Escabiose: aspectos gerais e a importância no reconhecimento e tratamento precoces / Scabies: general aspects and the importance of early recognition and treatment

A escabiose é uma dermatose infecto parasitária mais prevalente no mundo, sobretudo nas regiões tropicais e em países de baixa renda. Surtos são comuns em locais de aglomeração como presídios, escolas e campos de refugiados, e tanto o atraso no diagnóstico como o tratamento inadequado são responsáveis pela propagação da doença. Este trabalho tem por objetivos destacar os principais aspectos da escabiose bem como as apresentações dermatológicas, a fim de auxiliar no diagnóstico e tratamentos precoces, tendo como foco o médico generalista. O estudo foi realizado no Departamento de Clínica de Dermatologia do Hospital das Clínicas da Faculdade de Medicina de São Paulo (HCFMUSP), através de uma revisão de literatura com acesso aos bancos de dados eletrônicos PubMed. A escabiose é causada pelo Sarcoptes scabiei, caracterizada pelo prurido intenso e por lesões cutâneas sugestivas e localizações típicas, mas que podem variar de acordo com a faixa etária ou estados de imunossupressão. É considerada pela Organização Mundial da Saúde uma doença tropical negligenciada, podendo causar grande impacto socioeconômico e, ainda que com menor frequência, levar a complicações, muitas vezes decorrentes de infecções bacterianas secundárias, sobretudo nas formas mais graves da doença (vistas principalmente em pacientes imunossuprimidos). Por esses motivos, o reconhecimento das principais formas de apresentação clínica e sintomas associados são importantes para que o diagnóstico seja estabelecido de forma breve, possibilitando a instituição correta do tratamento e, com isso, cessando o ciclo de transmissão do ácaro.

Cutaneous metastases from solid neoplasms - Literature review.

Cutaneous metastases from solid tumors are uncommon events in clinical practice. Most of the time, the patient already has the diagnosis of a malignant neoplasm when the cutaneous metastasis is detected. However, in up to one-third of cases, cutaneous metastasis is identified before the primary tumor. Therefore, its identification may be essential for starting treatment, although it is usually indicative of poor prognosis. The diagnosis will depend on clinical, histopathological, and immunohistochemical analysis. Sometimes the identification of the primary site is difficult; however, a thorough analysis using imaging tests and constant surveillance is important.

Mycosis fungoides and Sézary syndrome: clinical presentation, diagnosis, staging, and therapeutic management.

Mycosis fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas. MF is the most common cutaneous lymphoma, and it is classified into classic Alibert-Bazin MF, folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin, each with characteristic clinical presentation, histopathological findings, and distinct clinical behaviors. SS is an aggressive leukemic variant of cutaneous lymphoma, and it is characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by malignant cells. There is a wide range of dermatological manifestations of MF/SS, and prompt recognition is essential for early diagnosis. Skin biopsy for histopathology and immunohistochemical analysis is imperative to confirm the diagnosis of MF/SS. Histopathology may also provide information that may influence prognosis and treatment. Staging follows the TNMB system. Besides advanced stage, other factors associated with poorer prognosis are advanced age, male gender, folliculotropism in histopathology of patients with infiltrated plaques and tumors in the head and neck region, large cell transformation, and elevated lactate dehydrogenase. Treatment is divided into skin-directed therapies (topical treatments, phototherapy, radiotherapy), and systemic therapies (biological response modifiers, targeted therapies, chemotherapy). Allogeneic bone marrow transplantation and extracorporeal photopheresis are other treatment modalities used in selected cases. This review discusses the main clinical characteristics, the histopathological/immunohistochemical findings, the staging system, and the therapeutic management of MF/SS.

Imbalanced IL-1B and IL-18 Expression in Sézary Syndrome.

Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3, whereas the pathway analysis indicated a further downregulation of IL1B-associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.

Mastocitose sistêmica: visão do dermatologista e relato de um caso associado a líquen plano / Systemic mastocytosis: a dermatologist's view and report of a case associated with lichen planus

Contexto: A mastocitose ocorre devido a uma proliferação neoplásica e clonal de mastócitos que se acumulam em um ou mais sistemas de órgãos. A doença é heterogênea, com manifestações que vão desde lesões cutâneas que podem regredir espontaneamente até neoplasias altamente agressivas associadas à falência de múltiplos órgãos e baixa sobrevida. Não há relatos na literatura de sua associação com líquen plano. Descrição do caso: Relatamos o caso de uma paciente com diagnóstico de mastocitose sistêmica agressiva que apresentou durante o acompanhamento quadro compatível com líquen plano. Discussão: O diagnóstico da mastocitose sistêmica é baseado em critérios que foram refinados recentemente. O tratamento classicamente envolve bloqueio de mediadores de mastócitos e terapia citorredutora para variantes avançadas da doença. Novas drogas como a midostaurina e o avapritinibe são promissoras. Conclusões: Mesmo não fazendo parte da rotina do dermatologista, a mastocitose sistêmica deve ser uma doença lembrada pelo acometimento da pele e potencial gravidade do quadro.

An update on viral-induced cutaneous lymphoproliferative disorders. CME Part I.

Viral-induced cutaneous T-cell lymphomas are an uncommon group of lymphoproliferative disorders characterized by a viral infection of T and natural killer (NK) cells. This group of cutaneous T-cell lymphomas is more commonly encountered in Asians and Native Americans from Central and South America compared with Western populations. Viral-associated lymphoproliferative disorders include a spectrum of entities that range from nonneoplastic lesions, such as chronic active Epstein-Barr virus infection and infective dermatitis to malignant diseases, such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and adult T-cell leukemia/lymphoma. This review article will focus on hydroa vacciniforme-like lymphoproliferative disorder, extranodal NK/T-cell lymphoma, adult T-cell leukemia/lymphoma, lymphomatoid granulomatosis, and Epstein-Barr virus-positive mucocutaneous ulcers. We will review the pathogenesis of these conditions and the challenges of making a timely diagnosis in early-stage disease and discuss the common clinicopathologic manifestations, mutational landscape, and approaches to treat these highly aggressive and frequently lethal types of lymphoma.

An update on Epstein-Barr virus-and human T-lymphotropic virus type-1-induced cutaneous manifestations. CME Part II.

The Epstein-Barr virus (EBV) is a DNA virus that infects 90% of the human population, is responsible for certain cutaneous lymphomas (extranodal NK/T-cell lymhoma, hydroa vacciniforme lymphoproliferative disorder, lymphomatoid granulomatosis, others), and can be associated with a variety of cutaneous manifestations (eg, infectious mononucleosis, severe mosquito bite allergy, chronic active EBV disease, Gianotti-Crosti syndrome). EBV-related skin disorders are frequent in certain populations (South and Cental America, Africa, Asia, and Oceania) and can be diagnostically challenging. The human T-lymphotropic virus type-1 is a retrovirus, which is known to be associated with adult T-cell leukemia/lymphoma, neurologic disorders, but also cutaneous non-neoplastic manifestations (infective dermatitis, infections, and infestations). We performed an updated revision of the clinical dermatologic and histopathologic findings associated with the cutaneous non-neoplastic and preneoplastic disorders occurring in association with the EBV and human T-lymphotropic virus type-1.

Cutaneous metastases from solid neoplasms - Literature review

Abstract Cutaneous metastases from solid tumors are uncommon events in clinical practice. Most of the time, the patient already has the diagnosis of a malignant neoplasm when the cutaneous metastasis is detected. However, in up to one-third of cases, cutaneous metastasis is identified before the primary tumor. Therefore, its identification may be essential for starting treatment, although it is usually indicative of poor prognosis. The diagnosis will depend on clinical, histopathological, and immunohistochemical analysis. Sometimes the identification of the primary site is difficult; however, a thorough analysis using imaging tests and constant surveillance is important.

High-dose extended-field radiotherapy plus chemotherapy improved survival in extranodal NK/T-cell lymphoma in a real-life setting: results from the multicenter T-Cell Brazil Project.

Extranodal natural-killer/T-cell lymphoma (ENKTL) is a rare and aggressive Epstein-Barr virus related mature T-cell and natural-killer malignancy. Although highly prevalent in South America, few studies covering data from this geographic location have been published. Therefore, this study aims to report clinical characteristics, prognostic factors, and outcomes in a multicenter cohort of ENKTL patients from Brazil. This retrospective, observational and multicenter study included 98 ENKTL patients treated during two decades in Brazil. Data were extracted from the T-Cell Brazil Project database. In our cohort, 59/98 patients (60.2%) were male, with a median age of 50 years. Sixty-two patients (63.3%) had B-symptoms, 26/98 (26.5%) had Eastern Cooperative Oncology Group scale ≥ 2; 16/98 (16.3%) presented extranasal disease and 34.7% (34/98) were advanced-stage (Ann Arbor/Cotswolds III/IV). The median follow-up for the whole cohort was 49 months, with an estimated 2-year overall survival (OS) and progression-free survival (PFS) of 51.1% and 17.7%, respectively. In early-stage disease (IE/IIE), the median OS was 21.8 months for patients treated with concurrent radiotherapy plus chemotherapy (CCRT-VIPD [etoposide/vp-16, ifosfamide, cisplatin and dexamethasone), 16.2 months for sequential chemoradiotherapy (SCRT) followed by asparaginase-based regimens, and 56.7 months for SCRT followed by CHOP-like (cyclophosphamide, doxorrubicin, vincristine and prednisone) treatments, p = 0.211. CCRT was associated with higher rates of early-mortality, hematological toxicity, and mucositis. Median OS was 8.2 months for patients with advanced-stage disease receiving regimens containing asparaginase compared to 3.2 months for anthracycline-based therapy, p = 0.851. Chemo-radiotherapy (CRT) regimens demonstrated better OS (p = 0.001) and PFS (p = 0.007) than chemotherapy alone. Multivariate analysis revealed anemia, relapsed/refractory (R/R) disease and radiotherapy omission as poor outcome predictors for OS. Lymphopenia and radiotherapy omission adversely affected PFS. Concerning progression of disease within 24-months (POD-24), clinical stage III/IV was a poor outcome predictor. In this real-life Brazilian cohort, ENKTL presented dismal outcomes. Radiation therapy was an independent factor for increased OS and PFS, but CCRT regimens were associated with higher toxicities. Polychemotherapy based on anti-multi drug resistant agents was not associated with survival benefit in either early or advanced-stage disease in our patient cohort.

Extraordinary Case: Unique Presentation of an Aggressive Epstein-Barr Virus-Positive Mucocutaneous Ulcer.

ABSTRACT: Epstein-Barr virus-positive mucocutaneous ulcer is a recent and unusual type of lymphoproliferation, mostly associated with various forms of immunosuppression. In most cases, they regress spontaneously, but an increasing number of reports describe a spectral behavior of the lesion, which ranges from a simple ulcer with eosinophilia to aggressive ulcers. In these cases, Epstein-Barr virus-related lymphomas are the main differential diagnosis. We report a unique observation of this rare disease with mandibular involvement. Due to bone erosion, the patient was treated with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with complete healing of the ulcer on clinical examination and PET-scan control.

Cutaneous adverse events to systemic antineoplastic therapies: a retrospective study in a public oncologic hospital

Abstract Background: Mucocutaneous adverse events are common during anticancer treatment, with variable consequences for the patient and their therapeutic regimen. Objective: To evaluate the most common adverse events, as well as the drugs associated with their appearance and the consequences for cancer treatment. Methods: A retrospective study was carried out through the analysis of patients treated at the Clinical Dermatology Unit of a public oncologic hospital. Results: A total of 138 patients with 200 adverse events were evaluated. The most commonly identified adverse events were nail and periungual changes (20%), papulopustular eruptions (13%), acneiform eruptions (12%), hand-foot syndrome (6.5%), hand-foot skin reaction (6%), and xerosis (6%). The most frequently associated antineoplastic treatment groups were classical chemotherapy (46.2%), target therapy (32.3%), and other non-antineoplastic drugs used in neoplasia protocols (16.5%). Of the total number of patients, 17.4% had their treatment suspended or changed due to a dermatological adverse event. Study limitations: Retrospective study and analysis of patients who were referred for specialized dermatological examination only, not allowing the assessment of the actual incidence of adverse events. Conclusion: A wide variety of dermatological manifestations are secondary to antineoplastic treatment with several different drugs resulting, not rarely, in the interruption or modification of therapeutic regimens.

The Role of Tumor Microenvironment in the Pathogenesis of Sézary Syndrome.

Sézary syndrome is an aggressive leukemic variant of cutaneous T-cell lymphomas, characterized by erythroderma, lymphadenopathy, and peripheral blood involvement by CD4+ malignant T-cells. The pathogenesis of Sézary syndrome is not fully understood. However, the course of the disease is strongly influenced by the tumor microenvironment, which is altered by a combination of cytokines, chemokines, and growth factors. The crosstalk between malignant and reactive cells affects the immunologic response against tumor cells causing immune dysregulation. This review focuses on the interaction of malignant Sézary cells and the tumor microenvironment.

Cutaneous adverse events to systemic antineoplastic therapies: a retrospective study in a public oncologic hospital.

BACKGROUND: Mucocutaneous adverse events are common during anticancer treatment, with variable consequences for the patient and their therapeutic regimen. OBJECTIVE: To evaluate the most common adverse events, as well as the drugs associated with their appearance and the consequences for cancer treatment. METHODS: A retrospective study was carried out through the analysis of patients treated at the Clinical Dermatology Unit of a public oncologic hospital. RESULTS: A total of 138 patients with 200 adverse events were evaluated. The most commonly identified adverse events were nail and periungual changes (20%), papulopustular eruptions (13%), acneiform eruptions (12%), hand-foot syndrome (6.5%), hand-foot skin reaction (6%), and xerosis (6%). The most frequently associated antineoplastic treatment groups were classical chemotherapy (46.2%), target therapy (32.3%), and other non-antineoplastic drugs used in neoplasia protocols (16.5%). Of the total number of patients, 17.4% had their treatment suspended or changed due to a dermatological adverse event. STUDY LIMITATIONS: Retrospective study and analysis of patients who were referred for specialized dermatological examination only, not allowing the assessment of the actual incidence of adverse events. CONCLUSION: A wide variety of dermatological manifestations are secondary to antineoplastic treatment with several different drugs resulting, not rarely, in the interruption or modification of therapeutic regimens.

Characteristics and outcomes of 727 patients with mycosis fungoides and Sézary syndrome from a Brazilian cohort.

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most prevalent cutaneous lymphomas. They were not described in a large Brazilian cohort yet. We aimed, with this single-center, retrospective cohort analysis, to describe the characteristics and outcomes of MF/SS in a tertiary public health service in Brazil. METHODS: MF/SS patients evaluated at the University of São Paulo Medical School between 1989 and 2018 were included. Data were collected at diagnosis. Demographic, clinical, histopathological, immunopathological, molecular, laboratory, and follow-up data were analyzed. RESULTS: Among 727 patients, 92.6% (673) were diagnosed with MF, 7.4% (54) with SS. There were 51.2% (372) of males, 48.8% (355) of females. The median age was 51.8 years; it was higher in erythrodermic MF (60.2) and SS (60.9). Among MF, 41.8% (281) had classic MF, 4.9% (33) folliculotropic MF, 1.8% (12) granulomatous slack skin, and 0.3% (2) pagetoid reticulosis. Common subtypes included erythrodermic (14.1%, 95), hypopigmented (10.8%, 73), and poikilodermatous MF (10.8%, 73). Extracutaneous involvement was rare. Five, 10, 20, and 30-year overall survival rates were 97.3%, 92.4%, 82.6%, and 82.6% for early-stage, and 58.6%, 42.7%, 20.8%, and 15.4% for advanced-stage disease, respectively. After multivariate analysis, SS diagnosis, folliculotropic MF, erythrodermic MF, clinical stage, age (≥60 years), increased lactate dehydrogenase, and large cell transformation conferred poorer prognosis. CONCLUSIONS: We observed a higher percentage of hypopigmented MF compared to the literature, and demographic (older age) and prognostic (poorer prognosis) similarities between erythrodermic MF and SS, suggesting a possible relationship between these erythrodermic lymphomas. Factors associated with a poorer prognosis were compatible with the literature.

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

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.