non-melanotic oral lesions

1. The word pigment is a latin word ( colour or
colouring) , depending on degree of keratinization,
numbers and melanogenic activity of melanocytes,
vascularization and type of submucosal tissue
(muscle, bone, cartilage).
CLASSIFICATION:
1- EATIOLOGIC CLASSIFICATION
2-CLINICAL CLASSIFICATION

2. PIGMENTED LESIONS
Diffuse & bilateral Focal
Early onset Adult onset
Non
Blanching
No
systemic
Systemic Blanching
Red-blue-purple Blue-grey Brown
-
•Addisons
disease
•Heavy
metal
•Kaposi’s
sarcoma
• Drug
induced
• Post infl
ammatory
• Smokers
melanosis
•Melanotic
macule
•Pigmented
nevus
•Melanoma
•Melano
acanthoma
•Thrombus
•Hematoma
•Amalgam
Tattoo
•Foreign
Body tattoo
•Blue nevus
•Varix
•Hemagioma

3. 2-CLINICAL CLASSIFICATION
COLOR
SOLITARY MULTIFOCAL
BLUE/ PURPLE FOCAL
VARIX,
HEMANGIOMA
DIFFUSED
HEMANGIOMA
KAPOSI’S SARCOMA
HEMANGIOMA
HEREDITARY
HAEMORRAGIC
TELANGIECTASIA
BROWN MELANOTIC MACULE,
NEAVUS, MELANOMA
ECCHYMOSIS,DRUGS,
MELANOMA AND HAIRY
TONGUE
DRUG INDUCE
PETECHIAE
ALBRIGHT SYNDROME
ADDISON`S DISEASE
PHYSIOLOGIC
LICHEN PLANUS
PEUTZ JEGHER`S
GREY/ BLACK AMALGAM ,GRAPHITE
NEAVUS, MELANOMA
AMALGAM
HAIRY TONGUE
HEAVY METAL
INGESION

4. 1- According to the source
1. ENDOGENOUS PIGMENTATION
2. EXOGENOUS PIGMENTATION
3. DRUG RELATED PIGMENTED LESIONS
4. ASSOCIATED SYNDROMES
5. MISCELLANEOUS
- HIV INFECTIONS
- NEVI OF OTA

5. A - ENDOGENOUS PIGMENTATION
PIGMENT COLOR DISEASE PROCESS
MELANIN BROWN/,
BLACK/GREY
MELANIN MACULE, NEVUS,
MACULE
HEMOSIDERIN BROWN ECCHYMOSIS,PETECHIAE,
VARIX, HEMOCHROMATOSIS
HAEMOGLOBIN RED/BLUE/ PURPLE VARIX, HEMANGIOMA,
KAPOSI’S SARCOMA,
HEREDITARy
HAEMORRAGIC
TELANGIECTASIA
CAROTENE YELLOW CAROTENEMIA & JAUNDICE
LIPOFUSCHIN YELLOW

6. B- EXOGENOUS PIGMENTATION
SOURCE COLOR DISEASE PROCESS
SILVER AMALGAM GREY/ BLACK TATTOO, IATROGENIC
TRAUMA
GRAPHITE GREY/ BLACK TATTOO, IATROGENIC
TRAUMA
LEAD, BISMUTH,
MERCURY
GREY INGESTION OF PAINTS,
DRUGS
CHROMOGENIC BLACK/
BROWN/GREEN
SUPERFICIAL
COLONIZATION
BACTERIA

7. C - DRUG RELATED PIGMENTED LESIONS
• QUININE & OTHER ANTIMALARIAL DRUGS
• MINOCYLINE:is a tetracycline antibiotic that fights bacteria in the
body.Minocycline is used to treat many different bacterial infections, such as
urinary tract infections, respiratory infections, skin infections, severe acne,
gonorrhea and tick fever
• ORAL CONTRACEPTIVES
D- ASSOCIATED SYNDROMES
PEUTZ JEGHER’S SYNDROME
ADDISON’S DISEASE
ALBRIGHT SYNDROME
NEUROFIBROMATOSIS
E - MISCELLANEOUS LESIONS
HIV INFECTION
HAIRY TONGUE
NEVI OF OTA

8. Softtissue hardtissue(teeth)
 Tetracyclineinduced pigmentation.
 Dental fluorosis.
 Congenital hyperbilirubinemia
 Congenital erythropioeticporphyra
 Pulpal hemorrhagicproducts
 Aging
 Structural enamel defects(e.g.enamel
hypoplasia)
ACCORDING TO THE AFFECTED TISSUE

10. Non Melanotic Oral pigments
1-Vascular Lesions

11. 1-Hemangioma and Vascular Malformation:Both
lesions are developmental abnormalities,
characterized by onset during infancy.
Hemangioma is a benign proliferation of the endothelial cells that line
vascular channels. Vascular malformation is a structural anomaly of
blood vessels without endothelial proliferation.
**Diascopy usually shows blanching on pressure. This procedure is
performed by pressing gently on the lesion with a glass slide or a glass
test tube. A positive diascopy result (blanching) generally indicates that
the blood is within vascular spaces and is displaced out of the lesion by
pressure.

12. According to Enzinger and Weiss, haemangiomas are broadly classified into
capillary, cavernous, and miscellaneous forms like verrucous, venous,
arteriovenous haemangiomas.
Capillary haemangiomas further include juvenile, pyogenic granuloma, and
epitheliod haemangioma .
The term haemangioma has been commonly misused to describe a large number of
vaso-formative tumours .However, the International Society for the Study of
Vascular Anomalies (ISSVA) has recently provided guidelines to differentiate these
two conditions.
Vaso-formative tumours are broadly classified into two groups: haemangioma and
vascular malformation .Haemangioma is histologically further classified into
capillary and cavernous forms .
DD
Mucocele & Ranula: soft & fluctuant
Aneurysm: pulse is detected

13. Pathogenesis and origin of haemangioma remain incompletely understood. However,
various theories have been proposed to elucidate the mechanism and pathogenesis of
haemangioma.
Aberrant and focal proliferation of endothelial cells results in haemangioma, although the
cause behind this remains unclear .The placental theory of haemangioma origin has been
described by North et al, who studied various histology and molecular markers such as
GLUTI, Lewis Y Antigen.
Positive staining for GLUTI is considered highly specific and diagnostic for haemangioma,
and it is useful for making differential diagnosis between haemangioma and other vascular
lesions clinically related to it .More recently, somatic mutational events in gene involved in
angiogenesis are related to haemangioma growth .
Growth factors specifically involved in angiogenesis such as VEGF, and b-TGF, are often
increased during the proliferation phases of haemangioma growth .
Moreover, it has been noted that during the involution phase of haemangioma, there is a
decrease in angiogenic molecules (VEGF, PCNA, Type IV collagenase, Lewis V antigen, CD 31),
while there is increase in concentration of marker for apoptosis (T4, TUNNEL, INF, Mast cells,
and TGF) . Thus, role of molecular signalling is now clear in haemangioma development.

14. HAEMANGIOMA
Infantile hemangioma
The most common tumors of infancy
80 % of hemangiomas are found as single
lesions and 20 % multiple tumors
Immunohistochemistry:
CD31, CD34 & GLUT-1: for endothelial cells
VEGFR1 expression was markedly decreased
and VEGFR2 expression was increased due to
missense mutation

16. Skull radiograph: vessel wall calcification yield bilamellar
radiopaque tracks
“Tram line calcification”
Bubbly or honeycomb trabeculated appearance
Overlying cortex is expanded and thinned, but complete cortical
disruption and invasion into soft tissue are not present

17. Hemangioma Vascular malformation
Description Abnormal endothelial
cell proliferation
Abnormal blood vessel
development
Elements Includes no. of capillaries Mix of artery, vein,
capillaries (AV shunt)
Growth Rapid congenital, ceases
puberty
Grows throughout
Boundaries Circumscribed; rarely
affects bone
Poorly circumscribed
Resection Easy Difficult, surgical
haemorrhage
Recurrence Uncommon Common

18. Sturge Weber syndrome
•is a neurological disorder marked by a
distinctive port-wine stain on the forehead,
scalp, or around the eye. This stain is a
birthmark caused by an overabundance of
capillaries near the surface of the skin.
Blood vessels on the same side of the brain
may also be affected
•Pathogenesis :
1.Mutation of gene GNAQ gene on 9q21.
This embryonic mutation might cause
failure of cephalic venous plexus to regress
and become mature probably during the
1st trimester of the pregnancy.

20. Encephalotrigeminal angiomatosis
Port wine stain (nevus flammeus) –leptomeninges of cerebral
cortex .Mental retardation, hemiparesis, seizures
Ocular lesions
Calcification
DD - angio-osteo-hypertrophy syndrome
Port wine stain + varices + hypertrophy of bone

21. Blue rubber bleb nevus syndrome
Bean’s syndrome
is a rare condition that is characterized
by numerous malformations of the
venous system that significantly
involve the skin and visceral organs. is
an important condition due to the
potential for significant bleeding which
can be fatal.Life threatening-blood
loss-> anemia & Fe deficiency

22. HEREDITARY HEMORRHAGIC TELANGIECTASIA
Rendu-Osler-Weber syndrome
• The uncommon Osler-Weber-Rendu syndrome
(hereditary haemorrhagic teleangiectasia; HHT) is
inherited via an autosomal dominant trait, however,
family history can be negative.
• Clinically, oral and peri-oral telangiectasias are observed,
as well as telangiectasias in the nose, the gastro-intestinal
tract and on the palms of the hands. They may bleed
which may cause chronic iron-deficiency anaemia.
• Same lesion in nasal mucosa-epistaxis
differential diagnosis-petechial hemorrhages
(platelet disorder)-CREST syndrome

23. OSLER WEBER RENDU SYNDROME

24. Varix and Thrombus
Varices are abnormally dilated veins, seen mostly in patients older than
60 years of age. The most common intraoral location is the ventral
surface of the tongue“caviar tongue”, where varices appear as multiple
bluish purple, irregular, soft elevations that blanch on pressure . Painless
and not subject to rupture and haemorrhage
If the varix contains a thrombus, it presents as a firm bluish purple
nodule that does not blanch on pressure .. Thrombi are more common on
the lower lip and buccal mucosa.
Varix resembles hemangioma both clinically and histologically but
differs only in age of onset and etiology
DD
Hemangioma , Aneurysm , Mucocele
Ranula and Superficial nonkeratotic cyst

26. ANGIOSARCOMA
is a cancer of the inner lining of blood vessels, and it can occur in
any area of the body. The disease most commonly occurs in the
skin, breast, liver, spleen, and deep tissue.
Oral cavity extremely rare
If superficial - red / blue / purple
If deep – nodular tumour
Can arise from blood or lymph vessels
Prognosis is poor
Treated by radical excision

28. Immunohistochemical stains on angiosarcomas: strong diffuse Factor VIIIrag in
19/21 cases (A) and CD31 in 16/19 cases (B), yet more focal and not as reliable
CD34 in 7/12 cases

29. Kaposi’s Sarcoma
**Kaposi’s sarcoma (KS) is a multifocal vascular malignancy seen
predominantly in HIV-infected individuals.The development of this tumour is
considered diagnostic of AIDS progression.
**A human herpesvirus (HHV-8, also called Kaposi’s sarcoma-associated
herpesvirus) has been implicated as the cause. KS in the oral mucosa most
commonly affects the hard palate, gingiva and tongue.
**Early lesions appear as flat or slightly elevated brown to purple lesions that
are often bilateral.
**Advanced lesions appear as dark red to purple plaques or nodules that may
exhibit ulceration, bleeding and necrosis.
**Definitive diagnosis requires biopsy, which shows a proliferation of
spindle-shaped cells surrounding poorly formed vascular spaces or slits with
numerous extravasated red blood cells.

30. Oral lesions –
posterior hard palate
Begin as flat red macules of variable size
and irregular configuration
Numerous isolated and coalescing
plaques . Eventually- increase in size ->
nodular growths- entire palate,
protruding below the plane of occlusion
Facial gingiva
DD
Pyogenic granuloma, giant cell
granuloma, Bacillary angiomatosis .
Ecchymosis and salivary gland tumors.

31. Bacillary angiomatosis
Epithelioid angiomatosis
BARTONELLA INFECTION

34. Non Melanotic Oral pigments
RBCs defect
(extravasation or destruction )

36. Lesions caused by endogenous pigments (blood-related
pigmentations)
**Extravasations of blood in hematomas, petechiae, purpurae and
ecchymoses may cause pigmentation as a result of accumulation and
degradation of haemoglobin to bilirubin and biliverdin
**Color of the lesions depend on length of time from trauma and
may range from red to black.
**Typical traumatic events in the oral cavity possible associated with
blood extravasations and hyperpigmentation include biting, traumas
with eating and iatrogenic procedures.

37. ECCHYMOSIS
Traumatic ecchymosis – most commonly on the lips and face
Immediately after the trauma, erythrocytes extravasates into the
submucosa.
Clinically appear bright red macule or swelling if a hematoma
forms.
The lesion then assume a brown discoloration within few days
after haemoglobin is degraded to hemosiderin
TREATMENT :
Observation for 2 weeks

38. PETECHIAE
Capillary hemorrhages will appear red initially, turning brown in
few days once the extravasated red cells have lysed and degraded
to hemosiderin
DDx for petechiae and ecchymosis
Solitary- H/O trauma, change color from bluish-brown to green to
yellow and then finally diassapear within 4-5 days.
Do not blanch on pressure (as compared to telangiectasias)
Multiple:
Trauma from fellatio
Trauma from severe coughing
Trauma from severe vomiting
Prodromal sign of infectious mononucleosis
Prodromal sign of hemostatic disease

41. HAEMOCHROMATOSIS
Hereditary hemochromatosis is a disorder that causes the body to
absorb too much iron from the diet. The excess iron is stored in the
body's tissues and organs, particularly the skin, heart, liver, pancreas,
and joints.
Because humans cannot increase the excretion of iron, excess iron can
overload and eventually damage tissues and organs. For this reason,
hereditary hemochromatosis is also called an iron overload disorder.
Early symptoms of hereditary hemochromatosis are nonspecific and
may include fatigue, joint pain, and abdominal pain, Later signs and
symptoms can include arthritis, liver disease, diabetes, heart
abnormalities, and skin discoloration.
The appearance and progression of symptoms can be affected by
environmental and lifestyle factors such as the amount of iron in the
diet, alcohol use, and infections.

42. Pathogenesis
Mutations in several genes, including HAMP, HFE1, HFE2, SLC40A1,
and TFR2, can cause hereditary hemochromatosis.
The proteins produced from these genes play important roles in
regulating the absorption, transport, and storage of iron. Mutations
in any of these genes impair the control of iron absorption during
digestion and alter the distribution of iron to other parts of the
body. As a result, iron accumulates in tissues and organs, which can
disrupt their normal functions.

43. Oral mucosal lesions - Brown to Grey, diffuse macules
Usually seen on palate and gingiva .
The primary oral manifestation of hereditary
hemochromatosis, or any state of iron overload, is blue-
gray to brown hyperpigmentation that most commonly
affects the palate, buccal mucosa, and gingivae
Also called as BRONZE DIABETES

44. Bronze diabetes
Hemochromatosis is sometimes referred to as bronze diabetes because
it can lead to darkening of the skin and hyperglycemia.
**Patients with haemochromatosis (“bronze diabetes”) frequently
display bluish grey pigmentation of the hard palate, gingival and
buccal mucosa .
** The pigmentation is caused by deposition of iron containing
pigments (ferritin and hemosiderin) within the skin and mucous
membranes .
**Similarly, a diffuse black-brown pigmentation, most commonly
in the junction between the hard and soft palate, may be observed
in patients with beta-thalassemia

46. complications

47. Diagnosis
1-Prussion blue
• For hemosiderin granules accumulation in
hepatocytes and kupffer cells in liver

48. skin

49. 2-Serum ferritin 3-Transferrin saturation
 The ferritin blood test
measures the level of
ferritin in the blood.
 Normal level:
Males :12-300 ng/ml
if > 300 ng/ml
Females: 12-150
ng/ml if > 200 ng/ml
it means
hemochromatosis
 Is the ratio of serum iron
to total iron-binding
capacity
 Normal level:
Adult : 20-50%
Child: >16%
 It’s more sensitive than
serum ferrin
•Iron: 60-170 micrograms per
deciliter (mcg/dL)
•TIBC: 240-450 mcg/dL

50. Disorders of Heme metabolism
Heme biosynthesis
Porphyrias
Heme degradation
Jaundice

51. Porphyria
• Definition:
• A group of rare disorders caused by deficiencies of
enzymes of the heme biosynthetic pathway
• Affected individuals have an accumulation of heme
precursors (porphyrins), which are toxic at high
concentrations
• Attacks of the disease are triggered by certain drugs,
chemicals, and foods, and also by exposure to sun

52. • Group of inherited or
acquired disorders of
heme production
• 8 enzymes in heme
biosynthetic pathway
• First and the last 2 are
mitochondrial, while the
other five are in the
cytosol

53. Classification of the Porphyrias
• Multiple ways to categorize porphyrias:
– Hepatic vs. Erythropoietic: Organ in which accumulation of porphyrins and
their precursors appears
– Cutaneous vs. Non- cutaneous
– Acute and non-acute forms
• Acute:
– Aminolevulinate dehydratase deficiency porphyria (ALA-D)
– Acute intermittent porphyria (AIP)
– Hereditary coproporphyria (HCP)
– Variegate porphyria (VP)
• Chronic:
– Porphyria cutanea tarda (PCT)
– Erythropoietic protoporphyria (EPP)
– Congenital erythropoietic porphyria (CEP)
– Hepatoerythropoietic porphyria (HEP)

54. Congenital Erythropoietic porphyria
( Gunther's disease ):
It is a very rare autosomal recessive disorder.
Patients usually present during infancy and rarely present in adult life
with milder forms.
Pathogenesis
It is caused by elevation of both water-soluble and lipid-soluble porphyrin
levels due to deficiency of uroporphyrinogen III synthase enzyme.
Clinical features 1. Very severe photosensitivity with phototoxic burning
and blistering leading to mutilation of light exposed
parts.
2. Erythrodontia.
3. Hypersplenism.
4. Hemolytic anemia.
5. Thrombocytopenia
Uroporphyrin and Coproporphyrin in urine
Corproporphyrin in stool
Lab. finding

55. Oral manifestations:
• Are exclusively present in the
congenital erythropoietic porphyria (CEP)
(gunther’s syndrome)
• Affected teeth are pinkish brown, when
viewed with UV light fluorescence they
are bright scarlet.

59. Jaundice

60. Definition:
• A yellowish pigmentation of the
skin, sclera and other mucous
membranes caused by high blood
bilirubin levels. Jaundice is a sign
of an underlying disease process.

61. BLOOD
CELLS
LIVER
Bilirubin diglucuronide
(water-soluble)
2 UDP-glucuronic acid
via bile duct to intestines
Stercobilin
excreted in feces
Urobilinogen
formed by bacteria KIDNEY
Urobilin
excreted in urine
CO
Biliverdin IX
Heme oxygenase
O2
Bilirubin
(water-insoluble)
NADP+
NADPH
Biliverdin
reductase
Heme
Globin
Hemoglobin
reabsorbed
into blood
Bilirubin
(water-insoluble)
via blood
to the liver
INTESTINE
Figure 2. Catabolism of hemoglobin

62. Bilirubin is a by-product of the daily natural breakdown
and destruction of red blood cells in the body. The
hemoglobin molecule that is released into the blood by
this process is split, with the heme portion undergoing a
chemical conversion to bilirubin.
Normally, the liver metabolizes and excretes the
bilirubin in the form of bile. However, if there is a
disruption in this normal metabolism and/or production
of bilirubin, jaundice may result.
What Causes Jaundice? Jaundice may be caused by
several different disease processes that disrupt the
normal bilirubin metabolism and/or excretion.

63. I- Pre-hepatic (before bile is made in the liver)
Jaundice in these cases is caused by rapid increase in the
breakdown and destruction of the red blood cells (hemolysis),
overwhelming the liver's ability to adequately remove the
increased levels of bilirubin from the blood.
Examples of conditions with increased breakdown of red blood
cells include:
malaria,
sickle cell crisis,
spherocytosis,
thalassemia,
glucose-6-phosphate dehydrogenase deficiency (G6PD),
drugs or other toxins, and
autoimmune disorders.

64. II- Hepatic (the problem arises within the liver)
Jaundice in these cases is caused by the liver's inability to
properly metabolize and excrete bilirubin. Examples
include:
hepatitis (commonly viral or alcohol related),
cirrhosis,
drugs or other toxins,
Crigler-Najjar syndrome,
Gilbert's syndrome, and
cancer.

65. III-Post-hepatic (after bile has been made in the
liver)
Also termed obstructive jaundice, is caused by conditions
which interrupt the normal drainage of conjugated
bilirubin in the form of bile from the liver into the
intestines.
Causes of obstructive jaundice include:
gallstones in the bile ducts,
cancer (pancreatic and gallbladder/bile duct carcinoma),
strictures of the bile ducts,
cholangitis,
congenital malformations,
pancreatitis,
parasites,
pregnancy, and newborn jaundice.

67. Clinical picture:

68. Oral manifestation:

70. Non Melanotic Oral pigments
Lipo-pigment Lesions
lipochrome pigment is any of a group of fat-soluble
hydrocarbon pigments, such as carotene, xanthophyll,
lutein, chromophane, and the natural coloring material of
butter, egg yolk, and yellow corn.

72. Causes:
1. Increase intake
of carotene
rich food
2. Diseases
associated with
carotenemia
such as
hypothyroidism
& diabetes
mellitus.

74. clinically
• Its clinical
presentation is as a
yellowish
pigmentation in the
palate and,
occasionally, in
palms, soles and
naso-labial fold.

75. Diagnosis
• Lab investigation:
 It’s considered a
carotenemia if serum
carotene level is greater
than 250 mg/dL

76. DD
Differential diagnosis
Carotenemia Jaundice
 Serum level of carotene
elevated.
 Absence of yellowish
pigmentation of sclera.
 NO treatment needed only
decrease intake of
carotene rich food.
 Serum level of bilirubin
elevated
 Yellowish pigmentation of
sclera present.
 Treatment needed

80.  Fordyce granules are
ectopic sebaceous glands
are found at mucosa of lips
and inside the cheeks.
• By definition, they are not
associated with hair
follicles.
• The sebaceous duct directly
contacts the superjacent
mucosal epithelium.[

82. Fordyce
granules

83. pathogensis
 Most case either Fordyce`s granules sporadic / or these
Fordyce`s granules associated with cutaneous sebaceous
conditions Muri-Torre syndrome and Lynch syndromes
in both syndromes there is defect of DNA mismatch repair
of MMR genes leading to microsatellite instability
 (DNA mismatch repair is a system for recognizing and
repairing erroneous insertion, deletion, and mis-
incorporation of bases that can arise during DNA replication
and recombination, as well as repairing some forms of DNA
damage).).

84. When studies were done of case of Fordyce granules
lesions in normal patients (i.e. without any syndrome), it
was found that there was also DNA mismatch repair of
MMR gene.
In both Muri-Torre syndrome and Lynch syndrome
(hereditary non-polyposis colorectal cancer), due to
microsatellite instability this leads to carcinomas of GIT
mainly colon, these carcinomas mainly are low-grade
with good prognosis.

87. Amalgam pigmentation (amalgam tattoo)
The etiology of amalgam tattoos can be iatrogenic or traumatic.
Metal particles may over time leach in the soft oral tissues, resulting
in the discoloration. condensation of the material in abraded
mucosa during routine amalgam restorative work; introduction of
the material within the lacerated mucosa during removal of
amalgam fillings or crowns and bridges; introduction
of broken pieces into a socket or the periosteoum during extraction
of teeth; introduction of metal particles in a surgical wound during
root canal treatmentwith a retrograde amalgam filling
Radiographic features may show localized radiopacities 1. Biopsy is
indicated
only when suspicion of OMM .

90. Histopathologic investigation :
reveals amalgam particles dispersed in the connective
tissue and sometimes in the walls of vessels .These
particles may also line the basement membrane of the
surface epithelium. Brownish granules within phagocytic
cells and fibroblasts cytoplasm can also be observed .A
spreading of these pigmented lesions mediated by local
migration of
phagocytic cells containing metal has also been described
Instead, immunohistochemical markers such as HMB-45
and Melan A are more suitable for this purpose.
When dealing with metal pigmentation, one may be able
to identify the type of metal(s) by using electron-probe
micro-analysis.

92. Graphite
may be introduced into the oral mucosa through accidental injury
with a graphite pencil. The lesion occurs most frequently in the
anterior palate of young children, appearing as an irregular grey to
black macule.
A history of injury confirms the diagnosis; otherwise, a biopsy
should be performed to exclude the possibility of melanoma

93. Occupational hazards

94. Heavy Metal Pigmentation:
Increased levels of heavy metals (e.g., lead, bismuth, mercury, silver,
arsenic and gold) in the blood represent a known cause of oral
mucosal discolouration
The pigmentation appears as a blue–black line along the gingival
margin and seems to be proportional to the amount of gingival
inflammation. Other oral mucosal sites may also be involved.
Depending on the Depending on the type of metal implicated, a
number of systemic signs and symptoms may be associated with
chronic exposure.The importance of oral mucosal pigmentation
associated with heavy metals lies primarily in the recognition and
treatment of the underlying cause to avoid severe systemic toxic
effects.

95. In adults, the most common causes:
1.Occupational exposure to heavy metal
vapours.
2.Treatment with drugs containing heavy metals,
such as arsenicals for syphilis.
3.Children, possible sources of exposure include
lead-contaminated water or paint and mercury-
or silver-containing drugs.

96. Heavy Metal Pigmentation
Lead poisoning

97. Oral manifestation of lead poisoning
(“Burtonian line”).

99. Bismuth poisoning
• Increased levels of heavy metals (e.g., lead,
bismuth, mercury, silver, arsenic and gold) in
the blood represent a known cause of oral
mucosal discoloration.
Bismuth poisoning

100. Argyria
• Argyria: is a condition due to prolonged
contact with or ingestion of silver salts.
• Argyria is characterized by gray to gray-black
staining of the skin and mucous membranes
produced by silver deposition.

101. • Source of sliver salts:
• Localized argyria:
 prolonged use of topical medication of sliver
salts affects mainly eye, skin or oral cavity.
• Generalized argyria:
 Long term treatment with medication containing
sliver salts.
 Occupational exposure e.g. cutting or polishing
sliver …exposure to sliver dust.

102. Silver ingestion induced oral
lesions
Argyria

104. • Normal level of silver in human body 1mg
• Generalized argyria 4-40 g if reaches 50-500
mg/kg, it will be lethal to human

105. Drugs associated with oral mucosal
pigmentation
Antimalarials: quinacrine, chloroquine, hydroxychloroquine
Quinidine
Zidovudine (AZT)
Tetracycline
Minocycline
Chlorpromazine
Oral contraceptives
Clofazimine
Ketoconazole
Amiodarone
Busulfan
Doxorubicin
Bleomycin
Cyclophosphamide

106. The pathogenesis of drug-induced
pigmentation varies, depending on the
causative drug:
1. Accumulation of melanin.
2. Deposits of the drug or one of its
metabolites.
3. Synthesis of pigments under the influence
of the drug.
4. Deposition of iron after damage to the
dermal vessels.

107. Drug-Induced Pigmentation
**Chloroquine and other quinine derivatives are used in the treatment of
malaria, cardiac arrhythmia and a variety of immunologic diseases including
systemic and discoid lupus erythematosus and rheumatoid arthritis. Mucosal
discolouration associated with this group of drugs is described as blue–grey or
blue–black, and in most cases only the hard palate is involved.
**Laboratory studies have shown that these drugs may produce a direct
stimulatory effect on the melanocytes. However, the reason why this effect is
limited to the palatal mucosa is not understood .
**Minocycline is a synthetic tetracycline used in the long term treatment of
refractory acne vulgaris. It can cause pigmentation of the alveolar bone, which
can be seen through the thin overlying oral mucosa (especially the maxillary
anterior alveolar mucosa) as a grey discoloration.
Minocycline has also been reported to cause pigmentation of the tongue
mucosa.

109. Tetracycline induced
oral pigmentation:
It affects both soft and
hard tissues (teeth)
Oral soft tissues:causes
Grey discoloration of
alveolar mucosa and
tongue

110. Tetracycline Staining
Etiology
• Prolonged ingestion of tetracycline or its congeners during
tooth development
• Less commonly, tetracycline ingestion causes staining after
tooth formation is complete: reparative (secondary) dentin
cementum may be stained.
Severity of discoloration depends on:
 Age at the time of administration.
 Duration of administration.
 Dosage
 Type of staining according to type of tetracycline

111. Pathogenesis:
1.The 'extrinsic theory'
In which, authors supposed that tetracycline
attaches to the glycoproteins in acquired pellicles
which in turn etches the enamel, and
demineralization/remineralization cycles occur.
 It oxidizes on exposure to air or as a result of
bacterial activity and produce discoloration.

112. Pathogenesis:
• 2. The 'intrinsic theory' :
In which the tetracycline bound to plasma
proteins is deposited in collagen-rich tissues,
such as teeth. This complex oxidizes slowly over
time with exposure to light.

113. Pathogenesis:
• 3. Cohen and Parkin's found that tetracycline
incorporated into hydroxyapetite, when oxidized
by light produces the red quinone product.
• 4. Cale et al suggested that Minocycline(a
synthetic compound of tetracycline) causes
discoloration by formation of calcium-
minocycline complexes deposits in dentine.

114. Clinical Presentation:
• Yellowish to gray (oxidized tetracycline) color of enamel and dentin
• May be generalized or horizontally banded depending on duration
of tetracycline exposure
• Alveolar bone may also be stained bluish red (particularly with
minocyline use, 10% after 1 year and 20% after 4 years
of therapy).
Diagnosis:
• Clinical appearance and history
• Fluorescence of teeth may be noted with ultraviolet illumination.
Differential Diagnosis
• Dentinogenesis imperfecta
Treatment
• Restorative/cosmetic dental techniques

117. • Tetracycline ..flourescence under UV