Caracterización clínica de pacientes chilenos con displasia fibrosa/síndrome de McCune-Albright / Clinical features of Chilean patients with Fibrous Dysplasia/McCune-Albright Syndrome

BACKGROUND: Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) is characterized by a spectrum of manifestations that may include fibrous dysplasia of bone and multiple endocrinopathies. AIM: To describe the clinical spectrum, the study and follow-up of patients with FD/MAS cared at our institution. MATERIAL AND METHODS: Review of medical records of 12 pediatric and adult patients (11 women) who met the clinical and genetic diagnostic criteria for FD/ MAS. RESULTS: The patients' mean age at diagnosis was 4.9 ± 5.5 years. The most common initial clinical manifestation was peripheral precocious puberty (PPP) in 67% of patients and 75% had café-au-lait spots. Fibrous dysplasia was present in 75% of patients and the mean age at diagnosis was 7.9 ± 4.7 years. Ten patients had a bone scintigraphy, with an age at the first examination that varied between 2 and 38 years of age. The most frequent location of dysplasia was craniofacial and appendicular. No patient had a recorded history of cholestasis, hepatitis, or pancreatitis. In four patients, a genetic study was performed that was positive for the pathogenic variant of guanine nucleotide binding protein, alpha stimulating (GNAS). CONCLUSIONS: These patients demonstrate the variable nature of the clinical presentation and study of FD/MAS. It is essential to increase the index of diagnostic suspicion and adherence to international recommendations.

Conservative Treatment of Chronic Osteomyelitis Associated with Florid Osseous Dysplasia / Tratamiento Conservador de la Osteomielitis Crónica Asociada con Displasia Ósea Florida

ABSTRACT: Florid osseous dysplasia (FOD) is an extensive form of osseous dysplasia where normal trabecular bone is substituted by fibrous connective tissue and amorphous mineralized tissue. Usually, the lesions are mainly asymptomatic and the patients should be followed with clinical and imaging examination, requiring no intervention. Nevertheless, due to the poor vascularization of the lesion and to local trauma, secondary infections and osteomyelitis may occur. Patients may present with pain, mucosal ulceration, lesion exposure in the oral cavity, fistula and swelling. In such cases, the correct diagnosis and management of the lesion is decisive to reestablish patient's health and quality of life. The aim of this article is to present a case of complicating secondary chronic osteomyelitis treated successfully with conservative intervention. A 68-year-old black female patient reported a "swelling of the gums" that was present for eleven years, with episodes of periodic pain and swelling. On physical examination, a papule with suppuration in the alveolar mucosa in the right side of the mandible was observed. Panoramic radiography and CBCT showed a mixed lesion surrounded by sclerotic bone. The patient was diagnosed with chronic osteomyelitis in association with FOD and treated with antibiotic therapy together with surgical curettage. The incidence, etiophatology, differential diagnosis, treatment and prevention of secondary osteomyelitis associated with FOD are discussed in the light of literature. This information might assist the dentists while choosing the best treatment options for similar cases.

RESUMEN: La displasia ósea florida (DOF) es una forma de displasia ósea donde el hueso trabecular normal es sustituido por tejido conectivo fibroso y tejido mineralizado amorfo. En general, las lesiones son de origen asintomático y los pacientes deben ser seguidos con el examen clínico. Sin embargo, debido a la pobre vascularización de la lesión y al trauma local, pueden producirse lesiones secundarias y osteomielitis. Los pacientes pueden presentarse con dolor, ulceración mucosa, lesión de exposición en la cavidad oral, fístula y edema. En estos casos, el correcto diagnóstico y tratamiento de la lesión es decisivo para reestabilizar la salud y la calidad de la vida. El objetivo de este artículo consistió en presentar un caso de complicación secundaria crónica de osteomielitis tratados con tratamiento conservador. El paciente, negro, de 68 años de edad, consulta por "hinchazón de las encías" que se presentó durante once años, con episodios de dolor. En el examen intraoral, se observó una pápula con supuración en la mucosa alveolar en el lado derecho de la mandíbula. La radiografía panorámica y CBCT mostraron una lesión mixta rodeada de hueso esclerótico. El paciente fue diagnosticado con osteomielitis crónica en asociación con DOF y fue tratado con tratamiento antibiótico junto con curetaje quirúrgico. La incidencia, la etiopatología, el diagnóstico diferencial, el tratamiento y la prevención de la osteomielitis secundaria asociada con DOF se discuten a la luz de la literatura. Esta información puede ayudar a los dentistas a elegir las mejores opciones de tratamiento para casos similares.

Displasia cemento-óssea florida: relato de dois casos tratados por diferentes abordagen / Florid cemento-osseous dysplasia: report of two cases treated with different approaches

Objetivo: relatar dois casos de displasia cemento-óssea florida, descrevendo a evolução clínico-radiográfica ao longo de 5 anos em um paciente assintomático e a abordagem cirúrgica em um caso sintomático. Relato de caso 1: paciente, melanoderma, sexo feminino, 56 anos de idade, encaminhada ao Serviço de Cirurgia Bucomaxilofacial da Universidade Federal da Bahia, por cirurgião-dentista clínico que notou alterações imagiológicas em radiografia panorâmica de rotina. Apesar da importante extensão da lesão em maxila e mandíbula, não havia qualquer sintoma ou sinal clínico de infecção. A paciente foi acompanhada durante 5 anos, com exames de imagem bianuais e medidas clínicas profiláticas. Relato de caso 2: paciente, melanoderma, sexo feminino, 57 anos, apresentou-se ao ambulatório de cirurgia queixando-se de atraso em cicatrização após remoção de um dente. A radiografia panorâmica e a tomografia computadorizada, em conjunto com dados clínicos, permitiram o diagnóstico de displasia cemento-óssea florida com infecção secundária. A paciente foi abordada por meio de osteotomia em região do defeito em mandíbula. A análise microscópica do espécime obtido confirmou a alteração displásica cementoide. Os sinais e sintomas regrediram e a paciente segue em acompanhamento. Considerações finais: a displasia cemento-óssea florida, portanto, é uma doença pouco frequente, cujas manifestações podem demandar diferentes abordagens. É importante o domínio clínico do cirurgião-dentista, uma vez que o diagnóstico equivocado pode guiar a escolhas terapêuticas com resultados insatisfatórios. (AU)

Objective: the objective of this article is to report two cases of florid cemento-osseous dysplasia describing the clinical-radiographic evolution over 5 years in an asymptomatic patient and the surgical approach in a symptomatic one. Case report 1: patient, melanoderma, female, 56 years old, referred to the service by a clinical Dentist who noticed imaging alterations in a routine panoramic radiography. Despite the important extension of the maxillary and mandibular lesion, there was no clinical sign or symptom of infection. The patient has been followed for 5 years with biannual imaging exams and prophylactic clinical measures. Case report 2: patient, melanoderma, female, 57 years old, presented to the surgery outpatient complaining of delay in healing after removal of a tooth. Panoramic X-ray and Computed Tomography together with clinical data allowed the diagnosis of florid cemento-osseous dysplasia with secondary infection. The patient was approached through osteotomy in the region of the mandible defect. The microscopic analysis of the specimen confirmed the dysplastic cementenoid alteration. Signs and symptoms regressed and the patient is in follow up. Final considerations: florida cementoosseous dysplasia is an infrequent disease, whose manifestations may require different approaches. The clinical domain of the Dentist is important, since misdiagnosis can lead to therapeutic choices with unsatisfactory results. (AU)

Florid cemento-osseous dysplasia: a contraindication to orthodontic treatment in compromised areas

ABSTRACT Florid cemento-osseous dysplasia is a sclerosing disease that affects the mandible, especially the alveolar process, and that is, in most cases, bilateral; however, in some cases it affects up to three or even four quadrants. During the disease, normal bone is replaced with a thinly formed, irregularly distributed tissue peppered with radiolucent areas of soft tissue. Newly formed bone does not seem to invade periodontal space, but, in several images, it is confused with the roots, without, however, compromising pulp vitality or tooth position in the dental arch. There is no replacement resorption, not even when the images suggest dentoalveolar ankylosis. Orthodontists should make an accurate diagnosis when planning treatments, as this disease, when fully established, is one of the extremely rare situations in which orthodontic treatment is contraindicated. This contraindication is due to: (a) procedures such as the installment of mini-implants and mini-plaques, surgical maneuvers to apply traction to unerupted teeth and extractions should be avoided to prevent contamination of the affected bone with bacteria from the oral microbiota; and (b) tooth movement in the areas affected is practically impossible because of bone disorganization in the alveolar process, characterized by high bone density and the resulting cotton-wool appearance. Densely mineralized and disorganized bone is unable to remodel or develop in an organized way in the periodontal ligaments and the alveolar process. Organized bone remodeling is a fundamental phenomenon for tooth movement.

RESUMO A displasia cemento-óssea florida é uma doença óssea esclerosante exclusiva dos maxilares, relacionada ao osso do processo alveolar e, na maioria dos casos, envolvendo bilateralmente a mandíbula; mas há casos em que envolve três ou até os quatro quadrantes. Nesse processo, troca-se o osso normal por um tecido densamente formado, irregularmente distribuído e salpicado por áreas radiolúcidas com tecido mole. O osso neoformado parece não invadir o espaço periodontal, mas, em muitas imagens, confunde-se com as raízes, sem comprometer a vitalidade pulpar e a posição dentária na arcada. Não há reabsorção dentária por substituição, mesmo quando as imagens sugerem anquilose alveolodentária. Um diagnóstico preciso por parte do ortodontista deve ser feito em seus planejamentos, visto que essa doença, quando se encontra plenamente instalada, representa uma das raríssimas situações em que o tratamento ortodôntico está contraindicado. Nesses casos, o tratamento ortodôntico está contraindicado porque: a) alguns procedimentos, como a aplicação de mini-implantes e miniplacas, manobras cirúrgicas para tracionamento de dentes não irrompidos e exodontias, devem ser evitados, para se impedir a entrada de bactérias da microbiota bucal no osso comprometido; e b) a possibilidade de movimentação dos dentes nas áreas comprometidas praticamente inexiste, pela desorganização óssea no processo alveolar, caracterizada por elevada densidade óssea, que gera as imagens tipo flocos de algodão. O osso densamente mineralizado e desorganizado não é capaz de se remodelar e desenvolver organizadamente, nos ligamentos periodontais e no osso do processo alveolar. A remodelação óssea organizada é fundamental como um dos fenômenos necessários para o deslocamento dos dentes.

Displasia fibrosa ósea / Fibrous dysplasia of bone

La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son característicos, aunque variables y de carácter evolutivo. La gammagrafía ósea es la técnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnóstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)

Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)

Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1

Abstract: We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia.

Cefalea rinogénica ¿mito o realidad?: displasia fibrosa de cornete medio como causa de algia facial / Rhinogenic headache ¿myth or reality?: middle turbinate fibrous displasia, as a cause of facial pain

La cefalea es uno de los motivos de consulta más frecuentes en medicina y se clasifica como primaria en cefaleas tensionales o migrañas y secundaria a tumores, infecciones u otras causas. Dentro del grupo de cefaleas o algias faciales secundarias se plantea la existencia del cuadro clínico de cefalea rinogénica generada por puntos de contacto de la mucosa de la cavidad nasal. En este artículo se presenta un caso de una paciente que posterior al fracaso del tratamiento farmacológico para migraña, consultó por algia facial persistente. Al realizar un examen clínico y con tomografía computarizada de las cavidades perinasales, se diagnosticó una cefalea rinogénica por contacto de mucosa secundaria a una displasia fibrosa del cornete medio. La resección quirúrgica del punto de contacto a través de una turbinectomía media realizada por cirugía endoscópica nasal abolió totalmente el dolor facial. Este caso recalca la utilidad y necesidad del estudio de las cavidades perinasales en aquellos pacientes que presentan cefalea o algia facial.

Headache is one of the most frequent symptoms in medicine that can be classified as primary, like tensional headache and migraine or secondary as in tumors, infections, or other causes. Rhinogenic headache is proposed as a clinical entity secondary to mucosal contact points within the nasal cavity. In this article we present a case of a patient that after a pharmacological treatment failure for migraine, consulted for sustained facial pain. After clinical examination and a paranasal sinus computed tomography, a rhinogenic headache secondary to middle turbinate fibrous dysplasia was diagnosed. Endoscopic surgical extirpation of contact mucosal points by a medial turbinectomy produced complete abolition of facial pain. This case illustrates the need and utility of studying paranasal sinus in those patients with headache or facial pain.