Systemic Hypersensitivity Reaction Research Articles

Risk Factor Analysis of Anaphylactic Reactions in Patients With Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare disorder of abnormal mast cells in at least 1 extracutaneous organ/tissue. Anaphylaxis is an acute, severe systemic hypersensitivity reaction, and a strong association between SM and anaphylaxis has been shown. However, not all patients with SM experience anaphylaxis. Presently, there are no predictive markers to discriminate patients with SM at high risk of anaphylaxis from those at low risk. This study sought to determine risk factors for the occurrence of anaphylaxis in patients with SM. A cross-sectional study was conducted in 122 consecutive adult patients with SM admitted to the Mastocytosis Center at Karolinska University Hospital. All patients underwent medical evaluation, including bone marrow biopsy and a thorough allergy workup. To determine risk factors, study subjects were categorized into 2 groups according to the presence (n= 55) or absence (n= 67) of anaphylaxis and compared for their demographic, clinical, and biochemical characteristics. Patients with SM with anaphylaxis had less frequent presence of mastocytosis in the skin (P < .001), more atopic predisposition (P= .021), higher total IgE levels (P < .001), and lower baseline tryptase levels (27 ng/mL vs 42 ng/mL; P= .024) compared with patients with SM without anaphylaxis. Patients with SM with anaphylaxis display unique clinical and laboratory features. Hence, a risk analysis tool that is capable of discriminating patients with SM at high risk of anaphylaxis from those at low risk with 86% sensitivity was developed by using the variables male sex, absence of mastocytosis in the skin, presence of atopy, IgE levels of 15 kU/L or more, and baseline tryptase levels of less than 40 ng/mL.

A Pilot Study of Intralymphatic Immunotherapy for House Dust Mite, Cat, and Dog Allergies.

Several recent clinical trials reported that intralymphatic immunotherapy (ILIT) for some allergens, such as cat dander and pollen, induce tolerance more rapidly than conventional subcutaneous or sublingual immunotherapy, have a comparable duration of effect after only 3 injections, and do not provoke serious local or systemic reactions. However, the efficacy and safety of ILIT are using Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), and dog, which are indoor allergens that are commonly found globally, need to be evaluated. Furthermore, use of multiple allergens in ILIT should be investigated. We assessed the clinical efficacy and adverse effects of ILIT using aqueous Df, Dp, dog, and cat allergens or mixtures thereof in patients with allergic rhinitis. A total of 11 subjects with AR sensitized to Df, Dp, cat, and/or dog allergens received 3 intralymphatic inguinal injections of sensitized allergen extract (HollisterStier, New Orleans, LA, USA). Clinical parameters were assessed before ILIT, and 4 months and 1 year after the first injection. Rhinitis symptoms were alleviated and quality of life was improved 4 months after ILIT (P=0.012 and P=0.007, respectively), and these improvements lasted for 1 year after ILIT (P=0.047 and P=0.009, respectively). However, we observed 2 cases of anaphylaxis, one case of a moderate-to-severe systemic hypersensitivity reaction and the other case of a severe local reaction at the injection site after ILIT. In conclusion, ILIT can rapidly improve allergy symptoms and quality of life, and this effect lasts for 1 year. In hypersensitized patients, however, ILIT can provoke severe systemic and/or local hypersensitivity reactions when performed using aqueous allergen extracts.

Anaphylaxis as a Manifestation of Systemic Mastocytosis: A Case Report and Review of Literature

Introduction: Anaphylaxis is defined as “a serious, life-threatening generalized or systemic hypersensitivity reaction” and “a serious allergic reaction that is rapid in onset and might cause death”. The determination of different mast cells (MC) mediators, such as serum and/or plasma histamine and tryptase, is proposed for the diagnosis of anaphylaxis. There are differences in the clinical presentation of anaphylaxis in patients with indolent systemic mastocytosis versus idiopathic anaphylaxis. Case presentation: This is the case of a 72-year-old female patient presenting with acute bacterial pyelonephritis treated with intra venous antibiotics. She developed a facial flush then a diffuse flush with hypoxia and respiratory arrest. The patient recovered with non-invasive ventilation without the need for intubation. A full blood panel returned normal and two bone marrows biopsies were performed. The second one showed the presence of a perivascular infiltrate mast cell, consistent with systemic mastocytosis. Discussion: All aspects of systemic mastocyosis including the classification and the main clinical manifestations as well as the diagnosis were concisely reviewed. Then supportive and immunomodulator treatment were differentiated. Conclusion: Patients suffering of systemic mastocytosis typically present anaphylactic symptoms primarily involving the cardiovascular system in the absence of urticaria and/or angioedema, which makes such clinical presentation highly suspicious. Patients suffering of c-MCD (Cutaneous-mast cell disease) need assistance in identifying their triggers and education on proper avoidance.

Diagnosis and treatment of anaphylaxis: there is an urgent needs to implement the use of guidelines.

ABSTRACTAnaphylaxis is a severe, life-threatening generalized or systemic hypersensitivity reaction that requires rapid and adequate care. This study aimed to obtain an integrated view of the level of physicians' knowledge related with treatment of anaphylaxis in studies published within the last 5 years. Sixteen studies were found and four points were identified as of the great interest to the authors: (1) emergency pharmacological treatment, (2) epinephrine auto-injectors prescription, (3) knowledge of the main signs of anaphylaxis, and (4) admission of the patient to verify biphasic reactions. Concern about the use of intramuscular adrenaline as the first choice in relation with anaphylaxis was evident in most studies, rather than its use in the comparison dial, and especially low in a study that included data from Brazil, in which the frequency of its use was 23.8%. An adrenaline autoinjector is highly recommended among specialists for patients at risk of anaphylaxis, however, its use is still infrequent among non-specialists and in countries that this agent is not available. Intervention studies have shown improved medical knowledge of anaphylaxis following disclosure of the information contained in the international guidelines. The analysis of these studies reinforces the need to disseminate international guidelines for diagnosis and treatment of anaphylaxis, as well as providing an adrenaline autoinjector, to improve management and to prevent a fatal outcome.

Efficacy and Safety of Degarelix in Taiwanese Patients with Prostate Cancer Requiring Androgen Deprivation Therapy: An Open-label, Multicenter Phase III Study

Background: Pivotal phase III data have shown the efficacy and safety of degarelix (240 mg starting dose/80 mg maintenance dose [240/80 mg]) in North American and European patients with prostate cancer (PCa). This open-label, multicenter, single-arm trial has evaluated the efficacy and safety of degarelix in Taiwanese patients with PCa.Methods: Eligible patients received degarelix 240/80 mg monthly for 6 months. The primary objective was the efficacy of degarelix in achieving and maintaining serum testosterone below castrate levels (≤0.5 ng/mL). Secondary objectives included changes in serum testosterone and PSA, and safety.Results: One hundred and ten patients were allocated to treatment. Over six months, degarelix maintained serum testosterone at castrate levels; from Days 28-168, the cumulative probability of sustained castrate level testosterone was 97.2% (95% CI: 91.6-99.1%), meeting the primary objective. Degarelix rapidly suppressed serum testosterone levels, with castrate levels achieved by Days 3 in 93.5% of patients. PSA decreased rapidly from baseline, with a median reduction of 92.4% by Day 28. Degarelix was well tolerated, with the most frequent adverse events (AEs) being mild to moderate injection site reactions (ISRs), occurring mostly with the initial dose of degarelix. There were no immediate-onset systemic hypersensitivity reactions observed.Conclusions: In Taiwanese patients with PCa, a monthly degarelix 240/80 mg/mL dose regimen rapidly decreased testosterone and PSA levels, and maintained testosterone at castrate levels (≤ 0.5 ng/ mL) over 6 months. The safety profile of degarelix was consistent with that expected for elderly men with PCa undergoing androgen deprivation therapy (ADT).

Systemic hypersensitivity to fosaprepitant - A report of two cases.

Fosaprepitant is a widely administered antiemetic used mainly for moderately to highly emetogenic chemotherapy. Local injection site reactions are the most common type of infusion reaction reported from fosaprepitant. At our institution, two separate patients have experienced systemic hypersensitivity reactions to their infusions of fosaprepitant. We report a review of the literature and the details of these reactions.

Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni.

BackgroundSymptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection.Methodology/Principal FindingsSerum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells.Conclusions/SignificanceS. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.

Supportive care of patients with anaphylaxis — options and shortcomings: an assessment on behalf of the working group on anaphylaxis training and education (AGATE), Germany

Background: Anaphylaxis is an acute-onset, life-threatening, systemic hypersensitivity reaction. The acute reaction occurs due to a permanently immunologically altered response, which can result in mild to severe reactions and, in isolated cases, to fatal reactions upon allergen contact. The avoidance strategies required lifelong in affected individuals significantly impair quality of life.

Recurrent Anaphylaxis: An Unruptured Splenic Hydatid Cyst as an Unusual Cause

Anaphylaxis is an acute onset systemic hypersensitivity reaction that may result in death. Drugs, idiopathic triggers, Hymenoptera venom and food are the most common causes of anaphylaxis. In patients with a recurrent history of anaphylaxis and elevated IgE levels without evident etiology, spontaneous hydatid cyst rupture should be considered, especially in endemic areas.

Аnaphylaxis – specific and nonspecific hypersensitivity

Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction. With modern anaphylaxis position is considered as a syndrome with different pathogenesis, clinical manifestations and severity. The article discusses the epidemiology, classification, etiology, clinical criteria for diagnosis, pathogenesis, risk factors, complications and treatment of anaphylaxis.

Can we identify patients at risk of life-threatening allergic reactions to food?

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions.

A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning

Context: The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15–60 min and frequently results in adverse reactions. Objective: We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion. Materials and methods: A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4–9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 1000 U/L or abnormal ALT. Results: 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15–98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31–39%): 173 (26.5%; 95% CI: 23–30%) only gastrointestinal, 50 (8%; 95% CI: 6–10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1–1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13–28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. Conclusion: A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.

Incidence of serum sickness after the administration of Australian snake antivenom (ASP-22)

Context: Serum sickness is a delayed immune reaction resulting from the injection of foreign protein or serum. Antivenom is known to cause serum sickness but the incidence and characteristics are poorly defined. Objective: To investigate the incidence and clinical features of serum sickness following the administration of Australian snake antivenoms. Materials and methods: This was a prospective cohort study of patients recruited to the Australian Snakebite Project who received snake antivenom from November 2012 to March 2014. Demographics, clinical information, laboratory tests and antivenom treatment were recorded prospectively. Patients administered antivenom were followed up at 7–10 days and 6 weeks’ post-antivenom. The primary outcome was the proportion with serum sickness, pre-defined as three or more of: fever, erythematous rash/urticaria, myalgia/arthralgia, headache, malaise, nausea/vomiting 5–20 days post-antivenom. Results: During the 16-month period, 138 patients received antivenom. 23 were not followed up (unable to contact, tourist, child, bee sting) and 6 died in hospital. Of 109 patients followed up, the commonest reason for antivenom was venom induced consumption coagulopathy in 77 patients. An acute systemic hypersensitivity reaction occurred post-antivenom in 25 (23%) and 8 (7%) were severe with hypotension. Serum sickness occurred in 32/109 (29%) patients, including 15/37 (41%) given tiger snake, 6/15 (40%) given polyvalent and 4/23 (17%) given brown snake antivenom. There was no association between the volume of antivenom and serum sickness, p = 0.18. The commonest effects were lethargy, headache, muscle/joint aches and fever. Discussion: The incidence of serum sickness after snake antivenom in Australia was higher than earlier investigations which failed to define symptoms or follow-up patients, but similar to more recent studies of antivenoms in the United States. Conclusion: Serum sickness is common with Australian snake antivenom but does not appear to be predictable based on the volume of antivenom administered.

Management of Anaphylaxis

Anaphylaxis is a life-threatening systemic hypersensitivity reaction with a rapid onset. All healthcare professionals should be familiar with its recognition and management. The clinical diagnosis is important. It involves the sudden onset of characteristic symptoms and signs within minutes to hours after exposure to a known or potential trigger, often followed by rapid progression over hours. Symptoms usually involve two or more body systems, including the skin and mucous membranes, and respiratory, gastrointestinal, cardiovascular, and central nervous systems. Prompt initial basic treatment with intramuscular epinephrine in the mid-anterolateral thigh can be life-saving. Simultaneously, it is important to place the patient in a supine position, call for help when indicated, provide supplemental oxygen, start intravenous fluid, and provide cardiopulmonary resuscitation as required, while monitoring the patient’s vital signs and oxygenation status. Antihistamines and glucocorticoids are not initial treatments of choice. For self-management, patients at risk of anaphylaxis should carry epinephrine auto-injectors, have personalized emergency action plans, and follow-up with a physician about preventing anaphylaxis recurrence. Patient and caregiver training and education are essential in the management of anaphylaxis. Keywords: Anaphylaxis; Epinephrine 중심 단어: 아나필락시스; 에피네프린

Systemic contact dermatitis due to nickel

Introduction: Systemic contact dermatitis (SCD) is a systemic reactivation of a previous allergic contact dermatitis. The initial exposure may usually be topical, followed by oral, intravenous or inhalation exposure leading to a systemic hypersensitivity reaction. A case of a 27 year-old male with SCD due to nickel is reported Case Report: A 27 year-old male presented with recurrent pruritic eruption consist of deep seated vesicles on both palmar and left plantar since 6 months before admission. This complaint began after patient consumed excessive amounts of chocolate, canned food, and beans. The patient worked as a technician in a food factory. History of allergy due to nickel was acknowledged since childhood. The clinical presentation was diffuse deep seated vesicles, and multiple erythematous macules to plaques, with collarette scale. Patch test using the European standard showed a +3 result to nickel. The patient was diagnosed as systemic contact dermatitis due to nickel. The treatments were topical corticosteroid and patient education of avoidance of both contact and systemic exposure to nickel. The patient showed clinical improvement after 2 weeks. Discussion: SCD was diagnosed due to the history of massive consumption of food containing nickel in a patient who had initial sensitization to nickel, with clinical features and the patch test result. Advice to be aware of nickel and its avoidance is important in SCD management. Keywords: systemic contact dermatitis, nickel-sensitization, dietary nickel, patch test, food induced systemic contact dermatitis

Optimization of the THP-1 activation assay to detect pharmaceuticals with potential to cause immune mediated drug reactions

Despite important impacts of systemic hypersensitivity induced by pharmaceuticals, for such endpoint no reliable preclinical approaches are available.We previously established an in vitro test to identify contact and respiratory allergens based on interleukin-8 (IL-8) production in THP-1 cells. Here, we challenged it for identification of pharmaceuticals associated with systemic hypersensitivity reactions, with the idea that drug sensitizers share common mechanisms of cell activation. Cells were exposed to drugs associated with systemic hypersensitivity reactions (streptozotocin, sulfamethoxazole, neomycin, probenecid, clonidine, procainamide, ofloxacin, methyl salicylate), while metformin was used as negative drug. Differently to chemicals, drugs tested were well tolerated, except clonidine and probenecid, with no signs of cytotoxicity up to 1–2mg/ml. THP-1 activation assay was adjusted, and conditions, that allow identification of all sensitizing drugs tested, were established. Next, using streptozotocin and selective inhibitors of PKC-β and p38 MAPK, two pathways involved in chemical allergen-induced cell activation, we tested the hypothesis that similar pathways were also involved in drug-induced IL-8 production and CD86 upregulation. Results indicated that drugs and chemical allergens share similar activation pathways.Finally, we made a structure–activity hypothesis related to hypersensitivity reactions, trying to individuate structural requisite that can be involved in immune mediated adverse reactions.

Analysis of the clinical safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for adults with Peyronie's disease (PD).

To examine the safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for the treatment of Peyronie's disease (PD), using a pooled safety analysis of patients who received at least one dose of CCH in any of six clinical studies. Patients from six clinical studies, including three randomised, double-blind, placebo-controlled studies and three open-label safety and efficacy studies, were included if they had received at least one dose of 0.58mg CCH. Adverse events (AEs), including treatment-emergent AEs, treatment-related AEs, and serious AEs (SAEs), were characterised. Potential immunogenicity-related AEs were evaluated through examination of increased anti-AUX-I and anti-AUX-II antibody levels, AEs, and reported terms possibly associated with immunological or hypersensitivity events. Overall, 85.8% of 1044 pooled patients reported at least one treatment-related AE. The most frequently reported (≥25.0% of patients) treatment-related AEs included penile haematoma (82.7% had the verbatim 'penile bruising'), penile pain, and penile swelling. Most patients (75.2%) had mild- or moderate-severity treatment-related AEs, and 14.2% had no treatment-related AEs. Nine patients (0.9%) had treatment-related SAEs: five with penile haematoma and four with corporal rupture. There was no association between AEs and anti-AUX-I or anti-AUX-II antibody levels across treatment cycles, and no systemic hypersensitivity reactions occurred. This pooled safety analysis shows that although non-serious and serious treatment-related AEs can occur after CCH treatment for PD, most were non-serious and the SAEs were manageable. Providers should be prepared to manage possible SAEs.

Rapid subcutaneous desensitization for the management of local and systemic hypersensitivity reactions to etanercept and adalimumab in 12 patients

Rapid subcutaneous desensitization for the management of local and systemic hypersensitivity reactions to etanercept and adalimumab in 12 patients

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.

Objectives:We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab.Methods:HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration.Results:A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (pM-H = 3 × 10−7; odds ratio [OR]M-H = 8.96, 95% confidence interval [CI] = 3.40–23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (pM-H = 6 × 10−4; ORM-H = 0.2, 95% CI = 0.08–0.50), with a PPV of 81%.Conclusions:HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration.

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Calciphylaxis is most common in patients with end-stage renal disease, and hyperparathyroidism is often present as well. But several cases in patients with normal renal and parathyroid function have been reported; this article describes one such case. The etiology and pathophysiology of calciphylaxis aren't well understood. There are many risk factors, and the reported median survival time is 2.6 months after diagnosis. The condition is characterized by isolated or multiple lesions that progress to firm, nonulcerated plaques and then to ischemic skin necrosis and ulceration. In August 2010, a female patient arrived at the hospital with multiple deep, painful necrotic wounds. Given this patient's presentation on admission, the nurses kept expecting the physicians to initiate end-of-life discussions with her and were surprised when this did not happen. After five days, the patient was diagnosed with calciphylaxis in the unusual presentation of normal renal and parathyroid function, and the team realized that her chances for survival were greater than expected. The nursing staff was crucial in developing and implementing an intensive treatment plan. The patient survived and made a full recovery.