RESUMEN
The emergence of immune-based treatments for cancer has led to a growing field dedicated to understanding and managing iatrogenic immunotoxicities that arise from these agents. Immune-related adverse events (irAEs) can develop as isolated events or as toxicities affecting multiple body systems. In particular, this review details the neurological irAEs from immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell immunotherapies. The recognition and treatment of neurological irAEs has variable success, depending on the severity and nature of the neurological involvement. Understanding the involved mechanisms, predicting those at higher risk for irAEs, and establishing safety parameters for resuming cancer immunotherapies after irAEs are all important fields of ongoing research.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/terapia , Biomarcadores Farmacológicos/análisis , Biomarcadores de Tumor/análisis , Antígeno CTLA-4/antagonistas & inhibidores , Encefalitis/inducido químicamente , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia Adoptiva/métodos , Meningitis Aséptica/inducido químicamente , Meningitis Aséptica/inmunología , Neoplasias/inmunología , Síndromes Paraneoplásicos/inducido químicamente , Receptores Quiméricos de Antígenos/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
Patients with cancer may experience neuropathy at any stage of malignancy, ranging from symptoms that are the earliest signs of cancer to side effects of treatment. Peripheral nerves are affected most commonly in a symmetric, stocking-glove pattern. Sensory neuronopathies, plexopathies, and radiculopathies may also be seen. The most common type of neuropathy in patients with cancer is related to chemotherapy, and recently peripheral nerve complications have been described as an effect of immune checkpoint inhibitors too. Other causes include paraneoplastic syndromes, direct tumor infiltration, and radiation. Treatment focuses on addressing the underlying cancer and management of neuropathic pain.
Asunto(s)
Neuropatías del Plexo Braquial/etiología , Neoplasias/complicaciones , Síndromes Paraneoplásicos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Traumatismos por Radiación/complicaciones , Antineoplásicos/efectos adversos , Neuropatías del Plexo Braquial/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Neoplasias/tratamiento farmacológico , Síndromes Paraneoplásicos/inducido químicamente , Síndromes Paraneoplásicos/diagnóstico , Enfermedades del Sistema Nervioso Periférico/complicaciones , Traumatismos por Radiación/diagnósticoAsunto(s)
Dermatomiositis , Ectropión , Síndromes Paraneoplásicos , Autoanticuerpos , Capecitabina/efectos adversos , Dermatomiositis/inducido químicamente , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Ectropión/inducido químicamente , Ectropión/diagnóstico , Humanos , Síndromes Paraneoplásicos/inducido químicamente , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/tratamiento farmacológicoAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Síndromes Paraneoplásicos/inducido químicamente , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Enfermedades de la Médula Espinal/inducido químicamente , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Síndromes Paraneoplásicos/diagnóstico por imagen , Síndromes Paraneoplásicos/inmunología , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/inmunologíaAsunto(s)
Antagonistas de Andrógenos/efectos adversos , Tumores Neuroendocrinos/tratamiento farmacológico , Síndromes Paraneoplásicos/inducido químicamente , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/secundario , Síndromes Paraneoplásicos/patología , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/patologíaRESUMEN
BACKGROUND: Paraneoplastic hyperleucocytosis (PH) is sporadically seen in patients with advanced solid tumors. CASE PRESENTATION: We report a female patient with disseminated melanoma metastases. Two days after the first dosage of combined immunotherapy using the cytotoxic T lymphocyte antigen-4 (CTLA-4) blocker ipilimumab and the programmed death receptor-1 (PD-1) blocker nivolumab the patient developed asymptomatic hyperleucocytosis (over 120.000 leucocytes per µl) associated with elevated granulocyte colony-stimulating factor blood levels. Hematological and infectious disorders could be ruled out. Although paraneoplastic hyperleucocytosis spontaneously resolved she died from progressive disease about 60 days after start of treatment. CONCLUSIONS: PH is extremely rare in malignant melanoma, however, most patients who developed this complication had preceding immunotherapies such as interleukin-2. The latter observation and the fact that our patient developed PH rapidly after initiation of ipilimumab and nivolumab immunotherapy indicate an immune-mediated mechanism which may trigger PH under unknown circumstances. The development of paraneoplastic hyperleucocytosis indicates a very poor prognosis.
Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ipilimumab/efectos adversos , Leucocitosis/inducido químicamente , Nivolumab/efectos adversos , Síndromes Paraneoplásicos/inducido químicamente , Anciano , Resultado Fatal , Femenino , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patologíaRESUMEN
A 50-year-old man with lung adenocarcinoma (c-T1aN2M1b) experienced reddish purpura mainly on the lower legs after receiving 12 cycles of second-line chemotherapy with docetaxel. There was tumor enlargement on computed tomography performed to assess the therapeutic response, so paraneoplastic IgA vasculitis was considered. IgA vasculitis was diagnosed based on a biopsy of the skin lesion and histology of an upper gastrointestinal hemorrhagic mucosal erosion. As IgA vasculitis can lead to serious gastrointestinal or systemic complications, IgA vasculitis should be considered as a differential diagnosis for rashes in patients with malignancy.
Asunto(s)
Adenocarcinoma/complicaciones , Exantema/inducido químicamente , Neoplasias Pulmonares/complicaciones , Síndromes Paraneoplásicos/inducido químicamente , Púrpura/inducido químicamente , Taxoides/efectos adversos , Taxoides/uso terapéutico , Vasculitis/inducido químicamente , Adenocarcinoma del Pulmón , Diagnóstico Diferencial , Docetaxel , Exantema/diagnóstico por imagen , Humanos , Inmunoglobulina A , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos/diagnóstico por imagen , Síndromes Paraneoplásicos/terapia , Púrpura/diagnóstico por imagen , Resultado del Tratamiento , Vasculitis/diagnóstico por imagen , Vasculitis/terapiaRESUMEN
The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes associated with lung cancer appears useful. This article is the second of a series of five and deals with hematologic, cutaneous and vascular syndromes.
Asunto(s)
Enfermedades Autoinmunes/inducido químicamente , Neoplasias Pulmonares/complicaciones , Síndromes Paraneoplásicos/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Femenino , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/terapia , Humanos , Inmunoterapia/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Síndromes Paraneoplásicos/inducido químicamente , Enfermedades de la Piel/complicaciones , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/terapia , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/inmunología , Enfermedades Vasculares/terapiaRESUMEN
The authors present a case of suspected pseudo-Stauffer's syndrome in a male with treatment refractory schizoaffective disorder following asenapine use. We discuss our management of this case, and believe knowing about this potential adverse effect and it's management could be useful for clinicians.
Asunto(s)
Antipsicóticos/efectos adversos , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Hepatopatías/etiología , Síndromes Paraneoplásicos/inducido químicamente , Fosfatasa Alcalina/metabolismo , Dibenzocicloheptenos , Humanos , Hepatopatías/complicaciones , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos/complicaciones , Esquizofrenia/tratamiento farmacológico , gamma-Glutamiltransferasa/metabolismoRESUMEN
A patient diagnosed with metastatic melanoma developed the paraneoplastic syndrome of humoral hypercalcemia of malignancy and cachexia after receiving ipilumumab. The cause of the hypercalcemia was thought to be secondary to parathyroid hormone-related peptide (PTHrP) as plasma levels were found to be elevated. The patient underwent two tumor biopsies: at diagnosis (when calcium levels were normal) and upon development of hypercalcemia and cachexia. PTHrP expression was higher in melanoma cells when hypercalcemia had occurred than prior to its onset. Metabolic characterization of melanoma cells revealed that, with development of hypercalcemia, there was high expression of monocarboxylate transporter 1 (MCT1), which is the main importer of lactate and ketone bodies into cells. MCT1 is associated with high mitochondrial metabolism. Beta-galactosidase (ß-GAL), a marker of senescence, had reduced expression in melanoma cells upon development of hypercalcemia compared to pre-hypercalcemia. In conclusion, PTHrP expression in melanoma is associated with cachexia, increased cancer cell lactate and ketone body import, high mitochondrial metabolism, and reduced senescence. Further studies are required to determine if PTHrP regulates cachexia, lactate and ketone body import, mitochondrial metabolism, and senescence in cancer cells.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Hipercalcemia/metabolismo , Melanoma/tratamiento farmacológico , Proteína Relacionada con la Hormona Paratiroidea/metabolismo , Anticuerpos Monoclonales/efectos adversos , Caquexia/inducido químicamente , Femenino , Humanos , Hipercalcemia/inducido químicamente , Ipilimumab , Melanoma/patología , Persona de Mediana Edad , Transportadores de Ácidos Monocarboxílicos/metabolismo , Síndromes Paraneoplásicos/inducido químicamente , Simportadores/metabolismoAsunto(s)
Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Compuestos de Mostaza Nitrogenada/efectos adversos , Síndromes Paraneoplásicos/inducido químicamente , Pénfigo/inducido químicamente , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Clorhidrato de Bendamustina , Erupciones por Medicamentos/diagnóstico , Femenino , Humanos , Compuestos de Mostaza Nitrogenada/administración & dosificación , Síndromes Paraneoplásicos/diagnóstico , Pénfigo/diagnóstico , Recurrencia , Rituximab , Terapia Recuperativa/efectos adversosRESUMEN
OBJECTIVE: Review of the literature addressing the rheumatic manifestations of various malignancies as well as of common chemotherapeutic agents. METHODS: A literature search was performed to identify key articles regarding the association of rheumatic disease with malignancy. RESULTS: Our review focused on the association of rheumatic disease with malignancy, paraneoplastic syndromes with rheumatic manifestations, and chemotherapeutic agents related to rheumatic syndromes. We have discussed the importance of a newly described autoantibody that may identify patients at risk for malignancy associated myositis. CONCLUSION: Based on our literature review, recommendations are suggested regarding who and how patients should be screened for malignancy when presenting with various rheumatic symptoms.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Síndromes Paraneoplásicos/etiología , Enfermedades Reumáticas/etiología , Autoanticuerpos/sangre , Biomarcadores/sangre , Humanos , Síndromes Paraneoplásicos/inducido químicamente , Síndromes Paraneoplásicos/inmunología , Enfermedades Reumáticas/inducido químicamente , Enfermedades Reumáticas/inmunología , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Subacute cutaneous lupus erythematosus is an uncommon dermatosis characterised by a non-scarring, annular photo-distributed dermatosis associated with anti-Ro/SSA antibodies. It is remarkable as a paraneoplastic syndrome (12 cases in the literature). We report two cases of subacute cutaneous lupus erythematosus occurring in patients treated for metastatic breast adenocarcinoma. CASE REPORTS: Case 1: a 72-year-old woman with breast carcinoma relapsing after surgery, chemotherapy, hormone therapy, and without treatment for 6 months, was admitted for an acute erythematous slightly squamous and photo-distributed eruption. On clinical examination, she was found to be presenting polyadenopathy and pleural effusion. Case 2: a 46-year-old woman with a history of breast carcinoma was admitted for an erythematopapular, annular and photo-distributed eruption occurring after a second breast cancer relapse and five months after initiation of docetaxel. A new line of chemotherapy initially resulted in regression of the lesions, and progression of the breast cancer was associated with cutaneous relapse. DISCUSSION: The diagnosis of subacute cutaneous lupus erythematosus was supported in our two patients by the presence of an annular photo-distributed eruption associated with positive testing for anti-Ro/SSA antibodies. Occurrence of the eruption in both cases with relapse of the neoplasia and its improvement after oncological treatment reinforced the diagnosis of paraneoplastic syndrome in one case, and the use of chemotherapy known to trigger lupus could have suggested a diagnosis of drug-induced subacute cutaneous lupus erythematosus. Thus, the association between lupus and cancer is relevant.
Asunto(s)
Adenocarcinoma/complicaciones , Neoplasias de la Mama/complicaciones , Lupus Eritematoso Cutáneo/etiología , Síndromes Paraneoplásicos/etiología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Anciano , Anticuerpos Antinucleares/sangre , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Autoantígenos/inmunología , Bevacizumab , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Terapia Combinada , Ciclofosfamida/administración & dosificación , Docetaxel , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Lupus Eritematoso Cutáneo/inducido químicamente , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/inmunología , Mastectomía/métodos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Síndromes Paraneoplásicos/inducido químicamente , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/inmunología , Ribonucleoproteínas/inmunología , Terapia Recuperativa , Tamoxifeno/uso terapéutico , Taxoides/administración & dosificación , Taxoides/efectos adversos , TrastuzumabAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Eosinofilia/inducido químicamente , Linfoma Folicular/tratamiento farmacológico , Recurrencia Local de Neoplasia/diagnóstico , Síndromes Paraneoplásicos/inducido químicamente , Eosinofilia/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Síndromes Paraneoplásicos/tratamiento farmacológico , PronósticoRESUMEN
Acute promyelocytic leukemia (APL) has now become the most curable of all subtypes of acute myeloid leukemia. A cure rate of 75-80% can be anticipated with a combination of all-trans retinoic acid (ATRA) and anthracyclines. In Tunisia, the ATRA era began in 1998 with the use, consecutively, of two regimens of a combination of ATRA with anthracycline and cytarabine (APL93), and without cytarabine (LPA99). From 2004, 39 patients with confirmed APL either by t(15;17) or PML/RARA were treated by the PETHEMA LPA 99 trial. The rationale of this protocol by avoiding cytarabine is to reduce death in complete remission (CR) without increasing the incidence of relapse. Thirty-three patients achieved CR (84.6%). The remaining six patients were considered as failure due to early death: three caused by differentiation syndrome (DS) and three died from central nervous system hemorrhage. Baseline blood cell count (WBC) >10 x 10(9)/l (P=0.26) and creatinine >1.4 mg/dl (P=0.42) were not predictive of mortality. DS was observed in 11 patients (30.5%) with a median onset time of 12 days (range: 3-23 days) and median WBC of 29 x 10(9)/L (range: 1.2 x 10(9)-82.7 x 10(9)/l). DS was severe in seven cases, moderate in four, and fatal in three cases. Body mass index > or =30 (P=0.044) and baseline WBC > or =20 x 10(9)/l (P=0.025) are independent predictors of DS. The median follow-up of this study is 36 months. Thirty patients are alive in continuous complete remission; two patients died in CR from septic shock and secondary myelodysplastic syndrome respectively; one patient died 47 months after achieving two relapses. Event free survival from diagnosis was 80% and overall survival was 82%. Our results are quite acceptable and can be improved by reducing mortality rate.
Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Índice de Masa Corporal , Niño , Preescolar , Creatinina/sangre , Femenino , Humanos , Idarrubicina/efectos adversos , Idarrubicina/uso terapéutico , Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/complicaciones , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos/inducido químicamente , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tretinoina/efectos adversos , Tretinoina/uso terapéutico , Túnez/epidemiología , Adulto JovenAsunto(s)
Dermatomiositis/inducido químicamente , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Síndromes Paraneoplásicos/inducido químicamente , Simvastatina/efectos adversos , Anciano , Biopsia , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/patología , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Síndromes Paraneoplásicos/patología , Síndromes Paraneoplásicos/terapia , Resultado del TratamientoRESUMEN
Nausea and vomiting is a common and distressing symptom complex in patients with far-advanced cancer, affecting up to 60% of individuals at some stage of their illness. The current approach to the palliative care of patients with nausea and vomiting is based on identifying the cause, understanding its pathophysiology and knowing the pharmacology of the drugs available for its amelioration. The following six main syndromes are identified: gastric stasis, biochemical, raised intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A careful history, focused physical examination and appropriate investigations are needed to elucidate the syndrome and its cause, so that therapy is rational. Drugs are the mainstay of treatment in terminal cancer, and the main classes of antiemetic agents are prokinetics, dopamine antagonists, antihistamines, anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also used, especially in bowel obstruction. Non-drug measures are important in relieving the associated distress. Patients should be able to die comfortably, without tubes. Despite decades of practice affirming this approach, the evidence base is weak and well designed studies are urgently needed.
Asunto(s)
Quimioterapia/tendencias , Náusea/inducido químicamente , Náusea/prevención & control , Neoplasias/complicaciones , Enfermo Terminal , Vómitos/inducido químicamente , Vómitos/prevención & control , Quimioterapia/métodos , Humanos , Náusea/complicaciones , Neoplasias/fisiopatología , Síndromes Paraneoplásicos/inducido químicamente , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/fisiopatología , Cuidado Terminal/ética , Cuidado Terminal/métodos , Cuidado Terminal/tendencias , Terminología como Asunto , Vómitos/complicacionesAsunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Dermatomiositis/diagnóstico , Fluorouracilo/efectos adversos , Síndromes Paraneoplásicos/diagnóstico , Administración Oral , Antimetabolitos Antineoplásicos/administración & dosificación , Dermatomiositis/inducido químicamente , Dermatomiositis/patología , Diagnóstico Diferencial , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos/inducido químicamente , Síndromes Paraneoplásicos/patología , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
INTRODUCTION: Acquired ichthyosis is a rare condition that usually reveals malignant diseases. CASE REPORT: A 70-year-old man was admitted with weight loss, diffuse ichthyosis, lymphadenopathy of the inguinal lymph nodes and elevated inflammatory markers in peripheral blood. Histology of the lymph node revealed mixed-cellularity Hodgkin disease. The evolution was fatal in spite of the chemotherapy. DISCUSSION: Acquired ichthyosis is a cutaneous paraneoplastic syndrome, generally related to hematologic malignancies. A possible pathomecanism is the stimulation of epidermal growth secondary to the production of epidermal growth factor (EGF) by tumour cells. Acquired ichtyosis can rarely reveal systemic or infectious diseases. It can also be drug-induced or idiopathic.
Asunto(s)
Enfermedad de Hodgkin/diagnóstico , Ictiosis/etiología , Anciano , Biomarcadores/sangre , Enfermedad de Hodgkin/patología , Humanos , Ictiosis/patología , Inflamación/patología , Ganglios Linfáticos/patología , Masculino , Síndromes Paraneoplásicos/inducido químicamente , Síndromes Paraneoplásicos/patologíaRESUMEN
Paraneoplastic pemphigus is a severe mucocutaneous disease associated with B-cell lymphoproliferative disorders. A 51-yr-old man presented to the oncology clinic with mucocutaneous skin lesions after six cycles of fludarabine for non-Hodgkin's lymphoma. A punch biopsy from the skin showed suprabasal acantholysis and blister formation in the epidermis and upper dermis. Direct immunofluorescence demonstrated intercellular IgG deposition in all epidermal layers and complement (C3) at the basement membrane. The indirect immunofluorescence on rat bladder showed intercellular binding of IgG. These findings were consistent with paraneoplastic pemphigus associated with fludarabine use. The temporal association between fludarabine use and paraneoplastic pemphigus suggests there is an etiopathological link between these two entities.