D. Betty Lew

Airway Fluoroscopic Diagnosis of Vocal Cord Dysfunction Syndrome

BACKGROUND Vocal cord dysfunction syndrome is often misdiagnosed as refractory asthma. Airway fluoroscopy has recently been proposed as an alternative to laryngoscopy in the initial evaluation of certain cases of suspected vocal cord dysfunction. OBJECTIVE To evaluate the use of airway radiographs and fluoroscopy in a patient with suspected vocal cord dysfunction. METHODS We used soft tissue technique airway radiographs and fluoroscopy to evaluate the glottic function during inspiration and expiration in a 9-year-old boy with refractory asthma and suspected vocal cord dysfunction. RESULTS The study confirmed paradoxical vocal cord motion. CONCLUSIONS Airway radiographs and fluoroscopy provide a rapid and noninvasive means of diagnosing vocal cord dysfunction. Patients should still have laryngoscopy performed at the earliest possible moment to rule out the possibility of other laryngeal abnormalities.

Research Upregulation of CD23 (FcεRII) Expression in Human Airway Smooth Muscle Cells (huASMC) in Response to IL-4, GM-CSF, and IL-4/GM-CSF

BackgroundAirway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE.MethodsSerum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence.ResultsThe CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4), 15.6 ± 2.7% (GM-CSF) and 32.9 ± 13.9% (IL-4/GMCSF combination)(n = 3). The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc.ConclusionCD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue for new therapeutic options in asthma targeting ASMC.

Non-allergic rhinitis: a case report and review

Rhinitis is characterized by rhinorrhea, sneezing, nasal congestion, nasal itch and/or postnasal drip. Often the first step in arriving at a diagnosis is to exclude or diagnose sensitivity to inhalant allergens. Non-allergic rhinitis (NAR) comprises multiple distinct conditions that may even co-exist with allergic rhinitis (AR). They may differ in their presentation and treatment. As well, the pathogenesis of NAR is not clearly elucidated and likely varied. There are many conditions that can have similar presentations to NAR or AR, including nasal polyps, anatomical/mechanical factors, autoimmune diseases, metabolic conditions, genetic conditions and immunodeficiency. Here we present a case of a rare condition initially diagnosed and treated as typical allergic rhinitis vs. vasomotor rhinitis, but found to be something much more serious. This case illustrates the importance of maintaining an appropriate differential diagnosis for a complaint routinely seen as mundane. The case presentation is followed by a review of the potential causes and pathogenesis of NAR.

Cow's milk allergy in a patient with hyper-IgE syndrome

BACKGROUND Both hyper-IgE syndrome and food allergies can result in the early onset of skin rash, eosinophilia, and markedly elevated serum IgE. Occasionally, it can be difficult to distinguish the 2 disorders. Most patients with hyper-IgE syndrome do not have food allergy. OBJECTIVE To describe a child with cows milk allergy associated with hyper-IgE syndrome manifesting as failure to thrive (FTT). METHODS Epicutaneous skin prick test to cows milk, CAP radioallergosorbent test, atopy patch tests, and double-blind, placebo-controlled milk challenge (DBPCMC) were performed. RESULTS During initial presentation at 3 weeks of age, the circulating eosinophil count increased from 13,800/mm3 to 44,254/mm3 within 2 weeks while taking cephalexin. Despite treatment, he had worsening rash and FTT at 10 weeks of age with an IgE level of 8,454 U/mL. After changing from an infant milk formula with whey protein to an amino acid-based formula in combination with oral antibiotic treatment, his rash and growth velocity improved markedly within 2 months. IgE decreased to 2,747 U/mL. He remained clinically well for 12 months. He subsequently developed additional food and inhalant allergies with an increase in IgE to 12,150 U/mL. Cows milk allergy was confirmed by epicutaneous skin prick test, atopy patch test, and DBPCMC. CONCLUSIONS Traditional prophylactic antistaphylococcal antibiotics, in combination with Neocate formula, were effective in treating the early skin manifestations of hyper-IgE syndrome and FTT in this infant. Cows milk protein allergy should be considered in patients with hyper-IgE syndrome and FTT.

Evaluation of B Lymphocyte Deficiencies

The most common of the primary immunodeficiency diseases are those that involve inadequate antibody production. The characteristic presentation of these disorders is recurrent sinopulmonary infections. An arrest in B cell development at the pre-B cell stage leads to agammaglobulinemia and an insignificant number of B cells. X-linked agammaglobulinemia is the most common of these developmental arrests while the autosomal recessive agammaglobulinemias comprise a small minority of the total cases. Likewise, the most common form of the hyper-IgM syndromes (CD40 ligand deficiency) is X-linked. Of the autosomal recessive forms, CD40 deficiency is basically identical to the X-linked form in its clinical phenotype where, in addition to inadequate antibody production, there is defective T cell signaling through the CD40-CD40L interaction. Aside from CD40 deficiency, the other recessive forms of hyper-IgM syndrome have adequate T cell function. IgA deficiency is the most common and the most benign of the B cell disorders. Common variable immunodeficiency is diverse in its presentation and clinical course. The pathophysiology of this disease is multifactorial and frequently ill defined, often making it a diagnosis of exclusion. A working knowledge of identifiable PIDDs is essential in both recognizing when to suspect immunodeficiency and making a diagnosis.

A fatal presentation of dermatomyositis with facial swelling

Juvenile dermatomyositis (JDM) is the most common inflammatory autoimmune myopathy in children. Most common presentations consist of heliotrophic rash and/or gottrons papules in addition to proximal muscle weakness. A typical presentations have been reported. We present a 13-year-old African American male who presented with a two-week history of bilateral periorbital edema that was unresponsive to glucocorticoids. He had elevated transaminases but no detectable muscle weakness. A muscle biopsy was consistent with juvenile dermatomyositis. This case highlights the need to consider dermatomyositis in cases of facial swelling and the use of aggressive immunosuppressive therapies due to its associated vasculopathies.

Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models

One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM) remodeling effects. The mannose receptor (MR) family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR) and that mannan derived from Saccharomyces cerevisiae (SC-MN) inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2) expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

An Infant With Erythroderma, Skin Scaling, Chronic Emesis, and Intractable Diarrhea:

A 6-week-old Caucasian male was referred for evaluation of generalized pruritic rash, chronic emesis, and intractable diarrhea. He vomited after every feeding and had 5 to 6 loose stools per day. His symptoms did not improve after switching from cow milk formula to an extensively hydrolyzed formula. The family history obtained on admission was ‘‘negative for history of skin disease/eczema.’’ Physical examination showed an irritable infant with generalized erythroderma, severe skin scaling, purulent drainage from an ear canal, and crusted eyelids (Figure 1). His white blood cell count was 9900/mm, hemoglobin 8.3 mg/dL, and platelets 605 000/mm, with 31% neutrophils, 33% lymphocytes, 9% monocytes, and 27% eosinophils. The absolute eosinophil count was elevated at 3753 cells/mm. IgG and IgM were within normal limits, but IgE was elevated to 157 kU/L (normal range<17). Milk-specific IgE was not detected, but the infant’s diet was changed to an amino acid–based formula. Lymphocyte subset profile showed a normal percentage of T and B cells. Mitogen response tests were normal. He was diagnosed with otitis externa and started on intravenous broad-spectrum antibiotics. Eye culture grew methicillin-sensitive Staphylococcus aureus (MSSA), and ear culture grew Pseudomonas aeruginosa. Skin biopsy showed psoriasiform dermatitis. The differential diagnoses included severe seborrheic dermatitis, ichthyosis vulgaris, acrodermatitis enteropathica, hyper-IgE syndrome, and severe cow’s milk allergy. A more thorough family history was obtained (Figure 2), and the maternal grandmother reported that multiple males in her family had died in infancy because of dehydration, diarrhea, and ‘‘peeling skin.’’

A 9-year-old boy with chronic urticaria and progressive spondyloarthritis.

A 9-year-old African American boy presented with chronic urticaria and progressive spondyloarthritis. Laboratory tests were abnormal for persistently positive antinuclear antibodies and undetectable total hemolytic complement (CH50) despite normal levels of complement C2, C3, and C4. Ultimately, further testing revealed an underlying deficiency in the immune system that may be associated with autoimmune disease and thus have a bearing on the patients urticaria and spondyloarthritis. This is a unique presentation of a rare disease and underscores the importance of evaluating for systemic disease in the workup of chronic urticaria.

Saccharomyces cerevisiae-Derived Mannan Does Not Alter Immune Responses to Aspergillus Allergens

Severe asthma with fungal sensitization predominates in the population suffering from allergic asthma, to which there is no cure. While corticosteroids are the mainstay in current treatment, other means of controlling inflammation may be beneficial. Herein, we hypothesized that mannan from Saccharomyces cerevisiae would dampen the characteristics of fungal allergic asthma by altering the pulmonary immune responses. Using wild-type and transgenic mice expressing the human mannose receptor on smooth muscle cells, we explored the outcome of mannan administration during allergen exposure on the pathogenesis of fungal asthma through measurement of cardinal features of disease such as inflammation, goblet cell number, and airway hyperresponsiveness. Mannan treatment did not alter most hallmarks of allergic airways disease in wild-type mice. Transgenic mice treated with mannan during allergen exposure had an equivalent response to non-mannan-treated allergic mice except for a prominent granulocytic influx into airways and cytokine availability. Our studies suggest no role for mannan as an inflammatory regulator during fungal allergy.