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Recently, a significant propagation unveiled the method of Photo-Chemotherapy (PUVA) (PUVA - acronym is combination of the medication Psoralene and UV light A). Doctors from the USA in 1974 for the first time used plant photo-sensitizers (substances, which amplify the action of the sun, quartz etc.) with the subsequent irradiation by the ultraviolet rays of a certain spectrum. For this purpose there was obtained a number of photo-sensitizing preparations, in particular Puvalen (Methoxsalen; Oxsoralen; Oxsoralen-Ultra), Psoralene. Also created were installations, which give long-wave Ultraviolet light (UV radiation) with a wavelength of 320-400 nanometers. This method found wide use in the USA, England, Austria, Germany, France, Finland, Czech Republic, Poland, Russia and other countries.
PUVA-therapy or Photo-Chemotherapy is one of the most effective methods of psoriasis treatment. PUVA is a combined application of long-wave ultraviolet (wavelength from 320 to 400 nm (nanometer - one billionth of meter) UVA emission of an energy and photo-sensitizing preparations. The application of photosensitizers is used due to their ability to increase the sensitivity of the skin to the ultraviolet rays and to stimulate the formation of melanin (skin pigment that gives skin a pinkish, brownish, and black color). The peak of the effect falls on 1-3 hours after the consumption of photosensitizer. Photosensitizers are derived from the body in the urine within 24-48 hours.
Counter-indications to conducting PUVA-therapy are: lupus erythematosus (Systemic lupus erythematosus, SLE, lupus), oncologic problems, Porphyria (usually hereditary abnormalities of porphyrin metabolism, often causing rashes brought on by exposure to sunlight), conducted immunosuppressive therapy, cataract (clouding of the lens of the eye), dysfunction of the liver and kidneys, stomach ulcer, diabetes, severe endocrinopathies (abnormality of the internal glandular secretions), cardiovascular pathology, previous treatment with Methotrexate, increased sensitivity to solar rays, previous radiotherapy, roentgenotherapy (therapeutic use of X-rays) or radiation irradiation. Patients must pass an examination of liver and eyes before beginning the therapy because the application of Psoralene increases the risk of cataracts (clouding of the lens of the eye) and hepatic disorders.
PUVA-therapy can be unsafe because of the intensity of the irradiation of the skin.
Here are some of the criteria developed by physicians for the selection of patients for conducting the PUVA-therapy:
- patient must be not younger than 18 years old and not older than 55 years old;
- patient should not have any prior indications of chronic diseases of various organs and systems;
- no problems from past PUVA-treatments;
- the area of damage on the skin is not less than 30-40% (for the estimation: palm composes 1% of a body surface);
- patient did not use carcinogenic substances (substance, radionuclide or radiation that is an agent directly involved in the promotion of cancer) in the treatment of psoriasis (Arsenic etc.);
- not pregnant, or have any tumors;
- have an increased photosensitivity.
Independent of the area of coverage of the skin with psoriasis, PUVA can be prescribed also if other methods of treatment did not help a person.
Standard PUVA procedure is based on the calculation of the dosage of Psoralene, taken for the procedure. Dosage of preparation is selected, taking into consideration the weight of a patient. It is first determined the MPD (minimum photo-toxic dose), which is the determination of the UV irradiation dose leading to strong erythema (abnormal reddening of skin) of irradiated skin in a period of 72 hours.
There are 2 protocols for PUVA treatment. European protocol prescribes using MPD as a starting dose, increasing it by 4 procedures per week by 10-15%. American protocol does not require the determination of MPD, the starting dose is calculated according to a table with the type of the skin, and then with 3 procedures a week the dose rises by 10-20%. The success of PUVA therapy with psoriasis statistically is 90%. The opinions about the supporting therapy are dispersed. The majority of European specialists recommend conducting a periodic supporting course; however, British phototherapy group does not recommend conducting procedures between the courses, to avoid cumulative effect of UVA.
Photosensitizers can be used both topically in the form of ointments and also orally. Most usual is the designation of photosensitizer orally, and after1-3 hours of conducting the irradiation of the affected sections of skin. The designation of photosensitizer orally, makes it possible to obtain an even pigmentation.
Another method of PUVA treatment is a local topical application of PUVA.
The method of applying by brush is a method, with which Psoralene is applied locally directly onto the affected section of skin, especially on the palms and soles. Also, another method is the use of creams and lotions, which contain Psoralene for the external application before the use of UVA lights. These methods have one essential minus. Because it is not possible to evenly distribute the substance over the surface of the skin, very frequently the pigmentation becomes uneven and unpredictably patchy, which is completely unacceptable from a cosmetic point of view.
Soaking the affected sections such as feet or arms, they are immersed into a bath with water, which contains a photosensitizer. UVA light is then applied immediately after the patient took a bath with a psoralene-based substance.
Method of applying full baths in PUVA treatment is common in Scandinavia. Patient is placed into the bath with water, which contains Psoralene for the necessary period of time, and then the procedure of UV light is immediately conducted. This way there is achieved a stronger photo-toxic. Positive things are: a decrease in the quantity of procedures, the decrease of exposure to UVA light, and the decrease of any side effects, such as gastrointestinal problems, risk of cataract (clouding of the lens of the eye) and increase in the level of hepatic transaminases. Several studies in Europe proved Psoralene baths to considerably exceed the effectiveness of PUVA compared with the use of Psoralene orally.
Treatment is conducted employing 3-4 irradiations a week until the complete disappearance of all psoriatic lesions. An initial irradiation dose is determined taking into consideration the type of the skin and composes 0.25-1 J/cm2. Gradually the dose of UVA is increased - every two procedures by 0.5-1 J/cm2. On the average, to achieve a clinical recovery from psoriasis there will require approximately 20 - 25 procedures. With the slow disappearance of the psoriatic lesions on the lower parts of the legs after 7 - 10 usual procedures they usually will prescribe an additional local topical UVA irradiation for the legs (25 - 50% for a one-time dose).
Most frequently PUVA-therapy is used during the treatment of extended vulgar and exudative psoriasis, including Palmoplantar (located on the palms and soles) psoriasis and scalp psoriasis - for which they use special lamps for local topical irradiation. PUVA- installation is a special compartment, where the internal walls, of which, there are ultraviolet lamps fastened, which give long-wave UVA-light irradiation (320 - 400 nm). PUVA apparatuses have different modifications, which make it possible to carry out procedures for patients lying or standing, to irradiate separately the head, shins, palms, soles etc.
This method gives especially good results with extended psoriasis. PUVA therapy is successfully adapted with the severe forms of psoriasis - erythrodermic psoriasis and pustular psoriasis.
The advantage of PUVA therapy is the fact that the body does not get accustomed to it - even after 20 - 30 procedures. Furthermore, PUVA makes it possible to lengthen the remissions and can be used repeatedly.
Discovered in the middle seventies, PUVA to this day remains the leading method of psoriasis treatment. Even though it is called Photo-Chemotherapy, it has nothing in common with the chemotherapy, prescribed to oncologic (cancer) patients.
The mechanism of the action of Photo-Chemotherapy (PUVA) is complex and thus far not completely explained, but the incessant studies made it possible to determine the braking influence of photosensitizer and UVA light on the synthesis of the DNA (Deoxyribonucleic acid - molecular carrier of genetic information) in the cells of the epidermis (outer layer of skin). In the fundamental of the Photo-Chemotherapy (PUVA) it is assumed to lie in the ability of some coumarins (plant chemicals that prevent blood clotting) derivatives (8-MOP (Methoxypsoralen)) under the effect of the UV rays of a long-wave spectrum (UVA) to enter the photochemical reaction with the molecules-targets, first of all with the pyrimidine bases of the nuclear DNA. UVA-rays penetrate into the deep layers of skin and affect the dermal fibroblasts (connective-tissue cells), dendritic cells (cells that are antigen-presenting for T-cells) and the cells of inflammatory infiltration. They consider that the quanta of long-wave UV radiation - UVA - disrupt the integrity of the nucleic acids (large molecules composed of nucleotide subunits), whose free radicals (chemical compounds that can damage and oxidize cells) enter into the covalent bond with the medicines of Psoralen range. The generated connections considerably impede the replication of DNA (Deoxyribonucleic acid - molecular carrier of genetic information) and, therefore, the proliferation (rapid repeated production of new cells) of epidermal cells (cells making up the outer layer of skin). PUVA-therapy renders cytostatic (inhibiting cellular growth) action.
With psoriasis small doses of ultraviolet are therapeutic, and excessive doses - on the contrary, can bring on the development of psoriasis. The same relates to the Suns rays. PUVA treatment must be carried out under medical observation.
As with any method of treatment, phototherapy has side effects, which can be divided into early and remote side-effects.
Early side-effects appear during the conducting of the PUVA procedures or soon after. Early side-effects of PUVA include nausea, weakness, sleepiness, headache, epigastric pains (epigastric - upper middle region of the abdomen), edemas (excess fluid in body tissues; swelling), photo-toxic erythema (abnormal reddening of skin), itch and dryness of the skin.
Remote side-effects appear much later in the form of actinic damages (photo-aging), hyper-pigmentation, freckles and steadfast pigmentation changes on the skin.
Furthermore, Psoralenes can penetrate into the crystalline. In crystalline under the action of the UVA irradiation Psoralenes can form connections with the amino acids of the crystalline protein. Since these connections are not subject to reparation, frequent repetitive exposures to PUVA can lead to the accumulation of the altered crystalline protein. However, this only occurs if patients do not use special photo-protective glasses.
Finally, there does exist an opinion that phototherapy can increase the risk of malignant skin diseases, although mutagenic (can damage genes, possibly causing cancer) influence of PUVA were proven only in the test studies. Studies of the patients that used PUVA for a long time showed that the risk of non-aggressive forms of skin cancer - i.e. Basal cell carcinoma - rises with the lasting application of PUVA.
Basal cell carcinoma (BCC) is the most common (75-80% of all skin cancers) rarely metastasizing malignant skin cancer.
BCC starts in the basal (deepest) cell layer of the epidermis (the top layer of skin), grows very slowly and rarely spreads to vital organs.
Basal cell carcinoma is characterized by small, shiny, raised bumps on the skin that may bleed. BCC is commonly found on the neck, face, and arms.
It is easily detected and has a cure rate of 95% when treated promptly enough.
Treatment includes a procedure to remove the cancer, typically by cutting out the affected area or treating with a topical chemotherapy.
The risk of BCC is increased for individuals with a family history of the disease and with a high cumulative exposure to UV light via sunlight or UVA/UVB psoriasis treatments.
There are almost 1 million cases of BCC each year in America.
Apparently, PUVA can play a role of a pseudo-stimulator which suppresses the mechanisms of immunological supervision, thus giving the possibility to appearance of the effects, caused by the stronger risk factors (previous X-ray irradiation, past treatment with Tar etc.).
At its basis of PUVA-therapy lies the theory of the accelerated division of cells, which occurs with psoriasis.
Neither Psoralene nor ultraviolet separately render any therapeutic effect, they must be used only together.
The prevalence of PUVA psoriasis treatment in different countries is caused by its simplicity and possibility of its application at home. In many cities there are dermatological centers, rendering PUVA-therapy.
Even greater effect is possible to achieve during a treatment - combination of PUVA-therapy with the immunostimulating medicines and blood purification. Such treatment can increase psoriatic remission up to 3-5 years.
For increasing the effectiveness of PUVA and decreasing the side-effects (skin pigmentation, dryness, erythema (abnormal reddening of skin) etc.) some dermatologists recommend using a complex of Vitamin A and Vitamin F and sessions of Hyperbaric Oxygen Therapy (HBOT - medical use of oxygen at a higher than atmospheric pressure).
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