other derma lesions in oral cavity and genodermatosis
- 1. Dr. Harpreet Kaur Assistant Professor, Oral & Maxillofacial Pathology and Microbiology MDS (GDCH Nagpur -Gold Medalist) Senior Resident AIIMS Delhi (2019-2020)
- 2. ECTODERMAL DYSPLASIA • Relatively rare • represents a group of inherited conditions in which two or more ectodermally derived anatomic structures fail to develop • The various types of this disorder may be inherited in any one of several genetic patterns A. autosomal dominant, B. autosomal recessive, C. and X-linked patterns • Perhaps the best known of the ectodermal dysplasia syndromes is hypohidrotic ectodermal dysplasia • X-linked inheritance pattern, with the gene mapping to Xq12-q13.1; few • families have been identified that show autosomal recessive or autosomal dominant patterns of inheritance.
- 3. C/F • male predominance • 3H: hypohiderosis, hypotrichosis and hypodontia • heat intolerance because of a reduced number of eccrine sweat glands • infant simply cannot regulate body temperature appropriately because of decreased number of sweat glands; death results from the markedly elevated body temperature. • Other signs of this disorder include fine, sparse hair, including a reduced density of eyebrow and eyelash hair • The periocular skin may show a fine wrinkling with hyperpigmentation and midface hypoplasia • Xerostomia: Salivary glands are ectodermally derived, these glands may be hypoplastic or absent, • The nails may also appear dystrophic and brittle • oligodontia or hypodontia or anodontia
- 4. • Lyon hypothesis: with half of the female patient’s X chromosomes expressing the normal gene, and the other half expressing the defective gene. • Female patients may show partial expression of the abnormal gene; that is, their teeth may be reduced in number or may have mild structural changes.
- 5. sparse hair, periocular hyperpigmentation, and mild midfacial hypoplasia are characteristic features evident in this affected patient Fine periocular wrinkling, as well as sparse eyelash and eyebrow hair, can be observed
- 6. Histopathologic Features • Skin from a patient with hypohidrotic ectodermal dysplasia shows a decreased number of sweat glands and hair follicles • The adnexal structures that are present are hypoplastic and malformed
- 7. Treatment • genetic counseling for the parents and the patient • Dental problems are best managed by prosthetic replacement of the dentition with complete dentures, overdentures, or fixed appliances, depending on the number and location of the remaining teeth • endosseous dental implants may be considered for facilitating prosthetic management of patients older than 6 years of age.
- 8. WHITE SPONGE NEVUS (CANNON DISEASE; FAMILIAL WHITE FOLDED DYSPLASIA • relatively rare genodermatosis (a genetically determined skin disorder) • AD inheritance high degree of penetrance and variable expressivity. • defect in the normal keratinization of the oral mucosa • Mutations in keratin 4 and keratin 13 normally expressed in spinous layer responsible for the clinical manifestations of white sponge nevus
- 9. C/F • Usually appear at birth or in early childhood but sometimes during adolescence • Symmetrical, thickened, white, corrugated or velvety, diffuse plaques affect the buccal mucosa bilaterally in most instances • Other sites: ventral tongue, labial mucosa, soft palate, alveolar mucosa, and floor of the mouth. • Extraoral mucosal sites, such as the nasal, esophageal, laryngeal, and anogenital mucosa- less common
- 10. Histopathological features • Characteristic but not necessarily pathognomonic. • Prominent hyperparakeratosis and marked acanthosis with clearing of the cytoplasm of the cells in the spinous layer are common features • Similar findings are seen in leukoedema and hereditary benign intraepithelial dyskeratosis (HBID). • eosinophilic condensation is noted in the perinuclear region of the cells in the superficial layers of the epithelium, a feature that is unique to white sponge nevus • Ultrastructurally, this condensed material can be identified as tangled masses of keratin tonofilaments.
- 11. This high-power photomicrograph of a Papanicolaou-stained cytologic preparation shows the pathognomonic perinuclear condensation of keratin tonofilaments
- 12. Treatment • benign condition, • no treatment is necessary. • The prognosis is good
- 13. PEUTZ-JEGHERS SYNDROME • Relatively rare but well recognized condition, • It is characterized by freckle like lesions of the hands, perioral skin, and oral mucosa, in • conjunction with intestinal polyposis • predisposition for affected patients to develop cancer • autosomal dominant inheritance • Mutation of the tumor suppressor gene, STK11 (also known as LKB1) serine/threonine kinase, is located on chromosome 19p13.3.
- 14. C/F • Skin lesions: early in childhood and involve the periorificial areas (e.g., mouth, nose, anus, and genital region). • The skin of the extremities is affected in about 50% of patients • The lesions resemble freckles, but they do not wax and wane with sun exposure, as do true freckles • The intestinal polyps, generally considered to be hamartomatous growths are scattered throughout the mucusproducing areas of the gastrointestinal tract • The jejunum and ileum are most commonly affected. • intestinal obstruction • Gastrointestinal adenocarcinoma develops in a significant percentage of affected patients, although the polyps themselves do not appear to be premalignant • Other tumors affecting the pancreas, male and female genital tract,
- 15. Cutaneous lesions appear as brown, macular, freckle-like areas, often concentrated around the mouth or on the hands Oral manifestations include multiple, dark, freckle-like lesions of the lips
- 16. Oral lesions • extension of the perioral freckling • These 1- to 4-mm brown to blue-gray macules primarily affect the vermilion zone, the labial and buccal mucosa, and the tongue; • Some degree of fading of the pigmented lesions may be noted during adolescence
- 17. H/P • The gastrointestinal polyps of Peutz-Jeghers syndrome histopathologically represent benign overgrowths of intestinal glandular epithelium supported by a core of smooth muscle • Epithelial atypia is not usually a prominent feature, unlike the polyps of Gardner syndrome • Microscopic evaluation of the pigmented cutaneous lesions shows slight acanthosis of the epithelium with elongation of the rete ridges • No apparent increase in melanocyte number but the dendritic processes of the melanocytes are elongated as seen under electron microscopy.
- 18. Treatment • Monitoring for development of intussusception or tumor formation. • Genetic counseling is also appropriate.
- 19. HEREDITARY HEMORRHAGIC TELANGIECTASIA (OSLER-WEBERRENDU SYNDROME) • Hereditary hemorrhagic telangiectasia (HHT) is an uncommon mucocutaneous disorder that is inherited as an autosomal dominant trait • Oral lesions are often the most dramatic and most easily identified component of this syndrome. • Mutation of the endoglin (ENG) gene on chromosome 9, whereas mutation of activin receptor-like kinase-1 (ALK1; ACVRL1), a gene located on chromosome 12, produces HHT2. • A much less common mutation, involving the MADH4 gene, causing overlap syndrome characterized by HHT and juvenile polyposis. • Numerous vascular hamartomas develop, affecting the skin and mucosa; however, other vascular problems, such as arteriovenous fistulas, may also be seen. • The polyps involve both the upper and lower GIT, and • increased risk for developing colorectal carcinoma at an early age
- 20. C/F • A diagnosis of HHT can be made if a patient has three of the following four criteria: 1. Recurrent spontaneous epistaxis 2. Telangiectasias of the mucosa and skin 3. Arteriovenous malformation involving the lungs, liver, or CNS 4. Family history of HHT • These telangiectatic vessels are most frequently found on the vermilion zone of the lips, tongue, and buccal mucosa, although any oral mucosal site may be affected • The GIT telangiectasias have a tendency to rupture, which may cause significant blood loss. • Chronic iron-deficiency anemia is often a problem for such
- 21. The tongue of this patient shows multiple red papules, which represent superficial collections of dilated capillary spaces. Red macules similar to the tongue lesions are observed on the buccal mucosa. • In some instances, CREST syndrome should be in d/d so antibodies to differentiate?
- 22. H/P • If one of the telangiectasias is submitted for biopsy, the microscopic features essentially show a superficially located collection of thin-walled vascular spaces that contain erythrocytes
- 23. Treatment • For mild cases of HHT, no treatment may be required. • Moderate cases may be managed by selective cryosurgery or electrocautery of the most bothersome of the telangiectatic vessels. • More severely affected patients, may require a surgical procedure of the nasal septum (septal dermoplasty) • From a dental standpoint, some authors recommend the use of prophylactic antibiotics before dental procedures that might cause bacteremia in patients with HHT and evidence of a pulmonary arteriovenous malformation • The prognosis is generally good, although a 1% to 2% mortality rate is reported from complications
- 24. Ehlers Danlos Syndrome • Group of inherited connective tissue disorders, are relatively heterogeneous • At least 10 types have been described over the years, but recent clinical and molecular evidence suggests that 7 categories of this disease may be more appropriate. • Attributed to the production of abnormal collagen, the protein that is the main structural component of the connective tissue • Overlapping clinical features for each of the types of the Ehlers-Danlos syndrome
- 25. Typical clinical findings: • hypermobility of the joints, easy bruisability, and marked elasticity of the skin • have worked in circus sideshows as the “rubber” man and the “contortionist” as a result of their pronounced joint mobility and ability to stretch the skin.
- 26. C/F
- 27. Scarring that resembles crumpled cigarette paper (papyraceous scarring) is associated with minimal trauma in patients with Ehlers-Danlos syndromes The hyperelasticity of the skin is evident in this patient affected by the mild form of classical Ehlers-Danlos syndrome.
- 28. • One rare form of Ehlers-Danlos syndrome (type VIII) has dental manifestations as a hallmark feature • marked periodontal disease activity at a relatively early age. • Overlapping features with either the classical or vascular forms • specific mutation of a gene that has been mapped to chromosome 12p13 • 50% of these patients to touch the tip of their nose with their tongue (Gorlin sign), • easy bruising and bleeding of oral mucosa • oral mucosal friability • Recurrent subluxation of the temporomandibular joint (TMJ) • the development of other TMJ disorders • malformed, stunted tooth roots, large pulp stones, and Ehlers-Danlos syndrome (type VIII)
- 29. Treatment and prognosis • Depends upon type • Vascular type, can be very serious, • The mild classical type is generally compatible with a normal life span, • Accurate diagnosis is important because it affects the prognosis heavily
- 30. EPIDERMOLYSIS BULLOSA • Heterogeneous group of inherited blistering mucocutaneous disorders • Each has a specific defect in the attachment mechanisms of the epithelial cells, either to each other or to the underlying connective tissue • identification of approximately 34 different forms • Depending on the defective mechanism of cellular cohesion, there are four broad categories: • 1. Simplex • 2. Junctional • 3. Dystrophic • 4. Kindler syndrome • A variety of inheritance patterns may be seen, depending on the particular form
- 31. Because oral lesions are most commonly observed in the dystrophic forms, this discussion centers on these forms.
- 34. • Kindler syndrome is the most recently characterized pattern of this group of disorders, and mutations of the gene that encodes for a hemidesmosomal attachment protein, kindlin-1, are responsible for this rare condition.
- 35. Epidermolysis Bullosa Mutation Simplex Keratin K5,K14 Junctional Laminin-332, type XVII collagen, or α6β4 integrin Dystrophic Collagen type VII Hemidesmosomal Hemidesmosomal proteins – Plectin, BP 230
- 36. • Dental abnormalities, such as anodontia, enamel hypoplasia, pitting of the enamel, neonatal teeth, severe periodontitis, and severe dental caries, have been variably associated with several of the different types of epidermolysis bullosa; • prevalence of dental abnormalities is significantly increased only with the junctional type • A disorder termed epidermolysis bullosa acquisita is mentioned because of the similarity of its name; however, this is an unrelated condition, having an autoimmune basis
- 37. C/F Dominant Dystrophic Types: • AD inheritance • not usually life threatening vesicles or bullae, which are seen early in life and develop on areas exposed to low-grade, chronic trauma, such as the knuckles or knees • The bullae rupture, resulting in erosions or ulcerations that ultimately heal with scarring. (appendages such as fingernails may be lost) • The oral manifestations are typically mild, with some gingival erythema and tenderness • Gingival recession and reduction in the depth of the buccal vestibule may be observed
- 38. Recessive Dystrophic Types • Generalized recessive dystrophic epidermolysis bullosa represents one of the more debilitating forms of the disease • Vesicles and bullae form with even minor trauma • Secondary infections are often a problem because of the large surface areas that may be involved. • If the patient survives, hand function is often greatly diminished because of the repeated episodes of cutaneous breakdown and healing with scarring, resulting in fusion of the fingers into a mittenlike deformity
- 39. Oral manifestations • The oral problems are no less severe. • Bulla and vesicle formation is induced by virtually any food having some degree of texture. Even with a soft diet, the repeated cycles of scarring often result in microstomia and ankyloglossia. • Similar mucosal injury and scarring may cause severe stricture of the esophagus. • Because a soft diet is usually highly cariogenic, carious destruction of the dentition at an early age is common.
- 40. H/P • Vary with the type being examined. • The simplex form shows intraepithelial clefting by light microscopy • Junctional, dystrophic, and Kindler forms show subepithelial clefting • Electron microscopic examination reveals clefting at the level of the lamina lucida of the basement membrane in the junctional forms and below the lamina densa of the basement membrane in the dystrophic forms • In contrast, the Kindler form shows clefting just below the basal cell layer, at its interface with the lamina lucida. Complete separation in junctional type
- 41. Treatment and prognosis • Varies with type • milder cases, no treatment other than local wound care may be needed. • Sterile drainage of larger blisters and the use of topical antibiotics are often indicated in these situations • For the more severe cases, intensive management with oral antibiotics may be necessary if cellulitis develops; despite intensive medical care, some patients die as a result of infectious complications. • plastic surgery in mitten hand deformity • Patients with the recessive dystrophic forms are also predisposed to development of cutaneous squamous cell carcinoma • Oral problems to be managed as per the symptoms.
- 42. THANK YOU
Editor's Notes
- #21: CREST syndrome: anticentromere autoantibodies