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Approach to corticosteroid-dependent and corticosteroid-refractory Crohn's disease.

Corticosteroids are considered a drug of choice for the treatment of patients with moderately to severely active Crohn's disease (CD), an inflammatory bowel disease characterized by chronic recurrent flares of disease activity. However, among patients receiving corticosteroid therapy for induction of remission, 20% have corticosteroid-refractory disease and 36% of those with an initial response develop corticosteroid dependency within 1 year. Chronic corticosteroid exposure in patients who are corticosteroid dependent increases the risk for serious drug-related adverse effects. Withdrawal or reduction of corticosteroid therapy without exacerbation of symptoms is therefore recognized as an important goal of treatment. Therapies that have been shown to facilitate "steroid sparing' include the immunomodulators azathioprine/6-mercaptopurine and methotrexate and the antitumor necrosis factor-alpha monoclonal antibody infliximab. In corticosteroid-dependent patients, budesonide may be substituted for conventional corticosteroid therapy without loss of response and with less risk for toxicity, but its long-term efficacy requires further evaluation. A preliminary controlled study suggests that the investigational anti-TNF monoclonal antibody CDP-571 may also be clinically beneficial as a corticosteroid-sparing agent. This review summarizes the clinical evidence that supports consideration of these agents as alternatives in patients with CD who are dependent on, refractory to, or intolerant of conventional corticosteroid therapy.

Anti-Inflammatory Agents↗

Effect of inhaled corticosteroids on bronchial responsiveness in patients with "corticosteroid naive" mild asthma: a meta-analysis.

BACKGROUND: Inhaled corticosteroids are the most efficacious anti-inflammatory drugs in asthma. International guidelines also advocate the early introduction of inhaled corticosteroids in corticosteroid naive patients. A study was undertaken to assess the effects of inhaled corticosteroids on bronchial hyperresponsiveness in patients with corticosteroid naive asthma by conventional meta-analysis. METHODS: A Medline search of papers published between January 1966 and June 1998 was performed and 11 papers were selected in which the patients had no history of treatment with inhaled or oral corticosteroids. Bronchial responsiveness to bronchoconstricting agents was considered as the main outcome parameter. Doubling doses (DD) of histamine or methacholine were calculated. RESULTS: The total effect size of inhaled corticosteroids (average daily dose 1000 microg) versus placebo in the 11 studies was +1.16 DD (95% confidence interval (CI) +0.76 to +1.57). When only the eight short term studies (2-8 weeks) were analysed the effect size of the bronchoconstricting agent was +0.91 DD (95% CI +0.65 to +1.16). No relationship was found between the dose of inhaled corticosteroid used and the effect on bronchial responsiveness. CONCLUSION: This meta-analysis in patients with corticosteroid naive asthma indicates that, on average, high doses of inhaled corticosteroids decrease bronchial hyperresponsiveness in 2-8 weeks. It remains unclear whether there is a dose-response relationship between inhaled corticosteroids and effect on bronchial hyperresponsiveness.

Administration, Inhalation↗

Corticosteroid usage and binding to arginine: determinants of corticosteroid hypersensitivity.

Hypersensitivity to topical corticosteroids is a common cause of allergic contact dermatitis. The development of contact allergy is dependent on individual susceptibility, exposure to the potential allergen and the ability to penetrate the epidermis and react with epidermal protein. We looked at corticosteroid binding to arginine and relative usage of corticosteroids to see if these variables explain the number of allergic reactions seen to these structurally similar chemicals. A linear relationship was found between a measure of corticosteroid binding to arginine, the log of relative corticosteroid usage and the log of the relative number of corticosteroid allergies. Using multiple regression this association was significant (P = 0.01). Statistically, these two variables accounted for 73% of the variation in the results. Our results showed that the number of corticosteroid allergic reactions was dependent on usage and the intrinsic ability of the corticosteroid to degrade and bind to arginine. While total corticosteroid usage is unlikely to change, the prescription of individual corticosteroids with a reduced potential to degrade and bind to protein, but with equal efficacy, might reduce the overall prevalence of corticosteroid hypersensitivity.

Analysis of Variance↗

Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use.

BACKGROUND: Few data are available regarding vertebral fracture risk in patients treated with oral corticosteroids. The aim of this study was to determine the prevalence and the role of risk factors such as age, bone mineral density (BMD), and corticosteroid use for vertebral deformity in patients receiving long-term corticosteroid therapy. METHODS: Thoracolumbar x-ray films, BMD, and details on corticosteroid use were obtained on 229 consecutive patients treated with long-term corticosteroid regimens (> or = 6 months of prednisone, > or = 5mg/d or equivalent) seen at 4 referral centers. Comparisons were made with a population control group of 286 male and female controls not taking corticosteroids (aged > or = 60 years). RESULTS: Sixty-five patients (28%) had at least 1 vertebral deformity and 25 (11%) had 2 or more vertebral deformities. Older age, independent of BMD, was a significant risk factor for deformity. Patients aged 70 to 79 years had a 5-fold increased risk of deformity compared with patients younger than 60 years (odds ratio, 5.13; 95% confidence interval, 2.03-13.0). Compared with the population controls, the prevalence of deformities increased to a greater extent with each decade of age in the corticosteroid group (P =.005). Mean lumbar spine and femoral neck BMD Z scores were lower in the steroid-treated patients with deformities compared with the nonsteroid control group with deformities. When the effects of age, sex, body mass index, and duration of corticosteroid use were adjusted for in logistic regression analysis, low BMD was a modest predictor of deformity (for a 1-SD decrease in lumbar spine BMD: odds ratio, 1.31; 95% confidence interval, 1.02-1.68) and for a 1-SD decrease in femoral neck BMD: odds ratio, 1.77; 95% confidence interval, 1.07-2.94). CONCLUSIONS: The combination of increasing age and corticosteroid use is associated with a marked increase in the risk of vertebral deformity. Elderly patients commencing long-term corticosteroid therapy should be considered for antiosteoporotic therapy independently of their BMD. Arch Intern Med. 2000;160:2917-2922

Age Factors↗

Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma.

BACKGROUND: Anti-leukotriene (AL) agents are being considered as "add-on" therapy to inhaled corticosteroids (ICS), in chronic asthma. OBJECTIVES: To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid-sparing effect of AL when added to ICS in chronic asthma. SEARCH STRATEGY: We searched Medline, Embase, Cinahl (all up to 2001), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and ATS meeting abstracts (1998-2000). SELECTION CRITERIA: Randomised placebo-controlled trials of asthmatics aged 2 years and older lasting at least one month. DATA COLLECTION AND ANALYSIS: Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well-controlled) and dose of ICS in the control group (same or double). MAIN RESULTS: Of 336 citations, 11 trials (only adults) met inclusion criteria. Six were published in full-text, eight were high quality. Daily dose of ICS was 300-2000 mcg beclomethasone-equivalent. In symptomatic adults, AL (at 2-4 times licensed dose) combined with ICS reduced the number of patients with exacerbations that required systemic corticosteroids, compared to ICS alone [Relative Risk (RR) = 0.34; 95% Confidence Interval (CI) 0.13, 0.88]. This equates to 20 patients (95% CI 1,100 patients) treated to prevent one needing systemic corticosteroids. There was no difference in side effects. No trials tested the efficacy of licensed doses of ALs as add-on to ICS. In symptomatic adults, addition of zafirlukast to ICS did not reduce the number of exacerbations requiring systemic corticosteroids, compared to doubled dose ICS [RR= 1.39; 95% CI: 0.63, 3.08)]. There were no differences in any other measure of outcome. Higher doses of zafirlukast than currently licensed were associated with increased risk of liver enzyme elevation. In ICS-sparing trials of AL agents there was no difference in ICS dose after 12-16 weeks [Weighted Mean Difference (WMD) 1.9% change; 95% CI -3.5, 7.3], and no difference in lowest tolerated dose of ICS [WMD= 44 mcg/d; 95% CI -59, 148)]. REVIEWER'S CONCLUSIONS: Used as add-on therapy to inhaled corticosteroids, high dose anti-leukotrienes reduced exacerbations, but there is no evidence to support their use at currently licensed doses. There is insufficient evidence to indicate whether they confer benefit over doubling the dose of corticosteroids. There is no evidence that they have any significant inhaled corticosteroid-sparing effect.

Administration, Inhalation↗

Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years.

BACKGROUND: Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment. METHODS: Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism. RESULTS: Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck. CONCLUSION: In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.

Administration, Inhalation↗

[Changes in the cellular-humoral immune reactivity of patients with lupus nephritis and chronic glomerulonephritis treated with corticosteroids or corticosteroids and imuran].

The changes in cellular-humoral immune reactivity were followed up in 13 patients with lupus nephritis and 10 patients with chronic glomerulonephritis, treated with corticosteroids or with corticosteroids and imuran. A tendency to correction of lymphocyte and T-lymphocyte deficiency, inhibition of FsG- and FsM-receptor lymphocytes and of T-gamma and T-mu lymphocyte subpopulations was established in the patients with lupus nephritis, treated only with corticosteroids. The treatment with corticosteroids and imuran inhibited more sharply T gamma- and T-mu lymphocytes than with corticosteroids alone. It was established, in the patients with chronic glomerulonephritis, treated with corticosteroids, that GsG- and FsM-receptor lymphocytes were with significantly lower values than the non-treated ones. No significant changes were established in B-cellular reactivity and serum level of immunoglobulins (IgG, IgM, IgA) with the treatment with corticosteroids and corticosteroids and imuran in both nosological entities. C3- fraction of the complement in the lupus patients treated was with lower values than in the non-treated. The authors conclude that the corticosteroids and corticosteroids and imuran, inhibiting the reactivity of T-lymphocytes, regulating the immune-biological balance, should be cautiously used and under the control of the cellular populations, exposed to their effect.

Adrenal Cortex Hormones↗

Effects of photoperiod and feeding on plasma corticosteroid concentrations and maximum corticosteroid-binding capacity in pigs.

The effects of time of feeding and photoperiod on the circadian rhythm of total and free plasma corticosteroid concentrations and the maximum corticosteroid-binding capacity (MCBC) were measured in pigs. There were four photoperiod treatments: natural long and short daylengths (light:dark, 14:10; 101/2:131/2, respectively), artificial short daylength and reverse artificial short daylength (light:dark, 9:15). Photoperiod had a significant effect on corticosteroid concentrations. The corticosteroid concentrations on long daylength showed a major increase in the morning (from an average of 8 ng ml-1 at 0700 h to a peak level of 53.5 ng ml-1 at 0910 h). The amplitude of the morning peak was lower in the other treatments. Apart from this increase, corticosteroid levels at other times of day for pigs in all treatments were generally low. The MCBC varied greatly between animals (less than 25 - greater than 50 ng ml-1) but showed no circadian rhythm. There was no change in corticosteroid levels directly attributable to feeding. It was concluded that, in experiments where the effect of acute stressors on corticosteroid levels is examined, blood sampling should be performed in the afternoon-evening period because the between-animal variation in hormone levels is less and the hormonal levels are more stable, and also that time of feeding did not affect the rhythm of corticosteroids. A blood-sampling regime to define the circadian rhythm in corticosteroid concentration and to determine the MCBC is described.

Adrenal Cortex Hormones↗

Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids.

Corticosteroids mediate a variety of immunological actions and are commonly utilized in the treatment of a wide range of diseases. Unfortunately, therapy with this class of medications is associated with a large proportion of non-responders and significant side effects. Inhaled corticosteroids are the most commonly used asthma controller therapy. However, asthmatic response to corticosteroids also varies widely between individuals. We investigated the genetic contribution to the variation in response to inhaled corticosteroid therapy in asthma. The association of longitudinal change in lung function and single nucleotide polymorphisms from candidate genes crucial to the biologic actions of corticosteroids were evaluated in three independent asthmatic clinical trial populations utilizing inhaled corticosteroids as the primary therapy in at least one treatment arm. Variation in one gene, corticotropin-releasing hormone receptor 1 (CRHR1) was consistently associated with enhanced response to therapy in each of our three populations. Individuals homozygous for the variants of interest manifested a doubling to quadrupling of the lung function response to corticosteroids compared with lack of the variants (P-values ranging from 0.006 to 0.025 for our three asthmatic populations). As the primary receptor mediating the release of adrenocorticotropic hormone, which regulates endogenous cortisol levels, CRHR1 plays a pivotal, pleiotropic role in steroid biology. These data indicate that genetic variants in CRHR1 have pharmacogenetic effects influencing asthmatic response to corticosteroids, provide a rationale for predicting therapeutic response in asthma and other corticosteroid-treated diseases, and suggests this gene pathway as a potential novel therapeutic target.

Administration, Inhalation↗

Detection of contact hypersensitivity to corticosteroids in allergic contact dermatitis patients who do not respond to topical corticosteroids.

The delayed hypersensitivity development against topical corticosteroids which are used in allergic contact dermatitis (ACD) treatment is an important clinical problem. In our study, 41 ACD patients who did not show any response to topical corticosteroid treatment were patch tested with corticosteroid series and the commercial preparations of corticosteroids and their vehicles. In corticosteroid series, there were budesonide, bethametasone-17-valerate, triamcinolone acetonide, tixocortol pivalate, alclomethasone-17-21-dipropionate, clobetasole-17-propionate, dexamethasone-21-phosphate disodium and hydrocortisone-17-butyrate. We detected positive reaction to corticosteroids in 9 of our cases (22%) (5 single and 4 multiple). The sensitivity was mostly produced by tixocortol pivalate (6 patients). This was followed by triamcinolone acetonide (2 patients) budesonide (2 patients), alclomethasone dipropionate (2 patients), dexamethasone 21 phosphate disodium (2 patients) and betamethasone-17-valerate (1 patient). As a result, it should not be forgotten that the corticosteroids used to treat ACD patients may cause ACD themselves. In ACD patients who did not respond to corticosteroid treatment, routinely applying patch test with corticosteroids should be helpful in directing the treatment.

Administration, Topical↗

Use of corticosteroid sparing systemic immunosuppression for treatment of corticosteroid dependent optic neuritis not associated with demyelinating disease.

AIM: To describe the authors' experience and that in the published literature regarding the use of corticosteroid sparing systemic immunosuppression for patients with corticosteroid dependent optic neuritis not associated with demyelinating disease. METHODS: The records of 10 patients from the authors' clinical database, and 38 patients from the published literature with corticosteroid dependent optic neuritis, were retrospectively reviewed to determine patient demographics, diagnosis, clinical course, and outcomes. These patients had recrudescence of symptoms, such as decreased vision and pain, with attempted taper of corticosteroid. Many of these patients also suffered side effects from systemic corticosteroid use such as weight gain and uncontrolled hyperglycaemia. Antimetabolites (for example, methotrexate and azathioprine), cyclosporine and/or alkylating agents (for example, cyclophosphamide and chlorambucil) were given to enable taper of corticosteroid while effectively controlling optic neuritis. RESULTS: The study included 43 women and 5 men: 17 patients with systemic lupus erythematosus, 12 patients with sarcoidosis, 3 with other systemic autoimmune diseases, and 16 with no clinically identifiable systemic association. 79% of all patients benefited from the use of systemic immunosuppression in that they had successful corticosteroid taper, control of inflammation, improvement in symptoms, and/or tolerance of adverse effects. Mild toxicity was common and 19% of patients, most often those taking cyclophosphamide, discontinued medication because of adverse effects. 24 of 28 (86%) patients on alkylators benefited clinically, while 20 of 29 (69%) patients on antimetabolites had clinical benefit. CONCLUSION: Systemic immunosuppression may be a safer and more effective treatment alternative to chronic oral corticosteroid use in cases of corticosteroid dependent optic neuritis not associated with demyelinating disease.

Adrenal Cortex Hormones↗

Multiple corticosteroid orally elicited allergic contact dermatitis in a patient with multiple topical corticosteroid allergic contact dermatitis.

Corticoid allergic contact dermatitis (ACD) may be topically or systemically elicited. Allergic contact dermatitis to topical corticosteroids is relatively common, whereas reports of orally elicited ACD to corticosteroids are rarer. Patients allergic to one corticosteroid often exhibit cross-reactivity to other corticoids. We have previously reported a 46-year-old woman with contact allergy documented by patch and provocative use testing to multiple topical corticosteroids. On further testing, she was thought to have multiple corticoid orally elicited ACD to triamcinolone, methyl prednisolone, dexamethasone, and prednisone. Oral provocation tests were performed in a single-blind fashion following the method of Alanko and Kauppinen [Diagnosis of drug eruptions: clinical evaluation and drug challenges. In, Skin Reactions to Drugs (Kauppinen K, Alanko K, Hannuksela M, Maibach HI, eds). Boca Raton, FL, CRC Press, 1998.]. The five oral corticosteroids tested were triamcinolone, methyl prednisolone, dexamethasone, prednisone, and hydrocortisone. Four of the five challenged corticosteroids (i.e., triamcinolone, methyl prednisolone, dexamethasone, and prednisone) produced a generalized maculopapular eruption in a delayed manner. The fifth challenged corticoid, hydrocortisone, had no adverse effect on this patient. This patient was unusual in that she exhibited polysensitivity to a spectrum of oral and topical corticosteroids. Hydrocortisone was identified as a corticosteroid for future clinical use. This is an important finding since corticosteroids are important emergency drugs.

Administration, Oral↗

[The clinical analysis of corticosteroid ocular hypertension and corticosteroid glaucoma after photorefractive keratectomy].

OBJECTIVE: To inquire into the incidence, clinical characteristics and therapeutic effects of corticosteroid hypertension and corticosteroid glaucoma after photorefractive keratectomy (PRK). METHODS: The authors completed a follow up study on 1 590 eyes on which this procedure was performed and corticosteroid (0.1% fluoromethalone, FML) eye drops were applied 4 to 6 months post-operatively to observe intraocular pressure at 1, 3, 6, 12 and 24 months, and treated the eyes with increase of intraocular pressure. RESULTS: Corticosteroid ocular hypertension or corticosteroid glaucoma occurred in 2.70% of 1 590 eyes. The intraocular pressure of the eyes was recovered to normal in all patients after treatments of stopping FML eye drops, using topical 0.5% timolol (or 0.5% levobunolol hydrochloride), taking diamox orally or receiving trabeculectomy. CONCLUSIONS: Topical application of corticosteroid may cause corticosteroid hypertension and corticosteroid glaucoma after PRK, and visual function damage may occur in a few eyes. Under this situation, the corticosteroid eye drops should be stopped and glaucomatous treatment should be given.

Adult↗

Corticosteroids for acute ischaemic stroke.

BACKGROUND: Much of the brain swelling in ischaemic stroke is due to cytotoxic oedema, which is related to cell membrane dysfunction. Early treatment with corticosteroids may help reduce the swelling and improve the outcomes after a stroke. OBJECTIVES: The objective of this review was to assess the effect of corticosteroids in acute presumed ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register and contacted investigators in the field. SELECTION CRITERIA: Published randomised trials comparing corticosteroids with placebo or control in people with acute (presumed or definite) ischaemic stroke. Trials were included if treatment began within 48 hours of stroke onset and if clinical outcome was assessed. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted the data. MAIN RESULTS: Seven trials involving 453 people were included. Details of trial quality that may relate to bias were not available from most trials. No difference was shown in the odds of death within one year (odds ratio 1.08, 95% confidence interval 0.68 to 1.72). Treatment did not appear to improve functional outcome in survivors. Six trials reported neurological impairment but pooling the data was impossible because no common scale or time interval was used. The results were inconsistent between individual trials. The only adverse effects reported were small numbers of gastrointestinal bleeds, infections and deterioration of hyperglycaemia across both groups. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate corticosteroid treatment for people with acute presumed ischaemic stroke.

Anti-Inflammatory Agents↗

Subtenon's depot corticosteroid injections in patients with a history of corticosteroid-induced intraocular pressure elevation.

PURPOSE: To determine whether a history of intraocular pressure elevation from local corticosteroid administration could predict subsequent intraocular pressure elevation after posterior subtenon's corticosteroid injection. METHODS: A retrospective review was performed of 64 consecutive patients (64 eyes) receiving posterior subtenon's corticosteroid injection. Patients were categorized as either historical corticosteroid responders or nonresponders based on intraocular pressure response to topical corticosteroid drops in the same eye or to previous posterior subtenon's corticosteroid injection of the fellow eye. Historical responders were defined as having a relative intraocular pressure increase of 5 mm Hg and absolute intraocular pressure greater than 24 mm Hg with an anatomically open angle. Relative risk of intraocular pressure elevation was evaluated based on historical response and presenting diagnosis. RESULTS: Nine eyes were historical responders, and 55 eyes were historical nonresponders. A higher rate of recurrent intraocular pressure elevation developed in historical responder eyes (4 of 9, 44%) compared with nonresponders (7 of 55, 13%) after posterior subtenon's injection (P = .04, Fisher's test; P = .07, Kaplan-Meier analysis). Historical responders with uveitis were at significantly higher risk of intraocular pressure elevation than nonresponders without uveitis (hazard ratio = 10.8, P = .04, Cox proportional hazards). All but one eye that developed intraocular pressure elevation from posterior subtenon's injection was adequately controlled with topical antiglaucoma therapy. CONCLUSION: In nonglaucomatous eyes, a previous history of corticosteroid-induced intraocular pressure elevation is a relative, not absolute, contraindication to posterior subtenon's corticosteroid injection, because the risk of intraocular pressure elevation is not absolute, and because it can usually be well controlled with topical antiglaucoma therapy.

Adult↗

Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH.

BACKGROUND/AIMS: Controversy surrounding the efficacy of corticosteroids in severe alcoholic hepatitis (AH) persists. THE AIMS OF OUR STUDY WERE: (a) to analyze individual data of patients with severe AH discriminant function (DF)> or =32 from the last three randomized controlled trials; and (b) to identify the independent prognostic factors associated with short-term survival. METHODS: Individual data were collected from the three principal investigators. Survival analysis was performed at 28 days using the Kaplan-Meier method and log-rank test. The independent prognostic values were assessed by the proportional hazards regression model. RESULTS: About 102 placebo and 113 corticosteroid patients with DF > or =32 were analyzed. At 28 days, corticosteroid patients had significantly higher survival: 84.6+/-3.4% vs. 65.1+/-4.8%, P=0.001. In univariate analysis, corticosteroid treatment, age, DF, albumin, creatinine and encephalopathy were prognostic factors. In multivariate analysis, age (P=0.0001), serum creatinine (P<0.002) and corticosteroid treatment (P=0.002) were independent prognostic variables. A more dramatic decrease of median serum bilirubin values (micromol/l) was observed at 7 and 14 days in corticosteroid patients (P<0.05) : -76.5 vs. -35 and -105 vs. -45. CONCLUSIONS: Corticosteroids improved short-term survival of patients with severe AH. Age and serum creatinine are independent prognostic factors. Corticosteroids are recommended for patients with severe AH.

Adrenal Cortex Hormones↗

Contact allergy to corticosteroids in patients using inhaled or intranasal corticosteroids for allergic rhinitis or asthma.

BACKGROUND: Patients using topically applied corticosteroids are at risk of developing allergic contact hypersensitivity. OBJECTIVE: To assess prevalence of allergic contact hypersensitivity reactions to inhaled or intranasal corticosteroids. METHODS: A prospective study of 30 adult patients using inhaled or intranasal corticosteroids for conditions such as allergic rhinitis was performed. We used epicutaneous patch testing to determine the prevalence of allergic contact hypersensitivity to corticosteroids and common additives (propylene glycol and benzalkonium chloride) in inhaled and nasal corticosteroid preparations in this population. RESULTS: Of 30 patients, 4 (13%) had positive patch test results. 3 (10%) were allergic reactions and 1 (3%) was an irritant reaction. Half of the reactions were to a corticosteroid (budesonide) and half were to a common preservative in nasal preparations (benzalkonium chloride). CONCLUSION: This study supports other clinical evidence that contact dermatitis/mucositis from inhaled or intranasal corticosteroid products can occur. The corticosteroids or added agents such as preservatives can be causative and may result in allergic or irritant reactions, which can be relevant to clinical symptoms.

Administration, Inhalation↗

Comparison of effects of long-term corticotrophin and corticosteroid treatment on responses of plasma growth hormone, ACTH, and corticosteroid to hypoglycaemia.

The development of the highly sensitive cytochemical bioassay for ACTH has permitted the measurement of plasma ACTH levels during the insulin hypoglycaemia test (I.H.T.) in patients treated with corticosteroids and corticotrophin. The ACTH, corticosteroid, and growth hormone (GH) responses in the I.H.T. were measured in three groups of 12 rheumatoid arthritis patients. One group was receiving long-term corticotrophin treatment, the second was undergoing long-term corticosteroid treatment, and the third had never received systemic hormone therapy. The increments in plasma ACTH, corticosteroids, and GH were diminished in the corticosteroid-treated group, as were increments in plasma GH and ACTH in the corticotrophin-treated group; but in this group the corticosteroid increment was normal. Examination of the area under the curve of the ACTH response showed that the total amount of ACTH secreted was normal though the rate of secretion was reduced. In the corticosteroid-treated group both rate and total secretion were diminished.

Adrenal Cortex Hormones↗