DRUG INDUCED MUCOSAL

PIGMENTATION

Supervisor:
Dr. Hiba Al-Hessi

Done by:
Ayman Jendeya

ID:
12010333

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1. INTRODUCTION
Oral pigmentation is a common finding in the mouth. Pigmentation can be
either normal or abnormal discoloration of oral mucous membrane. Oral
mucosa is not uniformly colored. The color varies in different physiological and
pathological conditions. Physiological pigmentation is frequent in Asians,
Africans and Mediterranean people . The color change of the oral mucosa
could be due to accumulation of one or more pigments in tissues. [1]

Pigmentations represent in various clinical patterns that can range from just
physiologic changes to oral manifestations of systemic diseases and
malignancies. Color changes in the oral mucosa can be attributed to the
deposition of either endogenous or exogenous pigments as a result of various
mucosal diseases. The various pigmentations can be in the form of
blue/purple vascular lesions, brown melanotic lesions, brown heme-
associated lesions, gray/black pigmentations.[8]

Pigmentation is defined as the process of deposition of pigments in tissues.

Various diseases can lead to varied colorations in the mucosa. Pigmented
lesions of oral cavity are due to:
• Augmentation of melanin production
• Increased number of melanocytes (melanocytosis)
• Deposition of accidentally introduced exogenous
materials.[8,9,10,11,12]
Oral pigmentation may be physiologic or pathologic. Pathologic pigmentation
can be classified into exogenous and endogenous based upon the cause.[10]
Exogenous pigmentation could be induced by drugs, tobacco/smoking,
amalgam tattoo or heavy metals induced. And endogenous pigmentation can
be associated with endocrine disorders, syndromes, infections, chronic
irritation, reactive or neoplastic.[8]

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2. DRUG-INDUCED PIGMENTATION

Medications may induce a variety of different forms of mucocutaneous

pigmentation, including melanosis. [14]
A number of medications may cause oral mucosal pigmentation such
as Antimalarials (quinacrine, chloroquine, hydroxychloroquine, Quinidine, Zido
vudine (AZT), Tetracycline, Minocycline, and Chlorpromazine), Oral
contraceptives, Clofazimine, and Ketoconazole. The pathogenesis of drug-
induced pigmentation varies, depending on the causative drug. It may involve
accumulation of melanin, deposits of the drug or its metabolites, synthesis of
pigments under the influence of the drug or deposition of iron after damage to
the dermal vessels [1],[2].

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 discoloration associated with these drugs mostly involves
the hard palate only and appear as blue-gray or blue-black in color [2], [3], [4].
Laboratory studies have shown that these drugs may produce a direct
stimulatory effect on the melanocytes [5]. 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
gray discolouration [6]. Minocycline has also been reported to cause
pigmentation of the tongue mucosa. [7]. Drug induced lesions are local
reactions which are seen in oral cavity and no reports of malignant
transformation have been reported in this regard.[1]

Pigmentation can be produced by various drugs like, hormones, oral

contraceptives, chemotherapeutic agents like cyclophosphamide, busulfan,
bleomycin and fluorouracil, transquilizers, antimalarials like clofazamine,
chloroquine, amodiaquine, anti-microbial agents like minocycline, anti-
retroviral agents like zidovudine and antifungals like ketaconazole.
Palate and gingiva are most common sites affected. In addition to mucosal
changes, teeth in adults and children may be bluish gray owing to
minocycline/tetracycline use. The pathogenesis underlying drug-related
pigmentation can be categorized as that occurs because of drug or drug
metabolite deposition in dermis and epidermis, enhanced melanin deposition-
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-with or without increase in melanocytes, drug-induced post-inflammatory
changes to the mucosa especially if the drugs induce an oral lichenoid
reaction and bacterial metabolism, alone or in combination, may result in oral
pigmentations.[13]

3. DRUG INDUCED MELANOSIS

The chief drugs implicated in drug induced melanosis are antimalarials

including chlorquine,hydroxychloroquine, quinacrine and others [14,15,16].
These medications are typically used for the treatment of autoimmune
diseases. Other classes of medications that induce melanosis include the
phenothiazines such as chlorpromazine, oral contraceptives, cytotoxic
medications such as cyclophosphamide and busulfan [14,17].

4. CONCLUSION [18]

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5. REFERENCES
1. BasselTarakji ,AyeishaUmair ,DurgaPrasad ,MohammedAlsakran Altamimi , Diagnosis of oral
pigmentations and malignant transformations ,December 2014, 39-46.

2. O. DereureDrug-induced skin pigmentation, epidemiology, diagnosis and treatment

Am. J. Clin. Dermatol., 2 (2001), pp. 253-262.

3. C. Birek, J.H. MainTwo cases of oral pigmentation associated with quinidine therapy
Oral Surg. Oral Med. Oral Pathol., 66 (1988), pp. 59-61.

4. L.H. McAllan, K.F. AdkinsDrug-induced palatal pigmentation

Aust. Dent. J., 31 (1) (1986), pp. 1-4.

5. N.W. Savage, M.T. Barber, K.F. AdkinsPigmentary changes in rat oralmucosa following antimalarial
therapy J. Oral. Pathol., 15 (1986), pp. 468-471.

6. L.W. Westbury, A. NajeraMinocycline-induced intraoral pharmaco genicpigmentation: case reports

and review of the literature J. Periodontol., 68 (1997), pp. 84-91.

7. M.A. Meyerson, P.R. Cohen, S.R. HymesLingual hyperpigmentation associated with minocycline
therapy Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 79 (1995), pp. 180-184.

8. Sreeja, C et al. “Oral pigmentation: A review.” Journal of pharmacy & bioallied sciences vol. 7,Suppl
2 (2015): S403-8. doi:10.4103/0975-7406.163471.

9. Kauzman A, Pavone M, Blanas N, Bradley G. Pigmented lesions of the oral cavity: Review,
differential diagnosis, and case presentations. J Can Dent Assoc. 2004;70:682–3.

10. Greenberg M, Glick M. Burkets oral medicine diagnosis and treatment. 10th ed. Hamilton, Ontario:
B. C. Decker; 2003. pp. 126–36.

11. Gaeta GM, Satriano RA, Baroni A. Oral pigmented lesions. Clin Dermatol. 2002;20:286–8.

12. Sarswathi TR, Kumar SN, Kavitha KM. Oral melanin pigmentation in smoked and smokeless tobacco
users in India. Clinico-pathological study. Indian J Dent Res. 2003;14:101–6.

13. Anil Kumar N, Divya P. Adverse drug effects in mouth. International Journal Of Medical And Applied
Sciences. 2015;4:82–91.

14. Bhateja S, Bohra A, Arora G (2015) Drug Induced Oral Mucosal Pigmentation- A Review. Pigmentary
Disorders 2:198. doi:10.4172/2376- 0427.1000198.
15. Porter SR, Scully C (2000) Adverse drug reactions in mouth. Clin Dermatology18:222-230.

16. Lanier VC Jr, Pickrell KL, Georgiade NG (1976) Congenital giant nevi: clinical and pathological
considerations.PlastReconstrSurg 58: 48-54.

17. Marghoob AA1, Schoenbach SP, Kopf AW, Orlow SJ, Nossa R, et al. (1996) Large congenital
melanocytic nevi and the risk for the development of malignant melanoma. A prospective study.Arch
Dermatol 132: 170-175.

18. Bhateja S, Bohra A, Arora G (2015) Drug Induced Oral Mucosal Pigmentation- A Review. Pigmentary
Disorders 2: 198. doi:10.4172/2376- 0427.1000198.