Peter A. Ricketti

Investigational new drugs for allergic rhinitis

ABSTRACT Introduction: Allergic rhinitis (AR) is a multifactorial disease characterized by paroxysmal symptoms of sneezing, rhinorrhea, postnasal drip and nasal congestion. For over a century, subcutaneous allergen immunotherapy (SCIT) has been recognized as the most effective therapy to date that may modify the underlying disease course and provide long-term benefits for individuals refractory to pharmacotherapy. However, over the past 25 years, there has been substantial growth in developing alternative therapies to traditional SCIT. Areas covered: This article will review the most current literature focusing on advancements of AR therapies. Novel AR therapies that are currently under investigation include: the addition of omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody (mAb), to SCIT; altering the method of delivery of allergen immunotherapy (AIT) including sublingual (SLIT), epicutaneous (EIT), intralymphatic (ILIT), intranasal (INIT) and oral mucosal immunotherapy (OMIT); use of capsaicin spray; novel H3 and H4 antihistamines; activation of the innate immune system through Toll-like receptor agonists; and the use of chemically altered allergens, allergoids, recombinant allergens and relevant T-cell epitope peptides to improve the efficacy and safety of AIT. Expert opinion: These promising novel therapies may offer more effective and/or safer treatment options for AR patients, and in some instances, induce immunologic tolerance.

Central serous chorioretinopathy secondary to corticosteroids in patients with atopic disease.

Central serous chorioretinopathy (CSCR) is of unknown etiology and is the most common cause of retinopathy after age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion. Vision loss results from fluid leakage and serous detachment in the macula. Five percent of patients develop chronic CSCR. It is predominantly found in middle-aged men (age-adjusted rates per 100,000: 9.9 for men and 1.7 for women) and is usually unilateral and reversible. Three-quarters of CSCR patients resolve within 3 months but 45% have recurrences, usually with only minor visual acuity changes. Risk factors include type A personality, emotional stress, elevated catecholamines, hypertension, pregnancy, organ transplantation, increased levels of endogenous cortisol, psychopharmacologic medication, use of phosphodiesterase 5 inhibitors, obstructive sleep apnea, Helicobacter pylori infection, or treatment with corticosteroids. Five percent of patients develop chronic disease as a result of subretinal fibrin formation within the blister. CSCR is often bilateral, multifocal, and recurrent, and may be associated with subretinal fibrin formation within the blister. Permanent loss of vision may result from subretinal fibrin-fibrosis with scarring of the macula. Corticosteroid-associated CSCR occurs bilaterally in 20% of patients. Steroid-associated therapy may begin days to years after therapy with any form of drug delivery. We present three atopic patients who presented at various times after oral, inhaled, intranasal, and topical corticosteroid therapy. One patient developed CSCR after three separate types of administration of corticosteroids, which, to our knowledge, has not been observed in the literature.

Emerging Biomarkers and Therapeutic Pipelines for Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU) is defined as the appearance of evanescent wheals, angioedema, or both, for at least 6 weeks. CSU is associated with intense pruritus and poor quality of life, with higher odds of reporting depression, anxiety, and sleep difficulty. As of yet, the assessment of the activity and course of the disease along with the response to several treatments in CSU are based purely on the patients medical history and the use of the patient-reported outcomes. Recently, several reports have suggested that certain parameters could be considered as potential disease-related biomarkers. Moreover, with the advent of such biomarkers, newer biologic agents are coming forth to revolutionize the management of potential refractory diseases such as CSU. The purpose of this article is to review the most promising biomarkers related to important aspects of CSU, such as the disease activity, the therapeutic response, and the natural history of the disease, and discuss the mechanisms of action and therapeutic effectiveness of the latest agents available or currently under investigation for the management of antihistamine-refractory CSU. The knowledge of these features could have an important impact on the management and follow-up of patients with CSU.

A 41-year-old male with cough, wheeze, and dyspnea poorly responsive to asthma therapy.

Reactive airway disease is often triggered by an upper respiratory viral infection and readily responds to anti-inflammatory and bronchodilator therapy. The differential diagnosis for unresponsive disease includes poorly controlled asthma, noncompliance with medical regimen, vocal cord dysfunction, rhinosinusitis, gastroesophageal reflux disease or recurrent aspiration, foreign body aspiration, allergic bronchopulmonary aspergillosis, Churg-Strauss vasculitis, cardiac disorders such as congestive heart failure or mitral stenosis, or other pulmonary disorders such as chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, interstitial lung disease, bronchiectasis, sarcoidosis, hypersensitivity pneumonitis, pulmonary embolism, cystic fibrosis, airway neoplasms, or laryngotracheomalacia. As is often the case, a meticulous history can expeditiously direct the clinician to the diagnosis, especially in a patient without a smoking, asthmatic, or atopic history.

Honeybee Venom Allergy in Beekeepers

Honeybees, members of the order Hymenoptera, are a major cause of systemic allergic reactions (SARs) including anaphylaxis. In certain occupations, such as beekeeping, the risk of a SAR is higher than in the general population. Beekeepers and their family members are regularly exposed to honeybee stings making them a unique population to study Hymenoptera hypersensitivity. Therefore, beekeepers and their family members need information about how to avoid stings and differentiate a local reaction from a SAR. They also need information about how and when to use an epinephrine autoinjector for a SAR and when honeybee venom immunotherapy (VIT) is indicated to prevent future SARs. For beekeepers and their family members, VIT should be given indefinitely. Once VIT maintenance is achieved, multiple monthly bee stings or optimal maintenance VIT should be continued. Alternative employment should be considered when VIT is not effective.

Case study: Idiopathic hemothorax in a patient with status asthmaticus

Abstract Introduction: Idiopathic spontaneous hemothorax has been rarely described in the literature. Case Study: A case of status asthmaticus and spontaneous hemothorax is described in a 29-year-old female of African descent who presented to the emergency room after 2 days of severe cough productive of yellow sputum, otalgia, sore throat, subjective fevers, chills, headache, progressive wheezing, chest tightness and dyspnea. She had a history of 7 years of asthma and was non-adherent with her controller asthma medications. Prophylactic subcutaneous administration of enoxaparin 40 milligrams was initiated upon hospitalization. The patient initially had a normal chest radiograph but subsequently developed a large, left hemothorax that required tube thoracostomy placement followed by video-assisted thoracoscopic surgery (VATS). Results: The patient was transferred to the Intensive Care Unit (ICU) and tube thoracostomy resulted in evacuation of 1,400 milliliters of blood-like fluid, which had a pleural fluid hematocrit greater than 50% of the serum hematocrit. A contrast-enhanced computed tomography (CT) scan of the chest did not reveal any source for the bleeding and a technetium bone scan of the chest was normal. The patient required transfusion of 5 units of packed red blood cells. She was then taken to the operating room for VATS because of continued chest tube drainage (3,200 milliliters of fluid over a 48-hour period). Conclusion: The etiology of the hemothorax was unknown despite surgical exploration but was felt to be secondary to cough and bronchospasm associated with status asthmaticus.

A 15-year old girl with asthma and lower lobe bronchiectasis.

Wet cough, wheeze, and sputum in an adolescent with evidence for bronchiectasis is an uncommon presentation. The differential diagnosis includes cystic fibrosis (CF), immunodeficiency disorders, complement deficiency, allergic bronchopulmonary aspergillosis, alpha-1 antitrypsin disease, repeated aspiration pneumonia, foreign body, bronchial carcinoid, unresolved right middle lobe pneumonia, and primary ciliary dyskinesia (PCD). The likely diagnosis proceeds from the more to less common in patients with these symptoms. The location of disease on computed tomography scanning, nasal and bronchial exhaled nitric oxide, identification of ultrastructural defects on electron microscopy, and specific genetic mutation help separate CF and PCD. Although differentiating these conditions is vital, the chronic management of the bronchiectasis usually includes clearance mechanisms, bronchodilators, regular exercise, appropriate vaccinations, and judicious antibiotics for airway infections.

Anaphylaxis following cilantro ingestion

period, significant decreases in tree nutespecific IgE might be seen. Future studies will need to incorporate entry challenges to tree nuts, periodic challenges while on therapy, and long-term follow-up. Avoidance of the allergenic food and treatment of a reaction with auto-injectable epinephrine is still considered the standard therapy for food allergy.7 As new treatment options emerge, clinicians must be mindful of the implications of each treatment for the multi-food-allergic person. The data from this report do not support the notion that cross-reactive allergens may be treated with peanut OIT. Regardless of the modality of therapy used, if the therapy is only allergen-specific, the benefit of protection against 1 allergen while remaining allergic to other allergens must be considered. Tree nuteallergic individuals receiving peanut OIT should continue strict avoidance of tree nuts and should carry selfinjectable epinephrine in case of accidental ingestion.

A 55-year-old man with severe persistent asthma poorly responsive to asthma therapy.

Asthma is often triggered by allergic and nonallergic factors in atopic individuals and readily responds to anti-inflammatory and bronchodilator therapy. The differential diagnosis for poorly responsive disease includes severe persistent asthma with associated allergic rhinitis, cardiac disorders such as left ventricular failure or mitral stenosis, vocal cord dysfunction, gastroesophageal reflux disease, recurrent aspiration, chronic obstructive pulmonary disease, emphysema, alpha-1-antitrypsin deficiency, sarcoidosis, hypersensitivity pneumonitis, bronchiectasis, allergic bronchopulmonary aspergillosis, airway neoplasm, and Churg-Strauss vasculitis. A careful history and physical in conjunction with appropriate screening of laboratory information will usually direct the clinician to the correct diagnosis.