Sarcoidosis. Un enfoque global / Sarcoidosis. A global approach

La Sarcoidosis es una enfermedad multisistémica de causa desconocida, que frecuentemente se presenta con adenopatía hiliar bilateral, infiltraciónpulmonar, lesiones cutáneas y oculares. El diagnóstico se establece cuando los hallazgos clínico-radiológicos son sustentados por una histopatologíaque evidencia granulomas no caseosos de células epitelioides.La predisposición a adquirir Sarcoidosis parece genéticamente determinada, sin embargo solo un pequeño grupo de alelos de HLA han sido posiblesde identificar, asociados a la susceptibilidad de la enfermedad.La Sarcoidosis es un síndrome que puede deberse a muchos factores precipitantes. Hay quienes piensan que solo hay un ùnico agente antigénico, aúnno determinado, que condiciona la involución o persistencia de la enfermedad, por razones que son un enigma y motivo de intensa investigación.Se describen las manifestaciones cutáneas estableciendo un ordenamiernto de las múltiples y variables lesiones. Así como también se describen lasmanifestaciones sistémicas más relevantes.Se hace referencia a las enfermedades asociadas que pueden encontrarse en la Sarcoidosis, en especial la patología autoinmune y las neoplasiashematológicas.Las alternativas terapéuticas más utilizadas son los corticoesteroides y los antipalúdicos, El metotrexato, talidomida, tetraciclinas y el infliximab tienenindicación en ciertos casos especiales (AU)

Sarcoidosis is a multisystemic disease of unknown cause that frequently appears with bilateral hiliar adenopathy, lung infiltration and skin and eyelesions.Diagnosis is made when clinical and radiological findings are backed by histopathology evidencing granulomas no caseosos of epitelial cells.Predisposition to acquire sarcoidosis seems to be genetic, however only a small group of alelos de HLA could be identified in association to disease susceptibility.Sarcoidosis is a syndrome that can obey to many precipitant factors. Some people think that there is only one antigenic agent, not identified yet, thatconditions the involution or persistence of the disease, for reasons that are an enigma and a cause of intense research.It has been described different skin manifestations settling a range of multiple and variable lesions. Even more relevant systemic manifestations havebeen described.There is a special reference of diseases associated with sarcoidosis such as autoinmune pathology and hematological neoplasias.The most used alternative therapies are cortocoesteroids and antimalarials.The methotrexate, thalidomide, tetracyclines and the infliximab are indicatedin some special cases (AU)

Asthma mortality in Danish children and young adults, 1973-1994: epidemiology and validity of death certificates.

Several reports indicate that asthma mortality has increased during the last few decades. International comparisons reveal some striking differences in the pattern of asthma mortality. The authors investigated the asthma mortality rate in the Danish child and youth population 1973-1994 and studied the validity of death certificates. The authors reviewed all death certificates coded as asthma death in the International Classification of Diseases (ICD 8-ICD 10 (1994)) and adjacent respiratory code numbers for the age group 1-19 yrs. Hospital records and autopsy reports were assessed to validate the cause of death. Age-standardized and age-specific mortality rates were calculated. From 1973 to 1987 there was a significant upward trend in the mortality. On subdivision, this trend was limited to the age group 15-19 yrs. Generally the mortality rate decreased from 1988 to 1994. Four per cent coded as asthma were false positive. Twelve per cent were false negative asthma deaths, wrongly coded as due to other causes. Only 62% of all true positive death caused by asthma were appropriately coded. The number of false negative certifications increased with increasing autopsy frequency. Asthma mortality rates in Denmark increased in adolescents during 1973-1987 and decreased from 1988 to 1994. A possible explanation may be an increased awareness of asthma symptoms combined with a steadily improved treatment of asthma. Even in children and young adults under the age of 20 yrs, validity problems still make comparisons between countries difficult; even interpretation of national trends requires caution.

Prevalence of asthma in Danish children aged 8-10 years.

The aim of the study was to estimate the point prevalence of asthma in schoolchildren aged 8-10 y in the County of Copenhagen, Denmark. In all, 1040 schoolchildren were randomly chosen for the study and a total of 774 completed the study. The suspicion of asthma was based on a questionnaire about respiratory symptoms and on daily registration of respiratory symptoms and peak expiratory flow rate (PEF) for 4 weeks. The conclusive diagnosis was based on interview, clinical examination, spirometry and an exercise test. The prevalence of children with asthma diagnosed by their GPs was 31/774 (4.0%). A further 20/774 (2.6%) were diagnosed as having asthma. There is evidence to suggest that asthma is less frequent in Denmark than in Great Britain, New Zealand and Australia.

[Latex allergy]. / Latexallergi.

Latex allergy has been described with increasing frequency throughout the last years. The prevalence in Denmark is not yet known. The growing frequency is partly explained by the extensive use of latex-containing products (especially gloves), which has followed the appearance of the HIV-epidemic. The symptoms of latex allergy are usually those produced by type-I hypersensitivity. Type-IV allergy (contact dermatitis) to rubber chemicals is well described but is not directly associated with the latex proteins. The allergens in latex have nearly been identified; diagnostic tools are known but are not yet satisfactory. Cross-reacting antigens are found in banana, kiwi, avocado, chestnut and other plants. It is concluded, that attention to latex allergy has to be intensified and the risk factors reduced, especially concerning the health care units.

[Latex allergy in children]. / Latexallergi hos børn.

More than a thousand cases of type-1 latex allergy have been presented. In children the condition is most often described in patients with spina bifida. Six cases of latex allergy in atopic children are presented. Five of these had food allergies, especially to banana. The allergy was verified with prick-test, LHR-test and measurement of specific IgE. It is concluded that attention to latex allergy in atopic children has to be intensified. Prick-test with standardised latex extracts is the preferred method for diagnosis of the allergy. Latex dummies, latex toys, balloons etc, have to be avoided.

Nitrous oxide depresses the H-reflex in children with cerebral palsy.

Hoffmann's reflex or H-reflex (HR) is an electrically elicited reflex that measures excitability of motoneurons and shares some physiologic properties with the deep tendon reflex. Children with tendon hyperreflexia due to cerebral palsy usually have higher amplitude HRs. Nitrous oxide (N2O) depresses the HR in patients with normal spinal reflexes, although the effect of N2O in conditions with hyperreflexia such as cerebral palsy is not known. We propose to determine the effect of N2O on the amplitude of the HR under general anesthesia in children with hyperreflexia due to cerebral palsy. We studied eight children undergoing selective dorsal rhizotomy (SDR) for the relief of spasticity. The maximum amplitudes of the HR (HRmax) and direct motor response (MRmax) were routinely evoked under the following anesthetic conditions: 1) sufentanil and 66% N2O/33% oxygen; and 2) sufentanil and 100% oxygen. The HRmax amplitude was significantly lower when N2O was part of the inspired gas mixture. The differences between the no N2O and the 66% N2O groups were significant. The MRmax did not change significantly. Abnormal spinal reflexes seen in spastic diplegia can be abolished by inhaled N2O. This finding also suggests that N2O-induced depression of spinal reflexes should be a consideration during physiologic monitoring of the spinal cord under general anesthesia.

Bronchial responsiveness in children and adolescents: a comparison between previously asthmatic, currently asthmatic, and normal subjects.

The aim of this study was to examine the degree of bronchial responsiveness in previously asthmatic subjects. Of 253 patients, born within 1964-1974, followed in the pediatric department at the University hospital in Copenhagen, 224 subjects (89%) were successfully contacted by telephone; of these 195 complained of persistent asthma and 29 (13%) had had no asthmatic symptoms for at least 2 years. On the basis of the degree of respiratory symptoms, 58 individuals were examined at the outpatient clinic. Of these, (1) 19 were previously asthmatics, (2) 20 had current mild asthma, and (3) 19 had current severe asthma. Furthermore, 19 healthy individuals, age-matched with the preceding asthmatic subjects, were selected as controls. In all subjects, skin prick tests, lung function tests, and bronchial challenge tests with inhaled histamine and bronchodilator were performed. Furthermore, the subjects measured their peak expiratory flow (PEF) twice daily during a period of 4 weeks. Of the 39 current asthmatic subjects, 82% had a PC20 < or = 8 mg/ml, whereas all previously asthmatic subjects and the controls had a PC20 > 8 mg/ml. The degree of bronchial responsiveness as indicated by the dose-response slope (DRS), the percentage change in forced expiratory volume in 1 sec (FEV1) per inhaled mumol of histamine, was found to be significantly higher in previously asthmatic patients (median logDRS 0.1 delta %FEV1/mumol) than in controls (median logDRS-0.4 delta %FEV1/mumol) (p < 0.001). Furthermore previously asthmatic subjects had significantly increased change in FEV1 after inhalation of bronchodilator and peak expiratory flow variability compared to controls. These findings suggest that apparently asymptomatic previously asthmatic subjects have increased airway variability.

Pulmonary function in adolescents with childhood asthma.

The aim of this study was to determine the pulmonary function in former and present asthmatics. We examined 77 persons aged 12-24 years, classified into four groups: 1) healthy subjects (controls) (n = 19), 2) former asthmatics (n = 19), 3) present mild asthmatics (n = 20), and 4) present severe asthmatics (n = 19). Although exhibiting no respiratory symptoms, former asthmatics had reduced airflow values measured by FEV1 (median (range) 89.7 (83-99) vs 101.4 (91-110)) and MEF25 (76.5 (68-94) vs 103.0 (97-124)), as compared with controls. Furthermore, former asthmatics had significantly increased PEF variability, as compared with controls, whereas no significant differences were found in static lung parameters, i.e. total lung capacity and residual volume, as compared with controls. In conclusion, former asthmatics, although now exhibiting no respiratory symptoms, were found to have obstructive airflow limitation, increased bronchial responsiveness, and normal lung volumes.

Reduction of indoor airborne mould spores.

In 23 dwellings in Copenhagen high concentrations of airborne mould spores were shown by the "open Petri dish" method. The families were instructed how to reduce this contamination. One year later the number of mould spores was estimated again. At that time their number was 1/10 of that shown at the first sampling in 11 dwellings, and in 7 dwellings the reduction of mould spores decreased to 1/5. Only one dwelling showed no reduction.

Adrenocortical suppression following treatment with beclomethasone and budesonide.

The study was carried out to compare the adrenocortical suppression caused by inhaled beclomethasone dipropionate (BDP) with the suppression caused by budesonide (Bu). The study was of an open cross-over design. Sixteen children with asthma were treated with high-dose inhaled BDP and Bu via a 750 ml spacer (Nebuhaler). Each drug was used for periods of 6 weeks. The 24-hr urinary cortisol excretion was unchanged in 11 subjects. A reproducible suppression of the urinary cortisol excretion was shown in three subjects following BDP and in two subjects following treatment with Bu. The results of the study indicate the occurrence of interpersonal variations of the sensitivity to the adrenocortical suppressive effect of BDP and Bu.

Basophil histamine release in children with adverse reactions to cow milk. Comparison with RAST and skin prick test.

Basophil histamine release was examined in 26 children suspected of having cow milk allergy (CMA). Following oral challenge with cow milk, the initial adverse reaction reappeared in 20 children, the majority developing urticaria. The urticaria patients showed a high degree of correlation between the results of histamine test, RAST and skin test. Children with gastrointestinal symptoms reacted to milk challenge, but only a few showed a positive histamine test, RAST and skin test. Among the patients with atopic dermatitis, the tests gave mostly negative results, which was in accordance with the lack of response to a milk challenge. The results obtained by removal from and fixation to the cell surface of IgE indicate an IgE-mediated reaction in CMA, which, in connection with the correlation between histamine test and RAST or skin test, suggests basophil histamine release as a suitable method for testing Type I allergy in children suspected of CMA.

Adrenocortical function in children on high-dose steroid aerosol therapy. Results of serum cortisol, ACTH stimulation test and 24 hour urinary free cortical excretion.

The adrenocortical function was investigated in 18 children treated with high-doses of inhaled glucocorticoid aerosol (mean: 1965 micrograms/1.73 m2 body surface a day). Basal serum cortisol was only below the normal range in patients treated with doses exceeding 2500 micrograms/1.73 m2 body surface. 15 of 18 children had normal 24 h urinary free cortisol excretion, compared with 27 normal children matched for age, sex and body surface. Three patients taking more than 2400 micrograms/1.73 m2 body surface showed excretion values below the range for the normal controls. 10 of 12 patients showed a normal response to a short ACTH stimulation test. One patient treated with 3300 micrograms/1.73 m2 body surface showed no response and one patient gave a borderline response to ACTH. We concluded that doses up to 2000 micrograms/1.73 m2 body surface/24 can be administered by pressurized aerosol with little risk of adrenocortical suppression.

Decreased adreno-cortical suppression utilizing the Nebuhaler for inhalation of steroid aerosols.

The influence on the adrenocortical function of high-dose topical glucocorticoids inhaled via conventional devices and via a Nebuhaler, was studied in ten children with asthma. In patients treated with dosages of beclomethasone dipropionate or budesonide, in excess of 2100 micrograms/1.73 m2 body surface, the 24-h urinary excretion of free cortisol increased when the inhaler device was changed from a conventional one to a Nebuhaler. This suggests a decreased systemic influence of the inhaled glucocorticoids when these were administered via a Nebuhaler.

Jet-nebulized beclomethasone dipropionate in the management of bronchial asthma. Topical steroids for asthmatic children younger than 4 years.

The efficacy of jet nebulized beclomethasone dipropionate (BDP) in the management of asthma was evaluated in 18 children, 2-26 months old (mean 10 months). The children were selected on the basis of the severity of their symptoms and the lack of effect of conventional treatment. The effect of BDP was evaluated by comparing clinical data before and after the initiation of treatment. Fifteen of the 18 patients experienced a significant clinical improvement during treatment with BDP. BDP "nebulizer solution" is a valuable contribution to the management of severe asthma in young asthmatics.

Beta 2-agonists for the treatment of wheezy bronchitis?

Nebulized albuterol (salbutamol) for the treatment of wheezy bronchitis was evaluated in a double-blind trial comprising 28 acutely ill children younger than 18 months and in 13 children 18 to 36 months of age. No significant difference in clinical effect was shown between albuterol and saline in the youngest group of children. Albuterol had some beneficial effect in children older than 18 months.

Nebulised sodium cromoglycate in the treatment of wheezy bronchitis. A multicentre double-blind placebo controlled study.

The efficacy of nebulised sodium cromoglycate (SCG) used as a prophylactic treatment of wheezy bronchitis in children aged 1 to 4 years was evaluated in a multicentre double-blind placebo controlled, group comparative study. Fifty-four patients completed the 10-week trial (29 treated with SCG and 25 treated with placebo), preceded by 4-8 weeks baseline. Nebulised SCG did not prove significantly superior to placebo in reducing day wheezing, day coughing, or sleep disturbance due to wheezing or coughing at night. Neither was there significant difference in the use of supportive medicine (beta 2-agonist and theophylline) between the groups. Extra doctor visits, hospital admissions, and parental preference did not show significant difference either.

A clinical comparison of aerosol and powder administration of beclomethasone dipropionate in childhood asthma.

Forty children with childhood asthma were conducted through a double-blind cross-over study to compare the effect of 400 micrograms beclomethasone dipropionate administered as aerosol and powder (Rotacaps). Children with severe asthma derived more benefit from the steroid administered as aerosol judged from their peak flow performance in the morning, although neither evening peak flow nor symptom scores revealed any difference. It is concluded that the Rotacaps are an advantageous supplement to available medication for the treatment of asthmatic children, although it should be observed that, using equal amounts of BDP, powder administration seems less effective than aerosol.

Non-hydrolysed and hydrolysed soy protein. A human immunological study.

Daily consumption of soy protein has increased during recent years. Twelve healthy subjects and 12 atopic patients were given 30 g non-hydrolysed soy protein (NHS) or 30 g hydrolysed soy protein (HS) daily during a 3-month period. There were no changes in the following immunological parameters: IgE with specificity for NHS or HS, IgG with specificity for NHS, crossed radioimmunoelectrophoresis with NHS and skin prick test using NHS or HS. Hypertrophy of the pancreas in rats exposed to excessive peroral intake of soy flour has been reported. In our study the size of the pancreas was measured before dosing began and at the end of the study by means of ultrasound. No change in size was shown. Daily intake of 30 g NHS and 30 g HS gave rise to gastrointestinal discomfort, while 15 g of both soy protein preparations were usually accepted.