SYNDROMES AFFECTING THE PERIODONTIUM

Introduction

• Systemic conditions are defined as the naturally occurring or induced states that are expected to exert general effects throughout the body.

• They can be hormonal, nutritional, genetic or related to age or comprise drug intake or habits such as smoking.

• Systemic disorders are true abnormalities or diseases having signs and symptoms that deviate from normal and that define diseases, such as diabetes mellitus.

• It is well known that systemic conditions can manifest in the oral cavity.

Definition of a syndrome:

“A syndrome is a combination of symptoms resulting from a single cause or so commonly occurring as to constitute a distinct clinical entity. “

( Dorland’s medical dictionary)

Definition of a syndrome:

“A group of symptoms that together are characteristic of a specific disorder, disease, or the like “

( dictionary.com )

CLASSIFICATION OF SYNDROMES AFFECTING THE PERIODONTIUM

Classification

1. Syndromes causing white lesions in the gingiva- Focal palmoplantar and oral mucosa hyperkeratosis syndrome

2. Syndromes causing red lesions in the gingiva-Melkersson –Rosenthal syndrome, Sturge-Webber syndrome, Klippel-Trenaunay-Weber syndrome, Sjogren’s syndrome, Osler-Rendu-Weber syndrome

Classification

3. Syndromes causing ulcers and erosions in the gingiva- Bechet’s syndrome, Reiter’s syndrome, Myelodysplastic Syndrome

4. Syndromes causing pigmentation in the gingiva- Peutz-Jegher’s syndrome, Albright’s syndrome

Classification5. Syndromes causing localized lumps or swellings in the

gingiva- Gardener’s syndrome, Turner’s syndrome

6. Syndromes causing generalized lumps or swellings in the gingiva- Laband’s syndrome, Hurler’s syndrome, Sturge-Webber syndrome, Klippel-Trenaunay-Weber syndrome, Rutherford syndrome, Cowden’s syndrome, Goltz-Gorlin syndrome, Murray-Puretic-Dreshcer syndrome, Cross syndrome, Ramon syndrome, Bourneville-Pringle syndrome

Classification7. Syndromes causing gingival bleeding- Sturge-Webber syndrome,

Klippel-Trenaunay-Weber syndrome, Chediak-Higashi syndrome, Osler-Rendu-Weber syndrome

8. Syndromes causing periodontal destruction- Chediak-Higashi syndrome, Hyperimmunoglobulin E syndrome, Congenital neutropenia (Kostmann syndrome), Felty’s syndrome, Lazy leukocyte syndrome, Leukocyte adhesion deficiency syndrome, Ehlers–Danlos syndrome, Hypotrichosis osteolysis periodontitis palmoplantar keratoderma syndrome, Kindler syndrome

9. Syndromes causing defects in the gingivolabial fold- Orofaciodigital syndrome type I, Ellis van Crevald syndrome

10. syndromes affecting the periodontal ligament : CREST syndrome, Thibierge-Wissenbach syndrome

SYNDROMES CAUSING WHITE LESIONS IN THE GINGIVA

1. Focal palmoplantar and oral mucosa hyperkeratosis syndrome -OMIM 148730

Definition:• also called as hyperkeratosis or attached

gingival hyperkeratosis. • It is unusual genetic disorder characterized by

oral mucosal and dermal hyperkeratosis

Etiology: Genetic. Inherited as an autosomal dominant trait.

Clinical features:

• marked white hyperkeratosis of the attached gingival, presenting clinically as leukoplakia

• There is no inflammation or attachment loss.

• White hyperkeratotic lesions at the weight bearing and pressure related areas of the palms and soles are always present.

• Nail dystrophy and hyperhidrosis may also occur.

• The hyperkeratosis develops early in childhood and the severity increases with age.

Differential diagnosis:

• Leukoplakia• white sponge nevus• pachyonychia congenita• dyskeratosis congenita

Diagnosis: the diagnosis is mainly based on clinical criteria. Biopsy and histological examination are also used.

Treatment: local and systemic aromatic retinoids with partial success.

SYNDROMES CAUSING RED LESIONS IN THE GINGIVA

1. Klippel-Trenauny-Weber syndrome-OMIM 14900

• Definition: is an uncommon dysplastic vascular disorder.

• Etiology: dysplatic malformation

Haemangiomas on the leg

Clinical features:

• the gingival lesions appear as capillary or cavernous haemangiomas occasionally leading to gingival overgrowth that may cover the crown of the teeth.

• Premature tooth eruption and alveolar bone overgrowth may occur.

• The oral mucosa lesions are also haemangiomas, particularly on the hard and soft palate.

• Multiple facial haemangiomas, ocular disorders (scleral pigmentation, glaucoma, cataract, iris heterochromia), vascular masses that involve soft tissue and bone leading to assymetrical enlargement of the extremities, haemangiomas in the internal organs are common.

Diagnosis: the diagnosis is based on clinical criteria

Differential diagnosis: • isolated haemangiomas• Sturge Webber syndrome• Maffuci’s syndrome.

Treatment: palliative, Laser may improve skin lesions

2. Sturge-Webber syndrome- OMIM 176920 (Encephalotrigeminal angiomatosis)

• Definition: is a rare sporadic congenital hamartomatous vascular disorder typically involving areas innervated by the trigeminal nerve.

• Etiology: obscure, developmental anomaly.

Clinical features:

• typically unilateral haemangiomas, usually capillary, on the attached gingival and alveolar mucosa may be seen occasionally leading to gingival hyperplasia and premature or rarely delayed eruption.

• The lesions have a bright red or purple colour and are usually flat.

• Dentists must be careful during tooth extractions and periodontal surgery so as to avoid bleeding complications.

• Unilateral oral haemangiomas may be found on the buccal mucosa, tongue and lips.

• Unilateral facial haemagioma is the most characteristic and consistent feature, it is evident at birth and characteristically it is confined to the area supplied by the trigeminal nerve.

• Haemangiomas of the leptomeninges, brain calcification, epilepsy, ocular disorders may also be present.

Diagnosis:• Based on clinical examination.• CT scan,• Histopathological examinations.

Differential diagnosis:• solitary haemangioma • Klippel-Trenauny-Weber syndrome.

Treatment: laser therapy

3. Melkersson –Rosenthal syndrome-OMIM- 15590

Definition:• is a rare disorder. • It consists of the triad of recurrent facial

swelling, facial paralysis and fissured tongue.

Etiology: unknown

Clinical features:• gingival lesions are present as

irreregular, oedematous swelling, slightly erythematous, affecting mainly the anterior interdental papillae and free and attached gingiva.

• Granulomatous cheilitis presenting as diffuse recurrent swelling of the lips is the cardinal feature of the syndrome.

• Swelling of the lips is usually the first sign.

• After a long period of attacks, the swelling persists and can become permanent.

• Buccal, palatal and lingual swellings may also occur.

• Facial palsy and fissured tongue accompany the other lesions.

Diagnosis:• Based on clinical examination.• Allergy tests• biopsy and Histopathological examinations.

Differential diagnosis:• angioedema• cheilitis glandularis• Crohn’s disease• Sarcoidosis• Amyloidosis

Treatment: dental plaque control and surgical excision of the gingival lesions. Corticosteroid (topical or systemic) administration. Neurological consultation.

4. Sjogren’s syndrome- OMIM 270510

• Definition: is a relatively common, chronic autoimmune disorder.

• Etiology: obscure; viral infection, genetic factors and autoimmunity have been implied.

Clinical features:• chronic gingivitis, (localized or

generalized) due to xerostomia and/or candida infection may occur.

• Rarely, alveolar bone loss can also be seen.

• The oral mucosa is reddish, dry, smooth and shiny.

• Oral soreness, discomfort and dysphagia are seen.

• Candidiasis, angular cheilitis and dental caries are relatively common.

• Recurrent swellings of the parotid and other salivary glands can occur.

Diagnosis:• clinical diagnosis should be confirmed by laboratory tests.• Biopsy and Histopathological examinations of the salivary glands• Serological tests- Antinuclear antibodies, Anti-SSA (Ro) , Anti-SSB antibodies,

Rheumatoid factor

Differential diagnosis:• GVHD• Xerostomia due to drugs• Systemic sclerosis• Mixed connective tissue disease

Treatment: good dental plaque control. Saliva and tears substitute. Antimalarial drugs, corticosteroids, immunosuppresants

5. Osler-Rendu-Weber syndrome/ hereditary haemmorhagic telangiectasia- OMIM 187300

• Definition: is a rare disorder characterized by permanent small dilation of vessels.

• Etiology: genetic. Inherited as an autosomal trait.

Clinical features:• the gingival lesions appear as small, localized or multiple, bright red

macules that characteristically disappear when pressure is applied.

• Gingival recurrent bleeding, usually, during or after tooth brushing, is frequent.

• The oral mucosal manifestations are characterized by multiple telangiectasias and rarely bleeding.

• Persistent recurrent nose bleeding is usually the first and common clinical sign of the disease. Multiple telangiectasias of the gastrointestinal tract and skin are common.

Diagnosis:• Based on clinical examination.• Histopathological examinations.

Differential diagnosis:• CREST syndrome• Fabry’s disease• Maffuci’s syndrome

Treatment: not usually required. Laser therapy is suggested for lesions that bleed repeatedly.

SYNDROMES CAUSING DEFECTS IN THE GINGIVOLABIAL FOLD

1. Orofaciodigital syndrome type I-OMIM 311200

• Definition: is an uncommon disorder in the group of orofaciodigital syndromes

• Etiology: genetic. It is inherited as an X linked dominant trait

Clinical features:• the gingival involvement

characterized by multiple hyperplastic fibrous bands traversing the gingivolabial and gingivobuccal fold, hypertrophy and shortening of the frenulum of the lips and the tongue.

• These may result in hyperplastic gingivitis and gingival recession.

• The oral mucosal lesions include multilobed or bifid tongue, with multiple hamartoma, lips and palate clefts, supernumerary teeth, teeth malposition and missing teeth, hypoplastic mandible.

• Frontal bossing, ocular hypertelorism, short upper lip, broad nasal root, asymmetry of the nostrils, polydactyly, brachydactyly, clinodactyly and syndactyly are common.

• The skin manifestations are xerostomia, milia, alopecia and sparse hair.

• Learning disability and polycystic kidneys may occasionally occur.

Diagnosis: the diagnosis is based clinical criteria.

Differential diagnosis: orofaciodigital syndrome type II, chondroectodermal dysplasia, oculodigital syndrome.

Treatment: surgical reconstruction of oral frenulum, gingivolabial and gingivobuccal folds. Symptomatic for the rest of the lesions.

2. Ellis van Crevald syndrome- OMIM 225500

• Also called chondroectodermal dysplasia• It is an autosomal recessive disorder.

Clinical features• There is fusion of the middle portion of the

upper lip to the gingiva leading to the disappearance of the mucolabial fold and multiple frenula are the most characteristic oral manifestation. Oligodontia and small clinical crowns may be seen.

• Chondrodysplasia of the long bones, bilateral polydactyly, shortened extremities, thin and sparse hair, dystrophic nails, heart defects and genital abnormalities are common.

SYNDROMES CAUSING ULCERS AND EROSIONS IN THE GINGIVA

1. Bechet’s syndrome- OMIM 109650

• Definition: is a chronic multisystemic disorder that affects more commonly certain ethnic groups ( Japanese, Turkish, Greek and other Mediterranean groups)

• Etiology: obscure.

Clinical features:

• the main feature is recurrent apthous ulceration ( minor, major, herpetiform, atypical).

• Painful ulcers can develop on the attached gingiva.

• Conjunctivitis, iritis, iridocyclitis with hypopyon, uveitis are the frequent eye manifestation.

• The skin lesions present as round genital ulcers.

• Folluculitis, erythema, papules and necrosis are common cutaneous lesions.

Diagnosis:• Based on clinical examination.• Histopathological examinations.

Differential diagnosis:• Apthous ulcers• Pemphigous• Pemphigoid• Erythema multiformae• Necrotizing ulcerative gingivitis• Neutropenia• Leukaemia• Langerhans cell histiocytosis

Treatment: corticosteroid – topical and systemic

2. Reiter’s syndrome

• Definition: is an uncommon chronic multisystemic disorder that may be triggered by an infectious agent in a genetically susceptible individual.

• Etiology: the exact mechanism remains unknown. Immunological mechanisms have been implicated.

Clinical features:• the gingival lesions appear as

localized or generalized non specific erythema, usually on the attached gingiva, occasionally associated with superficial, slightly sensitive erosions.

• The mucosal lesions are characterized by diffuse erythematous areas intermixed with thin whitish dots or lines, and superficial erosions.

Localized loss of the tongue filiform papillae in the form of geographic tongue can occur.

• The skin manifestations appear as macular, vesicular or pustular, psoriasiform lesions and keratoderma. Other manifestations include conjunctivitis, cyclic balanitis, non gonococcal urethrits, prostatitis, cervicitis and nail disturbances.

• The most characteristic feature is the symmetrical arthritis of 6-7 joints.

Diagnosis:• Based on clinical examination.• Histopathological examinations.• Blood and serological tests, HLA antigens • Synovial fluid analysis.

Differential diagnosis:• Erythema multiformae• Bechet’s syndrome • Geographic stomatitis • Drug eruption

Treatment: corticosteroid – topical and systemic. NSAIDs

3. Myelodysplastic Syndrome

• Definition: forms a heterogeneous group of refractory anaemias often associated with thrombocytopenia, neutropenia and/or monocytosis.

• Etiology: unknown. Can develop secondarily to radiotherapy or chemotherapy.

Clinical features:

• the gingival lesions may appear as chronic, localized swellings and/or ulcerations, associated with bleeding.

• The oral lesions appear as persistent and recurrent painful ulcerations and bleedings.

• Less often candidiasis may develop.

• Multiple bacterial infections and haemmorhages are the main features of the disease due to neutropenia and thrombocytopenia.

• Malaise, fatigue, fever are common symptoms.

Diagnosis:• Clinical diagnosis should be confirmed by laboratory tests.• Complete blood count and bone marrow aspiration and biopsy

Differential diagnosis:• Leukemias• Agranulocytosis• Neutropenia• Aplastic anaemia• Thrombocytopenia• Non Hodgkins lymphoma• Multiple myeloma• Langherhans cell histiocytosis

Treatment: good oral hygiene. Topical oral antiseptics. Systemic treatment must be left to the hematologist.

4. PFAPA syndrome/Marshall syndrome

• Stands for- Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenopathy.

• Oral manifestations - aphthous ulceration on the oral mucosal tissues. Gingival involvement is uncommon.

SYNDROMES CAUSING PIGMENTATION IN THE GINGIVA

1. Peutz-Jegher’s syndrome-OMIM 175200

Consists of • Familial generalized intestinal polyposis• Pigmented spots on the face, oral cavity and

sometimes, hands and feet

2. Albright’s syndrome- OMIM 174800

Consists of –• Polyostotic fibrous dysplasia• Pigmented lesions of the skin and mucous

membrane• Endocrine disturbances- precocious puberty

SYNDROMES CAUSING LOCALIZED LUMPS OR SWELLINGS IN THE GINGIVA

1. Gardener’s syndrome- OMIM 175100

• Definition: is a rare disorder in the group of familial colorectal polyposis syndromes.

• Etiology: genetic. It is inherited as an autosomal dominant trait.

Clinical features:

• It is important for dentists to diagnose the oral lesions of the syndrome as early as possible and to refer the patient to a gastroenterologist.

• Central osteomas in other sites of the jaws, multiple odontomas, multiple impacted supernumerary teeth and rarely benign oral soft tissue tumors may occur.

• the alveolar bone lesions are characterized by multiple osteomas that present as painless, hard masses covered by normal attached gingival and alveolar mucosa.

• Multiple osteomas of the skull, paranasal sinuses and calvaria may develop.

• Gastrointestinal manifestations are common and appear as multiple polyps of the colon and rectum that are characterized by a high rate of malignant transformation into adenocarcinoma.

• Skin lesions are epidermoid cysts, multiple fibromas and hyperpigmentation.

Diagnosis: • radiographic examination of the jaws, skull and intestinal tract. • Biopsy and histolopathological examination of tumours and polyps.

Differential diagnosis:• isolated osteomas and exostoses, • odontogenic tumours, • Peutz-Jeghers syndrome, • Cowden’s syndrome

Treatment: osteomas do not require excision unless they cause symptoms or cosmetic problems. The intestinal polyps must be under observation by the specialist.

2.Turner’s syndrome OMIM 313000Oral manifestations- torus mandibularis- bony lumps, which grow

slowly, appear in adolescence and usually cease growth in late teens. The lumps are bone had with normal overlying mucosa, asymptomatic, benign and of no consequence.

Diagnosis: clinical features and radiographic examination

Differential diagnosis; exclude unerupted teeth

Treatment- excision only if it causes difficulty, as in placement of dentures.

SYNDROMES CAUSING GENERALIZED LUMPS OR SWELLINGS IN THE GINGIVA

1. Laband syndrome- OMIM 135500

• Definition: It is a rare disorder characterized by a broad spectrum of diseases.

• Etiology: genetic. It is an autosomal dominant disorder

Clinical features:

• consists of gingival fibromatosis, ear, nose, bone and nail defects with splenomegaly.

• Macroglossia and enlargement of lips are less common.

•Large nose and pinnae, hypoplastic or absent thumb nails, rudimentary or missing terminal phalanges, pes cavus, joint hypermobility are common.

•Hepatomegaly, splenomegaly and learning disability have been noted.

Diagnosis: based on clinical criteria

Differential diagnosis:• hereditary gingival fibromatosis, • drug influenced gingival enlargement, • other syndromes associated with gingival enlargement • alpha mannosidosis.

Treatment: good oral hygiene, gingivectomy

2. Cross syndrome

• It is autosomal dominant disorder manifesting as gingival fibromatosis, microphthalmia, mental retardation, atelosis and hypopigmentation

3. Murray-Puretic- Drescher syndrome-OMIM 228600

• It is an autosomal recessive disorder manifesting as gingival fibromatosis, multiple hyaline fibrous tumors on the scalp and back, joint changes with osteoporosis of terminal phalanges

4. Rutherford syndrome

• It is an autosomal dominant disorder with gingival fibromatosis, mental deficiency, aggressive behaviour, corneal opacities, impaired tooth eruption, root resorption and dentigerous cysts.

5. Hurler’s syndrome-OMIM 2607014

• Definition: It is also called as Mucopolysaccharidosis I (MPS I). It is a rare but most common form of Mucopolysaccharide metabolic disorders.

• Etiology: genetic. Inherited as an autosomal recessive trait. The basic defect is the deficiency of the enzyme alpha L iduronidase resulting in the accumulation and deposition of heparin sulphate and dermatan sulphate within the tissues and their excessive excretion in the urine

Clinical features:

• it becomes apparent in early childhood and the children usually die before the age of 10 due to respiratory infection or cardiac disease.

• There is deposition of mucopolysaccharides into the tissues.

•The main feature is gingival overgrowth that may fully or partially cover the crowns of the teeth, particularly in the anterior area of the maxilla.

•The overgrowth is mostly the result of microbial dental plaque, mouth breathing and deposition of dermatan sulphate and heparan sulphate in the gingival tissue.

• Other oral manifestations include macrocheila, macroglossia, open mouth with protruding tongue, numerous impacted teeth, large interdental spaces and teeth dislocation.

• Growth retardation, craniofacial malformation, characteristic facies, scoliosis, stiff joints and chondrodystrophy are common.

• There is corneal scarring and clouding that frequently leads to blindness, learning disability

• Cardiac failure and lung infections may also occur.

Diagnosis: is based on clinical and histochemical evaluation-• Histochemical evaluation of alpha L iduronidase• Detection of heparan sulphate and dermatan sulphate in the urine• Radiographic examination

Differential diagnosis:• hereditary gingival fibromatosis• Alpha mannosidosis.• Mouth breathing gingivitis• Other forms of mucopolysacharidoses.

Treatment: good oral hygiene, gingivectomy, management of dental problems, supportive for the other manifestations.

6. Focal Dermal Hypoplasia syndrome/ Goltz- Gorlin syndrome-OMIM 305600

• Definition: is an uncommon disorder characterized by multiple abnormalities.

• Etiology: genetic. It is inherited as an X linked dominant trait.

Clinical features:

• the gingival lesions are papillomas.

• Multiple papillomas on the oral mucosa are present in about 50% of the cases.

• Oligodontia, hypodontia, enamel dysplasia and malocclusion, oral clefts are common.

• Skin manifestations include atrophic linear lesions, atrophic and hyperpigmented plaques, telangectasias and soft yellowish nodules.

• Sparse hair and dystrophic nails may be seen.

• Syndactyly, brachydactyly, oligodactyly or polydactyly, clinodactyly extremity asymmetry, scoliosis and microcephaly may occur.

• Eye anomalies, learning disabilities are less common findings.

Diagnosis: the diagnosis is based on clinical criteria. Biopsy and histopatholoogical examination of the skin and oral lesions.

Differential diagnosis:• multiple oral papillomas • multiple oral condylomas• focal epithelial hyperplasia

7. Bourneville-Pringle syndrome-OMIM 191100

• Definition – tuberous sclerosis of the Bourneville-Pringle syndrome or epiloia, is an uncommon disorder characterized by mucocutaneous angiofibromas, learning disabilities and seizures.

• Etiology- genetic. It is inherited as an autosomal dominant trait with variable expressivity.

Clinical features-• the gingival lesions are the

most characteristics oral lesions and present as multiple, painless, fibrous nodules with smooth surface and normal or whitish colour.

• The anterior gingiva is more frequently affected.

• The oral mucosa lesions are similar to those seen on the gingiva.

• Cleft palate and lip, vaulted palate, macroglossia and enamel pits may occur.

• The skin lesions are common and present as multiple small, red to brown nodules (angiofibromas), mainly in the nasolabial folds and elsewhere in the face.

• Learning disability, seizures and neural hamartomas are common.

• Cardiac rhabdomyoma, multiple retinal hamartomas, lung and renal abnormalities may also occur.

Diagnosis: Is based on clinical and laboratory criteria.• Biopsy and histopathological examination of the cutaneous and oral

lesions. • Brain CT. • EEG.

Differential diagnosis:• Cowden’s disease • neurofibromatosis • lipoid proteinosis • acanthosis nigrans• focal dermal hypoplasia syndrome.

Treatment: symptomatic

8. Ramon Syndrome –OMIM 266270

• First described by Ramon et al. (1967)

• A familial disease characterized by mild mental retardation, growth retardation, epilepsy, fibrous dysplasia of the maxillae, narrow palate, cherubism, hypertrichosis, juvenile rheumatoid arthritis, and gingival fibromatosis.

• Inheritance is autosomal recessive.

Cowden’s syndrome/multiple hamartoma syndrome

• Is an uncommon disorder characterized by a wide spectrum of mucocutaneous lesions usually associated with breast, thyroid and other organ disorders

• It is a genetic disorder with an autosomal dominant trait.

• The gingival lesions appear as multiple, small, smooth pale/whitish painless papules or nodules that may be isolated or coalesce in a cobblestone pattern on the free or attached gingiva or the edentulous alveolar mucosa

• Skin lesions appear as multiple papillomatous papules or small nodules that are hair follicle hamartomas

• Dermal fibromas are also common

• Several breast and thyroid gland tumours are also common

SYNDROMES AFFECTING THE PERIODONTAL LIGAMENT

Scleroderma

• Scleroderma (OMIM 181750) is a connective tissue disorder the characteristic feature of which is an inflammatory, vascular and fibrotic change in the skin and other structures.

• Scleroderma is associated with two syndromes- CREST syndrome, Thibierge-Wissenbach syndrome

CREST syndrome

Thibierge-Wissenbach syndrome

• Describes extensive subcutaneous tissue calcinosis.

The periodontal manifestations of scleroderma are: ( Stafne, Austin 1944)• Widening of the periodontal ligament space occurs at the

expense of the alveolar bone

• The periodontal space of the posterior teeth is more likely to be affected than the anterior teeth. This may be due to the difference in occlusal loading.

• The increase in width of the periodontal ligament space is uniform all around the tooth.

• The affected teeth are not in supraocclusion.

• The gingival attachment is unbroken and the gingival crevice is normal.

The histological picture is as follows-

• Erratic bone resorption in the region of the alveolar bone approximating the periodontal ligament

• Thickening due to proportionate increase of collagen and oxytalan fibres which contain areas of degradation

• Sclerosis and hyalinization of collagen, particularly adjacent to the teeth. There is the development of elastic fibres in this region.

• There is formation of coal areas of bone or irreregular areas calcified deposits. ( Fulner and White, 1962)

Radiographic appearance of scleroderma

Other clinical manifestations• Higher incidence of periodontal disease in

scleroderma patients than in normal patients ( Mammary et al, 1981)

• Crenations are found on the buccal mucosa and this could lead to severe mucogingival problems. ( Eversole et al, 1983)

• Microstomia, limited mouth opening and hand changes associated with scleroderma can impede effective mechanical plaque control by the patient.

SYNDROMES AFFECTING THE PERIODONTIUM

PART II

SYNDROMES CAUSING PERIODONTAL DESTRUCTION

A. Neutrophil defects• The importance of PMN- the cellular defender, in the

pathogenesis of periodontal disease is dramatically brought to the forefront in those systemic diseases that are characterized by either an innate or an induced abnormality in the number and/or function of the neutrophil and a concomitant destruction of the periodontium.

• Defects in any of the functions (qualitative defect) or a marked decrease in the number of neutrophils (quantitative defect) capable of responding to the site of infection may result in varying degrees of susceptibility to infection.

Neutrophil defects

Quantitative

Qualitative

B M periphery

R & A Phago chemo

Quantitative defects• A relative deficiency in neutrophil number can dramatically

increase susceptibility to infectious diseases.

• Neutropenia is considered clinically significant when the absolute neutrophil count falls below 1,000 cells/ml (normal adult range: 1,800– 8,000 cells/ml).

• Diagnosis of neutropenia is based on clinical signs and symptoms as well as absolute neutrophil counts.

The pathophysiology of neutropenia may be -

• abnormalities of bone marrow stem cell development,

• impaired release of neutrophils from the bone marrow,

• abnormalities in distribution of neutrophils between the circulating and marginating pool in the blood,

• decreased survival of neutrophils in the blood

Quantitative defects

At the BM

At the periphery

Kostmann synd Felty’s synd

Lazy leukocyte synd

1. Kostmann syndrome (Congenital neutropenia) (OMIM 610738;OMIM 605998)

• Congenital neutropenia (Kostmann syndrome) was named after the Swedish pediatrician who first described the disease in 1950

• Congenital neutropenia is an inherited hematologic disorder manifesting in the first year of life and characterized by severe bacterial infections.

• The significant laboratory findings are an absolute neutrophil count of less than 2,000/ml and an arrest of neutrophil hematopoiesis at the promyelocyte/ myelocyte stage.

Oral manifestations

• gingivitis• alveolar bone loss

- Carlsson, 2001

• generalized severe periodontitis – Defraaia 2001

Other syndromes associated with decreased neutrophil counts and periodontal destruction

• Hermansky–Pudlak syndrome

• Shwachman–Diamond syndrome

• Inherited bone marrow failure syndrome

2. Felty’s syndrome

• Felty’s syndrome is an uncommon complication of rheumatoid arthritis, in which splenomegaly and leucopenia are the major additional features.

• Other features are- weight loss, progressive weakness, hyperpigmentation of the skin, generalized lymphadenopathy, hepatomegaly, increased susceptibility to infection, and a variety of abnormalities in white blood cell count and function.

The leukopenia noted in Felty’s syndrome is primarily due to a lack of circulating neutrophils. This could be

due to-• insufficient formation of neutrophils,• reduced release of neutrophils from the bone marrow, • a shortened neutrophil life span, and • excessive neutrophil margination

The decrease in bone marrow levels could be due to -(Coakley et al. and Kumakara et al.) anti-neutrophil antibodies, serum inhibitory factors directed against neutrophil precursors, suppressor action by cytotoxic T-cells, or phagocytosis of neutrophils within the bone marrow.

Oral manifestations

• oral ulceration • stomatitis• periodontitis ( rarely)

3. Lazy leukocyte syndrome• Lazy leukocyte syndrome is an extremely rare disorder that

manifests in both quantitative and qualitative neutrophil defects.

• Lazy leukocyte syndrome is characterized by recurrent infections due to both a deficiency in neutrophil chemotaxis and a systemic neutropenia, while the phagocytic function of the neutrophil remains intact.

• Within the bone marrow, the quantity and morphology of the neutrophils are normal.

• Peripherally, however, there exists not only a severe neutropenia but also functional defects of neutrophils with regard to chemotaxis and random migration.

• There is a defect in the microtubular structure of neutrophils which causes defective mobility.

• Impaired random and directional motility leads to a diminished in vivo migration of neutrophils into the tissue and to sites of inflammation.

Clinical findings- Constantopoulous et al, 1975

Systemic findings

• high fever• cough• bilateral pneumonia• purulent skin abscess

Oral manifestations

• stomatitis• gingivitis• recurrent ulcerations• periodontitis with advanced

alveolar bone loss and tooth loss.

Qualitative disorders

The neutrophil’s action can be divided into six stages or functions:

• rolling along vascular endothelium,• adherence to the endothelial lining,• migration (chemotaxis) toward the site of the

infection,• adherence to microorganisms,• engulfment of bacteria (phagocytosis), • intracellular killing.

Qualitaive Defects

1.Defects in rolling and adhesion –LAD I and LAD II

2.Defects in migration and chemotaxis-Hyperimmunoglobulin E syndrome, lazy leukocyte syndrome,

Papillon-lefvre syndrome, Down’s dsyndrome, Kindler syndrome

3. Defects in phagocytosis and intracellular killing-Chediak Higashi syndrome

I. Defects in the process of margination can occur at two levels.

• The first is a defect in a specific neutrophil ligand called the Sialyl-Lewis x (selectin) protein (CD15s).

• A defect in this glycoprotein will result in the loss of the neutrophil’s ability to ‘‘roll’’ along the endothelial lining of venules.

• Alterations in the selectin-mediated rolling function prevent the neutrophil’s egress from the venules.

• The defect is detected through flow cytometry using a commercially available monoclonal antibody directed against the membrane surface antigens associated with CD15s.

• The disease associated with this deficit is leukocyte adhesion deficiency type 2 (LAD-II).

• The second neutrophil defect involving margination is at the level of neutrophil adhesion to the endothelial cell.

• Defects in neutrophil surface integrins CD18/CD11a, CD18/CD11b, and CD18/CD11c prevent the neutrophil from adhering to the endothelium.

• Inability to adhere to endothelial cells prevents the migration of neutrophils to the site of infection.

• These integrins are responsible for neutrophil adhesion to opsonized bacteria and thus the neutrophil’s ability to phagocytize bacteria is compromised.

• Defects on CD18 and CD11 peptides are also identified by flow cytometry.

• Deficiency of these intergrins is termed LAD-I.

Leukocyte adhesion deficiency syndrome

• In 1979, a group of patients with similar symptoms of delayed umbilical cord separation and persistent bacterial infections in the absence of pus formation were found to share a common neutrophil motility defect.

• The name leukocyte adhesion deficiency was given to this condition by Anderson & Springer in 1986.

• Leukocytes adhere to vessel wall endothelium, other leukocytes, and to complement via cell surface integrins.

• These integrins are protein complexes that are stored within neutrophil granules and when activated, are found on the surface of the neutrophil cell membrane.

• The initial studies on leukocyte adhesion deficiency patients found a defect in the neutrophil integrins.

• Subsequent investigations into this disorder have identified two types of leukocyte adhesion deficiencies, LAD-I and LAD-II.

LAD-I• LAD-I is an inherited disorder that follows an autosomal recessive

pattern

• LAD-I is a disorder that involves a deficiency in three membrane integrins.

• CD18/CD11a (LFA-1) binds to leukocytes and to endothelium via intercellular adhesion molecules (ICAM).

• CD18/CD11b (Mac-1) binds to ICAM and complement and facilitates complement- mediated phagocytosis.

• The function of CD 18/Cd11c is not known.

(OMIM 116920)

• The deficiency of these integrins prevents the neutrophil from adhering to the vessel wall at the site of an infection.

• Therefore, in spite of a leukocytosis (20,000–80,000 cells/ml), neutrophils are unable to migrate into the affected tissues.

• The clinical appearance is one of ulceration and necrosis of tissue, but without signs of purulence.

Oral manifestations (Waldrop et al.)

• acute gingival inflammation of the primary and permanent dentition

• gingival proliferation• gingival recession• mobility of teeth• pathological migration

The oral findings in a LAD-I pt.

LAD-II (OMIM 266265)• LAD-II was first described in 1992 by Etziomi et al. Individuals with

LAD-II are characterized by short stature, mental retardation, and craniofacial abnormalities as well as recurrent infections.

• The neutrophil defect in LAD-II is of the sialyl-Lewis x glycoprotein (CD15s), which allows neutrophils to attach to selectins (CD62E) on the endothelial surface.

• The end result is similar to LAD-1, and neutrophils are unable to migrate extravascularly .

• While the oral condition of these patients has not been reported, it can be assumed that the neutrophil defect is such that severe periodontal disease and tooth loss is likely.

II. Deficits in neutrophil chemotaxis• Deficits in neutrophil chemotaxis can be either inherited, or

secondary to a number of other neutrophil defects caused by a variety of diseases or medications.

• Any alteration in the neutrophil cytoskeleton or its ability to sense or respond to a chemotactic gradient will interfere with the cell’s ability to reach the site of infection.

• Neutrophil chemotactic deficits are diagnosed in vivo through the use of the Rebuck skin window or in the laboratory using a Boyden chamber or the agarose technique.

1. Hyperimmunoglobulin E syndrome (Hill-Quie syndrome, Jobs syndrome) (OMIM 147060)

• Hyperimmunoglobulin E syndrome is a multisystem disorder inherited as an autosomal dominant trait that affects the dentition, the skeleton, connective tissues, and immune system .

• Classically, it has been characterized by a triad of symptoms including skin abscesses, pneumonia, and elevated serum immunoglobulin E levels.

Clinical features • Eosinophilia, candidiasis, arthritis, chronic eczematoid

dermatitis and other recurrent infections are also common .

• Typically, patients with hyperimmunoglobulin E syndrome have coarse facial skin with prominent pores.

• Other common findings include facial asymmetry, prominent forehead, deep-set eyes, broad nasal bridge and mild prognathism.

• A decrease in bone density is common, leading to a high incidence of long bone fractures .

Clinical features• Clinically, the appearance of the soft tissue lesions is rather

unique.

• Often described as ‘‘cold abscesses’’, these deep soft tissue lesions present as fluctuant masses that may be mistaken for cysts or tumors.

• These abscesses, typically caused by S. aureus, often lack the usual signs of inflammation, such as warmth, erythema, and tenderness.

• Extension of these lesions into bone may occur giving rise to an osteomyelitis.

• Recurrent infection is one of the chief features of hyperimmunoglobulin E syndrome.

Three hypotheses exist for the chemotactic defect in the neutrophils:

• A specific IgE against an infecting bacterium (S. aureus) causes the release of histamine that may inhibit neutrophil chemotaxis – Chikazawa et al, 1984

• Bacterial antigens cause monocytes to secrete chemotaxis inhibiting mediators or IgG – Seligmann BE, 1983

• Mononuclear cells may create a specific factor which inhibits neutrophil chemotaxis – Donabedian H, et al, 1982

Certainly contributing to the high rate of recurrentinfections in hyperimmunoglobulin E patients is a

defect in neutrophil chemotaxis

Oral manifestations

– ulcerations – gingivitis– over-retention of primary teeth

(Failure to shed the primary dentition in this case, in contrast with the early loss of primary teeth due to periodontitis seen in other disorders of host defenses, is surprising

2. Papillon-Lefèvre syndrome(OMIM 245000)

• The Papillon-Lefevre syndrome is described as a diffuse palmoplantar keratosis associated with aggressive periodontitis of both primary and permanent dentitions.

• The syndrome is named after the two authors who first introduced this condition to the literature in 1924.

• Papillon-Lefevre syndrome is a rare autosomal recessive disease with a prevalence of one to three cases per million in the general population.

• Consanguinity between parents has been reported in at least one third of the reported cases.

• The syndrome appears equally in males and females

The two essential features of Papillon-Lefevre syndrome are

1.hyperkeratosis of the palms and soles (either diffuse or localized)2. generalized rapid destruction of the periodontal attachment apparatus resulting in premature loss of both primary and permanent teeth.

Other findings are-

• ectopic calcifications of the falx cerebri and choroid plexus

• increased susceptibility to infection • mental retardation• endocrine disorders

• Papillon-Lefevre syndrome is but one of at least 19 different forms of palmoplantar keratoedema.

• While some of these other conditions may manifest with abnormalities of the teeth, Papillon-Lefevre syndrome is the only one associated with aggressive periodontitis.

• The association of Papillon-Lefevre syndrome with aggressive periodontitis, and in some cases recurrent infections, led investigators to study neutrophil functions in Papillon-Lefevre syndrome patients.

• Van Dyke et al. described neutrophil chemotaxis defects in two patients with Papillon-Lefevre syndrome and noted decreases in both random migration and directed migration toward a chemotactic factor.

• This alteration of polymorphonuclear neutrophil leukocyte function has not been observed in all cases.

• Both Lyberg and Schroeder et al. reported normal neutrophil function including margination, chemotaxis, phagocytosis, degranulation of lysosomes and intracellular destruction in several children with Papillon-Lefevre syndrome who did not exhibit an increased susceptibility to infection

3. The Haim-Munk syndrome(OMIM 245010)

• A particular form of Papillon-Lefevre syndrome has been named the Haim-Munk syndrome. While also characterized by palmoplantar keratosis and severe early onset periodontitis, the Haim-Munk syndrome additionally presents with digital abnormalities.

• These include osteolysis of the distal phalanges, abnormal length and slenderness of the fingers and toes, and a claw-like hypertrophic deformity of the nails

4. Down’s syndrome

• Down’s syndrome, one of the most common causes of mental retardation in children, was named after the English physician who in 1866 characterized the appearance and behavior of these patients.

• The distinct similarities in the features and conditions of the disease led early researchers to suspect a chromosomal aberration, and in the late 1950s Down’s syndrome was specifically linked to trisomy of chromosome 21.

Down’s syndrome and periodontitis

• In an extensive review of periodontal disease in Down’s syndrome, Roland-Bousma & Van Dijk examined both endogenous conditions and exogenous factors that may predispose affected patients to aggressive periodontitis.

• They divided the exogenous factors into local factors, related mostly to oral hygiene, and secondary factors, such as tongue thrust, malocclusion, and lack of lip seal, which are common features of Down’s syndrome.

• While certainly contributing to the extent of the disease, the bulk of the evidence suggests that these exogenous factors are not commensurate with the severity of the periodontitis noted in Down’s syndrome patients.

Among the endogenous factors that may exacerbate the periodontitis in Down’s syndrome are defects in

neutrophils.• the tendency of the nucleus in neutrophils of Down’s

syndrome patients to be consistently less segmented than in other patient groups.

• preponderance of younger cell forms that is independent of both the total leukocyte count and the relative number of neutrophils.

• tendency for the shortening of the half-life of circulating neutrophils in patients with Down’s syndrome.

Other Neutrophil defects reported -

• significant reduction in chemotaxis in the Down’s syndrome children.

• Reports on the phagocytic ability of neutrophils in Down’s syndrome are mixed.

• Reduced bacteriocidal capacity has been reported for a number of organisms, including S. aureus, Escherichia coli, and C. albicans.

• Halinen et al. found increased levels of neutrophil collagenase (MMP-8) in the saliva and gingival crevicular fluid of Down’s syndrome patients.

• These findings suggest that the active MMP-8 derived from triggered neutrophils and/or cytokine induced periodontal fibroblasts may reflect the periodontal destruction seen in patients with Down’s syndrome.

Clinical features

• Clinically the gingiva are red, swollen and bleed easily.

• Gingival hyperplasia can occur secondarily due to mouth breathing, poor hygiene, and local irritating factors.

• The gingivitis frequently progresses to generalized early periodontitis, which commences in the deciduous dentition and continues to affect the permanent dentition. Bone loss, migration of teeth and mobility are common. All these predispose to premature loss of teeth.

• Macroglossia, fissured and geographic tongue, high arched palate, cleft palate, delayed tooth eruption and hypoplastic teeth are the most frequent oral lesions

• Follicular hyperkeratosis, facial flushing, aloepecia aerata and dry skin are common.

• Polydactyly, syndactyly, clinodactyly, hyperextensibility of joints, other skeletal abnormalities, congential heart abnormalities, hormonal abnormalities, learning disabilities, mongoloid slanting of eyes, short ears and a flat face are common.

5. Kindler syndrome• Also called hereditary acrokeratotic poikiloderma, this

autosomal-recessive condition, first described by Kindler in 1954, is caused by mutation in the kinderlin gene (KIND1) .

• Kinderlin is expressed in multiple tissues, including the skin, where it may play a role in integrin signaling of cell-adhesion processes.

• Studies of the KIND1 gene homologue in the nematode (roundworm) Caenorhabiditis elegans suggest that it has an important role linking the actin cytoskeleton to the extracellular matrix

• Patients present with severe periodontitis of both the primary and secondary dentition, resulting in severe alveolar bone loss and premature exfoliation of the teeth .

• Kindler syndrome manifestations include multiple dermatological findings, including sun sensitivity, eczematoid dermatitis, skin fragility, patchy hyper and hypo-pigmentation, hyperkeratosis of the palms and soles, and diffuse skin wrinkling.

• Ridging and grooving of the nails may also be present.

6. Hypotrichosis osteolysis periodontitis palmoplantar keratoderma syndrome (OMIM 607658)

• Hypotrichosis osteolysis periodontitis palmoplantar keratoderma syndrome is a very rare condition that resembles Papillon–Lefevre syndrome and Haim– Munk syndrome.

• The condition has only been reported in three individuals from two different families and may be transmitted as an autosomal dominant trait.

• It has been noted that periodontitis and gingivitis occur in hypotrichosis osteolysis periodontitis palmoplantar keratoderma syndrome, although the teeth are reported to have been extracted in one patient as a result of advanced caries.

• Radiographic demonstration of periodontitis is not provided in reports of hypotrichosis osteolysis periodontitis palmoplantar keratoderma syndrome.

• More thorough evaluation of periodontal status in hypotrichosis osteolysis periodontitis palmoplantar keratoderma syndrome is warranted.

III. Defects in intracellular killing

• Defects in intracellular killing usually refers to degranulation defects

• Degranulation is either delayed or incomplete, leading to impaired intracellular killing.

• There are two main conditions with defects in degranulation – Chediak- Higashi syndrome and specific granule deficiency.

1. Chediak-Higashi syndrome(OMIM 214500)

• Chediak-Higashi syndrome is a rare autosomal recessive disorder that primarily affects neutrophils.

• Its genetic etiology manifests itself early in life in the form of partial oculocutaneous albinism, photophobia, frequent pyogenic infections and lymphadenopathy.

Clinical features

• Oral findings include severe gingivitis, ulcerations of the tongue and buccal mucosa, and early onset periodontitis leading to premature loss of both deciduous and permanent dentitions.

• The syndrome was first described by Beguez-Cesar in 1943, but acquired its name 10 years later from separate reports by Chediak in 1952 and Higashi in 1954, which described the same condition

Clinical features

• Clinically, the syndrome may present as abnormalities of pigmentation, recurrent infections, and bleeding tendencies .

• Oculocutaneous albinism can affect the skin, eyes, and hair.

• Hair color is characteristically metallic silver, the skin color white to gray due to defective melanosomes, and the eyes are affected by reduced pigmentation of the retina and iris.

Clinical features• Other ocular abnormalities can include nystagmus, photophobia

and reduced visual acuity.

• Infections are commonly skin abscesses, pneumonias, otitis media and sinusitis.

• Bleeding problems arise because of organelle abnormalities within platelets that inhibit normal clot formation.

• Peripheral or cranial neuropathies may develop similar to those seen in Parkinson’s disease.

• Weakness, sensory deficits, clumsiness, a wide-based gait, seizures and tremors have also been reported

Cellular level findings• On a cellular level, organelle abnormalities,

specifically of lysosomes, are present in cells throughout the body.

• One of the hallmarks of the Chediak- Higashi syndrome is the presence of large intracellular azurophilic inclusions in the cytoplasm of neutrophils.

Cellular level findings• These large inclusions impair neutrophil migration, possibly by

inhibiting cell deformability, and render neutrophils unable to metabolize and digest microbes.

• As a result, patients with Chediak- Higashi syndrome are prone to recurrent infections in early childhood

• a mutation in the LYST (lysosome trafficking regulation) gene, the only known Chediak-Higashi syndrome-causing gene, may be responsible for this phenomenon. Bone marrow transplantation appears to be the most effective treatment.

Oral manifestations• dental pain• swollen gingiva with frank purulence• severe horizontal bone loss• lymphadenopathy

- Delcourt-Deburyne, 2000

• severe mobility of teeth• generalized recession with deep probing depths

- Hamilton RE, 1974

• gingival bleeding – Huizing M et al, 2001

B. connective tissue disordersEhlers–Danlos syndrome

• The Ehlers–Danlos syndromes are a heterogeneous group of inherited connective tissue disorders characterized clinically by skin fragility, skin hyperextensibility, joint hypermobility, and excessive bruising.

• At least 17 different subtypes of Ehlers– Danlos syndrome have been classified based on genetic, biochemical, and clinical characteristics

• Poor wound healing is a component of a number of subtypes of Ehlers–Danlos syndrome, and severe, early-onset periodontitis has been associated with two subtypes: Ehlers–Danlos syndrome type 4 and Ehlers–Danlos syndrome type 8.

Ehlers–Danlos syndrome type IV (OMIM 130050) - Sack’s ecchymotic type

• Transmitted as an autosomal-dominant trait, Pope et al. (96) first identified that this form of Ehlers–Danlos syndrome is caused by defects in type III collagen.

• The majority of mutations that give rise to Ehlers–Danlos syndrome type IV are point mutations that result in substitution of a glycine residue within the triple helix and point mutations that alter splice junctions and lead to exon-skipping.

• These types of mutations disrupt the secretion of most of the type III procollagen molecules being synthesized.

• The severity of the phenotype appears to be related to the stability of mutant type III collagen protein and the extent to which it disrupts collagen fibrillogenesis in the extracellular matrix

• Since collagen type III comprises 9% of the gingival collagen and approximately 16-20% of the total collagen in the periodontal ligament, it was proposed that a defect in type III collagen would compromise the periodontal attachment apparatus.

The clinical presentation of Ehlers–Danlos syndrome type IV can include

• significant and life-threatening cardiovascular and cerebrovascular complications that predispose to rupture of arteries, the bowel, and the gravid uterus .

• Phenotypic findings include short stature, pinched thin nose, thin lips, lobeless ears, keratoconus, periodontitis, mitral valve prolapse, intracranial aneurism, pneumothorax, uterine prolapse, bladder prolapse, hypermobility of distal interphalangeal joints, acroosteolysis, fragile skin, easy bruising, cigarette-paper scars, and prominent venous markings.

• A number of reports document the presence of severe periodontitis in individuals with Ehlers–Danlos syndrome type IV, although many clinical reports of the condition do not mention if an oral examination was performed, possibly because attention was focused on more serious clinical manifestations

• More work needs to be done to determine the nature of the cellular and biochemical defects in patients with early periodontitis and Ehlers-Danlos syndrome.

Ehlers–Danlos syndrome type VIII (OMIM 130080) -Periodontitis type

• Transmitted as an autosomal-dominant condition, the gene mutations responsible for Ehlers–Danlos syndrome type VIII have not yet been identified.

• However, genetic linkage studies indicate that at least two genetically distinct forms of Ehlers–Danlos syndrome type VIII exist, with one form localized to chromosome 12 .

• The association of precocious periodontitis with Ehlers–Danlos syndrome type VIII has been reported by a number of investigators, suggesting that periodontal findings may be more common in Ehlers–Danlos syndrome type VIII than in type IV.

• The association of precocious periodontitis with Ehlers–Danlos syndrome type VIII has been reported by a number of investigators, suggesting that periodontal findings may be more common in Ehlers–Danlos syndrome type VIII than in type IV.

AIDS

AIDS

• Stands for Acquired Immuno Deficiency Syndrome

• This is the end stage disease in a patient with HIV infection representing the irreversible breakdown of immune defence mechanisms, leaving the patient a prey to progressive opportunistic infections and malignancies.

• The definition of AIDS has now been broadened to include all seropositive persons (irrespective of clinical manifestations) with CD4 T cell counts of less than 200 per cu.mm

• The clinical severity of AIDS varies with the type of infection or malignancy present.

• In early AIDS, many patients are ill only during episodes of infection, which may respond to treatment.

• Between episodes they may be relatively well and able to resume normal life.

• The illness progresses inexorably and death ensues in months or years.

CDC Surveillance Case Classification (1993):

Category A includes patients with acute symptoms or asymptomatic diseases, along with individuals with persistent generalized lymphadenopathy, with or without malaise, fatigue, or low-grade fever.

Category B patients have symptomatic conditions such as oropharyngeal or vulvovaginal candidiasis; herpes zoster; oral hairy leukoplakia; idiopathic thrombocytopenia;or constitutional symptoms of fever, diarrhea, and weight loss.

Category C patients are those with outright AIDS as manifested by life-threatening conditions identified by CD4+ T lymphocyte levels of less than 200 per cubic millimeter.

According to the system most affected patients present with various complaints, some of which are as follows:

a. Respiratory system- The commonest presentation is with increasing dry cough, dyspnea and fever.

b. Gastrointestinal system – Dysphagia, intestinal infections, Chronic colitis

c. CNS- opportunistic infections- toxoplasmosis and cryptococcosis

d. malignancies- Kaposi’s sarcoma

e. Cutaneous lesions - herpes lesions, candidiasis, xeroderma, seborrheic dermatitis,

prurigo, folliculitis, impetigo and molluscum contagiosum

ORAL AND PERIODONTAL MANIFESTATIONS OFHIV INFECTION

• Oral Hairy Leukoplakia• Oral Candidiasis• Kaposi's Sarcoma• Bacillary (Epithelioid)

Angiomatosis• Oral Hyperpigmentation• Atypical Ulcers and Delayed

Healing• Adverse Drug Effects

• Periodontal D’se-• L.G.E• N.U.G• N.U.P• N.U.S

Oral Hairy Leukoplakia

• Oral hairy leukoplakia primarily occurs in persons with HIV infection.

• Found on the lateral borders of the tongue, it frequently has a bilateral distribution and may extend to the ventrum.

• This lesion is characterized by an asymptomatic, poorly demarcated keratotic area ranging in size from a few millimeters to several centimeters.

• Often, characteristic vertical striations, imparting a corrugated appearance, are present, or the surface may be shaggy and may appear "hairy" when dried.

• The lesion does not rub off and may resemble other keratotic oral lesions.

Oral Candidiasis

• Candidiasis is the most common oral lesion in HIV diseases and has been found in approximately 90% of AIDS patients.

• It usually has one of four clinical presentations: pseudomembranous, erythematous, or hyperplastic candidiasis or angular cheilitis.

• Although candidiasis in HIV-infected patients may respond to antifungal therapy, it is often refractory or recurrent.

Kaposi's Sarcoma

• Kaposi's sarcoma is a rare, multifocal, vascular neoplasm; it was originally described in 1872 as occurring in the skin of the lower extremities of older men of Mediterranean origin.

• Although KS is a malignant tumor, in its classic form it is a localized and slowly growing lesion.

• In the early stages, the oral lesions are painless, reddishpurple macules of the mucosa.

• As the lesions progress, they frequently become nodular and can easily be confused with other oral vascular entities such as hemangioma, hematoma, varicosity, or pyogenic granuloma (when occurring in the gingiva).

Bacillary (Epithelioid) Angiomatosis

• Bacillary (epithelioid) angiomatosis (BA) is an infectious vascular proliferative disease with clinical and histologic features very similar to those of KS.

• BA is believed to be caused by rickettsia-like organisms, Bartonellaciae henselia, quintana, or others.

• Gingival BA manifests as red, purple, or blue edematous soft tissue lesions that may cause destruction of periodontal ligament and bone

• The condition is more prevalent in HIV-positive individuals with low CD4 levels.

Linear Gingival Erythema• A persistent, linear, easily bleeding,

erythematous gingivitis (LGE) has been described in some HIV-positive patients.

• This may or may not serve as a precursor to rapidly progressive necrotizing ulcerative periodontitis

• LGE is often unresponsive to corrective therapy, yet such lesions may undergo spontaneous remission.

Necrotizing Ulcerative Gingivitis

• Some reports have described an increased incidence of necrotizing ulcerative gingivitis among HIV-infected individuals, although this has not been substantiated by other studies.

Necrotizing Ulcerative Periodontitis• A necrotizing, ulcerative, rapidly progressive

form of periodontitis occurs more frequently among HIV-positive individuals.

• NUP is characterized by soft tissue necrosis, rapid periodontal destruction, and interproximal bone loss

• Lesions may occur anywhere in the dental arches and are usually localized to a few teeth, although generalized NUP is sometimes present after marked CD4+ cell depletion

Conclusion • It is well established that many systemic conditions express

their effects on the periodontium.

• Future epidemiological studies designed to assess the role of systemic conditions and disorders in periodontal disease are needed, particularly to refine experimental design and data analysis; to identify gaps in knowledge with respect to mechanisms of factors known to play a role in increasing susceptibility to periodontal disease; and to address gaps in knowledge of the correlation with the systemic conditions suspected of being related to periodontal disease.

References • Carranza’s clinical periodontology-8th edition- Takei, Newman, Klokkevold

and Carranza

• Carranza’s clinical periodontology-9th edition- Takei, Newman and Carranza

• A textbook of oral pathology- 4th edition- Shafer, Hine and Levy.

• Drugs, diseases and the periodontium- Robin A Seymour

• Periodontal manifestations of local and systemic diseases- Laskaris G, Scully C.

• Influences of systemic diseases on periodontitis in children and adolescents - Joerg Meyle & Jose R. Gonzales Periodontology 2000, vol. 26, 2001, 92–112

References• Systemic disease and periodontitis: manifestations of neutrophil

dysfunction- David E. Deas, Scott A. Mackey & Howard T. McDonnell-Periodontology 2000, vol. 32, 2003, 82–104

• Gingival and periodontal aspects of diseases of the blood and blood forming organs and malignancy- Stephen r. Porter Periodontology 2000, vol. 18, 1998, 102-110

• Mendelian forms of periodontitis- Thomas C. Hart & Jane .C. Atkinson-Periodontology 2000, vol. 45, 2007, 95–112

• www.ncbi.nlm.nih.gov

• www.whonamedit.com/synd.cfm/3648.html

• www.wikepedia.com

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