RESUMEN
OBJECTIVE: The radiologically isolated syndrome (RIS) represents the earliest detectable pre-clinical phase of multiple sclerosis (MS). This study evaluated the impact of therapeutic intervention in preventing first symptom manifestation at this stage in the disease spectrum. METHODS: We conducted a multi-center, randomized, double-blinded, placebo-controlled study involving people with RIS. Individuals without clinical symptoms typical of MS but with incidental brain MRI anomalies consistent with central nervous system (CNS) demyelination were included. Within 12 MS centers in the United States, participants were randomly assigned 1:1 to oral dimethyl fumarate (DMF) 240 mg twice daily or placebo. The primary endpoint was the time to onset of clinical symptoms attributable to a CNS demyelinating event within a follow-up period of 96 weeks. An intention-to-treat analysis was applied to all participating individuals in the primary and safety investigations. The study is registered at ClinicalTrials.gov, NCT02739542 (ARISE). RESULTS: Participants from 12 centers were recruited from March 9, 2016, to October 31, 2019, with 44 people randomized to dimethyl fumarate and 43 to placebo. Following DMF treatment, the risk of a first clinical demyelinating event during the 96-week study period was highly reduced in the unadjusted Cox proportional-hazards regression model (hazard ratio [HR] = 0.18, 95% confidence interval [CI] = 0.05-0.63, p = 0.007). More moderate adverse reactions were present in the DMF (34 [32%]) than placebo groups (19 [21%]) but severe events were similar (DMF, 3 [5%]; placebo, 4 [9%]). INTERPRETATION: This is the first randomized clinical trial demonstrating the benefit of a disease-modifying therapy in preventing a first acute clinical event in people with RIS. ANN NEUROL 2023;93:604-614.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Dimetilfumarato/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Imagen por Resonancia Magnética , Método Doble CiegoRESUMEN
ABSTRACT: We report a case of an unusual and aggressive gamma delta T-cell lymphoproliferative disorder/lymphoma presenting in the skin that lacked the expected cytotoxic markers and had increased expression of CD5, CD20, CD79a, CD30, and PD-1 without CD56. Monoclonal TCR-γ gene rearrangement was identified. A computed tomography scan of the chest, abdomen, and pelvis revealed a 7.7-cm soft-tissue inguinal mass and prominent retroperitoneal and pelvic lymphadenopathy, without hepatosplenomegaly. Flow cytometry finding on peripheral blood was normal. The clinical, morphologic, and immunophenotypic features of this case defy the current World Health Organization and European Organization for Research and Treatment of Cancer classifications, and a similar case has not been reported previously.
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Linfoma , Linfocitos T , Antígenos CD20 , Humanos , Inmunofenotipificación , Linfoma/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genéticaRESUMEN
Bioactivation through drug metabolism is frequently suspected as an initiating event in many drug toxicities. The CYP450 and peroxidase enzyme systems are generally considered the most important groups of enzymes involved in bioactivation, producing either electrophilic or radical metabolites. Drug design efforts routinely consider these factors, and a number of structural alerts for bioactivation have been identified. Among the most frequently encountered structural alerts are aromatic systems with electron-donating substituents and some five-membered heterocycles. Metabolism of these groups can lead to chemically reactive electrophiles. Strategies that have been used to minimize the associated risk involve replacing the structural-alert moiety, blocking or making metabolism less favorable, and incorporating metabolic soft spots to facilitate metabolism away from the structural-alert substituent. The metabolism of drugs to radicals usually leads to cellular oxidative stress. The formation of radical metabolites can be minimized through the use of similar approaches but remains an area less frequently considered in drug design.
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Biotransformación , Diseño de Fármacos , Preparaciones Farmacéuticas/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Estrés Oxidativo/efectos de los fármacos , Peroxidasas/metabolismo , Preparaciones Farmacéuticas/químicaRESUMEN
Drug rechallenge (or reinitiation), following an event of drug-induced liver injury, can lead to serious or fatal liver injury. A retrospective review of a large pharmaceutical safety database was conducted to assess clinical outcomes of positive drug rechallenge following possible drug-induced liver injury. Positive rechallenge with suspect drug was reported in 770 of 36,795 hepatic adverse events. A total of 88 cases met inclusion criteria for analysis. Mean age was 44 years (range 0.5-83) and 56% were male. A broad spectrum of suspect drugs were identified. Many patients exhibited hepatitis symptoms or jaundice on the initial and rechallenge liver event. Twelve patients (14%) exhibited clinically worrisome severe hepatocellular injury and jaundice on either initial or rechallenge event and two died, reflecting a 2.3% fatality rate in those with positive rechallenge. The two fatalities developed severe hepatocellular injury with jaundice only upon rechallenge. Liver injury recurred in most rechallenges. Improved identification and communication of possible drug-induced liver injury is needed to avoid potentially serious and/or fatal drug rechallenges. Clinicians should generally avoid such rechallenges.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Preparaciones Farmacéuticas/administración & dosificación , Adulto , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Esquema de Medicación , Femenino , Humanos , Ictericia/inducido químicamente , Ictericia/epidemiología , Fallo Hepático/inducido químicamente , Fallo Hepático/epidemiología , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: There is concern that the immunologic tumor malignant melanoma (MM) may have worse outcomes in immunosuppressed hosts than in the general population. OBJECTIVE: We sought to describe outcomes of MM in immunosuppressed solid organ transplant recipients and compare them with the general population. METHODS: We conducted a retrospective review of medical charts and pathology slides of cases of MM and solid organ transplantation between 1978 and 2007, with comparison of outcomes. RESULTS: In all, 48 MMs were identified in 43 transplant recipients. No patient with MM before transplant receipt had melanoma recurrence, subsequent metastasis, or death caused by melanoma. Of patients with MM diagnosed after transplantation, metastases developed in 3 patients, and two patients died of melanoma. LIMITATIONS: Retrospective review and low number of cases are limitations. CONCLUSIONS: Outcomes of MM in immunosuppressed transplant recipients appeared similar to those in prognostically matched nonimmunosuppressed hosts. The small number of cases limited statistical comparisons.
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Huésped Inmunocomprometido , Melanoma/etiología , Trasplante de Órganos , Neoplasias Cutáneas/etiología , Piel/patología , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/diagnóstico , Melanoma/mortalidad , Melanoma/secundario , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/secundario , Factores de Tiempo , Estados UnidosRESUMEN
The occurrence of primary cutaneous ganglioneuroma is rare. We report 2 separate cases of primary cutaneous ganglioneuroma, both of which are associated with prominent overlying hyperkeratosis. The first case was in a 38-year-old woman with overlying verrucous keratosis. The second case was in a 93-year-old man with epidermal changes reminiscent of a seborrheic keratosis. Histologically, both lesions were composed of a proliferation of hyperplastic nerve fibers with spindled Schwann cells and axons with intermingled ganglion cells. Immunohistochemistry for neurofilament highlighted nerve fascicles; S100 protein displayed the associated Schwann cells, and neuron-specific enolase stained the interspersed ganglion cells. Variation in immunohistochemical staining was present between the 2 cases. A review of the literature demonstrates variable immunohistochemical staining of ganglion and Schwann cells in prior cases. Familiarity with these findings is important in establishing a diagnosis. The significance of the associated hyperkeratosis remains speculative.
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Ganglioneuroma/complicaciones , Ganglioneuroma/diagnóstico , Queratosis/complicaciones , Queratosis/diagnóstico , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano de 80 o más Años , Proliferación Celular , Femenino , Ganglión/metabolismo , Ganglión/patología , Ganglioneuroma/patología , Humanos , Queratosis/patología , Masculino , Fosfopiruvato Hidratasa/metabolismo , Proteínas S100/metabolismo , Células de Schwann/metabolismo , Células de Schwann/patología , Neoplasias Cutáneas/patologíaAsunto(s)
Azatioprina/efectos adversos , Inmunosupresores/efectos adversos , Síndrome de Sweet/inducido químicamente , Síndrome de Sweet/diagnóstico , Anciano de 80 o más Años , Azatioprina/administración & dosificación , Biopsia , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Prednisona/administración & dosificación , Síndrome de Sweet/tratamiento farmacológico , Síndrome de Sweet/patología , Resultado del TratamientoRESUMEN
The presence of sebaceous skin tumors with visceral neoplasms is known as Muir-Torre syndrome (MTS). It is a phenotypic subset of hereditary nonpolyposis colorectal cancer and is caused by mutations in genes encoding for mismatch repair (MMR) proteins. The presence of a sebaceous gland neoplasm should raise concern for a potential diagnosis of MTS. Immunohistochemical analysis of the sebaceous skin tumors can be helpful in screening for an MMR defect and preselecting patients who are at increased risk of a visceral malignancy. We report a case of MTS and show immunohistochemical analysis of the sebaceous neoplasm. We also review the literature on MTS and the effectiveness of immunohistochemical analysis in screening patients at risk for MTS.
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Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias de las Glándulas Sebáceas/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Sebáceas/genética , SíndromeRESUMEN
Structure-activity relationships in rhesus monkeys for a novel mixed-onium class of ultra-short-acting nondepolarizing tetrahydroisoquinolinium neuromuscular blockers (NMBs) are described. Bis-onium chlorofumarate 20a with (1R,2S)-benzyltetrahydroisoquinolinium groups was a potent lead compound (ED(95) = 0.079 mg/kg) with an ultra-short duration of NMB effect (7.1 min) and a selectivity index (SI: defined as a ratio of the cardiovascular threshold dose to the ED(95)) similar to that of mivacurium (3). The mean threshold dose for cardiovascular effects with 20a was ca. 20 times its ED(95) value (SI = 20). A novel mixed-onium analogue of 20a was prepared by replacing the benzyltetrahydroisoquinolinium group distal to the fumarate chlorine atom with a (1S,2R)-phenyltetrahydroisoquinolinium moiety. The resulting mixed-onium chlorofumarate 24a displayed good NMB potency (ED(95) = 0.063 mg/kg), ultra-short duration of action (5.6 min) and an improved selectivity index (SI = 57). Several other mixed-onium derivatives containing octanedioate (25a; ED(95) = 0.103 mg/kg), difluorosuccinate (27c; ED(95) = 0.056 mg/kg), and fluorofumarate (28a; ED(95) = 0.137 mg/kg) linkers were also potent, ultra-short-acting NMBs with good to excellent selectivity index values (SI = 37-96). Octanedioate 25a was longer acting at higher doses compared to difluorosuccinate 27c and chlorofumarate 24a. Durations of NMB effect following a 0.4 mg/kg bolus dose (100% block) of 25a, 27c, and 24a were 16.9, 13.0, and 10.0 min, respectively. Recovery time for mixed-onium chlorofumarate 24a following a 1 h continuous infusion at 10-20 microg/kg/min (95-100% block) was ca. 5 min which is similar to that observed following a 0.2 mg/kg bolus dose of this compound and indicates a lack of cummulative effects. Preliminary studies with chlorofumarate 24a in whole human blood revealed that mixed-onium thiazolidine 29 was the major metabolite and that plasma cholinesterases do not play the primary role in duration of NMB effect. The NMB properties of 24a in rhesus monkeys led to its clinical evaluation as a possible alternative to succinylcholine.
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Anisoles/síntesis química , Fumaratos/síntesis química , Isoquinolinas/síntesis química , Bloqueantes Neuromusculares/síntesis química , Compuestos de Amonio Cuaternario/síntesis química , Succinatos/síntesis química , Animales , Anisoles/sangre , Anisoles/farmacología , Presión Sanguínea/efectos de los fármacos , Fumaratos/sangre , Fumaratos/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Técnicas In Vitro , Isoquinolinas/sangre , Isoquinolinas/química , Isoquinolinas/farmacología , Macaca mulatta , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Bloqueantes Neuromusculares/sangre , Bloqueantes Neuromusculares/farmacología , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Estereoisomerismo , Relación Estructura-Actividad , Succinatos/sangre , Succinatos/farmacologíaRESUMEN
OBJECTIVES: To review the clinical presentations of nodular amyloidosis, examine these cases for evidence of plasma cell monoclonality, and obtain long-term follow-up data on progression to systemic amyloidosis. DESIGN: Retrospective case series with long-term follow-up data obtained by phone survey. SETTING: Mayo Clinic, Rochester, Minn, and Mayo Clinic, Jacksonville, Fla. PATIENTS: All patients diagnosed with nodular amyloidosis between 1971 and 2001. MAIN OUTCOME MEASURES: Clinical records and histopathologic characteristics were reviewed. Polymerase chain reaction to assess immunoglobulin gene rearrangement and immunohistochemical analysis to detect kappa and lambda light chain restriction were performed on paraffin-embedded specimens. Patients were contacted by phone to determine if progression to systemic disease had occurred. RESULTS: We identified 16 patients with nodular amyloidosis. Mean age at diagnosis was 60.8 years (range, 41-87 years). Eight (50%) of 16 patients had acral involvement. Immunohistochemical analysis demonstrated light chain restriction in 6 of 10 patients. At the time of diagnosis, no patient was known to have systemic amyloidosis. One patient, however, had a serum monoclonal lambda protein and died 4 years later secondary to systemic amyloidosis. Follow-up data were obtained in 14 of the remaining 15 patients, with a mean follow-up time of 10 years (range, 8 months to 24 years). None of the 14 patients had signs or symptoms suggesting progression to systemic amyloidosis. CONCLUSIONS: Nodular amyloidosis affects both sexes during middle age, with a tendency to affect acral sites. The relatively high rate of light chain restriction in our series provides further evidence for the presence of a local plasma cell clone. Progression to systemic amyloidosis is uncommon.
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Amiloidosis/patología , Amiloidosis/fisiopatología , Enfermedades de la Piel/patología , Enfermedades de la Piel/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Enfermedades de la Piel/terapia , Factores de TiempoRESUMEN
Abacavir (ZIAGEN) is a reverse transcriptase inhibitor marketed for the treatment of HIV-1 infection. A small percentage of patients experience a hypersensitivity reaction indicating immune system involvement and bioactivation. A major route of metabolism for abacavir is oxidation of a primary betagamma unsaturated alcohol to a carboxylic acid via an aldehyde intermediate. This process was shown to be mediated in vitro by human cytosol and NAD, and subsequently the alphaalpha and gamma2gamma2 human isoforms of alcohol dehydrogenase (ADH). The alphaalpha isoform effected two sequential oxidation steps to form the acid metabolite and two isomers, qualitatively reflective of in vitro cytosolic profiles. The gamma2gamma2 isozyme generated primarily an isomer of abacavir, which was minor in the alphaalpha profiles. The aldehyde intermediate could be trapped in incubations with both isozymes as an oxime derivative. These metabolites can be rationalized as arising via the aldehyde which undergoes isomerization and further oxidation by the alphaalpha enzyme or reduction by the gamma2gamma2 isozyme. Non-extractable abacavir protein residues were generated in cytosol, and with alphaalpha and gamma2gamma2 incubations in the presence of human serum albumin (HSA). Metabolism and residue formation were blocked by the ADH inhibitor 4-methyl pyrazole (4-MP). The residues generated by the alphaalpha and gamma2gamma2 incubations were analyzed by SDS-PAGE with immunochemical detection. The binding of rabbit anti-abacavir antibody to abacavir-HSA was shown to be dependent on metabolism (i.e. NAD-dependent and 4-MP sensitive). The mechanism of covalent binding remains to be established, but significantly less abacavir-protein residue was detected with an analog of abacavir in which the double bond was removed, suggestive of a double bond migration and 1,4 addition process.
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Alcohol Deshidrogenasa/metabolismo , Didesoxinucleósidos/farmacocinética , Hígado/metabolismo , Inhibidores de la Transcriptasa Inversa/farmacocinética , Alcohol Deshidrogenasa/antagonistas & inhibidores , Anticuerpos/metabolismo , Biotransformación , Western Blotting , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Citosol/enzimología , Citosol/metabolismo , Didesoxinucleósidos/toxicidad , Inhibidores Enzimáticos , Fomepizol , Humanos , Isoenzimas , Hígado/enzimología , Espectrometría de Masas , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , Pirazoles/farmacología , Inhibidores de la Transcriptasa Inversa/toxicidad , Albúmina Sérica/metabolismo , Resonancia por Plasmón de SuperficieRESUMEN
S-1360, a 1,3-diketone derivative, was the first HIV integrase inhibitor to enter human trials. Clinical data suggested involvement of non-cytochrome P450 clearance pathways, including reduction and glucuronidation. Reduction of S-1360 generates a key metabolite in humans, designated HP1, and constitutes a major clearance pathway. For characterization of subcellular location and cofactor dependence of HP1 formation, [(14)C]-S-1360 was incubated with commercially available pooled human liver fractions, including microsomes, cytosol, and mitochondria, followed by HPLC analysis with radiochemical detection. Incubations were performed in the presence and absence of the cofactors NADH or NADPH. Results showed that the enzyme system responsible for generation of HP1 in vitro is cytosolic and NADPH-dependent, implicating aldo-keto reductases (AKRs) and/or short-chain dehydrogenases/reductases (SDRs). A validated LC/MS/MS method was developed for investigating the reduction of S-1360 in detail. The reduction reaction exhibited sigmoidal kinetics with a K(m,app) of 2 microM and a Hill coefficient of 2. The ratio of V(max)/K(m) was approximately 1 ml/(min mg cytosolic protein). The S-1360 kinetic data were consistent with positive cooperativity and a single enzyme system. The relative contributions of AKRs and SDRs were examined through the use of chemical inhibitors. For these experiments, non-radiolabeled S-1360 was incubated with pooled human liver cytosol and NADPH in the presence of inhibitors, followed by quantitation of HP1 by LC/MS/MS. Quercetin and menadione produced approximately 30% inhibition at a concentration of 100 microM. Enzymes sensitive to these inhibitors include the carbonyl reductases (CRs), a subset of the SDR enzyme family predominantly located in the cytosol. Flufenamic acid and phenolphthalein were the most potent inhibitors, with > 67% inhibition at a concentration of 20 microM, implicating the AKR enzyme family. The cofactor dependence, subcellular location, and chemical inhibitor results implicated the aldo-keto reductase family of enzymes as the most likely pathway for generation of the major metabolite HP1 from S-1360.
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Oxidorreductasas de Alcohol/metabolismo , Fármacos Anti-VIH/metabolismo , Citosol/enzimología , Inhibidores Enzimáticos/metabolismo , Inhibidores de Integrasa VIH/metabolismo , Hígado/enzimología , Aldehído Reductasa , Aldo-Ceto Reductasas , Radioisótopos de Carbono , Furanos , Humanos , Microsomas Hepáticos/enzimología , Mitocondrias Hepáticas/enzimología , Oxidación-Reducción , TriazolesRESUMEN
OBJECTIVE: To determine malignant melanoma cause-specific and overall survival among patients with melanoma diagnosed after organ transplantation compared with a national sample with malignant melanoma. DESIGN: Retrospective review. SETTING: Mayo Clinic sites. PATIENTS: Immunosuppressed organ transplant recipients with malignant melanoma identified from surgical and medical databases at Mayo Clinic (1978-2007), the Organ Procurement and Transplantation Network/United Network for Organ Sharing database (1999-2006), and the Israel Penn International Transplant Tumor Registry (1967-2007). MAIN OUTCOME MEASURES: Prognostic analyses by Breslow thickness and Clark level of overall and melanoma cause-specific survival. Expected survival rates were estimated by applying the age-, sex-, and calendar year-specific survival rates of patients with malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program to the study cohort. RESULTS: Malignant melanoma was diagnosed in 638 patients (724 cases) after transplantation. Breslow thickness was available for 123 patients; Clark level, for 175. Three-year overall survival rates for patients stratified by Breslow thickness (≤ 0.75, 0.76-1.50, 1.51-3.00, and >3.00 mm) were 88.2%, 80.8%, 51.2%, and 55.3%, respectively, and 3-year cause-specific survival rates (95% confidence intervals) were 97.8% (93.7%-100%), 89.4% (76.5%-100%), 73.2% (53.2%-100%), and 73.9% (56.4%-96.6%), respectively. Three-year cause-specific survival rates (95% confidence intervals) for patients stratified by Clark level (I-IV) were 100%, 97.4% (92.4%-100%), 82.8% (65.3%-100%), and 65.8% (51.8%-83.7%), respectively. For patients with Breslow thickness of 1.51 to 3.00 mm and Clark level III or IV, the cause-specific survival rate in the study sample was significantly different from the expected estimates for patients with the same Breslow thickness or Clark level. CONCLUSIONS: Compared with the expected survival rates derived from malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program, immunosuppressed organ transplant recipients with thicker melanomas (ie, with a Clark level of III or IV or a Breslow thickness of 1.51 to 3.00 mm) had a significantly poorer malignant melanoma cause-specific survival rate. The overall survival rate was worse among patients with a prior history of transplantation, regardless of Breslow thickness or Clark level.
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Terapia de Inmunosupresión/efectos adversos , Melanoma/epidemiología , Trasplante de Órganos/efectos adversos , Neoplasias Cutáneas/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Melanoma/etiología , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Neoplasias Cutáneas/etiología , Resultado del Tratamiento , Adulto JovenAsunto(s)
Cara , Granuloma/inducido químicamente , Granuloma/patología , Siliconas/efectos adversos , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/patología , Anciano , Técnicas Cosméticas/efectos adversos , Femenino , Glucocorticoides/uso terapéutico , Granuloma/tratamiento farmacológico , Humanos , Inyecciones , Prednisona/uso terapéutico , Siliconas/administración & dosificación , Enfermedades de la Piel/tratamiento farmacológico , Insuficiencia del TratamientoAsunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Dermatosis de la Mano/tratamiento farmacológico , Histiocitosis de Células no Langerhans/tratamiento farmacológico , Inmunoglobulina G/administración & dosificación , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Diagnóstico Diferencial , Etanercept , Dermatosis de la Mano/diagnóstico , Dermatosis de la Mano/diagnóstico por imagen , Dermatosis de la Mano/patología , Histiocitosis de Células no Langerhans/diagnóstico , Histiocitosis de Células no Langerhans/diagnóstico por imagen , Histiocitosis de Células no Langerhans/patología , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , RadiografíaAsunto(s)
Sustancias para la Guerra Química/envenenamiento , Servicios Médicos de Urgencia/organización & administración , Salud Laboral , Terrorismo/prevención & control , Guerra Biológica , Bioterrorismo/prevención & control , Humanos , Equipos de Seguridad , Administración de la Seguridad , Estados UnidosRESUMEN
We report a case of a 27-year-old woman with a known history of Burkitt-like lymphoma (BLL), who presented with a rapidly enlarging nodule in the suprapubic area. Skin biopsy of the suprapubic nodule was consistent with cutaneous involvement of BLL. BLL is a highly aggressive B-cell lymphoma with a high proliferative rate. Like Burkitt lymphoma, BLL is characterized by a translocation of the c-MYC proto-oncogene. Histopathologic characteristics are considered borderline between those of classic Burkitt lymphoma and diffuse large B-cell lymphoma. Cutaneous involvement of BLL is rare and poorly documented in the literature.
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Linfoma de Burkitt/patología , Linfoma de Células B Grandes Difuso/patología , Neoplasias Cutáneas/patología , Adulto , Linfoma de Burkitt/genética , Linfoma de Burkitt/inmunología , Antígenos CD79/análisis , Femenino , Regulación Neoplásica de la Expresión Génica , Genes myc , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Linfocitos/inmunología , Linfocitos/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Invasividad Neoplásica , Proto-Oncogenes Mas , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/inmunología , Translocación GenéticaRESUMEN
BACKGROUND: Because of its unique mechanism of action and safety profile, imiquimod, a topical immune response modifier, is used for many benign and malignant dermatologic conditions. Adverse effects are typically limited to treatment site erythema and erosion. OBJECTIVE: To describe a newly recognized adverse effect of imiquimod. METHODS: A 79-year-old woman being treated with imiquimod 5 days per week for a nodular basal cell developed a verrucous plaque over the treatment area after 7 weeks of therapy. RESULTS: Scouting biopsies demonstrated multiple comedones and ruptured epidermoid cysts. There was no evidence of residual basal cell carcinoma. CONCLUSIONS: Imiquimod is a new and novel treatment option for cutaneous malignancies. We report its successful use in the treatment of a nodular basal cell carcinoma. The multiple comedones and ruptured epidermoid cysts are newly reported adverse effects of imiquimod therapy.
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Aminoquinolinas/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma Basocelular/tratamiento farmacológico , Enfermedades de la Piel/etiología , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Anciano , Aminoquinolinas/administración & dosificación , Antineoplásicos/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Femenino , Humanos , Imiquimod , Retinoides/administración & dosificación , Enfermedades de la Piel/tratamiento farmacológico , Resultado del TratamientoRESUMEN
We report a unique case of a 69-year-old man who presented with a 1-year history of pink nodules and plaques limited to the anterior plantar surface of the right foot and a 30-year history of a callus on the right heel. Histologic examination findings of both areas showed deposits of amorphous, eosinophilic material and an infiltrate of plasma cells in the dermis. Congo red-stained deposits exhibited apple-green birefringence with polarized light. Results of an extensive clinical and laboratory evaluation showed no evidence of systemic amyloidosis. The diagnosis of nodular primary localized cutaneous amyloidosis (PLCA) was made. Nodular PLCA isolated to pedal or strictly plantar surfaces is an unusual presentation of PLCA. The origin and the clinical and histopathologic features of nodular PLCA are reviewed.
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Amiloidosis/diagnóstico , Callo Óseo , Enfermedades de la Piel/diagnóstico , Anciano , Amiloidosis/patología , Diagnóstico Diferencial , Dermatosis del Pie/diagnóstico , Humanos , Masculino , Enfermedades de la Piel/patologíaRESUMEN
Candesartan cilexetil is an angiotensin II receptor antagonist that is widely used in the treatment of hypertension. It is generally well tolerated and rarely has adverse effects. We report the case of a 50-year-old man with a 3-year history of hypertension that was difficult to manage because of intolerance to multiple medications. Treatment with candesartan cilexetil was initiated, and blood pressure control improved markedly. Five weeks later, the patient presented with a 2 x 3-cm ulcerative plaque covered with a fibrinous exudate on the right upper lip. Findings from a biopsy of the upper lip were diagnostic for erythema multiforme. Treatment with candesartan cilexetil was discontinued, and the lesions resolved completely within a few weeks. To our knowledge, this is the first report of erythema multiforme induced by the antihypertensive medication candesartan cilexetil.