OBJECTIVE: To investigate the changes of skin temperature, blood infusion and inflammatory cytokines of cutaneous tissue in the sensitized area of colitis model rats, as well as the relationship between sensory and sympathetic nerves and the formation of sensitized area, and to initially reveal the partial physical-chemical characteristics of the sensitized area in the colitis model rats. METHODS: Thirty-five male SD rats were randomly divided into a control group (n=10), a model group (n=18) and a guanethidine group (n=7). 5% dextran sulfate sodium (DSS) was adopted for 6-day free drinking to establish colitis model in the model group and the guanethidine group. On day 6 and 7, in the guanethidine group, guanethidine solution (30 mg/kg) was injected intraperitoneally for sympathetic block. On day 7, after injection of evans blue (EB) solution, the EB extravasation areas on the body surface were observed to investigate the distribution and physical-chemical characteristics of the sensitized area. The control area was set up, 0.5 cm away from the sensitized area, and with the same nerve segment innervation. Disease activity index (DAI) score of rats was compared between the normal group and the model group, and the morphological changes in the colon tissue were investigated with HE method. Using infrared thermal imaging technology and laser speckle flow imaging technology, skin temperature and blood infusion were determined in the sensitized area and the control area of the rats in the model group. Immunofluorescence technique was adopted to observe the expression levels of the positive nerve fibers of substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), and the correlation with blood vessels; as well as the expression levels of SP positive nerve fibers/tryptase⁺ mast cells, and tryptase⁺ mast cells/5-hydroxytryptamine (5-HT) in skin tissue in the sensitized area and the control area of the rats in the model group. MSD multi-level factorial method and ELISA were applied to determine the contents of pro-inflammatory and anti-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6, IL-4 and IL-10) and anti-inflammatory substance corticosterone (CORT). RESULTS: Sensitization occurred at the T₁₂-S₁ segments of the colitis model rats, especially at L₂-L₅ segments. Compared with the normal group, DAI score was increased in the rats of the model group (P<0.05), and the colonic mucosal damage was obvious, with the epithelial cells disordered, even disappeared, crypt destructed, submucosal edema and a large number of inflammatory cells infiltrated. In comparison with the control area, the skin temperature and blood infusion were increased in the sensitized area of the model group (P<0.05, P<0.01); as well as the expression levels of the positive nerve fibers of SP, CGRP and TH of skin tissue (P<0.05), which was specially distributed in peripheral vessels, the expression levels of SP positive nerve fibers/tryptase⁺ mast cells, and tryptase⁺ mast cells/5-HT of the skin tissue were all expanded (P<0.05) in the sensitized area of the model group. Compared with the model group, the number of sensitized areas was reduced in the guanethidine group (P<0.05). In comparison with the control area of the model group, in the sensitized area, the contents of pro-inflammatory cytokines, e.g. TNF-α, IL-1β and IL-6, and the anti-inflammatory substance CORT of skin tissue were all increased (P<0.05); and the contents of IL-6 and TNF-α were negatively correlated with CORT (P<0.05). CONCLUSION The sensitized areas on the body surface of colitis rats are mainly distributed in the L₂-L₅ segments. Sensory and sympathetic nerves are involved in the acupoint sensitization, and the sensitized areas may have the dynamic changes in pro-inflammatory and anti-inflammatory substances.
Animals ; Anti-Inflammatory Agents ; Calcitonin Gene-Related Peptide/metabolism* ; Colitis/metabolism* ; Cytokines/metabolism* ; Guanethidine ; Interleukin-6 ; Male ; Rats ; Rats, Sprague-Dawley ; Serotonin ; Skin Temperature ; Substance P/genetics* ; Tryptases ; Tumor Necrosis Factor-alpha

PURPOSE: Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults.METHODS: A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated.RESULTS: PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis.CONCLUSIONS: In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.
Adult ; Anaphylaxis ; Anxiety ; C-Reactive Protein ; Depression ; Hospitals, University ; Humans ; Hypersensitivity ; Interleukin-6 ; Korea ; Multivariate Analysis ; Necrosis ; Prevalence ; Prospective Studies ; Stress Disorders, Post-Traumatic ; Tryptases

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.
Anaphylaxis ; chemically induced ; diagnosis ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; toxicity ; Histamine ; blood ; Immunoglobulin E ; blood ; Injections, Intravenous ; Mice ; Shock ; chemically induced ; diagnosis ; Toxicity Tests ; Tryptases ; blood

BACKGROUND: Hydroxyethyl starch (HES), a class of synthetic colloid solutions, has been widely used to treat perioperative hypovolemia. The use of HES, however, is associated with the risk of allergic reactions.CASE: An 83-year-old man was scheduled to undergo an open reduction and internal fixation of a pertrochanteric fracture under spinal anesthesia. He had no history of allergy. Five minutes after HES administration, hypotension, agitation, and skin rash were developed. HES infusion was terminated due to a suspected anaphylactic reaction. The vital signs recovered following administration of phenylephrine, dexamethasone, and hydrocortisone. Serum tryptase and total immunoglobulin E levels were elevated in plasma samples collected following the commencement of the allergic reaction during surgery.CONCLUSIONS: In the present report, the risk of anaphylactic reaction with HES and the laboratory tests needed to support the diagnosis are highlighted.
Aged, 80 and over ; Anaphylaxis ; Anesthesia ; Anesthesia, Spinal ; Colloids ; Dexamethasone ; Diagnosis ; Dihydroergotamine ; Exanthema ; Humans ; Hydrocortisone ; Hypersensitivity ; Hypotension ; Hypovolemia ; Immunoglobulin E ; Immunoglobulins ; Phenylephrine ; Plasma ; Starch ; Tryptases ; Vital Signs

PURPOSE: We aimed to analyze the frequency of eosinophilia-associated diseases and to search for possible markers that may be useful for their differential diagnosis. METHODS: We retrospectively reviewed the medical records of 148 patients with peripheral blood eosinophil count of more than 500/µL who visited the Allergy Department of Chonnam National University Hospital for the first time from January to December 2016. Blood eosinophilia was categorized as mild (<1,500/µL), moderate (1,500–5,000/µL), and severe (>5,000/µL). RESULTS: Blood eosinophilia was mostly caused by allergic diseases (41.9%), parasitic infestation (23.6%), and drug allergy (19.6%). Eosinophil count was higher in patients with parasitic infestation (P<0.01), drug allergy (P<0.01), hypereosinophilic syndrome (HES, P<0.001), or eosinophilic granulomatosis with polyangiitis (EGPA, P<0.001) than in those with allergic diseases. The eosinophilic cationic protein level was higher in patients with HES than in those with allergic diseases (P<0.05) and parasitic infestation (P<0.05). The total IgE level was lower in patients with HES than in those with parasitic infestation (P<0.05) and EGPA (P<0.05). The vitamin B12 level was higher in patients with HES than in those with parasitic infestation (P<0.05). There was no statistically significant difference in tryptase levels between the groups. The most common cause of mild eosinophilia was allergic diseases (59.8%), followed by parasitic infestation (22.7%) and drug allergy (13.4%). The common causes of moderate eosinophilia were drug allergy (37.8%), parasitic infestation (29.7%), and allergic diseases (10.8%). The common causes of severe eosinophilia were EGPA (28.6%), HES (21.4%), parasitic infestation (14.3%), and drug allergy (14.3%). CONCLUSION: Common causes of blood eosinophilia in patients who visit the allergy department are allergic diseases, parasitic infestation, and drug allergy. Several markers, including eosinophil count, total IgE, and vitamin B12, may be useful for the differential diagnosis of eosinophilia-associated diseases.
Diagnosis, Differential ; Drug Hypersensitivity ; Eosinophilia ; Eosinophils ; Granulomatosis with Polyangiitis ; Humans ; Hypereosinophilic Syndrome ; Hypersensitivity ; Immunoglobulin E ; Jeollanam-do ; Medical Records ; Parasitic Diseases ; Retrospective Studies ; Tryptases ; Vitamin B 12

BACKGROUND/AIMS: The epidemiology and pathogenesis of eosinophilic esophagitis (EoE) remain unclear in Asian countries. We investigated clinicopathological characteristics and diagnostic trends of EoE, and evaluated 3 tissue biomarkers for correlation with disease activity and treatment response in Korean patients with EoE. METHODS: We retrospectively reviewed 25 271 esophageal biopsies performed during upper endoscopies between 2006 and 2017. We diagnosed EoE based on ≥ 15 eosinophils/high-power field (HPF) and, symptoms of esophageal dysfunction. We performed immunohistochemical analysis for tryptase, eosinophilic derived neurotoxin (EDN), and eotaxin-3. RESULTS: We diagnosed EoE in 72 patients (53 men and 19 women; mean age, 46.2 years) with presenting symptoms of, dysphagia (15.3%), epigastric pain (31.9%), and heartburn (30.6%). The diagnostic rate of EoE considerably increased between 2006 and 2017, from 0.29 diagnoses to 7.99 diagnoses per 1000 esophageal biopsies (P < 0.001). The mean peak eosinophil count (PEC) was 56.0 (± 77.8)/HPF. Whereas the EDN (rho = 0.667, P < 0.001) and eotaxin-3 levels (rho = 0.465, P < 0.001) correlated with PEC, tryptase and PEC were weakly correlated (rho = 0.291, P = 0.013). EDN (rho = 0.279, P = 0.017), and tryptase (rho = 0.279, P = 0.033) correlated with the inflammatory score of Eosinophilic Esophagitis Endoscopic Reference Score. Immunohistochemical analysis and changes in tryptase, EDN, and eotaxin-3 levels were associated with histologic and endoscopic improvements. CONCLUSIONS: EoE incidence considerably increased during the 12-year period, regardless of endoscopic esophageal biopsy rate. Tryptase, EDN, and eotaxin-3 levels in esophageal biopsy specimens could be promising biomarkers for disease activity, symptom, and endoscopic response in Korea.
Asian Continental Ancestry Group ; Biomarkers ; Biopsy ; Deglutition Disorders ; Diagnosis ; Endoscopy ; Eosinophilic Esophagitis ; Eosinophils ; Epidemiology ; Esophagus ; Female ; Heartburn ; Humans ; Incidence ; Korea ; Male ; Retrospective Studies ; Tryptases

BACKGROUND/AIMS: Postoperative ileus (POI) is characterized by impaired propulsive function of the gastrointestinal tract after surgery. Although inflammation is considered to be an important pathogenesis of POI, significant data are lacking. We aim to correlate the recovery time of postoperative dysmotility with that of inflammation and mucosal permeability. METHODS: An experimental POI model of guinea pig was used. Contractile activity of the circular muscle of the stomach, jejunum, ileum, and proximal colon was measured through a tissue bath study. Inflammatory cells were counted, and the expression of calprotectin and tryptase were analyzed. The expression of protease-activated receptor 2 (PAR-2), claudin-1, and claudin-2 were analyzed with immunofluorescence. RESULTS: The small bowel and colon showed decreased contractile amplitude in the POI groups compared to control. In contrast to the colon, the contractile amplitude of the small bowel significantly recovered in the POI group at 6 hours after the operation compared to the control group. Inflammation was highly significant in the POI groups compared to the control and sham groups, especially in the colon. Immunofluorescence showed increased PAR-2 expression in the POI groups compared to sham. The decreased claudin-1 expression and increased claudin-2 expression may suggest increased mucosal permeability of the small bowel and colon in the POI groups. CONCLUSIONS: Increased inflammation and mucosal permeability may play an important role in the differential recovery stages in POI. These data may provide further insights into the pathophysiology and potential new therapeutic prospects of POI.
Animals ; Baths ; Claudin-1 ; Claudin-2 ; Colon ; Fluorescent Antibody Technique ; Gastrointestinal Tract ; Guinea Pigs ; Guinea ; Ileum ; Ileus ; Inflammation ; Jejunum ; Leukocyte L1 Antigen Complex ; Permeability ; Receptor, PAR-2 ; Stomach ; Tryptases

Mastocytosis is a disorder characterized by abnormal mast cell proliferation and accumulation in one or more tissues. It presents in two major variants: cutaneous mastocytosis and systemic mastocytosis. Because the symptoms are related to mast cells, histamine receptor antagonists and leukotriene receptor antagonists are recommended as therapeutic options. Here, we report a 54-year-old male patient with a history of urticaria pigmentosa who presented with recurrent anaphylaxis. His serum tryptase level was 31.7 ng/mL and mast cell infiltration was observed in his bone marrow. He had frequent attacks of anaphylaxis despite treatment with ketotifen, levocetirizine, and montelukast. Symptoms related to systemic mastocytosis were controlled and the patient exhibited no recurrence of anaphylaxis following the introduction of monthly omalizumab injection. Omalizumab can be considered as a treatment option in patients with systemic mastocytosis unresponsive to conventional oral medications.
Anaphylaxis ; Bone Marrow ; Humans ; Ketotifen ; Leukotriene Antagonists ; Male ; Mast Cells ; Mastocytosis ; Mastocytosis, Cutaneous ; Mastocytosis, Systemic ; Middle Aged ; Omalizumab ; Receptors, Histamine ; Recurrence ; Tryptases ; Urticaria Pigmentosa

Perioperative anaphylaxis, although rare, is a severe, life-threatening unexpected systemic hypersensitivity reaction. Simultaneous administration of various drugs during anesthesia, the difficulty of communicate with patients in sedation and anesthesia, and coverage of the patient with surgical drapes are considered to be factors that impede early recognition of anaphylactic reactions. It is very important to perform an intradermal skin test because antibiotics are the most common cause of perioperative anaphylaxis. We report a case of negative-intradermal skin test antibiotic anaphylaxis mistaken for local aesthetic systemic toxicity without increase of serum tryptase for confirmative diagnostic biomaker during surgery under brachial plexus block. It is not possible to exclude the danger of anaphylaxis completely, even if it is negative-intradermal skin test and normal tryptase level. Therefore, anesthesiologists should be closely monitored and treated early for antibiotics related hypersensitive reaction, like other medicines during anesthesia.
Anaphylaxis ; Anesthesia ; Anti-Bacterial Agents ; Brachial Plexus Block ; Brachial Plexus ; Humans ; Hypersensitivity ; Skin Tests ; Surgical Drapes ; Tryptases

Wheat allergy is one of the commonest food allergies in childhood and it typically presents with IgE mediated reactions, including anaphylaxis. Seizures are not typically reported to be a direct manifestation of anaphylaxis, though it can occur secondary to hypoxia following significant haemodynamic compromise. We describe a case of a previously well infant, who presented with anaphylactic shock to wheat and responded well to the initial management, but subsequently developed a cluster of brief generalised tonic clonic seizures without any ongoing haemodynamic instability. The tryptase level that was performed at 4–5 hours post reaction was raised at 49.1 µg/L. Skin prick test to wheat, wheat specific IgE, the omega-5 gliadin IgE were positive. Extensive work-up was performed to look for an underlying cause of seizures and all returned negative. To our knowledge, this is the first case report describing an unusual presentation of multiple seizures in a young infant, in association with an anaphylactic episode. In the absence of any other seizure provoking factor and underlying cause, we believe the association is more likely causative than coincidental.
Anaphylaxis ; Anoxia ; Child ; Food Hypersensitivity ; Gliadin ; Humans ; Immunoglobulin E ; Infant ; Seizures ; Skin ; Triticum ; Tryptases ; Wheat Hypersensitivity