Clinical Guide to Oral Diseases. Crispian Scully
3.1), floor of the mouth and soft palate. This discoloration is the result of increased production of melanin pigment by normal melanocytes.
3 No
4 No
5 No
Comments: Brown pigmentation is the result of increased melanin production and deposition in the melanocytes of the basal layers of the epithelium. Apart from racial pigmentation other conditions may be the cause such as Addison's disease, melasma, heavy metals, or drug effects. Drugs induced or metal poisoning pigmentation was easily discounted as the patient did not take any causative drugs nor was she exposed to chemicals in her hob or at home.. In melasma, the pigmentation is limited to facial skin and never involves the oral mucosa, and it mainly appears in young women during pregnancy. Normal blood pressure and Na, K, Ca, and cortisol levels as well as a normal Synacthen test excludes Addison's disease from the diagnosis.
Q2 Which are the histological characteristics of racial pigmentation?
1 Increased production of melanin from an adequate number of melanocytes
2 Increased number of melanocytes at the basal layer
3 Presence of melanophages within the superficial lamina propria
4 Atrophic epithelium
5 Reduced number of melanocytes
Answers:
1 Racial pigmentation is connected with the increased production of melanin from melanocytes at the basal layer which is transported to adjoining keratinocytes through membrane‐bound organelles known as melanocytes.
2 No
3 Melanophages are macrophages within the upper corium containing melanin.
4 No
5 No
Comments: The brown discoloration is the result of increased melanin production in normal or increased number of melanocytes. The brightness or not of this discoloration depends on the epithelial thickness’ atrophic epithelium presents melanin pigment closer to the examiners’ eyes,
Q3 In which other parts of the human body apart from the mouth is melanin commonly found?
1 Heart
2 Skin and its appendages (hairs/nails)
3 Brain
4 Joint cartilage
5 Eyes
Answers:
1 Heart valves, aortic sinuses and coronary vessels are often found with increased melanin pigmentation induced by antibiotics such as minocycline.
2 Increased skin pigmentation is often seen among patients with dark complexion and nails (melanonychia) or in patients exposed to solar radiation (solar dermatitis, lentigines, freckles), or in chronic inflammation (lichen planus), and hormone changes (melasma). Hair pigmentation is the result of sequential interaction between follicular melanocytes, matrix keratinocytes and dermal papillae fibroblasts. Hair color is also based on the ratio between eumelanin and pheomelanin. The higher the level of eumelanin, the darker the hair.
3 Brain pigmentation is seen in catecholaminergic cells of the substantia nigra of the brain and is caused by the accumulation of neuromelanin (one of the three components of melanin), the role of which remains obscure.
4 No
5 Eye color is the result of iris pigmentation, as dark brown eyes have a higher quantity of melanin than blue eyes.
Comments: Cartilage pigmentation is rarely seen and is associated with the accumulation of homogentisic acid rather than melanin in the connective tissues of nails, cartilage and bones.
Case 3.2
CO: A 72‐year‐old woman was referred for evaluation of multiple brown lesions in her mouth.
PMH: She suffered from polycythemia vera which was diagnosed 15 years ago. It was controlled with hydroxyurea tablets. A small hormone‐sensitive carcinoma in situ of her right breast was removed; letrozole tablets are now her maintenance treatment. She has never been hypotensive or allergic to various drugs or foods, nor a smoker or drinker.
HPC: The brown lesions in her mouth were accidentally found during a clinical examination by her physician two weeks ago.
OE: During the examination, multiple brown lesions scattered on the dorsum and lateral margins of the tongue (Figure 3.2a), buccal mucosae and soft palate and were linked with skin pigmentation and brown discoloration of the nail hands and feet (melanonychia) (Figure 3.2b). No other abnormalities either on the skin or other organs were reported, and her blood tests, including various hormone tests, were in a normal range.
Q1 What is the cause of her oral and skin pigmentation?
1 Addison's disease
2 Melanoma, widespread
3 Chemical poisoning
4 Drug‐induced pigmentation
5 Cushing's disease
Answers:
1 No
2 No
3 No
4 The use of hydroxyurea and not letrozole has been associated with the increased pigmentation in this patient. Hydroxyurea is routinely used as an anti‐neoplastic agent for the treatment of various myeloproliferative disorders such as leukemias, thrombopenias, polycythemia, and sometimes in psoriasis. Hydroxyurea can cause increased melanin production thus showing dark brown pigmentation of skin, sclera, nails of hands and feet and oral mucosa within a few months of treatment.
5 No
Comments: The normal blood pressure together with the normal hormone levels and the clinical characteristics and slow pigmentation progress exclude Cushing's, Addison's diseases and melanoma from the diagnosis.
Q2 What other drugs can cause hyper‐pigmentation?
1 Anti‐malarials
2 NSAIDs
3 Antibiotics
4 Cytotoxic drugs
5 Anti‐emetics
Answers:
1 Anti‐malarials such as chloroquine or hydroxychloroquine, having been used for months, can cause blue or gray pigmentation on face, neck, legs, and nails.
2 NSAIDs are used for pain or inflammation relief and sometimes cause a fixed drug reaction which initially appears in the form of erythematous lesions on the face, lower extremities or genitalia, leaving, eventually, a brown discoloration.
3 Antibiotics and especially tetracyclines cause brown discoloration of nails, sclera, skin, and bones.
4 Cytotoxic drugs cause a brown discoloration