Sunit Jariwala

The role of vitamin D in the immunopathogenesis of allergic skin diseases

To cite this article: Benson AA, Toh JA, Vernon N, Jariwala SP. The role of vitamin D in the immunopathogenesis of allergic skin diseases. Allergy 2012; 67: 296–301.

The role of dendritic cells in the immunopathogenesis of psoriasis

Psoriasis vulgaris is a chronic inflammatory skin disease that is marked by a complex interplay of dendritic cells (DCs), T-cells, cytokines, and downstream transcription factors as part of a self-sustaining type 1 cytokine network. As integral players of the immune system, DCs represent antigen-presenting cells that are crucial for efficient activation of T-cells and B-cells. DCs have also been linked to distinct chronic inflammatory conditions, including psoriasis. In the setting of psoriasis therapy, DC/T cell interactions serve as a potential target for biologic response modifiers. Here we describe the major DC subsets as well as the immunologic involvement of DCs within the context of psoriatic lesions.

The role of thymic stromal lymphopoietin in the immunopathogenesis of atopic dermatitis.

Atopic dermatitis (AD), a skin disease characterized by pruritus and chronic inflammation, results from a complex interplay between environmental and genetic factors. Thymic stromal lymphopoietin (TSLP), an IL‐7‐like cytokine, is believed to propagate AD lesions through T helper 2 (Th2) polarization. This paper describes the immunologic mechanisms involving TSLP in the generation of allergic disease. Specifically in AD, TSLP has been shown to be an inducer of myeloid dendritic cells, Th2 responses, mast cells, and natural killer T cells, thereby leading to cytokine secretion and the development of AD. We hope that further understanding of the TSLP pathway and its role in the pathogenesis of AD will lead to improved clinical management of AD in the future.

Association between tree pollen counts and asthma ED visits in a high-density urban center.

Background. Asthma exacerbation patterns are cyclic in nature and often correlate with air particle concentrations. Objective. To examine the relationship between asthma-related emergency department (ED) visits and outdoor air quality for pediatric and adult patients in a high asthma prevalence area, the New York City borough of the Bronx. Methods. Numbers of daily asthma-related adult and pediatric ED visits during one complete year (1999) were obtained from the seven major Bronx hospitals. Daily values of nitrogen oxides (NOx), ozone (O3), sulfur dioxide (SO2), and pollen counts were acquired. Results. Asthma-related ED visit numbers were highest in December–January and lowest in July. There were three distinct peaks of increased asthma ED visits: winter (December–January), spring (late April–May), and fall (October). The spring peak was the most striking and coincided with high tree pollen counts (tree pollen: r = 0.90, p = .03). We observed a positive correlation between asthma ED visits in the winter and SO2 and NOx levels. Winter peaks of SO2 and NOx in early December appeared to precede the winter asthma peak. Conclusions. The spring asthma peak is closely associated with increased tree pollen counts, and the asthma increase at this time is likely due to allergic reactions to pollen. No significant associations could be established with the fall peak. The winter peak correlates with elevated SO2 and NOx levels.

Dichlorophenol-containing pesticides and allergies: results from the US National Health and Nutrition Examination Survey 2005-2006

BACKGROUND Epidemiologic studies support the hypothesis that reduced microbial exposure in westernized societies promotes atopy. Dichlorophenols are widely used as pesticides and for chlorination of water. They have a strong bactericidal effect that could affect microflora in the environment. However, it is unknown whether their use is associated with a higher prevalence of allergies. OBJECTIVE To test the association between exposure to environmental pesticides represented by dichlorophenols and allergic sensitization measured by allergen-specific serum IgE levels in a US nationally representative sample of 2,211 persons 6 years and older in the National Health and Nutrition Examination Survey 2005-2006. METHODS Exposure to dichlorophenols was defined as high if their levels in urine were present at the 75th percentile and above. Association of the high exposure to dichlorophenols with sensitization to food and environmental allergens was assessed in logistic regression models after adjustment for sample weights and potential confounders. RESULTS Sensitizations to 1 or more food allergens were more common in those with exposure to 2 dichlorophenol metabolites. After multivariable adjustment, urine dichlorophenol levels at the 75th percentile and above were associated with the presence of sensitization to foods (odds ratio, 1.8; 95% confidence interval, 1.2-2.5; P = .003). No significant association was found between dichlorophenol exposure and sensitization to aeroallergens alone. CONCLUSION High urine levels of dichlorophenols are associated with the presence of sensitization to foods in a US population. Excessive use of dichlorophenols may contribute to the increasing incidence of food allergies in westernized societies.

The association between asthma-related emergency department visits and pollen and mold spore concentrations in the Bronx, 2001–2008

Abstract Background: The incidence of asthma morbidity and mortality is highest among minority inner-city populations. Among New York City’s five boroughs, the Bronx has the highest rate of asthma-related hospitalizations and mortality. Outdoor air pollutants have been associated with increased asthma-related ED visits (AREDV) in this borough. Objective: To better understand the contribution of pollen and mold to asthma severity in the Bronx. Methods: The numbers of daily adult and pediatric AREDV and asthma-related hospitalizations (ARH) from 2001 to 2008 were obtained from two Bronx hospitals. AREDV and ARH data were acquired retrospectively through the Clinical Looking Glass data analysis software. Daily counts for tree, grass and weed pollen and mold spore counts from March 2001 to October 2008 were obtained from the Armonk counting station. All data were statistically analyzed and graphed as daily values. Results: There were a total of 42 065 AREDV and 10 132 ARH at both Bronx hospitals. There were spring and winter peaks of increased AREDV. Tree pollen counts significantly correlated with total AREDV (rho = 0.3639, p < 0.001), and pediatric (rho = 0.33, p < 0.001) and adult AREDV (rho = 0.28, p < 0.001). ARH positively correlated with tree pollen counts (Spearman rho = 0.2389, p < 0.001). Conclusions: There exists a significant association between spring AREDV and ARH and tree pollen concentrations in a highly urbanized area such as the Bronx. Early anticipation of spring pollen peaks based on ongoing surveillance could potentially guide clinical practice and minimize asthma-related ED visits in the Bronx.

Vitamin D and pulmonary function in obese asthmatic children.

Asthma‐related morbidity is higher among children with vitamin D deficiency and obesity, morbidities that frequently co‐exist among minority children. However, the effect of co‐existent obesity and vitamin D deficiency on pulmonary function is poorly understood.

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Successful Graded Dose Challenge to Iodixanol Radiocontrast Media in a Patient With Delayed Anaphylaxis to Iohexol

We present a case of an 82-year-old male with known radiocontrast media (RCM) hypersensitivity who was admitted to our hospital with gangrene of his right toe. The plan for revascularization of his lower extremity required an angiogram. This presented a management challenge as the patient had experienced 2 episodes of delayed anaphylaxis to Omnipaque (iohexol) RCM, and based on a literature review, there was no known or established precedent on a safe procedure in these situations. The patient was premedicated and given a graded dose challenge of an alternative RCM (iodixanol) prior to the radiographic study. He was given 1% of the total expected dose 1 hour before to the procedure and an additional 10% for the 30 minutes prior. He was then given the final dose in the operating room. Following angiogram, the patient was monitored for 18 hours in the postanesthesia care unit, with no adverse reactions. He was placed on a prednisone taper for 1 week, with daily diphenhydramine. The patient remained asymptomatic throughout the hospital course. This novel approach to RCM hypersensitivity management lends itself to a hope that graded dose challenges may play a greater role in the management of these patients.

Severe Angioedema Associated With Angiotensin‐Converting Enzyme Inhibitor Therapy in Two Patients With Pollen‐Food Allergy Syndrome

Angiotensin-converting enzyme (ACE) inhibitor therapy can be associated with bradykinin-mediated angioedema, which may occur at any time during the course of therapy. Pollen-food allergy syndrome (PFAS) represents an immunoglobulin E (IgE)–mediated hypersensitivity reaction recognized in patients with birch pollen allergy and is characterized by mouth and throat itching following the ingestion of certain fruits, nuts, and vegetables. PFAS occurs as a result of the structural homology between major allergens from certain fruits and the birch pollen major allergen Bet v 1. In rare cases, PFAS may present with angioedema and/or anaphylaxis. We present the first report of two cases of severe PFAS in patients with concomitant use of ACE inhibitor therapy. Patient 1 was a 65-year-old man with history of hypertension (taking lisinopril 10 mg daily for the previous 10 years) and seasonal allergic rhinoconjunctivitis who experienced two episodes (1 week apart) of tongue and lip angioedema and mouth itching within 10 minutes after apple consumption. During the second episode, he required treatment with epinephrine, corticosteroids, and antihistamine. Laboratory testing demonstrated increased serum-specific IgE levels to apple (3.01 kU/L; class 2) and birch (47.70 kU/L; class 4) and normal serum levels of C1-esterase inhibitor and eosinophils. Given the high suspicion for severe PFAS in the setting of ACE inhibitor therapy, lisinopril was changed to losartan. Three years after this event, no further episodes of angioedema have occurred. Patient 2 was a 45-year-old man with a history of hypertension (taking lisinopril 10 mg daily for the previous year) and seasonal allergic rhinoconjunctivitis who developed three episodes of tongue angioedema and mouth itching within several minutes after the ingestion of jackfruit and cashew nuts. The third episode required treatment with oral prednisone and antihistamine. Laboratory testing demonstrated increased serum levels of birch-specific IgE (8.19 kU/L; class 3), normal serum levels of specific IgE levels to jackfruit (0.13 kU/L; class 0), and C1-esterase inhibitor and eosinophils. Severe PFAS in the setting of concurrent ACE inhibitor therapy was suspected and lisinopril was changed to losartan. No further episodes of angioedema have occurred within 1 year after the ACE inhibitor was changed (Table). ACE inhibitor–related angioedema is bradykininmediated and is distinguished from IgE-mediated angioedema by a slower onset of action, longer duration, lack of urticaria/pruritus, and failure to respond to antihistamines, corticosteroids, or epinephrine. However, our patients most likely did not experience typical bradykinin-induced angioedema, despite being on ACE inhibitor therapy, but rather an IgE-mediated reaction for the following reasons. Both patients were sensitized to birch pollen and developed oral symptoms within minutes after ingestion of foods containing allergens homologous to birch Bet v 1, thereby suggesting a diagnosis of severe PFAS. Moreover, the symptoms responded promptly to the administration of epinephrine, antihistamine, and corticosteroids. Data from in vitro studies demonstrate that a bradykinin analog was a potent inducer of skin mast cell histamine release. Therefore, we believe that the concomitant ACE inhibitor therapy may have been responsible for the severe clinical symptoms. The usual PFAS treatment involves avoiding the raw forms of culprit foods. Developing severe PFAS in the