Biomedical subjects

Timothy J Craig

Publications and source records attributed to Timothy J Craig.

At least 19 recordsLinked to original sources

PubMed2007

Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma.

RATIONALE: One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control. OBJECTIVES: To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke. METHODS: In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast. MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV(1), bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers. CONCLUSIONS: In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke.

Acetates↗

PubMed2007

The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial.

BACKGROUND: Although guidelines recommend anti-inflammatory therapy for persistent asthma, recent studies suggest that 25% to 35% of patients with asthma may not improve lung function with inhaled corticosteroids. OBJECTIVE: To evaluate potential biomarkers of predicting short-term (6-week) response to inhaled corticosteroid with subsequent evaluation of responders and nonresponders to asthma control over a longer interval (16 additional weeks). METHODS: Eighty-three subjects with asthma off steroid were enrolled in this multicenter study. Biomarkers and asthma characteristics were evaluated as predictors of inhaled corticosteroid response over a 6-week trial for changes in FEV(1) and methacholine PC(20). After this, an additional 4-month trial evaluated asthma control. RESULTS: Although multiple baseline predictors had significant correlations with improvements for short-term inhaled steroid success, the only strong correlations (r >or= +/- 0.6) were albuterol reversibility (r = 0.83; P < .001), FEV(1)/forced vital capacity (r = -0.75; P < .001), and FEV(1) % predicted (r = -0.71; P < .001). Dividing the subjects in the short-term inhaled steroid trial into responders (>5% FEV(1) improvement) and nonresponders (<or=5%) determined the longer-term need for steroids. For the nonresponders, asthma control remained unchanged whether inhaled corticosteroids were continued or were substituted with a placebo (P = .99). The good short-term responders maintained asthma control longer-term only if maintained on inhaled steroids (P = .007). CONCLUSION: The short-term response to inhaled corticosteroids with regard to FEV(1) improvement predicts long-term asthma control. CLINICAL IMPLICATIONS: The decision to use long-term inhaled steroids could be based on a short-term trial. Different therapeutic strategies would need to be established for nonresponders.

Adult↗

PubMed2006

Combination therapy with a long-acting beta-agonist and a leukotriene antagonist in moderate asthma.

RATIONALE: Long-acting beta-agonists (LABAs) and inhaled corticosteroids administered together appear to be complementary in terms of effects on asthma control. The elements of asthma control achieved by LABAs (improved lung function) and leukotriene receptor antagonists (LTRAs; protection against exacerbations) may be complementary as well. OBJECTIVE: We sought to determine whether the combination of the LTRA montelukast and the LABA salmeterol could provide an effective therapeutic strategy for asthma. METHODS AND MEASUREMENTS: In a randomized, placebo-controlled, crossover study of 192 subjects with moderate asthma, we compared the clinical efficacy of regular treatment over 14 weeks with the combination of montelukast and salmeterol to that with the combination of beclomethasone and salmeterol in moderate asthma. The primary efficacy outcome was time to treatment failure. MAIN RESULTS: Three months after the randomization of the last subject, the Data and Safety Monitoring Board determined that the primary research question had been answered and terminated the trial. The combination of montelukast and salmeterol was inferior to the combination of beclomethasone and salmeterol as judged by protection against asthma treatment failures (p = 0.0008), lung function (26 L/min difference in a.m. peak expiratory flow rate, p = 0.011), asthma control score (0.22 difference in Asthma Control Questionnaire score, p = 0.038), and markers of inflammation and airway reactivity. CONCLUSIONS: Patients with moderate asthma similar to those we studied should not substitute the combination of an LTRA and an LABA for the combination of inhaled corticosteroid and an LABA.

Acetates↗

PubMed2006

Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma.

OBJECTIVE: The reduction of oral prednisone use by mometasone furoate (MF) delivered by HFA-227 metered dose inhaler (MDI) was examined in oral corticosteroid (OCS)-dependent patients with severe persistent asthma. METHODS: A 3-month, double-blind, placebo-controlled clinical trial (n=123), followed by a 9-month open-label phase (n=120). The study was conducted at 26 medical centers in the United States. Patients were randomized to treatment with MF-MDI 400 or 800 microg twice-daily (bid) doses, or placebo in the double-blind trial. All patients received MF in the open-label phase. RESULTS: At the endpoint of the double-blind trial, MF-MDI 400 and 800 microg bid reduced the daily OCS dose by 39.4% and 31.1%, respectively, while placebo increased the OCS dose by 107.2% (P<0.01). The OCS requirement was reduced by 50% or more in 63% and 60% of patients treated with MF-MDI 400 and 800 microg bid, respectively, compared with 14% of patients receiving placebo. After 12 weeks, despite prednisone reductions, pulmonary function, asthma symptoms, albuterol use, nocturnal awakenings, and physician-evaluated response to therapy also showed significant improvement with MF-MDI treatment compared with placebo. Further reductions in OCS requirements were achieved with long-term MF-MDI treatment in the open-label phase, with an overall 67% reduction in prednisone usage and 51% of patients completely eliminating prednisone usage by the 1-year time point. CONCLUSION: MF delivered by HFA-227 MDI significantly reduces daily OCS use compared with placebo and facilitates elimination of OCS use in patients with severe persistent asthma.

Administration, Inhalation↗

PubMed2006

Clinical and entomological factors influence the outcome of sting challenge studies.

BACKGROUND: The reported frequency of systemic reactions to challenge sting varies greatly. OBJECTIVE: To evaluate the interaction of clinical and entomological factors that determine the outcome of a challenge sting. METHODS: Patients allergic to yellow jacket were stung and monitored for systemic reaction. The frequency and severity of sting reactions were analyzed in relation to the species of insect used and patient characteristics. RESULTS: Objective systemic reactions occurred in 21 of 69 patients (30%) stung with Vespula maculifrons and in 8 of 71 patients (11%) with Vespula germanica (P=.005). Systemic reactions were more frequent in patients with a severe history (9/30; 30%) than in those with a mild or moderate history (21/145; 14%; P=.04). In only 1 of 111 patients (0.9%) was the reaction to sting challenge more severe than previous reactions. The reaction rate was higher when venom skin tests were positive at <1.0 microg/mL (17/75=23%) than when sensitivity was milder (9/100=9%; P=.012). We compared sting outcome and venom-induced histamine release in relation to insects collected in July or in October, and found no difference. CONCLUSION: Allergic reactions to sting challenge are determined by the species of yellow jacket used, the severity of previous sting reactions, and the degree of skin test sensitivity, but not by the time of year. These factors are important to clinicians when they evaluate the chance of reaction to a future sting and to researchers when they design and report sting challenge studies.

Adult↗

PubMed2006

Allergic rhinitis and its effect on sleep, fatigue, and daytime somnolence.

OBJECTIVE: To examine the adverse effects of sleep impairment on the quality of life of patients with the disorder and how these effects can be treated with therapies targeted at the underlying problems that influence sleep. DATA SOURCES: Medline and Ovid search for sleep and rhinitis. STUDY SELECTION: All literature on this topic were reviewed, and, if significant, were incorporated into this review. RESULTS: Intranasal corticosteroids used as treatment for allergic rhinitis have been shown to reduce the nasal congestion characteristic of the disorder. Data on sleep-related end points from clinical trials on intranasal corticosteroids also reveal that the treatment's effectiveness in alleviating nasal congestion leads to better sleep, reduced daytime somnolence, and improved quality of life. CONCLUSION: Further research, specifically using sleep measurements as primary end points, is needed to definitively show that intranasal corticosteroids reduce nasal congestion, thereby improving sleep and, consequently, quality of life in patients with allergic rhinitis. These future trials will serve to identify the most effective therapies that target the adverse effects of sleep impairment in this disorder.

Adrenal Cortex Hormones↗

PubMed2006

The importance of rhinitis on sleep, daytime somnolence, productivity and fatigue.

PURPOSE OF REVIEW: The goal of treatment of allergic rhinitis should include improvement of daytime and nighttime symptoms, sleep, and quality of life. Congestion from allergic rhinitis is associated with decreased learning and productivity at work and school and a reduced quality of life. The release of inflammatory mediators and activation of inflammatory cells results in nasal congestion, causing disrupted sleep and subsequent daytime somnolence. RECENT FINDINGS: This review presents evidence that allergic rhinitis causes sleep disruption, and discusses the pathophysiology of this process. The medications used to treat allergic rhinitis and their ability to improve sleep in patients with allergic rhinitis are reviewed. SUMMARY: Some allergic rhinitis medications can be sedating; therefore, it is important to treat allergic rhinitis with medications that improve symptoms while producing few adverse effects. Medications such as the second-generation antihistamines and anticholinergic drugs are well tolerated, but have little effect on congestion. Intranasal corticosteroids reduce congestion, improve sleep and sleep problems, and reduce daytime sleepiness, fatigue, and inflammation. Recently, montelukast, a leukotriene receptor antagonist, has been added to the therapies approved for allergic rhinitis. Montelukast significantly improves both daytime and nighttime symptoms.

Circadian Rhythm↗

PubMed2006

A safety review of long-acting beta2-agonists in patients with asthma.

Inhaled corticosteroids are the mainstay of asthma therapy; however, inhaled long-acting beta2-agonists (LABAs) are frequently used in the treatment of patients with asthma. LABAs are combined with high-dose inhaled corticosteroids (ICSs) for patients with severe persistent asthma, and they are combined with low-dose ICSs for patients older than 5 years with moderate persistent asthma. Recent safety concerns raised by data from the Salmeterol Multi-Center Research Trial (SMART) have indicated that use of LABAs in some populations may contribute to increased mortality. These concerns are warranted when LABAs are used as monotherapy in the treatment of patients with asthma in whom they may cause increased exacerbations, blunting of rescue-medication effect, and worsening symptoms. However, when used in combination with an ICS, they decrease both rescue-medication use and symptoms, increase lung function, and act as steroid-sparing agents.

Adrenal Cortex Hormones↗

PubMed2005

beta-Adrenergic receptor polymorphisms and response to salmeterol.

RATIONALE: Several studies suggest that patients with asthma who are homozygous for arginine at the 16th position of the beta2-adrenergic receptor may not benefit from short-acting beta-agonists. OBJECTIVES: We investigated whether such genotype-specific effects occur when patients are treated with long-acting beta-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use. METHODS: We compared salmeterol response in patients with asthma homozygous for arginine at B16 (B16Arg/Arg) with those homozygous for glycine at B16 (B16Gly/Gly) in two separate cohorts. In the first, subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy. In the second, subjects were randomized to regular therapy with salmeterol while continuing concomitant ICS. RESULTS: In both trials, B16Arg/Arg subjects did not benefit compared with B16Gly/Gly subjects after salmeterol was initiated. In the first cohort, compared with placebo, the addition of salmeterol was associated with a 51.4 L/min lower A.M. peak expiratory flow (PEF; p = 0.005) in B16Arg/Arg subjects(salmeterol, n = 12; placebo, n = 5) as compared with B16Gly/Gly subjects (salmeterol, n = 13; placebo, n = 13). In the second cohort, B16Arg/Arg subjects treated with salmeterol and ICS concurrently (n = 8) had a lower A.M. PEF (36.8 L/min difference, p = 0.048) than B16Gly/Gly subjects (n = 22) treated with the same regimen. In addition, B16 Arg/Arg subjects in the second cohort had lower FEV1 (0.42 L, p = 0.003), increased symptom scores (0.2 units, p = 0.034), and increased albuterol rescue use (0.95 puffs/d, p = 0.004) compared with B16Gly/Gly subjects. CONCLUSIONS: Relative to B16Gly/Gly patients with asthma, B16Arg/Arg patients with asthma may have an impaired therapeutic response to salmeterol in either the absence or presence of concurrent ICS use. Investigation of alternate treatment strategies may benefit this group.

Administration, Inhalation↗

PubMed2005

Daily versus as-needed corticosteroids for mild persistent asthma.

BACKGROUND: Although guidelines recommend daily therapy for patients with mild persistent asthma, prescription patterns suggest that most such patients use these so-called controller therapies intermittently. In patients with mild persistent asthma, we evaluated the efficacy of intermittent short-course corticosteroid treatment guided by a symptom-based action plan alone or in addition to daily treatment with either inhaled budesonide or oral zafirlukast over a one-year period. METHODS: In a double-blind trial, 225 adults underwent randomization. The primary outcome was morning peak expiratory flow (PEF). Other outcomes included the forced expiratory volume in one second (FEV1) before and after bronchodilator treatment, the frequency of exacerbations, the degree of asthma control, the number of symptom-free days, and the quality of life. RESULTS: The three treatments produced similar increases in morning PEF (7.1 to 8.3 percent; approximately 32 liters per minute; P=0.90) and similar rates of asthma exacerbations (P=0.24), even though the intermittent-treatment group took budesonide, on average, for only 0.5 week of the year. As compared with intermittent therapy or daily zafirlukast therapy, daily budesonide therapy produced greater improvements in pre-bronchodilator FEV1 (P=0.005), bronchial reactivity (P<0.001), the percentage of eosinophils in sputum (P=0.007), exhaled nitric oxide levels (P=0.006), scores for asthma control (P<0.001), and the number of symptom-free days (P=0.03), but not in post-bronchodilator FEV1 (P=0.29) or in the quality of life (P=0.18). Daily zafirlukast therapy did not differ significantly from intermittent treatment in any outcome measured. CONCLUSIONS: It may be possible to treat mild persistent asthma with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen. Further studies are required to determine whether this novel approach to treatment should be recommended.

Administration, Inhalation↗

PubMed2005

Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids.

BACKGROUND: Although inhaled corticosteroids (ICSs) are effective in preventing deterioration in asthma control, at least half of subjects with mild-to-moderate asthma will remain stable when these agents are discontinued. OBJECTIVE: We sought to determine whether noninvasive markers of inflammation predict which individuals maintain asthma control after discontinuation of ICSs. METHODS: We analyzed data obtained from 164 subjects with mild-to-moderate asthma who participated in a 16-week trial comparing the effects of continued ICS use with the effects of a switch to salmeterol or placebo. RESULTS: In comparison with continued ICS use, a switch to salmeterol or placebo was associated with increased rates of asthma deterioration over 16 weeks (9.3% vs 24.1% and 37.5%, respectively; P = .04 and P < .001, respectively). We found that neither exhaled nitric oxide nor methacholine PC 20 , when measured at randomization or 2 weeks after randomization, were significant predictors of subsequent asthma control in subjects who discontinued ICSs. However, both induced sputum eosinophil counts measured 2 weeks after a switch from ICS to placebo and changes in sputum eosinophil counts from before cessation of ICSs to after a switch to placebo predicted subsequent asthma deterioration (area under the receiver-operating characteristic curve, 0.771 [ P < .001] and 0.825 [ P < .001], respectively). CONCLUSION: On the basis of a model treatment strategy, we estimate that allocating subjects to ICS therapy on the basis of changes in sputum eosinophil counts after a trial discontinuation could allow 48% of subjects with mild-to-moderate asthma to discontinue ICS therapy without an increased risk of asthma deterioration over a period of at least 14 weeks.

Administration, Inhalation↗

PubMed2005

Statistical issues in clinical trials that involve the double-blind, placebo-controlled food challenge.

The double-blind, placebo-controlled food challenge is a rigorous tool that has become popular for evaluating adverse reactions to foods. The standard use of the double-blind, placebo-controlled food challenge has been to document food allergies for individual patients, but it recently has been gaining acceptance as a procedure for investigating the effectiveness of therapies to prevent/minimize food-induced anaphylaxis. The purpose of this study was to describe the statistical design and analysis issues for clinical trials that use the double-blind, placebo-controlled food challenge in measuring sensitivity to food allergens. Nonparametric tests for within-group and between-group comparisons are described, as well as a discrete-time survival analysis. The statistical methods are applied to simulated data from a clinical trial that compares control therapy and experimental therapy groups. The results indicate that the experimental therapy is significantly better than control in improving the tolerance to peanut flour in patients with peanut allergy. Although simple nonparametric tests for within-group and between-group comparisons are easy to apply, a discrete-time survival analysis provides the best approach because of its flexibility in accounting for important independent variables (regressors) and longitudinal data. Statistical software packages can be adapted to perform such analyses.

Anaphylaxis↗

PubMed2005

How do topical nasal corticosteroids improve sleep and daytime somnolence in allergic rhinitis?

Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness. This improvement with therapy may be secondary to anti-inflammatory effects, leading to a reduction of inflammatory mediators, or to a mechanical reduction of congestion directly leading to improvement in sleep disturbance. We combined our data from 3 placebo-controlled studies of intranasal corticosteroids in patients with perennial rhinitis to determine whether a correlation between the reduction of congestion and improved sleep and daytime somnolence existed. The pooled data of budesonide, flunisolide, and fluticasone demonstrated significantly decreased nasal congestion, sleep problems, and sleepiness in treated patients. The data demonstrated a correlation between a reduction in nasal congestion and an improvement of sleep (P < .01) and daytime somnolence (P = .01). Thus, topical intranasal corticosteroids should be used to decrease nasal congestion and to improve sleep and daytime somnolence in patients manifesting these symptoms.

Administration, Intranasal↗

PubMed2005

Asthma and the diver.

Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with nearly 9 million sport divers in the United States alone. Approximately 7% of the population has been diagnosed with asthma, which is similar to the percentage of divers admitting they have asthma. Numerous concerns exist regarding subjects with asthma who choose to participate in recreational diving. Among these concerns are pulmonary barotrauma, pneumomediastinum, pneumothorax, arterial gas embolism, ear barotrauma, sinus barotrauma, and dental barotrauma. Despite these concerns, a paucity of information exists linking asthma to increased risk of diving complications. However, it has long been the norm to discourage individuals with asthma from participating in recreational scuba diving. This article examines the currently available literature to allow for a more informed decision regarding the possible risks associated with diving and asthma. It examines the underlying physiological principles associated with diving, including Henry's law and Boyle's law, to provide a more intimate understanding on physiological changes occurring in the respiratory system under compressive stress. Finally, this article offers a framework for guiding the patient with asthma who is interested in scuba diving. Under the right circumstances, the patient with asthma can safely participate in recreational diving without apparent increased risk of an asthma-related event.

Asthma↗

PubMed2005

Nasal obstruction, the airway, and the athlete.

Rhinitis is a common condition that affects a significant proportion of the general population, as well as a high proportion of athletes. Nasal congestion is a predominate symptom of the late-phase reaction in allergic rhinitis and can have far-reaching effects that extend through the airway and beyond the nose. Rhinitis is often found in conjunction with asthma and is a risk factor for asthma. Nasal obstruction, which does not permit conditioning of inspired air by the nasal turbinates, may contribute to asthma symptoms and the development of asthma. These adverse conditions may be especially troublesome for the high-performance athlete who has increased nasal airflow turbulence and who competes under extreme conditions that may worsen rhinitis and asthma. Under the theory of the unified airway, an immune response induced in the nose may extend into the lungs via cytokines and other inflammatory mediators. Nasal congestion can significantly contribute to sleep dysfunction, leading to daytime fatigue and decreased performance. Treatment of allergic rhinitis can improve sleep and foster productivity. Control of rhinitis and nasal congestion, which is obtained by various therapies, may reverse lower airway tendency to bronchoconstriction.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

The correlation between allergic rhinitis and sleep disturbance.

Nasal congestion, a common symptom related to allergic rhinitis (AR), often is associated with poor sleep quality, leading to decreased learning ability, decreased productivity at work or school, and a reduced quality of life. The release of inflammatory mediators and activation of inflammatory cells results in nasal congestion, causing disrupted sleep and subsequent daytime somnolence. Therefore it is important to treat AR with medications that improve congestive symptoms without exacerbating sedation. Second-generation antihistamines and anticholinergic drugs are well tolerated but have little effect on congestion and therefore are limited in their ability to reduce AR-associated daytime somnolence. However, intranasal corticosteroids reduce congestion, improve sleep and sleep problems, and reduce daytime sleepiness, fatigue, and inflammation. Recently, montelukast, a leukotriene receptor antagonist, has joined the approved therapies for AR. Montelukast significantly improves both daytime and nighttime symptoms. AR treatment should endeavor to improve daytime and nighttime symptoms, sleep, and productivity, thereby improving quality of life.

Circadian Rhythm↗

PubMed2004

Assessment of care and disease management of patients with asthma in an overseas U.S. Army health clinic.

The objective of this study was to evaluate care and management provided by family practitioners to patients with asthma. A retrospective chart review was conducted on patients treated for asthma at a military health clinic in Germany. Pertinent information from the National Asthma Education Program guidelines was gathered using a questionnaire. Eighty-five charts were reviewed and 44 charts were included in this study. Overall compliance was calculated using the 22 National Asthma Education Program points (12 questions) investigated by the questionnaire. Overall compliance was 64%. Components of four major categories of asthma care were examined. All categories except one were above or close to the overall compliance percentage--diagnosis (74%), treatment/control (90%), monitoring (61%), and patient education (25%). It appears from this study that family practitioners are providing adequate, but not optimal, care and management to patients with asthma. Although our findings were encouraging, this study has highlighted that there is opportunity for improvement.

Asthma↗

PubMed2004

Early diagnosis is key in vancomycin-induced linear IgA bullous dermatosis and Stevens-Johnson syndrome.

BACKGROUND: With the emergence of highly resistant beta-lactam gram-positive organisms, vancomycin hydrochloride usage has increased considerably. Consequently, adverse drug reactions, including unfavorable cutaneous events, have also increased. Important adverse skin reactions are linear IgA bullous dermatosis (LABD) and Stevens-Johnson syndrome (SJS). These blistering disorders can have clinical manifestations that are difficult to distinguish; however, it is important to make the distinction because treatment and prognosis are different. OBJECTIVE: The purpose of this study is to review the literature on LABD and SJS and compare important differentiating characteristics to assist physicians in making the correct diagnosis. METHODS: The authors used MEDLINE to search for all published studies on vancomycin adverse events, and combined LABD, SJS, exanthema, and skin rashes each separately with vancomycin adverse events. Furthermore, the authors searched PubMed for all meta-analyses and randomized controlled clinical trials relating to treatment of patients with SJS. RESULTS: Clinically, LABD and SJS both present similarly with bullae. Diagnosis is made by use of perilesional skin biopsy and direct immunofluorescence. Direct immunofluorescence shows linear IgA deposition along the basement membrane zone in LABD, whereas this is absent in SJS. The treatment for both vancomycin-induced SJS and vancomycin-induced LABD is prompt discontinuation of the drug. However, if SJS is diagnosed early, systemic corticosteroids appear to decrease morbidity. CONCLUSIONS: In cases of SJS or LABD that are difficult to distinguish clinically, the authors recommend performing a skin biopsy and direct immunofluorescence early to confirm the diagnosis so that effective treatment can be instituted.

Adrenal Cortex Hormones↗