Case Report and DiscussionA 22-year-old Asian American man was seen for atopic dermatitis, pollenosis, oral allergy syndrome, and peanut/tree nut allergies in August 2017. He had a history of hypothyroidism and childhood eczema but no history of eye disease or prior ophthalmology visits. Examination revealed atopic dermatitis of hands, head, neck, and legs. His past treatment included corticosteroid and calcineurin inhibitor creams and allergen immunotherapy. The IgE level was 1792 kU/L, and blood eosinophils were 600/mm3. Pollen, dust mite, dander, peanut, and tree nut prick skin tests were positive. Dupilumab (300 mg every 2 weeks) was started in February 2018 with rapid skin improvement. By the summer of 2019, the patient had developed eye irritation (burning and foreign body sensation) and stopped dupilumab. An ophthalmologist treated him with ocular lubricants and tobramycin/dexamethasone that resolved eye symptoms. Dupilumab was restarted in the fall of 2019, but after 1.5 months, he developed ocular irritation and redness more on the right despite concurrent olopatadine ophthalmic administration. He stopped dupilumab in April 2020. Slit-lamp examination in September 2020 noted areas of punctate keratitis bilaterally and mild pannus of corneal neovascularization superiorly with mild encroachment of the right eye conjunctiva onto the cornea inferiorly. There was bilateral injection of the conjunctiva and areas of punctate fluorescein staining of both corneas and a discrete area of staining inferotemporally at the limbus of the right eye. Tobramycin/dexamethasone and artificial solutions were represcribed. Improvement was noted in the following 2 monthly appointments. Dupilumab was restarted in January 2021 but then again stopped in April 2021 because of health insurance lapse. When seen in May 2021, the patient was noted to have symptomatic mild conjunctival injection more on the right where some whitish appearance was noted on the inferior aspect of the cornea along the limbus (Figure 1). Dupilumab was restarted with the improvement of atopic dermatitis. In June 2021, continued conjunctival injection, right greater than left, was noted and treated with prednisolone ophthalmic solution for 2 weeks, and lifitegrast ophthalmic solution was initiated twice daily in both eyes. In October 2021, the patient returned with recurrent right eye irritation and redness. The right conjunctiva showed bulbar injection with whitish conjunctival encroachment primarily onto the inferior cornea (Figure 2). Because of insurance lapse, the patient discontinued dupilumab in the beginning of 2022. In a return visit, in April 2022, the patient reported worsened atopic dermatitis. The ocular examination showed only mild right conjunctival erythema with no limbic inflammation.Figure 2External photograph of the right eye in October 2021. Conjunctival hyperemia with limbal inflammation (blue arrow) and limbal infiltrates (green arrow) with keratinization of the inferior cornea along the corneal-limbal junction.View Large Image Figure ViewerDownload Hi-res image Download (PPT)The limbic inflammation has been noted in superior limbic keratoconjunctivitis (SLK), a disorder associated with thyroid disease, dry eye syndrome, and contact lenses.1Lahoti S. Weiss M. Johnson D.A. Kheirkhah A. Superior limbic keratoconjunctivitis: a comprehensive review.Surv Ophthalmol. 2022; 67: 331-341Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar The patient described herein had 2 of the known disorders associated with SLK but did not have limbic inflammation focused superiorly, nor were there any limbal filament characteristics of SLK. Given the known propensity of dupilumab to cause conjunctivitis in atopic dermatitis treatment, it seems plausible that the conjunctival inflammation in this patient extended to the limbus creating the striking appearance shown in Figure 2. The cumulative conjunctivitis adverse effect was maximal at the 12-month time point of CHRONOS trial treatment. The current patient did not return for follow-up for more than a year after initiation. It is conceivable that symptoms and ocular inflammation were present before follow-up. Although limbitis was present even after several months of dupilumab discontinuation, it was not present at a later visit when the patient again stopped dupilumab. Clinicians who prescribe dupilumab should be aware of this pattern of ocular inflammation as an adverse effect of this medication. Dysfunction of goblet cells caused by IL-13 blockade has been postulated to be a mechanism for dupilumab-induced ocular surface disorders.2Park S. Lee J.H. Park J.H. Park S.H. Park S.Y. Jung Y.W. et al.Ocular surface disorders associated with the use of dupilumab based on WHO VigiBase.Sci Rep. 2021; 1114293Google Scholar Limbitis and purported stem cell dysfunction has also been described with dupilumab. Case Report and DiscussionA 22-year-old Asian American man was seen for atopic dermatitis, pollenosis, oral allergy syndrome, and peanut/tree nut allergies in August 2017. He had a history of hypothyroidism and childhood eczema but no history of eye disease or prior ophthalmology visits. Examination revealed atopic dermatitis of hands, head, neck, and legs. His past treatment included corticosteroid and calcineurin inhibitor creams and allergen immunotherapy. The IgE level was 1792 kU/L, and blood eosinophils were 600/mm3. Pollen, dust mite, dander, peanut, and tree nut prick skin tests were positive. Dupilumab (300 mg every 2 weeks) was started in February 2018 with rapid skin improvement. By the summer of 2019, the patient had developed eye irritation (burning and foreign body sensation) and stopped dupilumab. An ophthalmologist treated him with ocular lubricants and tobramycin/dexamethasone that resolved eye symptoms. Dupilumab was restarted in the fall of 2019, but after 1.5 months, he developed ocular irritation and redness more on the right despite concurrent olopatadine ophthalmic administration. He stopped dupilumab in April 2020. Slit-lamp examination in September 2020 noted areas of punctate keratitis bilaterally and mild pannus of corneal neovascularization superiorly with mild encroachment of the right eye conjunctiva onto the cornea inferiorly. There was bilateral injection of the conjunctiva and areas of punctate fluorescein staining of both corneas and a discrete area of staining inferotemporally at the limbus of the right eye. Tobramycin/dexamethasone and artificial solutions were represcribed. Improvement was noted in the following 2 monthly appointments. Dupilumab was restarted in January 2021 but then again stopped in April 2021 because of health insurance lapse. When seen in May 2021, the patient was noted to have symptomatic mild conjunctival injection more on the right where some whitish appearance was noted on the inferior aspect of the cornea along the limbus (Figure 1). Dupilumab was restarted with the improvement of atopic dermatitis. In June 2021, continued conjunctival injection, right greater than left, was noted and treated with prednisolone ophthalmic solution for 2 weeks, and lifitegrast ophthalmic solution was initiated twice daily in both eyes. In October 2021, the patient returned with recurrent right eye irritation and redness. The right conjunctiva showed bulbar injection with whitish conjunctival encroachment primarily onto the inferior cornea (Figure 2). Because of insurance lapse, the patient discontinued dupilumab in the beginning of 2022. In a return visit, in April 2022, the patient reported worsened atopic dermatitis. The ocular examination showed only mild right conjunctival erythema with no limbic inflammation.The limbic inflammation has been noted in superior limbic keratoconjunctivitis (SLK), a disorder associated with thyroid disease, dry eye syndrome, and contact lenses.1Lahoti S. Weiss M. Johnson D.A. Kheirkhah A. Superior limbic keratoconjunctivitis: a comprehensive review.Surv Ophthalmol. 2022; 67: 331-341Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar The patient described herein had 2 of the known disorders associated with SLK but did not have limbic inflammation focused superiorly, nor were there any limbal filament characteristics of SLK. Given the known propensity of dupilumab to cause conjunctivitis in atopic dermatitis treatment, it seems plausible that the conjunctival inflammation in this patient extended to the limbus creating the striking appearance shown in Figure 2. The cumulative conjunctivitis adverse effect was maximal at the 12-month time point of CHRONOS trial treatment. The current patient did not return for follow-up for more than a year after initiation. It is conceivable that symptoms and ocular inflammation were present before follow-up. Although limbitis was present even after several months of dupilumab discontinuation, it was not present at a later visit when the patient again stopped dupilumab. Clinicians who prescribe dupilumab should be aware of this pattern of ocular inflammation as an adverse effect of this medication. Dysfunction of goblet cells caused by IL-13 blockade has been postulated to be a mechanism for dupilumab-induced ocular surface disorders.2Park S. Lee J.H. Park J.H. Park S.H. Park S.Y. Jung Y.W. et al.Ocular surface disorders associated with the use of dupilumab based on WHO VigiBase.Sci Rep. 2021; 1114293Google Scholar Limbitis and purported stem cell dysfunction has also been described with dupilumab. A 22-year-old Asian American man was seen for atopic dermatitis, pollenosis, oral allergy syndrome, and peanut/tree nut allergies in August 2017. He had a history of hypothyroidism and childhood eczema but no history of eye disease or prior ophthalmology visits. Examination revealed atopic dermatitis of hands, head, neck, and legs. His past treatment included corticosteroid and calcineurin inhibitor creams and allergen immunotherapy. The IgE level was 1792 kU/L, and blood eosinophils were 600/mm3. Pollen, dust mite, dander, peanut, and tree nut prick skin tests were positive. Dupilumab (300 mg every 2 weeks) was started in February 2018 with rapid skin improvement. By the summer of 2019, the patient had developed eye irritation (burning and foreign body sensation) and stopped dupilumab. An ophthalmologist treated him with ocular lubricants and tobramycin/dexamethasone that resolved eye symptoms. Dupilumab was restarted in the fall of 2019, but after 1.5 months, he developed ocular irritation and redness more on the right despite concurrent olopatadine ophthalmic administration. He stopped dupilumab in April 2020. Slit-lamp examination in September 2020 noted areas of punctate keratitis bilaterally and mild pannus of corneal neovascularization superiorly with mild encroachment of the right eye conjunctiva onto the cornea inferiorly. There was bilateral injection of the conjunctiva and areas of punctate fluorescein staining of both corneas and a discrete area of staining inferotemporally at the limbus of the right eye. Tobramycin/dexamethasone and artificial solutions were represcribed. Improvement was noted in the following 2 monthly appointments. Dupilumab was restarted in January 2021 but then again stopped in April 2021 because of health insurance lapse. When seen in May 2021, the patient was noted to have symptomatic mild conjunctival injection more on the right where some whitish appearance was noted on the inferior aspect of the cornea along the limbus (Figure 1). Dupilumab was restarted with the improvement of atopic dermatitis. In June 2021, continued conjunctival injection, right greater than left, was noted and treated with prednisolone ophthalmic solution for 2 weeks, and lifitegrast ophthalmic solution was initiated twice daily in both eyes. In October 2021, the patient returned with recurrent right eye irritation and redness. The right conjunctiva showed bulbar injection with whitish conjunctival encroachment primarily onto the inferior cornea (Figure 2). Because of insurance lapse, the patient discontinued dupilumab in the beginning of 2022. In a return visit, in April 2022, the patient reported worsened atopic dermatitis. The ocular examination showed only mild right conjunctival erythema with no limbic inflammation. The limbic inflammation has been noted in superior limbic keratoconjunctivitis (SLK), a disorder associated with thyroid disease, dry eye syndrome, and contact lenses.1Lahoti S. Weiss M. Johnson D.A. Kheirkhah A. Superior limbic keratoconjunctivitis: a comprehensive review.Surv Ophthalmol. 2022; 67: 331-341Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar The patient described herein had 2 of the known disorders associated with SLK but did not have limbic inflammation focused superiorly, nor were there any limbal filament characteristics of SLK. Given the known propensity of dupilumab to cause conjunctivitis in atopic dermatitis treatment, it seems plausible that the conjunctival inflammation in this patient extended to the limbus creating the striking appearance shown in Figure 2. The cumulative conjunctivitis adverse effect was maximal at the 12-month time point of CHRONOS trial treatment. The current patient did not return for follow-up for more than a year after initiation. It is conceivable that symptoms and ocular inflammation were present before follow-up. Although limbitis was present even after several months of dupilumab discontinuation, it was not present at a later visit when the patient again stopped dupilumab. Clinicians who prescribe dupilumab should be aware of this pattern of ocular inflammation as an adverse effect of this medication. Dysfunction of goblet cells caused by IL-13 blockade has been postulated to be a mechanism for dupilumab-induced ocular surface disorders.2Park S. Lee J.H. Park J.H. Park S.H. Park S.Y. Jung Y.W. et al.Ocular surface disorders associated with the use of dupilumab based on WHO VigiBase.Sci Rep. 2021; 1114293Google Scholar Limbitis and purported stem cell dysfunction has also been described with dupilumab.

Dermographism is a common feature in patients with chronic urticaria (CU). When allergy skin testing is performed in patients with dermographia, positive reactions may be noted including at negative control testing sites, thus obfuscating the significance of specific allergen reactivity. Diagnostic values of even the minimally invasive prick skin tests have been reported to be affected by the presence of dermographia. We report a unique pattern of dermographia associated with a commercial percutaneous skin testing device that has a stainless-steel lancet tip whose 1.2 mm depth penetration is ensured by a surrounding circular plastic restraining rim (∼4mm diameter). Case reports of several patients with a history of pruritic cutaneous eruptions and who underwent percutaneous skin testing (PST) with the ComfortTenTM device, are described. Perimeter donut shaped edema at one or more skin test sites were noted in 4 patients tested resulting in a “dimple” appearance of the wheals. The age/sex of the patients were 27/F, 34/M, 51/M, 54/F. 2 had rhinitis symptoms, 2 had histories of penicillin allergy and 3 had purported food reactions. All patients had histories of recurrent pruritic rashes but had normal skin examinations at the time of their visits. Complete wheals that did not have a dimple effect were noted at histamine and select specific aero-allergen test sites., One patient had dimpling reaction at a fish mix extract test site but had negative test site reactions for individual fish. Stroking of the skin with a blunt object is felt to be the diagnostic standard for documenting simple and symptomatic dermographism (Black AK, Lawlor F, Greaves MW Consensus meeting on the definition of physical urticarias and urticarial vasculitis. Clin Exp Dermatol. 1996;21:424-6.). The application of the ComfortTenTM PST device appears to elicit dermographism through a stimulus similar to the blunt non-stroking pressure applied by one previously described dermographometer (Termklinchan V, Kulthanan K, Bunyaratavej S. Assessment of dermographism at different anatomical regions by dermographometer. J Med Assoc Thai. 2006;89:992-6.). In patients in whom the diagnosis of CU is suspected, a "dimple" pattern noted in routine allergy evaluation with PST using the ComfortTenTM may be an important clue to the presence of dermatographic urticaria, the most frequently noted form of physical urticaria noted in CU, as this circumferential pattern of edema is unlikely to result from an IgE mediated skin test wheal. This also has implications in interpreting PST positivity.

Background: Patients with chronic urticaria infrequently have etiologic factors identified despite common laboratory testing. One non-specific gauge of inflammation, C-reactive protein(CRP), has not been routinely used to evaluate such patients. Objective: To describe a series of patients with recurrent urticaria and/or angioedema and who had elevated(>5 mg/L) Creactive protein levels. Methods: Adult patients seen a single office practice with recurrent urticaria and angioedema for a period 6 weeks or greater were identified. Those who had physician observed angioedema or urticaria, and who had an elevated C-reactive protein had their charts reviewed and cases summarized. Results: Eleven patients were identified for description. The highest CRP levels for each patients ranged from 5.4 to 23.2 mg/L, with a median of 12.6 mg/L. Most patients did not have correspondingly elevated erythrocyte sedimentation rates(ESR's), and there was no concordance between CRP levels and ESR's. Physical factors and thyroid auto-antibodies were noted in some patients. None of the elevated CRP levels were associated with a history of recent infection or overt comorbid inflammatory disease. The pattern of CRP levels appeared to have correspondence with disease activity in several patients. Conclusions: Modest elevations in C-reactive protein may be observed in some patients with recurrent urticaria and/or angioedema in the apparent absence of infectious or inflammatory comorbidities. It is conceivable that this reflects an acute phase reaction pattern in these patients due to their urticaria/angioedema disease process itself. Further studies are required to confirm if this is a prevalent phenomenon.

Introduction: Mepolizumab targets eosinophils in the treatment of asthma. The dose used for asthma is considerably lower than that used for treating eosinophilic granulomatosis with polyangiitis, a recently approved indication. While intravenous mepolizumab use has reported utility in non-asthma eosinophilic disorders, the efficacy of the subcutaneous asthma dosing of the drug for eosinophilic pneumonia is not known. Case study: A middle-aged female was diagnosed with eosinophilic pneumonia. The patient?s clinical/radiologic/laboratory findings, response to treatment, and respiratory function studies are described. Results: A woman, born in 1962, had repeated pneumonia hospitalizations from 2007 through 2010. In October 2010, a lung biopsy showed findings consistent with chronic eosinophilic pneumonia and chronic asthma. The patient also had chronic sinusitis. Long term systemic corticosteroids were prescribed but the patient became oxygen dependent by 2014. Omalizumab was administered for 1 year starting in 2015 without improvement in symptoms. In 2016, mepolizumab 100?mg subcutaneously every 4?weeks was initiated. Symptomatic improvement with decreased oxygen and systemic corticosteroid requirements were noted. A chest CT performed in February 2018 showed marked improvement compared to a study in 2016. Interval spirometric improvements were noted. Peripheral blood eosinophils/mm(3) prior to mepolizumab were 237, and while on mepolizumab were 10. Conclusion: Parenchymal eosinophilic lung disease may respond to asthma-dosed mepolizumab. Mepolizumab treatment in asthma where concomitant interstitial disease is suspected, may offer an advantage over omalizumab in the ability to reduce eosinophils not only in airways, but also in lung parenchyma.

Up to 5% of the US population has suffered anaphylaxis. Fatal outcome is rare, such that even for people with known venom or food allergy, fatal anaphylaxis constitutes less than 1% of total mortality risk. The incidence of fatal anaphylaxis has not increased in line with hospital admissions for anaphylaxis. Fatal drug anaphylaxis may be increasing, but rates of fatal anaphylaxis to venom and food are stable. Risk factors for fatal anaphylaxis vary according to cause. For fatal drug anaphylaxis, previous cardiovascular morbidity and older age are risk factors, with beta-lactam antibiotics, general anesthetic agents, and radiocontrast injections the commonest triggers. Fatal food anaphylaxis most commonly occurs during the second and third decades. Delayed epinephrine administration is a risk factor; common triggers are nuts, seafood, and in children, milk. For fatal venom anaphylaxis, risk factors include middle age, male sex, white race, cardiovascular disease, and possibly mastocytosis; insect triggers vary by region. Upright posture is a feature of fatal anaphylaxis to both food and venom. The rarity of fatal anaphylaxis and the significant quality of life impact of allergic conditions suggest that quality of life impairment should be a key consideration when making treatment decisions in patients at risk for anaphylaxis.

The effects of corticosteroid therapy on IgE levels in asthmatics without allergic bronchopulmonary aspergillosis (ABPA) has not been well described. IgE level reduction may be desirable when considering omalizumab treatment in asthmatics with very elevated IgE levels, as omalizumab treatment using clinically approved doses will not provide adequate IgE binding in these patients and insurers will typically not authorize reimbursement for this treatment. The clinical course of a patient with asthma is described with respect to IgE levels and treatment. A 74-year-old male presented with adult onset severe steroid-dependent asthma. He had an FEV1 of 27% predicted. His IgE was 1142 kU/L and allergen specific IgE was elevated for several aeroallergens but not for molds, including aspergillus fumigatus. There was no bronchiectasis. Eight years earlier, he had normal pulmonary function tests and his IgE level was 809 kU/L. He had prior sinus surgery for polyposis/chronic sinusitis. After 60 mg/day prednisone treatment for 10 days, an IgE level was 989 kU/L. After 20 mg/day prednisone treatment for 1 month, 1000 mg/day methylprednisolone was administered intravenously for 2 days. A repeat IgE level was 460 kU/L. Omalizumab was initiated. Two months later the patient had discontinued prednisone and his FEV1 was 63% predicted. Even in the absence of effects from high dose oral prednisone, pulse corticosteroid treatment can result in significant reductions in IgE in non-ABPA asthma, allowing for omalizumab treatment to be given under current clinical indications.

BACKGROUND:The impact of dementia on hospitalization discharge dispositions (HDDs) in the United States has not been quantified, and dementia prevalence in various hospitalization categories has not been detailed in recent years.OBJECTIVE:To characterize hospitalizations prevalent with dementia, and to examine the relationship between dementia and HDDs.DESIGN:A retrospective cross-sectional study.SETTING:2000 to 2012 National Inpatient Sample databases.PATIENTS:Hospitalizations in persons ≥65 years old assigned to 1 of 12 Diagnosis Related Groups (DRGs) with a high number of dementia patients.INTERVENTION:None.MEASUREMENTS:The databases were queried for 12 DRGs (versions 18/24). Predictor effects for dementia on HDD categories were modeled adjusting for other defined comorbidities/covariates using logistic regression. Adjusted predictor effects of dementia on HDD in the DRG groupings were determined. Dementia prevalence and trends were assessed.RESULTS:Increasing proportions of dementia were noted in 4 DRGs studied. Dementia was strongly associated with being discharged to a nonhome setting. The most marked dementia effects were noted in DRGs 174 (gastrointestinal hemorrhage), 88 (chronic obstructive pulmonary disease), 182 (esophagitis/gastroenteritis), 138 (cardiac arrhythmias), 127 (congestive heart failure), and 89 (simple pneumonia and pleurisy), where there was at least a 76% reduction in the adjusted odds ratio (0.18-0.24) for home discharge. In contrast, DRGs 14 (stroke), 79 (respiratory infections/ inflammations), and 320 (kidney/urinary infections) had a smaller reduction in dementia-associated adjusted odds ratio (0.41-0.46) for home discharge. DRGs 79 and 320 had the highest proportions of dementia (>10%).CONCLUSIONS:Dementia proportions in many hospitalization categories have increased. The variable effect of dementia on home discharge suggests that dementia has a differential influence on hospital discharge disposition depending on the DRG. These findings have implications for healthcare allocation and long-term care planning.

Background: Anaphylaxis-related deaths in the United States have not been well characterized in recent years.Objectives: We sought to define epidemiologic features and time trends of fatal anaphylaxis in the United States from 1999 to 2010.Methods: Anaphylaxis-related deaths were identified by using the 10th clinical modification of the International Classification of Diseases system diagnostic codes on death certificates from the US National Mortality Database. Rates were calculated by using census population estimates.Results: There were a total of 2458 anaphylaxis-related deaths in the United States from 1999 to 2010. Medications were the most common cause (58.8%), followed by "unspecified" (19.3%), venom (15.2%), and food (6.7%). There was a significant increase in fatal drug-induced anaphylaxis over 12 years: from 0.27 (95% CI, 0.23-0.30) per million in 1999 to 2001 to 0.51 (95% CI, 0.47-0.56) per million in 2008 to 2010 (P < .001). Fatal anaphylaxis caused by medications, food, and unspecified allergens was significantly associated with African American race and older age (P <. 001). Fatal anaphylaxis to venom was significantly associated with white race, older age, and male sex (P < .001). The rates of fatal anaphylaxis to foods in male African American subjects increased from 0.06 (95% CI, 0.01-0.17) per million in 1999 to 2001 to 0.21 (95% CI, 0.11-0.37) per million in 2008 to 2010 (P < .001). The rates of unspecified fatal anaphylaxis decreased over time from 0.30 (95% CI, 0.26-0.34) per million in 1999 to 2001 to 0.09 (95% CI, 0.07-0.11) per million in 2008 to 2010 (P < .001).Conclusion: There are strong and disparate associations between race and specific classes of anaphylaxis-related mortality in the United States. The increase in medication-related deaths caused by anaphylaxis likely relates to increased medication and radiocontrast use, enhanced diagnosis, and coding changes.

Since angiotensin-converting enzyme (ACE) inhibitors became common treatments, there have been increasing reports of angioedema (AE). AE hospitalization (AEH) trend data in the new millennium are limited. This study calculates hospitalization rates for AEs and describes clinical characteristics of AEHs in the United States, especially as related to specific adverse drug effects (ADEs). The National Inpatient Samples 2000-2009 were queried for AEHs to calculate hospitalization rates and to examine for associations with specified ADEs, certain comorbidities, and demographic features. AEHs requiring intubation or tracheostomy were also examined for associations. There was a significant increase in the AEH rates (3.4 per 10(5) to 5.4 per 10(5)) over the study period (p < 0.0001) and the hospitalization rates for African Americans (AAs) were consistently higher. Throughout the study the proportions of AEH coding any ADEs, or an ADE due to a cardiovascular (CV) or antihypertensive (aHTN) drug increased over time. By 2009, 61.7% AEHs coded an ADE. Of these, 58.7% were caused by CV or aHTN drugs. In AEHs, having an ADE from a CV or aHTN medication had the strongest adjusted associations with hypertension and renal disease as well as with alcohol-related disorders. In AEHs, intubation/tracheostomy had the strongest ADE associations related to CV or aHTN medication (adjusted odds ratio, 1.4; 95% CI, 1.3, 1.6). AEHs continue to increase, but this can only be partially attributed to ACE inhibitor usage. Intubation/tracheostomy appears to be greater in AEHs with ADE due to CV/aHTN drugs. Alcohol-related disorders may have a role in ACE inhibitor-associated AEH.

Angiocardiography hospitalizations (n=1,971,571) in New York State were examined for adverse drug effects between 1996 and 2010 focusing particularly on radiocontrast material (RCM) related hypersensitivity manifestations. Using the E code E947.8 (adverse drug effect from radiocontrast) and coding for other anaphylaxis (ICD9 995.0), allergic urticarial (ICD9 708.0), angioedema (ICD9 995.1), laryngospasm (ICD9 478.6) or laryngeal edema (ICD9 478.75) , an overall immediate hypersensitivity rate of 16.04x10-5 was found. Logistic regression modeling found that these immediate hypersensitivity manifestations were most strongly predicted by coding for E947.8 (odds ratio 501: 95%CI 433-580) followed by adverse coding to anti-infective, analgesic/anti-rheumatic, anti hypertension or cardiovascular drugs(odds ratio of any of these 84.91: 95% CI 69-104). There was an overall increase in the proportion of hospitalizations coding for these immediate hypersensitivity manifestations over the study period(binomial regression for time effect p<0.0001). Multivariate modeling showed not only a year effect but also a significant predictor effect from younger age, longer length of stay and female gender. Although a history of allergy to food, insect, latex, RCM or other substances were also multivariate predictors, asthma was not. Over a period of time when non-ionic RCM has predominated, the inpatient rate of RCM associated immediate hypersensitivity reactions associated with cardiac angiography has continued to exceed the combined rate of other common drug associated immediate hypersensitivity reactions, overall by more than 2 fold.

Anaphylaxis is an acute, potentially life-threatening event. The treatment of choice is epinephrine. In patients with coronary artery disease, the adrenergic effects of such treatment have the potential for increasing myocardial demand in the face of limited blood flow, with acute ischemic consequences. We describe a patient who, after anaphylaxis treatment, developed an acute coronary arterial thrombus, which is an uncommon complication of anaphylaxis/anaphylaxis treatment. Possible pathophysiologic mechanisms and clinical questions that bear on this case are discussed.

Since the 1999 US Food and Drug Administration (FDA) warning of renal failure/dysfunction associated with intravenous gammaglobulin (IVIg), there has been a movement towards developing safer, more convenient formulations. Until now, the scope of renal failure associated with IVIg, has not been well described. The FDA Adverse Event Reporting System (AERS) from 2004 through 2009 was examined for renal impairment reactions due to IVIg and associated demographic features, comorbidities and indications. Anaphylaxis cases associated with IVIg administration were used as a comparison group. There were 90 renal impairment cases associated with IVIg administration. Neuromuscular disorders (33/37%) and hematologic disorders (32/36%) were the predominant treatment indications. When reported anaphylaxis versus renal impairment due to IVIg was examined as a binary outcome in logistic regression modeling, renal impairment was predicted by sucrose presence, increasing age and non-hypogammaglobulinemic indications. Of the 34 hemodialysis cases, the excipient was known in 28 and all but 1 consisted of sucrose. IVIg containing sucrose was used in 33 of 48 nonhemodialysis cases. More hemodialysis cases also had diabetes mellitus. When the interval between renal impairment and the first IVIg infusion was determined, the renal impairment was reported by the second day in 43.3% of cases, and between 3 and 5 days in 41.7% of cases. Despite an evolution in clinical usage and formulations, renal impairment after IVIg administration continues to be reported. Sucrose as the excipient in IVIg plays a major role, but other factors are also important. These findings have implications in the management of patients treated with IVIg.

Anaphylaxis incidence rates and time trends in the United States have been reported using different data sources and selection methods. Larger studies using diagnostic coding have inherent limitations in sensitivity and specificity. In contrast, smaller studies using chart reviews, including reports from single institutions, have better case characterization but suffer from reduced external validity due to their restricted nature. Increasing anaphylaxis hospitalization rates since the 1990s have been reported abroad. However, we report no significant overall increase in the United States. There have been several reports of increasing anaphylaxis rates in northern populations in the United States, especially in younger people, lending support to the suggestion that higher anaphylaxis rates occur at higher latitudes. We analyzed anaphylaxis hospitalization rates in comparably sized northern (New York) and southern (Florida) states and found significant time trend differences based on age. This suggests that the relationship of latitude to anaphylaxis incidence is complex.

Background. The ability to assess adequate reductions in immunoglobulin E (IgE) in allergic bronchopulmonary aspergillosis (ABPA) has been a concern with regards to omalizumab treatment. Objective. To describe the clinical course and serial measured IgE levels in two adult patients with elevated IgE levels, hypersensitivity to Aspergillus fumigatus, and bilateral bronchiectasis who were treated with omalizumab. Clinical Descriptions. Patient 1 met commonly used critieria for ABPA and had a more than 3-fold increase (from 702 to 2462 IU/ml) in measured IgE 4 months after starting omalizumab. Two years after starting omalizumab, the IgE level decreased to baseline (473 IU/ml) even when corticosteroids were discontinued. Patient 2 had near normalization of elevated IgE levels when treated with corticosteroids but IgE levels subsequently rose again to over 10,000 IU/ml. After reducing the IgE level to 586 IU/ml with higher corticosteroid doses, omalizumab was initiated. Twenty months after starting omalizumab, the measured IgE was 510 IU/ml. Based on published omalizumab treatment-associated total/free IgE ratios, the estimated free IgE levels for both patients after more than a year of omalizumab treatment was less than their pre-omalizumab treatment IgE levels. Conclusions. These data suggest that omalizumab can be beneficial in treating ABPA and that measured IgE levels can still be useful in this context. Noting the pattern of IgE levels associated with ABPA exacerbations and with corticosteroid treatment may help both with achieving an IgE level appropriate for omalizumab treatment and with the interpretation of measured IgE changes associated with omalizumab treatment.