Exogenous Pigmentation of Oral Mucosa

Oral Medicine Seminar
Suruthi.S

Contents
➢ What is Pigmented lesions?
➢ What is Exogenous Pigmentations ?
➢ Classification of Exogenous Pigmentations
➢ Amalgam Tattoo
➢ Graphite Tattoo
➢ Ornamental Tattoo/Cosmetic Tattoo
➢ Heavy Metal poisoning
➢ Mercury poisoning
➢ Lead
➢ Arsenic
➢ Bismuth
➢ Silver
➢ Drug Induced Pigmentations

A pigmented lesion can be defined as an area of altered
coloration of the oral mucosa either because of physiologic or
pathologic process because of deposition of endogenous or
exogenous pigments or embedded foreign material in the
tissues.
The various pigmentations can be in the form of blue/purple
vascular lesions, brown melanotic lesions, brown heme-
associated lesions, gray/black pigmentations.
What is Pigmented Lesion??
Reference :Greenberg, Glick, Ship. Burket’s Oral Medicine.11th ed, BC Decker Inc, 2008
http://www.oraljournal.com/pdf/2019/vol5issue2/PartG/5-2-71-962.pdf

What is Exogenous Pigmentations?
Def :A pigment produced outside the human body.
Exogenous substances cause oral mucosal pigmentation
because these substances are embedded in the oral tissues
either by direct trauma or iatrogenic implantation.
Exogenous pigmentation could be induced by drugs,
tobacco/smoking, amalgam tattoo or heavy metals induced.
Reference :exogenous pigment. (n.d.) Medical Dictionary. (2009). Retrieved July 1 2020 from https://medical-
dictionary.thefreedictionary.com/exogenous+pigment
Greenberg M, Glick M. Burkets oral medicine diagnosis and treatment. 10th ed. Hamilton, Ontario: B. C. Decker;
2003. pp. 126–36

Classifications
Classification Proposed By Faizan Alawi
Exogenous Pigmentation
1. Amalgam Tattoos
2. Graphite Tattoos
3. Ornamental Tattoos
4. Medicinal Metal-induced Pigmentation
5. Drug-induced Pigmentation
6. Hairy Tongue

According To Thibodeau Ea et al
Classifications
Reference :Thibodeau. Durgesh N Bailoor, Nagesh KS. Fundamentals of Oral Medicine and Radiology.1st ed. Jitender P Vij, 2005
a) Mercury
b) Bismuth
c) Lead
d) Silver
e) Mercury
f) Gold
g) Arsenic
a) Amalgam Tattoo
b) Graphite
Exogenous Pigmentation
Systemically
Introduced metallic
substances
Locally
introduced pigments
Miscellaneous
Conditions
a) Black Hairy Tongue
b) Carotenaemia
c) Stains from tobacco
etc.

According To Sr Prabhu et al. :
Classification of Pigmented Lesions of the Oral Mucosa based on the
source or origin of Pigment:
Lesions produced by exogeneous pigmentation:
1. Amalgam Tattoo (Focal Agyrosis)
2. Heavy-metal pigmentation.
3. Tattoos-cultural and social.
Classifications
Reference :. Prabhu SR. Textbook Of Oral Medicine.1st ed.Oxford University Press, 2004

Classifications

Amalgam Tattoo
Etiology and Pathogenesis
• The most common pigmented lesion in the oral mucosa is
amalgam tattoo.
• These are iatrogenic in origin and typically a consequence of the
inadvertent deposition of amalgam restorative material into the
submucosal tissue.
Amalgam tattoo is a grey, blue or black area of discoloration on
the mucous membranes of the mouth, typically on the gums of the
lower and upper jaws. Also called as focal argyrosis
Clinical Features
• Epidemiology :Amalgam tattoos may be found in up to 1%-3% of
the general population.
• About the lesion :The lesions are typically small,
asymptomatic, macular, and bluish gray or even black in
appearance.
2)Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 2nd Ed. Saunders, Philadelphia, p: 390-2, 2002.

• Site : They may be found on any mucosal surface. However, the
gingiva, alveolar mucosa, buccal mucosa, and floor of the mouth
represent the most common sites.
• The lesions are often found in the vicinity of teeth with large
amalgam restorations or crowned teeth that probably had amalgams,
around the apical region of endodontically treated teeth with
retrograde restorations or obturated with silver points, and in areas
in and around healed extraction sites
• Amalgam tattoo of the head and neck skin may occur in dentists and
represents an occupational hazard resulting from failure to use facial
protective barriers
• Oral manifestations : include increased salivation (ptyalism) as
mercury is excreted in saliva. Tongue may be enlarged and painful
(glossodynia). There may be hyperemia and swelling of gingiva,
ulcerative stomatitis, loosening and exfoliation of teeth.
Reference :. Meleti M, Vescovi P, Mooi WJ, Van der Waal L. Pigmented lesions of the oral mucosa and perioral tissues:
a flow-chart for the diagnosis and some recommendations for the management. Oral Surg Oral Med Pathol Oral
Radiol Endod 2008;105:606–616..

Histopathology
• Microscopically: amalgam tattoos show a fine brown granular stippling of
collagen fibers, with a particular affinity for vessel walls and nerve fibers
with little or no inflammation.
• large aggregates of black material may be seen and could result in a foreign
body–type giant cell granulomatous inflammation.
• a mild to moderate lymphocytic inflammatory infiltrate is more commonly
seen
Management
• Investigation : dental radiographs.
• the focal argyrosis may compromise esthetics;
• Treatment : surgical removal A report on a two-stage surgical approach
(subepithelial connective tissue graft followed by laser surgery) to eliminate
an amalgam tattoo has yielded excellent results. However, since amalgam
tattoos are innocuous, their removal is not always necessary, particularly in
the absence of radiographic evidence of amalgam.
• if the lesion is not in proximity to a restored tooth, or if the lesion suddenly
appears, a biopsy is warranted.
Differential diagnosis includes melanotic macule, nevus, and melanoma.

Graphite Tattoo
Graphite tattoos are an unusual source of focal
exogenous pigmentation.
• Site :They are most commonly seen on the palate and
gingiva
• Etiology : traumatic implantation of graphite
particles from a pencil
• Clinical Features :The lesions may be indistinguishable
from amalgam tattoos, often presenting as a solitary
gray or black macule.
• Since the traumatic event
• often occurs in childhood, many patients may not
report a history of injury.
• Thus, a biopsy is often warranted.
• Microscopically,:graphite particles resemble those of
amalgam
• Treatment: an excisional incision. The incineration
method was used as a differential diagnosis for the
histopathologic examination.
• Differential Diagnosis: Amalgam tattoo, melanoma
Reference :Rihani F B, Da'ameh D M. Intraoral graphite tattoo. Arch Dis Child 2006; 91:563.
http://www.jordi.com.br/detalhe_artigo.asp?id=75

Reference :http://www.jordi.com.br/detalhe_artigo.asp?id=75

Ornamental Tattoo/Cosmetic Tattoo
• Tattooing for ornamental purposes is an ancient practice that remains
popular in modern times
• Dye injected into dermis is phagocytosized by macrophages, which are
permanent .Image does fade over time
• In certain tribal cultures, ornamental mucocutaneous tattooing is
considered a rite of passage and esthetically pleasing.
• Complications include infections introduced at time of tattooing; cutaneous
diseases that localize in tattoos, often in a koebner-type phenomenon;
allergic reactions to tattoo pigments and photosensitivity reactions
• Clinical features
• Lymph nodes:May cause lymphadenopathy, usually resolves
spontaneously
• Pigment initially within keratinocytes, fibroblasts, macrophages and mast
cells; later only within dermal fibroblasts surrounded by connective tissue;
eventually tattoo ink appears in regional lymph nodes
• Melanoma patients should be questioned regarding history of tattoos,
particularly prior to sentinel node treatment Histologic confirmation of
melanoma in nodes is necessary to avoid unnecessary surgery
Reference :Shinohara, MM, Nguyen, J, Gardner, J, Rosenbach, M, Elenitsas, R. The histopathologic spectrum of
decorative tattoo complications.

Treatment
• Laser therapy
Microscopic (histologic) description
• Tattoo pigments are easily visualized in tissue sections
• After several weeks, they localize around vessels in the upper and
mid-dermis in macrophages and fibroblasts
• Extracellular deposits of pigment are also found between collagen
bundles; the pigment is generally refractile, but not doubly refractile
• No foreign body granulomatous reaction except in presence of other
severe reactions
• Hypersensitivity reactions vary from a diffuse dermal
lymphohistiocytic infiltrate with plasma cells and eosinophils, to a
lichenoid reaction sometimes with associated epithelial hyperplasia
• Sarcoidal granulomas, a granuloma annulare-like reaction,
vasculitis, pseudolymphomatous patterns and scarring may be
present
• Rare features are a morphea-like reaction, epidermal spongiosis and
pseudoepitheliomatous hyperplasia
Reference :Hamodat M. Tattoo. PathologyOutlines.com website.
https://www.pathologyoutlines.com/topic/skinnontumortattoo.html. Accessed June 30th, 2020.
2)Vellaisamy G, Tirumalae R, Inchara Y K. Histopathologic spectrum of reactions to black tattoo pigment: a report of five cases from
India. Egypt J Dermatol Venerol 2018;38:18-22

Mercury poisoning can be because of acute or chronic
exposure of mercury vapors.
Clinical features
• include gastric disturbances, diarrhea, excitability,
headache and mental depression. Patients complain of
gastric disturbances, diarrhea, excitability, headaches and
mental depression.
• Patient may have tremors of lips and extremities,
dermatitis and nephritis.
Oral manifestations
• increased salivation (ptyalism) as mercury is excreted in
saliva.
• Tongue may be enlarged and painful (glossodynia).
• hyperemia and swelling of gingiva, ulcerative stomatitis,
• loosening and exfoliation of teeth.
Mercury Poisoning

Acrodynia(Swift disease, Pink disease) is idiosyncratic reaction to
large doses of amalgam. It is an uncommon mercury toxicity reaction in which
skin is also involved.
• Etiology : It usually occurs after ingestion of mercury from powder,
ammoniated mercury ointment, calomel lotion.
• Age :It is mainly seen in the children below the age of 5–6 years.
• Manifestations : are widespread involving the hand, feet, nose and cheeks
which become red or pink in color, cold and clammy like a raw beef.
• Skin may have maculopapular rashes with pruritis.
• Patients may complain of irritability, photophobia and muscular weakness.
Children may be able to remove their hair in patches.
• Oral manifestations include profuse salivation, gingiva is painful and
ulcerated, teeth may become loose and exfoliate and bruxism is a common
finding.
Reference :James K. HartsfieldJr., Angus C. Cameron, in McDonald and Avery's Dentistry for the Child and Adolescent
(Tenth Edition), 2016

• Reduce Exposure
• Gastric lavage with 250ml of sodium formaldehyde sulphoxylate. Sodium
formaldehyde sulphoxylate is chemical antidote that reduces the
perchloride to metallic mercury .
• 5-10% sulphoxylate and 5% sodium-bi-carbonate is used for stomach
wash of which 200ml should be left in stomach. This is beneficial if given
only in first half an hour.
• The goal of treatment is to remove the mercury and correct any fluid or
electrolyte imbalances. Chelating agents such as meso 2,3-
dimercaptosuccinic acid are used to prevent methylmercury uptake
by erythrocytes (red blood cells) and hepatocytes (liver cells).
• Hemodialysis with and without the addition of L-cysteine as a chelating
agent has been used in patients with acute renal failure from mercury
toxicity.
• Dimercaprol is effective in treating inorganic mercury poisoning, should
not be used in case of methylmercury poisoning
• D-Penicillamine
• vitamin B1 given parenterally
Reference : 1) WHO. JAMA,1991 2)Campbell,J.R.et.al JAMA,1986
3) Goyer, RA, Clarkson TM. Toxic effects of metals, In: Klaassen CD. ed Casarett & Doull’s toxicology. New York:
McGraw-Hill, 2001, 811-868
4) P Williams, BG Shapiro, R Bartelot - Lancet, 1940 - cabdirect.org
Treatment for Mercury Poisoning

Lead (plumbism) is an occupational hazard seen in plumbers
due to acute or chronic exposure because of inhalation of lead
vapors or dust. It is also seen among the children who chew
wood painted with lead.
Clinical features :
• gastrointestinal symptoms like nausea, vomiting and
constipation.
• Patients may have encephalitis or peripheral neuritis
characterized by wrist drop or foot drop.
• Patients may have hypochromic anemia with basophilic
stippling in red blood cells.
Oral manifestations
• linear bluish black discoloration seen in the gingival margin
called Burtonian line.
• Gingivitis, ulcerative stomatitis, excessive salivation, metallic
• taste, or rarely bismuth may get deposited in the deciduous
• teeth too.
Lead Poisoning - Plumbism

Burtonian line
An X ray demonstrating the
characteristic finding of lead
poisoning in humans—
dense metaphyseal lines.

Arsenic in both organic and inorganic forms may produce
acute or chronic symptoms.
Oral manifestations
may include increased salivation, gingivitis, and oral
ulcerations.
Clinical Features :
severe edema of the eyelids, gastrointestinal
irritation, and both central and peripheral neuropathies.
Diagnosis :
Arsenic levels can be assessed by complete blood
count, urine analysis and hair and finger nail clippings.
Management:
The condition can be managed by removing the offending
agent followed by gastric lavage and chelation therapy with d-
penicillamine.
Reference :https://dghs.gov.in/WriteReadData/userfiles/file/Guidelines_on_Arsenicosis_Final.PDF
https://www.researchgate.net/publication/322668037_Groundwater_Arsenic_Contamination_in_the_Ganga_River_
Arsenic Poisoning - Arsenicosis

Bismuth
• Bismuth is used in treatment of syphilis and dermatological disorders.
Bismuth salts likewise have modest antibiotic properties, which may be
useful in surface inflammation and for deodorizing fecal material. It is no
wonder that bismuth salts have been widely used since antiquity, and still
hold a secure place in medicinal therapy today.
• Bismuth toxicity like that of other heavy metals is attributable to its
predilection to combine with sulhydril groups. Because sulhydril groups
are components of many vital enzymes, the effect of bismuth is to
denature and destroy the function of these enzymes.
Clinical Features :
• Patients usually have systemic complaints and it is characterized by
‘bismuth grip’, muscular cramps in the abdomen.
• In the skin a lichen planus-like rash .Inflammation and inclusion bodies in
the liver, kidney, and bone are characteristic.
• In the brain, the lesions will cause encephalitis.
• weight loss, gastrointestinal symptoms, signs of encephalopathy including
confusion, disorientation and rarely seizures, and black stools.
Reference :DiPalma, Joseph R. MD Bismuth Toxicity, Often Mild, Can Result in Severe Poisonings, Emergency Medicine News: April 2001 - Volume 23
- Issue 3 - p 16
https://journals.lww.com/em-
news/fulltext/2001/04000/bismuth_toxicity,_often_mild,_can_result_in_severe.12.aspx#:~:text=Renal%20toxicity%20in%20acute%20poisoning,a%20
blue%20black%20gum%20line.

Oral manifestations :
• Bismuth line which is a bluish black line in marginal gingiva confined to
gingival papilla.
• Bismuth may react with hydrogen sulfide produced by the bacteria to
form bismuth sulfide that gets precipitated around periphery of an
ulcer or erupting molar.
• burning sensation and metallic taste in the mouth
Diagnosis :
• Modified Reinsch's test -A simple, reliable, and fast bedside test. It can
identify mercury, arsenic, antimony, and bismuth. Use 10 to 15 g of
gastric contents or tissue homogenate. Add 3 ml of concentrated
hydrochloric and insert a copper wire spiral. Heat gently for two hours.
• A silvery deposit is mercury;
• shiny black is bismuth;
• dull black is arsenic;
• purple is antimony.
• Confirmatory tests such as the Gutzeit test can confirm each deposit,
and they can even be quantified.
Treatment:
• Chelation therapy with BAL is often recommended.
Reference :Kaye S. Handbook of Emergency Toxicology, Charles C. Thomas, Springfield, IL. 1980, pp. 55, 84.)

Silver Poisoning-Argyria
Argyria or Argyrosis is a condition caused by excessive
exposure to chemical compounds of the element silver, or to
silver dust.The most dramatic symptom of argyria is that
the skin turns blue or blue-grey. It may take the form
of generalized argyria or local argyria. Generalized argyria
affects large areas over much of the visible surface of the body.
Local argyria shows in limited regions of the body, such as
patches of skin, parts of the mucous membrane or
the conjunctiva.. Exposure to silver causes a violet
marginal line,often is accompanied by a diffuse bluish-
gray discoloration throughout the oral mucosa. It can
also be associated with neurologic and hearing damage.
Histologically we can observe silver particles staining the
reticular fibers.
Reference :James, William D.; Berger, Timothy G.; Elston, Dirk M.; Odom, Richard B. (2006). Andrews' diseases of the skin: clinical
dermatology. Saunders Elsevier. p. 858. ISBN 0-7216-2921-0. OCLC 62736861

Treatment
There is currently no cure for argyria, but recent research
indicates that laser therapy using the quality switch (QS) laser
may significantly improve skin discoloration. The QS laser
delivers high-intensity pulses of light to affected areas of skin.
steps to prevent further exposure:
•If you must work with silver, cover your skin with gloves and
other protective wear.
•Avoid dietary supplements and medicines that contain silver.
•Avoid cosmetics containing silver
Differential Diagnosis
•Exogenous ochronosis. Skin discoloration that usually results
from the prolonged use of skin-lightening creams, such as
hydroquinone.
•Chrysiasis. Skin discoloration due to the long-term use of gold
salts to treat rheumatoid arthritis.
•Hemochromatosis or “iron overload.” A condition in which the
body absorbs too much iron. It can be fatal without treatment.
Reference :https://www.medicalnewstoday.com/articles/325581#outlook

Reference:https://www.researchgate.net/publication/7464295_Chelators_as_Antidotes_of_Metal_Toxicity_Therapeutic_and_Experimental_Aspect
Chelators as ANTIDOTES for Metal Toxicity

Drug-Induced Pigmentations
List of drugs that can
Induce pigmentations
• Bleomycin
• Busulphan
• Clofazimine
• Chloroquine
• Chlorpromazine
• Cyclophosphamide
• Doxorubicin
• Estrogen
• 5-Fluorouracil
• Gold
• Hydroxychloroquine
• Ketoconazole
• Minocycline
• Tetracycline
• Quinacrine
hydrochloride
• Zidovudine
• Many medications when taken over a long period of time can cause oral mucosal
pigmentation. Drug-induced pigmentation can be due to increased synthesis and
accumulation of melanin pigments, deposition of the drug or its metabolites into
the oral tissues or deposition of iron after damage to the dermal vessels
• Chloroquine and other quinine derivatives which are usually used in the treatment
of malaria and cardiac arrhythmia can cause pigmentation of oral tissues due to a
direct stimulating effect on the melanocytes (Figure 3). According to some of the
studies these drugs usually cause pigmentation of the palatal tissues.
• Minocycline is another drug causing pigmentation of oral tissues. It is a synthetic
tetracycline that is commonly used in the treatment of acne vulgaris. Tetracycline
causes pigmentation of only the bones and teeth but minocycline can also cause
pigmentation of soft tissues. It usually causes diffuse brownish discoloration of
the hard palate, gingiva, mucous membranes and tongue. Oral pigmentation can
also be due to intake of birth control pills.
• Chloasma is the term which is used to describe perioral and periorbital
pigmentation in such patients The pigmentation usually occurs as a diffuse brown
macular pigmentation which is asymptomatic and lesions resolve upon cessation
of drug intake. These lesions usually occur due to the hormonal changes which
influence melanocyte stimulation.
• Imatinib (a tyrosine kinase inhibitor used for the treatment of chronic myeloid
leukemia) has the potential to induce mucosal pigmentation.

Reference :Nisar, M.S., Iyer, K.R., Brodell, R.T., Lloyd, J.R., Shin, T.M., & Ahmad, A. (2013). Minocycline-induced hyperpigmentation:
comparison of 3 Q-switched lasers to reverse its effects. Clinical, Cosmetic and Investigational Dermatology, 6, 159 - 162.

Exogenous Pigmentation of Oral Mucosa

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