIONS: 18α-GA inhibited gingival fibroblast growth by suppressing the G1 /S phase transition and inducing apoptosis. In conclusion, 18α-GA may be used as a pharmacotherapy for nifedipine-induced gingival overgrowth.

Effect of chlorhexidine varnish on gingival growth in orthodontic patients: a randomized prospective split-mouth study.

INTRODUCTION: Fixed orthodontic appliances patients suffer limitations on the effective control of biofilm by mechanical methods, bringing the need of a coadjutant in the control of inflammation and oral health improvement. OBJECTIVE: The aim of this prospective split-mouth blind study was to analyze the effect of a 40% chlorhexidine (CHX) varnish on gingival growth of patients with orthodontic fixed appliances. METHODS: Healthy teenage patients with fixed orthodontic appliances and increased gingival volume were recruited (n = 30). Each individual was his own control, having in the maxilla one control side and one treatment side. An application of varnishes occurred on the vestibular area of the upper premolars and first molar crowns, on the control side (placebo varnish) and on the experimental side (EC40(r) Biodentic CHX varnish). The varnishes and sides were randomly chosen and its identification and group was kept by a third party observer and it was not revealed to the researchers and participants until the end of study. In order to establish a baseline registration, digital photographs were taken by a trained photographer before varnish application at baseline (T0), as well as 14 days (T14) and 56 days (T56) after the application. The gingival volume was calculated indirectly using the vestibular areas (mm2) of the upper second premolars' clinical crowns by RapidSketch(r) software, at all study times. The data were analyzed using ANOVA and the Turkey-Krammer test. RESULTS: It was observed, in the final sample of 30 individuals, that at T0, the control and treatment groups were similar. At T14 and T56, a progressive reduction of the clinical crown area was seen in the control group, and an increase in the average area was detected in the experimental group (p < 0,05). CONCLUSIONS: The use of 40% CHX varnish decreases the gingival overgrowth in patients undergoing orthodontic treatment. Further studies are necessary to set the action time and frequency of application.

Effect of chlorhexidine varnish on gingival growth in orthodontic patients: a randomized prospective split-mouth study

Introduction: Fixed orthodontic appliances patients suffer limitations on the effective control of biofilm by mechanical methods, bringing the need of a coadjutant in the control of inflammation and oral health improvement.Objective: The aim of this prospective split-mouth blind study was to analyze the effect of a 40% chlorhexidine (CHX) varnish on gingival growth of patients with orthodontic fixed appliances. Methods: Healthy teenage patients with fixed orthodontic appliances and increased gingival volume were recruited (n = 30). Each individual was his own control, having in the maxilla one control side and one treatment side. An application of varnishes occurred on the vestibular area of the upper premolars and first molar crowns, on the control side (placebo varnish) and on the experimental side (EC40(r) Biodentic CHX varnish). The varnishes and sides were randomly chosen and its identification and group was kept by a third party observer and it was not revealed to the researchers and participants until the end of study. In order to establish a baseline registration, digital photographs were taken by a trained photographer before varnish application at baseline (T0), as well as 14 days (T14) and 56 days (T56) after the application. The gingival volume was calculated indirectly using the vestibular areas (mm2) of the upper second premolars' clinical crowns by RapidSketch(r) software, at all study times. The data were analyzed using ANOVA and the Turkey-Krammer test.Results:It was observed, in the final sample of 30 individuals, that at T0, the control and treatment groups were similar. At T14 and T56, a progressive reduction of the clinical crown area was seen in the control group, and an increase in the average area was detected in the experimental group (p < 0,05).Conclusions: The use of 40% CHX varnish decreases the gingival overgrowth in patients undergoing orthodontic treatment. Further studies are necessary to set the action time and frequency of application.

Introdução: pacientes com aparelhos ortodônticos fixos sofrem limitações no controle efetivo de biofilme por métodos mecânicos, trazendo a necessidade de um coadjuvante no controle na inflamação e melhora na saúde bucal.Objetivo:esse estudo cruzado prospectivo randomizado teve como objetivo analisar o efeito do verniz de clorexidina (CHX) a 40% no crescimento gengival de pacientes com aparelhos ortodônticos fixos.Métodos:indivíduos adolescentes com aparelhos ortodônticos fixos e aumento de volume gengival foram recrutados para a pesquisa (n = 30). Cada participante atuou como seu próprio controle, tendo, na maxila, um lado controle e um tratamento. No lado controle, aplicou-se verniz placebo e no lado experimental, o verniz EC40(r) Biodentic CHX, ambos na face vestibular das coroas dos pré-molares e primeiro molar superiores. Os vernizes e lados foram escolhidos de forma aleatória e a identificação deles e a que grupo pertenciam foi mantida por um terceiro observador, não sendo revelada aos pesquisadores nem aos participantes até o final do estudo. Fotografias digitais foram tiradas por um fotógrafo treinado, antes da aplicação do verniz no tempo inicial (T0), bem como 14 dias (T14) e 56 dias (T56) após a aplicação. O volume gengival foi calculado indiretamente, por meio das áreas vestibulares (mm2) das coroas dos segundos pré-molares superiores, com o softwareRapidSketch(r), em todos os tempos de estudo. Os dados foram analisados usando ANOVA e teste de Turkey-Krammer.Resultados:na amostra final de 30 indivíduos, observou-se que, em T0, os grupos controle e tratamento foram semelhantes. Já em T14 e T56, foi observada uma progressiva redução na área da coroa clínica no grupo controle, e um aumento na área média do grupo experimental (p< 0,05).Conclusão:o uso do verniz de CHX a 40% diminui o excessivo crescimento gengival em pacientes sob tratamento ortodôntico. Estudos futuros são necessários para se determinar o tempo de ação e a frequência de aplicação.

Cellular crosstalk mechanism of Toll-like receptors in gingival overgrowth (review).

Gingival overgrowth is an undesirable outcome of systemic medication and is evidenced by the accretion of collagenous components in gingival connective tissues along with diverse degrees of inflammation. Phenytoin therapy has been found to induce the most fibrotic lesions in gingiva, cyclosporine caused the least fibrotic lesions, and nifedipine induced intermediate fibrosis in drug­induced gingival overgrowth. In drug­induced gingival overgrowth, efficient oral hygiene is compromised and has negative consequences for the systemic health of the patients. Toll­like receptors (TLRs) are involved in the effective recognition of microbial agents and play a vital role in innate immunity and inflammatory signaling responses. TLRs stimulate fibrosis and tissue repairs in several settings, although with evident differences between organs. In particular, TLRs exert a distinct effect on fibrosis in organs with greater exposure to TLR ligands, such as the gingiva. Cumulative evidence from diverse sources suggested that TLRs can affect gingival overgrowth in several ways. Numerous studies have demonstrated the expression of TLRs in gingival tissues and suggested its potential role in gingival inflammation, cell proliferation and synthesis of the extracellular matrix which is crucial to the development of gingival overgrowth. In the present review, we assessed the role of TLRs on individual cell populations in gingival tissues that contribute to the progression of gingival inflammation, and the involvement of TLRs in the development of gingival overgrowth. These observations suggest that TLRs provide new insight into the connection among infection, inflammation, drugs and gingival fibrosis, and are therefore efficient therapeutic target molecules. We hypothesize that TLRs are critical for the development and progression of gingival overgrowth, and thus blocking TLR expression may serve as a novel target for antifibrotic therapy.

Effect of adjunctive roxithromycin therapy on interleukin-1ß, transforming growth factor-ß1 and vascular endothelial growth factor in gingival crevicular fluid of cyclosporine A-treated patients with gingival overgrowth.

BACKGROUND AND OBJECTIVE: Systemic macrolide antibiotic administration has been shown to result in the elimination or reduction cyclosporine A-induced gingival overgrowth. Roxithromycin (ROX) is known to have anti-inflammatory, immunomodulatory and tissue reparative effects. This study was to evaluate the effect of adjunctive ROX therapy on cyclosporine A-induced gingival overgrowth and interleukin (IL)-1ß, transforming growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF) levels in gingival crevicular fluid of renal transplant patients. MATERIAL AND METHODS: Thirty-one patients with clinically significant overgrowth and 16 periodontally healthy subjects were included in this randomized, double-blind, placebo-controlled, parallel-arm study. Patients received scaling and root planing (SRP) at baseline and randomized to take either ROX or placebo for 5 d. The clinical parameters, including plaque index, papillary bleeding index, probing depth and gingival overgrowth scores, were recorded. The amounts of IL-1ß, TGF-ß1 and VEGF in gingival crevicular fluid were detected by ELISA. Periodontal parameters as well as gingival crevicular fluid biomarker levels were evaluated at baseline and at 1 and 4 wk post-therapy. RESULTS: Following SRP plus ROX and SRP plus placebo therapy, significant improvements in clinical periodontal parameters of both study groups were observed (p < 0.025). In the ROX group, adjunctive ROX therapy resulted in a greater gingival overgrowth scores reduction compared with those in the placebo group at 4 wk (p < 0.017). Initial amounts of IL-1ß, TGF-ß1 and VEGF for both the ROX and placebo groups were significantly higher than those for healthy subjects (p < 0.017), with no statistical difference between the two study groups. At 1 and 4 wk post-therapy, significant decreases in the amounts of IL-1ß, TGF-ß1 and VEGF were observed in both study groups when compared with baseline (p < 0.025), but there was no difference in the levels of IL-1ß and VEGF between the two study groups. The amount of decrease in TGF-ß1 levels for the ROX group was statistically significant compared to that for the placebo group at 4 wk after treatment (p < 0.017). CONCLUSION: Our study indicated that combination of ROX with non-surgical therapy improves gingival overgrowth status and decreases gingival crevicular fluid TGF-ß1 levels in patients with severe gingival overgrowth. The reduction of gingival crevicular fluid TGF-ß1 following ROX therapy suggests an anti-inflammatory/immunomodulatory effect of ROX on the treatment of cyclosporine A-induced gingival overgrowth.

Post-chemotherapeutic resolution of acute myeloid leukaemia-induced gingival enlargement: a case report.

INTRODUCTION: Leukaemia is a neoplastic dsorder characterized by an excessive proliferation of immature white blood cells and their precursors. Patients with this potentially fatal condition may often first present with gingival enlargement. Early diagnosis of the underlying condition and prompt referral for appropriate therapy, may be life-saving. CASE REPORT: A 27-year-old female was referred to the Department of Oral Medicine and Periodontology complaining of a generalised gingival enlargement that was aesthetically displeasing to her. She insisted on immediate surgical removal of the enlarged gingival tissue but, on counseling, agreed to have prior diagnostic tests performed. A full blood count suggested the presence of an underlying acute myeloid leukaemia. The patient was consequently referred to the Oncology Department for further investigation and management. The diagnosis was confirmed and the subsequent chemotherapeutic intervention was strikingly successful, leading to the complete resolution of the gingival enlargement. CONCLUSION: This paper emphasises the importance of a full diagnostic evaluation of all cases of gingival enlargement and immediate referral should a life-threatening condition be identified, such as, in the present case, acute myeloid leukaemia.

Histological and immunohistochemical features of gingival enlargement in a patient with AML.

Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells.

Azithromycin in periodontal treatment: more than an antibiotic.

Azithromycin is a macrolide antibiotic used extensively in medicine for the treatment of a wide range of infections such as upper respiratory tract infections, middle ear infections, sexually transmitted infections and trachoma. It is also effective against the most common periodontopathogens. The versatility of the macrolides extends beyond their antibiotic properties as a result of their well-documented immune-modulating/anti-inflammatory effects. Macrolides, including azithromycin, are therefore used to treat diseases not associated with bacteria, such as severe asthma, chronic obstructive pulmonary diseases and, more recently, cystic fibrosis. Azithromycin is concentrated in neutrophils, macrophages and particularly fibroblasts; all of these cells are central players in the pathogenesis of most periodontal diseases. This paper reviews the diverse properties of azithromycin and the clinical periodontal studies of its effects in both the treatment of periodontitis and in resolving drug-related gingival overgrowth. Evidence exists to support the use of a single course of azithromycin in the treatment of advanced periodontal diseases. Azithromycin could have a triple role in the treatment and resolution of periodontal diseases: suppressing periodontopathogens, anti-inflammatory activity and healing through persistence at low levels in macrophages and fibroblasts in periodontal tissues, even after a single course of three tablets. If future periodontal research confirms these properties, it could become a valuable host-modulator in periodontal treatment.