Pigmentation and Discoloration of Oral and Facial
Tissues
Pigmentation is a discoloration of the oral mucosa or gingiva due to the
wide variety of lesions and conditions. Oral pigmentation has been associated
with a variety of endogenous and exogenous etiologic factors. Also it can be
explained as Oral mucosal discolouration, which ranges from brown to
black may be due to superficial (extrinsic) or deep (intrinsic in or beneath
mucosa) causes.
Types of Oro-maxillofacial Pigmentation
Extrinsic discoloration
Extrinsic discoloration
is usually caused by extrinsic pigments. It is rarely of consequence and is
usually caused by colored foods, drinks or drugs. Extrinsic discoloration
usually affects both mucosae and teeth are discolored. Causes include the following:
• Foods and beverages, such as
beetroot, red wine, coffee and tea.
• Confectionery, such as
liquorice.
• Drugs, such as chlorhexidine,
iron salts, griseofulvin, crack cocaine, minocycline, bismuth subsalicylate, lansoprazole
and HRT.
• Tobacco: this may cause
extrinsic discolouration, but can also cause intrinsic pigmentary incontinence,
with pigment cells increasing and appearing in the lamina propria. This is
especially likely in persons who smoke with the lighted end of the cigarette
within the mouth (reverse smoking), as practiced mainly in some Asian communities.
Tobacco is a risk factor for cancer.
• Betel: this may cause a
brownish-red discolouration, mainly on the teeth and in the buccal mucosa, with
an irregular epithelial surface that has a tendency to desquamate. It is seen
mainly in women from South and Southeast Asia. Betel chewer’s mucosa epithelium
is often hyperplastic, and brownish amorphous material from the betel quid may
be seen on the epithelial surface and intra- and intercellularly, with
ballooning of epithelial cells. Betel chewer’s mucosa is not known to be
precancerous, but betel use predisposes to submucous fibrosis and to cancer.
Intrinsic staining
Causes for intrinsic
hyperpigmentation are Increased melanin or number of melanocytes, or other materials.
Intrinsic discolouration may have more significance than the extrinsic type. Normal
intrinsic pigmentation is due to melanin, produced by melanocytes dendritic
cells prominent in the basal epithelium.
Localized areas of
pigmentation are usually caused by benign conditions:
• Embedded amalgam (amalgam
tattoo)
• Embedded graphite (graphite
tattoo)
• Other foreign bodies
• Local irritation/inflammation
• Melanotic macule
• Naevi
• Melanoacanthoma.
However, neoplasms, such
as Kaposi sarcoma or malignant melanoma, are occasionally responsible. The
anterior pituitary gland releases melanocyte stimulating hormone (MSH), which
increases melanin production. Melanin pigmentation thus increases under
hormonal stimulation, either by MSH, or in pregnancy, or rarely due to the
action of adrenocorticotrophic hormone (ACTH), the molecule of which is similar
to MSH, or under the influence of other factors (e.g. smoking). Thus in all
patients systemic causes should be excluded, such as:
• Drugs; including smoking and
the contraceptive pill
• Hypoadrenalism; there is
increased ACTH production
• Peutz–Jeghers syndrome
• HIV infection
• Von Recklinghausen’s disease
• Albright syndrome
• Rarely, palatal pigmentation
from bronchogenic carcinoma.
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| Amalgam Tattoo |
 |
| Betel Stains |
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| Peutz Jeghers Syndrome |
List Causes of hyperpigmentation
Localized
• Amalgam,
graphite, carbon, dyes, inks or other tattoos
• Ephelis
(freckle)
• Epithelioid
angiomatosis
• Kaposi’s
sarcoma
• Malignant
melanoma
• Melanoacanthoma
• Melanotic
macule
• Naevus
• Pigmented
neuroectodermal tumour
• Verruciform
xanthoma
Multiple or
generalized
Genetic:
• Racial
• Carney syndrome
• Complex of myxomas, spotty pigmentation and endocrine
overactivity
• Laugier–Hunziker syndrome
• Lentiginosis profusa
• Leopard syndrome
• Peutz–Jeghers syndrome
Drugs:
• ACTH
• amiodarone
• antimalarials
• betel
• busulphan
• chlorpromazine
• clofazamine
• contraceptive pill
• ketoconazole
• menthol
• metals (bismuth, mercury, silver, gold, arsenic,
copper, chromium, cobalt, manganese)
• methyldopa
• minocycline
• phenothiazines
• smoking
• zidovudine
Endocrine:
• Addison’s disease
• Albright’s syndrome
• Nelson’s syndrome
• pregnancy
Post-inflammatory
Others:
• Gaucher’s disease
• generalized neurofibromatosis
• haemochromatosis
• HIV disease
• incontinentia pigmenti
• thalassaemia
• Whipple’s disease
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| List the Causes of Pigmentation |
Melanin
Melanin,
a nonhemoglobin derived brown pigment, is the most common of the endogenous pigments
and is produced by melanocytes present in the basal layer of the epithelium. Melancocytes
have a round nucleus with a double nucleus membrane and clear cytoplasm lacking
desmosomes or attachment plates. Melanin
accumulates in the cytoplasm, and the melanosome is transformed into a
structureless particle no longer capable of melanogenesis. The number of
melanocytes in the mucosa corresponds numerically to that of skin; however,in
the mucosa their activity is reduced. Various stimuli can result in an
increased production of melanin at the level of mucosa including trauma, hormones,
radiation, and medications.Thyrosinase activity is present in premelanosome and
melanosomes but absent in melanin granules.
Melanoid
Granules
of melanoid pigment are scattered in the stratum lucidum and stratum corneum of
the skin. Initially it was assumed melanoid was a degradation product of
melanin, but more recently it has been shown that such a relationship is highly
improbable. Melanoid imparts a clear yellow shade to the skin.3
Oxyhemoglobin and Reduced Hemoglobin
Oxyhemoglobin
and reduced hemoglobin are pigments resulting from hemosiderin deposits.
The
skin color is affected by the capillary and venom plexuses shining through the
skin.
Carotene
Carotene
is distributed in the lipids of the stratum corneum and stratum lucidum and
gives a deep yellow color to the skin. It is found in higher concentrations in
more women than in men. Pigmented lesions of the oral cavity are of multiple
origin. Different classifications are used at this time. Some researchers
divide the lesions into two main groups as either endogenous or exogenous
lesions. Brocheriou et al.
subdivides
pigmented lesions as follows:
• Non
tumoral pigmentations
• Non
melanin pigmented tumors or tumor like lesions
•
Benign melanin pigmented tumors
•
Malignant melanomas
In
several articles on oral pigmentation, Dummett and others implicate many
systemic and local factors as causes of changes in oral pigmentation.
Epidemiology
Oral
pigmentation occurs in all races of man.There were no significant differences
in oral pigmentation
between males and females. The intensity
and distribution of racial pigmentation of the oral mucosa is variable, not only between races, but also between different
individuals of the same
race and within different areas of the same mouth. Physiologic pigmentation is probably genetically determined, but as Dummett suggested , the degree of pigmentation is partially related to mechanical, chemical,
and physical
stimulation. In darker skinned people oral pigmentation increases, but there is no difference in the number of melanocytes
between fair-skinned
and dark-skinned individuals. The variation is related to differences in the activity of melanocytes.There is some controversy about the relationship between age and oral pigmentation. Steigmann and Amir et al. stated all kinds of oral pigmentation appear in young children. Prinz, on the other hand, claimed
physiologic pigmentation did not appear in children and was clinically visible
only after puberty.
Clinical Characteristics
The
gingivae are the most frequently pigmented intraoral tissues. Microscopically, melanoblasts are normally
present in the basal layers of the lamina propria.The most common location was
the attached gingiva (27.5%) followed in decreasing order by the papillary
gingiva, the marginal gingiva, and the alveolar mucosa.The total number of
melanophores in the attached gingival was approximately 16 times greater than in
the free gingival. The
prevalence of gingival pigmentation was higher on the labial part of the gingiva
than on the buccal and palatal/lingual parts of the arches.The shade of pigment
was
classified
as very dark brown to black, brown, light brown-yellow.3 Melanin pigmentation of the
oral
tissues usually does not present a medical problem, but patients complain of
black gums.
Classification and Differential Diagnosis
Oral
pigmentation has been associated with a variety of lesions and conditions. Differential
diagnosis of oral mucous membrane pigmentations are made according to the following
situations:
A. Localized Pigmentations: Amalgam tatoo, graphite or other tattoos, nevus,
melanotic macules, melanoacanthoma, malignant melanoma, Kaposi’s sarcoma,
epithelioid oligomatosis, verruciform xanthoma
B. Multiple or Generalized Pigmentations
1. Genetics: Idiopathic
melanin pigmentation (racial or physiologic pigmentation), Peutz-Jegher’s
syndrome, Laugier-Hunziker syndrome, complex of myxozomas, spotty pigmentation,
endocrine overactivity, Carney syndrome, Leopard syndrome, and lentiginosis profuse
2. Drugs: Smoking,
betel, anti-malarials, antimicrobials, minocycline, amiodarone, clorpromazine,
ACTH, zidovudine, ketoconazole, methyldopa, busulphan, menthol, contraceptive
pills, and heavy metals exposure (gold, bismuth, mercury, silver, lead, copper)
3. Endocrine: Addison’s
disease, Albright’s syndrome, Acanthosis nigricans, pregnancy, hyperthyroidism
4. Postinflammatory: Periodontal
disease, postsurgical gingival repigmentation
5. Others: Haemochromatosis,
generalized neurofibromatosis, incontinenti pigmenti, Whipple’s disease, Wilson’s
disease, Gaucher’s disease, HIV disease, thalassemia, pigmented gingival cyst,
and nutritional deficiencies
Systemic and Local Causes of Pigmentation
Many
systemic and local factors are caused by changes in oral pigmentation. Some of
the important factors are discussed below.
Amalgam Tattoo
The
pigmentation of the oral mucous membrane by tooth restoration material
(amalgam) is a
common
finding in dental practice. Amalgam
pigmentation is generally called amalgam tattoo.The lesion represents embedded
amalgam particles and usually manifests itself as an isolated bluish or black
macule in various areas of the mucosa. The color is usually described as black, blue, grey, or a
combination of these. Almost half were located on the gingiva and alveolar mucosa,
the mandibular region being affected more than the maxillary region. Almost half of the lesions were asymtomatic
and were discovered during routine dental examination. The amalgam granules and
fragments were found mainly in the lamina propria but were sometimes seen in
the submucosa.
Pigmented Nevi
Pigmented
nevi of the oral cavity are uncommon. The pigmented nevi are classified as intramucosal,
junctional, compound, or blue according to their histological features. Nevi are seen particularly on the
vermillion border of the lips and the gingivae. They are usually grey, brown,
or bluish macules and are typically asymptomatic. Melanocytes are pigment producing cells characterized by
the ability to syntesize via the enzyme dihydroxyphenylalanine (DOPA). A group
of melanocytes (generally four or more) are in contact with the basal layer of
the epithelium.
Oral Melanotic Macules
Oral
melanotic macules are relatively rare oral mucosal lesions, analogous to skin
freckles, due to the focal increase of melanin production.These melanotic
macules have been variously termed ephelis, melonosis, lentigo, solitary labial
lentigo, labial melanotic macule, and oral melanotic macule.The vermillion
border of the lower lip is most commonly involved.The buccal mucosa, palate,
and gingiva are less commonly affected. The color is usually described as grey,
brown, blue, black, or a combination of these.Histologically, ephelis shows
increased melanin pigmentation in the basal cell layer without an increase in
the number of melanocytes; otherwise, the epidermis is normal.
Melanoma
Melanoma
is a cancerous condition of the melanocyte. Special corpusles in this cell, known
as melanosomes, contain the necessary enzyme (tyrosine) to transform amino
acids into melanin. Melanocytes
are found among the basal cells of the epidermis. Histopathogically, the
mucosal epithelium is abnormal with large atypical melanocytes and excessive
melanin. Malignant
melanoma of the oral mucosa affects both sexes equally usually after 40 years
of age. The great majority of the lesions (about 70-80%) occur on the palate,
upper gingival, and alveolar mucosa.Initially there usually is a solitary small
asymtomatic brown or black macule.
Physiologic Pigmentation
Physiologic
pigmentation of the oral mucosa is clinically manifested as multifocal or
diffuse melanin pigmentation with variable prevalence in different ethnic
groups.2 Melanin is
normally found in the skin of all people. In dark skinned persons the gingiva
may contain melanin pigment to a greater extent than the adjacent alveolar
mucosa. The melanin pigment is synthesized in specialized cells, the melanocytes,
located in the basal layer of the epithelium. The melanin is produced as
granules. The melanosomes are stored within the cytoplasm of the melanocytes,
as well as in the cytoplasm of adjacent keratinocytes. Melanocytes are
embryologically derived from neural crest cells that eventually migrate into
the epithelium. If pigmented gingiva is surgically resected, it will often heal
with little or no pigmentation; therefore, surgical procedures should be
designed so as to preserve the pigmented tissues.
Peutz-Jeghers Syndrome
Peutz-Jeghers
syndrome (intestinal polyposis) is a genetic disorder characterized by mucocutaneous
pigmentation and hamartomas of the intestine.It manifests itself as frecklelike
macules about the hands, perioral skin, and intraorally to include the gingiva,
buccal, and labial mucosa. Pigmented
spots are 1 to l0 mm in diameter. Pigmented spots are particularly found on the
lower lip and buccal mucosa but rarely on the upper lip, tongue, palate, and
gingiva.
Smoker’s Melanosis
Smoker’s
melanosis is a benign focal pigmentation of the oral mucosa. It tends to increase significantly with
tobacco consumption. Tobacco
smokers have significantly more oral surfaces pigmented than non-tobacco users.Clinically,
the lesion usually presents as multiple brown pigmented macules less than 1 cm
in diameter, localized mainly at the attached labial anterior gingival and the
interdental papillae of the mandible. Smoker’s melonosis is more common in
females usually after the third decade of life.
Antimalaria Drug Use
Several
antimalarial drugs are known to be capable of inducing intraoral melanin pigmentation.
These drugs include: quinacrine, chloroquine, and hydroxychloroquine Longterm use
may cause pigmentation of the oral mucosa. The pigmentation of the oral mucosa is
described as slate-grey in color, bearing some resemblance to pigmentation
caused by silver arsplenamine.
Minocycline Use
Minocycline
is a synthetic tetracycline that is commonly used in the treatment of acne vulgaris.Although
tetracycline causes pigmentation of bones and teeth, minocycline alone is also
responsible for soft tissue pigmentation.It is usually seen as brown melanin
deposits on the hard palate, gingiva, mucous membranes, and the tongue.
Heavy Metals
Heavy
metals absorbed systemically from therapeutic use or occupational environments may
discolor the gingiva and other areas of the oral mucosa. Bismuth, arsenic, and mercury produce a
black line in the gingiva which follows the contour of the margin. Lead results
in a bluish red or deep blue linear pigmentation of the gingival margin
(Burtonian line). Exposure to silver causes a violet marginal line, often accompanied
by a diffuse bluish-grey discoloration throughout the oral mucosa.
Addison’s Disease
Addison’s
disease or primary adrenocortical hypofunction is due to adrenocortical damage
and
hypofunction.Bronzing of the skin and increased pigmentation of the lips,
gingivae, buccal mucosa, and tongue may be seen. Oral pigmentation may be the
first sign of the disease.A biopsy of the oral lesions shows acanthosis with silver-positive
granules in the cells of the stratum germinativum. Melanin is seen in the basal
layer.
Periodontal Diseases
Periodontal
diseases often produce discolorations of the oral mucosa. The pigmentation is worsened by gingivitis,
which increases vascular permeability and allows the heavy metals access to the
soft tissues.51 Melanin
re-pigmentation is related to after surgical inury.
Hemachromatosis
Hemachromatosis
(bronze diabetes) is a chronic disease characterized by the deposition of excess
iron (ferritin and hemosiderin) in the body tissues, resulting in fibrosis and
functional insufficiency of the involved organs. Hyperpig mentation may appear both in skin and mucous membranes
(oral and conjunctiva). Gingival
or mucosal pigmentation is reported to occur in 15 to 25% of patients with
hemachromatosis. The oral mucosa
shows diffuse homogeneous pigmentation of gray-brown or deep brown in about 20%
of the cases. The buccal
mucosa and the attached gingiva are the most frequently involved sites.
HIV Infection
In
patients infected with human immunodeficiency virus (HIV), progessive
hyperpigmentation of the skin, oral mucosa, fingernails, and toenails have been
reported being related to primary adrenocortical deficiency and to zidovudine (azidothymidine)
therapy in some cases.Clinically, oral pigmentation appears as irregular macules
with brown or dark brown color. The tongue, buccal mucosa, and palate are the
most commonly affected sites.
