RARE DENTAL DISEASES-1
RARE DENTAL DISEASES-1
Translated by Zehra Ebrar Şimşek
Gorham-Stout Disease (GSD)
Gorham-Stout disease (GSD), which is also known as vanishing bone disease, disappearing bone disease, massive osteolysis, and more than a half-dozen other terms in the medical literature, is a rare bone disorder characterized by progressive bone loss (osteolysis) and the overgrowth (proliferation) of lymphatic vessels. In this disease, bone resorption starts spontaneously and bone destruction continues for years and the etiological causes of GSD are unknown. GSD can affect any bone in the body and can be either monostotic or polyiostotic. Affected individuals experience progressive bone destruction and resorption. More than one bone may be affected.
GSD can occur at any age, but is usually diagnosed in children and young adults (13 years on average). GSD can affect any bone in the body, but most commonly affects the ribs, followed by the skull, clavicle, and cervical spine. Other affected areas include the maxillofacial bones (mostly jawbone), sternum, humerus, hand, femur, and foot. The diagnosis and treatment of the disease, which is common in the mandible in the maxillofacial region, contains difficulties.
GSD can be monostotic or polyostotic and the symptoms depend upon the specific bones involved. The most common symptom is localized pain. Swelling, weakness and functional impairment of the affected limbs are also noticed. Movable teeth, malocclusion, mandibular deviation and bone deformity can be seen in the dentoalveolar region. Patients with thoracic involvement may show respiratory distress (caused by chylothorax).
GENETIC CHANGES/ACTING FACTORS
The etiology of GSD is still unclear. The pathological process is benign vascular proliferation of the endothelial canals adjacent to or within the bone, leading to excessive thinning of the bone trabecula, osteoclast-mediated resorption, and replacement of the bone with fibrous tissue. Tissue samples test positive for lymphatic endothelial cell markers, suggesting that GSD is a disease involving irregular lymphangiogenesis.
Bone loss (osteolysis) can be caused by a variety of different conditions including infection, inflammation, cancer, and some endocrine disorders. The differential diagnosis of GSD includes Hajdu-Cheney syndrome, Paget’s disease, rheumatoid arthritis, fibrous dysplasia, Langerhans cell histiocytosis, Winchester syndrome, carpal tarsal osteolysis, idiopathic multicentric osteolysis, multicentric osteolysis with nephropathy and eosoposophysitis.
Generalized lymphatic anomaly (GLA, previously known as lymphangiotosis) is closely related to GSD. GLA patients have multifocal lymphatic malformations. These malformations may be present in bone, but they do not cause cortical bone loss as seen in GSD.
SIGNS AND SYMPTOMS
Gorham’s disease (pronounced GOR-amz), also known as Gorham’s extinct bone disease and phantom bone disease, is a very rare skeletal condition characterized by uncontrolled proliferation of defective, thin-walled vascular or lymphatic ducts. It is a bone disease that causes the bone to be absorbed and replaced by angiomas and / or fibrosis. Areas commonly affected by GSD include the ribs, spine, pelvis, skull, collarbone (clavicle), and jaw. Pain and swelling may occur in the affected area. The disease may stabilize after a few years, go into spontaneous remission, or be fatal in cases involving the chest and upper spine. The disease may recur after remission. Involvement of the spine and skull base may cause a poor outcome from neurological complications. In many cases, the consequence of Gorham’s disease is severe deformity and functional disability.
If the disease is present in the ribs, scapula or thoracic vertebrae, symptoms such as difficulty breathing and chest pain may be seen. These may indicate that the disease has spread from the bone to the chest cavity. Breathing problems can be misdiagnosed as asthma because damage to the lungs can cause the same kind of changes in the lung function test seen in asthma. The extension of the lesions to the chest can lead to the development of chylous pleural and pericardial effusions. Chyle is rich in protein and white blood cells that are important in fighting infection. Chyle’s disappearance to the chest can cause serious consequences such as infection, malnutrition, and respiratory distress and failure. These complications or symptoms such as difficulty breathing, chest pain, weak growth or weight loss and infection were sometimes the first signs of the condition.
THE GENETIC INCIDENCE
The specific cause of Gorham’s disease is unknown. Beginning in the 1990s, high levels of a protein called interleukin-6 (IL-6) were reported in people with the disease, suggesting that some may contribute to increased levels of IL-6 and vascular endothelial growth factor (VEGF).
In 1999, Möller et al said, “Gorham-Stout syndrome may be a monocentric bone disease with severely increased bone resorption, mainly due to an increasing number of paracrine or autocrine-stimulated hyperaclasts. The apparent discrepancy regarding the presence or absence of osteoclasts or the number of osteoclasts can be explained by the different stages of the syndrome. ” They also stated that their histopathological studies provide good evidence that the osteolytic changes seen in Gorham’s disease are the result of hyperactive osteoclastic bone. However, others have concluded that lymphangiotosis and Gorham’s disease should be considered as a spectrum of diseases rather than separate diseases. Although there is a consensus that Gorham is caused by unbalanced osteoclastic activity, there is no conclusive evidence as to the exact cause of this behavior initiation.
Approximately 300 cases have been reported in the literature to date. GSD does not show a clear race, gender preference (1.6: 1; male to female ratio) or geographic distribution. The exact cause of GSD is unknown. Because GSD is a very rare disease, many cases are either undiagnosed or misdiagnosed, making it difficult to determine the true prevalence of the disorder in the general population.
DIAGNOSIS AND TREATMENT METHODS
Diagnosis is based on radiographic findings showing progressive osteolysis and cortical destruction. Magnetic resonance imaging shows full resorption in bone and replacement with infiltrative soft tissue with low signal intensity in T1-weighted imaging and high signal intensity in T2 and a dense increase in contrast imaging. Immunohistochemical markers of lymphatic endothelial cells (LYVE-1, podoplanin / D2-40) reveal the presence of lymphatic vessels in the medullary and cortical regions of the bones and in the affected soft tissues. Rib lesions should not be biopsied, as this procedure may reveal a refractory chylous effusion.
Treatment of GSD may include medications to stabilize progressive disease (bisphosphonates and / or interferon alpha 2b, sirolimus are also being investigated) and supportive procedures (pleurectomy, pleurodesis, thoracentesis, and thoracic duct embolization or ligation) that can reduce or stop chylothorax or stabilize affected areas of the skeleton. Radiotherapy can be used in combination with these therapies, but is usually divided into refractory or rapidly progressing diseases.
The prognosis depends on the size and location of the affected areas. While mild disease may remain stable for years, severe cases involving the craniofacial and / or thoracic regions can be fatal. Lung involvement is an indicator of a worsening prognosis.
Treatment of Gorham’s disease is mostly palliative and limited to symptom management.
Sometimes the bone destruction ends on its own and no treatment is required, but aggressive intervention may be required when the disease progresses. Duffy and colleagues found that about 17% of people with Gorham’s disease in the ribs, shoulders, or upper spine experienced the enlargement of the disease to the chest and caused chylothorax with serious consequences, and the mortality rate in this group can be up to 64% without surgical intervention.
KISSING MOLARS DISEASE
The term ‘kissing molars’ was first described in 1973. This term refers to multiple impacted mandibular molars within a single follicular space whose roots lie in opposite directions and whose occlusal surfaces are in contact with one another. The ‘rosetting formation (rose-shaped ring or lump)’ or ‘kissing molars’ formation of molar teeth has been associated with mucopolysaccharidosis (MPS) disease in the literature.
“Kissing molars” is one of the interesting and rare findings of mandibular permanent impacted molar teeth. The diagnosis of “kissing molars” phenomenon can be made radiologically. In order to be diagnosed radiologically;
- It is sufficient for the relevant teeth to be in a single follicular bag,
- the directions of the roots to be opposite to each other,
- and the occlusal surfaces to be in contact with each other.
At the same time, “Kissing molars” is a pathological finding that can be diagnosed clinically, radiologically and histopathologically. As a result, only 7 cases of kissing molars have been encountered in the literature so far.
PRE-ERUPTIVE INTRACORONAL REZORPTION
Pre-eruptive intracoronal resorption is an extremely rare condition in primary teeth, and the etiology of the resorption process and related factors are still unknown. Pre-eruptive intracoronal resorption is a well-circumscribed and abnormal lesion in the coronal dentin tissue, which is a developmental defect of the tooth.
In the dentine of unerupted teeth, just below the dentino-enamel junction, well-circumscribed intracoronal radiolucencies are defined as “pre-eruptive intracoronal radiolucency / resorption” (PEIR). Since the radiolucent radiographic image is similar to dental caries, it was frequently named as “pre-eruptive caries” in the literature, but there is no histopathological evidence supporting this theory. Unlike caries, these teeth that are not completely erupted have no connection with oral microbial flora. Today, “pre-eruptive intracoronal radiolucency / resorption” is an accepted term and is diagnosed by routine radiographic examination, usually located in the central or mesial part of the crown. The depth of the lesion is versatile and generally does not include pulp.
PEIR can also cause tooth loss by resorbing the crown of an unerupted permanent tooth. Pre-eruptive intracoranal resorption is seen in 3-6% of patients, while the rate of occurrence in teeth is 0.5-2%. Özden and Açıkgöz reported that PEIR was seen in 1.55% of patients and 0.95% in teeth in their study in Turkey. It has been stated that while only one tooth is affected, several teeth are also affected. It is also reported that PEIR often affects molar and premolar teeth.
Although various theories have been defined for the etiology of pre-eruptive intracoranal resorption, such as chronic periapical inflammation of the primary tooth and tooth decay, today it is accepted that PEIR is a resorption process. In addition, there is sufficient clinical and histological evidence to support that these lesions in the pre-eruptive stage contain soft tissue. Many cells representing resorption, such as multinucleated giant cells, osteoclasts, and chronic inflammatory cells, have been shown histopathologically in case reports. However, it has been suggested that abnormal local pressures, such as the ectopic position of the tooth bud, may be a stimulating factor, although the triggering factors are still unclear.
It has been hypothesized that pre-eruptive intracoronal resorption will progress without intervention, but various case reports have shown significant differences in clinical course for PEIR lesions. Although some lesions progress rapidly, the progression of the lesion is slow before the tooth is located in the oral cavity. Surgical exposure of the unerupted tooth is recommended to prevent the ongoing destruction of the coronal structure and to restore the lesion. However, no progress has been reported when the lesion is removed and restored.
Routine dental check-ups of patients should include panoramic and / or periapical radiographs and should be carefully evaluated. Especially in teeth with delayed eruption, it is very important to complete the treatment as soon as possible to define pre-eruptive intracoronal resorption and to protect the pulp.