KAAACI Allergic Rhinitis Guidelines: Part 2. Update in nonpharmacotherapy

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and nonmedical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the “KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy” in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on nonpharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

An unexpected association between the blood bilirubin level and eosinophil count

Purpose@#Little is known about blood markers related to eosinophils in healthy individuals. We aimed to identify blood markers from routine tests associated with blood eosinophil count (BEC) in healthy individuals. @*Methods@#Based on the complex interactions among blood markers, we used comprehensive analysis methods (regression, Bayesian network [BN], and partial correlation) and a health check-up database. To test consistency, we repeated the analysis using data from 3 check-ups of the same healthy individual. @*Results@#A total of 12,625 individuals were enrolled in this study. Four groups were defined according to sex and smoking status: nonsmoking men (n=1,737), smoking men (n=6,518), nonsmoking women (n=3,995), and smoking women (n=375). The blood bilirubin and γ-glutamyltransferase levels showed significant associations with BEC by regression analysis. However, BN analysis found that only the bilirubin node was directly connected to the BEC node. By partial correlation analysis, the blood bilirubin level showed significantly negative association with BEC. The same results were obtained across all the 3 health check-ups, except in smoking women. In addition, a lower blood bilirubin level predicted a significantly elevated BEC (especially ≥200/µL). The blood bilirubin levels measured at 3 time-points were significantly associated with BEC in men and nonsmoking women. @*Conclusion@#The blood bilirubin level, which is easily obtained by routine test in clinical practice, may be a useful marker for BEC.

Oxygen Therapy in Cluster Headache, Migraine, and Other Headache Disorders

Oxygen therapy (OT) can relieve head pain in certain primary headache disorders, including cluster headache (CH). The exact underlying mechanism is currently uncertain, but suggested mechanisms include inhibition of the trigeminoautonomic reflex, modulation of neurotransmitters, and cerebral vasoconstriction. OT is the standard for acute treatment of CH, but patients with CH often experience considerable difficulties accessing home OT due to problems with insurance coverage. Inhalation of 100% oxygen at 6–12 L/min for 15–30 min using a non-rebreather face mask is one of the most effective acute therapies for CH, but several trials have indicated the superiority of higher oxygen flow rates of up to 15 L/min and/or using a demand-valve oxygen mask that can produce very high flow rates. Two randomized controlled trials have demonstrated the efficacy of OT in migraine, but obtaining reliable evidence is considered difficult because of different inhalation protocols, varying outcome measures, and small samples. There are some reports on the efficacy of OT as an adjuvant therapy in hypnic headache, primary headache in the emergency department, and even postdural puncture headache. The goal of this review article is to expand the knowledge regarding the use of oxygen in the treatment of headache disorders.

Analysis of Adverse Drug Reactions to First-Line Anti-Tuberculosis Drugs Using the Korea Adverse Event Reporting System

Background@#Adverse drug reactions (ADRs) to first-line anti-tuberculosis (TB) drugs are common; however, there have been few reports of nationwide epidemiologic studies on ADRs to anti-TB drugs in Korea. This study aimed to investigate the clinical characteristics of various ADRs to first-line anti-TB drugs using a nationwide database of ADRs. @*Methods@#We used the Korea Adverse Event Reporting System (KAERS) database (2009– 2018). The study subjects were selected using the Korean Standard Classification of Diseases codes for pulmonary and extrapulmonary TB and electronic data interchange codes for isoniazid (INH), rifampicin (RIF), ethambutol (ETB), and pyrazinamide (PZA). The causality assessment of “possible,” “probable,” or “certain” by World Health Organization-Uppsala Monitoring Center System causality category was selected. @*Results@#A total of 1,562,024 ADRs were reported in the KIDS-KAERS database from 2009 to 2018, where ADRs to first-line anti-TB drugs were 17,843 cases (1.14%). The most common causative drugs were RIF (28.7%), INH (24.0%), ETB (23.4%), and PZA (23.9%) in that order. 48.5% of cases were reported in the older patients (≥ 60 years). According to organ system, gastro-intestinal system disorder was most common (32.0%), followed by skin and appendage (25.9%), liver and biliary system (14.2%). Nausea was the most common ADR (14.6%), followed by hepatic enzyme elevation (14.2%), rash (11.7%), pruritus (9.1%), vomiting (8.9%), and urticaria (4.2%). Most ADRs appeared within 1 month, but ADRs such as neuropathy, paresthesia, hematologic abnormalities, renal function abnormalities and liver enzyme abnormality were also often reported after 2 months. @*Conclusion@#Our data are clinically informative for recognizing and coping with ADRs of antiTB drugs.

A case of rapid desensitization for rituximab-induced delayed hypersensitivity reaction

Rituximab is a monoclonal antibody used for the treatment of B-cell malignancies, including diffuse large B-cell lymphoma. Infusion-related hypersensitivity reactions to rituximab is well known, and delayed hypersensitivity reactions to rituximab are also reported. Desensitization is commonly used to prevent immediate hypersensitivity reactions, but recently there have been cases of successful desensitization therapy for delayed hypersensitivity reactions. A 66-year-old patient who underwent rituximab treatment for diffuse large B-cell lymphoma showed repeated rituximab-induced delayed hypersensitivity reactions with whole body rashes. Intravenous rapid desensitization was performed by using a 1-bottle, 11-step protocol for 6 cycles and thereafter hypersensitivity reaction did not recur. We herein reported a case of delayed hypersensitivity reaction caused by rituximab, which was successfully desensitized using our 11-step protocol.

Concurrent bilateral juvenile temporal arteritis and hypereosinophilic syndrome: a case report and review of the literature

Most of temporal arteritis occurs in the older patient over 50 years old, and the histopathologic finding shows a granulomatous inflammation, so this called giant cell arteritis. However, the young patients also present with a nodular lesion in their temple, and juvenile temporal arteritis (JTA) should be considered as one of the differential diagnosis, although it is very rare. For both diagnosis and treatment of JTA, excisional biopsy is essential. The pathologic finding of the temporal artery shows panarteritis with lymphoeosinophilic infiltrates, but no giant cell or granulomatous lesion. JTA is a localized disease with low level of systemic inflammatory marker, so the symptom is usually relieved by excision of affected lesion. Peripheral blood eosinophilia present in some cases of JTA, but its relation with clinical course and prognosis is not yet been known. Herein, we report the case of a 24-year-old man diagnosed with concurrent JTA and hypereosinophilic syndrome. We also reviewed the literature of JTA focusing on the impact of combined peripheral eosinophilia on the course of the disease. Combined peripheral eosinophilia may increase the risk of recurrence of JTA after local treatment such as excision only.

Changes in basophil activation during immunotherapy with house dust mite and mugwort in patients with allergic rhinitis

BACKGROUND: The basophil activation test (BAT) is a promising tool for monitoring allergen-specific immunotherapy responses. OBJECTIVE: We aimed to investigate the changes in basophil activation in response to the inhalant allergens of house dust mite (HDM) and mugwort pollen during immunotherapy in patients with allergic rhinitis. METHODS: We enrolled patients with allergic rhinitis who were to receive subcutaneous immunotherapy for the inhalant allergens HDM or mugwort. A BAT was performed to assess CD63 upregulation in response to allergen stimulation using peripheral blood collected from the patients prior to immunotherapy and at 3, 6, 12, and 24 months after beginning immunotherapy. Rhinitis symptoms were evaluated using the rhinitis quality of life questionnaire (RQLQ) at 1-year intervals. RESULTS: Seventeen patients (10 with HDM sensitivity, 3 with mugwort sensitivity, and 4 with sensitivity to both HDM and mugwort) were enrolled in the study. Basophil reactivity to HDM did not change significantly during 24 months of immunotherapy. However, a significant reduction in basophil reactivity to mugwort was observed at 24-month follow-up. There was no significant association between the change in clinical symptoms by RQLQ and the change in basophil reactivity to either allergen. The change in allergen-specific basophil reactivity to HDM was well correlated with the change in nonspecific basophil activation induced by anti-FcεRI antibody, although basophil reactivity to anti-FcεRI antibody was not significantly reduced during immunotherapy. CONCLUSION: Suppression of CD63 upregulation in the BAT was only observed with mugwort at 2-year follow-up. However, the basophil response did not reflect the clinical response to immunotherapy.

Bullous hemorrhagic dermatosis due to enoxaparin use in a bullous pemphigoid patient

Adverse reactions of subcutaneous low molecular weight heparin or unfractionated heparin could be complications by bleeding, heparin-induced thrombocytopenia, drug-induced liver injury, osteoporosis, and cutaneous reactions. Heparin-induced skin lesions vary from allergic reactions like erythema, urticaria, eczema to intradermal microvascular thrombosis associated with heparin-induced thrombocytopenia. There is a rare cutaneous complication, called bullous hemorrhagic dermatosis. We experienced this rare case of the cutaneous complication caused by enoxaparin. Several tense bullous hemorrhagic lesions occurred after 3 days of enoxaparin in a known bullous pemphigoid patient who had aortic valve replacement surgery with a mechanical prosthesis. The bullous hemorrhagic lesions were regressed after the discontinuation of enoxaparin but recurred after re-administration. The lesions were controlled by the administration of systemic corticosteroid and alternative anticoagulant. To date, less than 20 cases have been reported worldwide. This is the first case of bullous hemorrhagic dermatosis induced by enoxaparin, a low-molecular-weight heparin in Korea. This is also the first case of bullous hemorrhagic dermatosis in a known bullous pemphigoid patient.

Analysis of clinical characteristics of food-dependent exercise-induced anaphylaxis at a single tertiary hospital

PURPOSE: Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare subtype of food allergy in which both sensitization to food allergen and exercise as a trigger contribute to its development. However, its pathogenesis is still under investigation. This study compared clinical features, the causative foods, and the degree of sensitization to food between FDEIA and food anaphylaxis to characterize FDEIA more clearly. METHODS: We retrospectively reviewed the medical records of patients who were diagnosed with FDEIA (n=89) or food anaphylaxis (n=115) between 2003 and 2015 at Seoul National University Hospital. RESULTS: Subjects with FDEIA more frequently had urticaria than those with food anaphylaxis (88.8% vs. 76.5%, P=0.024). Whereas patients with FDEIA had less laryngeal edema than those with food anaphylaxis (12.4% vs. 30.4%, P=0.02). Wheat (67.4%) was the most common causative food allergen in FDEIA, whereas seafood (40.9%) was the most common culprit food allergen in food anaphylaxis. Also, subjects with FDEIA showed a lower atopic index score than those with food anaphylaxis (0.55±1.07 vs. 1.21±1.82, P=0.006). CONCLUSION: There were significant differences in clinical manifestation, causative food allergens and the degree of sensitization to food between FDEIA and food anaphylaxis.

Successful rapid desensitization for cetuximab-induced anaphylaxis

Cetuximab, a chimeric mouse-human immunoglobulin, is an antiepidermal growth factor receptor monoclonal antibody. It has been approved by the U.S. Food and Drug Administration for the treatment of metastatic colorectal and head/neck cancer, but can cause fatal hypersensitivity reactions in some patients. A 66-year-old male with metastatic sigmoid cancer had cetuximab-induced anaphylaxis when the first dose of cetuximab was administered. Cetuximab was safely readministered for another 15 cycles based on the rapid desensitization protocol. We experienced a case of cetuximab-induced anaphylaxis on the first exposure which was successfully managed by rapid desensitization.