collagen disorders

1. COLLAGEN
DISORDERS
P R E S E N T E D B Y:
D R . B H A W N A PA N T
I I M D S
O R A L A N D M A X I L L O F A C I A L
PAT H O L O G Y 1

2. CONTENTS
• INTRODUCTION
• COLLAGEN IN HEALTH
• OSTEOGENESIS IMPERFECTA
• EPIDERMOLYSIS BULLOSA
• STICKLER’S SYNDROME
• MARFAN’S SYNDROME
• EHLER-DANLOS SYNDROME
• SYSTEMIC SCLEROSIS
• SYSTEMIC LUPUS ERYTHEMATOUS
• ORAL SUBMUCOUS FIBROSIS
• SCURVY
2

3. INTRODUCTION
• COLLAGEN : The fibrous protein constituent of bone, cartilage, tendon, and other
connective tissue that converts into gelatin by boiling.
(The American Heritage® Stedman's Medical Dictionary)
• The most abundant protein-family found in humans, constituting 25% of the total
protein mass.
• Collagen is the main fibrous component of all connective tissues.- skin, bone ,tendon,
cartilage and periodontium.
3

4. COLLAGEN IN HEALTH
SKIN HEALTH :
• Collagen dictates the structure of skin, connective tissues, tendons, bones and
cartilage.
• Collagen type I constitutes approximately 70% , type III : 10% and trace amounts of
collagen type IV, V, VI and VII.
• Maintains firmness and elasticity of skin.
• Collagen hydrolysate : Keeps skin hydrated.
• Ageing process : Sagging and wrinkle lines.
• Type III collagen synthesis decreases with age  Changes in skin tension, elasticity and
healing.
4

5. WOUND HEALING
• Collagen deposition and remodeling contribute to
the increased tensile strength of the wound
Approximately 20% of normal by 3 weeks after injury
gradually reaching a maximum of 70% of that of
normal skin.
• Collagen overproduction  Abnormal scars, which
impede wound healing.
5

6. BONE
• 22-25% of organic component : 94 to 98% is mainly
collagen type I and other noncollagen proteins and
2 to 5% are cells.
• Combination of collagen mesh and water forms a
strong and slippery pad in the joint that cushions
the ends of the bones in the joint during muscle
movement.
Bone is a complex and dynamic tissue that provides structural support
for the body, protection of internal organs and acts as levers to which
muscles are attached, allowing movement.
6

7. CARTILAGE, TENDON, LIGAMENTS
• Collagen, in the form of elongated fibrils, is
predominantly found in fibrous tissues such as
tendon and ligament.
• 75% of the dry tendon weight
• Withstand and transmit large forces between
muscle and bone.
• Cartilage collagen fibrils consist of collagen II, the
quantitatively minor collagens IX and XI.
7

8. A. DENTIN:
• 70% inorganic material, 20% organic material and 10%
water by weight.
• Organic phase : 30% collagen (mainly type I with small
amounts of types III and V) with fractional inclusions of
lipids and noncollagenous matrix proteins.
• Collagen type I acts as a scaffold that accommodates
large proportion (estimated at 56%) of the mineral in
the holes and pores of fibrils.
DENTAL TISSUES
8

9. B. PULP:
• The extracellular compartment of the pulp or
matrix consists of collagen fibers and ground
substance.
• Approximately 34% dry weight of pulp is
collagen.
• Type I and III collagen.
9

10. C. CEMENTUM:
• Predominant collagen present in cementum is
type I collagen (90%).
• Other collagen : type III and type XII
• Collagens found in trace amounts : types V, VI
and XIV.
10

11. D. PERIODONTAL LIGAMENT:
• Predominant collagens of the periodontal
ligament are types I, III and XII.
• Vast majority of collagen fibrils in the
periodontal ligament are arranged in
and distinct fiber bundles and these are
termed as principal fibers.
Periodontal ligament is composed of collagen fibers
bundles connecting cementum and alveolar bone
proper.
11

12. BASEMENT MEMBRANE
• The lamina densa consisting of type IV
collagen that is coated by heparan
sulfate, a glycosaminoglycan and
anchoring fibrils, that are composed of
type VII collagen and extend from the
lamina densa to the connective tissue.
The epithelial basement membrane and adjacent area is termed the epithelial basement
membrane zone.
12

13. COLLAGEN
DISORDERS
13

14. CLASSIFICATION
14

15. OSTEOGENESIS IMPERFECTA
• Heterogeneous group of heritable disorders characterized by impairment of collagen
maturation.
• Mutations in one of two genes that guide the formation of type 1 collagen : COL 1 A1
gene on chromosome 17 and COL 1 A2 gene on chromosome 7.
• Collagen forms a major portion of bone, dentin, sclera, ligaments and skin;
osteogenesis imperfecta demonstrate a variety of changes that involve these sites.
16

16. OSTEOGENESIS IMPERFECTA
17

17. CLINICAL FEATURES
• Extreme fragility and porosity of the bones,
with proneness to fracture.
• Blue sclera , altered teeth , hypoacusis ,
long bone and spine deformities , and joint
hyperextensibility.
• Many patients also have a tendency
towards capillary bleeding.
19

18. SILLENCE CLASSIFICATION
• Based on Sillence et al classification, 4 types of osteogenesis imperfecta exist –
1. TYPE 1 Osteogenesis imperfecta
2. TYPE 2 Osteogenesis imperfecta
3. TYPE 3 Osteogenesis imperfecta
4. TYPE 4 Osteogenesis imperfecta
 In 2004 “expanded Sillence classification”.
 According to this classification:
 7 types of OI, type I-VII.
 In 2007, an additional type, OI type VIII was proposed
20

19. Sillence
type
Clinical severity Mutated gene Mode of
inheritance
I Mild-non deforming COL1A1/2 AD
II Perinatal lethal COL1A1/2 AD
III Severely deforming COL1A1/2 AD
IV Moderately deforming COL1A1/2 AD
V Moderately deforming Unknown AD
VI Moderately to severely deforming Unknown AR
VII Moderately deforming CRTAP AR
VIII Severely deforming to perinatal lethal LEPRE1 AR 21

20. TYPE 1 OSTEOGENESIS IMPERFECTA
• AD
• Most common and mildest form.
• Symptoms : Blue sclera , in utero fractures in
10 % of patients , mild to moderate bone
fragility with frequency of fractures
decreasing after puberty , hearing loss , easy
bruising and short stature
• Associated with DI
TYPE 2 OSTEOGENESIS IMPERFECTA
• AD,AR
• Most severe form.
• Exhibits extreme bone fragility and frequent
fractures.
• In utero fractures : 100% cases.
• Blue sclera may be present
• Small nose, micrognathia and short trunk 22

21. TYPE 3 OSTEOGENESIS IMPERFECTA
• AD, AR
• Sclera of variable hue , limb shortening and progressive
deformities and pulmonary hypertension.
• In utero fractures occur in 50% of cases.
• No hearing loss.
TYPE 4 OSTEOGENESIS IMPERFECTA
• AD
• Associated with mild to moderately severe bone fragility.
• Normal sclera, normal hearing, fractures that begin in infancy and
mild angulation and shortening of long bones.
• Frequency of fractures decreases with puberty.
• Associated with DI
23

22. ORAL MANIFESTATIONS
• OI is a disturbance of mesodermal tissues, particularly calcified tissue : Dentinogenesis
Imperfecta
• Large head size, frontal bossing, and exaggerated occiput create a greater percentage
of class III malocclusion.
• Anterior and posterior crossbite are frequent.
• Impactions and ectopic teeth
• Unerupted 1st and 2nd molar
25

23. RADIOGRAPHIC FEATURES
• Osteopenia,
• Bowing, angulation or deformity of the
long bones,
• Multiple fractures and
• Wormian bones ( sutural bones ) in the
skull.
• Radiograph typically reveal premature
pulpal obliteration
• Shell teeth rarely may be seen.
26
BONES
TEETH

24. HISTOPATHOLOGY
• The bone cortex is thin and porous.
• Bone trabeculae are thin delicate and
widely separated.
• Osteoblastic activity appears retarded
and imperfect and for this reason the
thickness of long bone is deficient.
• Failure of woven bone to become
transformed to lamellar bone.
• Defective microvascular system and
decreased collagen fibril diameter.
27

25. DIFFERENTIAL DIAGNOSIS
• Jeune dystrophy: Short rib thoracic dysplasia
• Camptomelic dysplasia: bowing of femur & tibia
• Chondrodysplasia punctata: stippled epiphysis and skeletal dysplasia
28

26. TREATMENT AND PROGNOSIS
• There is no cure for OI, thus symptomatic improvement is the primary goal of currently
available treatment options.
• The mainstays of treatment are PHYSIOTHERAPY, REHABILITATION and ORTHOPEDIC
SURGERY.
• The prognosis varies from relatively good to very poor.
• Type 1A : Life expectancy is similar to that of the general population
• Type 11 : most patients die within 1st year of life.
• A slight decrease in life expectancy is seen in other types.
29

27. EPIDERMOLYSIS
BULLOSA
30

28. EPIDERMOLYSIS BULLOSA
• Group of genetically determined skin fragility disorders characterised by blistering of
skin and mucosae following mild mechanical trauma.
• Alternative term – Mechanobullous Diseases
• Epidermolysis bullosa was first described in 1870 by Von Hebra under the Name ‘Erblichen
Pemphigus’.
• Current name, ‘Epidermolysis Bullosa Hereditaria’, was coined by Koebner in 1886.
• Simplex and Dystrophic EB were clinically separated in 1898 by Hallopeau.
• Junctional EB was first identified in 1935 by Herlitz, and termed ‘EB letalis’.
• Precise characterization of these three major EB types, via the application of transmission electron
microscopy, was first performed by Pearson in 1962.
31

29. EPIDERMOLYSIS BULLOSA
• EB is classified into 3 major categories :
• Epidermolysis bullosa simplex (EBS) (Intraepidermal skin separation)
• Junctional epidermolysis bullosa (skin separation in lamina lucida or central basement
membrane zone)
• Dystrophic epidermolysis bullosa (sublamina densa basement membrane zone).
Researchers have recently proposed a new category termed hemidesmosomal epidermolysis bullosa (HEB)
32

30. ETIOLOGY
• EB simplex : associated with mutation of gene encoding for keratin 5 and 14.
• Junctional EB : Highly variable molecular etiology and represents a collection of
different disease.
• Dystrophic EB : All cases are associated with mutation for the gene encoding for
type VII collagen (COL7A1)
Anchoring fibrils are affected in patients with DEB, and the degree of involvement ranges
from subtle changes to complete absence.
33

31. DYSTROPHIC EPIDERMOLYSIS BULLOSA
• People with EB are referred to as "Butterfly Children"
 Skin as fragile as a butterfly's wing.
34

32. • DEB : 3 subtypes
1. Recessive DEB, severe generalized (formerly called Hallopeau-Siemens type (RDEB-HS)
2. Recessive DEB, generalized other (formerly called non-Hallopeau-Siemens type (RDEB-non-
HS)
3. Dominant DEB (DDEB)
 Cockayne-Touraine and Pasini subtypes of dominant dystrophic
epidermolysis bullosa
– Combined  'dominant dystrophic epidermolysis bullosa‘
– Both are caused by mutations in the COL7A1 gene and show overlapping clinical features
35

33. DYSTROPHIC EB
 COL7A1 gene (MUTATION)
 Gene: Providing instructions for making proteins ---pro-α1
(VII) chains
• Type VII collagen: strengthening and stabilizing the skin
• Main component anchoring fibrils: anchor epidermis to
dermis
36

34. AUTOSOMAL RECESSIVE DEB
• Strictures of the gastrointestinal tract from mucosal involvement
leading to poor nutrition
• Affected individuals: increased risk of developing aggressive
squamous cell carcinoma
• Recurrent blistering  mutilating scarring
and contractures of the hands, feet, and
joints
• Mitten hand deformity
37

35. ORAL MANIFESTATION
• Painful oral bullae
• Scar formation results in obliteration of the sulci and
restriction of the tongue.
• Hoarseness or dysphagia
• Esophageal involvement.
• Dental defects:
– Rudimentary teeth
– Congenitally absent teeth
– Hypoplastic teeth
– Crowns denuded of enamel
38

36. HISTOPATHOLOGY
• Separation and bulla formation occurs
immediately beneath the poorly defined PAS-
positive basement membrane, remains
attached to the roof of the blister.
• Basal layer of the cell is normal.
• Pre-elastic and oxytalan fibers are increased in
number
• Elastic fibers are also increased but appears
fragmented
H &E stained section Magnification:
40X
( leading edge of a fresh or mechanically induced bl
39

37. STICKLER’S
SYNDROME
46

38. STICKLER SYNDROME
• Group of hereditary conditions characterized by :
• Facial appearance
• Eye abnormalities
• Hearing loss
• Joint problems
 INCIDENCE: 1:7,500-1:9,000 / yr
• Mutation
• COL2A1, COL11A1 and COL11A2
 Inherited in an autosomal dominant pattern
• COL9A1 and COL9A2
 Inherited in an autosomal recessive pattern
47

39. CLINICAL FEATURES
• OPHTHALMOLOGIC
• Congenital or early-onset cataract
• Congenital vitreous anomaly
• retinal detachment
• Myopia
• AUDITORY
• Sensorineural or conductive hearing loss
• JOINT
• Hypermobility
• Precocious osteoarthritis
• CRANIOFACIAL
• Midface hypoplasia
• Depressed nasal bridge
• Anteverted nares (characteristic facies
typically more pronounced in childhood)
• Bifid uvula, cleft hard palate
• Micrognathia
• Robin sequence (micrognathia, cleft
palate, glossoptosis)
48

40. MARFAN’S
SYNDROME
49

41. MARFAN’S SYNDROME
• Autosomal dominant inherited disorder of connective tissue, characterised by loss of
elastic tissue, affects numerous body systems, including the musculoskeletal,
cardiovascular, neurological, and respiratory systems, and the skin and eyes.
• Antoine Bernard-Jean Marfan(1886), a French paediatrician described a hereditary
disorder of connective tissue in a 5 yr old girl with disproportionately long limbs that
later became to be known as Marfan syndrome.
• Incidence: 1 in 3000-5000 individuals
• Prevalence is thought to be similar
Antoine Bernard-Jean Marfan 50

42. ETIOLOGY
• Caused by a variety of mutations in the FBN1 gene located
at chromosome 15q21.1. FBN1 mutations have been
identified in over 90 percent patients
– 75% of patients - Autosomal Dominant
– 25% of patients - mutation occurs spontaneously and
may be associated with older paternal age.
51

43. CLINICAL FEATURES
• Increased facial and skull height
• Arachnodactyly
• Dolichostenomelia
• Anterior chest deformity
• Mild to moderate joint laxity
• Kyphosis and flat feet
• Myopia
• Increased axial globe length
• Corneal flatness
• Subluxation of the lenses
• Mitral valve prolapse
• Mitral regurgitation
• Dilatation of the aortic root
• Aortic regurgitation
EYES
HEART
52

44. ORO-FACIAL FEATURES
• High arched palate
• Bifid uvula
• Skeletal class II malocclusion
• Hypermobility of the temporomandibular joint
• Crowding
• Odontogenic cysts
53

45. RADIOGRAPHIC FEATURES
• Skull radiograph may demonstrate :
– High arched palate
– Increased skull height
– Enlarged frontal sinus
54

46. EHLER DANLOS
SYNDROME
55

47. EHLER DANLOS SYNDROME
• EDS is named after the Danish and French dermatologists Edvard Ehlers and Henri-
Alenxandre Danlos
• 1986 10 EDS subtypes were classified by Roman numerals based on clinical manifestations
and mode of inheritance  BERLIN CLASSIFICATION
• 1997  classified into 6 subtypes VILLEFRANCHE CLASSIFICATION
• Ehlers-Danlos syndrome can affect the skin, joints, and blood vessels.
• Hereditary connective tissue disorder
(autosomal dominant or recessive traits)
– Prevalence: 1/10000 to 1/25000
• Signs/Symptoms
– Joint hypermobility
– Skin hyperextensibility
– Tissue fragility
– Pain
(Tenascin-X deficiency syndrome, lysyl hydroxylase deficiency syndrome, cutis hyperelastica)
56

48. 58

49. • Classification and diagnosis of EDS is
difficult
• Diagnosis
– Clinical symptoms: Beighton Score,
Brighton/Villefranche criteria
– Laboratory studies
• Qualitative and quantitative testing of
collagen subtypes
• Genetic mutation analysis
– Positive family history
EDS DIAGNOSIS
60

50. ORAL MANIFESTATIONS
• Oral mucosa  Normal color but excessive fragile and bleed
easily.
• Healing  Slightly retarded with no defective scar formation.
• No hyperextensibility of mucous membrane and no difficulty
in wearing dentures.
• Gingival tissues Friable, bleed after tooth brushing.
• Gingival hyperplasia and fibrous nodules.
• Hypermobility of TMJ  Repeated dislocation of the jaw.
• Alteration in structure of teeth :
• Lack of normal scalloping of the DEJ
• Passage of dentinal tubules into the enamel
• Formation of much irregular dentin
• Increased tendency to form pulp stones
61

51. HISTOLOGIC FEATURES
TREATMENT
• Histologic study of skin and connective tissue by routine techniques usually fails to
reveal any characteristic or diagnostic abnormality.
• No known treatment for the disease.
• Surgical procedures should be carried out with care because difficulty in suturing and
healing problem may exist.
62

52. SYSTEMIC
SCLEROSIS
63

53. SSc is a multisystemic ,autoimmune disease affecting small arteries, micro vessels and
fibroblasts resulting in vascular obliteration, collagen accumulation and scarring
(fibrosis) of skin and internal organs.
Scleroderma is derived from the Greek words ‘Skleros’ (hard or indurated) and ‘Derma’
(skin).
HIPPOCRATES first described this condition as “thickened skin”.
First detailed description  Carlo Curzio in 1752.
Term scleroderma  Giovambattista Fantonetti
Systemic nature of the disease  Robert H.Goetz.
SYSTEMIC SCLEROSIS
(Scleroderma, Dermatosclerosis, Hidebound
disease)
64

54. SYSTEMIC SCLEROSIS
• Characterized by thickening of the skin caused by accumulation
of collagen , and by injuries to small arteries .
• RAYNAUD’S phenomenon is predominant feature seen.
LOCALIZED
(LIMITED)
SYSTEMIC
(DIFFUSE)
Affects the skin of only
the face, hands, and
feet.
SCLERODERMA
may progress to visceral
organs, including
the kidneys, heart, lungs,
and gastrointestinal tract
65

55. SYSTEMIC SCLEROSIS
• Autoimmune disease with unknown etiology.
• (HLA) histocompatability complex : HLA-B8, HLA-DR5, HLA-DR3, HLA-DR52, and HLA-
DQB2
• Affected organs  Skin, lungs, heart, digestive system, kidneys, muscles, joints, and
nervous system.
66

56. PREVALENCE
• Systemic sclerosis is estimated to occur in 2.3-10 people per 1 million.
• It may begin in children and young adult : greatest incidence 30-50 yrs
• F : M :: 3-6:1
67

57. CLINICAL FEATURES
• Systemic Sclerosis usually begin on the face, hands or trunk.
• Two forms are seen :
• LOCALIZED SCLERODERMA
– Morphea
– Linear scleroderma
• SYSTEMIC SCLEROSIS
– Diffuse
– Limited
– Sine scleroderma
– Overlap syndrome/ MCTD
SCLERODACTYLY
SALT AND PEPPER SKIN
HIDEBOUND SKIN
TELANGIECTASIAS
CALCINOSIS
68

58. SYSTEMIC SCLEROSIS
The AMERICAN COLLEGE OF RHEUMATOLOGY (ACR) criteria for the classification of systemic
sclerosis.
One major criteria, two or more minor criteria for diagnosis.
MAJOR CRITERION :
PROXIMAL scleroderma –characterized by SYMMETRICAL thickening, tightening and
induration of the skin of the fingers and the skin proximal to the MCP /MTP joints
MINOR CRITERION :
SCLERODACTYLY – Thickening, induration, tightening of the skin limited only to fingers.
DIGITAL PITTING SCARS/LOSS OF SUBSTANCE FROM THE FINGER PAD –Due to ischemia.
BIBASILAR PULMONARY FIBROSIS- B/L reticular pattern of linear or lineonodular densities in
basilar portions of the lung on CXR.
69

59. Alarcon-Segovia and his coworkers, studied 25 patients with progressive SS, found that all had pathologic
changes in the minor salivary gland characteristic of Sjogren’s disease.
Weisman and calcaterra also reported evidence of alterations of salivary gland function characteristic of
sicca syndrome in 12% of 71 patients with scleroderma.
ORAL MANIFESTATIONS
• Tongue, soft palate and larynx are the intraoral structures usually involved
in progressive SS.
• Early mild edema  atrophy and induration of mucosal and muscular
tissues.
• Tongue fibrosis
• Fibrosis of the hard and soft palate
• Gingival tissues are pale and unusually firm
• Microstomia
• Xerostomia
• Dysphagia
• Limited mouth opening
70

60. RADIOGRAPHIC
FEATURES
• Extreme widening of the
PDL : 2-4 times the
normal thickness.
• Bone resorption of the
angle of mandiblular
ramus, usually bilateral.
• Partial or complete
resorption of condyle and
or coronoid processes of
the mandible. Panoramic radiograph showing generalized symmetrical widening of the
periodontal ligament space with bilateral resorption of the angle, lower
border of the mandible and posterior border of ramus on right side
71

61. HISTOLOGIC FEATURES
• Thickening and hyalinization of the collagen fibers in the
skin
• Loss of dermal appendages (particularly the sweat glands)
• Atrophy of epithelium with loss of rete pegs
• Increased melanin pigmentation.
• Subcutaneous fat disappears and walls of the blood vessels
become sclerotic.
• PDL changes are due to an increase of collagen, oxytalan
fibers as well as an appearance of hyalinization and
sclerosis of collagen with diminution in the number of
connective tissue cells.
H and E stained section showing
Increase connective tissue
appandages and disappearance of
skin appendages
H and E stained section showing
thinning of the epidermis with loss
of rete pegs
72

62. SYSTEMIC LUPUS
ERYTHEMATOSUS
73

63. SLE
• Systemic lupus erythematosus (SLE) is a multi-system auto-immune disease
characterized by autoantibodies, immune complex formation, and immune
dysregulation resulting in damage to essentially any organ, including kidney, skin,
bone cells and the CNS.
• Natural history of this illness is unpredictable; patients may present with many years of
symptoms or with acute life threatening disease.
74

64. ETIOLOGY
Genetics Hormones
Environment
Autoimmune disease of unknown etiology
Patients with SLE produce autoantibodies against DNA, other nuclear antigens, ribosomes, platelets,
erythrocytes, leukocytes and other tissue specific antigen 75

65. CLINICAL FEATURES
• Peak age of onset : 30 years in females and 40 years in males.
• F : M ::
– 2:1 (before puberty)
– 4:1(after puberty)
• cutaneous lesions consists of erythematous patches on the face  coalesce to form a
roughly symmetrical pattern over the cheeks and bridge of the nose  butterfly
distribution.
• Generalized manifestation: Involvement of various organs including the kidney and the
heart.
76

66. SLE
• American Rheumatism Association in 1972: Criteria for the Classification of Systemic Lupus Erythematosus
 11 CRITERIA:
• Malar rash
• Discoid rash (thick, scarring, raised or flat, red, with well-defined borders)
• Photosensitivity
• Oral ulcers, usually painless
• Arthritis, nonerosive, involving two or more peripheral joints
• Serositis (pleurisy or pericarditis)
• Renal disorder (proteinuria exceeding 0.5 g/day or cellular casts)
• Neurologic disorders (seizures or psychosis)
• Hematologic disorders
– Hemolytic anemia
– Leukopenia of less than 4,000/mm3
– Lymphopenia of less than 1,500/ mm3
– Thrombocytopenia of less than 100,000/mm3
• Immunologic disorder (positive LE-cell preparation, anti-DNA in abnormal titer, antibody to Sm nuclear antigen, or false-
positive serologic test for syphilis)
• Antinuclear antibody
4 or more of the 11 criteria are present: Systemic lupus
erythematosus
77

67. SLE
• 3 TYPES :
• Systemic (acute) lupus erythematosus
• Discoid (chronic) lupus erythematosus
• Subacute lupus erythematosus
SLE
ORGANS Skin, oral, heart,
kidneys, joints
SYMPTOMS Fever, malaise, weight
loss
SEROLOGY Positive ANA, Anti-
DNA Antibodies
DIF Same
DLE
Skin & oral only
No
No detectable
antibodies
Granular/linear
basement membrane
deposits of IgG & C3
D i f f e r e n t i a t i on B e t we en “ L E ” S u bt y p e s I s B a s ed U p o n T h e
C o n s t e l l a t i on O f C l i n i c a l , H i s t o l o gi c , & I m m u n o f l u or es c e n c e F i n d i n gs 78

68. ORAL MANIFESTATIONS
• Frequency of oral lesions:
• 8 to 45 % [SLE]
• 4 to 25 % [DLE]
• Well-demarcated zone of atrophy / ulceration surrounded by
red halo as a result of local telengiectasia.
• Involves buccal mucosa, gingiva and palate.
• Superimposed oral moniliasis as well as xerostomia have been
reported.
Irregularly shaped ulcerations
of buccal mucosa
79

69. HISTOLOGIC FEATURES
DLE:
• Hyperkeratosis / Epithelial atrophy,
• Basal cell destruction,
• Lymphocytic infiltration (subepithelial and perivascular
distribution),
• Vascular dilation with oedema of the submucosa
SLE:
• Oral lesions: microscopically similar to lesions of DLE
• Inflammatory cell infiltrates are less intense and more diffuse.
• Other organs (SLE) : vasculitis, mononuclear infiltrates, and
fibrinoid necrosis.
Epidermal thinning with hyperkeratosis, vacuolar
alteration of the basal layer, and a superficial and
deep, perivascular and periadnexal lymphocytic
infiltrate. H&E 40x
80

70. DIRECT / INDIRECT IMMUNOFLUORESCENT TESTING
(SKIN & MUCOSAL LESIONS)
• Granular-linear deposits of immunoglobulins (IgG, lgM, IgA), complement (C3), and fibrinogen
along the basement membrane zone in a majority of patients.
81

71. ORAL
SUBMUCOUS
FIBROSIS
82

72. ORAL SUBMUCOUS
• (J.J Pindborg and Sirsat 1966)
– It is an insidious chronic disease affecting any part of the oral cavity
and sometimes the pharynx. Although occasionally preceded by and /or
associated with vesicle formation ,it is always associated with juxta-
epithelial inflammatory reaction followed by a fibro-elastic changes of the
lamina propria with epithelial atrophy leading to stiffness of the oral
mucosa and causing trismus and inability to eat.
83

73. PATHOGENESIS OF OSMF :
 Multifactorial
 Triggering factors include :-
a. chewing areca nut
b. nutritional deficiencies
c. genetic abnormalities
• Most important risk factor : the chewing of betel quid
84

74. Authors Year Nomenclature given
Schwartz 1952 Atrophia Idiopathica mucosae oris
Joshi 1953 Submucous fibrosis of palate and pillars
Lal 1953 Diffuse oral submucous fibrosis
Su 1954 Idiopathica scleroderma of mouth
De sa 1957 Submucous fibrosis of palate and cheek
George 1958 Submucous fibrosis of palate and mucous membrane
Pindborg and Sirsat 1964 Oral submucous fibrosis
Goleria 1970 Oral subepithelial fibrosis
85

75. EPIDEMIOLOGY
 OSMF is prevalent in South and South East Asia
owing to the habit of betel chewing
 Worldwide estimates  2.5 million people were
affected by the disease.
 Statistics for OSMF from the Indian continent 
 5 million people (0.5% of the population of India)
 Males affected more than females
 Malignant transformation rate  7- 13%
86

76. COLLAGEN PRODUCTION PATHWAY
• The three main events that are modulated by TGF-b, which favours the collagen
production are:
(1)Activation of procollagen genes;
(2)Elevation of procollagen proteinases levels:
(a) procollagen C-proteinase (PCP)/ bone morphogenetic protein1 (BMP1) and
(b) procollagen N-proteinase (PNP)
(3) Up-regulation of lysyl oxidase (LOX) activity
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77. • CLASSIFICATION:
I. CLINICAL STAGING
• Stage 1. (S1) – Stomatitis and/or blanching of oral mucosa.
• Stage 2. (S2) – Presence of palpable fibrous bands in buccal mucosa
and/or oropharynx, with/without stomatitis
• Stage 3. (S3) – Presence of palpable fibrous bands in buccal mucosa
and/or oropharynx, and in any other parts of oral cavity, with/without
stomatitis.
• Stage 4. (S4)
• A. Any one of the above stage along with other potentially malignant
disorders e.g. oral leukoplakia, oral erythroplakia, etc.
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78. II. FUNCTIONAL STAGING
• M1 : Inter-incisal mouth opening up to or >35 mm.
• M2 : Inter-incisal mouth opening between 25 mm and 35
mm.
• M3 : Inter-incisal mouth opening between 15 mm and 25
mm.
• M4 : Inter-incisal mouth opening <15 mm.
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79. • Prodromal symptoms(early OSF):
– Burning sensation of mouth
– Appearance of blisters on palate,
ulceration and recurrent
generalized inflammation,
excessive salivation.
– Periods of exacerbation- small
vesicles in cheek and palate.
– Focal vascular dilatations-
petechiae
– Pain in areas where submucotic
bands are developing when
ADVANCED OSF:
• Gingiva fibrotic, depigmented
with loss of stippling.
• Gradual stiffening of oral mucosa
tough and leathery consistency.
• buccal mucosa fibrous bands
which run in a vertical direction
involving the tissue around the
pterygomandibular raphae.
CLINICAL FEATURES
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80. HYPERPLATIC EPITHELIUM
CICI AND DILATED CAPILLARIES
LYPHOCYTES AND FIBROBLASTS
ATROPHIC EPITHELIUM
HYALINIZATION OF COLLAGEN
FIBROBLAST & BLOOD VESSELS REDUCED
HISTOPATHOLOGY
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81. SCURVY
94

82. SCURVY
• Deficiency of vitamin C is known as scurvy.
• Key function of ascorbic acid : Synthesis of collagen fibers from proline via hydroxyproline.
• DEFICIENCY: Alpha-chains of the tropocollagen molecules are unable to form stable helices
and the tropocollagen molecules.
• First affects connective tissues with a high turnover of collagen : periodontal ligament and
gingiva.
• Avitaminosis C : Failure of wound healing due to intrinsic intercellular weakness with lack of
connective tissue support of the capillary walls.
Vitamin C -known as ascorbic acid - water-soluble vitamin
“Ascorbic acid" comes from the New Latin "scorbutus"
meaning scurvy
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83. SCURVY
• Symptoms of scurvy generally develop after at
least 3 months of severe or total vitamin C
deficiency, these include:
– Weakness & fatigue
– Bruising easily & bleeding from weakening
blood vessel, connective tissue & bones due to
collagen loss.
– Hair, teeth loss & gingivitis
– Infants and children : Bone growth is impaired,
bleeding and anemia may occur.
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84. 97

85. REFERENCES
• Bailey’s Textbook of histology-7th Ed. Wilfred M. Copenhaver,Douglas E.
• Kelly, Richard L.Wood.
• Orbans Oral Histology and Embryology 13th Ed.-G.S.Kumar
• Essentials of Oral Histology and Embryology 3rd Ed –Avery
• Ten Cate’s Oral Histology Development, Structure and Function-7th Ed.
• Oral Histology Cell structure and Function Walter L. Davis.
• Advanced Dental Histology J.W. Osborn, A.R. Ten Cate.
• Oral cells and Tissues P.R. Garant.
• Harpers Illustrated Biochemistry; 26th Edition
• Ehlers-Danlos syndrome – 20 years experience with diagnosis and classification; JDDG; 2006 • 4:308–
318
• Ehlers-Danlos syndrome – a historical review; British Journal of Haematology, 141, 32–35
• Classification of Osteogenesis Imperfecta revisited; European Journal of Medical Genetics 53 (2010) 1-
5
• Scleroderma; N Engl J Med 360;19
• Head and Neck Manifestations of Epidermolysis Bullosa; Clinical Pediatrics; Feb 1992
• Textbook of Oral & Maxillofacial Pathology; Nevile,Damm,2nd edition
• Shafer’s Textbook Of Oral Pathology; 7th Edition
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86. THANK YOU
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