Nearly all people with Tuberous Sclerosis will have at least one of the signs of TSC on their skin. For many people these are one of the first signs of TSC. Signs of TSC on the skin are important for diagnosis of TSC as they comprise many of the minor and major features in the diagnostic criteria.
Although the signs of TSC on the skin are benign (non-cancerous) they can be a major concern for individuals with TSC and impact on self-esteem and social interactions.
A term used by health professionals for things to do with the skin is ‘dermatology’ and skin doctors are called dermatologists. Some treatments for the TSC skin signs can also be performed by a cosmetic surgeon.
Signs and Symptoms
Some TSC skin signs appear at birth, others develop later in childhood or even adulthood. Currently there is no way to predict how many TSC skin signs will develop during childhood, but they tend to remain stable during adulthood.
The skin signs of TSC are highly variable from one individual with TSC to the next, even within the same family. Some people have TSC skin signs that are hardly noticeable. Others may have larger TSC skin signs that cause pain or bleed easily.
The different signs of TSC on the skin are:
The white spots in TSC are called hypomelanotic macules (hypo, meaning less than normal; melanotic, referring to melanin or the pigment of skin). They are also referred to as ash-leaf spots when they are oval at one end and pointed at the other, resembling the leaf of the European mountain ash tree.
Almost all people with TSC have them; they may be present at birth and usually persist throughout life. They are often difficult to see in a newborn or in an individual with very pale skin. An ultraviolet light, called a Wood’s lamp, is used to help see them.
Hypomelanotic macules are usually the size of a thumbprint or larger. They can be scattered anywhere on the skin, but they are most common on the trunk, limbs and buttocks. If they are on the scalp, eyebrows or eyelashes they can cause a white patch of hair (poliosis).
An individual with TSC may have any number of white spots, from 1 to more than 100. In order to be useful for making a diagnosis, the individual should have 3 or more hypomelanotic macules. This is one of the major features in the diagnostic criteria for TSC (link). Fewer than 3 hypomelanotic macules do not count towards making a diagnosis because one or two hypomelanotic macules are common in the general population, occurring in about 5% of children. Sometimes numerous small macules may be present in TSC (especially on the arms and legs). These may resemble confetti, and these are a minor criterion for diagnosis.
Angiofibromas are found in a majority of individuals with TSC over 5 years of age. These small bumps are usually scattered on the face, especially on the nose and cheeks, and sometimes on the forehead, eyelids, and chin. They are often clustered in the grooves at the side of the nose. Angiofibromas are typically smaller than a peppercorn, but they can grow larger. They may be skin-colored, pink, or red. In darker skinned individuals they may be reddish brown or dark brown. People with TSC usually have several angiofibromas, and some individuals have hundreds.
Angiofibromas are overgrowths of normal skin cells, and they do not become cancers. They were originally called adenoma sebaceum because they were thought to be derived from sebaceous glands (grease glands) in the skin. However they have been shown in fact to be angiofibromas, composed of blood vessels (‘angio’) and fibrous tissue (‘fibroma’).
Angiofibromas may begin in early childhood as flat red “spots” on the face, or a diffuse redness of the cheeks. The redness is due to increased blood vessels in the skin. They later become elevated due to increased amounts of fibrous tissue. Fibrous tissue is similar to what is found in a scar.
The forehead fibrous plaque is similar to an angiofibroma but is a larger area of elevated pink skin. They are usually found on the forehead, but fibrous plaques may also occur on the cheeks or scalp. Another term used for these plaques is fibrous facial plaques.
Some individuals with TSC are born with these; some develop them gradually over the first 10 years of life. After that they generally stay the same size but they can become thicker over time.
The shagreen patch is an area of thickened, elevated pebbly skin usually found on the lower back. Some people say they look like orange peel. Sometimes the shagreen patch is located elsewhere on the back or on the buttocks or upper thighs. It consists of an excess amount of fibrous tissue, similar to that found in scars.
Only about half of people with TSC have a shagreen patch and some people have many. In most people they are hidden by clothing and do not cause any problems.
These are fibrous growths that are located around the fingernails or toenails . Nail lesions can be called subungual fibromas when they arise from beneath the nail and periungual fibromas when they arise from around the nail.
They do not normally affect children with TSC but often start to grow later in life. They eventually affect most adults with TSC and they can range in size from being barely detectable to almost 1 centimetre.
Ungual fibromas may distort the nail by causing a groove or by pushing the nail up from the nail bed causing infection and bleeding. On the toes, ungual fibromas can be painful when wearing shoes.
There are a number of other signs of TSC that sometimes appear on the skin. Because many of these are very common in the population and they do not help doctors to diagnose TSC. Most of these will also not cause any medical symptoms.
Skin tags in TSC may be skin coloured or darker. They are common around the head and neck, armpits and groin.
Café au Lait spots, which are flat brown marks, are also seen in individuals with TSC.
The negative effect of angiofibromas on social interactions and self-esteem can be a major concern of an individual with TSC, even when they are also living with more medically significant symptoms such as epilepsy, kidney tumours and lung problems.
Angiofibromas may also be treated for several medical reasons. The most common is bleeding and treatment lessens the likelihood of repeated episodes of bleeding.
A variety of surgical approaches can be used to treat angiofibromas, including the use of lasers. There are also new medicines being trialed that show positive results.
Many TSC families in Australia have said that daily sunscreen is an important part of taking care of their children’s skin.
Surgical treatment for angiofibromas usually involves the use of a laser
The main methods are:
- Flat and red spots in young children can be treated with a vascular (blood vessel) laser. This is a laser that is designed to destroy blood vessels with low risk of scarring. This is done because it is thought that early treatment decreases the development of raised lesions later in life.
- Raised and red agiofibromas in older children and adults may require the use of both a CO2 and vascular lasers either at the same time, or one after the other.
- Raised lesions that are the same colour as the person’s skin may require the use of a CO2 laser.
All laser treatments are uncomfortable and will require local or general anesthetic.
Treatment with the CO2 laser (or similar lasers, called ablative lasers) is usually performed as day surgery in a hospital or a day surgery center. Clear and detailed pre- and post-operative instructions are very important, and careful attention to care of the wounds is necessary for optimal healing. It is important that that the doctor is experienced in treating people with TSC and that all of these issues are discussed with the individual with TSC and/or their carers.
The decision when to treat can be a difficult one. If significant symptoms are present in early childhood, treatment may be carried out, but in the knowledge that further lesions may develop or enlarge, and require treatment later. Treatments later in life are more likely to be permanent, but the need for further treatment later cannot be excluded. Sometimes a range of different lasers may be needed to get the best results. The advantages and disadvantages of laser treatment have to be considered in each individual case.
The bio-chemical causes of angiofibromas are similar to other types of tumours in TSC. During clinical trials into new medicines for brain, kidney and lung tumours in TSC, many people with TSC also noticed their angiofibromas becoming less red and less raised.
These new medicines are called mTOR inihibitors and include:
- Sirolimus, which is also called Rapamycin
- Everolimus, which is also called Afinitor
A small number of doctors are already using these medicines to treat angiofibromas in TSC. This is on a case-by-case basis and the cost is not covered by the Australian or New Zealand government.
ATSS successfully raised over $200,000 during 2009-2011 to fund a clinical trial into these medicines. The trial team at Sydney Children’s Hospital are part of a larger study called the TREATMENT trial, which is the first randomized controlled trial for the use of these medicines for angiofibromas.
If the trial shows that the cream is successful, ATSS will advocate for topical Rapamycin to be approved by the Therapeutic Goods Administration (TGA) and subsequently included in the pharmaceutical benefits scheme (PBS). This is the way that we will ensure this treatment is made accessible and affordable for all TSC affected people that require the cream. A similar process can be followed in New Zealand. The TREATMENT trial will provide the clinical trial evidence required for this approval process. It will also help to confirm the strength of the cream and the way it should be used and give doctors and families more evidence of its safety.
During the trial and the lengthy approvals process that might follow, there is still a way for TSC families to access the treatment. You need to discuss this treatment option with a dermatologist who will assess each individual case. This is called using the medicine “off-label” and may also be subject to approval processes. The team at the Princess Margaret Hospital for Children in Perth have published their experience with the cream and their recipe. You may like to refer your dermatologist to this scientific journal article:
Foster, R. S., Bint, L. J. and Halbert, A. R. (2012), Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: A pilot study of four patients. Australasian Journal of Dermatology, 53: 52–56
This article suggests an annual cost of approximately $3000AUD. Because there is no centralized manufacturer and the medicine is not yet on the PBS, funding arrangements will differ between health services so you should also discuss this with your doctor. Please contact ATSS if you need any more information.
For most people with TSC, the other skin signs if TSC do not cause any discomfort and do not require treatment. In some individuals with TSC this is not the case. Available treatments include:
- If ungal fibromas cause bleeding or pain, they can be removed with surgery. This may be combined with a CO2 laser to maximize effectiveness while limiting scarring and damage to the nail. Ungual fibromas may recur even after this treatment.
- Treatments for hypomelanotic macules attempt to conceal the spots and do not permanently restore the normal skin color. One treatment option is to use a sunless tanning lotion (“fake tan”) that contains dihydroxyacetone (DHA) as the active ingredient. These work by temporarily dyeing the top layers of the skin. Another option is to apply concealing creams that are matched to the person’s skin color.
- Forehead plaques can be flattened by laser vaporisation or may require removal by plastic surgery.
- Shagreen patches can be shaved flat using a sharp knife called a dermatome or flattened by dermabrasion or laserbrasion.
Treatment of angiofibromas with laser is covered under Medicare and should not have any out of pocket expenses if performed in a public hospital.
It may be difficult to find a CO2 laser in a public children’s hospital. Some TSC families will go to a private dermatologist or cosmetic surgeon for this reason. In this situation, there may be out of pocket costs for families including day surgery fees.
Prepared by: Clare Stuart, The Australasian Tuberous Sclerosis Society
Reviewed by: Dr Orli Wargon, Dermatologist, Sydney Children’s Hospital
- Kwiatkowski D.J., Whittemore V.H. & Thiele E.A. (2010) Tuberous Sclerosis Complex: Genes, Clinical Features, and Therapeutics. Weinheim: Wiley-Blackwell
- Skin (Dermatological) Manifestations in TSC, Tuberous Sclerosis Alliance, viewed 30th March 2012, http://tsalliance.org/pages.aspx?content=601.
- Dermatological Features of TSC And Their Treatment, Tuberous Sclerosis Association (UK), viewed 30th March 2012, http://www.tuberous-sclerosis.org/publications/pub_the_dermatological_features_of_tsc_and_their_treatment.pdf