RESUMEN
Kimura disease (KD) is a rare, chronic angiolymphoproliferative inflammatory disease appearing to be mostly restricted to the skin and soft tissue. Cutaneous involvement of KD includes head and/or neck nodules showing suggestive histological features, frequently associated with an atopic dermatitis-like or prurigo-like presentation. KD is challenging to treat, with high rate of recurrence using current therapeutic strategies. Evidence for involvement of a T-helper type 2 (Th2) immune response in KD pathogenesis has been found in previous studies. Consequently, this study aimed to determine the efficacy and safety of dupilumab, a human monoclonal antibody that inhibits signalling of key Th2 cytokines, interleukin (IL)-4 and IL-13, within a single-centre cohort of patients with cutaneous KD. Two adults with a diagnosis of refractory (failure of at least one treatment line) cutaneous-restricted KD based on clinical, biological, histological, molecular and imaging findings received dupilumab for KD, and showed dramatic response with a good safety profile.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Enfermedad de Kimura , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Adulto , Enfermedad de Kimura/tratamiento farmacológico , Enfermedad de Kimura/patología , Persona de Mediana Edad , Femenino , Resultado del Tratamiento , Interleucina-4 , Interleucina-13/antagonistas & inhibidoresRESUMEN
BACKGROUND: VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by acquired somatic mutations in UBA1. Sweet-syndrome-like skin disorders [and especially histiocytoid Sweet syndrome (HSS)] may be associated with VEXAS syndrome. OBJECTIVES: To characterize the clinical and histopathological features of HSS in patients with VEXAS syndrome. METHODS: Skin biopsies with a histological diagnosis of HSS at Rennes University Medical Center (Rennes, France) between October 2011 and January 2022 were reviewed in this study. Sanger sequencing and digital polymerase chain reaction were used to screen skin, blood and bone marrow samples for UBA1 variants, and thus classify patients as having VEXAS syndrome or not. We evaluated the clinical, histological and molecular (UBA1) characteristics of patients with or without VEXAS syndrome. RESULTS: We compared 15 skin biopsies from 7 patients found to have VEXAS syndrome and 19 skin biopsies from 15 patients without VEXAS syndrome. Persistent C-reactive protein elevation, macrocytosis, anaemia and haematological malignancies were more prevalent in patients with VEXAS syndrome [6/7 (86%), 6/7 (86%), 7/7 (100%) and 6/7 (86%), respectively] than in patients without [5/14 (36%), 6/15 (40%), 8/15 (53%) and 8/15 (53%), respectively]. These features sometimes appeared after the first skin manifestations, and a UBA1 mutation was found in the skin of five patients with VEXAS syndrome. Dermal infiltration by reniform histiocytoid cells (myeloperoxidase-positive and/or CD163-positive) and a periadnexal distribution were more frequently observed in VEXAS syndrome biopsies [15/15 (100%) and 3/15 (20%), respectively, vs. 11/19 (58%) and 0/19 (0%) in non-VEXAS syndrome biopsies, respectively]. CONCLUSIONS: Our findings might help pathologists to consider a diagnosis of VEXAS syndrome and to initiate early genetic testing.
Asunto(s)
Mutación , Piel , Síndrome de Sweet , Enzimas Activadoras de Ubiquitina , Humanos , Síndrome de Sweet/patología , Síndrome de Sweet/genética , Masculino , Persona de Mediana Edad , Femenino , Biopsia , Enzimas Activadoras de Ubiquitina/genética , Piel/patología , Adulto , Anciano , Enfermedades Autoinflamatorias Hereditarias/genética , Enfermedades Autoinflamatorias Hereditarias/patología , Enfermedades Autoinflamatorias Hereditarias/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Enfermedades Genéticas Ligadas al Cromosoma X/complicacionesRESUMEN
BACKGROUND: Our objective was to describe the clinical, histological characteristics, and disease outcome of a cohort of mycosis fungoides (MF) diagnosed during childhood including disease status at adulthood. METHODS: This is a retrospective multicentre survey of patients aged under 18 years at diagnosis with histologically confirmed MF. Patients' clinical and histological characteristics, treatments, and disease outcome (for patients followed for more than 12 months) were analysed. RESULTS: Forty-six patients were included (median age at diagnosis: 11 years; M:F sex ratio: 3:1) with 39 (85%) followed for at least 12 months. Thirty-nine patients (85%) had stage I MF. Hypopigmented patches were observed in 48% and folliculotropism in 43% patients. Immunophenotype of the skin infiltrate was predominantly CD8+ in 17% of patients. Initial management included a wait-and-see strategy in 6/39 (15%), skin-directed treatment in 27 (69%), and systemic treatment in 6 (15%) patients, respectively, with partial or complete clinical response (PR or CR) observed in 28 patients (72%). 14/39 patients (36%) relapsed after initial response. After a median follow-up period of 54 months, disease status at last news was PR or CR in 31/39 (79%), stable disease in 6 (15%), and progression in 2 (5%) patients. Histological transformation was observed in 3/39 (8%). Of the 15 patients followed until adulthood, 13 (87%) had persistent MF. DISCUSSION: This survey confirms the high frequency of hypopigmented and folliculotropic lesions and of CD8+ immunophenotype compared to adult MF patients. The long-term course is usually indolent but transformation may occur sometimes long after disease onset and the disease may persist during adulthood.
Asunto(s)
Hipopigmentación , Micosis Fungoide , Neoplasias Cutáneas , Adulto , Humanos , Niño , Adolescente , Anciano , Neoplasias Cutáneas/diagnóstico , Micosis Fungoide/diagnóstico , Estudios Retrospectivos , Hipopigmentación/tratamiento farmacológico , Hipopigmentación/patología , Administración CutáneaRESUMEN
is missing (Short communication).
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Erupciones por Medicamentos/etiología , Erupciones Liquenoides/inducido químicamente , Enfermedades de la Boca/inducido químicamente , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Corticoesteroides/administración & dosificación , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/tratamiento farmacológico , Femenino , Humanos , Erupciones Liquenoides/diagnóstico , Erupciones Liquenoides/tratamiento farmacológico , Persona de Mediana Edad , Enfermedades de la Boca/diagnóstico , Enfermedades de la Boca/tratamiento farmacológico , Inducción de Remisión , Resultado del TratamientoRESUMEN
is missing (Short communication).
Asunto(s)
Enfermedad de Hodgkin , Lupus Eritematoso Cutáneo , Lupus Eritematoso Discoide , Linfoma de Células B de la Zona Marginal , Neoplasias Cutáneas , Humanos , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/diagnóstico , Neoplasias Cutáneas/diagnósticoAsunto(s)
Síndromes Mielodisplásicos , Enfermedades de la Piel , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Enfermedades de la Piel/genética , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patologíaAsunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfoma Cutáneo de Células T , Humanos , Recurrencia Local de Neoplasia , Nitrilos , Linfoma Cutáneo de Células T/tratamiento farmacológico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Estudios Retrospectivos , Enfermedad CrónicaAsunto(s)
Linfoma Cutáneo de Células T , Micosis Fungoide , Neoplasias Cutáneas , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/patología , Micosis Fungoide/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Piel/patología , PronósticoRESUMEN
A 62-year-old human immunodeficiency virus-positive man was admitted for multiple cutaneous and subcutaneous nodules on his lower limbs, corresponding to an undifferentiated proliferation of spindle and pleomorphic cells, with irregular nuclei and numerous mitoses. The tumor cells were negative for a large panel of immunohistochemical markers, except CD10. MDM2 immunohistochemical staining was also negative, leading to the diagnosis of Fédération Nationale des Centres de Lutte contre le Cancer grade III undifferentiated pleomorphic sarcoma (UPS). Array-comparative genomic hybridization showed a highly complex karyotype, with amplification of the 4q12 region, an area that contains only the platelet-derived growth factor receptor α (PDGFRa) gene. This amplification of PDFGRa, molecular hallmark of intimal sarcoma (IS), led to the diagnosis of skin IS metastasis. A positron emission tomography showed a hypermetabolic mass protruding in the preaortic area, consistent with the diagnosis of aortic IS. Our study shows that a rare differential diagnosis in peripheral UPS can be IS skin metastasis, and underlines the importance of molecular analyses in UPS.
Asunto(s)
Cromosomas Humanos Par 4/genética , Amplificación de Genes , Infecciones por VIH , Neoplasias de los Labios , Proteínas de Neoplasias , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Sarcoma , Neoplasias Cutáneas , Infecciones por VIH/diagnóstico , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , Humanos , Neoplasias de los Labios/diagnóstico , Neoplasias de los Labios/genética , Neoplasias de los Labios/metabolismo , Neoplasias de los Labios/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/metabolismo , Sarcoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaAsunto(s)
Glucocorticoides/uso terapéutico , Leucemia Mieloide Aguda/complicaciones , Síndromes Mielodisplásicos/complicaciones , Síndrome de Sweet/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/inmunología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/inmunología , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Piel/inmunología , Piel/patología , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/tratamiento farmacológico , Síndrome de Sweet/inmunología , Brote de los Síntomas , Factores de TiempoRESUMEN
BACKGROUND: Cutaneous polyarteritis nodosa (cPAN) is a skin medium vessel neutrophilic arteritis with livedo, nodules, and ulcerations. Macular lymphocytic arteritis (MLA) is a small arteritis with erythematous or pigmented macules and typical histologic features (a lymphocytic infiltrate, concentric fibrin ring, no disruption of the internal elastic lamina). OBJECTIVE: We sought to assess the frequency of clinical and histologic features of MLA in patients with cPAN. METHODS: This was a monocentric retrospective analysis of patients given the diagnosis of cPAN with blinded assessment of skin biopsy specimens. RESULTS: All 35 patients included had an infiltrated livedo, nodules, or both. Ulceration was rare. Erythematous or pigmented lesions were present in 54% of patients. Predominantly lymphocytic arteritis, a paucity of neutrophils, concentric fibrin ring, and absence of internal lamina elastic disruption were present in 60%, 20%, 18%, and 23% of patients, respectively. Median follow-up was 11 years. None of the patients had systemic involvement, and 57% had a complete remission. The incidence of complete remission was not different between patients having a predominant lymphocyte infiltrate or few neutrophils. LIMITATIONS: This was a retrospective, monocentric study without a control group of patients with MLA. CONCLUSIONS: Our data do not favor the classification of cPAN and MLA as distinct entities.
Asunto(s)
Arteritis/patología , Linfocitos/patología , Poliarteritis Nudosa/patología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Arteritis/diagnóstico , Arteritis/epidemiología , Biopsia con Aguja , Estudios de Cohortes , Bases de Datos Factuales , Diagnóstico Diferencial , Femenino , Francia , Humanos , Inmunohistoquímica , Incidencia , Estimación de Kaplan-Meier , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Poliarteritis Nudosa/diagnóstico , Poliarteritis Nudosa/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Distribución por Sexo , Método Simple Ciego , Estadísticas no Paramétricas , Adulto JovenRESUMEN
BACKGROUND: Neutrophilic dermatoses refer to a group of cutaneous inflammatory disorders characterized by neutrophilic infiltration of the skin. Neutrophilic dermatoses have been reported in association with various conditions including autoimmune diseases, inflammatory bowel diseases, and neoplasia. In the later condition, myeloproliferative disorders and monoclonal gammopathy (monoclonal immunoglobulin [MIg]) are the most frequent. Only few data are available in case of neutrophilic dermatoses associated with MIg regarding the pathophysiology and the clinical outcome. OBJECTIVE: We sought to gain further insight into clinical and biological aspects of neutrophilic dermatoses associated with MIg. METHODS: We report a retrospective series of 26 patients with neutrophilic dermatoses associated with MIg focusing on clinical and biological aspects, with a study of a large panel of cytokines, chemokines, and adhesion molecules. RESULTS: This study reveals an association between MIg IgA isotype and neutrophilic dermatoses, and a specific inflammatory pattern including elevated interleukin 6, vascular endothelial growth factor, monocyte chemotactic protein-1, epidermal growth factor, and intercellular adhesion molecule-1. LIMITATIONS: This is a retrospective study from a single institution with a limited number of participants. CONCLUSION: Our data highlight a strong association between IgA isotype and neutrophilic dermatoses, and the existence of a specific inflammatory profile involving several molecules.
Asunto(s)
Inmunoglobulina A/inmunología , Isotipos de Inmunoglobulinas/inmunología , Paraproteinemias/complicaciones , Paraproteinemias/inmunología , Enfermedades de la Piel/complicaciones , Enfermedades de la Piel/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Moléculas de Adhesión Celular/sangre , Quimiocinas/sangre , Citocinas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos , Paraproteinemias/diagnóstico , Estudios Retrospectivos , Enfermedades de la Piel/diagnósticoAsunto(s)
Antirreumáticos/uso terapéutico , Enfermedades Óseas/tratamiento farmacológico , Infliximab/uso terapéutico , Necrobiosis Lipoidea/tratamiento farmacológico , Enfermedades Óseas/etiología , Articulación del Codo , Humanos , Masculino , Persona de Mediana Edad , Necrobiosis Lipoidea/complicacionesRESUMEN
The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38-0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41-0.77) and progression-free survival 31% (95%CI: 0.19-0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1-0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3-6.2; P=0.01) but also transplant-related mortality (HR=10(-7), 95%CI: 4.10(-8)-2.10(-7); P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Francia , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Linfoma Cutáneo de Células T/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Recurrencia , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: A rare variant of mycosis fungoides (MF), syringotropic MF (STMF) is characterized by a particular tropism of the lymphocytic infiltrate for the eccrine structures, and included in the follicular subtype of MF in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. OBJECTIVE: We sought to determine the clinicopathologic features and disease course of patients with STMF. METHODS: A retrospective study was conducted to identify patients with STMF from 1998 to 2013. RESULTS: Nineteen patients were included: 15 men and 4 women, mean age 55 years (range, 24-86). Most had multiple lesions (n=16, 84%) with associated alopecia (n=12, 63%) and/or punctuated aspect (n=12, 63%). Palms or soles were involved in 10 cases (53%). Folliculotropism was found in 13 cases (68%). After a median follow-up of 70 months (range, 2-140), 3 patients died, 1 from disease-related death. The 5-year overall and disease-specific survival were 100%. The disease-specific survival was significantly higher than in 54 patients with folliculotropic MF without syringotropism (5-year disease-specific survival, 74%; 95% confidence interval, 58%-94%, P=.02). LIMITATIONS: Retrospective setting is a limitation. CONCLUSIONS: In the spectrum of adnexotropic MF, STMF appears as a distinct entity from follicular MF, with peculiar clinical characteristics and natural history.