A perspective on systemic corticosteroid therapy in severe bronchial asthma in adults.

BACKGROUND: Systemic corticosteroids have been used in the treatment of asthma since 1950 and are still required for the treatment of acute severe asthma and corticosteroid dependent asthma. OBJECTIVE: To provide an updated overview of clinical considerations of systemic corticosteroids use in severe adult bronchial asthma. METHODS: PubMed searches were undertaken of studies published between 1950 and 2015. RESULTS: In this review the following concepts are discussed. 1) The onset of action of intravenous methylprednisone is 1-2 hours with a peak at 4-6 hours and duration of 12-30 hours. 2) Each patient should serve as their own control, using their best flow rates in the previous 6 months to 2 years. 3) The individual response to corticosteroid relates to the degree of obstruction at the time of onset of steroid treatment. 4) The pattern of response is variable but tends to be consistent for an individual patient. 5) In monitoring response to steroids frequent measures of peak expiratory flow rate and forced expiratory flow in 1 second are more useful than complete spirometric and lung mechanic tests measured less often. 6) In most cases oral steroids are as effective as parenteral regimens. 7) Patients usually respond in 3 days to 40 to 100 mg of methylprednisolone equivalent. 8) In corticosteroid resistant asthma consider compliance issues, allergen sensitivity, concomitant conditions, psychiatric factors and drug interactions. 9) Corticosteroid toxicity relates to the total lifetime dosage and serious side effects are usually not observed until a total dosage of 6.8 grams of prednisone equivalent. CONCLUSION: Until we have a better understanding of the mechanisms of action of glucocorticoids, we will continue to rely on currently available systemic corticosteroids in severe asthma. The intrapatient consistency as discussed in this review, should guide therapy.

Clinical efficacy of omalizumab in an elderly veteran population with severe asthma.

Severe asthma in elderly patients is underdiagnosed, difficult to treat, and often accompanied by atopy. This study was designed to compare clinical outcomes of omalizumab therapy in an elderly veteran population with severe allergic asthma. A retrospective, observational data analysis was performed over 2 years. Cohort outcome measures 1 year before omalizumab therapy were compared with 1 year of active treatment. Statistical analysis included two sample t-tests. The total number of patients enrolled was 17 with median age of 60 years. Omalizumab therapy was associated with a significant reduction in acute asthma exacerbations requiring prednisone treatment (p < 0.01), a significant improvement in forced expiratory volume in 1 second of 0.28 L (p < 0.01), and significantly higher Asthma Control Test (ACT) scores at 3 (p = 0.043), 6 (p = 0.039), and 12 months of therapy (p < 0.01). Two of five patients on daily prednisone for >6 months were able to discontinue systemic steroid use within 3 months of omalizumab treatment. Our study suggests elderly patients with severe atopic asthma show a significant positive clinical response to omalizumab.

Epinephrine auto-injector use and demographics in a Veterans Administration population.

The epinephrine auto-injector has been widely used over a long period of time. Certain aspects of this therapy and demographic data, however, have not been well studied. This study investigates patient use and understanding of epinephrine auto-injector use. As part of an ongoing quality assurance program, we evaluated 66 patients who had been given an epinephrine auto-injector and followed in the Allergy and Immunology Clinics at the West Los Angeles Veterans Medical Center. Data analyzed included patient demographics, medical indications for epinephrine auto-injector prescriptions, and the patient's understanding and use of the device. The mean age of our patients was 50 years. There were 44 men (66.7%) and 22 women (33%). Twenty-three patients were prescribed epinephrine auto-injector for adverse food reactions. Ninety-two percent (92%) of the patients knew how to use their epinephrine auto-injector properly, however, only 58% carried their device with them consistently. Of the patients, 91% understood why the auto-injector was prescribed. Of the total patients prescribed epinephrine auto-injector, 79% refilled their medication before the 1 year expiration date. Only 12% of the patients studied had required the use of their auto-injector. Most patients knew how and when to administer their epinephrine auto-injector. Despite detailed instructions in a specialty clinic only a slight majority carried it consistently. These data clearly indicate that further patient education or other measures are needed to improve compliance and effective use.

Effects of omalizumab in patients with food allergy.

Omalizumab is a novel therapy approved for treating patients with moderate to severe persistent allergic asthma with a serum IgE ranging from 30 to 700 IU/mL. We examined the efficacy of omalizumab as a treatment for IgE-mediated food allergy. An Institutional Review Board-approved prospective pilot study was performed to assess the efficacy of omalizumab in 22 patients with persistent asthma and concomitant IgE-mediated food allergy. All patients showed skin test positivity to foods and experienced allergic food reactions based on history. Patients were interviewed on unintentional and/or unauthorized exposures to sensitized foods. Thirteen female and nine male patients (range, 4-66 years old; mean, 38 years) were evaluated in a private practice setting. Mean IgE level was 1120.74 IU/mL. Sensitized allergens included fish, shellfish, peanuts, tree nuts, egg, soybean, and wheat. All 22 (100%) patients maintained significant improvement as shown by a decrease/lack of clinical symptoms on reexposure to sensitized foods. Clinical improvement by the sixth dosage of omalizumab (150-300 mg q. 2-4 weeks) was noted by history and physical examination. Eight patients noted a decrease in their food-induced atopic dermatitis, 13 patients noted a decrease in their food-induced asthma symptoms, 3 patients noted a decrease in their food-induced urticaria, 6 patients noted a decrease in their food-induced rhinosinusitis symptoms, and 9 patients showed efficacy for angioedema and/or anaphylaxis. While treating asthma patients with omalizumab, patients subjectively observed a reduction in their concomitant IgE-mediated food allergy symptoms.

Penicillin skin testing: a 20-year study at the West Los Angeles Veterans Affairs Medical Center.

Penicillin (PCN) may cause a reaction in up to 10% of the population. No study has examined PCN skin testing longitudinally over a 20-year period. A total of 122 patients underwent PCN skin testing between September 1978 and May 1998. Patients were skin tested with the major determinant, penicilloyl polylysine, and three minor determinants, PCN, benzylpenilloate, and benzylpenicilloate. Ten of a total of 122 patients had positive skin test reactions. Nine reactions were to penicilloyl polylysine and one reaction was to the minor determinant benzylpenilloate. There was a total of four patients (3.6%) with false-negative results on skin testing. PCN skin testing with both the major and minor determinants should be performed when there is a history of PCN allergy, a serious illness, and no suitable alternatives. If either the major or minor determinants are positive without suitable alternative antibiotics, then the patient should undergo desensitization.

Angiotensin-converting Enzyme Inhibitor Angioedema Requiring Admission to an Intensive Care Unit.

OBJECTIVE: The purpose of this study was to review consecutive cases of angiotensin-converting enzyme (ACE) inhibitor angioedema admitted to an intensive care unit. METHODS: Fifty subjects with ACE-inhibitor angioedema admitted from 1998-2011 were reviewed. RESULTS: All 50 subjects were men, 62.8 ± 8.4 years of age, 76% African Americans. Fifteen (30%) required ventilatory support and 2 (4%) required tracheostomy. Over half (56%) had taken ACE inhibitors for over a year. Logistic regression identified dyspnea and tongue involvement with the need for ventilatory support (P < .01). Hypercapnia (PaCO2 = 45.2 ± 6.7; P = 0.046) also identified patients needing ventilatory support. CONCLUSIONS: Ventilatory support was provided for about one-third of those with ACE inhibitor-associated angioedema. Angioedema can occur even after extended use. Dyspnea and tongue involvement identified patients requiring ventilatory support.

Clinical control in the dual diagnosis of obstructive sleep apnea syndrome and rhinitis: a prospective analysis.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) and allergic rhinitis (AR) are common coexisting disorders. Upper airway, specifically nasal resistance, is thought to increase during exacerbations of AR and nonallergic rhinitis (NAR), as well as in OSAS. The study objective was to determine if a correlation exists between clinical control of rhinitis and OSAS. METHODS: This prospective study followed 43 patients with concurrent OSAS and AR or NAR. OSAS was diagnosed by polysomnography, and AR or NAR was diagnosed by history, skin testing, serum-specific IgE, and total IgE levels. Measurements of control of OSAS included the Epworth Sleepiness Scale (ESS) survey and compliance with continuous positive airway pressure (CPAP) device. Measurements of rhinitis control included Assessment of Nasal Symptom Severity and Assessment of Nonnasal Symptom Severity (NSS refers to both) and Global Assessment of Nasal and Nonnasal Symptom Severity surveys (GSS). Higher NSS scores correlate with more rhinitis symptoms, whereas higher GSS scores correlate with less symptoms. RESULTS: All patients completed the study. There was a positive correlation between ESS and NSS scores (p < 0.001), inverse correlation between ESS and GSS scores (p < 0.001), inverse correlation between CPAP compliance and NSS scores (p < 0.001), and positive correlation between CPAP compliance and GSS scores (p < 0.001). There was no statistically significant difference between the AR, NAR, and AR/NAR groups. CONCLUSION: Our study showed a statistically significant positive correlation between clinical control of rhinitis symptoms and clinical control of OSAS. This study emphasizes the importance of achieving concurrent optimal control of both OSAS and AR/NAR.

Intramuscular lipoma of the tongue masquerading as angioedema.

In most cases, the diagnostic evaluation of angioedema is challenging, as there are many possible etiologies. We report a case of an infiltrating lipoma of the tongue that masqueraded as angioedema. The patient, a 68-year-old man, presented with tongue swelling that had followed a waxing and waning course over a 6-month period. Physical examination showed a diffusely enlarged tongue with no discrete mass. A laboratory evaluation for angioedema was unremarkable. After the patient's condition did not respond to treatment with antihistamines and oral prednisone, a further workup was initiated. Magnetic resonance imaging of the neck and computed tomography of the oral cavity revealed only diffuse enlargement of the tongue. The patient underwent a tongue biopsy, which identified the cause of the swelling to be an infiltrating lipoma of the tongue. Clinicians should be aware that other causes of tongue swelling may mimic angioedema.

Diagnosis and management of hypersensitivity reactions related to common cancer chemotherapy agents.

OBJECTIVES: To review clinical hypersensitivity reactions related to common cancer chemotherapy agents and to discuss potential management strategies. DATA SOURCES: PubMed searches were performed for articles published from 1970 to 2008 regarding hypersensitivity to cancer chemotherapy and related agents using the keywords hypersensitivity, allergy, chemotherapy, platinums, taxanes, asparaginase, epipodophyllotoxins, and procarbazine. Retrieved articles were surveyed for additional citations. STUDY SELECTION: Articles were reviewed for relevance to the subject matter, and the most pertinent articles were included in this review. RESULTS: Hypersensitivity reactions are commonly associated with the use of certain cancer chemotherapy drugs, including platinums, taxanes, asparaginase, procarbazine, and epipodophyllotoxins. Platinum agents (cisplatin, carboplatin, oxaliplatin) are associated with IgE-mediated hypersensitivity reactions, and skin testing may be indicated. Taxane (paclitaxel, docetaxel)-related reactions are generally non-IgE mediated, and premedication with corticosteroids and antihistamines is usually effective. Asparaginase has a high rate of hypersensitivity reactions that are likely IgE mediated or related to complement activation. Skin testing has been recommended but has not been validated for asparaginase. Procarbazine reactions can be IgE mediated but are also associated with a type III reaction manifested by pulmonary toxicity and cutaneous reactions. Hypersensitivity reactions related to epipodophyllotoxins may involve both immunologic and nonimmunologic factors that may be avoided with a slow infusion and premedication. CONCLUSION: With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. Knowledge of the presentations of these reactions and management options give the treating physician the means to make an informed decision of how best to proceed.

Cephalosporin induced toxic epidermal necrolysis and subsequent penicillin drug exanthem.

BACKGROUND: Drug hypersensitivity is classically divided into IgE mediated and non-IgE mediated disease. We report a rare case of consequent IgE mediated and non-IgE mediated reactions within the beta lactam class of antibiotics. CASE SUMMARY: An 84-year-old man developed toxic epidermal necrolysis (TEN) due to ceftriaxone, a third generation cephalosporin, involving 72% of the body surface area. The patient recovered but within weeks subsequently developed an acute IgE mediated allergic reaction to piperacillin/tazobactam, an extended spectrum penicillin. Further IgE RAST revealed positive results to penicillin major determinant. DISCUSSION: This case demonstrates the complexity of drug hypersensitivity reactions. While it is accepted that IgE mediated penicillin allergy is a predisposition to cephalosporin allergy, this case displays an unusual correlation between drug hypersensitivity and drug class. There have been few studies that evaluate the cross reactivity with penicillin or other beta-lactams in subjects with primary hypersensitivity to cephalosporins. This clinical scenario emphasizes the need of more studies on cephalosporin allergy in particular as shown by this case of sequential non-IgE mediated cephalosporin induced TEN reaction pursuant by an IgE mediated penicillin allergy.

Emergency department utilization by patients not meeting Health Plan and Employer Data and Information Set (HEDIS) criteria for persistent asthma.

Emergency hospital utilization rates for asthma remain high despite advances in asthma controller medications and the presence of widely accepted asthma treatment guidelines. To explore this phenomenon, we analyzed administrative data to determine characteristics of patients seen in the emergency department (ED) for asthma. Complete pharmacy and diagnostic coding records were obtained from consecutive adults (aged 19-56 years) treated for asthma in the ED of a closed-network health maintenance organization between April and July of 2002. Subjects were stratified into asthma severity categories (persistent or non-persistent) based on the National Committee for Quality Assurance 2006 Health Plan and Employer Data and Information Set (HEDIS) criteria for persistent asthma. Eighty-one unique patients made a total of 89 ED visits for asthma during the study period. Of the 89 total ED visits for asthma, 44 (49%) occurred in patients that did not meet HEDIS criteria for persistent asthma. Of the 81 unique patients making asthma-related ED visits, 41 (51%) did not meet HEDIS criteria for persistent asthma. Over one-half (51%) of this nonpersistent population were not given either asthma reliever or asthma controller medications during the 12-month period before their index ED visit. Over the 24-month period before their index ED visit, 37% of nonpersistent patients were dispensed neither asthma reliever nor controller medications. Patients that do not meet HEDIS criteria for persistent asthma account for a substantial percentage of asthma-related ED visits. These patients have a history of low use of asthma medications before their ED visit.

Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study.

Omalizumab is a unique biologic therapeutic drug approved for treating atopic patients with moderate to severe persistent allergic asthma with a serum IgE ranging from 30 to 700 IU/mL. This study was performed to examine the efficacy of omalizumab for the treatment of atopic dermatitis (AD), a disease with significant morbidity. A prospective analysis was performed to assess the efficacy of omalizumab in 21 patients with moderate to severe persistent allergic asthma and AD. Patients were stratified into the following groups: very high IgE (>700 IU/mL), high IgE (186-700 IU/mL), and normal IgE (0-185 IU/mL). AD severity was assessed at 0, 1, 3, 6, and 9 months via an Investigator Global Assessment index. Twenty-one patients (14-64 years old) were evaluated. Pretreatment IgE levels ranged from 18.2 to 8396 IU/mL, (mean IgE level was 1521 IU/mL). All 21 patients showed clinical and statistically significant improvement of their atopic dermatitis (p<0.00052). In conclusion, this study indicates that omalizumab is effective in treating AD in patients with moderate to severe persistent allergic asthma.

Oral corticosteroid-dependent asthma: a 30-year review.

OBJECTIVE: To identify novel aspects of the pathogenesis, therapeutic options, and prophylaxis measures of corticosteroid-dependent asthma. DATA SOURCES: PubMed searches were undertaken of studies published between 1966 and 2006 on the pathogenesis of and corticosteroid-sparing therapies for corticosteroid-dependent asthma. Identified review articles were surveyed for additional and earlier citations. Recent American Academy of Asthma, Allergy, and Immunology meeting abstracts were also searched to identify other recently published and unpublished studies. STUDY SELECTION: Inclusion of studies in the review was decided by simple agreement of both reviewers, who independently read the "Methods" and "Discussion" sections of articles identified using the search strategy. Quality assessment was performed by the 2 reviewers. RESULTS: High-dose inhaled corticosteroids are the first-line option for corticosteroid-dependent asthmatic patients with clear efficacy. Omalizumab is effective in reducing oral corticosteroid requirements in allergic asthma. Methotrexate, gold, and cyclosporine have corticosteroid-sparing effects clinically that must be weighed against a serious adverse effect profile. Nebulized diuretics and lidocaine, with a low adverse effect profile, offer promising results but require further study. Clarithromycin and telithromycin seem to have an independent mechanism of inflammatory modulation, but their effect on corticosteroid-dependent asthma remains to be seen. Etanercept offers only early clinical evidence of a role in corticosteroid-dependent asthma. CONCLUSIONS: With no clear consensus on corticosteroid-sparing treatment in corticosteroid-dependent asthmatic patients, systemic glucocorticoids remain the foremost therapy, with adverse effects that require monitoring and prophylaxis.

Allergen immunotherapy in a patient with human immunodeficiency virus: effect on T-cell activation and viral replication.

BACKGROUND: Allergen immunotherapy is a major therapeutic modality in the treatment of allergic rhinitis. However, with T-cell activation potential, its role in patients with human immunodeficiency virus (HIV) was theoretically limited. OBJECTIVE: To report the results of allergen immunotherapy in a patient with HIV treated with highly active antiretroviral therapy (HAART). METHODS: A 44-year-old man with a history of HIV did not respond to medical therapy for allergic rhinitis. His HIV status was well controlled with HAART. Owing to the severity of his allergic rhinitis symptoms, he accepted the risk of allergy immunotherapy despite the unknown effect of immunotherapy in patients with HIV. RESULTS: After 6 weeks of weekly immunotherapy injections, his viral load remained undetectable and his CD4 cell count changed from 540 to 570 cells/microL. After 16 weeks of weekly immunotherapy, his viral load increased to 10,900 copies/mL, and his CD4 cell count increased to 665 cells/microL. After 24 weeks of weekly immunotherapy, his viral load returned to an undetectable level, and his CD4 cell count stabilized at 356 cells/microL. Despite his notable change in HIV status, he continues to receive the same HAART. He currently continues en route to maintenance immunotherapy. CONCLUSIONS: The effect of allergen immunotherapy on HIV infection has not been previously reported. A concern remains that any form of immunotherapy may negatively affect HIV disease progression. This case illustrates that weekly allergen immunotherapy may have induced limited T-cell proliferation and a modest increase in RNA viral load, which resolved with continuation of HAART.

Declining cell-mediated immunity and increased chronic disease burden.

BACKGROUND: The effects of chronic disease have been proposed as an explanation for conflicting results in studies of age effects on cell-mediated immunity. OBJECTIVE: To examine the hypothesis that declining cell-mediated immunity is more closely linked to chronic disease burden than to chronological age. METHODS: Fifty-eight elderly individuals were tested for delayed-type hypersensitivity (DTH) responses to Candida and tetanus antigens. Disease burden was quantified using the Cumulative Illness Rating Scale (CIRS). Higher CIRS scores reflect greater disease burden. Mean DTH response by age group (<71, 71-78, and >78 years) was compared with mean DTH response by CIRS score (<11, 11-15, >15). Total serum IgE levels were measured and similarly stratified by age and CIRS score. RESULTS: Mean Candida DTH responsiveness declined progressively with increasing disease burden (increasing CIRS score). Mean DTH responses were 7.78, 3.05, and 0.0 mm for CIRS scores less than 11, 11 to 15, and greater than 15, respectively. Candida DTH responses showed no progressive decline with advancing age. Mean DTH responses were 4.7, 3.5, and 5.0 mm in participants younger than 71, 71 to 78, and older than 78 years, respectively. Total serum IgE levels increased with advancing age. Mean total IgE levels were 182, 249, and 342 IU/mL in participants younger than 71, 71 to 78, and older than 78 years, respectively. No correlation was observed between mean total IgE levels and CIRS scores. CONCLUSIONS: An inverse relationship between Candida DTH response and CIRS score suggests that increased chronic disease burden is associated with diminished cell-mediated immune response. Advancing age did not predict a diminished DTH response in our patients. No relationship was observed between chronic disease burden and total serum IgE level.

Demographics and long-term follow-up in a Veterans Affairs Allergy/Immunology Center: a 10-year analysis.

Between 1985 and 1992, patients were evaluated as new outpatient consultations in the Allergy/Immunology Center at the Veterans Affairs Greater Los Angeles Health Care System (VAGLAHS). Data collected included age, gender, ethnicity, and diagnosis. After 10 years, patient follow-up status was determined and classified into five categories: gender, ethnic distribution, age distribution, disorders seen, and follow-up pattern. A total of 1116 patients were evaluated. The gender of our population was 7.8% women and 92.2% men. The ethnic distribution was 59.5% white, 32.2% black, 6.5% Hispanic, and 1.9% other. Neither age nor ethnic distribution was significantly different from the general veterans affairs population. Age of patients ranged from 20 to 90 years old. The largest peak for age at initial presentation was 60 years. The three most common disorders seen in the clinic were rhinitis (36.6%), asthma (24.5%), and sinusitis (12.3%). The 10-year follow-up pattern of patients revealed that 6% were seen in the past year, 6.2% of patients were seen longer than 1 year ago but within the 5 past years, 29% of patients who were still seen at VAGLAHS but were no longer patients of the allergy clinic, 32.7% of patients who were no longer seen at VAGLAHS, and 26.2% died. Women and patients who were 50-60 years old were more likely to follow-up. There was no difference in follow-up visits among ethnic groups.