На правах рукописи жилова марьянна борисовна эффективность и безопасность многокурсовой



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1. При многократном применении методов ПУВА-терапии и узкополосной (311нм) фототерапии у больных среднетяжелыми и тяжелыми формами псориаза эффективность лечения по мере увеличения количества курсов не снижается. Высокая эффективность (ΔPASI≥75) при однокурсовом и многокурсовом применении ПУВА-терапии отмечалась у 84,2% и 82,3% больных (p>0,05), узкополосной (311 нм) фототерапии – у 77,3% и 75% соответственно (p>0,05). У больных среднетяжелыми формами псориаза, длительно получавших ПУВА-терапию, возможна ротация на метод узкополосной (311 нм) фототерапии при сохранении высокой эффективности лечения.

2. Частота развития фототоксической эритемы у больных псориазом при проведении ПУВА-терапии и узкополосной (311 нм) фототерапии не различается (24,2%, 19,6%, p>0,05). Интенсивность эритемы и сроки её разрешения при проведении узкополосной (311 нм) фототерапии достоверно ниже (р<0,05), чем при ПУВА-терапии, что свидетельствует о большей безопасности этого метода.
3.Многокурсовая фототерапия псориаза приводит к дозозависимому повышению частоты развития симптомов хронического фотоповреждения кожи. При проведении 60-100 процедур единственным симптомом хронического фотоповреждения кожи является развитие веснушек/лентиго (36,4%). При проведении 101-200 процедур и более 200 процедур фототерапии развитие веснушек/лентиго встречается соответственно у 69% и 100% больных, актинический эластоз у 19% и 86,7%, ретикулярный себорейный кератоз – у 13,8% и 53,3%, необратимая диффузная гиперпигментация – у 41,4% и 60%, крапчатая пигментация у 0% и 20%, телеангиэктазии – у 0% и 20% (р<0,05).
4. У больных псориазом и здоровых добровольцев обнаружены следующие полиморфные варианты генов эксцизионной системой репарации ДНК: 35931A>C гена XPD; 32724C>A, 32864T>C, 32828C>G, 33343T>A, 33350A>G гена XPC; 27495Т>С, 28095G>A гена XPF;19007G>A гена ERCC1 и 28152G>A гена XRCC1. Лечение больных псориазом методами ПУВА-терапии и узкополосной (311 нм) фототерапии не вызывает развития клинически значимых мутаций генов эксцизионной системы репарации ДНК (XPC, XPF, XPDXRCC1, ERCC1) в коже при однокурсовом и многокурсовом применении.

5. Генотип ТТ гена XPF 27945 ассоциирован с высоким риском фототоксической эритемы у больных псориазом, получающих фототерапию, генотип СС гена XPF 27945 является протективным фактором и ассоциирован с низким риском развития фототоксической эритемы. Установлена ассоциация симптома хронического фотоповреждения кожи: необратимой диффузной гиперпигментации с гетерозиготным генотипом GG гена XRCC1 28152(еxon10)

6. Предикторами повышенного риска развития злокачественной меланомы кожи у больных псориазом являются генотип СС гена XPD в позиции 35931 и генотип ТС гена XPF в позиции 27945. Молекулярным предиктором повышенного риска развития злокачественной меланомы кожи у здоровых лиц является генотип СС гена XPD в позиции 35931.

7. На безопасность проведения многокурсовой фототерапии больных псориазом оказывают влияние общее количество полученных процедур (не более 200 процедур ПУВА-терапии), кумулятивная доза облучения ПУВА-терапии ( не более 1000 ДЖ/ cм2), клиническая оценка фотоповреждения кожи, характер предшествующего лечения и наличие молекулярно-генетических предикторов повышенного риска меланомы кожи.

 ПРАКТИЧЕСКИЕ РЕКОМЕНДАЦИИ


  1. Перед назначением больным псориазом методов фототерапии с целью определения предикторов риска развития побочных эффектов и злокачественной меланомы кожи рекомендуется проведение молекулярно-генетических исследований следующих полиморфизмов генов эксцизионной системой репарации ДНК: Т>C гена XPF27945 и А>C гена XPD35931.

  2. В случаях выявления генотипа СС 35931 гена XPD и/или генотипа ТС 27945 гена XPF, ассоциированных с повышенным риском развития меланомы кожи, пациенту не следует назначать ПУВА-терапию или узкополосную (311 нм) фототерапию.

  3. В случаях выявления генотипа ТТ гена XPF 27945, ассоциированного с высоким риском развития фототоксических реакций, курсовое лечение методами фототерапии необходимо проводить с осторожностью, используя невысокие разовые дозы и щадящий режим облучения.

  4. У больных среднетяжелыми формами псориаза предпочтительным является применение метода узкополосной (311 нм) фототерапии, обладающего большей безопасностью, по сравнению с ПУВА-терапией.

  5. Больных, получающих многокурсовую фототерапию, необходимо информировать о возможности развития у них симптомов хронического фотоповреждения кожи. В случаях выявления крапчатой пигментации дальнейшее проведение фототерапии не целесообразно в связи с возможностью развития неоплазии.

  6. Для учёта общего количества процедур и кумулятивной дозы облучения рекомендуется ведение паспорта фототерапии с указанием ФИО больного, даты проведения курса лечения, метода фототерапии, курсового количества процедур и курсовой дозы облучения.

  7. При проведении фототерапии необходимо учитывать данные анамнеза о длительности предшествующего лечения глюкокортикостероидными препаратами ввиду повышенного риска развития фототоксических реакций.



ПАСПОРТ ПАЦИЕНТА, ПОЛУЧАЮЩЕГО ФОТОТЕРАПИЮ

ФИО_____________________________________________________________________

ДАТА РОЖДЕНИЯ________________________________________________________

№АМБУЛАТОРНОЙ КАРТЫ ИЛИ ИСТОРИИ БОЛЕЗНИ ____________________



ДИАГНОЗ_________________________________________________________________

ДАТА НАЧАЛА ЗАБОЛЕВАНИЯ __________________________________________

КОЛИЧЕСТВО РАНЕЕ ПОЛУЧЕННЫХ КУРСОВ ФОТОТЕРАПИИ:

ПУВА-ТЕРАПИЯ ____________________________________________________________

СФТ_______________________________________________________________________

УЗКОПОЛОСНАЯ СРЕДНЕВОЛНОВАЯ ФОТОТЕРАПИЯ (311 нм)__________________

Даты

курса

фототерапии




























Вид фототерапии





























Количество полученных процедур на курс




























Курсовая доза облучения

Дж/см2




























Развитие на курсе лечения фототоксической эритемы (интенсивность и сроки регресса)




























Признаки хронического фотоповреждения кожи ( веснушки/лентиго, эластоз, крапчатая пигментация и др.)




























Примечание































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