Diagnosis Of Idiopathic Anaphylaxis Research Articles

Treating the untreatable: Somatoform disorder in an adolescent with organic symptoms mimicking idiopathic anaphylaxis

Idiopathic anaphylaxis (IA) is a rare life-threatening disorder that may present with severe symptoms similar to other forms of anaphylaxis. It is an exclusion diagnosis and requires careful consideration of all recognizable and rare causes of anaphylaxis. Psychiatric conditions, such as somatoform disorders, should be considered in the differential diagnosis when there is a paucity or absence of clinical signs. A 17-year-old female patient was admitted to the inpatient clinic for pediatric allergy due to recurrent anaphylaxis. In the last two years, the patient was administered intramuscular epinephrine more than 200 times and was admitted to the intensive care unit four times due to severe anaphylaxis. The attacks frequently appeared as flushing, itching, shortness of breath, and rarely hypotension, but without a defined trigger. The patient was diagnosed with IA and received oral steroids, omalizumab, and rituximab. However, none of her attacks were accompanied by elevated tryptase levels and the aforementioned pharmacotherapies did not prevent relapse. After psychiatric evaluation, somatoform disorders were suspected despite striking variations in the severity of the physical symptoms. The psychiatric diagnosis was also supported by a good response to fluoxetine and supportive individual psychotherapy. The patient is currently being followed up without any anaphylactic attacks. Somatoform disorders should be considered in the differential diagnosis of IA because of overlapping physical symptoms. In the clinical practice of diagnosing and managing IA, symptoms that are not only subjective but also objective and unresponsive to conventional treatments should alert physicians to the probability of the psychiatric condition and the requirement for psychiatric consultation.

Prevention of Anaphylaxis Episodes in Idiopathic Anaphylaxis by Omalizumab

Introduction: In 15–35 percent of patients with anaphylaxis, the triggering allergen cannot be found; therefore, a diagnosis of idiopathic anaphylaxis (IA) is made. We report on the outcomes in patients with IA treated with omalizumab. Methods: We included consequent omalizumab-treated IA adult patients treated with omalizumab 300 mg every 4 weeks. Results: Out of 7 patients, 6 were female, median age 40 years with the frequency of anaphylaxis episodes from 3 in 2 years to 5 in 4 months. Baseline tryptase ranged from 1.71 to 12.0 μg/L. An increase in tryptase during anaphylaxis was documented in 6 patients. Activating KIT p.D816V variant was detected in 2 patients. One patient also had hereditary alpha-tryptasemia (HαT). The duration of omalizumab treatment was 0.5–7.5 years. None of the patients have experienced an anaphylactic reaction since the start of treatment. Mild systemic reactions were reported in 6 patients (86%). The presence of underlying cMCD had no impact on the treatment outcome. Conclusion: All patients in our study had complete responses to omalizumab. The presence of KIT p.D816V and HαT did not influence the response to omalizumab treatment.

Use of in vitro and in vivo tests in the diagnosis of food-induced anaphylaxis – a case study

Food allergy is a chronic disease that affects both children and adults. Systemic allergic reactions in children are most commonly caused by foods, especially nuts, milk, and eggs. A conventional diagnostic work-up for allergy typically pinpoints the allergen source, while component-resolved diagnostics is an approach that identifies the allergen molecules responsible for causing anaphylaxis. In some cases, determining the causative agent of anaphylaxis requires the use of various diagnostic tests. In the following paper, we want to highlight the importance of a critical approach to allergy tests results and caution in the diagnosis of idiopathic anaphylaxis. Based on a case report of food-induced anaphylaxis, we discuss the diagnostic methods that can be applied following a negative IgE test result for allergens obtained with a multiplex platform.

Evaluation of post-traumatic stress disorder in parents of children with a history of anaphylaxis

IntroductionAnaphylaxis is a life-threatening systemic allergic reaction that has increased in prevalence in recent years. A meaningful proportion of children and parents showed post-traumatic stress disorder (PTSD) symptoms after anaphylaxis. ObjectiveThis study aims to reveal the presence of PTSD and clinical features associated with PTSD in parents of children with a history of anaphylaxis. Material and methodsThe study included 54 cases of anaphylaxis in children under the age of 18 years who applied to the pediatric allergy outpatient clinic of our hospital between 01.06.2020 and 31.05.2021 and their parents. Parents were evaluated with the “Posttraumatic Stress Disorder Checklist for DSM-5”. ResultsThe mean age of the children was 6.4±6.1 years and 28 (52%) of the patients were female. The triggering cause of anaphylaxis was determined from history-taking and physical examinations in 39 (72%) patients. The most common causative agents were foods (n=27, 50%), followed by drugs (n=7, 13%) and venom (n=5, 9%). PTSD was detected in 25 (46%) of parents. Factors affecting the development of PTSD in parents of children with a history of anaphylaxis were evaluated by logistic regression analysis. Accordingly, it was determined that having a history of food-induced anaphylaxis in the child (OR: 7.62, 95% confidence interval [CI]: 1.15–50.58), having a diagnosis of idiopathic anaphylaxis (OR: 9.91, 95% CI: 1.12–87.51), having severe anaphylaxis (OR: 9.09, 95% CI: 1.21–68.26) and having a child in the first two years of life (OR: 7.66, 95% CI: 1.16–50.42) increased the likelihood of PTSD in parents. ConclusionThe results of our study demonstrate that parents with children who have a history of anaphylaxis are at risk for PTSD. Psychological evaluation a part of routine medical examination of patients with anaphylaxis and their families may enable early detection of PTSD, which is strongly associated with a broad range of psychiatric disorders.

Idiopathic Anaphylaxis? Analysis of Data from the Anaphylaxis Registry for West Pomerania Province, Poland.

The most common causes of anaphylaxis, according to various authors and depending on the age of the studied groups, are: Hymenoptera venom, food, and medications. Unfortunately, we are not always able to indicate the cause of anaphylaxis. There are data in the literature where as many as 41% of all cases are idiopathic anaphylaxis. Since the introduction of new diagnostic methods such as molecular diagnostics (MD) in our centre, the percentage of idiopathic anaphylaxis in the Anaphylaxis Register has significantly decreased. The purpose of this study was to identify possible causes of idiopathic anaphylaxis in patients with a history of moderate to severe anaphylactic reactions. After using MD, the causative agent was found in another 29 people. The proportion of people with idiopathic anaphylaxis in the Registry decreased from 9.2% to 3.5%. There were no significant differences in the incidence, although men appear to be slightly more common in primary idiopathic anaphylaxis. The mean age of primary idiopathic anaphylaxis was 40 years, but this was as high as 51 for anaphylaxis with alpha-gal allergy. Exercise may or may not be present as a cofactor despite its established role, e.g., in wheat-dependent exercise-induced anaphylaxis (WDEIA). In most of the analyzed cases, i.e., 70%, the reaction took place within an hour. The longest time interval from exposure to the development of symptoms is in the case of alpha-gal allergy; in this analysis, it was at least 5 h after ingestion of the so-called "red meat". Patients are not aware of the disease, or further attacks cannot be prevented. As many as 80% had idiopathic anaphylaxis prior to visiting the centre, and 80% developed anaphylaxis after visiting the centre, which emphasizes the need to not stop the medical team in their search for the causes. As many as 93% of cases required medical intervention, of which adrenaline was used only in 34.5%, antihistamines in 86%, systemic glucocorticosteroids (sCS) in 75%, and fluids in 62% of cases. A total of 83% of patients received an emergency kit for self-administration. Idiopathic anaphylaxis can be resolved as known-cause anaphylaxis after a thorough medical history and, if possible, without exposing the patient after using appropriate, modern in vitro diagnostic methods, including molecular diagnostics. The diagnosis of idiopathic anaphylaxis should extend the diagnosis to include alpha-gal syndrome, LTP syndrome and WDEIA.

Use of omalizumab for management of idiopathic anaphylaxis: A systematic review and retrospective case series

BackgroundPatients with idiopathic anaphylaxis (IA) may fail to respond to a combination of high-dose H1 and H2 antihistamines and mast cell stabilizers. Treatment options for these patients are currently limited. ObjectiveTo describe the clinical experience of omalizumab use for the treatment of patients with IA with no evidence of underlying clonal mast cell disorders. MethodsWe performed a retrospective review at 2 separate institutions of medical records of patients with a diagnosis of IA without evidence of mast cell clonality who had received treatment with omalizumab. We searched PubMed for studies describing omalizumab use in similar patients. Information on symptoms and omalizumab therapy was compiled, and response pattern of anaphylaxis was determined. ResultsA total of 35 patients with IA and no evidence of mast cell clonality who received omalizumab were identified. The median age was 36 years at the start of omalizumab (range, 11-54 years; n = 29). The frequency of anaphylaxis episodes before omalizumab treatment varied from 2 total episodes to several episodes per month. The most often used initial omalizumab dose was 300 mg every 4 weeks (n = 16). Most patients ultimately achieved clinical response after starting omalizumab: complete response (63%, n = 22), partial response (28.5%, n = 10), with 3 nonresponders. ConclusionOmalizumab may be an effective treatment option for patients with IA who do not have evidence of mast cell clonality and fail to respond to antihistamines and mast cell stabilizers.

Idiopathic Anaphylaxis: A Form of Mast Cell Activation Syndrome

Idiopathic anaphylaxis is a condition caused by paroxysmal episodes of sudden-onset multiorgan involvement variably including laryngeal edema, urticaria, bronchoconstriction, dyspnea, hypoxia, abdominal pain, nausea, vomiting, diarrhea, and hypotension. Rarely, the episodes can lead to cardiovascular collapse and death in the absence of a clear trigger, especially in the presence of other cardiovascular comorbidities. Elevated mast cell mediators such as tryptase and histamine have been reported during episodes, and mast cells are considered the primary cells responsible for driving anaphylaxis in humans. Basophils also secrete histamine and LTC4 when activated and theoretically can contribute to symptoms. As our understanding of mast cell disorders continue to grow, the classification for these disorders evolves. The purpose of this article was 2-fold: toreview the epidemiology, clinical manifestations, and diagnosis of idiopathic anaphylaxis and to discuss the classification of idiopathic anaphylaxis within the broader context of mast cell activation disorders.

Idiopathic anaphylaxis

Idiopathic anaphylaxis (IA) is a diagnosis of exclusion when no cause can be identified. As with other forms of anaphylaxis, IA is life-threatening. Its prevalence is difficult to determine and the mechanism is not clearly understood. Investigation of a suspected case of idiopathic anaphylaxis involves 3 steps. First, objective criteria are sought to establish the diagnosis of anaphylaxis; next, differential diagnoses are ruled out; finally, screening for hidden allergens is performed. The aim of this approach is to reduce the chance of false negative diagnosis of IA. The management of acute reactions is no different than for any case of anaphylaxis. When symptoms are seen frequently, prophylactic therapy is required to prevent attacks. There is no standard long-term prophylaxis for IA. The prognosis is generally favourable. IA patients should be regularly re-evaluated since certain newly recognized aetiologies may account for some situations, as with α-gal allergies and mast cell disorders.

Idiopathic anaphylaxis yardstick: Practical recommendations for clinical practice

Anaphylaxis is considered idiopathic when there is no known trigger. The signs and symptoms of idiopathic anaphylaxis (IA) are identical to those of anaphylaxis because of a known cause and can include cutaneous, circulatory, respiratory, gastrointestinal, and neurologic symptoms. Idiopathic anaphylaxis can be a frustrating disease for patients and health care providers. Episodes are unpredictable, and differential diagnosis is challenging. Current anaphylaxis guidelines have little specific guidance regarding differential diagnosis and long-term management of IA. Therefore, the objective of the Idiopathic Anaphylaxis Yardstick is to use published data and the authors' combined clinical experience to provide practical recommendations for the diagnosis and management of patients with IA.

Characteristics and Outcomes of Patients with Idiopathic Anaphylaxis (IA) 2003-2018

We aimed to determine the longer term status of patients with IA. The current standard initial treatment is prednisone, H1 antihistamines, and self-administration of epinephrine for acute attacks. Patient charts were identified by ICD-10 code T78.2XXA and patient age ≥18 years. Patients were included if they had a working diagnosis of IA. The Northwestern University Institutional Review Board approved this study. We reviewed 209 charts, of which 56 had an initial working diagnosis of IA. But with time, 54 patients were considered to be compatible with the diagnosis of IA. All patients are currently alive. Thirty-five out of 54(64.8%) patients were women. The mean age at presentation was 48 years with mean BMI of 30.3. Forty-five out of 54(83%) patients had concomitant atopic diseases (including other causes of anaphylaxis or sporadic urticaria). Seven out of 54(13%) patients had thyroid disease. Thirteen of 54(24%) patients reported symptom onset during a meal or post-prandial at least once. However, no food triggers were confirmed, despite careful history taking, skin testing, food specific IgE, and re-introduction of the food. Data suggested that remission was present after 24 months without an attack of IA. The mean years from disease onset to remission was 4.2 years. After entering remission, 6/54(11.1%) patients experienced a single attack years later. Omalizumab was administered in 6 patients, with benefit in 4 patients within 4 months. Patients with IA are predominantly women, atopic and obese. IA often enters complete remission within 4 years, with relapse in a few cases.

Identification of alpha-gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis.

IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3-6hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked.

Management of Idiopathic Anaphylaxis: When Is Bone Marrow Examination Essential?

Idiopathic anaphylaxis is not an uncommon entity within the Allergy and Immunology field. Management of such patients can be extremely challenging at times. A thorough history, including an emphasis on possible mast cell disease, is an absolute necessity. A bone marrow biopsy is not only appropriate, but essential, when evaluating patients with recurrent anaphylaxis if a clonal mast cell disease is suspected as the underlying etiology. Clinical predictors for underlying clonal mast cell disease have been studied and include an elevated baseline tryptase, presence of hypotensive syncopal episodes, and absence of urticaria and angioedema during anaphylactic episodes. In the acute setting, there is no alternative to self-injectable epinephrine for treatment of suspected anaphylaxis of any type. It should be administered with repeated doses as deemed necessary to establish resolution of symptoms such as hypotension, bronchospasm, or cardiovascular collapse. Once the diagnosis of idiopathic anaphylaxis is made, we recommend starting maintenance therapy with a regimen of H1 antihistamines. Cases who are refractory to H1 antihistamine therapy alone will require the addition of at least low dose immune suppression with corticosteroids to provide continued relief from recurrent episodes. In many cases these medications can be weaned in less than a year without recurrent symptoms. In refractory cases or corticosteroid-dependent idiopathic anaphylaxis, adjunctive therapy with second line agents including montelukast or omalizumab has been used with some success.

Gastroesophageal hymenoptera stings add to causes of idiopathic anaphylaxis

Identification of the elicitor of an allergic reaction is crucial to permit an appropriate risk assessment and future avoidance strategies. However, in some cases it is difficult to detect the relevant trigger of anaphylaxis. Hidden or previously unconsidered allergens have to be ruled out carefully before a diagnosis of idiopathic anaphylaxis is made.1 Hymenoptera stings are not routinely considered to be a cause of unexplained anaphylaxis because they are perceived as markedly painful and can straightforwardly be recalled by the affected person.

Idiopathic anaphylaxis.

Anaphylaxis represents the maximal variant of an immediate-type allergic reaction involving the whole organism with manifestations in different organ systems. IgE-mediated mast cell and basophil activation is the major pathomechanism; however, immune complex and pseudo-allergic reactions also may lead to the same symptomatology. The most common elicitors are drugs, additives, occupational substances, animal venoms, aeroallergens, and contact urticariogens but also physical factors (cold, heat, ultraviolet light, exercise). When no eliciting factors can be detected, the term "idiopathic anaphylaxis" is used. The diagnosis of idiopathic anaphylaxis is, therefore, a diagnosis of exclusion and may be made only after careful allergy history taking and diagnosis involving in vitro tests. Possible mechanisms underlying the pathophysiology of idiopathic anaphylaxis include undetected diseases (eg, mastocytosis occulta), concomitant anaphylaxis-enhancing medication (b-blockers), secretion of histamine-releasing factor from T lymphocytes, autoantibodies against IgE or IgE receptors, and angiotensin II deficiency. One of the many differential diagnoses of anaphylaxis may have been overlooked. The treatment of idiopathic anaphylaxis follows the rules of antianaphylactic therapy.

Idiopathic anaphylaxis in children.

Idiopathic anaphylaxis is a disease where no identifiable antigen or disease initiates an anaphylactoid reaction. Unlike classic IgE antibody-mediated anaphylaxis, severe idiopathic anaphylaxis is treatable with corticosteroids. To date, only 22 pediatric cases from one referral center have been reported. To describe the characteristics of children with idiopathic anaphylaxis A retrospective review of medical records for children presenting to the pediatric allergy clinic with the diagnosis of idiopathic anaphylaxis was performed. The review identified eight children with idiopathic anaphylaxis. All eight patients had a cutaneous finding of either urticaria, angioedema, or generalized flushing. Six of the eight patients were noted to have wheezing or angioedema of the airway causing respiratory difficulties. Diarrhea was noted among six patients. Many of the children clearly had life threatening events. Response to appropriate therapy was generally good. Pediatric idiopathic anaphylaxis can present at any age. It may be that many pediatric cases are assumed to be anaphylaxis due to some unknown antigen, and the correct diagnosis is never appreciated. It is important to recognize this disease in children so that it may be appropriately treated, because its specific therapeutic regimen has been shown to prevent the potentially fatal consequences of this disease.

Serum Tryptase in Idiopathic Anaphylaxis: A Case Report and Review of the Literature

Anaphylaxis is a life-threatening disease that characteristically presents with multiple arrays of dermatologic, respiratory, cardiovascular, and gastrointestinal derangements, in general, suddenly after exposure to an allergen. It can, however, occur without an identifiable precipitant or event, and this well-defined entity has been called idiopathic anaphylaxis. The diagnosis of idiopathic anaphylaxis is made after an appropriate allergic evaluation and exclusion of a provocative trigger. We report an unusual case of manifesting with gastroenteritis, urticaria, hypotension, and syncope. Measurement of serum tryptase, a mast cell enzyme, was used to substantiate the diagnosis. Tryptase level is a useful test that can be used to help diagnose this potentially fatal disease. [Tanus T, Mines D, Atkins PC, Levinson AI: Serum tryptase in idiopathic anaphylaxis. Ann Emerg Med July 1994;24:104-107.]

Idiopathic anaphylaxis: diagnostic variants and the problem of nonorganic disease.

We report on an expanding series of cases of idiopathic anaphylaxis (IA) with development of a classification, therapeutic regimens, and control of disease and induction of remission. Simultaneously, a growing series of cases referred for diagnosis and management of IA do not have IA. These cases, which approximate 10% of our series of IA cases, present serious time-consuming diagnostic problems for physicians. We present a series of nine cases of this type of nonorganic disease and describe the presenting symptoms, failure to document clinical abnormalities, and the lack of a response to a regimen shown to be effective in altering the course of true IA. The classification of IA has been expanded to include IA variants for patients in whom the symptoms complex varies significantly from other types of IA. Diagnostic suggestions and the problems of management are reviewed.

Idiopathic anaphylaxis: total experience with 225 patients.

Idiopathic anaphylaxis (IA) is defined as anaphylaxis with no identifiable precipitating agent or event. Episodes of IA can be life threatening, and onset of episodes is unpredictable and usually recurrent. The epidemiologic features and clinical course of 225 patients diagnosed with IA and managed according to the described protocol with prednisone, H1 antagonists, and beta adrenergic agents were evaluated. There were no fatalities from IA in our series. There was a sevenfold reduction in the average rate of episodes requiring emergency care after initiation of pharmacologic management. Ninety five of 147 patients being observed are in remission, defined as absence of episodes for 1 year without corticosteroid therapy. During 636 patient years of observation, no inciting cause of anaphylaxis or alternative organic disease was defined. The diagnosis of IA was highly reliable in this series. Long-term prognosis is good, with the majority of patients experiencing remission.

Idiopathic anaphylaxis. A clinical summary of 175 patients

One hundred seventy-five patients with idiopathic anaphylaxis, treated by the same team of physicians, were retrospectively evaluated. The diagnosis of idiopathic anaphylaxis was made only after a careful evaluation had failed to identify an allergen or underlying disease. Before our care of these patients, there were a total of 76 hospital admissions, including 21 intensive care unit admissions and 291 emergency department visits. Prophylactic treatment with maintenance antihistamines and prednisone was appropriate for frequent episodes, and short-term treatment was given for infrequent episodes. No fatalities were reported from idiopathic anaphylaxis in the 124 patients who were available for follow-up. With the appropriate treatment, remissions can be induced in a substantial number of patients. Significant reductions in the frequency of emergency department visits and hospitalizations have been shown, which, in turn, are accompanied by decreases in overall medical costs. In this disease, the period before treatment serves as a control period for comparison after therapy.