Phillip Lieberman

Nocardia asteroides infection complicating neoplastic disease

Abstract During the decade 1960–1969, Nocardia asteroides was isolated from sputum, abscesses or exudates in twenty-two patients at Memorial Hospital. These patients could be divided into two groups. Group I consisted of thirteen patients with underlying neoplasms receiving radiation or chemotherapy in whom unequivocal evidence of nocardial infection developed. Clinical manifestations included bronchopneumonia, lobar pneumonia, necrotizing pneumonia with single or multiple abscesses, and brain, hepatic or scrotal abscesses. Ten patients had either leukemia or lymphoma. The simultaneous presence of tumor and nocardial infection in the lung was noted in five cases. Sputums or exudates from the patients in group I were positive for organisms simultaneously in both culture and smear in only a third of examinations; this stresses the need for multiple bacteriologic examinations when the diagnosis of nocardiosis is suspected. Although the underlying disease was usually progressively fatal, an excellent response to sulfonamides with resolution of pulmonary disease was noted in several patients who were maintained on anticancer therapy. Group II was composed of nine patients with predominantly respiratory symptoms and fever. Multiple positive cultures were obtained in many of these patients, but all lacked objective pulmonary findings and symptoms usually resolved without treatment. Such cases may represent milder nocardial infections of the upper respiratory tract although a saprophytic role for nocardia cannot be ruled out. These observations indicate that nocardiosis is a significant and often fatal opportunistic infection in patients being treated for cancer, but further studies are needed to define the clinical and epidemiologic spectrum of this disease in man.

Anaphylaxis--a practice parameter update 2015.

Phillip Lieberman, MD; Richard A. Nicklas, MD; Christopher Randolph, MD; John Oppenheimer, MD; David Bernstein, MD; Jonathan Bernstein, MD; Anne Ellis, MD; David B.K. Golden, MD; Paul Greenberger, MD; Steven Kemp, MD; David Khan, MD; Dennis Ledford, MD; Jay Lieberman, MD; Dean Metcalfe, MD; Anna Nowak-Wegrzyn, MD; Scott Sicherer, MD; Dana Wallace, MD; Joann Blessing-Moore, MD; David Lang, MD; Jay M. Portnoy, MD; Diane Schuller, MD; Sheldon Spector, MD; and Stephen A. Tilles, MD Chief Editors: Phillip Lieberman, MD; Richard A. Nicklas, MD; John Oppenheimer, MD; Christopher Randolph, MD Members of the Joint Task Force: David Bernstein, MD; Joann Blessing-Moore, MD; David Khan, MD; David Lang, MD; Richard Nicklas, MD; John Oppenheimer, MD; Jay M. Portnoy, MD; Christopher Randolph, MD; Diane Schuller, MD; Sheldon Spector, MD; Stephen A. Tilles, MD; Dana Wallace, MD Practice ParameterWorkgroup: David Bernstein, MD; Jonathan Bernstein, MD; Anne Ellis, MD; David B.K. Golden, MD; David Khan, MD; Dennis Ledford, MD; Jay Lieberman, MD; Dean Metcalfe, MD; Dana Wallace, MD

Hazards of unintentional injection of epinephrine from autoinjectors : a systematic review

OBJECTIVES To ascertain the rate of occurrence of unintentional injections from epinephrine autoinjectors used in the first aid treatment of anaphylaxis and to provide information about the resulting needle stick injuries. DATA SOURCES A systematic review was performed. The MEDLINE, Scirus, CINAHL, ISI Web of Science, and Google Scholar databases were searched by title and abstract to identify reports of unintentional injections from epinephrine autoinjectors published in peer-reviewed journals. STUDY SELECTION Publications were selected for inclusion based on predefined strict criteria. RESULTS In 26 reports published during the past 20 years, we identified 69 people with an unintentional injection of epinephrine from an autoinjector. More than 68% of them were reported in the past 6.3 years, 58% were female, 42% were injured in the home, and 91% sustained injury to a finger or thumb. More than 65% of the 69 individuals were evaluated in an emergency department; 13% of the 69 were not treated or were treated only with observation. Warming of the injured part was used in 25%, nitroglycerin paste application in 9%, local injections of phentolamine and/or lidocaine in 22%, and other treatments in 20%; treatment, or lack thereof, was not described in 12%. No permanent sequelae were reported. CONCLUSIONS The true rate of occurrence of unintentional injection of epinephrine from autoinjectors is unknown but is increasing. People at risk for anaphylaxis need regular coaching in how to use epinephrine autoinjectors correctly and safely. Improved autoinjector design will address the safety concerns identified in this review.

Effect of beta adrenergic stimulation and blockade on immediate hypersensitivity skin test reactions

Abstract The effects of isoproterenol (a β-adrenergic stimulating agent) and propranolol (a β-adrenergic blocking agent) were studied on immediate hypersensitivity skin test reactions in 15 atopic subjects. Forearm skin of these subjects was pretreated with these agents by local iontophoretic application and compared to areas locally pretreated with saline or diphenhydramine hydrochloride. Following pretreatment of skin, scratch or intradermal tests were performed with the most reactive antigen for each patient. A significant increase of skin reactivity occurred in areas of skin pretreated with propranolol. A significant decrease in reactivity followed pretreatment with isoproterenol. Thus the iontophoresis of β-adrenergic agents can alter the immediate hypersensitivity skin test reactions of atopic patients. This alteration is consistent with a modification of the local synthesis of cyclic adenosine monophosphate (CAMP) induced by these pharmacologic agents. It is not clear whether this presumed alteration in CAMP is exerting its effect on mediator release from dermal mast cells or directly on the dermal blood vessels or both.

Anaphylaxis treatment: current barriers to adrenaline auto-injector use

Anaphylaxis is a life‐threatening condition that is increasing in prevalence in the developed world. There is universal expert agreement that rapid intramuscular injection of adrenaline is life‐saving and constitutes the first‐line treatment of anaphylaxis. The unpredictable nature of anaphylaxis and its rapid progression makes necessary the availability of a portable emergency treatment suitable for self‐administration. Thus, anaphylaxis treatment guidelines recommend that at‐risk patients are provided with adrenaline auto‐injectors (AAIs). Despite these clear recommendations, current emergency treatment of anaphylaxis continues to be inadequate in many cases. The aim of this review is to highlight the barriers that exist to the use and availability of AAIs and that prevent proper management of anaphylaxis. In addition, we review the characteristics of all AAIs that are presently available in Europe and the USA and discuss the need for regulatory requirements to establish the performance characteristics of these devices.

Recognition and First-Line Treatment of Anaphylaxis

The International Classification of Diseases (ICD)-9 included a code only for anaphylactic shock. The improved ICD-10 coding defines the different symptoms and types of anaphylaxis and includes coding for anaphylaxis without shock. This new coding is consistent with the efforts of the National Institute of Allergy and Infectious Diseases (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN), who convened a panel to formulate a definition of and the diagnostic criteria for anaphylaxis. Anaphylaxis is a serious reaction that has a rapid onset and may cause death. It is a systemic immunoglobulin E-mediated reaction resulting from the sudden release of multiple mediators from mast cells and basophils. Foods are the most common triggers for anaphylactic reactions, followed by drugs, insect stings, and idiopathic anaphylaxis (anaphylaxis of unknown cause). If the NIAID/FAAN criteria are met and anaphylaxis is diagnosed, epinephrine administration is mandatory. Delays in epinephrine administration have been associated with fatalities. Patients should have ready access to >1 epinephrine autoinjector in the outpatient setting. An individualized emergency action plan should be developed for each patient at risk for anaphylaxis.

Intranasal fluocortin butyl in patients with perennial rhinitis: A 12-month efficacy and safety study including nasal biopsy

Fluocortin butyl (FCB) is a recently developed topical intranasal corticosteroid that is inhaled as a powder and has been demonstrated to be well tolerated and to improve symptoms and signs of perennial rhinitis in previous short-term studies. This multicenter, open-label study evaluated the efficacy and safety of FCB during a 12-month treatment period in patients with perennial rhinitis. Treatment was initiated with one inhalation of FCB in each nostril three times a day (total dosage, 3 mg/day). In subsequent months, one third of the patients was maintained at the dosage of 3 mg/day, one third at a lower dosage of 2 mg/day, and the remaining one third of the patients at a larger dosage of 4 to 8 mg/day. Of 109 patients enrolled in the study, 90 patients (82.6%) completed all 12 months of treatment. Symptom and sign scores decreased significantly (p less than 0.001) at the 2-month evaluation compared to scores at baseline, and the improvement was maintained throughout the 12-month study period. After 12 months, greater than 80% of the patients had substantial control of symptoms. Specimens of nasal biopsies, performed at the beginning and end of treatment, revealed a decrease in eosinophils and other cellular infiltrates, a slight tendency of an increase in mast cell counts, and a trend toward normalization of the nasal mucosa. There were few adverse effects. Mean plasma cortisol levels were normal before and after corticotropin stimulation at baseline and after 12 months of FCB therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis: Underdiagnosed, Underreported, and Undertreated

Diagnostic criteria and administrative codes for anaphylaxis have evolved in recent years, partly reflecting the challenges in recognizing anaphylaxis and understanding its symptoms. Before the diagnostic criteria were disseminated by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network, several studies showed that a substantial proportion of anaphylaxis cases presenting to the emergency department (ED) were not recognized as such. Furthermore, epinephrine, the first-line treatment, was used in fewer than half of cases, especially if anaphylaxis was not diagnosed at the time. Although management practices may have improved since that time, anaphylaxis continues to be underrecognized and undertreated in the US. Of particular concern are findings that the majority of patients who visited the ED for an acute allergic reaction or anaphylaxis were not given a prescription for an epinephrine autoinjector, educated about avoiding the offending allergen, or advised to consult with an allergist. Improvements in the recognition and management of anaphylaxis have the potential to reduce the substantial burden that it currently places on the health care system. The articles in this supplement cover a wide range of issues surrounding anaphylaxis and seek to disseminate information helpful to health care professionals in general and primary care providers in particular.

Double-blind trials of azelastine nasal spray monotherapy versus combination therapy with loratadine tablets and beclomethasone nasal spray in patients with seasonal allergic rhinitis

BACKGROUND Azelastine hydrochloride is an H1-receptor antagonist with antiinflammatory properties that is available in the US as Astelin Nasal Spray for the treatment of seasonal allergic rhinitis. The symptoms of seasonal allergic rhinitis can initially be treated with monotherapy using either an antihistamine or an intranasal corticosteroid. Patients whose symptoms do not respond adequately are often prescribed a combination of both an antihistamine and an intranasal corticosteroid. OBJECTIVE Three multicenter, randomized, double-blind studies were conducted to determine whether patients with moderate-to-severe symptoms of seasonal allergic rhinitis who had responded inadequately to monotherapy with either an oral antihistamine or an intranasal corticosteroid, and who were candidates for combination therapy with both an oral antihistamine and an intranasal corticosteroid, could be effectively treated with azelastine nasal spray monotherapy. METHODS Following a 1- to 2-week washout period, patients were randomized to 7 days of double-blind treatment with either azelastine nasal spray (2 sprays per nostril bid, 1.1 mg/day) monotherapy or combination therapy with oral loratadine (Claritin, one 10-mg tablet/day) plus intranasal beclomethasone dipropionate monohydrate (Beconase AQ, 2 sprays per nostril bid, 336 microg/day). Efficacy was determined at the end of the study by both a physician assessment of the need for additional anti-rhinitis medication and a patient global evaluation of therapeutic effectiveness. The three studies were conducted at 71 investigational sites during the 1998 spring allergy season. Three separate studies were conducted to verify the reproducibility of the new study design. RESULTS In all three studies a total of 1,070 patients were randomized to double-blind treatment. There were no statistically significant differences in the percentage of patients treated with azelastine nasal spray versus patients treated with a combination of loratadine tablets and beclomethasone nasal spray who did not require additional anti-rhinitis medication (32% to 45% and 39% to 46%, respectively). The patient global evaluation indicated that 77% to 84% of the patients treated with azelastine nasal spray had symptomatic improvement and 85% to 90% of the patients treated with loratadine tablets and beclomethasone nasal spray had symptomatic improvement. The most commonly reported adverse experience with azelastine nasal spray was a transient aftertaste (8%), while the most commonly reported adverse experience with loratadine tablets and beclomethasone nasal spray in combination was headache (6%). CONCLUSIONS Based on the percentage of patients not requiring additional antirhinitis medication and the patient assessment of efficacy, azelastine nasal spray monotherapy was as effective as the combination of oral loratadine plus intranasal beclomethasone in treating moderate-to-severe symptoms of seasonal allergic rhinitis.

Effect of rifampin on theophylline disposition.

Summary The concentrations of theophylline from single 400-mg oral doses were evaluated both before and after 7 days of oral rifampin administration (600 mg/day) in six healthy, nonsmoking adults. The mean oral clearance of theophylline was significantly increased from 54.9 ± 21.2 to 68.9 ± 26.5 ml/h/kg. The elimination rate constant was significantly increased in five of the six subjects, with a mean increase of approximately 25%. Although inter-subject variability was large, these data indicate the potential need to increase theophylline doses in some patients receiving rifampin.