Desensitization in patients with beta-lactam drug allergy

Background: Patients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients’ histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization. Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options. This paper reviews the safety of beta-lactam desensitization. Objective: To perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications. Methods: A retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed (AU)

Results: A total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36–92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full therapeutic courses of their antibiotic. Conclusion: Beta-lactam antibiotic sensitivity continues to present a challenging problem for physicians. Patients with drug resistant infections who are unable to obtain skin testing or who test positive to skin tests may need either a challenge or desensitization. Desensitization, saved for those with a convincing beta-lactam hypersensitivity history is often the choice of last resort given the associated cost and risk of anaphylaxis. However, once desensitization is complete, patients are usually able to tolerate full doses of antibiotics for full treatment length with minimal side effects (AU)

Desensitization in patients with beta-lactam drug allergy.

BACKGROUND: Patients with a history of beta-lactam antibiotic allergy are often admitted to the hospital with severe or life-threatening infections requiring beta-lactam antibiotics. Strict avoidance of beta lactams to such patients may prevent them from getting adequate coverage and can lead to an increase in the use of alternative antibiotics, which can predispose to antibiotic resistance. Past studies revealed a lower incidence of pen allergy then patients' histories suggest. Fortunately today, there are three options for patients presenting with a history of beta-lactam allergy. Penicillin skin testing, beta-lactam challenge or beta-lactam desensitization. Recently Pre Pen has been FDA re-approved and when combined with Pen G is a valid way to determine if patients are able to tolerate beta-lactam antibiotic. When these agents are not available one must decide about desensitization or challenge. When a patient has a positive penicillin skin test, desensitization or beta-lactam avoidance are the only options. This paper reviews the safety of beta-lactam desensitization. OBJECTIVE: To perform a chart review on patients desensitised with beta lactam to determine if desensitizations can be performed safely without minimal complications. METHODS: A retrospective chart review was performed on allergy and immunology inpatient consultations for beta-lactam desensitization between September 2003 and August 2006 at the Cedars-Sinai Medical Centre in Los Angeles. Patient data and outcomes of desensitization were analysed. RESULTS: A total of 13 intravenous desensitizations were performed on 12 patients. The patients consisted of eight females and four males with an average age of 65 years. Age range was 36-92 years old. All 13 intravenous desensitizations were completed without complications. No patient required a slower rate of desensitization or discontinuance of the desensitization. Patients were able to tolerate the initial therapeutic dose of their beta-lactam antibiotic and were then able to complete full therapeutic courses of their antibiotic. CONCLUSION: Beta-lactam antibiotic sensitivity continues to present a challenging problem for physicians. Patients with drug resistant infections who are unable to obtain skin testing or who test positive to skin tests may need either a challenge or desensitization. Desensitization, saved for those with a convincing beta-lactam hypersensitivity history is often the choice of last resort given the associated cost and risk of anaphylaxis. However, once desensitization is complete, patients are usually able to tolerate full doses of antibiotics for full treatment length with minimal side effects.

Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma.

BACKGROUND: Cell mediated immunity is suppressed by systemic corticosteroids. Inhaled corticosteroids have been shown to affect parameters including bone metabolism, hypothalamus-pituitary adrenal axis, linear growth, and lead to the development of cataracts. However, it is unclear if high dose inhaled corticosteroid therapy affects cell mediated immunity. STUDY OBJECTIVES: To evaluate if asthma patients taking high dose inhaled corticosteroids chronically have reduced cell mediated immunity compared to asthma patients not taking inhaled corticosteroids. METHODS: Eighteen asthmatic subjects participated in this cross-sectional study. Cell mediated immunity was evaluated in nine patients who had been taking high dose inhaled corticosteroids for >6 months and nine patients not taking inhaled corticosteroids. Cell mediated immunity was evaluated by delayed type hypersensitivity (DTH) skin testing with intradermal placement of candida and tetanus antigens. RESULTS: There was no significant difference in DTH skin test results between the high dose inhaled corticosteroid and no corticosteroid treated asthma group. CONCLUSION: Patients with asthma taking high dose inhaled corticosteroids chronically (>6 months) did not have significantly greater impaired cell mediated immunity than patients not taking inhaled corticosteroids in this study.

Serum IgE and eosinophil count in allergic rhinitis--analysis using a modified Bayes' theorem.

BACKGROUND: To use probability theory to establish threshold values for total serum IgE and eosinophil counts that support a diagnosis of allergic rhinitis and to compare our results with previously published data. METHODS: Prospective study of rhinitis patients using a modified version of Bayes' theorem. Study included 125 patients at the West Los Angeles VA Medical Center diagnosed with rhinitis who completed allergy consultation and immediate hypersensitivity skin testing. RESULTS: Eighty-nine of 125 patients were atopic by prick and/or intradermal skin testing. Using a modified version of Bayes' theorem and positive and negative probability weights, calculations for different thresholds of serum IgE and eosinophil counts were summated and a posttest probability for atopy was calculated. Calculated posttest probabilities varied according to the threshold used to determine a positive or negative test; however, IgE thresholds greater than 140IU/ml and eosinophil counts greater that 80cells/ml were found to have a high probability of predicting atopy in patients with rhinitis. Moreover, IgE had a greater influence than eosinophil count in determining posttest probability of allergy in this population. Considerable differences were noted in the IgE levels of atopic and non-atopic patients, including those with asthma or a history of smoking. However, these differences were not observed with eosinophil levels. CONCLUSIONS: Using a modified version of Bayes' theorem to determine posttest probability, IgE threshold levels greater than 140IU/ml and eosinophil counts greater than 80cells/ml in an individual with clinical signs and symptoms of rhinitis are likely to correlate with an atopic aetiology. This model of probability may be helpful in evaluating individuals for diagnostic skin testing and certain types of allergy-modifying treatment.

Response to medical or surgical therapy in chronic rhinosinusitis: A one year prospective analysis

Introduction: Chronic rhinosinusitis (CRS) is treated with both surgical and medication options. However, long term data on patient outcomes is rare. In a real world clinical environment, our objective was to identify CRS patients, gather patient characteristics, and follow symptoms over one year. Patients and methods: This observational study enrolled patients with CRS. Primary clinical markers included atopy testing, serum IgE, and complete blood counts. A sinus computerized tomography (CT) scan was performed serially. Patients were enrolled into medical treatment Arm A and into surgical treatment Arm B. Symptom scores were calculated using the chronic sinusitis survey (CSS). Results: Atopy testing was positive in 67%. IgE levels or atopy did not correlate with CSS scores. A 23% decrease in total CSS scores was noted in Arm A at one year (P=.01). Arm B demonstrated a 38% reduction in total CSS scores at 3 months (P=.02) only. CT evidence of CRS was found in 74% of patients. However, CT scores did not change significantly over 12 months. Conclusions: No correlation was found between serum IgE levels or atopy versus CSS scores. CT scan scores did not change significantly over 12 months in either treatment group. A reduction of CSS scores was seen in both treatment groups; however a rebound effect was suggested in the surgical arm. Our study demonstrates the disconnection between clinical markers, radiographic evidence and response to therapy in CRS in a common clinical setting. It exemplifies the need for controlled studies with years of chronic rhinosinusitis outcome analysis (AU)

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Response to medical or surgical therapy in chronic rhinosinusitis: A one year prospective analysis.

INTRODUCTION: Chronic rhinosinusitis (CRS) is treated with both surgical and medication options. However, long term data on patient outcomes is rare. In a real world clinical environment, our objective was to identify CRS patients, gather patient characteristics, and follow symptoms over one year. PATIENTS AND METHODS: This observational study enrolled patients with CRS, primary clinical makers included atopy testing, serum lgE, and complete blood counts. A sinus computerized tomography (CT) scan was performed serially. Patients were enrolled into medical treatment Arm A and into surgical treatment Arm B. Symptom scores were calculated using the chronic sinusitis survey (CSS). RESULTS: Atopy testing was positive in 67%. lgE levels or atopy did not correlate with CSS scores A 23% decrease in total CSS scores was noted in Arm A at one year (p =.01). Arm B demonstrated a 38% reduction in total CSS scores at 3 months (p =.02) only. CT evidence of CRS was found in 74% of patients. However, CT scores did not change significantly over 12 months. CONCLUSIONS: No correlation was found between serum lgE levels or atopy versus CSS scores. CT scan scores did not change significantly over 12 months in either treatment group. A reduction of CSS scores was seen in both treatment groups: however a rebound effect was suggest in the surgical arm. Our study demonstrates the disconnection common clinical setting. It exemplifies the need for controlled studies with years of chronic rhinosinusitis outcome analysis.

Age-related impaired proliferation of peripheral blood mononuclear cells is associated with an increase in both IL-10 and IL-12.

Reflective of age-associated decline in immune function among elderly individuals is a decrease in in vitro T cell proliferative ability. Impaired T cell proliferation in the elderly may result from disruption of the well-balanced network of regulatory cytokines produced during an immune response. The purpose of this study was to identify age-related changes in the production of interleukin (IL)-10 and IL-12, and to determine whether in vitro T cell proliferation can be enhanced in the elderly by modulation of these two key cytokines. The superantigen Staphyloccocus entertoxin B (SEB) was used to stimulate proliferation and IL-10 and IL-12 production in peripheral blood mononuclear cells (PBMC) in vitro. Proliferation was determined by standard tritiated thymidine uptake. Cytokine levels in culture supernatants were measured by ELISA. We observed impaired SEB-induced proliferation of PBMC in the elderly that is comparable to that seen with the polyclonal mitogen Con A. This age-related decline in proliferation was associated with increased production of both IL-10 and IL-12. Modulation of PBMC proliferative response with either recombinant IL-12 or IL-10-neutralizing antibodies can boost proliferation of elderly PBMC to the levels seen in unmodulated young controls.

Nomograms to follow recovery rate in status asthmaticus in a veteran population.

Data from 12 Department of Veterans Affairs patients hospitalized for status asthmaticus were analyzed to determine the rate and degree of response to therapy. The time to achieve recovery was directly related to the level of baseline obstruction at the time of hospital admission. The recovery rate was constant and could be described by a single second-degree polynomial regression equation. Nomograms were constructed showing this rate of improvement of pulmonary function over time at four levels of baseline pulmonary obstruction.

Comparative efficacy of terfenadine, loratadine, and astemizole in perennial allergic rhinitis.

Nonsedating H1 antihistamines such as terfenadine, loratadine, and astemizole are widely prescribed for the treatment of allergic rhinitis. The comparative efficacy of these agents has not been thoroughly studied. We studied 14 subjects in an open-label four-way crossover trial. Patients were recruited from an outpatient allergy clinic. Inclusion criteria were documented rhinitis symptoms for at least 2 years before the study and skin-test positivity in response to perennial allergens. Each subject underwent sequential 2-week trials of each of four H1 antihistamines: terfenadine, loratadine, astemizole, and chlorpheniramine. No placebo was included. Outcome measures were subjective rhinitis symptom scores, overall efficacy scores, and concomitant pseudoephedrine use. In addition, nasal-examination scores were obtained by way of physician assessment at the end of each 2-week trial, and side effects were tabulated. Nasal-examination scores for each of the four H1 antihistamines were significantly better than the baseline scores (p < 0.05). No statistically significant differences in rhinitis symptom scores, overall efficacy scores, or concomitant pseudoephedrine use were noted. We detected no clinically significant differences in efficacy among terfenadine, loratadine, astemizole, and chlorpheniramine in the treatment of perennial allergic rhinitis.

Allergic and immunologic profile of symptomatic Persian Gulf War veterans.

BACKGROUND: Persian Gulf War veterans have been enrolled in the Veterans Administration Persian Gulf Health Registry for evaluation of unexplained symptoms and illnesses. The allergy and immunology division at the West Los Angeles Veterans Administration Medical Center evaluated 20 consecutive symptomatic Persian Gulf War veterans. OBJECTIVE: The purpose of this study was to examine the immunologic profiles of symptomatic Persian Gulf War Veterans. METHODS: A detailed history was obtained that included duties/responsibilities, length of time in the Persian Gulf, location, and exposures during the Gulf War. A complete physical examination was performed, with extensive laboratory testing and immediate and delayed hypersensitivity skin testing. Data from these Persian Gulf War Veterans were compared with a control population consisting of 44 non-Persian Gulf War veterans enrolled in our allergy and immunology clinic. Presenting allergic symptoms, presence of atopy, and total serum IgE levels were compared. RESULTS: Persian Gulf study patients and registry patients had a broad spectrum of nonspecific symptoms as compared with allergy clinic control patients who had dermatologic and respiratory symptoms. Persian Gulf study patients with allergy symptoms had a higher mean IgE level (88.7 IU/mL) than Persian Gulf study patients without allergy symptoms (47.5 IU/mL). Persian Gulf study patients with positive skin tests had a higher mean IgE level (161.5 IU/mL) than Persian Gulf study patients with negative skin tests (22.3 IU/mL). Laboratory data showed no significant immune abnormalities. CONCLUSION: Our study showed that 20 Persian Gulf veterans with a multitude of nonspecific symptoms had no immune abnormality. Mean IgE levels and eosinophil counts correlated with atopic state and reported allergy symptoms.

Severe hypersensitivity reaction during hemodialysis.

BACKGROUND: Hemodialysis-associated hypersensitivity reactions are well documented in the literature. Ethylene oxide sensitization and activation of complement are important factors involved during such reactions. The majority of severe hypersensitivity reactions in dialysis patients, however, is due to sensitization to ethylene oxide. METHODS: We report a patient admitted to the hospital with worsening of his renal function. He subsequently required three hemodialysis treatments, all of which resulted in severe hypersensitivity reactions requiring endotracheal intubation. The initial hypersensitivity episode was thought to be due to complement activation to the cupramonium-rayon membrane dialyzer. Despite changing to a polyacrylonitrile membrane, which does not activate complement, a second hypersensitivity reaction developed. Suspecting ethylene oxide hypersensitivity, the third hemodialysis session incorporated a biocompatible dialyzer that was sterilized with gamma irradiation, not ethylene oxide. Yet again, an anaphylactoid reaction resulted. It was postulated that residual ethylene oxide in the tubing might have triggered this last attack. RESULTS: Despite a negative RAST (radioallergosorbent test) to ethylene oxide, the strong history surrounding each of the hypersensitivity episodes and high index of suspicion pointed to ethylene oxide hypersensitivity as the etiologic factor. To this end, the patient fared much better when peritoneal dialysis was initiated. The patient subsequently died from other complications of his illness. CONCLUSIONS: This case report demonstrates both the complex nature involving a hypersensitivity reaction to hemodialysis and the life-threatening severity of such a reaction. Replacing ethylene oxide with steam or gamma radiation to sterilize dialyzers and thoroughly rinsing new dialyzers and tubing with normal saline may help circumvent this problem.

Asthma: analysis of intubated patients over a one-year period.

Mortality rates for asthma have increased significantly since 1980. During a 12-month period [1990] at the West Los Angeles VA Medical Center, six asthma patients required intubation. Contributing factors to intubation were steroid dependence, atopy, beta-agonist overuse, infection, non-compliance, adverse drug reaction, and undertreatment with steroids.

Osteoporosis in steroid-dependent asthma.

BACKGROUND: Patients on prolonged corticosteroid therapy are at risk of developing osteoporosis. Some patients with severe asthma are difficult to wean off corticosteroids and are therefore at risk of developing bony complications due to steroids. OBJECTIVE: The purpose of this study was to examine the relationship of cumulative steroid dosage and duration of therapy with osteoporosis. METHODS: We obtained bone mineral density studies using dual photon absorptiometry, and radiographs of the lumbar spine of 16 steroid-dependent patients with asthma. Patients with conditions affecting bone metabolism were excluded. RESULTS: We studied 16 male steroid-dependent patients with asthma who received 4 to 41 grams equivalent dose of prednisone over a period of 1 to 15 years. The overall prevalence rate for abnormal age-matched bone mineral density was 50%. Abnormal bone mineral density was more commonly noted in the lumbar spine (38%) than in the femoral neck (19%). The lowest dose of corticosteroid associated with a decrease in bone mineral density was a cumulative steroid dose of 5.6 equivalent grams-prednisone. CONCLUSION: Prolonged corticosteroid therapy can cause significant osteoporosis among male patients with steroid-dependent asthma. Bone loss due to corticosteroid therapy occurs at different rates at different bony sites.