For many people with CNS, intensive blue light phototherapy is the only mechanism that maintains them free of brain damage until a cure is obtained. Effective phototherapy is absolutely critical to both the health and lifestyle of these CNS people. This section deals with the theoretical and practical aspects of phototherapy treatment.
G1. WHAT IS PHOTOTHERAPY?
Phototherapy literally means “treatment with light”. The benefits of natural light for a wide range of conditions both physical and psychological have been well known for a long time. The exact mechanisms by which the various benefits are obtained are being progressively understood. While the benefits are first noticed from natural sunlight, research usually shows the benefit is derived from a particular component of the colour spectrum that makes up white light. This has allowed physicists to artificially produce the exact wavelength of light that provides the benefits for each condition.
In the late 1950s, a nurse in a rural United Kingdom hospital first observed the value of sunlight in alleviating jaundice in newborn babies. Subsequent study showed that the benefit came from the blue component of the natural sunlight. Blue light phototherapy is now frequently used to assist bilirubin removal in many newborn infants who are jaundiced during their first few days of life
The use of blue light in the treatment of CNS was first reported in the early 1970’s. Prior to this most CNS children died in infancy. CNS people require blue light to be much more intensive than that used for normal newborn infants.
G2. HOW DOES BLUE LIGHT REDUCE BILIRUBIN?
When blue light contacts the blood vessels and tissue close to the skin, bilirubin undergoes a number of changes. For bilirubin removal, the most significant are the formation of photo-bilirubin products that have identical chemical formulae to normal bilirubin, but have different three-dimensional structures (isomers). Because of these structural differences some of these products are partially soluble in water. Once transported from the skin to the liver by the blood, they can transfer to the water-based bile and be removed from the body.
This process is completely separate from the normal system of bilirubin removal and is much less efficient. Its capacity to control rapid increases in bilirubin is much less than the normal enzyme process. However, at present, it is the only process available to protect many people with CNS from brain damaging kernicterus.
Since it does not use the mechanism of adding a sugar molecule to make the bilirubin water-soluble, this mechanism does not produce significant amounts of conjugated bilirubin in the bile.
G3. HOW VALUABLE IS SUNLIGHT?
About one seventh of visible light energy from the sun is in the blue colour range. Because of this, the sun is an excellent, but highly variable, source of blue light. For example, on a sunny summer’s day in Sydney, Australia, direct sunlight provides blue light energy levels comparable with the most intensive phototherapy equipment. Even on a relatively dull cloudy day, blue light energy per area of skin (irradiance) received from the sun is normally greater than that delivered by the phototherapy given to newborn babies.
Even in normal day-to-day living, CNS people get a useful contribution to bilirubin removal by sunlight impacting the skin areas normally exposed, such as the head, neck, arms and legs. In contrast, when weather conditions are such that little sunlight is received, there are marked increases in blood bilirubin, unless artificial phototherapy treatment is increased. For people with less serious forms of CNS, exposure of most skin to summer sun can significantly reduce or even eliminate the need for phototherapy. Even for CNS Type 1 people, exposure to summer sun can provide a substantial part of daily phototherapy needs.
Although an excellent source of blue light phototherapy, sunlight has several disadvantages. Firstly, it is highly variable in the irradiance delivered not only from winter to summer, but even within one day. Secondly, its value depends on getting as much skin as possible exposed. Although modesty considerations can be coped with, sunlight phototherapy requires that the air temperature be such that large skin areas can be exposed for significant periods without the person being cold.
Thirdly, sunlight is necessarily accompanied by radiation in the ultra-violet (UV) range. Unless precautions are taken, substantial exposure to UV can cause serious skin conditions. Sunscreens can provide UV protection, but some sunscreens also prevent benefits from blue light being obtained (See Question G4).
In summary, sunlight is a highly effective source of blue light phototherapy under certain conditions. Understanding and optimising these conditions can be very valuable.
G4. SHOULD SUNSCREENS BE USED WHEN USING SUNLIGHT?
The purpose of sunscreens is to protect the skin from damaging UV rays. The sunnier the climate the more the general population needs sunscreens. People with CNS also need protection from UV in sunlight.
Many sunscreens are suitable for CNS people. They utilise organic chemicals that absorb ultra-violet light, but allow normal visible light (including blue light) to reach the skin.
Some sunscreens provide protection from UV by blocking all wavelengths, including blue light. These use opaque pigments such as Zinc Oxide or Titanium Dioxide. These products not only ensure that the skin receives no phototherapy benefit from sunlight, but residual pigment can continue to block the blue light from phototherapy equipment. Pigmented sunscreens should not be used for people with CNS.
G5. WHAT ARE THE ARTIFICIAL SOURCES OF BLUE LIGHT?
It is possible to obtain blue light by using a white light source of which blue light makes up about one seventh of the radiation. Such an approach is used in Biliblankets used for small babies. The use of white light is very energy inefficient. Specially designed fluorescent tubes are far more effective.
The widespread use of phototherapy for newborn babies has ensured that there has been significant commercial development of artificial sources of blue light in the required wavelength range. Ideally the spectrum of light produced should have maximum energy at a wavelength of about 450 nanometers and virtually no energy below 400 nanometers (into the UV region) and above 520 nanometers (because it is less effective in altering bilirubin).
Netherlands-based Philips Lighting has been in the forefront of these developments and Philips’ special fluorescent tube products are commonly used in the USA, Europe and Australia. These tubes are valuable because they are specially developed to provide the best wavelength peak and range, have high-energy efficiency and relatively low heat output.
In the USA, Philips special blue BB tubes are used for CNS people, most commonly of four feet (1200mm) length. In Europe and Australia, Philips TL 52 tubes have proved to be very effective and to have a low tanning effect. In Australia, tubes of 2 feet (600mm) length are used. Both 2 feet and 4 feet sizes are available in Europe. In the Netherlands specially made 5 feet (1500mm) tubes have also been extensively used.
The light output of fluorescent tubes decreases significantly with hours of use. One figure quoted in the literature is that for BB and TL 52 tubes, light energy falls by about 35% of original after about 1200 running hours of use. Using fans to prevent overheating helps to prolong their effective life. Philips has indicated that, with good fan cooling, the deterioration should be significantly less than 35%.
The monitoring of light output using appropriate light meters is highly recommended. Some people routinely replace tubes at the start of winter and find that it is acceptable to have slightly lower output during summer months when CNS people should get phototherapy benefits from the sun.
Blue Light Emitting Diodes (LEDs) have the potential to produce narrow wavelength blue light with good energy efficiency and relatively low heat output. They also provide greater flexibility in the design of phototherapy devices since they do not have the limitation of a fixed tube length. Reference 5:Question B2 describes an “underneath” phototherapy device that utilises LEDs. There is substantial development taking place in the design and use of LEDs including the introduction of LEDs into textiles. Some of these developments are promising for possible use in portable phototherapy systems.
In mid 2006, fluorescent tubes remain the most common light source for home use. LEDs are still relatively expensive, but the costs are reducing.
G6. WHAT DETERMINES THE EFFECTIVENESS OF PHOTOTHERAPY?
The effectiveness of phototherapy in the treatment of CNS depends on a large number of factors. Some are subject specific, including:
More generally others factors include:
A good understanding of these factors and their interaction is vital to the effective day-to-day management of CNS, a task that normally falls to parents of a Crigler Najjar child.
In designing phototherapy equipment and its environment, and in managing phototherapy, it is very important to consider the relative importance of each factor. Striving for the ultimate in effectiveness of one factor may not be beneficial if it reduces the impact of another factor.
G7. HOW FAR SHOULD THE LIGHT SOURCE BE FROM THE PATIENTS BODY?
The energy falling on a given area (irradiance) depends on the distance from the light source. In phototherapy systems irradiance will be approximately halved if the distance from the light source is doubled. If the light source is farther from the user more of the light energy is wasted.
Subject to user comfort, it is important to get the source of light as close as possible to the CNS person’s body. Light that initially misses the patient may be reflected back using mirrors or other reflecting surfaces, albeit at a significantly lower irradiance.
With phototherapy lights above the bed (overhead lights), a person must sleep naked with enough room to turn over in sleep. For this reason lights for a small child are normally located about 8-10 inches (20 to 25 cms) above the sleeper. As a child grows to adolescence this distance needs to be increase to allow the person to comfortably turnover. For this reason overhead systems have difficulty providing the irradiance that can be provided by the underneath system or a daytime light box.
Some phototherapy equipment uses a light source under the sleeping user with the person lying on a netting bed that allows light to pass through. Using these systems the light source can be within 10 centimetres (4 inches) of the skin. The netting typically absorbs about 15% of the light energy, but for many, the advantages of being able to get the light source close to the body and the ability to sleep while covered outweighs this disadvantage.
The light box used for day phototherapy has the sources of light very close (less than 2 inches or 5 cms) from all the skin surfaces. The irradiance is substantially higher than in overhead systems in particular.
G8. HOW MUCH SKIN SHOULD BE EXPOSED?
The light energy is only valuable if it falls on skin. Bare skin must be exposed to the light to the maximum extent possible. The effectiveness of phototherapy or sunlight is directly proportional to the area of skin exposed to the light.
While the use of nappies (diapers) on small children has advantages, they do reduce the light access to the skin in an area where there is a significant amount of tissue containing bilirubin. Parents must make their own judgement about this depending on the ease with which bilirubin can be held to safe levels.
Night phototherapy with lights either above or below the user (referred to as “single-sided phototherapy”) allows only about 35% of the skin to be exposed to intense irradiance. Using some adjacent reflecting surfaces light may allow additional skin to receive radiation, but of low intensity.
Day phototherapy using a light box lined with acrylic mirrors allows the whole surface of the body, except the head, to be exposed to high levels of irradiance. The skin area exposed to intense irradiance is 2 to 2.5 times the area exposed with night phototherapy.
G9. SHOULD SAFETY SCREENS BE USED?
Yes. For safety reasons and heat insulation there must be a protective screen between fluorescent tubes and the user. The screen must allow maximum transmission of blue light energy, but should absorb as much as possible of any UV energy produced.
Plexiglas makes a clear acrylic sheet that claims to filter out more than 95 percent of UV radiation. Recent tests with the TL52 tube show that the amount of UV radiation produced by this tube is extremely low even in comparison with normal dull sunlight.
G10. WHAT PHOTOTHERAPY EQUIPMENT IS AVAILABLE?
Hospitals normally have available equipment to provide low-level phototherapy to many newborns until their livers begin functioning. Commonly a family with a CNS newborn may be provided with such equipment to use at home for say 20 hours per day. This, at best, is a short-term measure, even for the less serious cases.
Because of the rarity of the condition there has been no incentive for the commercial development of intensive phototherapy devices. In the Netherlands and elsewhere, equipment sold for sun tanning has been modified for use, using the correct blue fluorescent tubes.
In many cases family members or friends have made their own phototherapy equipment. This has often been with the advice of a small number of people internationally who have developed some experience at building such equipment.
G11. HOW MANY HOURS OF PHOTOTHERAPY ARE REQUIRED?
In the past some people have designated the seriousness of a CNS person’s condition by quoting the number of hours of phototherapy required. This is an entirely unsatisfactory measure.
The hours of phototherapy required depends on many factors other than the seriousness of the genetic defect. These include the age of the CNS person, the local climate and the type and effectiveness of phototherapy. Where good sunlight is obtained phototherapy hours can be markedly reduced. Double-sided phototherapy will require much less time than single-sided phototherapy. Using new fluorescent tubes will require much less phototherapy time than tubes that have degenerated by 35%.
Most people have phototherapy while asleep. With the light source either above or below the sleeper, only about 35% of the body surface is receiving intensive phototherapy at any one time. This is a major limitation on the effectiveness of night phototherapy and the ability to minimise phototherapy time required to maintain control of serum bilirubin.
Type 1 children are commonly reported to need 12 hours of night phototherapy each day. If the bilirubin level is to be held constant, the amount of phototherapy required is reported to need to increase with increasing age through childhood, adolescence and into adulthood. Reasons put forward for this include changes in skin and changes in the ratio of body surface area to body mass.
Young children may sleep 12 hours daily, but as people grow to adolescence and adulthood, hours of sleep progressively reduce to about 8 hours. As people with the most serious forms of CNS grow older, phototherapy while asleep may provide insufficient time to maintain bilirubin at relatively safe levels, particularly during winter. Increasing phototherapy time beyond normal sleeping hours has a major impact on the person’s lifestyle. Unless there are substantial improvements to the phototherapy for these people, the lifestyle impacts may be unacceptable and for many, a liver transplant may well become the preferred course of action.
For people with less serious CNS, the night phototherapy time required may be substantially lower. Even in these circumstances children requiring phototherapy normally would have at least 4-6 hours per night, particularly during winter.
As an alternative to having phototherapy while asleep, a light box has been developed that can provide very intensive phototherapy to nearly all skin surfaces while the user is sitting up, awake and able to undertake some activities. (See Question B2: Reference 6) Irradiance is higher and all skin surfaces other than the head receive intensive blue light at the same time. Phototherapy time required is about one quarter of that needed for overhead phototherapy.
In 1995 a CNS person, now aged 14, ceased 6 hours per night phototherapy and has used only the light box during daytime for an average of one hour per day, even during winter. Serum bilirubin has remained stable at relatively safe levels of about 15 mg/dL (256 umol/L). In another case a CNS lady successfully used innovative day phototherapy equipment during her pregnancy instead of her normal phenobarbital.
For the most serious CNS cases the light box has the potential to provide adequate day phototherapy in about 3 hours during winter and less in summer. For some, this may involve unacceptable limitations on daily life. In these cases a combination of day and night phototherapy may provide an acceptable alternative, but this involves the cost of acquiring the day equipment in addition to existing night equipment.
G12. WHAT IS PHOTOTHERAPY’S IMPACT ON LIFE STYLE?
Phototherapy treatment normally has a profound impact on the life of a child and its parents. A dedicated and disciplined caring approach is essential.
The design of phototherapy equipment and the room in which it is used must not only try to provide the best phototherapy, but must take into account the personality of the CNS person and carers and the impact on normal life. The most efficient equipment will have little value if the person with CNS finds it too uncomfortable or, for other reasons, cannot or will not, use it.
For overhead night phototherapy, the need to keep the CNS person warm (by keeping the room very warm), the difficulty in sleeping in the presence of intense light and the feeling of insecurity from sleeping virtually naked, are some of the problems involved.
While providing 12 hours of phototherapy each day to a sleeping baby may not inhibit the child’s life too much, as people get older they tend to sleep less and thus phototherapy tends to intrude further into daily waking life. By late teens this intrusion can be substantial.
When day phototherapy is used, most of these problems are reduced; however there can still be a significant impact on the life of an active child. For pre-teen children, two hours of day phototherapy (albeit in two or more sessions) may be the upper acceptable limit. Because people can eat, read, watch television, etc. during light box phototherapy, adults may be able to tolerate longer treatment times.
For many CNS adults who do not wish to sleep alone, night phototherapy is unacceptable and day phototherapy is the only alternative to having a liver transplant.
For most CNS people phototherapy equipment is in the home and is not readily portable. Travel away from home may be difficult and this may place limitations on the CNS person and their family as a whole. There have been several attempts to build equipment that is portable (See Reference 5: Question B2) and these are continuing as technology improves and LED costs decrease.
G13. WHAT ARE THE POSSIBLE SIDE EFFECTS OF PHOTOTHERAPY?
In the early days of phototherapy there was expressed some concern that blue light might damage the retina of the eyes. Certainly very intensive point sources of blue light such as those used in welding can cause damage and this is well documented in the literature of industrial medicine. Phototherapy lights are not point sources of light and the irradiance is much lower than that of a welding flash.
Because people who use night phototherapy are asleep with their eyes closed, any possible impact would be greatly reduced. Masks can also be worn. Where light box, day phototherapy is used the person’s head is outside the box from which very little light is allowed to escape.
In a study reported in Reference 1, Question B2 no adverse effects were detected in the vision of long-term phototherapy users.
Because of the short phototherapy time involved, and because they can easily eat, drink and eliminate waste, people using day phototherapy minimise the suggested cause of these problems. Appropriate tests have shown no such problems for the only child who has been using day phototherapy since aged 4 and is now aged 14.