Skin can be pigmented due to various reasons. The skin can be hyper-pigmented (darker than usual skin color) and hypo-pigmented (paler than usual skin color).
Hypopigmentation can be classified into generalized and localized causes. Generalized hypopigmentation can be due to albinism and hypo-pituitary disease. Localized hypopigmentation areas can be due to piebaldism,Pityriasis Alba, chemical toxins, Vitiligo, halo nevus, Pityriasis versicolor, leprosy, tuberous sclerosis and post-inflammatory hypopigmentation. These conditions will be discussed later below.
Hyperpigmentation can be classified into generalized and localized causes. Generalized hyperpigmentation can be due to Addison’s disease, nelson syndrome and drug induced e.g. chlorpromazine, phenytoin, phenothiazine and minocycline. Localized causes include Mongolian spots, café au lait spots, nevus, freckles, peutz Jeghers syndrome, melasma and post inflammatory hyperpigmentation. These conditions will be discussed later below.
Melanin is a photo-protective skin pigment which protects us from skin damage by absorbing the UV light from the sun. After suntan, the skin turns darker due to the increased melanin pigments in the skin.Melanin is produced by melanocyte cells which are controlled by melanocyte stimulating hormone (MSH).
Hypopituitarism refers to the condition when the pituitary gland found at the base of the brain does not produce/ does not produce enough one or more of its hormones. In hypopituitarism there is lack of melanocyte stimulating hormone (MSH) which stimulates formation of the melanin (skin pigment) resulting in generalized decrease in skin color. The precursor of MSH is AdrenoCorticoTropic Hormone (ACTH). Both MSH and ACTH regulate the skin pigmentation. Hence if there is pituitary deficiency in ACTH, there will be generalized hypopigmentation.
Albinism is an inherited disorder whereby there is an abnormality in the melanin (skin pigment) formation pathway. This condition is caused by gene mutations. There are two main subtypes of albinism which are OculoCutaneous Albinism (OCA) and Ocular Albinism (OA).
In Oculocutaneous albinism (OCA), there is absent/reduced melanin on the skin, hair and the optic system (including the optic nerves and the eyes). The generalized pale white skin color predisposes these patients to sun burns skin cancer.
In Ocular Albinism (OA), there is absent/reduced melanin only on the optic system (eyes and optic nerve) sparing the hair and skin.
Patients with albinism often have high problems like nystagmus (rapid eye movements), strabismus (crossed eyes), refractive error (visual problems), astigmatism (inability of cornea to focus image onto retina), Colored iris (blue-gray or brown color) and photophobia (light sensitivity).
The most definitive test to do is genetic sequence analysis. It is very useful in families with albinism to determine if the fetus is affected. An ophthalmologist consult will be necessary as albinism always have eye problems. A visual evoked potentials test may be conducted if diagnosis in doubt.
Currently there is no cure for albinism. Treatment is aim at protecting the skin and the eyes from the sun. Sunscreens and sunglasses will reduce sun burn and photosensitivity. Tinted glasses may help to reduce photophobia. Eye patching at very young age may help patients with strabismus. Sometime eye surgery is conducted in patients with nystagmus (abnormal eye movements) to correct the eye muscles.
Localized hypopigmentation refer to patches of lighter skin tone. It can be due to few conditions below:
Piebaldism is a rare inherited autosomal dominant condition characterized by the lack of melanocytes in certain areas (lighter pale colored areas) of the hair and skin. It is caused by gene mutations in the KIT proto-oncogene. As it is an auto dominant disease, it means that half of the affected patient’s offspring will be affected by the condition.
The name Piebaldism is derived from the Pie in magpie (a kind of bird with white and black plumage) and the Bald from the bald eagle which has white feathered head. About 80-90% of people with piebaldism has characteristic patch of white hair over the forehead.
Besides the white patch of hair, they may also have white patch over central forehead and white eyelash/eyebrows. Symmetrically distributed white spots may occur on face, trunk & limbs. Sometimes there maybe hyper-pigmented (darker skin) areas within these white spots or there may be a narrow hyper-pigmented border around the white spots.
Skin biopsy will show that the white spots areas have lack of melanocytes and the melanin skin pigment. The lighter colored skin patches are prone to sunburns and prolonged sun exposure may increase risk of skin cancer. Hence, sunscreens are important.
Dermabrasion followed by application of melanocyte- enriched cell suspensions, surgical melanocyte transplant, UV light therapy may be tried on patients to improve the pigmentation of the skin. Using cosmetic to cover up the white patches is another less invasive option.
Pityriasis Alba & Versicolor
Pityriasis Alba is dry, fine scaled round patches commonly found on children. It will be discussed further in another page.
Pityriasis Versicolor is a superficial fungal infection of the skin caused by Malassezia furfur. It can range from pale colored, pink or dark patches on the skin. It will be discussed further in another page.
Chemical toxins that are inhaled /ingested or contact with skin may cause hypopigmentation of skin. Chemicals that contain phenol, sulfhydryl compounds and catechol may be the causative agents. Things that contain alkyl phenol include motor oils, deodorants, insecticides, paints, photographic chemicals, resins, rubbers, adhesives, varnishes and printing inks. Most patients present with hypopigmentation due to occupational exposure to these chemicals. Ionizing radiation may also cause skin changes resulting in hypopigmented skin.
Vitiligo is a skin condition whereby there is loss of melanocytes on the affected areas of skin resulting in white patches of skin. This condition will be discussed further at another page.
Halo nevus is a mole surrounded by a ring of white pigmented skin. It is a non-cancerous condition. The exact cause of halo nevus is unknown. It has been hypothesized due to immunologic mechanisms against the melanocytes. They can occur at any part of the body. It is more common in children with an age onset of 15 years.
Halo nevus usually does not cause any symptoms. The central mole color may be pink, brown or black. Usually no tests are required. However if the mole is suggestive of melanoma (skin cancer) then biopsy is required.
As halo nevus is usually non-cancerous, no treatment is required.
Leprosy is also known as Hansen’s disease. It is chronic infection caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. It can cause damage to the eyes, skin, nerves and limbs.
The indeterminate and tuberculoid types of leprosy may cause hypopigmentation of skin. The affected area will have reduced pain sensation. Common symptoms of leprosy are disfiguring skin sore/lumps, reduced sensation to heat/touch/pain (nerves affected), muscle weakness and also numbness of limbs. Possible complications include neuropathic ulcer resulting in osteomyelitis (spread of infection to bones), blindness, facial palsy (facial nerve damage), and foot drop and claw hands.
Diagnostic test include biopsy of the lesion to identify typical histological changes and acid fast bacilli. Slit skin smear is a quick test to detect acid fast bacilli from the skin lesion. Lepromin skin test can help to detect which form of leprosy is causing the condition. Phenolic glycolipid-1 (PGL-1) IgM antibody detection is of limited clinical use.
It can be treated with antibiotics like dapsone, rifampicin, fluoroquinolones, minocycline, macrolides and clofazamine. Anti-inflammatory agents like prednisolone or thalidomide can be used to reduce the inflammation. The earlier treatment is started the better the prognosis and it reduces the risk of permanent complications.
Tuberous sclerosis is a rare genetic disorder that results in non-cancerous growths in the brain and other parts of the body. It is caused by mutation in the gene TSC1 and TSC2. If one parent is affected, he/she can pass the gene mutation to the child. In certain patients, the gene mutation may be spontaneous.
It is a neurocutaneous syndrome with symptoms affecting mainly the brain, spinal cord and the skin. Skin involvement includes lighter colored patches with ash leaf or confetti appearance, shagreen spots (Raised patches of skin with an orange-peel texture) and adenoma sebaceum (Red patches on the face containing many blood vessels).
Neurological symptoms include developmental delay, seizures, behavioral problems (aggression and hyperactivity) and intellectual disability. Sometimes lesions may occur in the kidneys and can be fatal. Growths in lungs are called leiomyomas which can cause shortness of breath; prolong cough and even lung failure. Growths in the heart (rhabdomyoma) may cause abnormal heart rhythms (dysrhythmia).
Other clinical features are non-cancerous growths on/around the tongue, rough growths beneath the nails and pitted tooth enamel. Brain imaging like CT/MRI of the brain will reveal tumors of the brain. Ultrasound kidneys may also reveal tumors of kidneys. Electroencephalogram (EEG) test may be useful if patient has seizures. DNA genetic testing is important for genetic counseling in affected families. Echocardiogram and ECG tests can be done to assess the heart condition.
There is no specific treatment for tuberous sclerosis; treatment is dependent on the clinical presentation. As there may be learning and developmental delay, occupational, education and psychological therapy is important. For patients with seizures, they will need medications like anti-epileptics.
Facial growths like adenoma sebaceum on face can be removed by laser. Rhabdomyoma in the heart often disappears after puberty so no intervention is required. Kidney tumors are often removed surgically. Brain tumors can be treated by medications called mTOR inhibitors e.g. evrolimus and sirolimus.
Post inflammatory hypopigmentation is ill defined white patches on the skin that occur post trauma and inflammatory processes. It is a benign condition and does not cause any symptoms.
Generalized hyperpigmentation can be caused by medical conditions and drugs which will be discussed below:
Addison’s disease is also known as adrenal insufficiency whereby the adrenal glands do not produce enough hormones. The adrenal glands produce glucocorticoid hormones, mineralocorticoid hormones and sex hormones. The incidence of this condition is rare and age of onset is about 30-50 years old.
The cause of Addison’s disease is due to the dysfunction or destruction of the adrenal cortex. The most common cause is idiopathic autoimmune adrenal insufficiency whereby antibodies attack the adrenal cortex cells. It is associated with other autoimmune diseases like celiac disease, type 1 diabetes, Vitiligo, Graves disease, Hashimoto Thyroiditis, Alopecia Areata, Pernicious of anemia and Myasthenia gravis.
Other causes of Addison’s disease are tuberculosis, cancers (e.g. Hodgkin and non-Hodgkin lymphoma), immunocompromised state (HIV and AIDS), congenital adrenal hyperplasia, previous abdomen radiation, acute stress reaction (trauma and surgery), bilateral adrenal hemorrhage and adrenal blood vessels thrombosis.
Glucocorticoid hormones like cortisol helps the body to respond to stress, maintain glucose (sugar level) and maintain our immune response. When there is lack of glucocorticoid, there will be a drop in blood pressure, dehydration, low glucose levels and generalized fatigue and weakness.
Mineralocorticoid hormones like aldosterone which monitor the sodium and potassium balance. In Addison’s disease there will be low sodium (may present as dizziness, nausea, vomiting and weakness) and high potassium levels (muscle ache and fatigue, heart arrhythmias).
Sex hormones like androgens in males and estrogens are reduced in Addison’s disease. This may affect sex drive and libido. Females may also show decreased hair in axilla and pubic areas.
Hyperpigmentation occur in Addison disease due to the secondary increase in ACTH (adrenocorticotrophic hormone) which acts on melanocytes to produce a generalized increase in melanin over the body. The darker skin tone tend to occur more on sun-exposed areas like sun-exposed areas of the skin, extensor surfaces, knuckles, elbows, knees, and scars formed after the onset of disease.
Investigations include blood tests to measure the electrolytes levels, cortisol levels, aldosterone level, sex hormones level, glucose level, and ACTH and prolactin levels. CT imaging of the adrenal glands may also be necessary. Rapid ACTH stimulation test i.e. synacthen test may be conducted to diagnose the etiology of the disease.
Treatment during adrenal crisis includes resuscitation to correct hypotension and electrolyte imbalance. Long term hormone replacement for glucocorticoids with hydrocortisone/steroids and mineralocorticoids with fludrocortisone may be necessary.
Nelson syndrome is a series of signs and symptoms that occur after surgical removal of bilateral adrenal glands as a treatment for Cushing’s syndrome due to ACTH (adrenocorticotrophic Hormone) secreting pituitary tumor. It is a very rare condition.
Patients with pituitary tumor may present with headaches, blur vision and symptoms of insufficient hormone production from the pituitary glands (thyroid diseases, growth issues and pubertal development disturbances).
Patients with Nelson syndrome have generalized hyperpigmentation (darker skin color) due to the excess ACTH which stimulates melanocytes to produce melanin.
Diagnostic tests include the measurements of hormones levels like ACTH, growth hormone, thyroid hormone, gonadotrophin and prolactin levels. Imaging study like MRI of the brain will review the presence of the pituitary tumor. Affected patients should also see an ophthalmologist for visual assessment.
Treatment involves surgical resection of the tumor or radiation therapy.
Drug induced hyperpigmentation
Certain drugs like phenytoin (anti-epileptic), NSAIDs, antibiotics like minocycline && tetracycline, amiodarone, antipsychotics (chlorpromazine), heavy metals and cytotoxic drugs accounts for 10-20% of drug induced skin hyperpigmentation.
The drugs cause pigmentation by stimulating melanin production, melanin accumulation or by deposition of the heavy metal for example into the skin dermis.
Localized Skin Hyperpigmentation
Localized skin hyperpigmentation can be caused by the conditions described below:
Mongolian spot is also called lumbosacral dermal melanocytosis. They are blue-grey skin discoloration often occur at birth (birthmark) commonly found over at the lower back and buttock regions. Some may occur on the face and limbs area.
Mongolian spot occurs because the melanin is trapped over at these spots during the development of the embryo. Most of the time the Mongolian spots fades away by age 4-5 hence no treatment is required. Some may persists indefinitely. Laser treatment may be beneficial for those spots that are persistent.
Café Au Lait Spots
Café au lait spots are flat light-brown to dark-brown colored oval patches on the skin. Multiple café au lait spots are a feature of the disease neurofibromatosis.
In general café au lait spots do not require treatment. However if they are associated with neurofibromatosis, then the latter condition should be addressed. Laser treatment for café au lait spots is equivocal.
Nevus also known as moles are usually non-cancerous. They can occur at birth or later on in life. More description of nevus will be covered inanother page in this blog.
Freckles medically known as Ephelides are brown patches found on the skin. They occur more commonly in fair-skinned, blonde/red haired people. They are commonly found in sun exposed areas hence sun screens are important. They are non-cancerous lesions and do not require treatment. It occurs because of pigment accumulating in the keratinocyte skin cells.
Freckles can be lightened by topical creams that contain hydroquinone. Cosmetically they can be lightened by chemical peel, cryotherapy, laser, intense pulsed light treatment.
Solar Lentiges are small pigmented flat/mild raised spots with clear edges surrounded by normal skin. The colors vary from tan brown to black and can occur at any part of the body. These are non-cancerous pigmentation that occurs with ageing and sun exposure.
Solar Lentiges can be lightened by topical creams that contain hydroquinone. Cosmetically they can be lightened by chemical peel, cryotherapy, laser, intense pulsed light treatment.
Melasma is blotchy brown pigmentation found often on the cheeks. They occur due to the over production of melanin (pigment) from melanocytes cells. Sun exposure, genetic predisposition, thyroid disorders, contact dermatitis and hormone therapy may also lead to formation of melasma.
It is more common in women and age of onset ranges from 20-40 years old. Basic measures include sunscreens and using cosmetics to camouflage the melasma. Topical creams that contain combination of hydroquinone, tretinoin and steroids can be used to lighten the pigmentation.
Laser and intense pulsed light therapy may be used aesthetically to lighten the pigmentation for cosmetic reasons.
Post inflammatory hyperpigmentation
Post inflammatory hyperpigmentation as the name implies is pigmentation of skin that occurs with healing after an inflammatory process. The skin inflammatory process can be due to infection, trauma,acne, dermatitis, lichen planus, mechanical injuries, medication side effects and allergic reactions.
Post inflammatory hyperpigmentation can occur anywhere and in anyone. Inflammatory process may induce melanocytes to produce more melanin resulting in the pigmentation. Sun exposure may worsen the pigmentation. They can range from brown to black in color.
Often after 6-12 months, the pigmentation may slowly fade back to normal skin color. Basic measures include sunscreens and using cosmetics to camouflage the melasma. Topical creams that contain combination of hydroquinone, tretinoin and steroids can be used to lighten the pigmentation.
Chemical peels, laser and intense pulsed light therapy may be used aesthetically to lighten the pigmentation for cosmetic reasons.
Peutz Jeghers syndrome
Peutz Jeghers syndrome is a rare inherited condition characterized by pigmentation of skin/mucosal surface and gastro-intestinal tract polyps. The polyps are often benign however there is a small chance of it turning cancerous.
It is a autosomal dominant inheritance disease which means 50% of the offspring of the affected person will inherit the disease. It is caused by mutation in the Serine Threonine Kinase tumor-suppressor gene.
The pigmented spots typically appear on the lips, mouth, gums, eyes, hands, feet, fingers, toes and genital-anal areas. The gastrointestinal polyps seldom occur in childhood. Complications include abdomen pain, bleeding, intussusception, intestinal obstruction and increased chance of turning cancerous. Patients affected not only have increased risk of colorectal cancer, other cancers like lung, breast, esophagus, testicles, ovary, pancreas and uterus may also be involved.
Diagnosis includes clinical presentation and endoscopic examination of polyps. There is no specific treatment. Surveillance for cancerous development is crucial. Intestinal polyps should be removed. Cancers are usually treated surgically or with adjuvant chemotherapy and radiotherapy. Involved family members can go for genetic testing.
Melanoma is a cancerous mole. Main modality of treatment is surgical removal. It will be discussed further here.
Risk factors for melanoma (cancerous moles)
1.Number of acquired moles: If patients have > 100 moles or Caucasians with > 40 moles by age 50, there is an increased risk of having a cancerous mole.
2.Dysplastic Nevi as discussed earlier is sometimes pre-cancerous moles.
3.Personal history of melanoma is also a risk factor.
4.Prolonged and excessive sun exposure as well as severe sunburns predispose to cancerous moles.
5.Large congenital nevi larger than 20 cm has increased risk of melanoma.
6.Certain genetic constitution may predispose one to melanoma.
Features of melanoma
Certain features distinguish a melanoma from a normal mole. If the mole changes in shape, size, and color and if patient has symptoms of itch or bleeds then the patient should seek a dermatologist advice. The appearance of a mole suspicious of a cancerous melanoma can be remembered by mnemonic ABCDE. The suspicious cancerous melanoma will be Asymmetric, Borders of mole are irregular, Color is variegated, Diameter (increases in size) and Erosion/elevation (ulcer forms).