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NUMBER 7
Skin Discolorations and Their Treatment
Loyd V. Allen, Jr., Ph.D.
Introduction
Having clear, smooth, evenly colored skin is desired
by many; some are fortunate to have it, but most are
not. Skin color can be altered by disease or exposure
to miscellaneous agents; some patients have a change
in pigment coloration as a result of some inflammatory disease, including acne or atopic dermatitis.
The skin cells contain melanocytes that produce
melanosomes, which are pigment granules containing the complex protein or brown skin-coloring
pigment, melanin. The pituitary hormone produces
melanocyte stimulating hormone, or MSH, which
stimulates melanin production. There are approximately 800 to 1000 melanocytes per square millimeter of human epidermis; being the same in both light
and dark skin individuals but the rate of production
of the pigment varies. A number of conditions cause
the melanocytes to become either abnormal or abnormally distributed in the skin.
Most skin conditions that cause discoloration are
actually harmless; causing more cosmetic and emotional discomfort than medical problems.1,2 Skin
hyperpigmentation and photoaging are considered
by many to be cosmetically unacceptable and they
search for treatment methods to minimize it.
Background
Exposure to such pigments as carotene can result in
carotenemia, iron can cause hemodiserin and silver
can cause argyria. Other pigmentation problems can
be caused by gold used in rheumatoid arthritis treatments, tattooing, homogentisic acid in ochronosis
and bile pigments.
Changes in skin color may be from hyperpigmentation or hypopigmentation; both can be primary or
secondary to other disorders in the body. Table 1
lists common causes of pigmentation disorders.
Primary hyperpigmentation disorders include those
that are nevoid, congenital or acquired. Disorders
include pigmented nevi, ephelides (juvenile freckles—an
inherited characteristic—age spots and café-au-lait
spots), and lentigines (solar lentigines, senile lentigines, senile freckles, liver-spots). Other hyperpigmentation disorders include arsenical melanosis and
those associated with Addison’s disease. Neurofibromatosis may produce axillary freckling and caféau-lait spots. A patterned facial hyperpigmentation
of the face, usually as a result of estrogen therapy,
is melasma, or chloasma; occurring in about 30 to
50% of women taking oral contraceptives.1
Primary hypopigmentation and depigmentation
disorders include vitiligo, albinism and piebaldism.
Pigment cells, or melanocytes, are destroyed in vitiligo, which occurs in aobut 1% of the population
and may be associated with hyperthyroidism, hypothyroidism, pernicious anemia, diabetes mellitus and
Addison’s disease. Albinism is a collection of genetically determined traits. Piebaldism is a localized hypomelanosis producing a white forelock. Tuberous
sclerosis may produce hypopigmented ash leaf spots
and hypopigmented halos can often be seen around
nevi and may occur around melanomas.1
Secondary hyperpigmentation disorders include
those occurring following a separate dermatologic
condition, including acne; it is most commonly seen
in dark-skinned individuals and is called postinflammatory hyperpigmentation. Another disorder is
called Berloque hyperpigmentation, which is due to
phototoxicity from chemicals in the rinds of limes
and other citrus fruits, and to celery. Pigmentation
disorders can also be caused by some drugs, including chloroquine, chlorpromazine, minocycline, and
amiodarone. Benzoyl peroxide, fluorouracil and
tretinoin can cause hyperpigmentation as well as
fixed drug eruptions resulting from phenolphthalein in laxatives, trimethoprim-sulfamethoxazole,
NSAIDs and tetracyclines.1
Secondary hypopigmentation, or leukoderma may
result as a complication due to atopic dermatitis,
Table 1: Causes of Generalized
Hyperpigmentation.
Congenital
• Familial
• Racial
Ultraviolet light irradiation
Endocrine disorders
• Acromegaly
• Chronic primary hypoadrenalism
• Cushing’s syndrome with high ACTH
• Estrogens
• Pregnancy
Systemic Disease
• Biliary cirrhosis, primary
• Chronic renal failure
• Cachexia (Tuberculosis, Malignancy)
• Hemochromatosis
• Malabsorption (Whipples disease, Celiac disease)
Drug Induced
(See table 2)
lichen planus, psoriasis, discoid lupus erythrematosus and lichen simplex chronicus.
Liquid nitrogen used on patients with olive or darker complexions may result in hypopigmentation or depigmentation. High concentrations of corticosteroid injected
intralesionally or intra-articularly may also cause localized temporary hypopigmentation.1
Some body chemicals, such as bilirubin, can be deposited in the skin and cause a
discoloration. Heavy metals, such as silver, gold and iron each have a characteristic
color when they can be seen within the skin. Table 2 lists a number of these agents
as well as some drugs that can cause pigmentation disorders.
Symptoms
Table 2: Agents or Drugs that can
Cause Skin Hyperpigmentation.
Amiodarone
Arsenic
Benzoyl peroxide
Bleomycin
Busulfan
Chloroquine
Chlorpromazine
Cyclophosphamide
Estrogens
Fluorouracil
Heavy metal poisoning
Hydroxychloroquine
Iron
Minocycline
Nicotinic acid (Niacin)
Nonsteroidal anti-inflammatory agents (NSAIDs)
Phenolphthalein
Phenothiazines
Phenytoin
Steroids
Tetracycline
Tretinoin
Trimethoprim-Sulfamethoxazole
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Questions for the medical history of the patient can involve family (Does anyone else in your family have
a similar problem?), timing (When did the discoloration begin? Was it sudden? Is it getting worse, and if
so, how quickly), quality (Describe the change. Is the skin getting darker or lighter?), location (Where is
the discoloration? Is there a pattern to it?), aggravating factors (What medications are you using? Are you
often exposed to the sun or a sun lamp? What is your diet?) and miscellaneous questions involving other
symptoms they might have as well as any rashes or skin lesions.
A trained dermatologist can generally recognize the pattern of discoloration immediately and name and
characterize the discoloration. Some of these pigment changes reflect internal diseases that must be identified and treated.
Table 3 lists some symptoms, diseases and causative factors related to hyperpigmentation disorders.
Table 3: Symptoms of and Disorders
Related to Hyperpigmentation.
Acanthosis nigricans
Actinic keratosis-sometimes causing a red-brown skin
Biliary cirrhosis
Birthmarks (Nevus)
Bruise
Blue skin
Café-au-lait spots
Chloasma
Dry gangrene
Erythema abigne—a red brown discoloration resulting from heat exposure
Familial polyposis; results in a darkening of the gums
Freckles
Frostbite
Hemochromatosis (Bronze diabetes)
Jaundice
Kaposi’s sarcoma-purple spots
Malignant melanoma
McCune-Albright Syndrome-increased pigmentation, “café au lait” spots
Moles
Mongolian blue spot
Necrotizing fasciitis-violet skin
Neurofibromatosis, or von Recklinghausen’s diseases
Peutz-Jeghers syndrome (peri-oral pigmentation)
Polycystic ovary syndrome-thickened darkened skin patches
Porphyria cutanea tarda
Port wine stains
Pregnancy: “Mask of pregnancy”, darkening of the cheeks and forehead; also, darkening of the nipples, genitals and a line down the central abdomen, linea nigra.
Purple skin
Sarcoidosis-purple skin patches
Scleroderma
Seborrheic wart
Senile wart
Sun sensitivity
Uremia-sallow complexion
Varicose veins
Venous ulceration from long-term varicose veins
Visceral leishmaniasis
Table 5: Example antioxidants and
adjuvants used in hydroquinone
preparations.*
Agent
Oil Soluble
Ascorbyl palmitate
Butylated hydroxyanisole
Butylated hydroxytoluene
Lecithin
-Lipoic acid
Tocopherols ( , Δ, )
Water Soluble
Ascorbic acid
Potassium metabisulfite
Sodium bisulfite
Sodium metabisulfite
Sodium sulfite
Adjuvants
Ascorbic acid
Citric acid
EDTA and salts
Tartaric acid
*See IJPC 3(1); 1999: 52-55.
Concentration
Range
0.01-0.5%
0.005-0.02%
0.005-0.02%
0.05-0.5%
0.01-0.5%
0.05-1%
0.05-1%
0.01-1%
0.01-0.2%
0.02-0.1%
0.005-0.01%
0.02-0.1%
0.01-0.02%
Treatment
This article will only address hyperpigmentation treatment. The goal of
therapy in hyperpigmentation disorders is to lighten the skin so it blends
into the normal skin in the area. Most
products (See Table 4) used to lighten
the skin contain hydroquinone. Other
drugs commonly used in the treatment
of hyperpigmentation disorders include
azelaic acid, glycolic acid, hydrocortisone, kojic acid, tretinoin and triamcinolone. These are listed in Table 4 and
antioxidants and adjuvants used in their
formulations are listed in Table 5. Normally, these agents are somewhat irritating to sensitive skin. Treatments may
take three to six months to produce improvement. Laser treatments are also
available. For treatment of freckles, age
spots and other discolorations, using a
sunscreen with a sun protection factor
(SPF) of at least 15 is a must.
References
1. Berger TG. Skin, Hair, & Nails.
In: Tierney LM Jr, McPhee SJ, Papadakis MA, eds. Current Medical
Diagnosis & Treatment. New York:
Lange Medical Books/McGrawHill; 2003: 138-140.
2. Esterly JS, West LE, West DP. Skin
Hyperpigmentation and Photoaging. In: Berardi RR, ed. Handbook
of Nonprescription Drugs. 14th
ed. Washington, DC: American
Pharmaceutical Association; 2004:
955-967.
Table 4: Active ingredients
used in the treatment of skin
hyperpigmentation.
Ingredient
Azelaic acid
Glycolic acid
Hydroquinone
Hydrocortisone
Kojic acid
Tretinoin
Triamcinolone
% Used
5-20
1-20
1-15
0.5-1
2-10
0.025-0.05
0.025-0.5
Example Formulations
Rx
Hydroquinone 5% in Isopropyl
Alcohol
Rx
Hydroquinone 5% Topical Gel
Rx
Hydroquinone 5% Topical StickWater Repellant
Rx
Hydroquinone 5% Topical StickWater Soluble
Rx
Dexamethasone 0.1%, Hydroquinone 5% and Retinoic Acid 0.1% Ointment
Rx
Hydroquinone 5%, Retinoic
Acid 0.1% and Triamcinolone 0.1% Gel
Rx
Hydroquinone 5%, Retinoic
Acid 0.1% and Triamcinolone 0.1% Cream
Rx
Hydroquinone 5%, Retinoic Acid 0.1% and Triamcinolone 0.1% Ointment
Rx
Hydrocortisone 1%, Hydroquinone 5% and Glycolic Acid 5% Lotion
Rx
Hydroquinone 5% Cream
RxTriad-A publication of the International Journal of Pharmaceutical Compounding. © 2007 IJPC. All rights reserved.