[Content validation for the Chilean population of the quality of life assessment instrument in children, adolescents and adults with Cystic Fibrosis: CFQ-R CYSTIC FIBROSIS QUESTIONNAIRE-REVISED version in Spanish, Chile]. / Validación de contenido del instrumento de evaluación de calidad de vida en niños, adolescentes y adultos con Fibrosis Quística: CFQ-R CYSTIC FIBROSIS QUESTIONNAIRE-REVISED versión en español, Chile.

INTRODUCTION: Cystic Fibrosis (CF) is the most frequent chronic hereditary disease in the white race. Although the impact on the quality of life of this disease is significant, there are no validated instruments in the Chilean population to measure it. OBJECTIVE: To carry out a cultural and linguistic adaptation and validate the content and reliability of the CFQ-R Cystic Fibrosis Questionnaire, Spanish version 2.0. PATIENTS AND METHOD: The process was carried out in two stages. The first stage consists of an ins trumental design to adapt it culturally and linguistically, evaluate content validity by consulting ex perts, and test the comprehension of the questionnaire in patients and parents through qualitative interviews and a focus group. In the second stage with an observational and cross-sectional design in a sample of 122 people with CF or their caregivers, the behavior of the questionnaire was analyzed using descriptive statistics and Cronbach's alpha for reliability. RESULTS: Stage 1: the instrument in its three versions is considered valid with Lynn's index > 0.8 and Validity Coefficient > 0.7. Stage 2: The adolescent/adult and parent/caregiver versions obtain Cronbach's a > 0.7 and an average > 3 in most dimensions. CONCLUSION: The questionnaire is adapted and validated in the Chilean population and requires minor modifications. This version is reliable, valid, and allows the assessment of the quality of life in people with CF. It is suggested to increase the sample for the analysis of construct validity with a larger number of patients.

Orbital Inflammation Caused by Aminobisphosphonates.

The aim of this review was to describe orbital inflammation secondary to aminobisphosphonates by analyzing demographic data, clinical presentation, and treatment of the disease. This is a narrative literature review. The search was performed using databases such as Ovid/MEDLINE and COCHRANE. The searches were limited to papers in the English language. We found 43 cases of orbital inflammation due to aminobisphosphonates. Zoledronate was the drug most associated with orbital side effects. Clinical presentation was evident by unilateral involvement (89%), palpebral edema (88%), conjunctival congestion (81%), chemosis (79%), ocular pain (77%), ocular motility impairment (65%), proptosis (56%), and blurred vision (39%). It can affect both eyes (11%) and is accompanied by anterior uveitis (23%). Orbital inflammation secondary to aminobisphosphonates is a severe side effect. Clinically, it cannot be distinguished from idiopathic inflammation of the orbit. Therefore, it is important to rule out previous drug exposure. Timely treatment is vital to expect a favorable outcome, with systemic corticosteroids being the treatment of choice.

Consenso chileno para la atención integral de niños y adultos con fibrosis quística

Resumen La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

Consenso chileno para la atención integral de niños y adultos con fibrosis quística / Chilean consensus for the integral care of children and adults with cystic fibrosis

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

A case report of a primary apocrine adenocarcinoma of the eyelid with literature review.

INTRODUCTION: Primary Apocrine adenocarcinomas (PAA) are very infrequent tumors that are often confused initially with benign lesions. Little is known about this disease and there is still much to be clarified. We present a case of PAA on the eyelid successfully treated with surgery alone and a literature review regarding what is currently described about this disease. METHODS: Noncomparative, retrospective case report of a patient with PAA on the eyelid succesfully treated with surgery alone and a literautre review. RESULTS: A 91-year-old man with a 2 months lesion on the upper left eyelid was treated with surgery alone with oncological margins of 5mm. The Hystopathology diagnosis was a PAA of the eyelid and free margins were obtained. After 12 months of follow-up, the patient does not show any signs of local recurrence or distant metastasis. A review of the literature suggests these tumors are located more frequently in the axilla (50%) and secondly in the head and neck (35%), with similar distribution in the upper (41%) and lower eyelid (45%). The most commonly used treatment is surgical excision, but radiotherapy and chemotherapy have also been used with variable results. CONCLUSIONS: PAA is a very rare and aggressive tumor. Because it is so infrequent, treatments are based on the sporadic cases encountered in the literature. As more cases are reported, more can be elucidated about the characteristics of this tumor, its behavior and best treatment choice and this may allow progress in the understanding and management of this disease.

Expandiendo el espectro mutacional en pacientes chilenos con fibrosis quística / Expanding the CFTR mutation spectrum in Chilean patients with cystic fibrosis

Introduction: Cystic Fibrosis (CF) is an autosomal recessive disease and affects 1 in 8000-9000 newborns in Chile. More than 1,800 different mutations have been identified in CFTR gene. The available molecular diagnosis analyzes the 36 most frequent mutations in Caucasian population, with an overall detection rate of80-85 percent, but with a much lower detection rate in Chilean patients of 42 percent. To analyze which other mutations are present in Chilean patients, we conducted an extensive analysis by direct DNA sequencing of coding sequences of the CFTR gene. Methods: Forty eight Chilean patients with clinical diagnosis of CF and one mutated allele in the CFTR gene identified, were studied by direct sequence analysis of exons 6, 7, 14, 19 and 20 of the CFTR gene. Results: We found 3 different mutations in 14 cases that had not been previously identified in Chilean patients. Four patients have a deletion of two nucleotides (c.2462_2463delGT/p.Ser821ArgfsX4) in exon 14, which is predicted to cause a frame shift and a premature stop codon. Eight patients have c.3196C>T mutation in the exon 20 and 2 cases has c.3039delC mutation in the exon 19. Both mutations had been previously described in other populations. Discussion: The identification of these mutations has notably increased the detection rate in our patients. Adapting the molecular diagnosis method by including these three mutations should increase the CF detection rate in Chilean patients. This analysis will improve CF diagnosis and allow an adequate genetic counseling to the families.

Introducción: La fibrosis quística (FQ) es una enfermedad con herencia autosómica recesiva, que presenta una incidencia de 1 en 8.000 a 9.000 recién nacidos en Chile. A la fecha se han descrito más de 1.800 mutaciones diferentes en el gen CFTR. El diagnóstico molecular disponible consiste en el análisis de las 36 mutaciones presentes con mayor frecuencia en población caucásica, donde se describe una tasa de detección de un 85 por ceinto. Sin embargo, en Chile el rendimiento corresponde a un 42 por ciento. Por esta razón, hemos iniciado un análisis sistemático en la región codificante del gen CFTR con el fin de identificar los restantes alelos en pacientes chilenos con FQ. Métodos: Análisis por secuenciación de los exones 6,7,14,19y 20, en 48pacientes chilenos del Programa Nacional de FQ. Se incluyeron pacientes con criterios clínicos y de laboratorio de FQ, y con sólo una mutación identificada en el panel de 36 mutaciones. Resultados: Se identificaron 3 mutaciones diferentes que no se analizan en el panel de diagnóstico molecular y que no habían sido reportadas en pacientes chilenos, totalizando 14 casos. Cuatro casos corresponden a una nueva mutación en el exón 14, que produce un corrimiento en el marco de lectura y un codón de término prematuro (c.2462_2463delGT/p.Ser821ArgfsX4). Ocho casos presentan la mutación c.3196C>T en el exón 20, mientras que en 2 casos se encontró la mutación c.3039delC en el exón 19. Ambas mutaciones han sido descritas previamente en otras poblaciones. Discusión: La identificación de estas mutaciones ha incrementado notablemente la tasa de detección obtenida en nuestros pacientes. Esto crea la necesidad de adaptar el análisis molecular inicial en pacientes chilenos con FQ, redundando en un diagnóstico de certeza en gran parte de los casos y permitiendo un adecuado asesoramiento genético para las familias.

Psoriasis following bariatric surgery: clinical evolution and impact on quality of life on 10 patients.

Psoriasis is a chronic systemic disease with important skin manifestations, affecting 2 % of the population. It is more frequent and severe in obese patients, and both have been associated with a higher cardiovascular risk. Recent studies suggest that weight loss may improve psoriasis and metabolic comorbidities in obese patients. We reviewed our prospective electronic database for all patients with psoriasis who underwent bariatric surgery between 2008 and 2011. We assessed surgical complications, weight progression, and psoriasis-related outcomes. The Dermatology Life Quality Index was used retrospectively to assess quality of life (QoL) before and after the operation. Ten patients were included; body mass index was 38.8 ± 5.2 kg/m(2). Pre-surgical treatment for psoriasis was topical (50 %) and systemic (40 %). Eight patients underwent laparoscopic Roux-en-Y gastric bypass and two underwent laparoscopic sleeve gastrectomy. At follow-up, the mean percent excess weight loss 1, 6, and 12 months after surgery was 45 %, 80 %, and 88 %, respectively. Comorbidity resolution was 75 % for diabetes mellitus, 100 % for insulin resistance, and 57 % for hypertension. Related to psoriasis, 70 % of the patients stayed in remission 6 months after surgery and three of the four patients who were previously medicated with systemic drugs discontinued medication. The impact of psoriasis on QoL improved from 14.9 ± 6.8 before surgery to 5 ± 6.3 after surgery (p = 0.005). Bariatric surgery for positive metabolic, skin, and quality of life results should be considered as a useful adjuvant therapy for obese patients with psoriasis.

Infección diseminada por BCG en la Región de Los Lagos, Chile: reporte de cinco casos clínicos / Disseminated infection by BCG in Región de Los Lagos, Chile: five cases report

The bacillus Calmette-Guerin (BCG) is the attenuated strain of Mycobacterium bovis used in developing countries for preventing serious forms of tuberculosis. The neonatal BCG vaccine is applied in countries with high prevalence of tuberculosis. Most of the vaccinated individuals develop no adverse reactions; although, some subjects show side effects due to a host altered immunity. These reactions range from a simple adenomegaly in the same side of BCG vaccine inoculation, to a spread infection, often fatal. A regional or systemic spread has been described in patients with secondary or primary immunodeficiencies and partial or total genetic defects of interleukin IL-12/23 and IFN-gamma called as a whole "Mendelian susceptibility to mycobacterial infections" (MSMD). We describe five patients infected with M. bovis BCG-diagnosed between 1995-2008, at the base hospital in the city of Puerto Montt, Region de Los Lagos, Chile. These patients have the clinical course of MSMD.

El bacilo Calmette-Guérin (BCG), es la cepa atenuada de Mycobacterium bovis utilizada en países en vías de desarrollo para la prevención de formas graves de tuberculosis. La vacuna BCG neonatal se administra en países con alta prevalencia de la enfermedad. La mayoría de los vacunados no presenta reacciones adversas, algunos evidencian reacciones secundarias a una inmunidad alterada del huésped. Dichas reacciones varían desde una simple adenomegalia ipsilateral a la inoculación de BCG, hasta una infección diseminada, a menudo mortal. La infección diseminada se ha descrito en pacientes inmuno deficientes secundarios, primarios y en pacientes con defectos genéticos del eje interleuquina 12-23 (IL12/23)-interferón gama (IFN-gamma ) denominados "Síndrome de predisposición mendeliana a infecciones micobacterianas" (PMIM). Describimos cinco pacientes con infección por M. bovis-BCG diagnosticados entre 1995-2008, en el Hospital Base de Puerto Montt, Región de Los Lagos, Chile que cumplen con los criterios del PMIM.

Gastrojejunal anastomotic stricture after Roux-en-Y gastric bypass: ambulatory management with the Savary-Gilliard dilator.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is currently one of the most frequently performed procedures for the surgical treatment of morbid obesity. The success of this procedure's restrictive component requires a small gastrojejunostomy (GJ), which occasionally results in stenosis. The treatment of choice for this complication is balloon dilation. This study aimed to evaluate the feasibility and safety of ambulatory management for stenosis of the GJ using endoscopically guided Savary-Gilliard dilators. METHODS: Between January 1998 and October 2003, 769 patients underwent RYGBP. The mean age of these patients was 38 +/- 12 years, and their mean body mass index (BMI) was 43 +/- 6 kg/m2. Of these 769 patients, 520 (68%) underwent open surgery and 249 (32%) underwent laparoscopic RYGBP. Patients suspected of GJ stenosis were referred for upper gastrointestinal endoscopy. Those who presented with stenosis were managed endoscopically with Savary-Gilliard dilators. RESULTS: Stenosis at the GJ was confirmed in 53 patients (6.9%). A total of 71 dilations were performed for these patients, resulting in a mean of 1.3 dilations per patient. One dilation was needed for 41 patients (75.5%), two dilations for 9 patients (16.9%), three dilations for 3 patients (5.7%), and four dilations 1 patient (1.9%). The patients subjected to open RYGBP required a mean of 1.57 dilations, and those who had laparoscopic RYGBP required mean of 1.08 dilations. The mean time for the first dilation was 51 +/- 28 days after surgery (range, 20-178 days). All the dilations were performed in ambulatory settings. One patient (1.9%) was admitted after GJ dilation for pain. He was discharged without symptoms after 2 days with no need for invasive procedures. CONCLUSIONS: The management and treatment of GJ stenosis after RYGBP can be effectively accomplished in ambulatory settings using endoscopically guided Savary-Gilliard dilators, with good and safe results.

Ventilación no invasiva como tratamiento de la insuficiencia respiratoria aguda en Pediatría / Pediatric non-invasive ventilation for acute respiratory failure in an Intermediate Care Unit

Background: Pediatric noninvasive ventilation (NIV) is infrequently used for acute respiratory failure (ARF), BiPAP/CPAP applied through nasal mask can be attempted if strict selection rules are defined. Aim: To evaluate the outcome of NIV in a Pediatric Intermediate Care Unit. Material and methods: The medical records of 14 patients (age range 1 month-13 years, six female), who participated in a prospective protocol of NIV from January to October 2004, were reviewed. Oxygen therapy, delivered through a reservoir bag attached to the ventilation circuit, was used to maintain SaO2 over 90%. Results: The main indication of BiPAP, in 80% of cases, was pulmonary restrictive disease. Indications of NIV were acute exacerbations in patients with chronic domiciliary NIV in three patients, hypoxic ARF in six and hypercapnic ARF in five. The diagnoses were pneumonia/atelectasis in seven patients, bilateral extensive pneumonia in three, RSV bronchiolitis in two, apnea in one, and asthma exacerbation in one. Only one patient required intubation for mechanical ventilation, all others improved. The procedures did not have complications. NIV lasted less than three days in 5 patients, 4 to 7 days in four patients and more than 7 days in five. One third of the patients required fiberoptic bronchoscopy for massive or lobar atelectasis and one third remained on domiciliary NIV program. Conclusions: NIV can be useful and safe in children with ARF admitted to a Pediatric Intermediate Care Unit. If strict inclusion protocols are followed, NIV might avoid mechanical ventilation.

Estenosis subglótica adquirida: tres años de experiencia (1999-2001) / Acquired subglottic stenosis: a three years experience (1999-2001)

Se presentan 10 niños con estenosis subglótica adquirida (ESA) post extubación durante 3 años de observación (enero 1999 - diciembre 2001) correspondiente al 3 por ciento de las fibrobroncoscopías (FBC) realizadas. Siete pacientes fueron hombres y 3 mujeres. El rango de edad fue desde recién nacidos a 14 años; 8 niños < 1 año. Tres eran prematuros y uno tenía displasia broncopulmonar severa. El tiempo de ventilación fue de 4 a 35 días, en 70 por ciento > 7 días. La presentación clínica fue estridor en 8 y en 2 prematuros fue un hallazgo endoscópico. Se realizó FBC en 8 pacientes y FBC más broncoscopia rígida en 2. Seis tenían disminución del área subglótica > 70 por ciento (ESA grado III); 3 de ellos (50 por ciento) con evolución rápida a estenosis puntiforme. El resto tenía ESA grado II. Cuatro pacientes se traqueostomizaron (TQ); con ESA grado III y uno con ESA grado II + granuloma subglótico obstructivo. Cuatro lactantes < 1 año (3 ESA grado III - 1 ESA grado II) se dilataron con tubos endotraqueales más aplicaión tópica de mitocima-C. Tres niños fallecieron. Dos pacientes TQ lograron ser exturbados. De los 5 pacientes dilatados 3 (60 por ciento) evolucionaron asintomáticos con mejoría en control FBC tardío. Conclusión: ESA es una patología de baja incidencia, asociada con período de intubación > 7 días; en menores de 1 año y con morbilidad. Se presenta como estridor o hallazgo endoscópico. La dilatación más aplicación tópica de mitomicima-C fue exitosa en ESA inmaduras grado II-III.

Asistencia ventilatoria no invasiva domiciliaria nocturna en pediatría / Pediatric nocturnnal noninvasive ventilation assistance at home

The nocturnal noninvasive ventilation (NNIV) at home is often used in chronic respiratory failure (CRF) and obstructive sleep apnea (OSA) and, less frequently, in central hypoventilation and cystic fibrosis. We present a 6 year period (1996-2002) retrospective review of 10 children treated with noninvasive respiratory support describing indications, type of NNIV and the follow-up. Patient's age ranged from 1 to 13 years old; 6 were females and 4 males. Six had a neuromuscular disease, three a cerebral palsy and one an Arnold Chiari Syndrome Type II. Nine children presented kyphoscoliosis. NNIV was indicated in the following conditions: compensated CRF (n = 3), decompensated CRF (n = 1), acute respiratory failure with underlying neuromuscular diseases and unclear diagnosis of CRF (n = 2); OSA with pharyngeal collapse (n = 3) and central hypoventilation (n = 1). Two patients had moderate to severe pulmonary restriction and subnormal maximal airway pressures. Six patients were discharged with CPAP and four with BiPAP after being hospitalized during 3 to 90 days. In average, the follow-up lasted 2 years. Three children had training of their respiratory muscles. One patient needed a tracheostomy, the other nine improved: five without re-admissions and four reduced them. Five patients went back to school. One patient with congenital myopathy and kyphoscoliosis, surgically treated, improved her pulmonary function and the 6 minutes walking test. Two patients used NNIV irregularly and other two stopped it after one year. No deaths were reported. In our experience NNIV at home lessens admissions and promotes a better social and school re-integration. BiPAP is useful in restrictive conditions meanwhile CPAP is helpful in upper airway obstruction with OSA.

La asistencia ventilatoria no invasiva domiciliaria nocturna (AVNIDN) se indica en insuficiencia respiratoria crónica (IRC), síndrome de apnea obstructiva del sueño (SAOS) y ocasionalmente por hipoventilación central y fibrosis quística. Se hace una revisión retrospectiva de 10 pacientes sometidos a esta técnica de soporte ventilatorio no invasivo durante un periodo de 6 años (1996-2002), describiendo las indicaciones, tipo de AVNIDN y el seguimiento. Sus edades fluctuaron entre 1 a 13 años; 6 mujeres y 4 hombres. Seis pacientes tenían enfermedad neuromuscular; 3 parálisis cerebral y uno Arnold Chiari tipo II. Nueve presentaban xifoescoliosis. Las indicaciones fueron: IRC estable 3 pacientes; posterior a IRC descompensada 1; luego de insuficiencia respiratoria aguda en enfermos neuromusculares sin diagnóstico claro de IRC, 2 pacientes. SAOS secundaria a faringomalacia en 3 y por hipoventilación central uno. Dos presentaban restricción pulmonar moderada a severa y presiones máximas de vía aérea subnormales. Seis pacientes recibieron CPAP y 4 Bipap. El tiempo de hospitalización previo al alta fue de 3 a 90 días y la duración promedio del seguimiento fue 2 años. Tres recibieron entrenamiento muscular respiratorio. No hubo mortalidad; un paciente fue traqueostomizado. Nueve mejoraron, 5 no tuvieron rehospitalizaciones y 4 las disminuyeron. Cinco pacientes asisten al colegio. Un paciente con miopatía congénita y artrodesis mejoró sus pruebas funcionales respiratorias y la distancia recorrida en 6 minutos. Dos usaron irregularmente la AVNIDN y dos suspendieron tratamiento luego de un año. En nuestra experiencia, la AVNID minimizó las hospitalizaciones y promovió la reinserción social y escolar. La modalidad Bipap fue útil en patologías restrictivas y el CPAP en obstrucción de vía aérea superior/SAOS.

[Endovascular therapy of superior vena cava syndrome: clinical case]. / Terapia endovascular en el sindrome de vena cava superior: caso clínico.

The treatment of superior vena cava syndrome is usually oriented to the underlying cause, that can be too slow in emergency cases. We report a 49 years old woman with a multiple myeloma that was admitted due to a superior vena cava syndrome caused by a central venous catheter used for chemotherapy for 20 weeks. She was successfully treated with thrombolysis, angioplasty and stent placement. The patient died 7 months later due to the underlying disease. Long term catheters are the responsible for 20 to 30% of superior vena cava syndromes. Endovascular treatment of the syndrome is successful in 60 to 100% of cases with a symptomatic relapse in 4 to 45% of patients.