PUVA-therapy for the treatment of psoriasis, alopecia, vitiligo

Physiotherapy is considered one of the most effective and relatively safe methods of treating many diseases. There is a wide variety of physiotherapy procedures that affect the human body in different ways. An interesting direction of physiotherapy is phototherapy, in which the therapeutic effect on the human body is carried out with the help of dosed ultraviolet radiation. If ultraviolet radiation is combined with the use of special photoactive drugs called psoralens (PUVA therapy), it is possible to achieve great success in the treatment of many intractable dermatological diseases.

What is PUVA therapy?

So, PUVA-therapy is one of the most effective methods of physiotherapy in pathologies that damage different layers of the skin. In this case, exposure to ultraviolet rays is used to activate photoactive agents.

The unusual name of the method is really easy to understand and clear. The word "PUVA" consists of 3 parts. In this case, П denotes the photoactive component of psoralen, the lettering of the UV signifies ultraviolet rays, the last letter of the abbreviation - the letter "A" - indicates the long-wave part of the spectrum of the applied light rays (320-400 nm).

Taking only psoralens does not have any effect on the skin of a person. After all, to activate photosensitizers, exposure to light from a certain spectrum is necessary. In this case, UV radiation, characterized by a long wavelength.

Under the influence of UV radiation, the photosensitizers interact with the DNA molecules of the epidermal cells, as a result of which the synthesis of DNA in cells is reduced. This effect only changes the structure of damaged cells, but does not affect their function. The emergence of cross-linking psoralenov and DNA, reducing the production of proteins and nucleic acids, thereby slowing the pathological growth of cells, and hence the further development of the disease.

Under the action of photosensitizers, active forms of oxygen form which damage the cell membranes and stimulate metabolic processes involving arachidonic acid. They also participate in chemical reactions aimed at suppressing excessive keratinization (keratinization of cells), resulting in inflammation, itching and flaking, and the skin is again soft and elastic without seals and crusts.

The effectiveness of the method is confirmed by many positive responses, which for a more than 20-year period of the existence of the methodology has accumulated a great many. PUVA therapy has a stronger therapeutic effect compared to conventional phototherapy without the use of photosensitizers.

Indications for the procedure

The therapeutic technique of PUVA therapy has found wide application in dermatology. With its help, even those skin diseases that are not amenable to conventional drug treatment are treated.

Most often PUVA-therapy is used to treat the following pathologies:

• psoriasis,
• vitiligo,
• atopic dermatitis,
• alopecia (alopecia),
• scleroderma,
• fungoid mycosis,
• ichthyosis,
• Bowen's disease,
• eczema,
• parapsoriasis,
• basal cell carcinoma of the skin,
• lymphoma,
• papillomas,
• Vulgar acne and other pathologies characterized by pathological changes in skin cells.

Therapy using this technique can be prescribed at any stage of the development of the disease.

PUVA therapy is also used to combat the effects of photoaging of the skin of the hands and face. This improves the condition of the skin and increases its elasticity by stimulating the production of collagen.

PUVA-therapy for various pathologies

The PUVA technique was originally developed to combat an almost incurable autoimmune pathology called psoriasis, characterized by the appearance on the body of scaly, itchy areas of the cornified skin, the cause of which was the pathologically rapid growth of cells. Seeing the good effectiveness of the method on the example of psoriasis, doctors began to apply it for the treatment of other skin diseases.

PUVA-therapy is considered indispensable for the treatment of psoriasis, characterized by extensive localization or severe course. This is a pathology in which the total area affected by the disease of the skin is from 20 to 30% of the total area of the skin.

PUVA therapy shows sufficient effectiveness in such severe forms of pathology as the common plaque form, exudative, erythrodermal and pustular psoriasis, as well as in the drop-shaped and palmar-plantar type of psoriasis, which, because of its localization, causes the greatest discomfort in patients. It is used as the last hope with the ineffectiveness of other methods of fighting the disease.

Promising results show PUVA therapy and with  alopecia. The idea to apply this method for the therapy of baldness has arisen in connection with the moment that catches eye when observing such patients. Patients, for a short time under the influence of sunlight, hair growth was more active than those who avoided the open sun. However, there were cases and exacerbations of the disease in the summer, but it was worth a try.

Treatment of mild and moderate severity is done locally, and in severe pathology a general approach is required with irradiation of the entire affected surface.

The results of treatment of many patients with focal alopecia showed that after 5 and a half months (more precisely 24 weeks) complete hair restoration is observed in 8 patients out of 9. This is quite a good indicator.

True there were cases and relapse of the disease after a reduction in the dose of irradiation. The symptoms of the disease were manifested after 2.5 months after the end of treatment. In order to prevent relapses, use topical corticosteroids, aromatic retinoids, anthralin and other drugs that gradually reduce the dose without negative consequences.

PUVA therapy is also actively used in the treatment of  vitiligo. For this pathology, the disappearance of pigmentation in some parts of the body is characteristic. Under the influence of PUVA therapy, melanin synthesis is activated on the affected areas and the skin color gradually becomes equal.

In small light areas of the skin, treatment is performed locally for as little as 1 or 2 weeks. If the area of the lesion exceeds 20% of the entire skin, a systematic approach is required, and the number of necessary procedures can reach 100, and in some severe cases, 150 procedures.

Positive result in the case of treatment of vitiligo by PUVA therapy is observed in more than 50% of patients.

Phototherapy can help patients with connective tissue diseases. For example, PUVA therapy is used for  scleroderma. The disease is chronic and manifests itself in the form of compaction and scarring of connective tissue.

The long-wavelength light flux of the UV spectrum is able to act not only on the surface layers of the skin, but also penetrate deep inside. Light energy, converted to thermal triggers chemical processes, leading to positive changes in the structure of cells. In addition, phototherapy has a bactericidal effect, which prevents inflammation in the connective tissue, leading to densification of skin cells.

The effectiveness of such treatment depends on the dose of irradiation and psoralens, as well as on the individual characteristics of the organism. Abroad, the technique of PUVA therapy has become widespread, as it allows for treatment of different population groups, especially children, with minimal risk to health.

Effective replacement of corticosteroids is considered to be PUVA therapy for atopic dermatitis (another name is  neurodermatitis ), which is one of the types of inflammatory skin diseases. PUVA therapy is used mainly during periods of exacerbations of often recurrent pathology and mainly in adult patients.

The number of sessions needed to relieve the symptoms of exacerbation of the heavily flowing neurodermatitis is 59. This is a lot, but the results of such treatment are not only good, but also long-term. The main thing is a gradual cancellation of the procedure with a decrease in the dose of UV radiation and psoralens.

In the case of mild disease, 10 to a maximum of 30 sessions are sufficient. But remission after such treatment can be delayed for several years, which significantly improves the quality of life of patients.

We examined the use of PUVA therapy for the treatment of intractable pathologies, but there are many other more or less serious diseases in which PUVA therapy shows worthy results in favor of this method of phototherapy, which is much more effective than conventional skin irradiation with UV rays.

[1], [2], [3], [4]

Preparation

PUVA therapy, despite seeming harmlessness, is still a serious procedure that requires some preparation. First, you need not only to establish an accurate diagnosis, but also to determine the severity of the disease, which will determine the way the procedure is performed (or its kind), the number of procedures, the type of psoralen used, the dose of radiation and photoactive drugs.

Let's consider what kinds of PUVA-procedures there are, and in what cases they are applied.

The systemic view of the procedure is considered the most common. It can be successfully used both for localized mild forms of pathology, and for diseases of medium and high severity, when the disease covers large areas of the body. Photosensitizers are taken in the form of tablets (often with lean food or milk). You need to do this in advance. Irradiation is carried out 2-3 hours after taking the medication.

A local procedure is performed if the skin has separate lesions and their total area is less than 20%. Psoralens (solutions, ointments, emulsions) in this case are applied topically to the affected areas, after which they are exposed to dosed radiation.

PUVA-baths are a kind of procedure combining local application of drugs and a systematic approach to treatment. The patient is immersed in a bath of water in which psoralen is dissolved. Irradiation with UV rays is carried out a quarter of an hour after taking a bath.

Based on the diagnosis and degree of skin lesion, the doctor prescribes this or that kind of PUVA therapy or a combination of systemic and local forms. In the second case, a systemic therapy is prescribed first, then a local therapy.

Photosensitizing drugs can also be assigned to two types: synthetic and natural. The most popular drugs in PUVA therapy are Metoxaline, Aminofurin, Oxsoralen, Psoberan, Trimetil psoralen, etc. Depending on the type of procedure performed, preparations of the appropriate form of release are prescribed.

Even before the preparation for the procedure begins, the doctor should be informed of all medications taken by the patient, as many drugs have such a side effect as increasing the photosensitivity of the skin. If this point is not taken into account to avoid the development of side effects of the procedure is very difficult.

As a preparation directly to the procedure of PUVA therapy, patients are advised to take a shower the day before. To reduce the intensity of possible side effects, doctors sometimes prescribe vitamin A drugs (retinoids) and medicines to improve liver function.

With system PUVA therapy, there is a need to protect against UV radiation from certain parts of the body (lips, eyes, genital area in men, the area of the mammary glands in women, etc.). For this, sunscreens, special glasses and covers are used.

[5], [6], [7], [8], [9], [10], [11]

Technique of the pUVA-therapy

The technique of the procedure will be slightly different, depending on the type of PUVA therapy.

The systemic procedure involves taking psoralens in water 2-3 hours before the start of irradiation. The entire body of the patient is irradiated. The duration of the procedure can vary from 3 to 20 minutes. Begin with a minimum of time, gradually increasing it towards the end of the therapeutic course.

The number of necessary procedures and the dose of psoralens is prescribed by the doctor, having studied the condition of the patients and the tolerability of the drugs. Procedures are recommended to be carried out once in 3 days.

So, with a local procedure, psoralens in the form of liquids and ointments are applied only to damaged areas of the skin. These same areas are exposed to ultraviolet rays after approximately 35-40 minutes, when the drug is well absorbed into the skin.

The duration of the procedure and the dosage of photosensitizers in this case is determined by the doctor and depends on the skin disease and the severity of its course. The therapeutic course of local PUVA therapy in most cases is limited to 10-20 procedures.

Such treatment is recommended to be conducted no more than 1-2 times a year, depending on the used dose of radiation and the severity of the disease. The total number of sessions for the entire period of the disease should be limited to 200.

PUVA therapy using psoralenovyh baths is effective in the case when the patient's body reacts poorly to oral administration of psoralens. In the same way, it is possible to treat skin diseases in children. The effectiveness of such a procedure is higher than that of local or systemic PUVA therapy.

Before starting the procedure in the bath, dissolve about 50 mg of the photosensitizing drug "Metaxaline" or 75-125 ml of "Ammifurin". A person is in such a bath for about 15 minutes, after which it is irradiated with UV rays. Usually appoint from 15 to 40 such procedures.

The dose of UV radiation can be low (10 to 20 J per 1 cm ² ), middle (50 to 60 J per 1 cm ² ) and high (130 joules per 1 cm ² ). Typically, physicians tend to ensure that may be used as a lower radiation dose and start therapy with minimal doses of 1.5-2 Joules per 1 cm ².

Phototherapy is recommended to be performed in medical institutions, where there are specially equipped treatment rooms and apparatus for PUVA therapy. To carry out the local procedure, compact lamp-emitters are used, and for booth therapy PUVA is used booths made by the type of solarium, where the patient can receive a dose of radiation in a standing or lying position.

Kabinka for PUVA therapy should be equipped with quartz, luminescent, erythemic and arc bactericidal lamps. The computer connected to it keeps records of the indices of each session (date, time of exposure and its dose). Some machines are equipped with a system that sorts data for each patient.

PUVA-therapy at home

There is nothing unusual in that some physiotherapeutic procedures can be carried out not at the clinic, but at home. But this does not mean that they should be assigned to oneself, at random, by determining the duration of the procedure, the type and dose of the materials used.

The questions concerning any physical procedure conducted at home should be discussed with the attending physician. Moreover, if this is a matter of dosing radiation and the drugs used. Irradiation with large doses does not pass without a trace, and only the specialist can calculate the minimum effective dose. In addition, the intensity and the time of irradiation vary from procedure to procedure, which must also be taken into account and adhered to this by conducting the procedure on their own.

At home, mainly local PUVA therapy is carried out. For this special compact devices are used: ultraviolet lamps and UV-comb. The latter is designed to have a therapeutic effect on the scalp, affected by the disease.

For systemic exposure to large areas of the body, affected by the disease, it is permissible to use a solarium. True, first you need to clarify the type of apparatus used and the range of waves. But again, you first need to specify this possibility of treatment with a doctor and adhere to his recommendations regarding the dose of radiation and applied psoralenov, as well as the time of exposure to UV rays on the body.

It would seem that everything is clear and quite safe, but most doctors are still against PUVA therapy at home. This is because there is no control over the performance of the appointments and the condition of the patient during the procedure. And the patient is tempted to try to speed up the cure by adjusting the doctor's appointments himself: by increasing the number of procedures, the dose of psoralens or UV rays.

Contraindications to the procedure

PUVA therapy is considered a relatively safe procedure if it is conducted professionally. However, this does not mean that this method of phototherapy has absolutely no contraindications.

First, photosensitizers are medicines, the administration of which the patient's body can react differently. If the reaction of intolerance concerns a particular drug, it can be replaced with another. If the body reacts negatively to the very group of drugs that differ in photosensitizing effect, they will have to look for other ways to fight the disease.

Sometimes the problem is solved by the usual replacement of the systemic form of PUVA therapy with a local or PUVA bath, in which the oral administration of psoralens is not required.

This procedure is not applied in case of increased sensitivity to ultraviolet radiation, and also when the photosensitivity of the organism is increased due to certain pathologies (albinism, pigment xeroderma, porphyria, a large number of melanomopod moles on the body, etc.).

Do not prescribe PUVA therapy for malignant melanoma, so as not to provoke tumor growth, and aphakia because of possible damage to the retina in the absence of the lens.

Contraindications for PUVA therapy are pregnancy and breastfeeding of the baby.

The possibilities of using different types of PUVA therapy for the treatment of children with skin pathologies are examined in each case by the attending physician.

With caution should be approached for PUVA therapy in light-skinned patients, in patients with low immunity, with cataracts, uremia and renal insufficiency, liver diseases. The question of the possibility of conducting UV irradiation sessions is also acute in patients who had previously undergone a course of exposure to ionizing radiation, as well as in patients with various oncological diseases.

[12], [13]

Consequences after the procedure

If the dose of psoralens is properly calculated and the irradiation procedure is adequately performed with PUVA therapy, the risk of negative consequences during or after the course of treatment is minimal. Some side effects that occur during the course of the course are considered the norm and are passed in a short time. Long-term consequences, which manifest themselves after decades, are associated more with numerous repeated courses of irradiation.

So, the side effects observed during the course of treatment may differ depending on the form in which psoralens are used. Peroral taking photosensitizing drugs is associated with a risk of nausea, vomiting and stomach pain. Such symptoms are observed in 10-20% of patients.

The appearance of allergic reactions in the form of itching and rashes on the skin most often require a revision of the appointment. In some cases, patients complain of headaches, worsening of sleep, insomnia, dizziness, anxiety, fatigue, increased blood pressure. All such undesirable manifestations must be reported to the doctor.

Local application of psoralens can cause dryness of the skin, itching on the skin. Sometimes there is a development of a contact or allergic form of dermatitis.

Some unpleasant symptoms can be associated with UV radiation itself. This appearance of hyperemic areas of the skin, dark spots and even burns in case of sensitive skin or a large dose of radiation.

[14], [15]

Complications after the procedure

Severe complications can be observed several years after PUVA therapy if the irradiation procedures were performed repeatedly with repetition of courses 2 or more times. Some patients noted the development of such dangerous pathologies as cataract and skin cancer (squamous and basal forms, melanoma). Premature photoaging of the skin as a result of active absorption by UV rays of the spectrum (appearance of early wrinkles, age spots, deterioration of the appearance of the skin) was also observed.

By the way, as regards oncology, the relationship between dosed UV irradiation and the development of cancer has not been finally confirmed. Many scientists have experimentally tried to establish the relationship between the appearance of tumors and longwave irradiation, but everything has remained at the hypothesis level.

Some side effects can be avoided if it is reasonable to approach the process of treatment itself. For example, oral agents from the psoralen group to reduce the negative effect on the digestive tract, doctors recommend taking with fatty foods, or at least drink with milk, and not with water. Milk and croup meals can effectively fight nausea. The gag reflex can be prevented by crushing (and in severe cases and decreasing) a dose of the drug or taking antiemetics (for example, "Metoclopromide").

Burning of the skin in the area undergoing irradiation and its dryness are noted 2-3 days after the start of therapy. Remove these unpleasant manifestations can be with the help of softening and moisturizing creams.

The appearance of multiple pronounced unpleasant symptoms indicates an incorrect procedure for PUVA therapy. The cause of worsening of the patient's condition may be improperly selected dose of irradiation and photosensitizer, high frequency and duration of procedures, which is often observed in case of PUVA therapy at home.

[16], [17], [18], [19], [20]

Care after the procedure

As after any procedure of phototherapy, after PUVA-therapy, skin requires special care. First, to prevent drying and burning of the skin at the site of exposure to UV rays, after consulting with a doctor, it is recommended to apply caring creams with a soothing, softening and moisturizing action. To relieve the itch, antihistamines can be used.

Secondly, the skin must be protected from natural radiation (sunlight), since there is a high risk of getting sunburn. For their prevention in the open air in clear weather, it is recommended to use sunscreens with a good filter and closed clothing.

During the day after the procedure, you need to protect the sun not only the skin, but also the eyes. Wearing quality sunglasses will help to avoid clouding the lens of the eye (cataracts).

Because long-term treatment with PUVA therapy can in some way contribute to the development of skin cancer, it is necessary to undergo preventive examinations with a dermatologist in order to detect possible pathological changes in time. Obligatory and annual consultations of the ophthalmologist.

When unusual symptoms appear, it is recommended to consult a doctor without waiting for the end of the course of treatment. Consultation and assistance of a doctor may be necessary:

• in the event of severe burns to the skin and pain,
• if the skin around the affected area is very red, and it was not clear discharge,
• when there are signs of intoxication of the body, manifested in the form of fever, chills, nausea, headaches, etc.
• if side effects are of high intensity or are observed for a long time.

[21], [22], [23], [24], [25]

Feedback about PUVA-therapy

Many patients who have been treated with PUVA-therapy respond only positively to the procedure. Take at least the same psoriasis, in which PUVA therapy is one of the most effective methods of combating the disease, which allows to prolong remission for several years and improve the quality of life of patients.

The effectiveness of the technique for most pathologies of light and moderate severity is about 85%. Even in the case of an intractable disease, one-fifth of patients note a significant improvement in skin condition.

Knowing how difficult it is to fight with pathologies such as psoriasis, vitiligo, allopecia, etc., and also how much time it takes to reduce the manifestations of the disease, patients and doctors note the rapid and long-lasting effects of phototherapy with psoralenes. Already after a total of 5-8 procedures, patients notice the positive effects of PUVA therapy, and after completing a full course of treatment, they can forget about the disease for a long period (from 2 years or more). This is immeasurably important for a person suffering from an incurable disease, negatively affecting the health, the attitude of others and the patient's self-esteem.

Another important feature of the PUVA therapy is that it is not addictive, so repeated courses remain no less effective than the first ones. This is very important for the treatment of severe forms of almost incurable pathologies.

There is also the possibility of prophylactic treatment, helping to prevent the exacerbation of the disease.

It is worth noting the convenience of using the technique, which is available in both inpatient and outpatient settings with the possibility of carrying out procedures even at home.

A small number of contraindications and good tolerability of PUVA therapy makes it possible to obtain quality treatment for many who wish. True, not everyone can afford a fairly high price.

[26], [27], [28], [29], [30], [31], [32], [33]