Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario

Abstract Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.

Variedades clínicas de micosis fungoide en una cohorte / Clinical variants of mycosis fungoides in a cohort

Resumen Introducción: La micosis fungoide es el linfoma primario de células T en piel más frecuente, con expresividad clínica heterogénea. Objetivo: Reportar las variedades clínicas y las características sociodemográficas de pacientes con micosis fungoide tratados en un hospital dermatológico. Métodos: Se incluyeron 290 pacientes con diagnóstico clínico e histopatológico de micosis fungoide atendidos en el transcurso de 11 años. Se realizó descripción sociodemográfica de los pacientes, quienes se clasificaron conforme las variantes clínicas e histopatológicas. Resultados: 58 % de los casos de micosis fungoide se presentó en mujeres y 42 % en hombres. La variedad clínica más común fue la clásica en 46.2 %; la discrómica representó 35.2 %, del cual la hipopigmentada fue la más representativa (7.6 %); la poiquilodérmica constituyó 4.1 % y la foliculotrópica, 3.1 %. La variedad papular se presentó en seis pacientes (2.1 %), la de placa única en tres (1 %) y la ictiosiforme, siringotrópica y la piel laxa granulomatosa, en un paciente cada una. La variedad granulomatosa se encontró en 0.7 % y 1.4 % presentó eritrodermia. Conclusiones: La variedad clínica más frecuente de micosis fungoide fue la clásica en fase de placa, seguida de las variedades discrómicas. Otras variedades clínicas representaron 18.6 %.

Abstract Introduction: Mycosis fungoides (MF) is the most common primary skin T-cell lymphoma, which is characterized for a heterogeneous clinical expressivity. Objective: To report clinical variants and sociodemographic characteristics in patients with MF under the care of a dermatological hospital. Methods: 290 patients with MF clinical and histopathological diagnosis attended to over the course of 11 years were included. Sociodemographic description of patients was made, who were classified according to clinical and histopathological variants. Results: MF was recorded in 57.9 % of women and 42 % of men. The most common clinical variant was the classic type in 46.2 %; dyschromic variants accounted for 35.2 %, out of which hypopigmented MF was the most representative (17.6 %); poikilodermatous MF accounted for 4.1 %, and folliculotropic, for 3.1%. The papular variant occurred in six patients (2.1 %), the single-plaque variety in three (1%), and the ichthyosiform, syringotropic and granulomatous slack skin varieties occurred in one patient each. The granulomatous variant was found in 0.7 %, and 1.4 % had erythroderma. Conclusions: The most common MF clinical variant was classic plaque stage, followed by dyschromic variants. Other clinical variants accounted for 18.6 %.

The efficacy and safety of phototherapy in geriatric patients: a retrospective study

Abstract: Background: While phototherapy is a well-established treatment for many dermatoses, data from the literature regarding its use in elderly patients are quite limited. Objective: In this study, we aimed to determine the phototherapy indications in geriatric patients and to evaluate the effectiveness and reliability of phototherapy in this group. Methods: This study included 95 patients of 65 years of age and older who were treated in our phototherapy unit between 2006 and 2015. The data for this study were collected retrospectively from patient follow-up forms in the phototherapy unit. Results: Phototherapy was administered to 28 (29.5%) patients for mycosis fungoides, 25 (26.3%) patients foplaque type psoriasis, 12 (12.6%) patients for palmoplantar psoriasis, 12 (12.6%) patients for generalized pruritus, and 18 (19%) for other dermatoses. Of the patients, 64.2% had received a narrowband UVB (NB-UVB), 21.1% oral psoralen UVA (PUVA), and 14.7% local PUVA treatment. A complete response was achieved in 76.9-85.7% of the mycosis fungoides and in 73.71-100% of the psoriasis vulgaris patients treated with NB-UVB and PUVA, respectively. All the patients with generalized pruritus were treated with NB-UVB, and 80% of these patients achieved significant improvement. The erythema rate was found to be 0.43% per session for NB-UVB treatment and 0.46% per session for PUVA treatment as a side effect. Study limitations: The limitations of our study are that it was retrospective and the remission durations of the patients are not known. Conclusion: This study showed that phototherapy is effective and reliable in the elderly population with proper dose increases and close follow-up.

Mycosis fungoides and Kaposi's sarcoma association in an HIV-negative patient

Abstract The association of mycosis fungoides and kaposi’s sarcoma in HIV-negative patients is a rare phenomenon. The presence of human herpesvirus 8 (HHV-8) – associated with all forms of Kaposi’s sarcoma – has also been recently identified in mycosis fungoides lesions. However, a causal association between HHV-8 and the onset of mycosis fungoides has not been established yet. The present case reports a patient who developed Kaposi’s sarcoma lesions after a two-year UVB phototherapy to treat a mycosis fungoides. Negative immunohistochemistry staining for Kaposi’s sarcoma-associated herpesvirus in the initial mycosis fungoides lesions strengthens the absence of a link between Kaposi’s sarcoma-associated herpesvirus and mycosis fungoides. Immunosuppression caused by the lymphoma and prolonged phototherapy were probably the contribut ing factors for the onset of Kaposi’s sarcoma.

Phototherapy for mycosis fungoides.

Background: Both phototherapy and photochemotherapy have been used in all stages of mycosis fungoides since they improve the symptoms and have a favourable adverse effect profi le. Materials and Methods: We performed an extensive search of published literature using keywords like “phototherapy”, “photochemotherapy”, “NBUVB”, “PUVA”, “UVA1”, “mycosis fungoides”, and “Sezary syndrome”, and included systematic reviews, meta-analysis, national guidelines, randomized controlled trials (RCTs), prospective open label studies, and retrospective case series. These were then arranged according to their levels of evidence. Results: Five hundred and forty three studies were evaluated, of which 107 fulfi lled the criteria for inclusion in the guidelines. Conclusions and Recommendations: Photochemotherapy in the form of psoralens with ultraviolet A (PUVA) is a safe, effective, and well tolerated fi rst line therapy for the management of early stage mycosis fungoides (MF), that is, stage IA, IB, and IIA (Level of evidence 1+, Grade of recommendation B). The evidence for phototherapy in the form of narrow-band UVB (NB-UVB) is less robust (Level of evidence 2++, Grade of recommendation B) but may be considered at least as effective as PUVA in the treatment of early-stage MF as an initial therapy. In patients with patches and thin plaques, NB-UVB should be preferentially used. PUVA may be reserved for patients with thick plaques and those who relapse after initial NB-UVB therapy. For inducing remission, three treatment sessions per week of PUVA phototherapy or three sessions per week of NB-UVB phototherapy may be advised till the patient achieves complete remission. In cases of relapse, patients may be started again on PUVA monotherapy or PUVA may be combined with adjuvants like methotrexate and interferon (Level of evidence 2+, Grade of recommendation B). Patients with early-stage MF show good response to combination treatments like PUVA with methotrexate, bexarotene or interferon- α-2b. However, whether these combinations hold a signifi cant advantage over monotherapy is inconclusive. For late stage MF, the above-mentioned combination therapy may be used as fi rst-line treatment (Level of evidence 3, Grade of recommendation C). Currently, there is no consensus regarding maintenance therapy with phototherapy once remission is achieved. Maintenance therapy should not be employed for PUVA routinely and may be reserved for patients who experience an early relapse after an initial course of phototherapy (Level of evidence 2+, Grade of recommendation B). Bath-water PUVA may be tried as an alternative to oral PUVA in case the latter cannot be administered as the former may show similar effi cacy (Level of evidence 2-, Grade of recommendation C). In pediatric MF and in hypopigmented MF, both NB-UVB and PUVA may be tried (Level of evidence 3, Grade of recommendation D).

Actualización en diagnóstico y manejo de micosis fungoide y síndrome de Sézary / Update on diagnosis and management of mycosis fungoides and Sézary's syndrome

Los linfomas cutáneos primarios consisten en una proliferación anormal de linfocitos T o B que muestran tropismo por la piel, sin evidenciarse compromiso extra cutáneo al momento del diagnóstico. Se dividen en linfomas de células T (75 por ciento-80 por ciento) y linfomas de células B (20 por ciento-25 por ciento). La micosis fungoide es una neoplasia de estirpe T y constituye el linfoma cutáneo primario más frecuente. Su presentación clínica clásica consiste en 3 etapas: parche, placa y tumor. Sin embargo, tiene múltiples variantes y un amplio diagnóstico diferencial, por lo que para su diagnóstico se requiere una estricta correlación entre la clínica y la histopatología. El síndrome de Sézary, por su parte, es considerado la variante leucémica de los linfomas cutáneos primarios y forma parte del diagnóstico diferencial de las eritrodermias. En esta revisión profundizaremos en los principales aspectos de la clínica, histopatología, criterios diagnósticos y tratamiento de la micosis fungoide y el síndrome de Sézary.

Primary cutaneous lymphomas represent an abnormal proliferation of T or B-cells with skin-homing ability, with no evidence of extra cutaneous disease at the time of diagnosis. They are divided in T-cell lymphomas (75 percent-80 percent) and B-cell lymphomas (20 percent-25percent). Mycosis fungoides (MF) is a T-cell malignancy, being the most common lymphoma. Classic MF presents 3 clinical phases: patch, plaque and tumor stage. However, it has numerous variants and a wide range of differential diagnosis, so that precise clinicopathologic correlation is necessary for make a correct diagnosis. Sézary syndrome is an aggressive leukemic primary cutaneous T-cell lymphoma variant and it is part of the spectrum of erythroderma. In this review we will analyze the main aspects about clinical presentation, histopathology, diagnosis and treatment of mycosis fungoides and Sézary syndrome.

Cutaneous T-cell lymphomas and their management strategies.

Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of lymphoproliferative disorders characterized by the proliferation of skin-homing post-thymic T-cells. It is the second most common extranodal non-Hodgekin's lymphoma. Many variants of mycosis fungoides and CTCLs are known to date, differing in clinical, histological, and immunophenotypic characteristics. Oral involvement has also been reported rarely in CTCLs. Treatment depends on the disease stage or the type of variant. New insights into the disease and the number of emerging novel therapeutic options have made it an interesting area for dermatologists and medical oncologists.

Micosis fungoide foliculotrópica / Folliculotropic mycosis fungoides

La micosis fungoide (MF) es una de las variantes más comunes del linfoma cutáneo de células T. Desde el punto de vista histológico, se observa un denso infiltrado de células blastoides de mediano a gran tamaño con cromatina dispersa, sin un nucléolo claramente distinguible localizado en la dermis media y superior pero separada de la epidermis. El estudio con inmunohistoquímica de la micosis fungoide folicular o foliculotrópica es similar al de la micosis fungoide: CD3+, CD4+, CD8-. Se presenta un paciente varón de 51 años de edad que presenta hace dos años lesiones papulares eritematosas en raíces de miembros superiores e inferiores asociado a prurito.

Mycosis fungoides (MF) is one of the most common forms of cutaneous T-cell lymphoma. There is a dense blast-cell infiltrate of medium to large size with dispersed chromatin without clearly distinguishable nucleoli located in the upper and middle dermis but separated from the epidermis. The immunohistochemical study is similar to mycosis fungoides: CD3 +, CD4+, CD8-. We present a male patient of 51 years who presented two years ago erythematous papules lesions roots in lower upper limbs associated with pruritus.

Linfoma de células cutáneas de células T, tipo micosis fungoide folicular: reporte de un caso / Cutaneous T-cell lymphoma type mycosis fungoides follicular: case report

La Micosis Fungoide (MF) es el linfoma cutáneo más común de células T. Tiene un comportamiento indolente, llevando a algunos a utilizar el término de linfoma cutáneo de células T (LLCT) como sinónimo de la MF. Se caracteriza por una erupción cutánea crónica, generalizada, y clínicamente por la evolución de los parches en placas y tumores. A continuación se presentará un caso clínico que tras un diagnóstico de liquen plano refractario a tratamiento, se diagnostica micosis fungoide folicular.

Mycosis fungoides (MF) is recognized as the most common cutaneous T-cell lymphoma (CTCL). It has an indolent behavior, leading some to use the term cutaneous T-cell lymphoma as synonymous of MF. It is characterized by chronic, widespread rash, and clinically by the evolution of patches in plaques and tumors. We describe our experience with a case that after a diagnosis of lichen planus refractory to treatment, we diagnosed follicular mycosis fungoides.

Fototerapia ultravioleta B de banda angosta para el tratamiento de psoriasis, micosis fungoide y vitiligo / Phototherapy UVB Narrow Band treatment of Psoriasis, Mycosis fungoides and Vitiligo

Numerosos estudios han demostrado el efecto beneficioso de la radiación ultravioleta para el tratamiento de enfermedades cutáneas inflamatorias o linfoproliferativas. Objetivos. Determinar la respuesta a la terapia con ultravioleta B, banda angosta (UVB-ba) en psoriasis, micosis fungoide en estadio IA, IB y vitiligo, en el Servicio de Dermatología del Hospital Privado desde mayo de 2009 a enero de 2011. Correlacionar la dosis de energía total utilizada y el número total de sesiones con la respuesta alcanzada en cada patología. Describir las reacciones adversas, determinar las características demográficas de la población y comorbilidades asociadas en psoriasis y vitiligo. Material y métodos. Se diseñó un estudio prospectivo, descriptivo, analítico, observacional. Se incluyó a todos los pacientes que consultaron para iniciar UVB-ba. De los pacientes que consultaron para inicio de UVB-ba, pero no iniciaron o abandonaron, se realizó una encuesta para evaluar las causas. Se calculó la dosis acumulada y el número de sesiones al final del tratamiento. Resultados. En psoriasis consultaron 49, pero iniciaron 25 pacientes. El 56% de los pacientes mejoró su score PASI más del 50%. En micosis fungoide, consultaron 16 pacientes y comenzaron 14. El 78,55% logró mejoría clínica mayor al 50%. A pesar de que el número de pacientes con vitíligo es escaso (6), el 50% logró repigmentación entre el 26 y 65% de su superficie corporal, y un paciente mayor al 66%. Conclusiones. La fototerapia con UVB-ba constituye una buena opción terapéutica en nuestros pacientes con patologías cuyo uso ya ha sido establecido en estudios previos, como psoriasis, vitiligo y micosis fungoide...

Micosis fungoides en niños / Mycosis fungoides in children

La micosis fungoides rara vez se describe en la niñez, aunque es el tipo más frecuente de linfoma cutáneo de células T en esta edad, en la que predomina el inmunofenotipo CD8+. Se manifiesta con parches hipopigmentados, por lo que se debe hacer diagnóstico diferencial con otras lesiones hipopigmentadas, como vitiligo, pitiriasis versicolor y lepra, entre otras. En niños es más común que se presente clínicamente en los estadios iniciales de mancha o placa, lo que hace que su pronóstico sea bueno. Las terapias más utilizadas para el tratamiento en niños son los corticosteroides tópicos de alta potencia y la fotoquimioterapia PUVA.

Es necesaria la terapia de mantenimiento con PUVA en pacientes con micosis fungoide en estadios tempranos?: evaluación de una guía de manejo / Is PUVA maintenance therapy necessary in patients with early stage mycosis fungoides?: evaluation of a treatment guideline

Objetivo: Evaluación de una guía de práctica clínica. Lugar: Centro Dermatológico CES de Sabaneta, Colombia. Diseño del estudio: Estudio de cohorte prospectivo. Materiales y métodos: Se realizó un estudio prospectivo de cohortes en 31 pacientes con micosis fungoide en estadios tempranos IA (n=16) y IB (n=15) tratados con PUVA (mínimo, 58 sesiones), en quienes se logró mejoría clínica e histológica de las lesiones. Se evaluaron como variables: tiempo de evolución, tiempo y dosis de tratamiento y antecedente de recaídas. Para la clasificación los pacientes se sometieron a examen físico completo y diversos exámenes complementarios. Además, fueron estadificados de acuerdo con el sistema TNM. La población se dividió en dos grupos según los resultados: los que recayeron durante el seguimiento (n=9) y los que no lo hicieron (n=22). Resultados: El antecedente de recaída fue la variable que más se asoció a futuras recaídas (RR=8,56) (IC95% 2,72-26,94). La presencia de terapia de mantenimiento, al igual que otras variables estudiadas, no mostró diferencias estadísticamente significativas (p=0,9) entre los grupos. Conclusión: El estudio sugiere, con alto grado de certeza, que el mantenimiento no evita recaídas futuras y que, por el contrario, el antecedente de recaída es un fuerte factor predictor de recaídas futuras.

Micosis fungoide en estadio de placas / Mycosis fungoide in stage of plates

La micosis fungoide es una neoplasia maligna originada en los linfocitos T, usualmente inicia con la aparición de manchas planas o estadio de mancha, con el correr de los años las lesiones van siendo infiltradas apareciendo las placas o estadio de placas. Presentamos a una paciente de 62 años de edad con hallazgos clínicos e histopatológicos de micosis fungoide en estadio de placas que cursa con compromiso ganglionar. Se hace una breve revisión de la presentación clínica de la enfermedad, su histopatología y tratamiento.

Mycosis fungoides is a malignant neoplasm originated in T lymphocytes, usually it initiates with the appearance of flat spots or stage of spot and as time goes by the injuries are infiltrated appearing the plates or stage of plates. Let's sense beforehand a 62-year-old patient of age with clinical finds and histopathologic of mycosis fungoide in stage of plates that it deals with commitment ganglionar. There is a brief review of the clinical presentation, histopathology and treatment of the disease.

Disease evolution of patients with mycosis fungoides--a report of 30 cases

Mycosis fungoides is the most common disease of the primary cutaneous T-cell lymphoma group. This is a retrospective study to evaluate the outcome of 30 patients with mycosis fungoides who were followed up for at least 3 years, 18 of them followed for 5 years and 9 of them followed for 7 years. A total of 10 patients achieved a sustained remission, 2 patients achieved a remission but then relapsed and three patients died from lymphoma-related death. It is concluded that the majority of the patients with T1 or T2 stage MF usually have a good prognosis. As a rule, those who do progress further in the disease have advanced stages at the moment of the diagnosis; the disease progression occurring during the first 3-5 years after diagnosis.

Micose fungóide hipocrômica / Hipopigmented mycosis fungoides

A clinical case of hipopigmented mycosis fungoides is reported concerning a negro race patient wich is considered a rarity because there have been only twenty five similar cases described in the world literature and only eight cases with the same clinical characteristics with hipopigmented macules as the only cutaneous manifestation. The diagnosis was made and confirmed by the histopathology examination demonstrating the need of this exam for the accomplishment of the diagnosis and mainly to differentiate from other hipopigmented diseases.

Feohifomicosis causada por una especie de cladosporium:localización en nalgas / Phaehyphomycosis causing by cladosphoryum specie:buttock localization

Se presenta un paciente con un cuadro de feohifomicosis causado por cladosporium cladosporoides. Se hace una revisión de sus características clínicas,resaltando la escasa frecuencia de esta micosis profunda y la buena respuesta obtenida con la terapeútica aplicada durante 24 meses de tratamiento y control evolutivo

Proposta de tratamento para as úlceras corneanas micóticas / A therapy option for Keratomycosis

Os autores apresentam uma proposta de tratamento para pacientes portadores de úlcera corneana micótica, baseados em 16 casos, estudados, prospectivamente, no Serviço de Oftalmologia do HUCAM-UFES.Esta proposta baseia-se no uso tópico da associaçäo de dois antimicóticos de amplo espectro(Natamicina e Ketoconazol), sendo o último também utilizado por via oral.Os autores concluem pela eficácia do tratamento, embora algumas intercorrências observadas durante o tratamento tenham interferido sensivelmente em seu resultado.Sugerem que propedêutica de pacientes com úlcera de córnea deve ser dirigida visando iniciar tratamento precocemente.Ressaltam a excelência do raspado corneano, para exame direto e cultura, no isolamento do fungo.Fazem referências acerca dos riscos de terapia inadequada, sem comprovaçäo etiológica das afecçöes corneanas, favorecendo o agravamento do quadro e comprometendo sensivelmente o resultado final.Enfatizam alternativas cirúrgicas que possibilitam controlar intercorrências e manter a integridade do globo ocular durante o tratamento específico visando procedimentos futuros de recuperaçäo da visäo.

Atividade de alguns antimicóticos contra fungos isolados de diferentes classes de pacientes / Some antifungals acrivity against isolated fungi from immunocompromised hosts

Pacientes imunocomprometidos säo considerados de alto risco para aquisiçöes fúngicas graves, disseminadas a partir de processos localizados. Os antifúngicos têm sido administrados de modo empírico e, em vários casos têm sido mostrado ineficazes e altamente tóxicos para o hospedeiro. Entre outros fatores, esses problemas médicos säo agravados pela carência de uma rotineira execuçäo de antibiograma para fungos a fim de subsidiar a clínica na escolha do antimicótico adequado a cada caso. Tais testes tornam-se cada vez mais necessários, em vista da crescente comprovaçäo da falta de resposta aos antifúngicos poliêmicos, azóicos e da griseofulvina contra fungos isolados da regiäo podal de indivíduos considerados sadios e de pacientes imunocomprometidos. A determinaçäo da concentraçäo inibitória mínima (CIM) foi realizada por meio da técnica de diluiçäo em ágar YNB modificado, e a da concentraçäo fungicida mínima (CFM) foi realizada em ASD. Os antifúngicos mostraram-se principalmente inibidores, e raras vezes letais, frente aos fungos isolados. De modo geral, o cetoconazol foi o antifúngico mais ativo e o fluconazol o menos ativo. Os dermatófitos, oriundos de pacientes transplantados foram menos sensíveis a determinadas concentraçöes das drogas. Com base neste trabalho, pode-se ressaltar a importância da execuçäo rotineira de antibiograma para fungos, notadamente para os isolados a partir de imunocomprometidos

Tratamiento de Linfoma T cutáneo ( Micosis fungoide ) con Interferon Alfa intralesional / Cutaneous T-cell Lymphoma (Mycosis fungoides): treatment with Interferon Alpha intralesional

Se presenta el caso de un paciente de 63 años de edad, portador de Linfoma T (Micosis Fungoide) de dos años de evolución, en todos sus estadíos (máculas, parches, placas y tumores); quien luego de haber recibido todas las opciones terapéuticas (algunas, por diversas razones, sólo parcialmente) sin resultado, inicia Interferon alfa intralesional, en dosis de 1.000.000 de U. por centímetro cuadrado de superficie cutánea que provocó remisión completa de las lesiones en seis meses, sin recaída en nueve meses de control. Presentamos una nueva modalidad terapéutica, en corto lapso de tiempo muy efectiva para una enfermedad de curso inexorable, en la que todos los resultados terapéuticos son muy poco efectivos.