Background
The full name for PUVA treatment is Oral Psoralen Photochemotherapy
and this term describes the treatment. It consists of taking a
medication called psoralen (pronounced soralen with a silent P)
by mouth and subsequent exposure to light (hence photo). The light
and the chemical then interact to produce a therapeutic effect
(hence photochemotherapy). The light involved in the interaction
is a particular type of ultraviolet light called UVA. The acronym
PUVA is of course derived from the P in psoralen and UVA.
PUVA treatment is both old and new. Psoralens are naturally occurring
chemicals found in the seeds of various plants. For more than
2,000 years herbal teas prepared from these seeds have been used
in combination with sunlight, which contains UVA light, to treat
skin disorders in India and the Middle East. However, the modern
use of PUVA treatment only dates back about thirty years and it
resulted from two important developments. First, pure psoralen
was isolated from plants in 1947 and this permitted the use of
precise doses of the medication.
The pure psoralen was introduced in the USA in 1952 for treatment
of a skin disorder called vitiligo and in combination with sunlight,
it was a moderately successful treatment. The second major advance
was the development of a high-intensity source of UVA radiation
at Harvard in 1974. This permitted giving short and precise doses
of UVA light so that sunlight, an unpredictable and unreliable
source of UVA light, has been almost entirely eliminated in modern
PUVA treatment.
Development of a precise form of PUVA treatment resulted in an
explosion of interest in determining how the treatment works and
what disorders of the skin might benefit from the therapy. Several
thousand articles have now been published in the scientific literature
as a result of study of these questions in many centers throughout
the world.
All the answers are not yet known but PUVA therapy is beneficial
in more than twenty different diseases and it appears to act via
at least three different mechanisms:
Prevention of Rapid
Multiplication of Skin Cells
In disease such as psoriasis, cells in the most superficial layer
(the epidermis) of the skin are multiplying at many times the
normal rate. PUVA treatment inhibits this multiplication by shutting
down the production of DNA in cells.
Killing of Cells in Skin
A number of skin disorders appear to be produced by cells from
the immune (defense) system of the body. These cells are either
multiplying too rapidly or behaving in an abnormal manner. PUVA
treatment selectively kills off these cells and fortunately, it
can do this without producing any clinical evidence of harm to
our normal immunity. Eczema, lichen planus, alopecia and mycosis
fungoides, are a few of the diseases that appear to respond to
PUVA therapy via this mechanism.
Production of Increased Resistance to
Sunlight
PUVA therapy induces increased pigmentation in the skin and also
increase the thick-ness of the epidermis. Both these effects diminish
sensitivity to sunlight by decreasing the amount of ultraviolet
light entering the deeper layers of the skin. This appears to
be the mechanism whereby PUVA treatment is beneficial in disorders
characterized by heightened sensitivity to sunlight, such as polymorphous
light eruption and solar urticaria. The response of vitiligo to
PUVA therapy is also partly due to this effect, but in addition
PUVA is probably also affecting the function of immune cells in
this disorder.
Let us now turn to the basic elements of the treatment before
discussing the actual treatment process.
UVA Light
Sunlight consists of a spectrum of so-called electromagnetic radiation
ranging from cosmic rays to radiowaves.
Ultraviolet light consists of wavelengths shorter than visible
light and is called ultraviolet because it begins next to the
violet end of visible light. Visible light is light that we can
see and it provides us with vision. Ultraviolet light is invisible
to the human eye.
Ultraviolet light is divided into UVA, UVB and UVC. UCV light
is only of interest to cosmonauts since it is absorbed by ozone
in the atmosphere and does not reach the surface of the earth.
UVB light does reach earth and this waveband is responsible for
producing a sunburn and a suntan when we are exposed to sunlight.
Sunlamps mainly emit UVB light.
UVA light is composed of the longest wavelengths in the ultraviolet
spectrum. Under normal conditions UVA light from sunlight does
not produce any noticeable change in skin. However, UVA light
does have the property of being able to react with light-activated
chemicals in the skin, so-called photosensitizing agents. These
chemicals include some antibiotics, tranquilizers, diuretics and
psoralens. If these chemicals are present in our skin when we
are exposed to UVA light, redness like sunburn, and even blistering
can occur.
Psoralens
These are a family of photosensitizing compounds that are activated
by UVA light. Thus, if they are present in skin at the time of
exposure to UVA light, they greatly increase the effect of the
light on skin. This increased sensitivity is the key to the beneficial
effect of PUVA treatment of skin disorders.
It is important to emphasize that psoralens alone have no effect
on the skin or skin disorders.
Likewise, UVA light alone produces no noticeable change in the
skin or beneficial effect on skin disorders.
The psoralen most frequently used in treatment has the chemical
name of methoxsalen and the trade names of Oxsoralen Ultra and
8-MOP.
The Treatment
The photochemotherapy process involves the ingestion of psoralen
and then exposure to UVA light one hour later. The dose of psoralen
you take is held constant and is determined by your weight. The
interval between taking psoralen and being exposed to light is
also held constant because peak levels of psoralen in the skin
are usually reached between one and two hours after ingestion.
For example, if you take your Oxsoralen capsules at 11am, you
should aim to be treated at 12 noon and certainly before 1pm.
Take the capsules with water or low-fat milk and avoid eating
until after the treatment.
The variable in the treatment is the dose of UVA light you are
given. The initial dose is low and determined by either your past
history of sunburning and suntanning or by testing your response
to PUVA. The dose of UVA light is gradually increased in subsequent
treatment as your tolerance to the treatment increases.
The dose of UVA light is measured in joules per square centimeter,
which is an amount of energy, and this is translated into a certain
number of minutes of treatment. The output of the treatment units
varies over time and different units emit different amounts of
energy. Therefore, even if your dose of UVA light is constant,
the time for your treatment will vary from day to day. Treatments
will be required 2-4 times each week until your skin disease has
cleared. Less frequent treatment is necessary to maintain a clear
state.
A Few Helpful Hints
• If your skin disorder involves the scalp you have to help
the light reach it. Short hair is obviously one answer. Hair bands
and bobby pins should be used to hold hair off the face and neck.
• Nail polish may be worn even if the fingernails and toenails
are involved by your skin disorder. However, if the disorder affects
the skin under the nail, do not paint your nails.
• Scales on the skin tends to block UVA light from penetrating.
Try to remove as much scale as possible before each treatment
by soaking or applying an emollient.
• Regular, punctual treatments are the key to success with
PUVA therapy. Missed treatments simply delay a good response and
sometime lead to failure of therapy. If you are having problems
keeping appointments, discuss the matter with the physician so
a fresh approach can be developed.
Conclusion
PUVA therapy has been the subject of more investigation than almost
any other treatment used in dermatology, or for that matter, any
treatment used in any field of medicine. The reason for this is
that the treatment was largely developed in its present form in
one center, Massachusetts General Hospital, and people there had
the foresight to start a prospective study of the effects of the
treatment over a long period. This study involves 1,600 patients
treated with PUVA therapy, who were followed with yearly reports
for nearly twenty years. This study has provided us with a wealth
of precise information on the effect of the treatment.
At this point in time, we can conclude from all this investigation
that PUVA therapy continues to be successful, people do not become
refractory to the treatment and the adverse effects are infrequent,
well-characterized and controllable.
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