Anne M. Ditto

Elimination Diet Effectively Treats Eosinophilic Esophagitis in Adults; Food Reintroduction Identifies Causative Factors

BACKGROUND & AIMS Adults with eosinophilic esophagitis (EoE) typically present with dysphagia and food impaction. A 6-food elimination diet (SFED) is effective in children with EoE. We assessed the effects of the SFED followed by food reintroduction on the histologic response, symptoms, and quality of life in adults with EoE. METHODS At the start of the study, 50 adults with EoE underwent esophagogastroduodenoscopies (EGDs), biopsies, and skin-prick tests for food and aeroallergens. After 6 weeks of SFED, patients underwent repeat EGD and biopsies. Histologic responders, defined by ≤ 5 eosinophils/high-power field (eos/hpf) (n = 32), underwent systematic reintroduction of foods followed by EGD and biopsies (n = 20). Symptom and quality of life scores were determined before and after SFED. RESULTS Common symptoms of EoE included dysphagia (96%), food impaction (74%), and heartburn (94%). The mean peak eosinophil counts in the proximal esophagus were 34 eos/hpf and 8 eos/hpf, before and after the SFED, and 44 eos/hpf and 13 eos/hpf in the distal esophagus, respectively (P < .0001). After the SFED, 64% of patients had peak counts ≤ 5 eos/hpf and 70% had peak counts of ≤ 10 eos/hpf. Symptom scores decreased in 94% (P < .0001). After food reintroduction, esophageal eosinophil counts returned to pretreatment values (P < .0001). Based on reintroduction, the foods most frequently associated with EoE were wheat (60% of cases) and milk (50% of cases). Skin-prick testing predicted only 13% of foods associated with EoE. CONCLUSIONS An elimination diet significantly improves symptoms and reduces endoscopic and histopathologic features of EoE in adults. Food reintroduction re-initiated features of EoE in patients, indicating a role for food allergens in its pathogenesis. Foods that activated EoE were identified by systematic reintroduction analysis but not by skin-prick tests.

Outcome analysis of endoscopic sinus surgery in patients with nasal polyps and asthma

Objective: To investigate the efficacy of endoscopic sinus surgery (ESS) in the management of chronic sinusitis and asthma in patients with nasal polyps and steroid‐dependent asthma. Study Design: Retrospective chart review. Methods: The study included 17 patients who underwent ESS with nasal polyps, steroid‐dependent asthma with or without aspirin sensitivity and a minimum of 1 year postoperative follow‐up. Nine patients were ASA sensitive, and eight patients were ASA tolerant. Chronic sinusitis and asthma were evaluated using subjective (patient complaints) and objective (computed tomography scans, pulmonary function tests, steroid doses) criteria. Preoperative data were compared with data obtained 12 to 18 months postESS. Tissue samples were graded for degree of inflammation and edema. Results: Thirteen of the 17 (76.5%) patients reported improved clinical symptoms postESS. The postoperative Lund‐Mackay scores were statistically lower for the 17 patients (P < .0001). The group experienced improvement in postoperative forced expiratory volume at 1 second (FEV1) (P < .014). Twelve of 17 (70.6%) experienced reduction in systemic steroid usage (P < .048). The ASA sensitive patients did not have a statistical improvement in postoperative FEV1 (P > .08) and sinonasal symptoms (P > .16) compared with the ASA tolerant group. Polyp tissue from the ASA sensitive patients demonstrated more edema and more inflammation on average than ASA tolerant polyps, but the results were not statistically significant. Conclusion: ESS demonstrates a beneficial effect on the sinonasal and asthma symptomatology in patients with nasal polyps and asthma using objective measures. Subset of aspirin‐tolerant patients have statistically better outcome for sinonasal symptoms and pulmonary function testing than aspirin‐sensitive patients.

Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy.

BACKGROUND To date, no predictive tests for the clinical response to allergen-specific immunotherapy (ASI) are available. Therefore an in vivo or in vitro test would be of great value. OBJECTIVE We sought to evaluate pretreatment parameters used in diagnosing allergic rhinitis and determining serum specific IgE (s-IgE) levels, serum total IgE (t-IgE) levels, and blood eosinophil counts and to identify whether can be used to predict clinical improvement in monosensitized patients with allergic rhinitis with or without asthma treated with immunotherapy. METHODS We analyzed 279 patients who had undergone 4 years of ASI administered either by means of the subcutaneous immunotherapy (76 patients) or sublingual immunotherapy (203 patients) routes. Serum t-IgE and s-IgE levels, blood eosinophil counts, and serum s-IgE/t-IgE ratios were calculated and tested for correlation with clinical response to ASI. Receiver operating characteristic curves were determined. Predicted probabilities and predictive areas under the curve were calculated. RESULTS The clinical response to ASI was effective in 145 (52.0%) of 279 total patients, 42 (55.2%) of 76 patients treated with subcutaneous immunotherapy, and 103 (50.7%) of 203 patients treated with sublingual immunotherapy. A significant correlation was found between the serum s-IgE/t-IgE ratio and the clinical response to ASI, with high ratios (>16.2) associated with an effective response. The sensitivity and specificity of the area under the curve of the ratio were higher than those of serum s-IgE and t-IgE alone. CONCLUSION The calculation of the serum s-IgE/t-IgE ratio for predicting the clinical response to ASI offers an advantage over measuring t-IgE and s-IgE levels in monosensitized patients for the following allergens: grass, Parietaria judaica, Olea europea, and house dust mite.

Review of Alleged Reaction to Monosodium Glutamate and Outcome of a Multicenter Double-Blind Placebo-Controlled Study

Monosodium glutamate (MSG) has a long history of use in foods as a flavor enhancer. In the United States, the Food and Drug Administration has classified MSG as generally recognized as safe (GRAS). Nevertheless, there is an ongoing debate exists concerning whether MSG causes any of the alleged reactions. A complex of symptoms after ingestion of a Chinese meal was first described in 1968. MSG was suggested to trigger these symptoms, which were referred to collectively as Chinese Restaurant Syndrome. Numerous reports, most of them anecdotal, were published after the original observation. Since then, clinical studies have been performed by many groups, with varying degrees of rigor in experimental design ranging from uncontrolled open challenges to double-blind, placebo controlled (DBPC) studies. Challenges in subjects who reported adverse reactions to MSG have included relatively few subjects and have failed to show significant reactions to MSG. Results of surveys and of clinical challenges with MSG in the general population reveal no evidence of untoward effects. We recently conducted a multicenter DBPC challenge study in 130 subjects (the largest to date) to analyze the response of subjects who report symptoms from ingesting MSG. The results suggest that large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, the frequency of the responses was low and the responses reported were inconsistent and were not reproducible. The responses were not observed when MSG was given with food.

Corticosteroid therapy in an additional 13 cases of Stevens-Johnson syndrome: a total series of 67 cases.

Stevens-Johnson syndrome (SJS) is a severe cutaneous eruption that can be a life-threatening emergency. Previously, we have reported our favorable experience in treating 54 patients with SJS with systemic corticosteroids. We continued our prospective analysis of consecutive patients with SJS treated with corticosteroids. Possible etiologic factors and clinical outcomes of the patients are described. All 13 patients improved with initiation of systemic corticosteroid therapy. There was no mortality or permanent sequelae attributable to SJS. Drugs were the offending agents in all 13 cases. There was one death unrelated to SJS. In conclusion, prompt treatment with systemic corticosteroids reduces morbidity and improves outcome of SJS patients. This analysis extends our series to 67 consecutive patients with SJS who were treated with corticosteroids and had a favorable outcome.

Idiopathic Anaphylaxis: a Series of 335 Cases

BACKGROUND Idiopathic anaphylaxis is anaphylaxis with no definable etiology and no trigger by exogenous allergens. Initially described in 1978, idiopathic anaphylaxis has been subsequently characterized and treatment protocols have been established. OBJECTIVE The demographics and course of 335 patients (225 previously reported) treated with prednisone, hydroxyzine, and albuterol are now reported. RESULTS Ages ranged from 5 to 83 years. There were nine new pediatric patients in this series totaling 14 (4.2%). Atopy was common (48%) with 34 new patients with asthma. The duration of symptoms prior to presentation ranged from three days to 27 years. One hundred thirty-two patients with idiopathic anaphylaxis were available for follow-up. Twenty of these are currently receiving prednisone for control of idiopathic anaphylaxis, seven of them as part of their initial therapy, and ten for control of recurrence of symptoms. Three patients required continuous alternate day prednisone for control of symptoms (corticosteroid-dependent idiopathic anaphylaxis). Of the 335 patients, there were no longer any patients with the diagnosis of malignant idiopathic anaphylaxis defined as requiring prednisone, 20 mg daily, or 60 mg every other day, for control of idiopathic anaphylaxis. Of the six patients previously diagnosed with malignant idiopathic anaphylaxis, five no longer required prednisone and one has a decreased prednisone requirement of 20 mg on alternate days. Hospital visits were significantly reduced by the management regimens. There were no fatalities from idiopathic anaphylaxis in this series. CONCLUSIONS The incidence of idiopathic anaphylaxis is increasing in our practice with more patients being evaluated each year. During 1104 patient years of observation (the longest period of single patient observation being 24 years), no inciting agent has been found responsible for the anaphylactic symptoms. Prognosis continues to remain good with the majority of patients achieving remission with pharmacotherapy.

Immunoglobulin E to Staphylococcal and Streptococcal Toxins in Patients with Chronic Sinusitis/Nasal Polyposis†

Background: The role of infectious agents and their contribution to the inflammation in chronic sinusitis/nasal polyposis (CS/NP) is not clear. Staphylococcal and streptococcal toxins have superantigen activity and have been implicated in inflammatory conditions such as atopic dermatitis, psoriasis, and asthma.

Efficacy of endoscopic sinus surgery in the management of patients with asthma and chronic sinusitis.

An association between chronic sinusitis and asthma has been noted for many years, although the precise nature of the relationship is poorly understood. Earlier studies, using traditional surgical techniques, have demonstrated subjective improvement in asthmatic complaints. Reports demonstrating improvement following endoscopic sinus surgery for chronic sinusitis are rare. To report our experience with endoscopic sinus surgery and asthmatics, we reviewed the charts of 75 consecutive patients with asthma and chronic sinusitis who underwent endoscopic sinus surgery between 1994 and 1996. Study criteria included the following: chronic sinusitis, one year preoperative and one year postoperative follow-up from endoscopic sinus surgery, and asthma requiring inhaled steroids and oral prednisone for control. Many patients required prednisone bursts for control of asthma. Number of days and total dose of oral prednisone were used as objective measures of asthma control. Number of weeks of antibiotics was used as a relative measure of sinusitis. Fourteen of the 15 patients meeting study criteria decreased their postoperative prednisone requirement by total number of days (preoperative 84 versus postoperative 63 days [p < 0.0001]). Postoperatively, patients required an average of 1300 mg less oral prednisone (p < 0.033). Antibiotic use also decreased, with an average use of antibiotic nine weeks preoperatively versus seven weeks postoperatively (p < 0.045). This study provides corroborative objective evidence that, at least in the short term, endoscopic sinus surgery is efficacious in the management of patients with chronic sinusitis and asthma.

Chronic sinusitis with nasal polyps: Staphylococcal exotoxin immunoglobulin e and cellular inflammation

Background The etiology of chronic sinusitis with nasal polyposis (CS/NP) remains enigmatic. Frequently, Staphylococcus aureus is present in the nose of CS/NP patients, although the significance is unclear. Recent reports have suggested the hypothesis that these bacteria may secrete exotoxins triggering the inflammatory mucosal changes seen in CS/NP. This mechanism of immunopathology has been established in other diseases associated with Staphylococcus colonization and exotoxin secretion such as atopic dermatitis. In atopic dermatitis, the exotoxins incite a local superantigen response in which clonal T-cell activation and massive cytokine release occur in the affected skin. Second, these exotoxins can act as traditional allergens, stimulating a typical immunoglobulin E (IgE) response in the serum, which has been correlated with disease severity. This study is designed to begin the assessment of the hypothesis that a similar mechanism takes place in CS/NP. Methods Serum was drawn from patients with CS/NP undergoing endoscopic sinus surgery as well as 13 atopic and nonatopic control subjects without sinusitis. IgE levels to S. aureus exotoxins A (SEA), SE exotoxins B (SEB), and toxic shock syndrome toxin 1 were measured using enzyme-linked immunosorbent assay. Tissue eosinophilia and the presence of lymphocytes on hemotoxylin and eosin-stained sections of polyps were scored by a blinded pathologist and correlated to presence of toxin IgE in the serum. Results Staphylococcal exotoxin (SE)-specific IgE was found in the serum of 5/10 (50%) of the patients with CS/NP. In contrast, 0/13 control patients had IgE to the exotoxins (p = 0.031). Polyp eosinophil, lymphocyte, and mononuclear cell counts were compared in IgE exotoxin-positive and -negative subjects. A trend toward increased eosinophil counts in patients with SE IgE (SE IgE+) was present, but not statistically significant. Conclusion These results indicate that a high percentage of CS/NP patients show a systemic IgE response to S. aureus exotoxins in comparison with controls without CS/NP. Although these results are consistent with the actions of Staphylococcus toxins in other diseases, additional work is necessary to establish a local superantigen response in the nasal mucosa of CS/NP patients. (American Journal of Rhinology 18, 273–278, 2004)

Prevalence and onset of rhinitis and conjunctivitis in subjects with occupational asthma caused by trimellitic anhydride (TMA)

Individuals with occupational asthma may also report symptoms of rhinitis or conjunctivitis. The objective of this study was to investigate the prevalence of rhinitis and conjunctivitis in subjects with occupational asthma as a result of trimellitic anhydride (TMA). Additionally, we wanted to evaluate the onset of rhinitis and conjunctivitis symptoms as compared with the occupational asthma symptoms. In a case series design, we studied 25 consecutive employees with TMA-induced asthma; each of them had participated in an annual surveillance program in which they were queried about rhinitis, conjunctivitis, and other respiratory symptoms. Twenty-two of the 25 (88%) reported rhinitis symptoms whereas 17 of the 25 (68%) reported conjunctivitis symptoms. In 17 of the 22 (77%) individuals with rhinitis and asthma, the rhinitis symptoms preceded the asthma symptoms. In 14 of the 17 (82%) individuals with conjunctivitis, those symptoms preceded the asthma symptoms. In summary, symptoms of rhinitis and conjunctivitis are common in subjects with occupational asthma because of TMA and often precede the respiratory symptoms.