Chapter 24: Anaphylaxis.

Anaphylaxis is a sudden-onset, immediate reaction that implies a risk of death. Think of a "rule of 2's" for anaphylaxis implying that reactions usually begin within 2 minutes to 2 hours after injection, infusion, ingestion, contact, or inhalation. Fatalities can be from asphyxiation from laryngeal or oropharyngeal swelling, collapse from hypotensive shock, cardiac arrest, or acute severe bronchoconstriction causing respiratory failure and arrest. When there is activation of mast cells and basophils in anaphylaxis, chemical mediators are detectable. The preformed mediators from mast cells include histamine, tryptase, carboxypeptidase A, and proteoglycans (heparin and chondroitin sulfates). Newly synthesized mediators include prostaglandin D(2), leukotriene D(4), and platelet-activating factor. Crucial actions of the mediators include an abrupt increase in vascular permeability, vascular smooth muscle relaxation, and bronchial smooth muscle contraction. Anaphylaxis can be classified into immunologic, nonimmunologic, or idiopathic based on the associated mechanism. For example, immunologic causes of anaphylaxis are those mediated by IgE antibodies acting through the FcεR I (foods, insect venom, and beta-lactam antibiotics) whereas non-IgE immunologic anaphylaxis is mediated without presence of antiallergen IgE antibodies or via FcεRI activation (radiographic contrast material). Nonimmunologic anaphylaxis involves mast cell mediator release such as occurs with exercise, cold temperature exposure, or from medications such as opioids or vancomycin. Idiopathic anaphylaxis involves mast cell activation (acutely elevated urine histamine or serum tryptase) and activated lymphocytes. Because anaphylaxis is a medical emergency, the drug of choice is epinephrine, not H(1)-receptor antagonists.

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.

Skin prick testing does not reflect the presence of IgE against food allergens in adult eosinophilic esophagitis patients: a case study.

Skin prick testing is widely used to predict the presence of allergen-specific IgE. In eosinophilic esophagitis patients, who frequently exhibit polysensitization and broad reactivity upon skin prick testing, this is commonly used to aid avoidance recommendations in the clinical management of their disease. We present here the predictive value of skin prick testing for the presence of allergen-specific IgE, in 12 patients, determined by immunoblot against the allergen extracts using individual-matched serum. Our results demonstrate a high degree of predictive value for aeroallergens but a poor predictive value for food allergens. This suggests that skin prick testing likely identifies IgE reactivity towards aeroallergens in adult eosinophilic esophagitis but this is not true for foods. Consequently, IgE immunoblotting might be required for determining food avoidance in these patients.

Aeroallergen hypersensitivity: comparing patients with nasal polyps to those with allergic rhinitis.

Immunoglobulin E-mediated allergy generally has not been considered to be important in the pathogenesis of nasal polyps, despite elevated immunoglobulin E in polyp exudates, tissue eosinophilia, and degranulated mast cells. In previous reports, patients with nasal polyps were more likely to have positive skin tests to perennial than to seasonal allergens. It is postulated that nasal polyps result from the constant nature of perennial allergen exposure. The objective of this report is to compare the prevalence of sensitization to six aeroallergens in a group of nasal polyp (NP) patients, a group of allergic rhinitis (AR) patients, and those subjects with positive skin tests in the National Health and Nutrition Examination Survey (NHANES) II. Twenty-five consecutive NP patients evaluated over a 3-month period of time at Northwestern Allergy and Immunology Outpatient Center, in addition to 50 of the allergic rhinitis patients evaluated over the same time, were chosen randomly. All were skin tested with the following antigens: dog, cat, dust mite, grass, tree, and ragweed. Published skin test data from the NHANES II study of 14,367 individuals was obtained also. The percent of NP patients, AR patients, and NHANES II subjects with sensitization to perennial allergens was 72, 96, and 7.6%, respectively. The difference between the AR and NP patients was statistically significant (p = 0.006). The percent of NP, AR, and NHANES II subjects sensitized to seasonal allergens was 84, 86, and 17.7%, respectively. No statistical significance existed between the AR and NP patients, regarding seasonal allergens. Although the AR and NP had similar levels of reactivity to perennial and seasonal allergens, the NHANES II group was more than twice as likely to be sensitized to a seasonal allergen. The NP and AR groups were similar in prevalence of reactivity to seasonal allergens, but the NP patients in our population actually were less likely to be sensitized to perennial allergens than individuals with AR.

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.

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. OBJECTIVE: We investigated the presence of immunoglobulin (Ig)E antibodies to staphylococcal and streptococcal toxins in the serum of individuals with CS/NP. METHOD: IgE antibodies to staphylococcal exotoxins, A, B, and toxic shock syndrome toxin-1 and streptococcal pyrogenic exotoxin A, B, and C were measured in 23 individuals with CS/NP before functional endoscopic sinus surgery and in controls (7 atopic and 6 nonatopic) individuals without chronic sinusitis. Presence of IgE to the toxins was also correlated with disease severity on sinus computed tomography (CT) scans. RESULTS: Staphylococcal and streptococcal toxin specific IgE antibodies were detected in 18 of 23 (78%) and 7 of 21 (33.3%) patients, respectively. None of the controls had IgE to the staphylococcal or streptococcal toxins (P <.0001). There was no association between radiographic severity of sinus disease and the presence of IgE antibody to the toxins. CONCLUSION: A significantly greater proportion of CS/NP patients had IgE to staphylococcal or streptococcal toxins. Evidence of IgE antibodies directed against staphylococcal and streptococcal toxins in the sera of patients with CS/NP suggests a potential role of these toxins with established superantigen effects in the pathogenesis of CS/NP.

Specific inflammatory cell types and disease severity as predictors of postsurgical outcomes in patients with chronic sinusitis.

Chronic sinusitis is a common condition that is frequently refractory to medical and surgical intervention. It has not been well defined as to which patient subgroups benefit from surgical intervention and which do not. Our purpose is to determine whether the presence of certain inflammatory cell types is predictive of postoperative outcome in sinus surgery for chronic sinusitis. We performed a retrospective chart review of 75 patients who underwent endoscopic sinus surgery or polypectomy between 1994 and 1996. Of these patients, 15 met inclusion criteria for chronic sinusitis, asthma requiring inhaled steroids, and 1 year preoperative and postoperative management by the allergist or otolaryngologist at Northwestern Medical Faculty Foundation. Ten of these 15 patients had a complete set of data allowing immunohistochemical analysis. Sections of sinus tissue obtained at surgery were hematoxylin and eosin stained and evaluated for the presence of lymphocytes, plasma cells, eosinophils, and macrophages. Immunostains for T lymphocytes, B lymphocytes, and macrophages were performed also. The total number of antibiotic courses patients received were enumerated into 6-month blocks for 1 year preoperatively and 1 year postoperatively as markers of disease activity. Postoperatively, four patients improved, three patients worsened, and three patients remained unchanged, as defined by the number of antibiotic courses required 1 year postoperatively compared with 1 year preoperatively. We found no difference in the magnitude or specific type of inflammatory cells present at the time of surgery between the groups. However, when the difference between the preoperative versus postoperative antibiotic courses was compared between patients who improved versus patients who did not improve, the improved group required markedly fewer courses relative to the nonimproved group (p < 0.009). Neither total magnitude of inflammation nor specific inflammatory cell types correlated with surgical outcome in this group. The patients who did not improve postoperatively had a statistically significantly lower number of preoperative antibiotics than the patients who improved. These findings suggest that patients with less severe disease may be less likely to benefit from sinus surgery.

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.

Hymenoptera sensitivity: diagnosis and treatment.

Hymenoptera anaphylaxis is responsible for 50 deaths annually. This may be an underestimation because not all anaphylactic episodes are recognized or reported. Unexplained deaths at the poolside or on golf courses, as well as those attributed to cardiac causes, may be caused by unrecognized anaphylaxis. Venom immunotherapy (VIT) is highly effective in reducing an individual's risk of anaphylaxis. This review will discuss the diagnosis and treatment of hymenoptera sensitivity, patient selection for IT, standard VIT, and modified allergens.