William B. Klaustermeyer

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.

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.

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.

Delayed cutaneous hypersensitivity in normals: choice of antigens and comparison to in vitro assays of cell-mediated immunity

In 81 normal subjects, ages 19 to 100 yr (mean 52), we studied the prevalence of positive 48 hr skin reactions to six antigens: fluid tetanus toxoid, Candida albicans, SK/SD, Trichophyton, PPD, and coccidioidin. Of these, C. albicans was most frequently reactive (92%); SK/SD (51%) and tetanus (49%) were less so. Each of the remaining three antigens was reactive in less than 42% of the subjects. The minimum number of antigens required to detect delayed hypersensitivity in 100% of subjects was two: C. albicans and tetanus. We found no correlation between skin reactivity at 20 min, 6 hr, and 48 hr for most of the antigens studied, suggesting different mechanisms for reactions occurring at each time. In 60 of the subjects, lymphocyte stimulation index (LSI) with tetanus toxoid and monocyte chemotaxis (MC) assays were done. The natural log of the area of induration at 48 hr after tetanus skin testing (I48) increased as a function of LSI (p less than 0.005) and MC (p less than 0.025) by multiple regression analysis. Skin testing was less sensitive than LSI as a test for cell-mediated immunity in our population. However, because of availability and correlation with LSI, delayed cutaneous hypersensitivity should be tested initially. For this purpose, tetanus toxoid appears to be a useful antigen when used in combination with C. albicans.

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.

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.

Mortality in status asthmaticus: A nine-year experience in a respiratory intensive care unit

Failure to recognize the severity of an asthmatic attack and its consequent lack of aggressive management have been incriminated as contributing factors in mortality from asthma. We reviewed our experience with patients in status asthmaticus admitted to the Respiratory Intensive Care Unit (RICU) over a nine-year period to determine the course and mortality of patients managed in the RICU. Between May, 1968, and April, 1977, 86 patients in status asthmaticus were admitted, 11 with multiple admissions, for a total of 111 admissions. There were two fatalities recorded. Psychological dependence on therapeutic modalities probably contributed to these two deaths, and both may have been preventable. The low mortality rate probably reflects the more intensive management and monitoring that these severe asthmatics receive in an RICU setting.

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.

Enalapril induced angioedema

A report of three patients who developed angiodema while receiving enalapril. Patient 1 came in with an 8-hour history of facial swelling after enalapril had been started 2 days earlier. The second patient came in with severe angiodema of the tongue, larynx, and glottis requiring emergency tracheostomy, hydroxyzine, and steroids. He had been treated with enalapril for 1 year. The third patient developed facial swelling within a few hours of the first dose of enalapril. Angiodema with enalapril can occur early or late in the course of therapy. A possible mechanism for this drug reaction is the potentiation of bradykinin with resultant kinin system activation.

Comparison of Nifedipine with a New Calcium Channel Blocker, Flordipine, in Exercise-Induced Asthma

Four patients with documented exercise-induced asthma (EIA) were pretreated orally in random, double-blind fashion with the calcium channel blockers nifedipine 20 mg and flordipine 25 and 50 mg and placebo, then subjected to exercise challenge on a cycloergometer. Each patient served as his own control, undergoing exercise challenge with the different pretreatments on 4 separate days. No statistically significant protection from EIA was found with either nifedipine or flordipine.