Cyclosporine A-Induced Conchal Hyperplasia with Nasal Obstruction in a Patient with Membranous Nephropathy.

BACKGROUND The immunomodulatory and pharmacokinetic effects of cyclosporine A are used to treat diverse disease entities in different medical fields, including organ transplantation and/or autoimmune diseases. It is also applied in patients with nephrotic range proteinuria as an adjunct to steroids and supportive antihypertensive/antiproteinuric medications. Cyclosporine has a small therapeutic window and is dosed with respect to the underlying disease entity and severity via trough level adaptations. Among its most frequent adverse effects are hypertension, nephrotoxicity, neurotoxicity, and electrolyte disturbances. Hypertrichosis and gingival hyperplasia are obvious and widely recognized adverse effects. CASE REPORT We report on a 66-year-old woman who was treated with cyclosporine A for primary membranous nephropathy. During treatment with cyclosporine, she developed hirsutism and gingival hyperplasia. Later, she reported having impaired nasal breathing and dyspnea on mild physical exercise. Clinical, rhinoscopic, and radiological evaluations showed marked conchal hyperplasia as a potential cause of her symptoms. An extensive medical work-up did not show evidence of allergic, immunologic, or other drug adverse effects, suggesting cyclosporine-induced hyperplasia of the turbinates as a hypothetical causative factor. Dose reductions did not lead to resolution of symptoms but resulted in increasing proteinuria. Therefore, cyclosporine was stopped, and the patient was treated with rituximab. Thereafter, hirsutism and gingival and conchal hyperplasia gradually regressed over 2-4 months, showing complete resolution of conchal hyperplasia on computed-tomography follow-up after 6 months. CONCLUSIONS Cyclosporine can not only result in gingival hyperplasia but also in hyperplasia of the turbinates leading to impaired nasal breathing and shortness of breath on exertion. An extensive search for many other known causes of conchal swelling is warranted to finally suggest an adverse effect of cyclosporine. Discontinuation of cyclosporine resulted in complete remission of conchal hyperplasia as well as other adverse 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.

Role of Cyclosporine in Gingival Hyperplasia: An In Vitro Study on Gingival Fibroblasts.

BACKGROUND: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. MATERIALS AND METHODS: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the "Extracellular Matrix and Adhesion Molecules" pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control. RESULTS: Expression levels of different genes were significantly de-regulated. The gene CDH1, which codes for the cell adhesion protein E-cadherin, showed up-regulation. Almost all the extracellular matrix metalloproteases showed down-regulation (MMP8, MMP11, MMP15, MMP16, MMP24, MMP26). The administration of cyclosporine A was followed by down-regulation of other genes: COL7A1, the transmembrane receptors ITGB2 and ITGB4, and the basement membrane constituents LAMA2 and LAMB1. CONCLUSION: Data collected demonstrate that cyclosporine inhibits the secretion of matrix proteases, contributing to the accumulation of extracellular matrix components in the gingival connective tissue, causing gingival overgrowth. Patients affected by gingival overgrowth caused by cyclosporine A need to be further investigated in order to determine the role of this drug on fibroblasts.

A Conservative Approach for Localized Spongiotic Gingivitis Hyperplasia Using Photodynamic Therapy: A Case Report and Review of the Literature.

Objective: To describe a clinical case of successful conservative management of Localized Juvenile Spongiotic Gingivitis Hyperplasia (LJSGH) using photodynamic therapy (PDT) and reviews the current literature on this pathology. Background data: LJSGH is a recently described rare disease with controversial treatment results. As of today, 13 publications report surgical treatment approaches. The use of CO2 laser and cryotherapy was reported only in one study. The use of PDT was not previously reported. Patients and methods: A 9-year-old male patient was referred to our institution with the chief complaint of asymptomatic "inflamed gingiva" starting 1 year before. Clinical examination revealed an erythematous line accompanying the gingival contour, with a certain degree of hyperplasia. The diagnosis of LJSGH was performed based on clinical features and later confirmed histopathologically. A novel approach using PDT was then proposed. The photosensitizer was methylene blue, and a semiconductor laser diode was used. Results: One week after starting PDT, gingival hyperplasia was partially reduced. Immediately after the end of treatment, a significant reduction of gingival hyperplasia was observed. PDT proved to be safe, quick and painless, with no esthetic harm. Conclusions: This case illustrates the benefit of a more conservative approach as opposed to surgical procedure, with good clinical response and decreased morbidity over a 2-year follow-up period.

Utilização do gel de clorexidina em crianças com hiperplasiagengival induzida pela ciclosporina / Use of chlorhexidine gel in children with cyclosporine-induced gingival hyperplasia

Crianças que apresentam insuficiência hepática e transplante de fígado tem uma condição sistêmica comprometida. Algumas alterações bucais podem ocorrer nessas crianças, inclusive hiperplasia gengival. OBJETIVO: Utilizar um gel de clorexidina para controlar e minimizar a hiperplasia gengival ocasionada pelo uso de ciclosporina associada a corticosteróide. RELATO DO CASO: Em uma criança de 2 anos e 8 meses, submetida a transplante de fígado com prescrição de ciclosporina associada à corticosteróide, que apresentava hiperplasia gengival em que a opção de remoção cirúrgica do aumento gengival não foi autorizada, foi aplicado gel inibidor de placa clorexidina, uma vez por semana durante quatro semanas. CONSIDERAÇÕES FINAIS: O gel de clorexidina mostrou-se eficaz como auxiliar na terapêutica de impedir a hiperplasia gengival...

Oroantral communication is a pathological communication that occurs between the oral cavity and the maxillary sinus. When this communication suffers epithelialization it is called oroantral fistula. It can occur mainly after extraction of posterior maxillary teeth, due to the close relationship between their roots and the maxillary sinus floor. Aim: To present the surgical options for the treatment of oroantral communication and report a case of a large oroantral fistula, explaining the technique step. Case Report: Female patient female, 37-year-old, presented bucossinusal fistula in the left upper molars area and was surgically treated for its closure. Under local anesthesia an incision was made around the fistula, cutting epithelial tissue to allow the union of the wound edges, and it was sutured by layers: initially sinus mucosa with 4-0 catgut and then the gums, with nylon. The suture was removed 10 days later and by this time the complete closure of the fistula was observed. Conclusion: The decision of which treatment modality to use for oroantral communication is influenced by many factors, such as its size, the tissue conditions and the surgeon’s skills. The surgical technique presented in this case proved effective and easy to perform, with a confortable postoperative period for the patient and with no recurrence of the communication...

A rare case of idiopathic multiple hyperplasia of inflammatory granulation in the oral cavity.

Cases of idiopathic gingival enlargement are so infrequent that the etiology and treatment are subjects of discussion. The case of a 49-year-old woman who presented with a rapidly diffuse enlargement of gingiva, clusters of patches on the buccal mucosa, and a furry-coated tongue within 2 months is reported. Results of various laboratory investigations and additional tests, such as the antineutrophil cytoplasmic antibodies (ANCA) and autoantibody to nuclear antigen (ANA) tests, were all negative. Histopathologic examination showed hyperplasia of inflammatory granulation tissues. Oral steroid therapy was effective. Although cases of multiple hyperplasia of inflammatory granulation in the oral cavity are very rare, clinicians should be aware of such cases and understand the efforts to further delineate the etiology, the management, and the prevention of the recurrence of this condition.

Can chlorhexidine mouthwash twice daily ameliorate cyclosporine-induced gingival overgrowth?

BACKGROUND/PURPOSE: Gingival overgrowth can be induced in patients treated with cyclosporine-A (CsA), an immunosuppressant often used following organ transplantation. A pre-existing rat model designed to mimic CsA-induced gingival overgrowth in humans was used to test the effectiveness of frequent application of a chlorhexidine antiplaque solution in reducing the overgrowth. METHODS: Four groups of rats were fed CsA. One group received chlorhexidine mouthwash twice a day, the second group received chlorhexidine mouthwash once a day, the third group received chlorhexidine mouthwash every other day, and the fourth group did not receive chlorhexidine mouthwash all. A fifth negative control group received only mineral oil. Overgrowth was determined by measuring the changes in the gingival probing depth and the keratinized gingival width on molars. A gingival histological examination was performed. RESULTS: Rats treated with mouthwash twice daily exhibited decreased probing depths and gingival widths without statistical significance. Histological examination revealed that CsA treatment caused gingival enlargement, whereas chlorhexidine treatment twice a day diminished the enlargement. CONCLUSION: These findings suggest that chlorhexidine mouthwash used twice daily may reduce the severity of CsA-induced gingival overgrowth. Further research is warranted to determine the optimal dose and treatment regimen.

Conversion to tacrolimus once-daily from ciclosporin in stable kidney transplant recipients: a multicenter study.

This 24-week, open, single-arm, prospective, multicenter study evaluated the effects of conversion from ciclosporin to Tacrolimus QD in adult kidney transplant patients. Stable patients receiving ciclosporin were converted to Tacrolimus QD at 0.1mg/kg/day. Relative change in renal function (primary endpoint) was assessed using estimated creatinine clearance (eCrCl) with a noninferiority margin set at -10%. A total of 346 patients were enrolled; and 301 patients were treated per protocol (PPS) in the hyperlipidemia (n=42), hypertrichosis (n=106), hypertension (n=77) and gingival hyperplasia (n=76) groups. Relative change in eCrCl was -0.6% in all PPS patients (95% CI, -2.2; 0.9) and -5.3% in the hyperlipidemia (CI, -9.59; -0.97), 0.9% in the hypertrichosis (CI, -2.59; 4.45), -0.1% in the hypertension (CI, -3.8; 3.68), and -1% in the gingival hyperplasia groups (CI, -4.63; 2.65) (PPS), meeting noninferiority criteria. There was no acute rejection. Decreases in serum lipids and blood pressure were moderate but without meaningful change in the number of treatment medications. Substantial decreases in severity of ciclosporin-related cosmetic side effects were evident from investigator and patient self-report of symptoms. Renal function remained stable after conversion to Tacrolimus QD. The effect of conversion on cardiovascular parameters was not clinically meaningful, however, marked improvement in ciclosporin-related cosmetic side effects was observed. (ClinicalTrials.gov number: NCT00481481).

Amlodipine-induced gingival hyperplasia in chronic renal failure: a case report.

Amlodipine is a dihydropyridine calcium channel blocker that is used in the management of both hypertension and angina. Amlodipine induced side effects are headache, dizziness, edema, flushing, palpitations, and rarely gingival hyperplasia. The exact reason of amlodipine-induced gingival hyperplasia is not known. We presented a case with chronic renal failure (CRF) that developed gingival hyperplasia due to amlodipine use, which improved after ceasing the drug.

Comparison of azithromycin and oral hygiene program in the treatment of cyclosporine-induced gingival hyperplasia.

BACKGROUND: It has been shown that azithromycin improves cyclosporine-induced gingival hyperplasia (GH), but its efficacy was never compared against an efficient oral hygiene program (OHP). The aim of this study was to analyze the effects of azithromycin plus OHP versus OHP alone in patients with cyclosporine-induced GH. METHODS: After periodontal evaluation, 20 renal transplant recipients received detailed oral hygiene instructions and a complete OHP, and were randomized to control (OHP) or azithromycin groups (OHP plus azithromycin). Patients were re-evaluated after 15 and 30 days. Both groups were similar in time after transplant, age, gender, cyclosporine dose, and cyclosporine through level and serum creatinine. The control group had fewer patients using calcium cannel blockers (10% vs. 70%, p = 0.02). RESULTS: All patients improved in pain, halitosis, and gum bleeding after OHP. The control group did not improve plaque index (PI) or GH. In contrast, baseline PI decreased from 1.52 +/- 0.28 to 0.50 +/- 0.16 on day 15 (p < 0.01) and to 0.46 +/- 0.14 on day 30 (p < 0.01) in the azithromycin group, and the GH score decreased from 1.9 +/- 0.27 to 0.90 +/- 0.27 on day 15 (p < 0.05) and to 0.70 +/- 0.21 on day 30 (p < 0.01). CONCLUSION: Azithromycin associated to efficient OHP induced a striking reduction in cyclosporine-induced GH, while efficient OHP alone improved oral symptoms but did not decrease cyclosporine-induced GH.

Oral manifestations of Wegener's granulomatosis: a report of three cases and a literature review.

BACKGROUND: Hyperplastic granular gingivitis or "strawberry gingivitis" is a rare manifestation of Wegener's granulomatosis (WG), but it is nearly pathognomonic for this multisystem autoimmune vasculitis. The dentist may be the first health care professional to see patients with symptoms and findings of this condition. Early diagnosis and treatment is the most important factor in the management of this potentially fatal disease. METHODS: The authors present three case reports that demonstrate the disease spectrum and conducted a literature review focused on current understanding of this disease. RESULTS: The first patient had only the classic gingival manifestations of the disease. The second patient had simultaneous typical gingival lesions, as well as dermatologic findings. The third patient had an atypical oral presentation of aphthous ulcers and erythematous gingiva, as well as respiratory and genital involvement. Reaching a definitive diagnosis sometimes is challenging owing to the subtle onset of the disease and variable clinical and laboratory findings. CONCLUSION AND CLINICAL IMPLICATIONS: Clinicians should be familiar with the broad variety of oral and systemic components of WG, as well as strategies to facilitate prompt disease recognition and to provide continued oral health care to these medically complex patients.

Hiperplasia gengival medicamentosa: parte I / Drug induced gingival hyperplasia: part I

INTRODUÇÃO: A hiperplasia gengival pode ser causada por alguns medicamentos, entre os quais a fenitoína. Torna-se importante a prevenção, o diagnóstico precoce e o seguimento de pessoas com epilepsia por profissional da área odontológica. OBJETIVO: O presente artigo tem o propósito de discutir os aspectos etiológicos, clínicos e terapêuticos da hiperplasia gengival medicamentosa. METODOLOGIA: Revisão da literatura. RESULTADOS: A necessidade de aliar o tratamento odontológico ao tratamento medicamentoso é enfatizada como forma de prevenir e/ou minimizar a hiperplasia gengival medicamentosa conseqüente à ação farmacológica de algumas drogas e fatores irritantes localizados nos tecidos dentais e periodontais.

INTRODUCTION: Gingival hyperplasia may be caused by some drugs including phenytoin. There are very important factors in this area, including prevention, early diagnosis, and follow-up of people with epilepsy by an specialist in odontological area. OBJECTIVE: The aim of this paper is to discuss the etiology, clinical and therapeutic aspects of drug induced gingival hyperplasia. METHODOLOGY: Literature review. RESULTS: The need to combine dental and drug treatment is emphasized as a way to prevent and/or minimize drug induced gingival hyperplasia due to pharmacological action of some drugs, as well as, local dental and periodontal irritants.

Drug-associated gingival enlargement: case report and review of aetiology, management and evidence-based outcomes of treatment.

"Gingival enlargement" is the term now used to describe medication-related gingival overgrowth or gingival hyperplasia (AAP, 2004), a condition commonly induced by three main classes of drugs: anticonvulsants, antihypertensive calcium antagonists and the immunosuppressant cyclosporin. It is important that the health practitioner is aware of the potential aetiologic agents and characteristic features in order to be able to accurately diagnose and successfully manage patients who present with a condition such as outlined in the following case presentation.

Effects of azithromycin on cyclosporine-induced gingival hyperplasia in renal transplant patients.

BACKGROUND: Gingival hyperplasia is a well-known complication of cyclosporine therapy, affecting 21% to 35% of renal transplant patients. Metronidazole, clarithromycin, and azithromycin, all azalid antimicrobial agents derived from the macrolide antibiotic erythromycin, have been used for treatment. Marked improvements in gingival hyperplasia have been recorded in particular with azithromycin. The aim of the present study was to investigate histopathological features of cyclosporine-induced gingival hyperplasia and to evaluate the quantitative efficacy of short-term azithromycin therapy. METHODS: Eighteen renal transplant patients with cyclosporine-induced gingival hyperplasia were included in the study. All patients received azithromycin with a dose of 500 mg/d for 3 consecutive days. Changes in gingival hyperplasia were evaluated by measuring the gingival sulcus depth to the cementum-enamel junction of every tooth in each of the four quadrants on days 0, 7, 30, 90, 180. Gum biopsies were obtained on days 0 and 30; the degree of inflammation was classified as "mild," "intermediate," and "severe". RESULTS: Gingival hyperplasia was reduced in all treated patients throughout the study. The degree of improvement was more significant between 0 to 7 and 7 to 30 days than at other times (respectively, P < .0001 and P < .002). Histopathologically, eight patients had severe and one patient moderate chronic inflammation at the beginning of therapy. Three other biopsies were reported as papilloma, mucosal hyperplasia, and normal gingival tissue biopsy. CONCLUSIONS: Azithromycin appears to be useful to treat cyclosporine-induced gingival hyperplasia in renal transplant patients. Treatment is inexpensive and free from known adverse effects.