Severe Gingival Hyperplasia Research Articles

CongenitalSTAT3mutation Mediates Primary Persistent Polymorphic Inflammatory Activation and T Cell Leukemogenesis

Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways play a pivotal role in inflammation and immunity, among which, JAK/STAT3 pathway is the most potent and leads the crosstalk of immunity and oncogenesis. Somatic STAT3 activatingmutations have been found in about 40% of T cell large granular lymphocytic leukemia (T-LGLL) patients, most of which are located in exon 21 which encodes Src homology 2 (SH2) domain leading to the increased activity of aberrant STAT3 protein and the upregulation of its transcriptional targets. While germline STAT3activatingmutations represent a newly defined entity of immune dysregulations named infantile-onset multisystem autoimmune disease-1 (ADMIO1, #MIM 615952). Both the two diseases are rare and poorly understood. Here, we report a pedigree including a proband, a six-year-old girl, primarily manifesting as thrombocytopenia and lymphadenopathy and her father diagnosed as T-LGLL with pure red cell aplastic anemia without autoimmune disorders preceding or during his disease course. Morphology of the bone marrow smears of the proband indicated normal hyperplasia without evident dyspepsia or increased blast cells. However, the vacuoles in monocytes and the density and size of granules in neutrophils increased, and megaloblast transformation was observed in some neutrophils. (Fig. 1A, 1B) Biopsy of an enlarged lymph node showed the reactive follicular hyperplasia. (Fig. 1C) Whole exon sequencing and pedigree analysis of the family revealed the germline STAT3 c.833G>A/p.R278Hmutation harbored by the proband which originated de novo from her father who additionally carried a germline TAL1G62Rmutation and somatically accumulated an FLT3-ITD mutation. (Fig. 2) Through single-cell RNA sequencing, we also found the increase of circulating CD8+ T cells and the decrease of NK cells of the proband. (Fig. 3) The STAT3 target genes were generally overactivated, and the expression of cytokines decreased in transcription level. In the genes participating in JAK/STATs pathways, the expression of JAK3, STAT1, and STAT3was up-regulated significantly. (data not shown) Immunophenotype of the proband by flow cytometry confirmed change in immunocyte compartments, (Fig. 4) but the serum cytokine concentrations measured by flow cytometry yielded controversial results, that most of cytokines were moderately elevated, and IL-1β, IL-5, TNF-α, and IFN-γ were of the most evident. (data not shown) During the treatment and follow-up, Cyclosporin A (CsA) was efficient in maintaining her circulating platelets in the range of 166×109/L to 302×109/L, but the enlarged lymph nodes and hepatosplenomegaly had no response. Eleven months later, CsA was replaced by tacrolimusfor the severe gingival hyperplasia, which has efficiently stabilized her platelets count and normalized the enlarged lymph nodes, liver, and spleen. On the contrary, in the three and a half years' span of illness, the father was refractory to CsA and methotrexate (MTX), moreover, lethal bone marrow suppression was induced by one course of fludarabine. For the high level of HLA-I and HLA-II antibodies in the circulation, plantlets transfusions were only efficient after plasmapheresis. The father eventually died from pulmonary and gastrointestinal infection due to the failure of maternal HLA-haploidentical hematopoietic stem cell transplantation (HSCT). We comprehensively elaborated the immunophenotype of the proband and thoroughly elucidated the genetic alternations of the father which led to the T cell leukemogenesis, which brought new insight on these two rare diseases and highlighted a more scrupulous therapeutic strategy in T-LGLL with congenital mutations. Figure 1 Disclosures No relevant conflicts of interest to declare.

KNIEST SYNDROME: CASE REPORT AND REVIEW OF LITERATURE

Background Kniest syndrome (dysplasia) is a rare autosomal dominant chondrodysplasia that is characterized by distinct musculoskeletal and craniofacial irregularities. These abnormalities result from a mutation of the collagen type II gene (COL2A1) resulting in an abnormal type II collagen product. Craniofacial abnormalities seen in this syndrome include prominent eyes, flat nasal bridge, cleft palate, midface anomalies, tracheomalacia, and hearing loss. This report illustrates a case of Kniest syndrome with severe dentoskeletal malformation with cleft palate treated at Eastman Institute for Oral Health. In addition, the report also outlines clinical, histopathological and radiographic findings of the condition with a review of literature of Kniest syndrome. Method Case study of a 16 year old male with a history of Kniest syndrome presented to the Orthodontic clinic seeking treatment for misaligned teeth. The patient showed clinical features of this syndrome which included dwarfism, severe midface hypoplasia, flattened and rounded face with prominent eyes and nasal atresia. Patient had a history of cleft palate repair. Intraoral findings included severe gingival hyperplasia, high arched palate and abnormal dentoalveolar development. Conclusion Kniest syndrome (dysplasia) is a rare chondrodysplasia with differential diagnosis that can include Spondy-loepiphyseal dysplasia, Spondyloepimetaphyseal and Metatropic dwarfism. In addition to genetic testing, distinct radiographic features and histopathological studies are crucial in determining the proper diagnosis of the condition.

Gingival hyperplasia as an early manifestation of acute myeloid leukemia. A retrospective review.

BackgroundWe study the prevalence of acute myeloid leukemia (AML) among patients with severe gingival enlargement.Material and MethodsWe retrospective reviewed the clinical records of patients with severe gingival enlargement, between 2011 and 2018. The Saxer and Mühlemann index were used to measure inflammation and gingival bleeding. The degree of dental mobility was measured by the Nyman and Lindhe technique.ResultsA correlation analysis was carried out to test whether there were any associations among the different variables. In the sample of 117 patients the mean gingival bleeding index was ≥3 and the degree of dental mobility ≥2.3. 1.7% of patients, with severe gingival hyperplasia were diagnosed with AML. We found a significant association between gingival bleeding and aging (p<0.001) and a trend (0.54) between bleeding and suffering from AML.ConclusionsSevere gingival enlargement, abundant gingival bleeding, and dental mobility could be early manifestations of a blood dyscrasia. Key words:Acute myeloblastic leukemia, gingival hyperplasia, bleeding, tooth motility, oral health.

Juvenile Hyaline Fibromatosis: A 10-year Follow-up.

Juvenile hyaline fibromatosis (JHF) is a rare hereditary disease with an autosomal recessive transmission. JHF is characterized by papulonodular skin lesions, osteolytic bone lesions, flexural joint contractures, and gingival hyperplasia and usually diagnosed in infancy or early childhood. JHF is thought to be a disorder of collagen metabolism and characterized by homogenous amorphous eosinophilic material and fibrous tissue. We report the case of a 14-year-old male child with multiple papulonodular skin lesions, progressive flexion contractures of joints, and severe gingival hyperplasia, with a 10-year follow-up. Although the lesions were totally removed thrice during the last 10 years, they recurred rigorously.

Effects of Antimicrobial Peptide Cathelicidin (Ll-37) by 625 nm Led Irradiation in Porphyromonas Gingivalis Infected Immortalized Gingival Fibroblasts

SEVERE RECURRENT GINGIVAL HYPERPLASIA IN A 7-YEAR-OLD PATIENT Kate Parker, Muhammed Almomen, Peter Ayliffe, Robert Evans, Maxillofacial and Dental Department, Great Ormond Street Hospital, London, UK A 7-year-old boy has been managed at Great Ormond Street Hospital since infancy for severe recurrent gingival hyperplasia. The patient first presented at 18 months of age with severe gingival hyperplasia covering the upper and lower dentition, causing aesthetic and functional concerns. There was no family history of neurofibromatosis or other medical conditions associated with gingival hyperplasia. Medically, the patient has multiple sutural synostoses; however, no causes of the gingival hyperplasia were identified. Multiple gingivetcomies and the exposure of teeth have been performed over a period of 5 years. Histopathological diagnoses have alternated between juvenile hyaline fibromatosis and gingival fibromatosis, with the patient still being investigated for a confirmed aetiology. This case report outlines the diagnostic difficulties of this case and highlights the patient management and histopathological findings over a 5-year period. This is a rare case of paediatric severe recurrent gingival hyperplasia where the aetiology remains unknown.

The Role of MDR1 C3435T Gene Polymorphism on Gingival Hyperplasia in Turkish Renal Transplant Patients Treated With Cyclosporine in the Absence of Calcium Channel Blockers

ObjectiveTo investigate the occurrence of MDR1 C3435T gene polymorphisms in the Turkish renal transplant patients treated with cyclosporine (CsA), and correlate these findings with prevalence and degree of gingival hyperplasia (GH). MethodsBefore to renal transplantation, dental treatment and oral hygiene education of 300 renal disease patients was completed. Peripheral blood samples were collected from 154 renal transplant recipients on CsA treatment without calcium channel blockers. MDR1 C3435T gene polymorphism and GH were analyzed at posttransplant month 6. ResultsNo difference was detected among groups for age, posttransplant period, creatine levels, serum concentration of CsA, or plaque and bleeding indices (P > .05). Out of all transplanted patients, 42.8% were found to have the heterozygote genotype. This was reduced to 37.5% when individuals with GH were taken into account. However, when degree of GH was analyzed, those with severe GH were found to have the heterozygote genotype significantly more often (P < .05). ConclusionsThe MDR1 gene polymorphism is not associated with GH frequency, but may be associated with GH severity.

Non syndromic gingival fibromatosis in a mild mental retardation child

Gingival fibromatosis is a benign oral condition characterized by enlargement of gingival tissues. It usually develops as an isolated disorder but can be one of the features of a syndrome. This case report is of a 5-year-old male with severe gingival hyperplasia and mild mental retardation which was complicated by open bite, abnormal occlusion, open lip posture, and disabilities associated with mastication and speech. Full mouth gingivectomy in single sitting under general anesthesia was done with electrocautery.

Amlodipine-Induced Gingival Hyperplasia in a Great Dane

A 3 yr old, 70 kg (154 lbs) female spayed Great Dane developed gingival hyperplasia after treatment of systemic hypertension with amlodipine 7.5 mg q 12 hr for 16 mo. Physical examination was unremarkable except for systemic hypertension and severe gingival hyperplasia. Amlodipine was replaced with hydralazine (0.72 mg/kg [0.32 mg/lb]). Nine months later, gingival hyperplasia was nearly resolved and hypertension was well controlled. Calcium channel blockers such as amlodipine are a rare cause of gingival hyperplasia in the canine patient. Recognition of this side effect is important because a full recovery can be achieved when the offending agent is removed.

Two-Year Experience With Tacrolimus in Renal Transplantation After Late Conversion From Cyclosporine Therapy

Calcineurin inhibitors are associated with chronic allograft nephropathy. Protocols to reverse nephrotoxicity incorporate dosage reduction or withdrawal of these agents. Using ketoconazole as a sparing agent with mean cyclosporine doses of less than 50 mg/d, we have usually observed adverse cosmetic effects. One cohort of patients exhibited severe gingival hyperplasia that required gum resection; some also had hypertricosis. To evaluate the effects of conversion from cyclosporine (CsA) to a tacrolimus generic formulation (TAC) in patients with adverse cosmetic effects from CsA. Twenty-three patients were studied at a mean (SD) of 56 (48) months posttransplantation; serum creatinine concentration was 1.91 (0.68) mg/dL. All had eyebrow and facial hypertricosis, and 10 also had gum hyperplasia. Cyclosporine C0 or C2 levels and CsA dosage had previously been changed simultaneously with ketoconazole. The day after withdrawal of CsA, TAC therapy was started at a dose of 0.065 to 0.030 mg/kg/d. Patients were followed up for 18 months (12.76 [7.57]) with routine laboratory tests. Twenty patients without proteinuria demonstrated improved renal function at 1-month follow-up; serum creatinine concentration was 1.76 (0.42) mg/dL vs 1.47 (0.37) mg/dL (P < .02). Levels of tacrolimus were 13.82 (7.95) ng/mL at 15 days and 7.3 (3.5) ng/mL at 2 months after the dosage was decreased to 0.042 mg/kg/d. Gum hypertrophy and hypertrichosis resolved in all patients. One patient died 18 months after conversion of cardiovascular disease and chronic allograft nephropathy. Neither diabetes nor dislipidemia were noted. Generic TAC is a good therapeutic alternative in renal transplant recipients with adverse reactions to CsA.

Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, “neurotoxic” adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drugsparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

Complete response to tacrolimus in a child with severe aplastic anemia resistant to cyclosporin A

Aplastic anemia (AA) is a rare disorder in children, usually treated with immunosuppressive therapy (IST) including antithymocyte globulin (ATG) and cyclosporin A. There are no current widely used alternative therapies with comparable efficacy. We describe a child with severe aplastic anemia (SAA), who developed severe gingival hyperplasia secondary to cyclosporin A, unresponsive to intensive dental intervention. When IST was changed to tacrolimus there was a significant improvement in the gingival hyperplasia, but equally important, he achieved complete response of his AA within several months. The use of tacrolimus in children with AA may be a potential modality of treatment.

Three siblings with juvenile hyaline fibromatosis

Juvenile hyaline fibromatosis (JHF) is an extremely rare hereditary genetic disease of autosomal recessive transmission that is characterized by large cutaneous tumors commonly involving the scalp, papulonodular skin lesions, flexural joint contractures, gingival hyperplasia, and osteolytic bone lesions. JHF is usually diagnosed in young infants and in children younger than 5 years, and the lesions characteristic of this disorder consist of fibrous tissue and homogenous amorphous eosinophilic hyaline material. We report the case of a 9-year-old girl with severe gingival hyperplasia, nasal enlargement, mild osteoporosis, and multiple papulonodular skin lesions. Her two brothers (7 and 13 years of age, respectively) were also diagnosed as having JHF. In the patient described in this report, the maintenance of oral hygiene after gingivectomy enabled the continued resolution of gingival hyperplasia, although skin lesions recurred and nasal overgrowth persisted.

Juvenile hyaline fibromatosis: a case report

Juvenile hyaline fibromatosis ( JHF ) is a rare autosomal recessive disease characterized by papulonodular skin lesions, gingival hyperplasia, joint contractures, and bone lesions. The skin lesions may consist of multiple large tumors, commonly on the scalp and around the neck, and small pearly, pink papules and plaques on the trunk, chin, ears, and around the nostrils. Here, we report a 2-year-old boy with characteristic stiffness of the knees and elbows and pink confluent papules on the paranasal folds, and periauricular and perianal regions. He also had hard nodules all over the scalp and around the mouth, and severe gingival hyperplasia. The lesions were totally excised and clinicopathological diagnosis was JHF.

Ethical issues in antiepileptic trials: old issues in a new world.

Clinical trials of new antiepileptic drugs and therapies raise a number of challenging issues. Some would call them methodological issues. Others would call them safety issues. Still others would focus on ethical issues. Taking them altogether, they should be called responsibility issues. Responsible conduct of human studies of epilepsy, its pathophysiology, and its therapy, as in any clinical condition, must, of course, consider study design, procedures, safety, and ethics. These essential components cannot be separated, nor can the responsibility for ensuring that all studies are sound in all respects. The goals of scientists, of their subjects, and of society are ultimately shared goals; there may be differing emphasis and competing interests, but all parties to the research mission share common goals and share a common responsibility to ensure that studies are properly designed and conducted with all these elements in mind. At least four perspectives must be considered in human trials: those of the investigators, the sponsors, the subjects, and the research ethics review board (RERB), which used to be called the institutional review board, or IRB. Traditionally, the interests of sponsors and investigators have been aligned and linked together, as are those of the subjects and IRBs. These pairings have contributed to a confrontational environment, one that began with the imposition on the scientific and corporate communities of regulations for protection of human subjects in research, an environment that has existed for the past three decades. This paradigm pits the interests of those who want to do research against those on whom it will be done. Consider, for example, a 15-year-old female patient with a history of grand mal seizures since 2 years of age. She has taken four different drugs over the years, is now stable, has been without seizures for >1 year, and is succeeding in school. Her medication is reasonably well tolerated, except for severe gingival hyperplasia. This has been on her mind lately as she is getting ready to attend her junior prom.

Gingival hyperplasia induced by Nifedipine: case report

Nifedipine, a calcium channel blocker, is commonly used in the treatment of cardiovascular disorders. In this paper a case report is presented which describes a patient medicated with Nifedipine for angina pectoris and arterial hypertension, who developed severe gingival hyperplasia.

Cyclosporin A-induced gingival overgrowth is unrelated to allograft function in renal transplant recipients.

Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of Cyclosporine-A (CsA). This study statistically modeled the medical and dental risk factors for the development of GH following CsA administration to determine whether renal function post-transplantation was related to the incidence or extent of GH in 236 consecutive renal transplant patients. All patients were at least 6 months post-transplant and medicated with both traditional oral CsA (n=220 individuals) and the new microemulsion form CsA-Me (n=229 individuals). Patients had either received CsA alone (n=45 individuals) or cyclosporine and nifedipine (n=191 individuals). Gingival overgrowth was assessed and computerized data, available for all patients included; pre- and post-transplant medical history and post-transplant renal function, i.e., serum creatinine levels, documented rejection episodes and glomerular filtration rates (GFR). These data together with CsA serum levels and last-recorded dose of CsA, CsA-Me, nifedipine, azathioprine and prednisolone, were analysed by multivariate regression analysis using SPSS. The extent and severity of hyperplasia was significantly correlated with the dosage and serum level of CsA at 3, 6 and 12 months post-transplantation; last recorded dosage, however (p<0.0001), was the most accurate predictor of hyperplasia. Gingivitis (p<0.0001) and plaque (p<0.002), were associated with hyperplasia. Duration of renal replacement therapy, age at transplantation, post-transplant interval serum creatinine levels and documented rejection episodes were unrelated with the extent and severity of GH. Of all the renal variables only the correlation of GFR with last recorded doses of CsA and CsA-Me, approached significance; this was then considered for inclusion in the model. In a multiple regression analysis including GFR, however, only last CsA (and CsA-Me) doses and gingivitis score were selected for inclusion in the final model. These data demonstrate that inter-patient variation in the extent and severity of GH and renal function post-transplantation are unrelated and are mediated independently.

Risk factors in the development of cyclosporine-induced gingival overgrowth.

Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of cyclosporine-A (CsA). Using the largest group of renal allograft recipients assembled for this purpose, in this study, we statistically modeled the genetic (HLA), medical, and dental risk factors for the development of GH subsequent to administration of CsA. Two hundred thirty-six renal transplant patients underwent full dental examination to quantify the extent and distribution of hyperplasia and dental disease (gingivitis, plaque, and calculus). Computerized data from all patients included pre-transplant medical history and dosage of nifedipine and azathioprine, as well as dose and serum levels of CsA and CsA microemulsion. Donor and host HLA haplotype were studied to investigate potential association of haplotype and donor-host mismatching with the development of GH. We evaluated the data by multivariate regression analysis, using Statistical Package for Social Sciences (SPSS). There was no association with age, sex, duration of renal replacement therapy, or interval since transplantation or pre-transplant disease (P>0.05). There also was no association of disease with host HLA haplotype, but degree of HLA-A mismatching was protective for GH development (P<0.002). GH was associated with the dose and serum levels of CsA (P<0.001) and the last dose of CsA microemulsion (P=0.009) but not nifedipine (P=0.10). Gingival inflammation and plaque were also strongly associated with GH (P<0.0003). In multivariate analysis, however, the last recorded dose of CsA (P<0.0001), presence of local gingival inflammation (P<0.0001), and gingivitis (P<0.003) were the independent predictors of the extent and severity of GH. Inter-patient variation in the extent and severity of GH is related to CsA dose and serum levels. Differences in host HLA phenotype do not explain individual susceptibility to GH, but donor-host HLA-A mismatching may be important. Inter-site variation in the extent and severity of the disease is related to local gingival inflammation.

Treatment of pemphigus vulgaris with cyclosporine

Eight patients (two males and six females), between 35 and 67 years of age (mean age 52.7 years), with pemphigus vulgaris resistant to corticosteroids and azathioprine or in whom such treatments had provoked severe side-effects, were treated with cyclosporine. The drug was administered at a starting dosage ranging between 3 and 5 mg/kg per day. This dosage was gradually reduced to the minimum effective dosage ranging between 2 and 5 mg/kg per day. In all patients prednisone was also used. Complete remission was observed in five patients, partial remission in one and no response in two. Side-effects and laboratory abnormalities were mild and transitory: in only one patient with severe gingival hyperplasia was it necessary to reduce the dosage of cyclosporine. This drug can be used, in combination with prednisone, in patients with pemphigus vulgaris who are resistant to traditional treatments or in whom such treatments give rise to severe side-effects. Furthermore, cyclosporine allows a reduction of the dosage of prednisone (in our study by about one-third) and therefore, theoretically, the number and severity of side-effects caused by prednisone itself.

Gingival hyperplasia caused by nifedipine. Histopathologic findings.

Thirty-four cardiac patients, treated with nifedipine (Adalat, Procardia) during a period of 1 year or more, developed slight to severe gingival epithelial hyperplasia, and five cases presented nodular overgrowth of the gingiva. In terms of histopathologic and clinical morphology, nifedipine-induced gingival hyperplasia is similar to that known to be caused by phenytoin (Dilantin). Both drugs have the ability to alter calcium metabolism. We believe that the hyperplastic condition is related to calcium imbalance.

Dental management of a child with tuberous sclerosis: report of case

SUMMARYA case of an 8‐year‐old male with tuberous sclerosis was presented. A description of the clinical, radiologic, neurologic, and histologic manifestations of this disease was discussed. Severe gingival hyperplasia, associated with this disease, and concomitant delayed eruption of permanent teeth requiring surgical intervention were observed. The result of extensive gingival excision to uncover teeth for function and esthetic appearance was stable for five years.