Treatment of acute urticaria: A systematic review.

There are only a few clinical trials which address the treatment of acute urticaria (AU). Especially, the added value of systemic corticosteroids to antihistamines is unclear in treatment of severe AU. To review the existing evidence-based approaches for AU treatment. A systematic electronic search was done in PubMed and Web of Science to retrieve all studies on the treatment of patients with AU. A descriptive synthesis was conducted based on the PRISMA statement. Quality assessment was independently performed by both reviewers ('Cochrane risk-of-bias tool' for RCTs). Ten randomized controlled trials (RCTs) (n = 857 participants) were included. Four studies assessed corticosteroid effectiveness added to antihistamines and six studies compared the efficacy of H1 and/ or H2-antihistamines. The addition of corticosteroid (prednisone) to an antihistamine (levo)cetirizine did not improve symptoms of AU compared to antihistamine alone in two out of three RCTs. The combination of diphenhydramine (50 mg, IV) and ranitidine (50 mg, IV) or cimetidine (300 mg, IV) was most efficient for relief of urticaria in two out of five studies. Most frequent adverse effects were sedation and drowsiness. Recent guidelines on urticaria treatment mainly focus on chronic urticaria rather than on AU. Moreover, only few, small RCTs provide evidence for the management of AU. Thus, the state-of-the-art management of this frequent condition remains unclear. The addition of corticosteroids to an antihistamine as treatment for AU needs to be further investigated. Well-designed, high-quality interventional trials are needed to establish evidence-based treatment guidelines for AU.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper.

BACKGROUND: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized. METHOD: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. RESULTS: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. CONCLUSIONS: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.

Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis.

BACKGROUND: Oral wheat plus cofactors challenge tests in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) produce unreliable results. OBJECTIVE: We sought to confirm WDEIA diagnosis by using oral gluten flour plus cofactors challenge, to determine the amount of gluten required to elicit symptoms, and to correlate these results with plasma gliadin levels, gastrointestinal permeability, and allergologic parameters. METHODS: Sixteen of 34 patients with a history of WDEIA and ω5-gliadin IgE underwent prospective oral challenge tests with gluten with or without cofactors until objective symptoms developed. Gluten reaction threshold levels, plasma gliadin concentrations, gastrointestinal permeability, sensitivities and specificities for skin prick tests, and specific IgE levels were ascertained in patients and 38 control subjects. RESULTS: In 16 of 16 patients (8 female and 8 male patients; age, 23-76 years), WDEIA was confirmed by challenges with gluten alone (n = 4) or gluten plus cofactors (n = 12), including 4 patients with previous negative wheat challenge results. Higher gluten doses or acetylsalicylic acid (ASA) plus alcohol instead of physical exercise were cofactors in 2 retested patients. The cofactors ASA plus alcohol and exercise increased plasma gliadin levels (P < .03). Positive challenge results developed after a variable period of time at peak or when the plateau plasma gliadin level was attained. Positive plasma gliadin threshold levels differed by greater than 100-fold and ranged from 15 to 2111 pg/mL (median, 628 pg/mL). The clinical history, IgE gliadin level, and baseline gastrointestinal level were not predictive of the outcomes of the challenge tests. The challenge-confirmed sensitivity and specificity of gluten skin prick tests was 100% and 96%, respectively. CONCLUSION: Oral challenge with gluten alone or along with ASA and alcohol is a sensitive and specific test for the diagnosis of WDEIA. Exercise is not an essential trigger for the onset of symptoms in patients with WDEIA.

Usability of Graphical User Interfaces With Semiautomatic Delabeling Feature to Improve Drug Allergy Documentation.

BACKGROUND: The quality of allergy documentation in electronic health records is frequently poor. OBJECTIVE: To compare the usability of 3 graphical user interfaces (GUIs) for drug allergy documentation. METHODS: Physicians tested 3 GUIs by means of 5 fictional drug allergy scenarios: the current GUI (GUI 0), using mainly free-text, and 2 new coded versions (GUI 1 and GUI 2) asking information on allergen category, specific allergen, symptom(s), symptom onset, timing of initial reaction, and diagnosis status with a semiautomatic delabeling feature. Satisfaction was measured by the System Usability Scale questionnaire, efficiency by time to complete the tasks, and effectiveness by a task completion score. Posttest interviews provided more in-depth qualitative feedback. RESULTS: Thirty physicians from 7 different medical specialties and with varying degrees of experience participated. The mean System Usability Scale scores for GUI 1 (77.25, adjective rating "Good") and GUI 2 (78.42, adjective rating "Good") were significantly higher than for GUI 0 (56.58, adjective rating "OK") (Z, 6.27, Padj < .001 and Z, 6.62, Padj < .001, respectively). There was no significant difference in task time between GUIs. Task completion scores of GUI 1 and GUI 2 were higher than for GUI 0 (Z, 9.59, Padj < .001 and Z, 11.87, Padj < .001, respectively). Quantitative and qualitative findings were combined to propose a GUI 3 with high usability. CONCLUSIONS: The usability and quality of allergy documentation was higher for the newly developed coded GUIs with a semiautomatic delabeling feature without being more time-consuming.

111 years of allergen-immunotherapy: A long and successful history of the only available disease-modifier in allergic diseases.

The great milestones in medicine almost always have their precursors, which help the great event to break through. So it was with allergen-specific immunotherapy (AIT) and the great work of Noon and Freeman and their world-renowned publication in 1911. In this article, we want to outline AIT's long journey, from early attempts to achieve tolerance to allergens in the environment. Many very different methods were used; from homeopathy to the use of recombinant allergens. Initially, the allergen extracts were given only subcutaneously, but then also through other routes, such as nasal, rectal, intradermal, epicutaneous, in lymph nodes, or oral. It was the great merit of Bill Franklin, whom many of us still experienced as active participants in congresses, to point out that the effect of AIT must be documented not only by clinical observation but in a controlled form including placebo injections. AIT was thus transferred to evidence-based medicine, which we successfully apply today. We would like to express our gratitude to Bill Franklin himself and all others involved in the development of AIT with this summary of 111 years of immunotherapy.

Usability of Three Graphical User Interfaces for Drug Allergy Documentation.

The current drug allergy documentation module in the electronic health record of our institution is in a free-text format. Two versions of a structured and coded drug allergy documentation module were developed. Twenty-five physicians tested the three interfaces via 3x5 test scenarios. The usability was measured for each interface with a system usability scale questionnaire. Both new versions scored significantly better than the current free-text version. User feedback will be used to further optimize the new module.

Patient-doctor interaction, psychobehavioural characteristics and mental disorders in patients with suspected allergies: do they predict "medically unexplained symptoms"?

In approximately 20% of patients with suspected allergies, no organic symptom explanation can be found. Limited knowledge about patients with "medically unexplained symptoms (MUS)" contributes to them being perceived as "difficult" and being treated inadequately. This study examined the psychobehavioural characteristics of patients presenting for a diagnostic allergy work-up. Patients were interviewed and completed various self-rating questionnaires. Patient-Doctor interaction was evaluated, and the organic explicability of the patients' symptoms was rated by allergists. Patients with vs. those without MUS differed in several respects. Mental comorbidity, female sex, dissatisfaction with care, and a problematic countertransference (the interviewer's feelings towards the patient) independently predicted MUS. Patients whose symptoms could be explained organically reported more psychobehavioural problems than a control group of immuno-therapy patients. There were no differences in patient-doctor interaction. In patients with suspected allergies, recognition of psychological burden and concurrent mental disorders is important. Mental comorbidity and a difficult patient-doctor interaction may predict MUS.

Eosinophilic esophagitis due to red yeast rice (Monacoline K) in a dietary supplement for hypercholesterolemia.

We present a case of eosinophilic esophagitis (EoE) with positive skin-prick testing for type I allergy to red yeast rice (RYR, Artechol®). RYR is an over-the-counter supplement for hypercholesterolemia, since years famous in Asian countries and now also more and more popular in Western countries. The clinical relevance of IgE-mediated inflammation was proven by a rapid clearance of EoE-symptoms upon discontinuation of RYR. The role of skin-prick testing and allergy testing in general in EoE is controversial, but was of high importance in our patient. It demonstrates that in cases of a clear-cut allergy history, together with positive skin-prick (IgE) testing, a broad elimination diet can thus be avoided.

Psychobehavioral predictors of somatoform disorders in patients with suspected allergies.

OBJECTIVE: To explore a combination of health-related psychobehavioral features as potential positive criteria for somatoform disorders (SFD). Currently, SFD can only be diagnosed in the absence of sufficient organic symptom explanation, resulting in low criterion validity and delay of appropriate therapy. METHODS: Cross sectionally, we studied various psychobehavioral characteristics of 197 inpatients with suspected allergies. At the beginning of the medical work-up, patients were interviewed and completed a set of self-rating questionnaires (Illness Perception Questionnaire-Revised, Whiteley Index-7, Cognitions About Body And Health Questionnaire, Scale for the Assessment of Illness Questionnaire, Health Attitude Survey, Reassurance Questionnaire, and Patient Health Questionnaire). Organic explicability of the presenting symptoms was assessed by allergists at the end of the work-up. Forty-eight patients with SFD were compared with 149 patients without SFD, and predictive models were set up. To control for effects of the work-up situation, we also investigated 47 patients with an established diagnosis of hymenoptera venom allergy. RESULTS: In the work-up group, various self-reported psychobehavioral features discriminated patients with SFD from patients without SFD. In logistic regression analysis, self-reported dissatisfaction with medical care, disease conviction, reduced symptom controllability, and reduced body scanning independently predicted SFD. A predictive model based on these psychobehavioral characteristics had high sensitivity and specificity (area under the curve = 0.86, 95% Confidence Interval = 0.79-0.93; p < .001), which was comparable to the Patient Health Questionnaire-15, an established SFD screening tool assessing somatization. CONCLUSIONS: Psychobehavioral characteristics in patients with SFD cannot solely be attributed to the uncertainty of a work-up situation. Their predictive value is comparable to that of the traditional measuring of symptom number and severity; hence, they should be considered as SFD positive criteria in Diagnostic and Statistic Manual of Mental Disorders, 5th Edition.

Acrokeratosis Can Be a Warning Sign of an Underlying Malignancy.

INTRODUCTION: Some cutaneous manifestations can be the first presentation of an underlying malignancy. These so-called paraneoplastic syndromes can sometimes be very subtle or strongly resemble other benign cutaneous diseases. AIMS: In this report, we want to emphasize the need for further investigation of eczema-like cutaneous presentations which develop at a later age and are recalcitrant to therapy. Exclusion of an underlying malignancy needs to be considered. PATIENTS AND METHODS: A 53-year-old man with thickening of the skin, more pronounced on the hands, feet and face, was diagnosed with classic nodular sclerosing Hodgkin disease based on cutaneous presentation. RESULTS: After two rounds of chemotherapy (adriamycin, bleomycin, vinblastine and dacarbazine), the cutaneous symptoms had disappeared. After six rounds of chemotherapy and 14 months of follow-up, the patient is still in remission without recurrence of the cutaneous symptoms. CONCLUSIONS: Cutaneous symptoms recalcitrant to adequate treatment should raise suspicion and prompt further investigation to exclude an underlying malignancy. A multidisciplinary approach with the dermatology department can accelerate diagnosis and improve the patient's prognosis. LEARNING POINTS: Skin diseases can reflect internal manifestations or diseases.Vigilance, timely recognition and a multidisciplinary approach are important in a patient with atypical cutaneous manifestations.A paraneoplastic skin syndrome should be considered in persistent skin disease not responding to treatment and starting in middle-aged patients with B symptoms.

Epidemiology of staphylococcal scalded skin syndrome in Germany.

Staphylococcal scalded skin syndrome (SSSS) is a blistering skin disorder caused by Staphylococcus aureus. The "Dokumentationszentrum schwerer Hautreaktionen", a unique population-based registry for severe skin reactions, included SSSS during a time period of 2 y in Germany. Statistical calculations indicated a low overall incidence between 0.09 and 0.13 cases per 1 million inhabitants per year with 95% confidence interval of [0-4]. The age distribution showed two clusters; one in young children and one in adults. The mortality rate was much lower in children than in adults. Young age was the main risk factor, whereas immunosuppression and consumptive infectious disease were the detected risk factors in adults.