Enfermedad de Castleman, fisiopatología, avances en el diagnóstico y tratamiento / Castleman's disease, pathophysiology, advances in diagnosis and treatment

La enfermedad de Castleman (EC) engloba a un conjunto heterogéneo de procesos linfoproliferativos que comparten rasgos histológicos bien definidos. Se considera una enfermedad rara o minoritaria u su incidencia no es del todo conocida, aunque se estima en menos de uno por cada 100.000 habitantes. Tiene una distribución bimodal (30-40 años y luego los 60-80 años). Su incidencia es similar en ambos sexos, aunque la variante unicéntrica parece tener ligero predominio en mujeres con proporción 2:1. La EC se clasifica en una forma hialinovascular (siendo esta la más frecuente) y otra plasmocelular, relacionadas con el virus de la inmunodeficiencia humana (VIH) y el virus herpes humano tipo 8 (VHH-8), que junto a otros mecanismos autoinmunitarios desarrollan la hiperproducción de interleucina-6 (IL-6) por parte de los linfocitos B. Existen diferentes líneas de tratamiento, donde destaca el uso de anti IL-6, siendo el siltuximab el más utilizado y catalogado como el fármaco huérfano de esta patología.(AU)

Castleman's disease (CD) encompasses a heterogeneous set of reactive lymphoproliferative processes that share well-defined histologic features. CD is considered a rare or minority disease. The incidence of CD is not fully known, although it is estimated at less than 1 per 100,000 inhabitants. It has a bimodal distribution (30–40 years and then 60–80 years). The incidence is similar in both sexes, although the unicentric variant seems to have a slight predominance in women with a 2:1 ratio. CD is classified into a hyalinovascular form (this being the most frequent) and a plasmocellular form, related to the HIV and VHH-8 viruses, which together with other autoimmune mechanisms develop hyperproduction of interleukin-6 (IL-6) by B lymphocytes. There are different lines of treatment, where the use of anti IL-6 stands out, being siltuximab the most used as orphan drug in this pathology.(AU)

[Castleman's disease, pathophysiology, advances in diagnosis and treatment]. / Enfermedad de Castleman, fisiopatología, avances en el diagnóstico y tratamiento.

Castleman's disease (CD) encompasses a heterogeneous set of reactive lymphoproliferative processes that share well-defined histologic features. CD is considered a rare or minority disease. The incidence of CD is not fully known, although it is estimated at less than 1 per 100,000 inhabitants. It has a bimodal distribution (30-40 years and then 60-80 years). The incidence is similar in both sexes, although the unicentric variant seems to have a slight predominance in women with a 2:1 ratio. CD is classified into a hyalinovascular form (this being the most frequent) and a plasmocellular form, related to the HIV and VHH-8 viruses, which together with other autoimmune mechanisms develop hyperproduction of interleukin-6 (IL-6) by B lymphocytes. There are different lines of treatment, where the use of anti IL-6 stands out, being siltuximab the most used as orphan drug in this pathology.

Characterisation of the coexistence between sarcoidosis and Sjögren's syndrome. Analysis of 43 patients.

OBJECTIVES: To characterise the key epidemiological, clinical, immunological, imaging, and pathological features of the coexistence between sarcoidosis and Sjögren's syndrome (SS). METHODS: All centres included in two large multicentre registries (the Sjögren Syndrome Big Data Consortium and the Sarco-GEAS-SEMI Registry) were contacted searching for potential cases of coexistence between SS and sarcoidosis seen in daily practice. Inclusion criteria were the fulfilment of the current classification criteria both for SS (2016 ACR/EULAR) and sarcoidosis (WASOG). The following features were considered for evaluating a coexisting immunopathological scenario between the two diseases: non-caseating granulomas (NCG), focal lymphocytic sialadenitis (FLS) and positive anti-Ro antibodies. RESULTS: We identified 43 patients who fulfilled the inclusion criteria (38 women, with a mean age of 53 years at diagnosis of SS and of 52 years at diagnosis of sarcoidosis). In 28 (65%) cases, sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of patients with an already diagnosed SS, while in the remaining 15 (35%), SS was diagnosed during the follow-up of an already diagnosed sarcoidosis. Patients in whom sarcoidosis was diagnosed first showed a lower mean age (43.88 vs. 55.67 years, p=0.005) and were less frequently women (73% vs. 96%, p=0.04) in comparison with those in whom sarcoidosis was diagnosed concomitantly with SS, or during the follow-up of an already diagnosed SS. We identified the following immunopathological scenarios: a combination of NCG involving extrasalivary tissues and anti-Ro antibodies in 55% of patients, a coexistence of both pathological scenarios (extrasalivary NCG and FLS in MSGB) in 42% (with positive anti-Ro antibodies in two thirds of cases), and NCG involving salivary glands and anti-Ro antibodies in 3% of cases. CONCLUSIONS: We have characterised the largest reported series of patients who fulfilled the current classification criteria for both SS and sarcoidosis. This implies that sarcoidosis (and not just the presence of isolated NCG on salivary gland biopsy) may, like other systemic autoimmune diseases, coexist with SS, and that a sarcoidosis diagnosis does not preclude the development of SS in the future.

Therapy-resistant dermatomyositis with extensive 'lumbar belt' calcinosis.

Calcinosis cutis (CC) is the umbrella term for calcium salt deposition on skin and subcutaneous tissue. We present a unique case of CC associated with anti-Mi2-positive dermatomyositis, having a distinctive distribution of subcutaneous calcifications appearing as a 'lumbar belt'. Treatment of CC remains challenging for clinicians due to a lack of high-quality evidence. Corticosteroids, methotrexate, bisphosphonates, intravenous immunoglobulin replacement, rituximab and sodium thiosulfate failed to halt calcinosis progression in this case. Newer therapies, such as Janus kinase inhibitors, should be considered.

Cutaneous and Ganglion Sarcoidosis Induced by Polycaprolactone Facial Filler: A New Expression of ASIA Syndrome?

Dermal fillers are applied using a minimally invasive technique with a good safety profile. However, they can have side effects. We present the case of a patient who, 2 months after undergoing polycaprolactone (Ellansé®) injections, developed nodular facial and nodal lesions that were compatible with sarcoidosis on histology. This complication has not been previously described for polycaprolactone and could be the expression of an autoimmune syndrome induced by adjuvants. LEARNING POINTS: Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) is a recently devised umbrella term for autoimmune diseases caused by adjuvants.Aesthetic procedures, which are increasingly common, may be a cause of ASIA syndrome.Polycaprolactone is a bioabsorbable polymer with a safe profile but can have adverse events, including systemic sarcoidosis.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Proceso de transición de la asistencia pediátrica a la adulta en pacientes con errores congénitos del metabolismo. Documento de consenso / Transition process from paediatric to adult care in patients with inborn errors of metabolism. Consensus statement

Antecedentes y objetivo: El proceso de transición de la asistencia pediátrica a la adulta es un tema de gran interés en los últimos años, especialmente en enfermedades crónicas de inicio en la infancia, como los errores congénitos del metabolismo (ECM). Los avances en el diagnóstico y el tratamiento de estas enfermedades han mejorado su pronóstico, encontrando en la actualidad un elevado número de pacientes con ECM que alcanzan la edad adulta y necesitan ser atendidos por profesionales no pediátricos. El objetivo de este trabajo es establecer unas pautas de actuación para que los especialistas involucrados garanticen una transición exitosa de la atención sanitaria de estos pacientes. Metodología: Tras realizar una revisión bibliográfica del tema, los autores, partiendo de su propia experiencia, elaboraron un documento inicial que fue sometido a sucesivos debates hasta obtener el documento definitivo. En caso de discrepancia de criterio, la recomendación de consenso se decidió por mayoría. Resultados: Se presentan una serie de recomendaciones para el mejor abordaje clínico de la transición asistencial de los pacientes con ECM desde el entorno pediátrico a la asistencia de adultos, con el objetivo de conseguir los mejores resultados en este proceso, dadas las características especiales de este subgrupo de pacientes, así como las principales dificultades que conlleva el proceso de transición Conclusiones: Se resalta el papel del médico internista en este proceso de transición y su correcta articulación con el entorno pediátrico y social. Asimismo, se recomiendan acciones y actitudes para mejorar la calidad de dicha transición (AU)

Background and objective: The transition process from paediatric to adult care is a subject of great interest in recent years, especially in chronic diseases with childhood onset, such as inborn errors of metabolism (IEM). Advances in diagnosis and treatment of these diseases have improved their prognosis, with a high number of patients with IEM who currently reach adult age and need to be attended to by non-paediatric professionals. The objective of this work is to establish action guidelines so that the specialists involved can guarantee a successful transition of these patients’ healthcare. Methodology: After carrying out a bibliographic review of the subject, the authors, beginning with their own experience, produced an initial document which was subjected to successive debates until the final document was obtained. The consensus recommendation was decided by the majority in case of criterion discrepancy. Results: A series of recommendations are presented for the best clinical management of the transitions of care of patients with IEM from the paediatric to adult care setting in order to achieve the best results in this process given the special characteristics of this patient subgroup and the main difficulties entailed in the transition process. Conclusions: The role of the internal medicine doctor in this transition process and correct interrelation with the paediatric and social setting is stressed. Furthermore, actions and attitudes are suggested to improve the quality of said transition (AU)

[Transition process from paediatric to adult care in patients with inborn errors of metabolism. Consensus statement]. / Proceso de transición de la asistencia pediátrica a la adulta en pacientes con errores congénitos del metabolismo. Documento de consenso.

BACKGROUND AND OBJECTIVE: The transition process from paediatric to adult care is a subject of great interest in recent years, especially in chronic diseases with childhood onset, such as inborn errors of metabolism (IEM). Advances in diagnosis and treatment of these diseases have improved their prognosis, with a high number of patients with IEM who currently reach adult age and need to be attended to by non-paediatric professionals. The objective of this work is to establish action guidelines so that the specialists involved can guarantee a successful transition of these patients' healthcare. METHODOLOGY: After carrying out a bibliographic review of the subject, the authors, beginning with their own experience, produced an initial document which was subjected to successive debates until the final document was obtained. The consensus recommendation was decided by the majority in case of criterion discrepancy. RESULTS: A series of recommendations are presented for the best clinical management of the transitions of care of patients with IEM from the paediatric to adult care setting in order to achieve the best results in this process given the special characteristics of this patient subgroup and the main difficulties entailed in the transition process. CONCLUSIONS: The role of the internal medicine doctor in this transition process and correct interrelation with the paediatric and social setting is stressed. Furthermore, actions and attitudes are suggested to improve the quality of said transition.

Disfunción tiroidea y lipídica asociada a bexaroteno en el linfoma cutáneo de células T / Thyroid and lipidic dysfunction associated with bexarotene in cutaneous T-cell lymphoma

Fundamento y objetivo: El bexaroteno es un rexinoide sintético selectivo del receptor X aprobado para el tratamiento sistémico del linfoma cutáneo de células T. Durante el tratamiento es muy frecuente la aparición de hipotiroidismo e hiperlipidemia mixta grave, siendo ambos efectos adversos reversibles y dependientes de la dosis. La elevación del colesterol LDL y los triglicéridos (hasta unos niveles aumentados que incluso se han asociado a pancreatitis en algunos casos) está ampliamente descrita (al igual que sucede con otros retinoides), siendo el descenso del colesterol HDL menos conocido. Revisamos nuestra experiencia con el uso de bexaroteno. Material y métodos: Se presenta una serie de 3 casos de pacientes tratados con bexaroteno en los que, además de sufrir los efectos adversos bien conocidos, se observó un grave descenso del colesterol HDL. Resultados: Los 3 pacientes estudiados presentaron complicaciones metabólicas en forma de hipotiroidismo central e hiperlipidemia mixta grave, con especial énfasis en el marcado descenso que experimentaron nuestros pacientes (descenso medio > 83%) en las cifras de colesterol HDL. El tratamiento hipolipidemiante y hormonal sustitutivo con levotiroxina dio lugar a una mejoría de los parámetros, sin llegar a alcanzarse los objetivos. Conclusiones: El bexaroteno produce, como efectos secundarios predecibles, una hiperlipidemia mixta grave con descenso marcado de los niveles de colesterol HDL e hipotiroidismo central, los cuales son reversibles y dependientes de la dosis. Se incluye una reflexión sobre los posibles mecanismos etológicos e implicaciones de este fenómeno (AU)

Background and objective: Bexarotene is a synthetic selective X receptor rexinoide approved for the systemic treatment of cutaneous T-cell lymphoma. During treatment is very frequent the occurrence of hypothyroidism and severe mixed hyperlipidemia, both are reversibles and dose-dependent adverse events. Increase of triglycerides and LDL-cholesterol level (up to even higher levels have been associated with pancreatitis in some cases) is widely described (as is the case with other retinoids) but decrease in HDL-cholesterol is poored know. We review our experience with the use of bexarotene. Material and methods: We present a serie of 3 clinical report of patients treated with bexarotene in whose, in addition to these well-known adverse event, a serious lowering of HDL-cholesterol was observed. Results: The 3 patients studied had metabolic complications like central hypothyroidism and severe mixed hyperlipidemia; with special emphasis on the sharp fall (mean decrease > 83%) in the HDL-cholesterol level. Cholesterol lowering medication and substitutive hormonal replacement with levotiroxine resulted in an improvement of the biochimical parameters without reaching the correct goals. Conclusions: Bexarotene produce as predictable side effects severe mixed hyperlipidemia with marked decrease in HDL-cholesterol levels and central hypothyroidism, being the both reversible and dose-dependent. A reflection on the possible aetiological mechanisms and implications of this phenomenon are included (AU)

[Thyroid and lipidic dysfunction associated with bexarotene in cutaneous T-cell lymphoma]. / Disfunción tiroidea y lipídica asociada a bexaroteno en el linfoma cutáneo de células T.

BACKGROUND AND OBJECTIVE: Bexarotene is a synthetic selective X receptor rexinoide approved for the systemic treatment of cutaneous T-cell lymphoma. During treatment is very frequent the occurrence of hypothyroidism and severe mixed hyperlipidemia, both are reversibles and dose-dependent adverse events. Increase of triglycerides and LDL-cholesterol level (up to even higher levels have been associated with pancreatitis in some cases) is widely described (as is the case with other retinoids) but decrease in HDL-cholesterol is poored know. We review our experience with the use of bexarotene. MATERIAL AND METHODS: We present a serie of 3 clinical report of patients treated with bexarotene in whose, in addition to these well-known adverse event, a serious lowering of HDL-cholesterol was observed. RESULTS: The 3 patients studied had metabolic complications like central hypothyroidism and severe mixed hyperlipidemia; with special emphasis on the sharp fall (mean decrease>83%) in the HDL-cholesterol level. Cholesterol lowering medication and substitutive hormonal replacement with levotiroxine resulted in an improvement of the biochimical parameters without reaching the correct goals. CONCLUSIONS: Bexarotene produce as predictable side effects severe mixed hyperlipidemia with marked decrease in HDL-cholesterol levels and central hypothyroidism, being the both reversible and dose-dependent. A reflection on the possible aetiological mechanisms and implications of this phenomenon are included.

[Clinical characteristics, cellular and molecular basis of hypertension in elderly]. / Características clínicas, bases celulares y moleculares de la hipertensión arterial del anciano.

The prevalence of arterial hypertensión (AH) increases with ageing, and, on the other hand, it acquires a series of clinical characteristics that differentiates it from AH in young persons or in subjects in average ages of the life. In the present article we will study several cellular or molecular mechanisms, which relate AH and aging. Moreover, we will discuss certain clinical peculiarities of AH in the elderly such as the relation with arterial stiffness and with isolated systolic hypertension. We will finalize proposing objectives of control of blood pressure in the elderly as well as marking strategies to delay, or prevent, the development of this, not always well-known, form of AH.

Características clínicas, bases celulares y moleculares de la hipertensión arterial del anciano / Clinical characteristics, cellular and molecular basis of hypertension in elderly

Con la edad aumenta la prevalencia de hipertensión arterial (HTA),que, por otra parte, adquiere una serie de características clínicas quela diferencian de la HTA en el joven o en las edades medias de la vida.En la presente revisión estudiamos los mecanismos moleculares y celularesque relacionan HTA y envejecimiento, y discutimos ciertas peculiaridadesclínicas de la HTA del anciano, como son la relación conla rigidez arterial y la HTA sistólica aislada. Finalizamos planteandoobjetivos de control de la presión arterial en el anciano y medidaspara retrasar o prevenir el desarrollo de esta forma, no siempre bienconocida, de HTA

The prevalence of arterial hypertensión (AH) increases with ageing,and, on the other hand, it acquires a series of clinical characteristicsthat differentiates it from AH in young persons or in subjects in averageages of the life. In the present article we will study several cellularor molecular mechanisms, which relate AH and aging. Moreover, wewill discuss certain clinical peculiarities of AH in the elderly such asthe relation with arterial stiffness and with isolated systolic hypertension.We will finalize proposing objectives of control of blood pressurein the elderly as well as marking strategies to delay, or prevent, the development of this, not always well-known, form of AH (AU)

Absceso hepático por Klebsiella pneumoniae en inmigrante oriental / Hepatic abscess due to Klebsiella pneumoniae in an oriental immigrant

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Réplica. Manejo del paciente pluripatológico en una unidad de hospitalización domiciliaria / Reply. Managing the patient with multimorbidity in a hospital at home unit

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[Incidence and clinical features of patients with comorbidity attended in internal medicine areas]. / Incidencia y características clínicas de los pacientes con pluripatología ingresados en una unidad de medicina interna.

BACKGROUND AND OBJECTIVE: Our objective was to assess the incidence and clinical features of patients with numerous disorders--comorbidity patients (CP)--and to clinically validate the CP criteria defined by a panel of experts (patients with 2 or more chronic diseases, distributed into seven categories). PATIENTS AND METHOD: Prospective observational study of all patients, attended in internal medicine areas of a tertiary teaching hospital, during June 2003. Patients were stratified in 3 cohorts: CP, palliative, and general (GE). Incidence of CP, functional evaluation (at baseline, at admission, and at discharge), and burden of hospital care (by means of urgent and programmed visits, as well as episodes of hospitalization) in the last 12 months were analyzed. A multivariate analysis of predictors of survival and functional deterioration (fall in Barthel's scale > or = 10 points between baseline-discharge values) was performed in the CP cohort. RESULTS: 339 patients (CP cohort: 132; palliative: 52; GE: 155) were included. The overall incidence was 38.9/100 admissions/month. CP were older (75 [11] vs 67 [16]); had higher mortality (19.3% vs 6.1%; relative risk [RR]: 3.66 [95% confidence interval [CI], 1.65-8.13]; lower functional ability at baseline (45 vs 95), at admission (20 vs 75), and at discharge (20 vs 95); higher rates of significant functional deterioration (16% vs 7%; RR = 2.47 [95% CI, 1.15-5.35]); and required more burden of hospital care by means of urgent care (3.6 [3.4] episodes vs 2.4 [1.9]), and hospitalizations (1.9 [1.3] vs 1.5 [1]) than GE patients. Chronic digestive/hepatic diseases (odds ratio [OR] = 48.3 [2.4-980.9], peripheric vascular disease/diabetes with visceral involvement (OR = 5.6 [CI 95%, 1.1-28.6]), and better functional ability at admission were associated with survival. Female gender (OR ) 46.6 [CI 95%, 4.5-486.9]), chronic lung disease (OR = 8.9 [CI 95%, 1.2-64]), and neurologic disease with disability (OR = 8 [CI 95%, 1.1-58.9]), were associated with significant functional deterioration during hospital stay. CONCLUSIONS: The defined CP criteria were highly accurate in detecting a population of patients with high attention in Internal Medicine areas, high mortality rates, clinical frailty (more need of hospital care), and significant functional deterioration. Barthel's scale identified correctly this group of patients, and was independently associated with survival.