Клинические рекомендации: Грибовидный микоз

Грибовидный микоз (ГМ) – первичная эпидермотропная Т-клеточная лимфома кожи (ЛК), характеризующаяся пролиферацией малых и средних Т-лимфоцитов с церебриформными ядрами.

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Клинические рекомендации
Грибовидный микоз
Кодирование по Международной статистической классификации болезней и проблем, связанных со здоровьем:	С84.0
Возрастная группа:	Взрослые и дети
Год утверждения:
Разработчик клинической рекомендации:
Общероссийская общественная организация «Российское общество дерматовенерологов и косметологов» Региональная общественная организация «Общество онкогематологов»

Оглавление
TOC \o "1-3" \h \z \u
Оглавление
PAGEREF _Toc84161263 \h 2
Список сокращений
PAGEREF _Toc84161264 \h 4
Термины и определения
PAGEREF _Toc84161265 \h 5
1. Краткая информация по заболеванию или состоянию (группе заболеваний или состояний)
PAGEREF _Toc84161266 \h 6
1.1 Определение
заболевания или состояния (группы заболеваний или состояний) PAGEREF _Toc84161267 \h 6
1.2 Этиология и патогенез
заболевания или состояния (группы заболеваний или состояний) PAGEREF _Toc84161268 \h 6
1.3 Эпидемиология
заболевания или состояния (группы заболеваний или состояний) PAGEREF _Toc84161269 \h 6
1.4
Особенности кодирования заболевания или состояния (группы заболеваний или состояний) по Международной статистической классификации болезней и проблем, связанных со здоровьем PAGEREF _Toc84161270 \h 7
1.5 Классификация
заболевания или состояния (группы заболеваний или состояний) PAGEREF _Toc84161271 \h 7
1.6 Клиническая картина
заболевания или состояния (группы заболеваний или состояний) PAGEREF _Toc84161272 \h 7
2. Диагностика заболевания или состояния (группы заболеваний или состояний), медицинские показания и противопоказания к применению методов диагностики
PAGEREF _Toc84161273 \h 10
2.1 Жалобы и анамнез
PAGEREF _Toc84161274 \h 11
2.2 Физикальное обследование
PAGEREF _Toc84161275 \h 11
2.3
Лабораторные диагностические исследования PAGEREF _Toc84161276 \h 12
2.4 Инструментальные диагностические исследования
PAGEREF _Toc84161277 \h 13
2.5 Иные диагностические исследования
PAGEREF _Toc84161278 \h 14
3. Лечение, включая медикаментозную и немедикаментозную терапии, диетотерапию, обезболивание, медицинские показания и противопоказания к применению методов лечения
PAGEREF _Toc84161279 \h 21
3.1 Лечение пациентов с ранними стадиями грибовидного микоза
PAGEREF _Toc84161280 \h 21
3.2 Лечение пациентов с распространенными стадиями грибовидного микоза и рецидивных и рефрактерных форм грибовидного микоза
PAGEREF _Toc84161281 \h 23
3.3 Иное лечение
PAGEREF _Toc84161282 \h 27
4. Медицинская реабилитация, медицинские показания и противопоказания к применению методов реабилитации
PAGEREF _Toc84161283 \h 27
5. Профилактика и диспансерное наблюдение, медицинские показания и противопоказания к применению методов профилактики
PAGEREF _Toc84161284 \h 28
6. Организация медицинской помощи
PAGEREF _Toc84161285 \h 28
7. Дополнительная информация (в том числе факторы, влияющие на исход заболевания или состояния)
PAGEREF _Toc84161286 \h 30
Критерии оценки качества медицинской помощи
PAGEREF _Toc84161287 \h 30
Список литературы
PAGEREF _Toc84161288 \h 31
Приложение А1. Состав рабочей группы по разработке и пересмотру клинических рекомендаций
PAGEREF _Toc84161289 \h 38
Приложение А2. Методология разработки клинических рекомендаций
PAGEREF _Toc84161290 \h 39
Приложение Б. Алгоритмы действий врача
PAGEREF _Toc84161291 \h 42
Приложение В. Информация для пациента
PAGEREF _Toc84161292 \h 43
Приложение Г1. Алгоритм диагностики ранних форм грибовидного микоза
PAGEREF _Toc84161293 \h 44
Приложение Г2. Стадирование грибовидного микоза согласно рекомендациям
ISLE-EORTC PAGEREF _Toc84161294 \h 45


Список сокращений
ВИЧ – вирус иммунодефицита человека
ЛДГ - лактатдегидрогеназа
ЛК – лимфомы кожи
ПУВА (Psoralen + UltraViolet A) – псорален-ультрафиолет А
ПЦР – полимеразная цепная реакция
СОД – суммарная очаговая доза
ТКР – T-клеточный рецептор
ТОК – тотальное облучение кожи
УЗИ – ультразвуковое исследование
Термины и определения
Грибовидный микоз (ГМ) – первичная эпидермотропная Т-клеточная лимфома кожи (ЛК), характеризующаяся пролиферацией малых и средних Т-лимфоцитов с церебриформными ядрами.
ISLE-Международного общества по лимфомам кожи
EORTC - Европейской организации по изучению и лечению рака

1. Краткая информация по заболеванию или состоянию (группе заболеваний или состояний)
1.1 Определение заболевания или состояния (группы заболеваний или состояний)
Грибовидный микоз (ГМ) – первичная эпидермотропная Т-клеточная лимфома кожи (ЛК), характеризующаяся пролиферацией малых и средних Т-лимфоцитов с церебриформными ядрами.
1.2 Этиология и патогенез заболевания или состояния (группы заболеваний или состояний)
Этиология заболевания неизвестна. Cчитается, что лимфомы кожи возникают вследствие хронической антигенной стимуляции, что ведет к неконтролируемой клональной пролиферации и накоплению неопластических Т-клеток в коже. Предполагают роль золотистого стафилококка в возникновении лимфом кожи. Некоторые исследователи сообщают о значении вируса Эпштейна-Барр и цитомегаловируса в этиологии заболевания. Есть данные о развитии лимфом кожи у людей, получающих иммуносупрессивную терапию после трансплантации органов и у ВИЧ-инфицированных.
1.3 Эпидемиология заболевания или состояния (группы заболеваний или состояний)
Грибовидный микоз является наиболее часто встречающейся формой кожной Т-клеточной лимфомы и составляет 1% всех неходжкинских лимфом, 50% первичных лимфом кожи и 65% кожных Т-клеточных лимфом. Заболеваемость грибовидным микозом в мире равна 6–7 случаев/106 в год с регулярным повышением в последние десятилетия. Этот показатель значительно варьирует в различных географических регионах: в США заболеваемость грибовидными микозом составляет 0,46 случаев на 100 000 человек, в странах Европы этот показатель колеблется от 0,26 до 1,0 на 100 000 человек в год (55% мужчин и 45% женщин). Более 75% случаев грибовидного микоза наблюдается у пациентов старше 50 лет, средний возраст дебюта заболевания составляет 55–60 лет. Грибовидный микоз может также поражать детей и подростков (1% случаев). Соотношение заболевших мужчин и женщин составляет 2,0:1,0 с преобладанием пациентов с темным цветом кожи (1,7:1) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1001/jamadermatol.2013.5526","ISSN":"21686068","PMID":"24005876","abstract":"IMPORTANCE: Cutaneous T-cell lymphoma (CTCL) incidence and survival have been increasing steadily for over 25 years. OBJECTIVE: We sought to measure changes in CTCL incidence trends and survival rates. DESIGN, SETTING, AND PARTICIPANTS: Population-based study. The CTCL incidence and survival data were obtained from the 9 original registries (1973-2009) and the 4 additional registries (1992-2009) of the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (NCI). Trend analysis was performed using the Joinpoint Regression Program provided by the NCI. Survival analysis was performed using the SeerSTAT statistical software of the NCI. The total number of cases of CTCL from 1973 to 2009 was 6230. MAIN OUTCOMES AND MEASURES: Diagnoses of CTCL. RESULTS: Overall CTCL incidence has stabilized since 1998 (95% CI, 1994-2002), with an annual percent change (APC) of 5.7% from 1973 to 1998 (95% CI, 4.9%-6.5%) and an APC of 0.1% from 1998 to 2009 (95% CI, -1.4% to 1.5%). Similar incidence stabilization patterns were found in subgroup analyses of race, sex, age, diagnosis, and registry. Five-year CTCL survival rates increased until 2004. CONCLUSIONS AND RELEVANCE: The incidence of CTCL is no longer increasing. Causes for this trend change may include real incidence stabilization, stabilization of physician detection, or artifact. Copyright 2013 American Medical Association. All rights reserved.","author":[{"dropping-particle":"","family":"Korgavkar","given":"Kaveri","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xiong","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Weinstock","given":"Martin","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"JAMA Dermatology","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2013","11"]]},"page":"1295-1299","publisher":"JAMA Dermatol","title":"Changing incidence trends of cutaneous T-cell lymphoma","type":"article-journal","volume":"149"},"uris":["http://www.mendeley.com/documents/?uuid=6e6368bf-1f43-3b17-9d32-0abaa0e4545c"]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/sj.leu.2403934","ISSN":"0887-6924","PMID":"16151466","abstract":"In this randomized phase III study of the EORTC Leukemia Cooperative Group, patients with myelodysplastic syndromes (MDS) with 10-30% bone marrow blasts and hematopoietic failure were treated with low-dose cytosine arabinoside (LD-AraC) (2 x 10 mg/m2/day subcutaneously (s.c.) days 1-14) either alone or in combination with rhGM-CSF or interleukin-3 (IL-3) both given s.c. at a dose of 150 microg/day from day 8 to 21. A total of 180 evaluable patients with a median age of 65 years and refractory anemia with an excess of blasts (RAEB, n = 107) or RAEB in transformation (RAEBt, n = 73) were randomized. There were no differences among the three treatment regimens with respect to numbers of courses applied or treatment delays. Hemorrhage occurred in approximately 40% in all arms, whereas infection rates were higher in the granulocyte/macrophage colony stimulating factor (GM-CSF)- or IL3-containing arm. The overall response rate was 38.6% with no statistically significant difference among the three arms. In summary, a substantial proportion of patients had achieved relatively durable responses in all the three arms. No influence of either growth factor was detected on the grade of cytopenia. Thus, the combination of LD-AraC with GM-CSF or IL-3 cannot be recommended for routine use in a high-risk MDS population.","author":[{"dropping-particle":"","family":"Zwierzina","given":"H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suciu","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Loeffler-Ragg","given":"J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Neuwirtova","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fenaux","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beksac","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Harousseau","given":"J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nuessler","given":"V","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cermak","given":"J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Solbu","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willemze","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Witte","given":"T","non-dropping-particle":"de","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Amadori","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"EORTC Leukemia Cooperative Group","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Leukemia","id":"ITEM-2","issue":"11","issued":{"date-parts":[["2005","11"]]},"page":"1929-33","title":"Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group.","type":"article-journal","volume":"19"},"uris":["http://www.mendeley.com/documents/?uuid=0ffc611e-69e6-3bba-a3f7-9ccd701ac181"]}],"mendeley":{"formattedCitation":"[1,2]","plainTextFormattedCitation":"[1,2]","previouslyFormattedCitation":"[1,2]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[1,2].
1.4 Особенности кодирования заболевания или состояния (группы заболеваний или состояний) по Международной статистической классификации болезней и проблем, связанных со здоровьем
C84.0 – Грибовидный микоз.
1.5 Классификация заболевания или состояния (группы заболеваний или состояний)
Грибовидный микоз (классический трехстадийный вариант)
Другие формы грибовидного микоза:
входят в ВОЗ-классификацию опухолей кожи:
фолликулотропный грибовидный микоз;
педжетоидныйретикулез;
синдром гранулематозной вялой кожи.
редко встречающиеся варианты:
эритродермический;
фолликулярный;
сиринготропный;
буллезный/везикулезный;
гранулематозный;
пойкилодермический;
гиперпигментный;
гипопигментный;
одноочаговый;
ладонно-подошвенный;
гиперкератотический/веррукозный;
вегетирующий/папилломатозный;
ихтиозиформный;
пигментно-пурпурозный;
пустулезный.
1.6 Клиническая картина заболевания или состояния (группы заболеваний или состояний)
При классическом варианте грибовидного микоза заболевание протекает стадийно с нарастанием распространенности процесса и делится на 3 клинических стадии: пятнистая (эритематозная), бляшечная и опухолевая.
Заболевание начинается с пятен разных размеров, с четкими краями, которые расположены несимметрично и чаще локализуются на ягодицах и участках кожи, защищенных от солнечного облучения – молочных железах, нижних отделов живота, в подмышечных и паховых складках, на внутренней поверхности бедер и плеч. Цвет пятен варьирует от розовато-красного до желтовато-оранжевого и коричневого оттенков. Поверхность пятен может быть морщинистой (псевдоатрофичной) и слегка лихенифицированной, в случае появления телеангиоэктазий и участков пигментации развивается пойкилодемия. В эритематозной стадии болезнь может проявляться разнообразными и нехарактерными эритемами, уртикароподобными, псориазо- и парапсориазоподобными, экземоподобными высыпаниями.  
Для бляшечной стадии характерно образование инфильтрированных бляшек различной величины, желтовато-красной или синюшной окраски. Поверхность их может быть гладкой, слегка шелушащейся или лихенифицированной. Образование бляшек протекает бессимптомно или сопровождается очень сильным зудом, иногда их рост идет неравномерно за счет периферической части, в результате чего образуются дугообразные очаги. Разрешаются бляшки медленно и неравномерно, при разрешении в центре они приобретают кольцевидную форму.
Клиническими симптомами, характерными для ранних стадий грибовидного микоза, являются:
вариабельность формы, размеров и цвета высыпаний;
феномен одновременного прогрессирования и регрессирования отдельных высыпаний;
пойкилодермия (пятнистая пигментация, телеангиоэктазии, атрофия кожи);
множественные высыпания, несколько зон вовлечения;
характерная локализация высыпаний на участках кожи, не подвергающихся солнечному облучению;
зуд, сопровождающий высыпания ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1177/107327480701400203","ISSN":"15262359","PMID":"17387295","abstract":"Background: Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases composed of malignant T lymphocytes. The most common type is mycosis fungoides (MF). An accurate diagnosis of early MF may be difficult because of the varied clinical and histologic expressions of the disease. Methods: The authors review the epidemiology, possible risk factors, clinical manifestations, diagnostic techniques, staging, prognosis, and treatment options for MF. Results: The varied and often nonspecific clinical and histologic presentations of MF may delay diagnosis and staging, thus necessitating further studies such as immunophenotyping and T-cell receptor gene rearrangement analysis. Conclusions: A multidisciplinary approach to the diagnosis, staging, and treatment of MF assists in optimizing outcomes from management of patients with this disease.","author":[{"dropping-particle":"","family":"Keehn","given":"Connie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Belongie","given":"Iriana P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shistik","given":"Galina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fenske","given":"Neil A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Glass","given":"L. Frank","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cancer Control","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2007"]]},"page":"102-111","publisher":"H. Lee Moffitt Cancer Center and Research Institute","title":"The diagnosis, staging, and treatment options for mycosis fungoides","type":"article-journal","volume":"14"},"uris":["http://www.mendeley.com/documents/?uuid=60fdb40e-510a-3e65-a5e4-4e7abed6c350"]},{"id":"ITEM-2","itemData":{"DOI":"10.12788/j.sder.2018.002","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype. Cytotoxic variants are well described and do not have specific clinical, histopathological, or prognostic features. MF should be differentiated from other cutaneous epidermotropic lymphomas and from many inflammatory dermatoses with some similar clinicopathological features. The therapy of MF is planned mainly according to the stage and extent of the disease. In early phases, nonaggressive options represent the first-line strategy (eg, local corticosteroids, psoralen, and ultraviolet A [UV-A] irradiation, etc.). In patients with advanced disease, good results with potential for cure have been obtained with allogeneic stem cell transplantation, but toxicity is a serious limiting factor for this treatment. Conventional systemic chemotherapy and single-agent chemotherapy (eg, gemcitabine) give usually good results in advanced MF, but recurrences are the rule. Monoclonal antibodies directed against cluster of differentiation (CD)52 (alemtuzumab), CD30 (brentuximab vedotin), and chemokine receptor 4 (CCR4; mogamulizumab), as well as several other experimental therapies, have shown promising results and represent a valid alternative.","author":[{"dropping-particle":"","family":"Cerroni","given":"Lorenzo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"2-10","publisher":"Frontline Medical Communications","title":"Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=0eef9cf6-6919-34c1-a5e7-dca806294a6c"]},{"id":"ITEM-3","itemData":{"DOI":"10.12788/j.sder.2018.004","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.","author":[{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-3","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"11-17","publisher":"Frontline Medical Communications","title":"Mycosis fungoides variants-clinicopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=4b1bd90a-5293-39d9-9282-b73a3621782a"]}],"mendeley":{"formattedCitation":"[3–5]","plainTextFormattedCitation":"[3–5]","previouslyFormattedCitation":"[3–5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[3–5].
В опухолевой стадии у пациента обычно обнаруживается сочетание пятен, бляшек и узлов. Узлы могут формироваться как в области существующих бляшек, так и на непораженной ранее коже. Их локализация и количество могут варьировать от единичных до множественных. В опухолевой стадии могут поражаться лимфатические узлы и внутренние органы ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1177/107327480701400203","ISSN":"15262359","PMID":"17387295","abstract":"Background: Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases composed of malignant T lymphocytes. The most common type is mycosis fungoides (MF). An accurate diagnosis of early MF may be difficult because of the varied clinical and histologic expressions of the disease. Methods: The authors review the epidemiology, possible risk factors, clinical manifestations, diagnostic techniques, staging, prognosis, and treatment options for MF. Results: The varied and often nonspecific clinical and histologic presentations of MF may delay diagnosis and staging, thus necessitating further studies such as immunophenotyping and T-cell receptor gene rearrangement analysis. Conclusions: A multidisciplinary approach to the diagnosis, staging, and treatment of MF assists in optimizing outcomes from management of patients with this disease.","author":[{"dropping-particle":"","family":"Keehn","given":"Connie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Belongie","given":"Iriana P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shistik","given":"Galina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fenske","given":"Neil A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Glass","given":"L. Frank","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cancer Control","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2007"]]},"page":"102-111","publisher":"H. Lee Moffitt Cancer Center and Research Institute","title":"The diagnosis, staging, and treatment options for mycosis fungoides","type":"article-journal","volume":"14"},"uris":["http://www.mendeley.com/documents/?uuid=60fdb40e-510a-3e65-a5e4-4e7abed6c350"]},{"id":"ITEM-2","itemData":{"DOI":"10.12788/j.sder.2018.002","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype. Cytotoxic variants are well described and do not have specific clinical, histopathological, or prognostic features. MF should be differentiated from other cutaneous epidermotropic lymphomas and from many inflammatory dermatoses with some similar clinicopathological features. The therapy of MF is planned mainly according to the stage and extent of the disease. In early phases, nonaggressive options represent the first-line strategy (eg, local corticosteroids, psoralen, and ultraviolet A [UV-A] irradiation, etc.). In patients with advanced disease, good results with potential for cure have been obtained with allogeneic stem cell transplantation, but toxicity is a serious limiting factor for this treatment. Conventional systemic chemotherapy and single-agent chemotherapy (eg, gemcitabine) give usually good results in advanced MF, but recurrences are the rule. Monoclonal antibodies directed against cluster of differentiation (CD)52 (alemtuzumab), CD30 (brentuximab vedotin), and chemokine receptor 4 (CCR4; mogamulizumab), as well as several other experimental therapies, have shown promising results and represent a valid alternative.","author":[{"dropping-particle":"","family":"Cerroni","given":"Lorenzo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"2-10","publisher":"Frontline Medical Communications","title":"Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=0eef9cf6-6919-34c1-a5e7-dca806294a6c"]}],"mendeley":{"formattedCitation":"[3,4]","plainTextFormattedCitation":"[3,4]","previouslyFormattedCitation":"[3,4]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[3,4].
Фолликулотропный грибовидный микоз является самостоятельным вариантом грибовидного микоза, характеризующимся наличием фолликулотропных инфильтратов, часто с сохранением межфолликулярного эпидермиса и преимущественным поражением головы и шеи. Фолликулотропный грибовидный микоз развивается главным образом у взрослых, но описан также у детей и подростков. Мужчины болеют чаще, чем женщины. Поражение кожи располагается преимущественно на лице и шее, где оно наиболее выражено Заболевание может проявляться сгруппированными фолликулярными папулами, пятнами, ассоциированными с фолликулами, плотными бляшками или опухолями.Другими клиническими проявлениями являются акнеформные высыпания (комедоны, кисты) и высыпания, напоминающие волосяной кератоз, которые локализуются главным образом на туловище и конечностях. Поражение кожи при фолликулотропном грибовидном микозе часто ассоциировано с алопецией. У детей заболевание чаще всего проявляется гипопигментированными, приуроченными к волосяным фолликулам пятнами, и ассоциированной алопецией. Частым и очень характерным признаком болезни являются инфильтрированные бляшки в области бровей, сопровождающиеся выпадением волос. Зуд зачастую очень интенсивный. Часто наблюдаются вторичные бактериальные инфекции. В редких случаях фолликулотропный грибовидный микоз может проявляться солитарными очагами поражения (солитарный или одноочаговыйфолликулотропный грибовидный микоз) или эритродермией ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.12788/j.sder.2018.004","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.","author":[{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"11-17","publisher":"Frontline Medical Communications","title":"Mycosis fungoides variants-clinicopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=4b1bd90a-5293-39d9-9282-b73a3621782a"]}],"mendeley":{"formattedCitation":"[5]","plainTextFormattedCitation":"[5]","previouslyFormattedCitation":"[5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[5].
Сиринготропный грибовидный микоз представляет собой редкий вариант заболевания, имеющим много общего с фолликулотропным грибовидным микозом. Он характеризуется выраженным поражением эккринных желез, часто ассоциируясь с пилотропизмом. Поражения кожи могут быть солитарными или, чаще, генерализованными ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.12788/j.sder.2018.002","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype. Cytotoxic variants are well described and do not have specific clinical, histopathological, or prognostic features. MF should be differentiated from other cutaneous epidermotropic lymphomas and from many inflammatory dermatoses with some similar clinicopathological features. The therapy of MF is planned mainly according to the stage and extent of the disease. In early phases, nonaggressive options represent the first-line strategy (eg, local corticosteroids, psoralen, and ultraviolet A [UV-A] irradiation, etc.). In patients with advanced disease, good results with potential for cure have been obtained with allogeneic stem cell transplantation, but toxicity is a serious limiting factor for this treatment. Conventional systemic chemotherapy and single-agent chemotherapy (eg, gemcitabine) give usually good results in advanced MF, but recurrences are the rule. Monoclonal antibodies directed against cluster of differentiation (CD)52 (alemtuzumab), CD30 (brentuximab vedotin), and chemokine receptor 4 (CCR4; mogamulizumab), as well as several other experimental therapies, have shown promising results and represent a valid alternative.","author":[{"dropping-particle":"","family":"Cerroni","given":"Lorenzo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"2-10","publisher":"Frontline Medical Communications","title":"Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=0eef9cf6-6919-34c1-a5e7-dca806294a6c"]}],"mendeley":{"formattedCitation":"[4]","plainTextFormattedCitation":"[4]","previouslyFormattedCitation":"[4]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[4].
Педжетоидныйретикулез представляет собой редкий вариант грибовидного микоза, характеризующийся локализованными пятнами или бляшками с интраэпидермальной пролиферацией неопластических Т-лимфоцитов. Термин педжетоидныйретикулез следует использовать только для локализованного типа болезни (тип Ворингера-Колоппа), но не для диссеминированного типа (тип Кетрона-Гудмана), так как в настоящее время у большинства пациентов с генерализованными высыпаниями заболевание рассматривают как первичную кожную CD8+ агрессивную эпидермотропную цитотоксическую лимфому, первичную кожную γ/δ Т-клеточную лимфому или опухолевую стадию грибовидного микоза ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.12788/j.sder.2018.004","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.","author":[{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"11-17","publisher":"Frontline Medical Communications","title":"Mycosis fungoides variants-clinicopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=4b1bd90a-5293-39d9-9282-b73a3621782a"]}],"mendeley":{"formattedCitation":"[5]","plainTextFormattedCitation":"[5]","previouslyFormattedCitation":"[5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[5]. Поражение кожи у пациентов обычно представлено солитарными, медленно прогрессирующими псориазиформными или гиперкератотическими бляшками, которые обычно локализуются на конечностях, чаще всего на кистях и стопах ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.12788/j.sder.2018.004","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.","author":[{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"11-17","publisher":"Frontline Medical Communications","title":"Mycosis fungoides variants-clinicopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=4b1bd90a-5293-39d9-9282-b73a3621782a"]}],"mendeley":{"formattedCitation":"[5]","plainTextFormattedCitation":"[5]","previouslyFormattedCitation":"[5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[5].
Синдром гранулематозной вялой кожи – это крайне редкий вариант грибовидного микоза, характеризующийся медленным формированием складок вялой кожи и гранулематозным инфильтратом с клональными Т-лимфоцитами. Первоначальным проявлением поражения кожи при синдроме гранулематозной вялой кожи, как и при классическом грибовидном микозе, являются пятна и бляшки, которые трансформируются в крупные, висящие складки атрофичной кожи в области сгибов (подмышки и пах), напоминающие синдром вялой кожи — cutislaxa. Внекожная диссеминация патологического процесса развивается крайне редко, и у большинства пациентов заболевание имеет индолентноетечение ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.12788/j.sder.2018.004","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.","author":[{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"11-17","publisher":"Frontline Medical Communications","title":"Mycosis fungoides variants-clinicopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=4b1bd90a-5293-39d9-9282-b73a3621782a"]}],"mendeley":{"formattedCitation":"[5]","plainTextFormattedCitation":"[5]","previouslyFormattedCitation":"[5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[5].
Гипопигментный грибовидный микоз часто обнаруживается у людей с темной кожей и часто встречается у детей и подростков. У пациентов с белой кожей гипопигментированные очаги поражения обычно сосуществуют вместе с эритематозными высыпаниями, типичными для классического грибовидного микоза. Заболевание проявляется гипопигментированными пятнами, которые локализуются преимущественно на туловище и конечностях и не сопровождаются субъективными ощущениями ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.12788/j.sder.2018.004","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.","author":[{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"11-17","publisher":"Frontline Medical Communications","title":"Mycosis fungoides variants-clinicopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=4b1bd90a-5293-39d9-9282-b73a3621782a"]}],"mendeley":{"formattedCitation":"[5]","plainTextFormattedCitation":"[5]","previouslyFormattedCitation":"[5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[5].
Помимо вариантов, подробно рассмотренных выше, описано еще несколько клинических вариантов грибовидного микоза. Варианты, подобно гиперпигментному, буллезному/везикулезному, пойкилодермическому, пигментному пурпуроподобному, пустулезному, ихтиозиформному, ладонно-подошвенному грибовидному микозу были названы согласно их характерным клиническим проявлениям. Тем не менее, обычно они характеризуются теми же гистологическими признаками и таким же течением, что и классический грибовидный микоз, и поэтому не включены в последнюю классификацию лимфом кожи как самостоятельные заболевания ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.12788/j.sder.2018.004","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.","author":[{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"11-17","publisher":"Frontline Medical Communications","title":"Mycosis fungoides variants-clinicopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=4b1bd90a-5293-39d9-9282-b73a3621782a"]}],"mendeley":{"formattedCitation":"[5]","plainTextFormattedCitation":"[5]","previouslyFormattedCitation":"[5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[5].
2. Диагностика заболевания или состояния (группы заболеваний или состояний), медицинские показания и противопоказания к применению методов диагностики
Диагностика грибовидного микоза    базируется на основании комплексной оценки клинической картины заболевания, патолого-анатомического исследования биопсийного (операционного) материала кожи, в том числе с применением иммуногистохимического метода, определения перестройки гена Т-клеточного рецептора, согласно рекомендациям Международного общества по лимфомам кожи и Европейской организации по изучению и лечению рака для грибовидного микоза и синдрома Сезари (Приложение Г1) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1177/107327480701400203","ISSN":"15262359","PMID":"17387295","abstract":"Background: Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases composed of malignant T lymphocytes. The most common type is mycosis fungoides (MF). An accurate diagnosis of early MF may be difficult because of the varied clinical and histologic expressions of the disease. Methods: The authors review the epidemiology, possible risk factors, clinical manifestations, diagnostic techniques, staging, prognosis, and treatment options for MF. Results: The varied and often nonspecific clinical and histologic presentations of MF may delay diagnosis and staging, thus necessitating further studies such as immunophenotyping and T-cell receptor gene rearrangement analysis. Conclusions: A multidisciplinary approach to the diagnosis, staging, and treatment of MF assists in optimizing outcomes from management of patients with this disease.","author":[{"dropping-particle":"","family":"Keehn","given":"Connie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Belongie","given":"Iriana P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shistik","given":"Galina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fenske","given":"Neil A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Glass","given":"L. Frank","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cancer Control","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2007"]]},"page":"102-111","publisher":"H. Lee Moffitt Cancer Center and Research Institute","title":"The diagnosis, staging, and treatment options for mycosis fungoides","type":"article-journal","volume":"14"},"uris":["http://www.mendeley.com/documents/?uuid=60fdb40e-510a-3e65-a5e4-4e7abed6c350"]},{"id":"ITEM-2","itemData":{"DOI":"10.1182/blood-2007-03-055749","ISSN":"00064971","PMID":"17540844","abstract":"The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions. © 2007 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vonderheid","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pimpinelli","given":"Nicola","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knobler","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zackheim","given":"Herschel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Estrach","given":"Teresa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lamberg","given":"Stanford","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wood","given":"Gary","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dummer","given":"Reinhard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranki","given":"Annamari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burg","given":"Gunter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heald","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pittelkow","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernengo","given":"Maria Grazia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sterry","given":"Wolfram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laroche","given":"Liliane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trautinger","given":"Franz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-2","issue":"6","issued":{"date-parts":[["2007","9","15"]]},"page":"1713-1722","publisher":"Blood","title":"Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","type":"article","volume":"110"},"uris":["http://www.mendeley.com/documents/?uuid=5ce55666-1265-39b6-bdc7-8edcb4f47df4"]},{"id":"ITEM-3","itemData":{"DOI":"10.6004/jnccn.2008.0033","ISSN":"15401413","PMID":"18433609","abstract":"The NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin's Disease were recently revised to include recommendations for treating mycosis fungoides and Sézary syndrome. These uncommon lymphomas require a specialized evaluation and use a unique TNMB staging system. Unlike the other forms of non-Hodgkin's lymphomas, stage overwhelmingly determines prognosis and defines radically different treatment approaches. For patients with early-stage disease, initial treatment with skin-directed therapies is preferred, and many patients never require systemic therapy. For patients with refractory or advanced-stage disease, biologic therapies are often the first choices, whereas chemotherapies are reserved for later in the disease course. Many milder therapies may be repeated several times in the disease course, and maintenance and tapering strategies are common. This article also discusses the emerging role of allogeneic stem cell transplantation. © Journal of the National Comprehensive Cancer Network.","author":[{"dropping-particle":"","family":"Horwitz","given":"Steven M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Olsen","given":"Elise A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Porcu","given":"Pierliugi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"JNCCN Journal of the National Comprehensive Cancer Network","id":"ITEM-3","issue":"4","issued":{"date-parts":[["2008"]]},"page":"436-442","publisher":"Jones and Bartlett Publishers","title":"Review of the treatment of mycosis fungoides and Sézary syndrome: A stage-based approach","type":"article","volume":"6"},"uris":["http://www.mendeley.com/documents/?uuid=8c24f6d3-1d66-3630-96e4-a59fd5e84bd6"]}],"mendeley":{"formattedCitation":"[3,6,7]","plainTextFormattedCitation":"[3,6,7]","previouslyFormattedCitation":"[3,6,7]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[3,6,7].

Согласно рекомендациям Международного общества по лимфомам кожи и Европейской организации по изучению и лечению рака выделяют 4 стадии грибовидного микоза – I стадию, выделяя стадии IA и IB, а также II, III и IV стадии.
План обследования варьирует в зависимости от стадии грибовидного микоза:
- при Ia и Ib стадиях необходимо проведение физикального осмотра с картированием кожи, рентгенография органов грудной клетки и УЗИ периферических лимфатических узлов ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1177/107327480701400203","ISSN":"15262359","PMID":"17387295","abstract":"Background: Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases composed of malignant T lymphocytes. The most common type is mycosis fungoides (MF). An accurate diagnosis of early MF may be difficult because of the varied clinical and histologic expressions of the disease. Methods: The authors review the epidemiology, possible risk factors, clinical manifestations, diagnostic techniques, staging, prognosis, and treatment options for MF. Results: The varied and often nonspecific clinical and histologic presentations of MF may delay diagnosis and staging, thus necessitating further studies such as immunophenotyping and T-cell receptor gene rearrangement analysis. Conclusions: A multidisciplinary approach to the diagnosis, staging, and treatment of MF assists in optimizing outcomes from management of patients with this disease.","author":[{"dropping-particle":"","family":"Keehn","given":"Connie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Belongie","given":"Iriana P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shistik","given":"Galina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fenske","given":"Neil A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Glass","given":"L. Frank","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cancer Control","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2007"]]},"page":"102-111","publisher":"H. Lee Moffitt Cancer Center and Research Institute","title":"The diagnosis, staging, and treatment options for mycosis fungoides","type":"article-journal","volume":"14"},"uris":["http://www.mendeley.com/documents/?uuid=60fdb40e-510a-3e65-a5e4-4e7abed6c350"]},{"id":"ITEM-2","itemData":{"DOI":"10.6004/jnccn.2008.0033","ISSN":"15401413","PMID":"18433609","abstract":"The NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin's Disease were recently revised to include recommendations for treating mycosis fungoides and Sézary syndrome. These uncommon lymphomas require a specialized evaluation and use a unique TNMB staging system. Unlike the other forms of non-Hodgkin's lymphomas, stage overwhelmingly determines prognosis and defines radically different treatment approaches. For patients with early-stage disease, initial treatment with skin-directed therapies is preferred, and many patients never require systemic therapy. For patients with refractory or advanced-stage disease, biologic therapies are often the first choices, whereas chemotherapies are reserved for later in the disease course. Many milder therapies may be repeated several times in the disease course, and maintenance and tapering strategies are common. This article also discusses the emerging role of allogeneic stem cell transplantation. © Journal of the National Comprehensive Cancer Network.","author":[{"dropping-particle":"","family":"Horwitz","given":"Steven M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Olsen","given":"Elise A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Porcu","given":"Pierliugi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"JNCCN Journal of the National Comprehensive Cancer Network","id":"ITEM-2","issue":"4","issued":{"date-parts":[["2008"]]},"page":"436-442","publisher":"Jones and Bartlett Publishers","title":"Review of the treatment of mycosis fungoides and Sézary syndrome: A stage-based approach","type":"article","volume":"6"},"uris":["http://www.mendeley.com/documents/?uuid=8c24f6d3-1d66-3630-96e4-a59fd5e84bd6"]}],"mendeley":{"formattedCitation":"[3,7]","plainTextFormattedCitation":"[3,7]","previouslyFormattedCitation":"[3,7]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[3,7].
- Пациенты с II, III и IV стадиями должны быть обследованы в соответствии со стандартами обследования пациентов с нодальными лимфомами. Кроме того, при наличии пятен/бляшек необходимо определение площади поражения кожного покрова, при наличии узлов – определение их общего количества, размеров наибольшего узла и вовлеченных областей кожи.
Установление стадии заболевания является важным фактором при планировании лечения и определения прогноза течения заболевания. У большинства пациентов с ранними стадиями средняя выживаемость равна 12 лет. В поздних стадиях у пациентов с узлами, эритродермией, вовлечением л/у и крови, но без поражения внутренних органов средняя выживаемость равна 5 годам. Пациенты с узлами (Т3) имеют более плохой прогноз, чем с эритродермией (Т4). Внутренние органы вовлекаются редко, средняя выживаемость при этом меньше 2,5 лет. Пациенты со стадиями IB/IIA, имеющие фолликулярную форму грибовидного микоза или пациенты с очень «толстыми» бляшками имеют более плохой прогноз из-за сниженной чувствительности к наружным видам терапии, что необходимо учитывать при назначении лечения. В поздних стадиях наличие множественных узлов, крупноклеточной трансформации и снижения количества CD8+Т-клеток в дермальном инфильтрате и/или крови также ассоциировано со снижением выживаемости.
2.1 Жалобы и анамнез
Для грибовидного микоза характерно постепенное начало заболевания и медленное развитие. Высыпания часто спонтанно бесследно разрешаются. Пациенты предъявляют жалобы на высыпания на коже, которые часто сопровождаются чувством зуда ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1177/107327480701400203","ISSN":"15262359","PMID":"17387295","abstract":"Background: Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases composed of malignant T lymphocytes. The most common type is mycosis fungoides (MF). An accurate diagnosis of early MF may be difficult because of the varied clinical and histologic expressions of the disease. Methods: The authors review the epidemiology, possible risk factors, clinical manifestations, diagnostic techniques, staging, prognosis, and treatment options for MF. Results: The varied and often nonspecific clinical and histologic presentations of MF may delay diagnosis and staging, thus necessitating further studies such as immunophenotyping and T-cell receptor gene rearrangement analysis. Conclusions: A multidisciplinary approach to the diagnosis, staging, and treatment of MF assists in optimizing outcomes from management of patients with this disease.","author":[{"dropping-particle":"","family":"Keehn","given":"Connie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Belongie","given":"Iriana P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shistik","given":"Galina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fenske","given":"Neil A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Glass","given":"L. Frank","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cancer Control","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2007"]]},"page":"102-111","publisher":"H. Lee Moffitt Cancer Center and Research Institute","title":"The diagnosis, staging, and treatment options for mycosis fungoides","type":"article-journal","volume":"14"},"uris":["http://www.mendeley.com/documents/?uuid=60fdb40e-510a-3e65-a5e4-4e7abed6c350"]},{"id":"ITEM-2","itemData":{"DOI":"10.12788/j.sder.2018.002","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype. Cytotoxic variants are well described and do not have specific clinical, histopathological, or prognostic features. MF should be differentiated from other cutaneous epidermotropic lymphomas and from many inflammatory dermatoses with some similar clinicopathological features. The therapy of MF is planned mainly according to the stage and extent of the disease. In early phases, nonaggressive options represent the first-line strategy (eg, local corticosteroids, psoralen, and ultraviolet A [UV-A] irradiation, etc.). In patients with advanced disease, good results with potential for cure have been obtained with allogeneic stem cell transplantation, but toxicity is a serious limiting factor for this treatment. Conventional systemic chemotherapy and single-agent chemotherapy (eg, gemcitabine) give usually good results in advanced MF, but recurrences are the rule. Monoclonal antibodies directed against cluster of differentiation (CD)52 (alemtuzumab), CD30 (brentuximab vedotin), and chemokine receptor 4 (CCR4; mogamulizumab), as well as several other experimental therapies, have shown promising results and represent a valid alternative.","author":[{"dropping-particle":"","family":"Cerroni","given":"Lorenzo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"2-10","publisher":"Frontline Medical Communications","title":"Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=0eef9cf6-6919-34c1-a5e7-dca806294a6c"]},{"id":"ITEM-3","itemData":{"DOI":"10.12788/j.sder.2018.004","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, which typically presents with erythematous patches and plaques, histopathologically characterized by superficial infiltrates of small to mediumsized atypical epidermotropic T cells. Apart from this classic type of MF, many clinical and/or histopathologic variants have been described. Correct diagnosis of these MF variants is important, but may be difficult, because they may mimic a wide variety of inflammatory skin diseases. In this review, clinical and histopathologic characteristics of distinct variants of MF are presented, and their differential diagnosis and therapeutic options are discussed.","author":[{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-3","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"11-17","publisher":"Frontline Medical Communications","title":"Mycosis fungoides variants-clinicopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=4b1bd90a-5293-39d9-9282-b73a3621782a"]}],"mendeley":{"formattedCitation":"[3–5]","plainTextFormattedCitation":"[3–5]","previouslyFormattedCitation":"[3–5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[3–5].
2.2 Физикальное обследование
Клиническое обследование пациента остается основополагающим методом в диагностике начинающегося грибовидного микоза, так как дает возможность не только заподозрить грибовидный микоз, но и определить разновидность и стадию этого заболевания, а также определить оптимальное место для получения биоптата кожи. При клиническом обследовании необходимо оценить вид кожных высыпаний (пятна, бляшки, узлы или их сочетание) и площадь поражения кожных покровов. Критерии клинической диагностики ранних стадий грибовидного микоза приведены в разделе 1.6 «Клиническая картиназаболевания или состояния (группы заболеваний или состояний)»
Для установления стадии заболевания согласно рекомендациям ISLE-EORTC при наличии пятен/бляшек необходимо определение площади поражения кожного покрова, при наличии узлов – определение их общего количества, размеров наибольшего узла и вовлеченных областей кожи. Необходима также пальпация лимфатических узлов и оценка их размеров, консистенции, подвижности, спаянности с окружающими тканями, болезненности ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1182/blood-2007-03-055749","ISSN":"00064971","PMID":"17540844","abstract":"The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions. © 2007 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vonderheid","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pimpinelli","given":"Nicola","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knobler","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zackheim","given":"Herschel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Estrach","given":"Teresa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lamberg","given":"Stanford","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wood","given":"Gary","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dummer","given":"Reinhard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranki","given":"Annamari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burg","given":"Gunter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heald","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pittelkow","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernengo","given":"Maria Grazia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sterry","given":"Wolfram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laroche","given":"Liliane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trautinger","given":"Franz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2007","9","15"]]},"page":"1713-1722","publisher":"Blood","title":"Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","type":"article","volume":"110"},"uris":["http://www.mendeley.com/documents/?uuid=5ce55666-1265-39b6-bdc7-8edcb4f47df4"]}],"mendeley":{"formattedCitation":"[6]","plainTextFormattedCitation":"[6]","previouslyFormattedCitation":"[6]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[6].
2.3 Лабораторные диагностические исследования
Рекомендуется общий (клинический) анализ крови развернутый для выявления возможных отклонений ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1182/blood-2007-03-055749","ISSN":"00064971","PMID":"17540844","abstract":"The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions. © 2007 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vonderheid","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pimpinelli","given":"Nicola","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knobler","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zackheim","given":"Herschel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Estrach","given":"Teresa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lamberg","given":"Stanford","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wood","given":"Gary","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dummer","given":"Reinhard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranki","given":"Annamari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burg","given":"Gunter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heald","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pittelkow","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernengo","given":"Maria Grazia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sterry","given":"Wolfram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laroche","given":"Liliane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trautinger","given":"Franz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2007","9","15"]]},"page":"1713-1722","publisher":"Blood","title":"Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","type":"article","volume":"110"},"uris":["http://www.mendeley.com/documents/?uuid=5ce55666-1265-39b6-bdc7-8edcb4f47df4"]}],"mendeley":{"formattedCitation":"[6]","plainTextFormattedCitation":"[6]","previouslyFormattedCitation":"[6]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[6] и состояний, являющихся противопоказаниями к назначению системной терапии грибовидного микоза и для контроля безопасности проводимой системной терапии или фототерапии ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/ced.12572","ISSN":"13652230","PMID":"25622648","abstract":"Adverse drug reactions (ADRs) - that is, unintended and harmful responses to medicines - are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time-course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens-Johnson syndrome with abacavir is much commoner in patients with HLA-B∗5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs.","author":[{"dropping-particle":"","family":"Ferner","given":"R. E.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical and Experimental Dermatology","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2015","3","1"]]},"page":"105-110","publisher":"Blackwell Publishing Ltd","title":"Adverse drug reactions in dermatology","type":"article","volume":"40"},"uris":["http://www.mendeley.com/documents/?uuid=9ca54e2b-524d-390a-8a82-dfd9690144e6"]},{"id":"ITEM-2","itemData":{"DOI":"10.1111/bjh.15258","ISSN":"13652141","PMID":"29672827","abstract":"Different models to investigate the prognosis of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) have been developed by means of retrospective analyses. Here we report on a new model designed on data from the prospective T Cell Project. Twelve covariates collected by the T Cell Project were analysed and a new model (T cell score), based on four covariates (serum albumin, performance status, stage and absolute neutrophil count) that maintained their prognostic value in multiple Cox proportional hazards regression analysis was proposed. Among patients registered in the T Cell Project, 311 PTCL-NOS were retained for study. At a median follow-up of 46 months, the median overall survival (OS) and progression-free survival (PFS) was 20 and 10 months, respectively. Three groups were identified at low risk (LR, 48 patients, 15%, score 0), intermediate risk (IR, 189 patients, 61%, score 1–2), and high risk (HiR, 74 patients, 24%, score 3–4), having a 3-year OS of 76% [95% confidence interval 61–88], 43% [35–51], and 11% [4–21], respectively (P  50% and complete responses of > 20%. Side-effects are predictable, generally well tolerated and dose-related. The efficacy of IFN has increased with combination therapy without any significant increase in attendant side-effects. An update on the specifics of the different IFN subtypes, their inherent biologic activity, pharmacokinetics, efficacy and safety in CTCL is presented in this paper.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Dermatologic Therapy","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2003"]]},"page":"311-321","publisher":"Dermatol Ther","title":"Interferon in the treatment of cutaneous T-cell lymphoma","type":"article","volume":"16"},"uris":["http://www.mendeley.com/documents/?uuid=ab8a433e-5050-333a-88f9-6308f8021cb6"]},{"id":"ITEM-2","itemData":{"DOI":"10.1007/s00280-016-3043-5","ISSN":"14320843","PMID":"27142726","abstract":"Purpose: Methotrexate chemotherapy is associated with various toxicities which can result in the interruption or discontinuation of treatment and a subsequently raised risk of relapse. This umbrella systematic review was conducted to synthesize the results of all existing systematic reviews that investigate the pharmacogenetics of methotrexate-induced toxicity, with the aim of developing a comprehensive reference for personalized medicine. Methods: Databases searched were PubMed, Embase, JBI Database of Systematic Reviews and Implementation Reports, DARE, and ProQuest. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Results: Three systematic reviews on methotrexate-induced toxicity were included in the review. Meta-analyses were reported across Asian, Caucasian, pediatric and adult patients for the MTHFR C677T and A1298C polymorphisms. Toxicity outcomes included different forms of hematologic, ectodermal and hepatic toxicities. Results varied considerably depending on the patient groups and subgroups investigated in the different systematic reviews, as well as the genetic models utilized. However, significant associations were found between the MTHFR C677T allele and; hepatic toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity. Additionally, limited evidence suggests that the MTHFR A1298C polymorphism may be associated with decreased risk of skin toxicity and leukopenia. Conclusion: This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of methotrexate toxicity. The next step in making personalized medicine for methotrexate therapy a clinical reality is research on the effectiveness and cost-effectiveness of MTHFR genotype testing to enable the close monitoring of at-risk patients for the timely initiation of rescue therapies.","author":[{"dropping-particle":"","family":"Campbell","given":"Jared M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bateman","given":"Emma","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stephenson","given":"Matthew D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bowen","given":"Joanne M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Keefe","given":"Dorothy M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Peters","given":"Micah D.J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cancer Chemotherapy and Pharmacology","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2016","7","1"]]},"page":"27-39","publisher":"Springer Verlag","title":"Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses","type":"article","volume":"78"},"uris":["http://www.mendeley.com/documents/?uuid=ccaf774a-6f06-39d6-9e18-30d58c8adc43"]},{"id":"ITEM-3","itemData":{"DOI":"10.1634/theoncologist.12-10-1247","ISSN":"1083-7159","PMID":"17962618","abstract":"On October 6, 2006, the U.S. Food and Drug Administration granted regular approval to vorinostat (Zolinza(R); Merck & Co., Inc., Whitehouse Station, NJ), a histone deacetylase inhibitor, for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or recurrent disease on or following two systemic therapies. The pivotal study supporting approval was a single-arm open-label phase II trial that enrolled 74 patients with stage IB and higher CTCL who had failed two systemic therapies (one of which must have contained bexarotene). Patients received vorinostat at a dose of 400 mg orally once daily, which could be reduced for toxicity to 300 mg daily or 300 mg 5 days a week. The median age of patients was 61 years. Sixty-one patients (82%) had stage IIB or higher CTCL and 30 patients (41%) had Sézary syndrome. The median duration of protocol treatment was 118 days. The primary efficacy endpoint was objective response assessed by the Severity-Weighted Assessment Tool. The objective response rate was 30% (95% confidence interval [CI], 19.7%-41.5%), the estimated median response duration was 168 days, and the median time to tumor progression was 202 days. An additional single-center study enrolled 33 patients with similar baseline and demographic features as the pivotal trial. Thirteen of the 33 received vorinostat (400 mg/day). The response rate in these 13 patients was 31% (95% CI, 9.1%-61.4%). The most common clinical adverse events (AEs) of any grade were diarrhea (52%), fatigue (52%), nausea (41%), and anorexia (24%). Grade 3 or 4 clinical AEs included fatigue (4%) and pulmonary embolism (5%). Hematologic laboratory abnormalities included thrombocytopenia (26%) and anemia (14%). Chemistry laboratory abnormalities included increased creatinine (16%), increased serum glucose (69%), and proteinuria (51%). Most abnormalities were National Cancer Institute Common Terminology Criteria for Adverse Events grade 1 or 2. Grade 3 or greater chemistry abnormalities included hyperglycemia, hypertriglyceridemia, and hyperuricemia, hypoglycemia, hypokalemia, hyponatremia, hyperkalemia, hypercholesterolemia, hypophosphatemia, and increased creatinine.","author":[{"dropping-particle":"","family":"Mann","given":"Bhupinder S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Johnson","given":"John R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cohen","given":"Martin H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Justice","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pazdur","given":"Richard","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The Oncologist","id":"ITEM-3","issue":"10","issued":{"date-parts":[["2007","10"]]},"page":"1247-1252","publisher":"Wiley","title":"FDA Approval Summary: Vorinostat for Treatment of Advanced Primary Cutaneous T‐Cell Lymphoma","type":"article-journal","volume":"12"},"uris":["http://www.mendeley.com/documents/?uuid=06d55968-0a58-3fe0-b758-b48bfd9e87a8"]},{"id":"ITEM-4","itemData":{"DOI":"10.1016/S0140-6736(17)31266-7","ISSN":"1474547X","PMID":"28600132","abstract":"Background Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. Methods In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. Findings Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4–26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1–58·4; p30%. >50%. При наличии в инфильтрате CD30-позитивных клеток (независимо от их количества) при формулировке диагноза должно быть указано: грибовидный микоз (CD30-позитивный).
Рекомендуется проведение патолого-анатомического исследования биопсийного (операционного) материала лимфатического узла в случае выявления признаков поражения лимфатических узлов (увеличение размеров > 1,5 см в диаметре и/или с плотной, неравномерной структурой) в результате ультразвукового исследования и/или рентгенографии грудной клетки и/или МРТ и/или позитронно-эмиссионной томографии совмещенной с компьютерной томографией (ПЭТ/КТ) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1182/blood-2007-03-055749","ISSN":"00064971","PMID":"17540844","abstract":"The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions. © 2007 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vonderheid","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pimpinelli","given":"Nicola","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knobler","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zackheim","given":"Herschel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Estrach","given":"Teresa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lamberg","given":"Stanford","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wood","given":"Gary","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dummer","given":"Reinhard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranki","given":"Annamari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burg","given":"Gunter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heald","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pittelkow","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernengo","given":"Maria Grazia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sterry","given":"Wolfram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laroche","given":"Liliane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trautinger","given":"Franz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2007","9","15"]]},"page":"1713-1722","publisher":"Blood","title":"Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","type":"article","volume":"110"},"uris":["http://www.mendeley.com/documents/?uuid=5ce55666-1265-39b6-bdc7-8edcb4f47df4"]}],"mendeley":{"formattedCitation":"[6]","plainTextFormattedCitation":"[6]","previouslyFormattedCitation":"[6]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[6].
Уровень убедительности рекомендаций С (уровень достоверности доказательств – 5)
Комментарии: Для проведения биопсии выбирают лимфатические узлы размером > 1,5 см и более и/или с плотной, неравномерной. Биопсия выполняется врачами-специалистами с хирургической специализацией, в том числе врачом-онкологом/гематологом. Цель патолого-анатомического исследования биопсийного (операционного) материала лимфоузла – исключить или верифицировать наличие специфического поражения лимфатического узла/узлов, провести дифференциальную диагностику с дерматопатическим лимфаденитом. При выявлении специфического поражения лимфатических узлов пациент направляется для дальнейшего ведения и лечения к врачу-гематологу или врачу-онкологу.
Рекомендуется проведение ПЦР-исследования лимфатического узла в случае обнаружения опухолевого субстрата при патолого-анатомическом исследовании ткани лимфатического узла ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1182/blood-2007-03-055749","ISSN":"00064971","PMID":"17540844","abstract":"The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions. © 2007 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vonderheid","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pimpinelli","given":"Nicola","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knobler","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zackheim","given":"Herschel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Estrach","given":"Teresa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lamberg","given":"Stanford","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wood","given":"Gary","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dummer","given":"Reinhard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranki","given":"Annamari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burg","given":"Gunter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heald","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pittelkow","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernengo","given":"Maria Grazia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sterry","given":"Wolfram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laroche","given":"Liliane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trautinger","given":"Franz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2007","9","15"]]},"page":"1713-1722","publisher":"Blood","title":"Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","type":"article","volume":"110"},"uris":["http://www.mendeley.com/documents/?uuid=5ce55666-1265-39b6-bdc7-8edcb4f47df4"]},{"id":"ITEM-2","itemData":{"DOI":"10.1111/bjd.15266","ISSN":"0007-0963","abstract":"nodes biopsied were similar in size to the largest node. This reflects real-world practice and suggests that dependence on the size of a single node may not be reliable. We thus found that use of the combined surface area of enlarged LNs (SPD-T) as a surrogate value for LN tumour burden, better selected patients with lymphomatous nodes. In addition, six of eight N3 nodes had B2 staging, a criterion currently not factored in. Our results are limited by the relatively small retrospective study. International data are currently being collected for the PROCLIPI study (PROspective Cutaneous Lymphoma International Prognostic Index) to validate these findings with a mul-ticentre prospective design.","author":[{"dropping-particle":"","family":"Haththotuwa","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zilinskiene","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Oliff","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vydianath","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Amel‐Kashipaz","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stevens","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shah","given":"F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chaganti","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scarisbrick","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2017","9"]]},"page":"877-878","publisher":"Blackwell Publishing Ltd","title":"Biopsy correlation of surface area vs. single‐axis measurements on computed tomography scan of lymph nodes in patients with erythrodermic mycosis fungoides and Sézary syndrome","type":"article-journal","volume":"177"},"uris":["http://www.mendeley.com/documents/?uuid=3a353ffb-2abd-32e9-b499-74c43f7e1c1a"]}],"mendeley":{"formattedCitation":"[6,35]","plainTextFormattedCitation":"[6,35]","previouslyFormattedCitation":"[6,35]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[6,35].
Уровень убедительности рекомендаций С (уровень достоверности доказательств – 5)
Комментарии: ПЦР-исследование позволяет определить клональность субстрата лимфатического узла. При выявлении специфического поражения лимфатических узлов пациент направляется для дальнейшего ведения и лечения к врачу-гематологу или врачу-онкологу.
Рекомендуется применение иммуногистохимического метода в случае обнаружения опухолевого субстрата при патолого-анатомическом исследовании лимфатического узла ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1182/blood-2007-03-055749","ISSN":"00064971","PMID":"17540844","abstract":"The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions. © 2007 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vonderheid","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pimpinelli","given":"Nicola","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willemze","given":"Rein","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Knobler","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zackheim","given":"Herschel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Estrach","given":"Teresa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lamberg","given":"Stanford","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wood","given":"Gary","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dummer","given":"Reinhard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ranki","given":"Annamari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burg","given":"Gunter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heald","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pittelkow","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernengo","given":"Maria Grazia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sterry","given":"Wolfram","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laroche","given":"Liliane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trautinger","given":"Franz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2007","9","15"]]},"page":"1713-1722","publisher":"Blood","title":"Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: A proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","type":"article","volume":"110"},"uris":["http://www.mendeley.com/documents/?uuid=5ce55666-1265-39b6-bdc7-8edcb4f47df4"]},{"id":"ITEM-2","itemData":{"DOI":"10.1111/bjd.15266","ISSN":"0007-0963","abstract":"nodes biopsied were similar in size to the largest node. This reflects real-world practice and suggests that dependence on the size of a single node may not be reliable. We thus found that use of the combined surface area of enlarged LNs (SPD-T) as a surrogate value for LN tumour burden, better selected patients with lymphomatous nodes. In addition, six of eight N3 nodes had B2 staging, a criterion currently not factored in. Our results are limited by the relatively small retrospective study. International data are currently being collected for the PROCLIPI study (PROspective Cutaneous Lymphoma International Prognostic Index) to validate these findings with a mul-ticentre prospective design.","author":[{"dropping-particle":"","family":"Haththotuwa","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zilinskiene","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Oliff","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vydianath","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Amel‐Kashipaz","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stevens","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shah","given":"F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chaganti","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scarisbrick","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"British Journal of Dermatology","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2017","9"]]},"page":"877-878","publisher":"Blackwell Publishing Ltd","title":"Biopsy correlation of surface area vs. single‐axis measurements on computed tomography scan of lymph nodes in patients with erythrodermic mycosis fungoides and Sézary syndrome","type":"article-journal","volume":"177"},"uris":["http://www.mendeley.com/documents/?uuid=3a353ffb-2abd-32e9-b499-74c43f7e1c1a"]}],"mendeley":{"formattedCitation":"[6,35]","plainTextFormattedCitation":"[6,35]","previouslyFormattedCitation":"[6,35]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[6,35].
Уровень убедительности рекомендаций С (уровень достоверности доказательств – 5)
Комментарии: иммуногистохимическое исследование позволяет определить фенотип лимфоцитов в субстрате лимфатического узла. При выявлении специфического поражения лимфатических узлов пациент направляется для дальнейшего ведения и лечения к врачу-гематологу или врачу-онкологу.
Рекомендуется проведение патолого-анатомическое исследование биопсийного (операционного) материала костного мозга у пациента с поздними стадиями грибовидного микоза и/или подозрением на поражение костного мозга ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/ajcp/92.6.747","ISSN":"00029173","PMID":"2531542","abstract":"Cutaneous T-cell lymphomas (CTCLs), including Sezary syndrome, are generally assumed to spare the marrow until the disease is far advanced. The authors reviewed marrow sections from 60 patients with CTCL, looking carefully for aggregates of cerebriform cells, and found marrow involvement in 13 patients (21.7%); another 19 had abnormal lymphoid nodules that were not diagnostic of involvement, and 28 had marrows with negative results. Involved marrows had nodules or infiltrates of dysplastic cerebriform cells that were often subtle, without a significant increase in cellularity; only one case showed massive involvement. Patients with CTCL with an infiltrative component of marrow involvement had associated peripheral blood involvement (eight of eight), generalized erythroderma (six of eight), lymph node involvement (five of eight), visceral progression (five of eight), and significantly shortened median survival compared with patients with CTCL with negative marrows (11 months and 70 months, respectively; P = 0.007). In contrast, five patients with nodules of tumor in the marrow but lacking an infiltrative component did not have peripheral blood involvement; only one patient had adenopathy or visceral progression develop, and two patients have died. Significant hematologic abnormalities were generally absent. Eight of 13 patients with marrow involvement had advanced skin disease, but skin disease was limited to plaques in five patients. Eight patients had marrow involvement develop within three months of initial diagnosis. Thus, marrow involvement occurs in approximately 20% of patients with CTCL, is often present at initial diagnosis, and is associated with wide-spread dissemination and shortened survival time when an infiltrative component is present.","author":[{"dropping-particle":"","family":"Salhany","given":"K. E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Greer","given":"J. P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cousar","given":"J. B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Collins","given":"R. D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Clinical Pathology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["1989"]]},"page":"747-754","publisher":"Am J Clin Pathol","title":"Marrow involvement in cutaneous T-cell lymphoma. A clinicopathologic study of 60 cases","type":"article-journal","volume":"92"},"uris":["http://www.mendeley.com/documents/?uuid=76bee555-8042-387d-a0f9-f89e2d43644a"]}],"mendeley":{"formattedCitation":"[36]","plainTextFormattedCitation":"[36]","previouslyFormattedCitation":"[36]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[36]. При обнаружении патологических изменений в субстрате костного мозга рекомендуется проведение ПЦР-исследования, иммуногистохимического исследования и/или проточной цитофлуориметрии ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/ajcp/92.6.747","ISSN":"00029173","PMID":"2531542","abstract":"Cutaneous T-cell lymphomas (CTCLs), including Sezary syndrome, are generally assumed to spare the marrow until the disease is far advanced. The authors reviewed marrow sections from 60 patients with CTCL, looking carefully for aggregates of cerebriform cells, and found marrow involvement in 13 patients (21.7%); another 19 had abnormal lymphoid nodules that were not diagnostic of involvement, and 28 had marrows with negative results. Involved marrows had nodules or infiltrates of dysplastic cerebriform cells that were often subtle, without a significant increase in cellularity; only one case showed massive involvement. Patients with CTCL with an infiltrative component of marrow involvement had associated peripheral blood involvement (eight of eight), generalized erythroderma (six of eight), lymph node involvement (five of eight), visceral progression (five of eight), and significantly shortened median survival compared with patients with CTCL with negative marrows (11 months and 70 months, respectively; P = 0.007). In contrast, five patients with nodules of tumor in the marrow but lacking an infiltrative component did not have peripheral blood involvement; only one patient had adenopathy or visceral progression develop, and two patients have died. Significant hematologic abnormalities were generally absent. Eight of 13 patients with marrow involvement had advanced skin disease, but skin disease was limited to plaques in five patients. Eight patients had marrow involvement develop within three months of initial diagnosis. Thus, marrow involvement occurs in approximately 20% of patients with CTCL, is often present at initial diagnosis, and is associated with wide-spread dissemination and shortened survival time when an infiltrative component is present.","author":[{"dropping-particle":"","family":"Salhany","given":"K. E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Greer","given":"J. P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cousar","given":"J. B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Collins","given":"R. D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Clinical Pathology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["1989"]]},"page":"747-754","publisher":"Am J Clin Pathol","title":"Marrow involvement in cutaneous T-cell lymphoma. A clinicopathologic study of 60 cases","type":"article-journal","volume":"92"},"uris":["http://www.mendeley.com/documents/?uuid=76bee555-8042-387d-a0f9-f89e2d43644a"]}],"mendeley":{"formattedCitation":"[36]","plainTextFormattedCitation":"[36]","previouslyFormattedCitation":"[36]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[36].
Уровень убедительности рекомендаций С (уровень достоверности доказательств – 5)
Комментарии: поражение костного мозга встречается примерно у 20% пациентов с грибовидным микозом и чаще всего ассоциировано с агрессивным течением заболевания и низкой выживаемостью ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/ajcp/92.6.747","ISSN":"00029173","PMID":"2531542","abstract":"Cutaneous T-cell lymphomas (CTCLs), including Sezary syndrome, are generally assumed to spare the marrow until the disease is far advanced. The authors reviewed marrow sections from 60 patients with CTCL, looking carefully for aggregates of cerebriform cells, and found marrow involvement in 13 patients (21.7%); another 19 had abnormal lymphoid nodules that were not diagnostic of involvement, and 28 had marrows with negative results. Involved marrows had nodules or infiltrates of dysplastic cerebriform cells that were often subtle, without a significant increase in cellularity; only one case showed massive involvement. Patients with CTCL with an infiltrative component of marrow involvement had associated peripheral blood involvement (eight of eight), generalized erythroderma (six of eight), lymph node involvement (five of eight), visceral progression (five of eight), and significantly shortened median survival compared with patients with CTCL with negative marrows (11 months and 70 months, respectively; P = 0.007). In contrast, five patients with nodules of tumor in the marrow but lacking an infiltrative component did not have peripheral blood involvement; only one patient had adenopathy or visceral progression develop, and two patients have died. Significant hematologic abnormalities were generally absent. Eight of 13 patients with marrow involvement had advanced skin disease, but skin disease was limited to plaques in five patients. Eight patients had marrow involvement develop within three months of initial diagnosis. Thus, marrow involvement occurs in approximately 20% of patients with CTCL, is often present at initial diagnosis, and is associated with wide-spread dissemination and shortened survival time when an infiltrative component is present.","author":[{"dropping-particle":"","family":"Salhany","given":"K. E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Greer","given":"J. P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cousar","given":"J. B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Collins","given":"R. D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Clinical Pathology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["1989"]]},"page":"747-754","publisher":"Am J Clin Pathol","title":"Marrow involvement in cutaneous T-cell lymphoma. A clinicopathologic study of 60 cases","type":"article-journal","volume":"92"},"uris":["http://www.mendeley.com/documents/?uuid=76bee555-8042-387d-a0f9-f89e2d43644a"]}],"mendeley":{"formattedCitation":"[36]","plainTextFormattedCitation":"[36]","previouslyFormattedCitation":"[36]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[36]. Трепанобиопсия костного мозга выполняется врачами-специалистами, владеющими методикой забора трепанобиоптата костного мозга (врачами-хирургами, врачами-гематологами или врачами-онкологами). Патолого-анатомическое исследование биопсийного (операционного) материала костного мозга позволяет определить наличие специфического поражения костного мозга. При выявлении специфического поражения костного мозга пациент направляется для дальнейшего ведения и лечения к врачу-гематологу или врачу-онкологу.
Патолого-анатомическое исследование биопсийного (операционного) материала костного мозга с применением иммуногистохимического метода позволяет определить характер клеток пролиферата в костном мозге.
Рекомендуется молекулярно-генетическое исследование перестройки гена Т-клеточного рецептора ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1177/107327480701400203","ISSN":"15262359","PMID":"17387295","abstract":"Background: Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases composed of malignant T lymphocytes. The most common type is mycosis fungoides (MF). An accurate diagnosis of early MF may be difficult because of the varied clinical and histologic expressions of the disease. Methods: The authors review the epidemiology, possible risk factors, clinical manifestations, diagnostic techniques, staging, prognosis, and treatment options for MF. Results: The varied and often nonspecific clinical and histologic presentations of MF may delay diagnosis and staging, thus necessitating further studies such as immunophenotyping and T-cell receptor gene rearrangement analysis. Conclusions: A multidisciplinary approach to the diagnosis, staging, and treatment of MF assists in optimizing outcomes from management of patients with this disease.","author":[{"dropping-particle":"","family":"Keehn","given":"Connie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Belongie","given":"Iriana P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shistik","given":"Galina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fenske","given":"Neil A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Glass","given":"L. Frank","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cancer Control","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2007"]]},"page":"102-111","publisher":"H. Lee Moffitt Cancer Center and Research Institute","title":"The diagnosis, staging, and treatment options for mycosis fungoides","type":"article-journal","volume":"14"},"uris":["http://www.mendeley.com/documents/?uuid=60fdb40e-510a-3e65-a5e4-4e7abed6c350"]},{"id":"ITEM-2","itemData":{"DOI":"10.12788/j.sder.2018.002","ISSN":"15580768","abstract":"Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype. Cytotoxic variants are well described and do not have specific clinical, histopathological, or prognostic features. MF should be differentiated from other cutaneous epidermotropic lymphomas and from many inflammatory dermatoses with some similar clinicopathological features. The therapy of MF is planned mainly according to the stage and extent of the disease. In early phases, nonaggressive options represent the first-line strategy (eg, local corticosteroids, psoralen, and ultraviolet A [UV-A] irradiation, etc.). In patients with advanced disease, good results with potential for cure have been obtained with allogeneic stem cell transplantation, but toxicity is a serious limiting factor for this treatment. Conventional systemic chemotherapy and single-agent chemotherapy (eg, gemcitabine) give usually good results in advanced MF, but recurrences are the rule. Monoclonal antibodies directed against cluster of differentiation (CD)52 (alemtuzumab), CD30 (brentuximab vedotin), and chemokine receptor 4 (CCR4; mogamulizumab), as well as several other experimental therapies, have shown promising results and represent a valid alternative.","author":[{"dropping-particle":"","family":"Cerroni","given":"Lorenzo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Seminars in Cutaneous Medicine and Surgery","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2018","3","1"]]},"page":"2-10","publisher":"Frontline Medical Communications","title":"Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment","type":"article-journal","volume":"37"},"uris":["http://www.mendeley.com/documents/?uuid=0eef9cf6-6919-34c1-a5e7-dca806294a6c"]},{"id":"ITEM-3","itemData":{"DOI":"10.1182/blood.v96.9.2987","ISSN":"0006-4971","abstract":"It is now widely accepted that polymerase chain reaction (PCR) analysis of cutaneous T-cell clonality is of diagnostic value in cutaneous T-cell lymphomas (CTCLs) and most helpful in the diagnosis of mycosis fungoides (MF). However, the diagnostic and prognostic value of circulating clonal T cells remains unclear. We studied T-cell clonality in the peripheral blood (PB) and the cutaneous lesion, sampled at the same time, in 363 consecutively seen patients with a clinical suspicion of cutaneous lymphoma. Using a PCR technique providing a specific imprint of T-cell clones (PCRγ–denaturing gradient gel electrophoresis), we found that detection of identical circulating and cutaneous T-cell clones was associated with the diagnosis of CTCL (P < .001). Detection of circulating tumor cells in patients with MF was infrequent (12.5%), except in those with erythrodermic MF (42%; P = .003). Moreover, among the 46 patients who had identical circulating and cutaneous T-cell clones, 25 (56%) had erythroderma. The finding of a dominant clone in the PB but not in the skin was frequent, regardless of the clinicohistologic classification; it occurred in 30% of patients with CTCL, 41% with non-CTCL malignant infiltrates, and 34% with benign infiltrates. This pattern was significantly more frequent in patients over 60 years of age (P < .002), even in the CTCL group (P < .01). In conclusion, dominant T-cell clones detected in the PB of patients with MF by using a routine PCR technique are rarely tumoral and are more often related to age. A multicenter prospective study is under way to establish the prognostic value of circulating tumor cells.","author":[{"dropping-particle":"","family":"Delfau-Larue","given":"Marie-Hélène","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laroche","given":"Liliane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wechsler","given":"Janine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lepage","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lahet","given":"Chantal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Asso-Bonnet","given":"Marianne","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bagot","given":"Martine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Farcet","given":"Jean-Pierre","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-3","issue":"9","issued":{"date-parts":[["2000","11","1"]]},"page":"2987-2992","publisher":"American Society of Hematology","title":"Diagnostic value of dominant T-cell clones in peripheral blood in 363 patients presenting consecutively with a clinical suspicion of cutaneous lymphoma","type":"article-journal","volume":"96"},"uris":["http://www.mendeley.com/documents/?uuid=d147eb90-73a0-3186-a34a-47ef78e654f3"]},{"id":"ITEM-4","itemData":{"DOI":"10.1111/j.1365-2133.2005.06649.x","ISSN":"00070963","PMID":"16120144","abstract":"Background: A dominant T-cell clone can be detected by polymerase chain reaction (PCR) in 40-90% of cutaneous samples from patients with cutaneous T-cell lymphoma (CTCL). Materials and methods: From 1996 to 2003 we analysed 547 cutaneous biopsies performed to exclude CTCL (mycosis fungoides, MF/Sézary syndrome, SS). The final diagnosis was benign inflammatory disease (BID) in 353 samples (64.5%) and CTCL in 194 (35.5%). T-cell receptor (TCR)-γ gene rearrangement was studied by using a multiplex PCR/heteroduplex (HD) analysis. The PCR results were correlated with the clinical picture, the histological pattern and the presence of T-cell lineage antigen loss, using univariate and multivariate logistic regression analyses. Objective: To determine the sensitivity and specificity of the multiplex PCR/HD analysis and to identify which are the clinical, histopathological or immunophenotypical features significantly associated with a positive T-cell clonality. Results: A clonality was demonstrated in 83.5% of CTCL and in 2.3% of BID (P 50% and complete responses of > 20%. Side-effects are predictable, generally well tolerated and dose-related. The efficacy of IFN has increased with combination therapy without any significant increase in attendant side-effects. An update on the specifics of the different IFN subtypes, their inherent biologic activity, pharmacokinetics, efficacy and safety in CTCL is presented in this paper.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Dermatologic Therapy","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2003"]]},"page":"311-321","publisher":"Dermatol Ther","title":"Interferon in the treatment of cutaneous T-cell lymphoma","type":"article","volume":"16"},"uris":["http://www.mendeley.com/documents/?uuid=ab8a433e-5050-333a-88f9-6308f8021cb6"]}],"mendeley":{"formattedCitation":"[18]","plainTextFormattedCitation":"[18]","previouslyFormattedCitation":"[18]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[18].
Уровень убедительности рекомендаций С (уровень достоверности доказательств 5)
Комментарии: лечение проводят до достижения полного контроля (отсутствия признаков дальнейшего прогрессирования). Можно комбинировать с ПУВА-терапией, ретиноидами и химиотерапией. На фоне длительного приема препарата возможны изменения со стороны щитовидной железы. У пациентов с заболеваниями щитовидной железы перед началом лечения необходимо определить концентрацию тиреотропного гормона, рекомендуется контролировать его уровень не реже 1 раза в 6 месяцев. Очень редко – сахарный диабет. При длительном применении, обычно после нескольких месяцев лечения, возможны нарушения со стороны органа зрения. До начала терапии рекомендуется провести офтальмологическое обследование. При жалобах на любые офтальмологические нарушения необходима немедленная консультация врача-офтальмолога. Пациентам с заболеваниями, при которых могут происходить изменения в сетчатке, например, с сахарным диабетом или артериальной гипертензией, необходимо проходить офтальмологический осмотр не реже 1 раза в 6 месяцев. Пациентам с заболеваниями сердечно-сосудистой системы и/или прогрессирующими онкологическими заболеваниями требуется тщательное наблюдение и мониторинг ЭКГ.В случае появления изменений со стороны психической сферы и/или ЦНС, включая развитие депрессии, рекомендуется наблюдение психиатра в период лечения, а также в течение 6 месяцев после его окончания.
Рекомендуется пациентам с грибовидным микозом на поздних стадиях, а также в случае неэффективности или недостаточном ответа на ранее проведенную наружную терапию и/или фототерапию и/или терапию интерфероном-α вне зависимости от стадии #метотрексат** в дозе не более 50 мг в неделю (стандартная доза – 25 мг 1 раз в неделю перорально) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S0190-9622(03)01591-3","ISSN":"01909622","PMID":"14576667","abstract":"Background: Although low-dose methotrexate has been used to treat mycosis fungoides for many years, documentation is very limited. Objective: Our purpose was to review our experience with methotrexate in the treatment of 69 patients with patch/plaque and tumor stage mycosis fungoides observed for up to 201 months. Methods: This was a retrospective study. Data are presented in terms of response rates and time to treatment failure. Results: The greatest number of patients (60) had patch/plaque stage T2 disease (≥10% skin involved). Of these, 7 (12%) achieved complete remission and 13 (22%) achieved partial remission for a total response rate of 20 of 60 (33%). The median time to treatment failure was 15 months. Only 1 of 7 patients with tumor stage disease responded. Side effects caused treatment failure in 6 (9%) of the total cohort of 69 patients. Conclusion: Low-dose methotrexate may be of value in the treatment of a subset of patients with patch/plaque mycosis fungoides resistant to other therapies.","author":[{"dropping-particle":"","family":"Zackheim","given":"Herschel S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kashani-Sabet","given":"Mohammed","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McMillan","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of the American Academy of Dermatology","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2003"]]},"page":"873-878","publisher":"Mosby Inc.","title":"Low-dose methotrexate to treat mycosis fungoides: A retrospective study in 69 patients","type":"article-journal","volume":"49"},"uris":["http://www.mendeley.com/documents/?uuid=0bd3fd24-f2bb-3445-9d83-37281426c671"]}],"mendeley":{"formattedCitation":"[48]","plainTextFormattedCitation":"[48]","previouslyFormattedCitation":"[48]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[48].
Уровень убедительности рекомендаций С (уровень достоверности доказательств – 4)
Комментарии: лечение проводят до достижения полного контроля (отсутствия признаков дальнейшего прогрессирования) или до появления признаков неприемлемой токсичности можно комбинировать с IFN-α.
Перед началом лечения метотрексатом или при возобновлении терапии после перерыва необходимо проводить клинический анализ крови с подсчетом лейкоцитарной формулы и количества тромбоцитов, оценивать активность «печеночных» ферментов, концентрацию билирубина, альбумина сыворотки, а также рентгенографическое исследование органов грудной клетки и функциональные почечные тесты. При наличии клинических показаний назначают исследования с целью исключения гепатита и других соматических заболеваний.
В процессе лечения метотрексатом (ежемесячно в первые 6 месяцев и не реже, чем каждые 3 месяца в дальнейшем, при повышении доз целесообразно повышать частоту обследований) проводят следующие исследования:
Обследование ротовой полости и горла для выявления изменений слизистых оболочек.
Анализ крови с определением лейкоцитарной формулы и количества тромбоцитов. Даже при применении в обычных терапевтических дозах метотрексат может вызвать угнетение системы кроветворения. В случае значительного снижения количества лейкоцитов или тромбоцитов лечение метотрексатом немедленно прекращают и назначают симптоматическую поддерживающую терапию.
Функциональные печеночные пробы. Особое внимание необходимо уделять выявлению признаков повреждения печени. Лечение метотрексатом не следует начинать или необходимо приостанавливать в случае любых отклонений результатов функциональных печеночных тестов или биопсии печени. Обычно показатели нормализуются в течение 2 недель, после чего лечение по решению может быть возобновлено.
Функциональные почечные пробы и исследование мочи. Поскольку метотрексат экскретируется преимущественно почками, у пациентов с нарушениями функции почек может наблюдаться повышение концентрации метотрексата в крови, следствием чего могут быть тяжелые побочные реакции. Необходимо тщательно контролировать состояние пациентов, у которых возможны нарушения функции почек (например, пожилых пациентов).
Поскольку метотрексат оказывает воздействие на иммунную систему, он может изменять реакцию на вакцинацию и влиять на результаты иммунологических тестов. Особая осторожность необходима при лечении пациентов с неактивными, хроническими инфекциями (такими как опоясывающий лишай, туберкулез, вирусный гепатит В или С) ввиду их возможной активации. В период лечения метотрексатом не следует проводить вакцинацию живыми вакцинами.
В связи с возможностью активации хронической инфекции пациентам, которым планируется или проводится терапия метотрексатом, может потребоваться определение антител к поверхностному антигену (HBsAg) вируса гепатита B (Hepatitis B virus), определение антител к вирусу гепатита C (Hepatitis C virus) в крови, определение антител классов M, G (IgM, IgG) к вирусу иммунодефицита человека ВИЧ-1 (Human immunodeficiency virus HIV 1) в крови, определение антител классов M, G (IgM, IgG) к вирусу иммунодефицита человека ВИЧ-2 (Human immunodeficiency virus HIV 2) в крови.
Рекомендуются при поздних стадиях (IIB–IVB) грибовидного микоза, а также в качестве второй линии ранних стадий грибовидного микоза при отсутствии или недостаточном эффекте от проводимой терапии #вориностат 200–400 мг перорально ежедневно ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1182/blood-2009-07-202895","ISSN":"00064971","PMID":"19696197","abstract":"The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a \"stage-based\" approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-α, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used. © 2009 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Prince","given":"H. Miles","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hoppe","given":"Richard T.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-1","issue":"20","issued":{"date-parts":[["2009","11","12"]]},"page":"4337-4353","publisher":"Blood","title":"How I treat mycosis fungoides and Sézary syndrome","type":"article","volume":"114"},"uris":["http://www.mendeley.com/documents/?uuid=f9ca00c1-2f14-34eb-960a-77c45505e71d"]},{"id":"ITEM-2","itemData":{"DOI":"10.1182/blood-2006-06-025999","ISSN":"00064971","PMID":"16960145","abstract":"The activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) were evaluated in patients with refractory cutaneous T-cell lymphoma (CTCL). Group 1 received vorinostat 400 mg daily, group 2 received vorinostat 300 mg twice daily for 3 days with 4 days rest, and group 3 received vorinostat 300 mg twice daily for 14 days with 7 days rest followed by 200 mg twice daily. Treatment continued until disease progression or intolerable toxicity. The primary objective was to determine the complete and partial response (PR) rate. Time to response (TTR), time to progressive disease (TTP), response duration (DOR), pruritus relief, and safety were determined. Thirty-three patients who had received a median of 5 prior therapies were enrolled. Eight patients achieved a PR, including 7 with advanced disease and 4 with Sézary syndrome. The median TTR, DOR, and TTP for responders were 11.9, 15.1, and 30.2 weeks, respectively. Fourteen of 31 evaluable patients had pruritus relief. The most common drug-related AEs were fatigue, thrombocytopenia, diarrhea, and nausea. The most common grade 3 or 4 drug-related AEs were thrombocytopenia and dehydration. Vorinostat demonstrated activity in heavily pretreated patients with CTCL. The 400 mg daily regimen had the most favorable safety profile and is being further evaluated. © 2007 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Talpur","given":"Rakshandra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ni","given":"Xiao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhang","given":"Chunlei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hazarika","given":"Parul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kelly","given":"Cecilia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chiao","given":"Judy H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reilly","given":"John F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ricker","given":"Justin L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Richon","given":"Victoria M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Frankel","given":"Stanley R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2007","1","1"]]},"page":"31-39","publisher":"Blood","title":"Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL)","type":"article-journal","volume":"109"},"uris":["http://www.mendeley.com/documents/?uuid=b0a90e5e-79db-33ac-b61e-08085878b852"]},{"id":"ITEM-3","itemData":{"DOI":"10.1200/JCO.2006.10.2434","ISSN":"0732183X","PMID":"17577020","abstract":"Purpose: To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes. Patients and Methods: Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief (≥ 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated. Results: Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be ≥ 185 days (34+ to 441+). Median TTP was 4.9 months overall, and ≥ 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE. Conclusion: Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile. © 2007 by American Society of Clinical Oncology.","author":[{"dropping-particle":"","family":"Olsen","given":"Elise A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Youn H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuzel","given":"Timothy M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pacheco","given":"Theresa R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Foss","given":"Francine M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parker","given":"Sareeta","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Frankel","given":"Stanley R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Cong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ricker","given":"Justin L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arduino","given":"Jean Marie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Clinical Oncology","id":"ITEM-3","issue":"21","issued":{"date-parts":[["2007","7","20"]]},"page":"3109-3115","publisher":"J Clin Oncol","title":"Phase IIB multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous t-cell lymphoma","type":"article-journal","volume":"25"},"uris":["http://www.mendeley.com/documents/?uuid=bcd28bbc-61ba-30b6-ace9-dfd8899cd8f9"]},{"id":"ITEM-4","itemData":{"DOI":"10.3816/CLM.2009.n.082","ISSN":"15579190","abstract":"Introduction: Vorinostat, an orally active histone deacetylase inhibitor, was approved in October 2006 by the US Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or recurrent disease during or after treatment with 2 systemic therapies. Patients and Methods: A multicenter, open-label phase IIb trial evaluated the activity and safety of vorinostat 400 mg orally daily in patients with ≥ stage IB, persistent, progressive, or treatment-refractory mycosis fungoides or Sézary syndrome CTCL subtypes. We report the safety and tolerability of long-term vorinostat therapy in patients who experienced clinical benefit in the previous phase IIb study. Results: As of December 11, 2008, 6 of 74 patients enrolled in the original study had received vorinostat for ≥ 2 years: median age, 65 years; median number of previous therapies, 2.5; median time from diagnosis to enrollment, 1.8 years. At enrollment into the continuation phase, 5 of the 6 patients had achieved an objective response, and 1 patient had prolonged stable disease. During the follow-up study, the most common drug-related grade 1-4 adverse events (AEs) were diarrhea, nausea, fatigue, and alopecia (6, 5, 4, and 3 patients, respectively). Incidence of grade 3/4 AEs was low: anorexia (n = 1), increased creatinine phosphokinase (n = 1), pulmonary embolism (n = 1), rash (n = 1), and thrombocytopenia (n = 1). Five patients have discontinued the study drug, and 1 patient is continuing therapy. Conclusion: This post hoc subset analysis provides evidence for the long-term safety and clinical benefit of vorinostat in heavily pretreated patients with CTCL, regardless of previous treatment failures.","author":[{"dropping-particle":"","family":"Duvic","given":"Madeleine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Olsen","given":"Elise","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Breneman","given":"Debra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pacheco","given":"Theresa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parker","given":"Sareeta","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vonderheid","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Abuav","given":"Rachel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ricker","given":"Justin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rizvi","given":"Syed","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Cong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Boileau","given":"Kathleen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gunchenko","given":"Alexandra","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sanz-Rodriguez","given":"Cesar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Geskin","given":"Larisa","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical Lymphoma and Myeloma","id":"ITEM-4","issue":"6","issued":{"date-parts":[["2009","12","1"]]},"page":"412-416","publisher":"Cancer Information Group, LP","title":"Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma","type":"article-journal","volume":"9"},"uris":["http://www.mendeley.com/documents/?uuid=2ed8665e-c74a-32eb-8127-c3a483fcbdc5"]}],"mendeley":{"formattedCitation":"[49–52]","plainTextFormattedCitation":"[49–52]","previouslyFormattedCitation":"[49–52]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[49–52].
Уровень убедительности рекомендаций С (уровень достоверности доказательств – 4)
Комментарии: из побочных эффектов ингибитора гистондеацетилаз вориностата встречаются тромбоцитопения, анемия, анорексия, тошнота, мышечные спазмы. Лечение проводят до достижения отсутствия признаков дальнейшего прогрессирования или до появления признаков неприемлемой токсичности. Противопоказанием является детский возраст до 18 лет. При приеме вориностата возможно развитие тромбоцитопении и анемии, которые могут потребовать прекращения приема препарата или прекращения лечения. Возможно развитие лейкопении и нейтропении, требующих уменьшения дозы препарата. Отмечалось увеличение плазменной концентрации креатинина. Возможно также развитие гипокалиемии и увеличения плазменной концентрации креатинина, что может потребовать снижения дозы препарата. На фоне приема вориностата отмечались гипергликемия, в связи с чем может потребоваться назначение диеты и/или гипогликемической терапии. Возможно развитие протеинурии.
Применение комбинированной химиорадиотерапии не только не улучшает среднюю выживаемость пациентов по сравнению с «консервативной» терапией, а даже увеличивает частоту рецидивов, поэтому предпочтительно использовать наружную терапию, биологические препараты или их комбинацию ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1182/blood-2009-07-202895","ISSN":"00064971","PMID":"19696197","abstract":"The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a \"stage-based\" approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-α, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used. © 2009 by The American Society of Hematology.","author":[{"dropping-particle":"","family":"Prince","given":"H. Miles","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Whittaker","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hoppe","given":"Richard T.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Blood","id":"ITEM-1","issue":"20","issued":{"date-parts":[["2009","11","12"]]},"page":"4337-4353","publisher":"Blood","title":"How I treat mycosis fungoides and Sézary syndrome","type":"article","volume":"114"},"uris":["http://www.mendeley.com/documents/?uuid=f9ca00c1-2f14-34eb-960a-77c45505e71d"]}],"mendeley":{"formattedCitation":"[49]","plainTextFormattedCitation":"[49]","previouslyFormattedCitation":"[49]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[49].
Рекомендуется у пациентов с грибовидным микозом на поздних стадиях с агрессивным течением и/или неэффективностью других методов лечения применение в качестве системной химиотерапии монотерапия #гемцитабином по схеме 1200 мг/м2 в 1, 8 и 15-й дни 28-дневного цикла, всего 6 циклов ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1200/JCO.2000.18.13.2603","ISSN":"0732183X","abstract":"Purpose: To evaluate the efficacy and toxicity of gemcitabine, a novel pyrimidine antimetabolite with a low-toxicity profile and activity in several solid tumors, in patients with relapsed or refractory cutaneous T-cell lymphomas. Patients and Methods: Between May 1997 and February 1999, 44 previously treated patients with mycosis fungoides (MF; n = 30) and peripheral T-cell lymphoma unspecified (PTCLU) with exclusive skin involvement (n = 14) were enrolled onto a two-institution, phase II trial and treated with gemcitabine. This drug was given on days 1, 8, and 15 of a 28- day schedule at a dose of 1,200 mg/m2 intravenously over 30 minutes for a total of three courses. Results: Of the 44 patients, five (11.5%) achieved complete responses (CRs), 26 (59%) partial responses (PRs), and the remaining 13 showed no benefit from the treatment. Two of the CRs were histologically confirmed. The CR and PR rates were the same for patients with MF and those with PTCLU, respectively. No difference in terms of overall response rate was observed between relapsed and refractory patients. The median durations of CR and PR were 15 months (range, 6 to 22 months) and 10 months (range, 2 to 15 months), respectively. Treatment was well tolerated; hematologic toxicity was mild, and no nausea/vomiting or organ toxicity was recorded. Conclusion: The results of the present phase II study show activity of gemcitabine as a single agent in patients with pretreated cutaneous T-cell lymphoma. Further studies that use gemcitabine alone or in combination with other drugs in earlier stages of the disease are needed. (C) 2000 by American Society of Clinical Oncology.","author":[{"dropping-particle":"","family":"Zinzani","given":"Pier Luigi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Baliva","given":"Gianandrea","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Magagnoli","given":"Massimo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bendandi","given":"Maurizio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Modugno","given":"Gino","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gherlinzoni","given":"Filippo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Orcioni","given":"Giulio Fraternali","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ascani","given":"Stefano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Simoni","given":"Romeo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pileri","given":"Stefano A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tura","given":"Sante","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Clinical Oncology","id":"ITEM-1","issue":"13","issued":{"date-parts":[["2000"]]},"page":"2603-2606","publisher":"American Society of Clinical Oncology","title":"Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: Experience in 44 patients","type":"article-journal","volume":"18"},"uris":["http://www.mendeley.com/documents/?uuid=60bcf654-5fd0-3d60-93f7-2bdfa8832859"]}],"mendeley":{"formattedCitation":"[53]","plainTextFormattedCitation":"[53]","previouslyFormattedCitation":"[53]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}[53]
Уровень убедительности рекомендаций С (уровень достоверности доказательств –4)
Рекомендуется брентуксимаб ведотин** для лечения взрослых пациентов при отсутствии или недостаточном эффекте после минимум одной линии предшествующей системной терапии при наличии экспрессии CD30 + антигена ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1200/JCO.2014.60.3969","ISSN":"15277755","PMID":"26195720","abstract":"Purpose: In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored Patients and Methods: In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results: Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with №
Критерии качестваОценка выполненияВыполнен общий (клинический) анализ крови: лейкоциты, эритроциты, гемоглобин, гематокрит, тромбоциты, тромбокрит,нейтрофилыпалочкоядерные, нейтрофилы сегментоядерные, эозинофилы, базофилы, лимфоциты, моноциты, скорость оседания эритроцитов при поступлении в стационар или при проведении системной терапии или ультрафиолетового облучения кожиДа/Нет

	Выполнено патолого-анатомическое исследование биопсийного материала кожи	Да/Нет
	Проведена пациенту с ранними стадиями грибовидного микоза терапия топическими глюкокортикостероидными препаратами и/или ультрафиолетовое облучение кожи	Да/Нет
	Проведена пациенту со стадией II, IIIили IV грибовидного микоза системная терапия интерфероном альфа-2b человеческим рекомбинантным**и/или противоопухолевыми препаратами и/или антиметаболитами и/или дистанционная лучевая терапия при поражении мягких тканей	Да/Нет
	Достигнут частичный или полный регресс высыпаний у пациента с ранней стадией грибовидного микоза	Да/Нет

Список литературы
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Приложение А1. Состав рабочей группы по разработке и пересмотру клинических рекомендаций
Кубанов Алексей Алексеевич – член-корреспондент РАН, доктор медицинских наук, профессор, Президент Российского общества дерматовенерологов и косметологов.
Поддубная Ирина Владимировна – академик РАН, заслуженный деятель образования РФ, доктор медицинских наук, профессор, председатель Российского общества онкогематологов.
Белоусова Ирена Эдуардовна – доктор медицинских наук, член Российского общества дерматовенерологов и косметологов.
Самцов Алексей Викторович – доктор медицинских наук, профессор, Заслуженный деятель науки РФ, Заслуженный врач РФ, член Российского общества дерматовенерологов и косметологов.
Знаменская Людмила Федоровна – доктор медицинских наук, член Российского общества дерматовенерологов и косметологов.
Чикин Вадим Викторович – доктор медицинских наук,  член Российского общества дерматовенерологов и косметологов
Карамова Арфеня Эдуардовна – кандидат медицинских наук, член Российского общества дерматовенерологов и косметологов. 
Кузьмин Алексей Александрович, главный врач КОГКБУЗ «Центр онкологии и медицинской радиологии», г. Киров.
Горенкова Лилия Гамилевна – кандидат медицинских наук, член Национального гематологического общества.
Кравченко Сергей Кириллович – кандидат медицинских наук, член Национального гематологического общества
Чернова Наталья Геннадиевна – доктор медицинских наук, к.м.н., заведующая отделением гематологии и имиотерапии ГБУЗ «ГКБ40 ДЗМ40»
Стефанов Дмитрий Николаевич – научный сотрудник, зав. научно-организационным отделом, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России, член Российского общества онкогематологов.
Воронцова Анастасия Александровна – научный сотрудник отдела дерматологии ФГБУ «Государственный научный центр дерматовенерологии и косметологии» Минздрава России, член Российского общества дерматовенерологов и косметологов. 
Конфликт интересов: авторы заявляют об отсутствии конфликта интересов.
Приложение А2. Методология разработки клинических рекомендаций
Целевая аудитория данных клинических рекомендаций:
1.Врачи-специалисты: дерматовенерологи, гематологи, онкологи.
2.Преподаватели медицинских образовательных учреждений ВО и ДПО по специальности «Дерматовенерология»
Таблица SEQ Таблица \* ARABIC 1.Шкала оценки уровней достоверности доказательств (УДД)для методов диагностики (диагностических вмешательств)

УДД	Расшифровка
1	Систематические обзоры исследований с контролем референсным методом или систематический обзор рандомизированных клинических исследований с применением мета-анализа
2	Отдельные исследования с контролем референсным методом или отдельные рандомизированные клинические исследования и систематические обзоры исследований любого дизайна, за исключением рандомизированных клинических исследований, с применением мета-анализа
3	Исследования без последовательного контроля референсным методом или исследования с референсным методом, не являющимся независимым от исследуемого метода или нерандомизированные сравнительные исследования, в том числе когортные исследования
4	Несравнительные исследования, описание клинического случая
5	Имеется лишь обоснование механизма действия или мнение экспертов

Таблица SEQ Таблица \* ARABIC 2.Шкала оценки уровней достоверности доказательств (УДД)для методов профилактики, лечения и реабилитации (профилактических, лечебных, реабилитационных вмешательств)

УДД	Расшифровка
1	Систематический обзор РКИ с применением мета-анализа
2	Отдельные РКИ и систематические обзоры исследований любого дизайна, за исключением РКИ, с применением мета-анализа
3	Нерандомизированные сравнительные исследования, в т.ч. когортные исследования
4	Несравнительные исследования, описание клинического случая или серии случаев, исследования «случай-контроль»
5	Имеется лишь обоснование механизма действия вмешательства (доклинические исследования) или мнение экспертов

Таблица 3.Шкала оценки уровней убедительности рекомендаций(УУР) для методов профилактики, диагностики, лечения и реабилитации (профилактических, диагностических, лечебных, реабилитационных вмешательств)

УУР	Расшифровка
A	Сильная рекомендация (все рассматриваемые критерии эффективности (исходы) являются важными, все исследования имеют высокое или удовлетворительное методологическое качество, их выводы по интересующим исходам являются согласованными)
B	Условная рекомендация (не все рассматриваемые критерии эффективности (исходы) являются важными, не все исследования имеют высокое или удовлетворительное методологическое качество и/или их выводы по интересующим исходам не являются согласованными)
C	Слабая рекомендация (отсутствие доказательств надлежащего качества (все рассматриваемые критерии эффективности (исходы) являются неважными, все исследования имеют низкое методологическое качество и их выводы по интересующим исходам не являются согласованными)

Порядок обновления клинических рекомендаций.
Механизм обновления клинических рекомендаций предусматривает их систематическую актуализацию – не реже чем один раз в три года,а также при появлении новых данных с позиции доказательной медицины по вопросам диагностики, лечения, профилактики и реабилитации конкретных заболеваний, наличии обоснованных дополнений/замечаний к ранее утверждённым КР, но не чаще 1 раза в 6 месяцев.
Приложение А3. Справочные материалы, включая соответствие показаний к применению и противопоказаний, способов применения и доз лекарственных препаратов, инструкции по применению лекарственного препарата
Нет
Приложение Б. Алгоритмы действий врача

Приложение В. Информация для пациента
Грибовидный микоз относят к злокачественным заболеваниям кожи, с относительно благоприятным течением и медленной прогрессией. У большинства пациентов с ранними стадиями грибовидного микоза не происходит прогрессирования в более поздние стадии. Причина развития грибовидного микоза не установлена.
Проведение биопсии кожи с последующим гистологическим и/или иммуногистохимическим исследованием позволяет с высокой степенью достоверности верифицировать диагноз.
На поздних стадиях заболевания возможно поражение лимфатических узлов и внутренних органов. Поэтому необходимо находиться под постоянным диспансерным наблюдением, регулярно посещать врача-дерматовенеролога c целью стадирования грибовидного микоза, коррекции тактики лечения, своевременной диагностики возможной трансформации грибовидного микоза в более тяжелое заболевание – крупноклеточную лимфому.

Приложение Г1. Алгоритм диагностики ранних форм грибовидного микоза

Признаки	Критерии оценки	Количество баллов
Клинические
Основные: Наличие стабильных и/или прогрессирующих пятен или «тонких» бляшек. Дополнительные: Локализация высыпаний в областях, не подвергающихся инсоляции. Вариабельность формы и размеров высыпаний. Пойкилодермия.	2 балла за основной и два дополнительных критерия 1 балл за основной и 1 дополнительный критерий
Гистопатологические
Основные: Поверхностный лимфоидный инфильтрат. Дополнительные: Эпидермотропизм без спонгиоза. Лимфоидная атипия (клетки с гиперхромными увеличенными ядрами или неправильным или церебриформнымконткром ядра).	2 балла за основной и два дополнительных признака 1 балл за основной и 1 дополнительный признак
Молекулярно-биологические
Клональная перестройка гена Т-клеточного рецептора	1 балл
Иммунопатологические
Количество CD2+, CD3+, и/или CD5+ Т-клеток < 50%. Количество CD7+ Т-клеток < 10%. Эпидермально/дермальное несоответствие экспрессии CD2, CD3, CD5 и CD7 (дефицит экспрессии в эпидермисе).	1 балл за один или более признак
Итого	*

*Диагноз грибовидного микоза считается правомерным при общей сумме ≥ 4 баллов из любых разделов таблицы.

Приложение Г2. Стадирование грибовидного микоза согласно рекомендациям ISLE-EORTC

Кожа Т1   Ограниченные пятна, папулы, и/или бляшки, покрывающие <10% кожного покрова.            Т1а – только пятна            Т1b – бляшки ± пятна Т2   Пятна, папулы, и/или бляшки, покрывающие >10% кожного покрова.           Т2а – только пятна           Т2b - бляшки ± пятна Т3   Один или более узлов (≥1 см в диаметре) Т4   Сливающаяся эритема, покрывающая ≥80% поверхности тела Лимфатические узлы N0   Нет увеличения периферических лимфатических узлов, их биопсия не требуется N1   Периферические лимфатические узлы увеличены; гистопатология Dutchgrade 1 или NCI LN0-2             N1a – клон-негативны            N1b – клон-позитивныN2   Периферические лимфатические узлы увеличены; гистопатология Dutchgrade 2 или NCI LN3             N2a – клон-негативны            N2b – клон-позитивныN3   Периферические лимфатические узлы увеличены; гистопатология Dutchgrade 3-4 или NCI LN4, клон-позитивны или негативны NX   Периферические лимфатические узлы увеличены, нет гистологического подтверждения Внутренние органы M0   Нет вовлечения внутренних органов M1   Вовлечение внутренних органов (с уточнением органа и морфологическим подтверждением) Кровь B0   Отсутствие значительного вовлечения крови: атипичные (Сезари) клетки составляют ≤5% лимфоцитов периферической крови             B0a – клон-негативны            B0b – клон-позитивныB1   Умеренное вовлечение крови: атипичные (Сезари) клетки составляют >5% лимфоцитов периферической крови             B1a – клон-негативны            B2b – клон-позитивныB3   Значительное вовлечение крови: ≥1000/µL клеток Сезари с позитивным клоном
Стадии	T	N	M	B
Ранние IA IB IIA Поздние IIB III IIIA IIIB IVA1 IVA2 IVB	1 2 1,2 3 4 4 4 1-4 1-4 1-4	0 0 1,2 0-2 0-2 0-2 0-2 0-2 3 0-3	0 0 0 0 0 0 0 0 0 1	0,1 0,1 0,1 0,1 0,1 0 1 2 0-2 0-2

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