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[This corrects the article on p. 57 in vol. 7, PMID: 37056444.].
Patient education is increasingly acknowledged as an important aspect of the management of systemic lupus erythematosus (SLE). The aim of the study was to develop the SLE Knowledge Assessment score (SLAKE), a digital multilingual self-assessment tool designed to quantify essential SLE knowledge. International healthcare professionals (HCPs) and patient representatives engaged in a multi-step process to: identify essential SLE knowledge domains, select key domains via rating, and generate an item bank of 394 questions across 11 domains, which was then adapted into 19 languages. For validation, participants completed 44 questions (including 33 randomly selected), with scores calculated for total knowledge and the 11 specific domains. Statistical analyses examined associations between scores and demographic, clinical, and educational variables. SLAKE was used by 1182 SLE participants (1120 [94.8%] women, median age: 45 years [IQR: 35-54 years]), with a median SLE duration of 10 years (IQR: 4-20 years). The median SLAKE score was 37 (IQR: 34-40) of a maximum of 44 points while the median score across the 11 SLAKE domains ranged between 3 and 4 over a maximum of 4 points. There was a significant positive association between SLAKE score and SLE duration (p= 0.006), previous participation to a patient education course or a patient training for lupus (p< 0.0001) and the education level (p< 0.0001) but not with age (p= 0.48) or gender (p= 0.39). SLAKE is a valid, multilingual, digital self-assessment tool that effectively measures essential SLE knowledge. Its randomized question bank and domain-specific scoring enable targeted education, ultimately supporting better disease management.
Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to β-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection. The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies. The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE. Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.
In vitro assays are essential tools in diagnosing IgE-mediated allergic diseases and complement clinical history and skin testing across food, inhalant, venom, and drug allergies. This methodological review is intended for clinicians seeking a more detailed understanding of current laboratory-based allergy diagnostics. It summarizes current humoral and cellular diagnostic methods, including total IgE, singleplex and component-resolved specific IgE testing, multiplex IgE platforms, and functional cellular assays such as the basophil activation test and T-cell-based approaches. Humoral assays remain the quantitative foundation of molecular allergy diagnostics, while multiplex arrays broaden diagnostic scope and map sensitization profiles, although platform variability requires cautious interpretation. Cellular assays may add functional information in selected constellations but remain technically demanding, insufficiently standardized, and are best regarded as adjunctive tools in specialized or research settings, with evidence largely derived from selected cohorts. Additional areas - immunotherapy monitoring, mast cell disorders, contact allergy, and oncology - illustrate the broader methodological spectrum of in vitro methods. Persistent unmet needs include harmonization, validated reference standards, and robust interpretive frameworks. Disease-specific applications are discussed in companion articles in this issue.
Mutations in genes encoding proteins of the SWI/SNF complex are highly recurrent in select tumor entities. Among primary cutaneous tumors, only 4 SMARCA4- deficient undifferentiated neoplasms and 3 primary cutaneous SMARCB 1 -deficient carcinomas have been documented. In this report, we describe the morphologic, immunohistochemical, genomic, and methylation profile features of 5 additional SMARCA4 -deficient undifferentiated neoplasms and 2 SMARCB1 -deficient carcinomas of the skin. The patients (6M;1F) had a median age of 82 years (range: 60 to 94). Morphologically, all lesions showed poorly differentiated, dermal-based neoplasms, 5 of which were associated with subcutaneous involvement. The tumor cells were organized into nests, strands, and solid sheets. These cells displayed moderate to abundant cytoplasm, large, round vesicular nuclei, and prominent nucleoli. Immunohistochemical analysis revealed expression of cytokeratin AE1/AE3 in all cases, along with loss of SMARCA4 expression in 5 cases. Loss of SMARCB1 expression was identified in 2 cases and was mutually exclusive with SMARCA4 alterations. DNA sequencing revealed a high tumor mutation burden and a prominent UV signature in 4 of the 5 analyzed cases. Methylation analysis, in which tumors were compared with a control group of 68 SNF/SWI-deficient neoplasms and 18 cutaneous squamous cell carcinomas, revealed that primary cutaneous SMARCA4 -deficient and SMARCB1- deficient neoplasms, along with SMARCA4 -deficient carcinomas of other organs, constitute a unique group of neoplasms, distinct from other analyzed tumor entities. These results support the theory that these primary cutaneous SWI/SNF-deficient tumors represent a distinctive group of morphologically undifferentiated cutaneous carcinoma.
Hereditary angioedema (HAE) is a rare, potentially life-threatening disease caused in most cases by C1 inhibitor deficiency. Lanadelumab, a monoclonal antibody targeting plasma kallikrein, is an effective long-term prophylactic (LTP) treatment for HAE. However, consensus on best practices remains lacking. This study aimed to report consensus statements on key principles on long-term lanadelumab therapy for HAE in Germany developed at an HAE LTP Expert Meeting in the year 2024 in Frankfurt, Germany. A multidisciplinary panel of seven German HAE experts participated in a consensus process to align current guidelines with real-world clinical practice. Following literature review and debate, keynotes were drafted, refined, and voted on. Consensus was defined as ≥ 70% agreement. Key domains included: shared decision-making; flexibility in initiating or adjusting prophylaxis; structured patient education; self-administration; individualized dosing; emergency medication availability; and proactive follow-up, including specific guidance for women of childbearing age. Ten core consensus statements were developed, achieving unanimous (100%, n = 9/10 statements) or strong (≥ 85%, n = 1/10 statements) agreement. It is recommended that the decision to initiate long-term prophylaxis be made through shared decision-making and that the decision made can and should be adjusted again in the further course of treatment. It is advisable to train patients in the technique of self-injection and to start therapy with lanadelumab with a 2-week injection interval in accordance with the product information. The injection interval should be adjusted to the individual patient, and all well-controlled patients should be offered the option of extending the interval without compromising the goal of complete disease control. Even and especially when the prophylaxis is well tolerated, emergency medication must not be neglected. These consensus statements provide a practical, expert-endorsed framework for implementing lanadelumab LTP in clinical practice emphasizing individualized treatment aligned with international guidelines and patient needs.
Many patients with suspected or confirmed allergy to penicillin or β-lactam antibiotics are unnecessarily denied all β-lactam antibiotics (BLA) and instead given a less effective antibiotic with more side effects. However, cefazolin, a first-generation cephalosporin, is a safe and effective treatment option for these patients in most cases. Recent studies show that immunological cross-reactions among BLAs are primarily caused by structural similarities in the side chains and not by the common β-lactam ring. Cefazolin has unique R1 and R2 side chains that largely rule out cross-reactivity with other BLAs. In a case series, 21 patients with a history of alleged or confirmed allergy to BLAs were exposed to cefazolin under real-life conditions, and all but 1 patient (who developed an uncomplicated maculopapular rash) showed no reaction. Therefore, the use of cefazolin is acceptable under clinical supervision in cases of a previous uncomplicated delayed-type reaction. However, in cases of reported or documented clinical reactions to BLA that are indicative of a type I allergy (such as urticaria, angioedema, anaphylaxis), prior to (titrated) administration of cefazolin under appropriate monitoring measures, a diagnostic evaluation in accordance with guidelines, including a negative skin test for cefazolin, is advisable. This procedure avoids the use of less suitable reserve antibiotics and ensures effective treatment without incalculable risk for anaphylaxis.
Wheat allergy may present with different phenotypes. Childhood-onset wheat allergy is characterized by immediate-type IgE-mediated reactions to wheat ingestion alone. It typically affects atopic individuals and often resolves spontaneously. The predominant adult-onset phenotype is WALDA (wheat allergy dependent on augmentation factors), triggered only when wheat is consumed in combination with augmentation factors. Phenotypic transition between these forms is rarely described. We present the case of a 30-year-old atopic female patient with a history of wheat-induced anaphylaxis, who presented with three distinct stages, compatible with a phenotypic transition. In infancy, the patient was diagnosed with classical IgE-mediated wheat allergy. In early adulthood, she developed augmentation factor-dependent reactions compatible with WALDA. At the age of 30, comprehensive oral food challenge testing and serological analysis revealed full clinical tolerance and loss of sensitization. This case illustrates a possible transient clinical course of wheat allergy with WALDA as an intermediate stage prior to resolution. Such cases may be underreported, as patients with declining wheat allergy may not be identified as having WALDA reactions, but rather as having inconstant reactivity. Allergy reassessment in adult patients with food allergy in childhood is essential to detect phenotypic shifts or to confirm resolution.
Various delayed-type hypersensitivity reactions have been reported following teicoplanin administration, including drug rash with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP). Until recently, IgE-mediated hypersensitivity reactions to teicoplanin were considered to be rare. However, reports of such reactions have increased in recent years. These case reports also suggest that teicoplanin skin testing can predict IgE-mediated hypersensitivity reactions. In the present case, teicoplanin skin prick and intradermal tests were negative, yet an immediate skin reaction occurred during provocation.
The rising demand for sustainable diets has led to an increased consumption of alternative protein sources. While ecologically promising, these foods may pose new allergenic risks. We surveyed 127 European allergy experts regarding their clinical perception towards emerging allergenic food sources. Allergic reactions to non-priority allergenic foods were most frequently reported for legumes (83%), followed by hemp (33%), edible insects (21%), and jackfruit (20%). Experts highlighted risks related to cross-reactivity, particularly between edible insects and crustaceans or house dust mites, and between non-priority legumes and peanut, soy, or lupine. Legumes other than peanut, soy, and lupine, as well as edible insects and hempseeds/cannabis, were also rated as most clinically relevant for future practice. Experts also noted rising symptoms due to changes in pollen exposure and insect distribution linked to climate change. Our data underscore the need for the diagnosis of emerging allergenic sources.
This guideline is a partial update of the S3 guideline on atopic dermatitis (AWMF register no. 013-027) published in 2023. The chapters on systemic therapy with biologics and Janus kinase inhibitors as well as the chapter on pregnancy, breastfeeding and family planning in the context of systemic therapies for atopic dermatitis have been updated. This was prompted by new approvals (lebrikizumab, nemolizumab), approval extensions (abrocitinib from 12 years of age, baricitinib from 2 years of age) and new evidence on the use of biologics before and during pregnancy. In addition, a new chapter on treatment goals, treatment expectations and criteria for treatment adjustment ("treat-to-target") in systemic therapies has been added to the guideline. This article only presents the updated and newly added chapters. The complete guideline is available on the AWMF website.
To investigate changes in demographic characteristics, parental smoking habits, and the prevalence of asthma, atopic dermatitis, and rhinitis among children in South Korea before and after the COVID-19 pandemic. A retrospective analysis of national health survey data from 2019 and 2021 was conducted, including children aged 3 - 18 years. Factors such as gender, age, location, housing type, family size, income, body mass index, subjective health status, influenza vaccination, family structure, and parental smoking habits were analyzed. No significant differences were found in most demographic characteristics and parental features between 2019 and 2021, except for influenza vaccination rates and mothers' age at first childbirth. The influenza vaccination rate increased from 69.3% in 2019 to 77.8% in 2021, and the average maternal age at first birth increased from 28.46 years to 29.22 years. Asthma diagnoses showed no significant differences between the 2 years after adjusting for general and parent-related characteristics. For atopic dermatitis, significant differences in gender distribution were observed in 2021. Rhinitis diagnoses showed significant differences in age, area, and breastfeeding status between the two years. The COVID-19 pandemic may have influenced certain demographic characteristics, such as influenza vaccination rates and mothers' age at first childbirth, but the prevalence of asthma, atopic dermatitis, and rhinitis among children remained largely unchanged between 2019 and 2021. This study underscores the importance of monitoring the impact of social changes on children's health, particularly during significant events like the COVID-19 pandemic. Further research is required to understand the long-term effects of these changes on child health.
This review provides an overview of recent advances in understanding T-cell inflammation in atopic dermatitis (AD), a common chronic inflammatory skin disease. After recognizing their cognate antigen in the acute phase of the disease, the homing of T cells from the circulation into the skin via cutaneous lymphocyte antigen (CLA) is the prerequisite to skin inflammation and subsequent systemic and local, tissue resident, memory (TRM) formation. Initial observations suggest that antigen presentation occurs in structures such as induced skin-associated lymphoid tissue (iSALT), in addition to lymphatic organs. Aside from environmental antigens, such as aeroallergens, other antigen sources also appear to play a role: humoral and cellular responses to microbial antigens and autoantigens are discussed to drive and shape skin inflammation in AD. In-depth characterization of differentiated, activated Th2 cells in AD shows their ability to recognize different signals from epithelial cells directly. The heterogeneity of patients with antigen sensitizations and T-cell phenotypes is believed to influence therapeutic success. This suggests that a more precise characterization of patient subgroups would enable targeted, individualized therapy.
In collaboration with certified allergy centers (CACs) in Germany, a standardized procedure was developed for the allergologic evaluation of hypersensitivity reactions to SARS-CoV-2 vaccines. Our CAC prospectively evaluated 60 subjects with prior allergic reactions to SARS-CoV-2 vaccines or components. The investigations included a comprehensive medical history, in-vitro and skin tests. Prick tests were negative in all participants. Two positive basophil activation tests suggested a hypersensitivity to the component polyethylene glycol; however, no clinical relevance was found. Approximately 73% of the subjects reported symptoms during subsequent immunizations, which were milder than the reactions prior to the diagnostic procedures. Most index reactions manifested as non-specific symptoms. The results suggest that subsequent vaccinations following diagnostic procedures were well tolerated, underscoring the importance of careful allergological evaluation prior to vaccination.
Chronic urticaria (CU) is a skin disease characterized by recurrent episodes of vascular dilation and increased permeability of the cutaneous and mucosal microvasculature. Although antihistamines and omalizumab remain first-line and second-line therapies, respectively, a significant proportion of patients develop recalcitrant disease phenotypes, highlighting critical unmet needs for innovative therapeutic paradigms. In recent years, emerging insights into Mas-related G protein-coupled receptor X2 (MRGPRX2) have revealed transformative perspectives for elucidating the pathobiology of refractory CU. As a class A G protein-coupled receptor (GPCR) that is predominantly localized to mast cells, MRGPRX2 orchestrates non-IgE-mediated mast cell degranulation through its pluripotent ligand recognition capacity, engaging diverse exogenous cationic compounds, neuropeptides, and certain pharmacological agents. This comprehensive review evaluates recent advancements in deciphering the mechanistic contributions of MRGPRX2 to CU pathogenesis, with the ultimate aim of informing the development of precision diagnostic and therapeutic frameworks for CU management.
Biological agents used in the treatment of rheumatic diseases and malignancies cause an increase in herpes zoster susceptibility. This may also be the case for monoclonal antibody treatments used in asthma based on recent pharmacovigilance data. Herpetic lesions occurred on the anterior chest wall of a 43-year-old patient who was initiated on benralizumab treatment for severe eosinophilic asthma. The patient received diagnosis of herpes zoster and showed significant clinical improvement with oral valacyclovir treatment. Since it was not certain whether the herpes eruption was directly related to benralizumab treatment, benralizumab treatment was continued at the patient's request and with the approval of the dermatology department. The patient did not experience recurrent herpes eruptions or any other clinical problems with the repeated doses given.
Kounis syndrome is a rare type of allergic or hypersensitivity-induced acute coronary syndrome. The release of numerous inflammatory mediators induces vasospasms and potential thrombosis leading to myocardial infarction. We present the case of a 65-year-old woman with metastatic melanoma who experienced chest tightness and dyspnea after her 3rd infliximab infusion and who had transitory ST elevations. Suspecting allergic reactions and acute coronary syndrome she was simultaneously treated for both conditions with complete resolution of symptoms and electrocardiographic alternations without the need for further percutaneous coronary intervention. This case highlights the importance of considering Kounis syndrome as a potentially life-threatening complication during monoclonal antibody infusion, even in the absence of a prior allergic history and typical skin manifestations. Early recognition and treatment are crucial and spared our patient further invasive diagnostical and therapeutical interventions.
Wheat is a frequent cause of food-induced allergic reactions in adults. In this study we aimed to assess the diagnostic value of skin prick test (SPT), specific immunoglobulin E (sIgE), but also quality of life in wheat-sensitized and allergic patients. In this prospective, clinical study 80 patients were screened for eligibility. Subsequently, 36 wheat-sensitized patients underwent oral food challenges (OFCs) with supraphysiological amounts of gluten at rest and in combination with exercise. The challenge was stopped when objective symptoms occurred. Prior to the challenge, sIgE measurement and a SPT were conducted. The Food Allergy Quality of Life Questionnaire (FAQLQ), Food Allergy Independent Measure (FAIM), and Beck Anxiety Inventory (BAI) were used to assess the quality of life, perceived disease severity, and anxiety of the patients. The OFC was performed with increasing amounts of gluten reaching a supraphysiological level. 24 patients (67%) were OFC positive with 21 reacting at rest. 3 patients reacted after the implementation of exercise. 60% of patients with a self-reported exercise dependency reacted in the OFC at rest. 8 of 21 patients who reacted at rest were rechallenged with exercise and lower doses of gluten, of which 5 reacted again. Exercise lowered the reaction threshold by 50% in these 5 patients. OFC-positive patients had stronger sensitization to gluten and its constituents and showed higher impairment in their quality of life and perceived burden of disease than OFC-negative patients. The receiver operator characteristics model including gluten SPT, omega-5-gliadin sIgE, and the FAIM score to predict OFC positivity yielded a 95.2% sensitivity and 83.3% specificity. Males displayed a higher degree of sensitization, but females had higher FAQLQ and FAIM scores. Although a high rate of exercise dependency was reported, most reactions were elicited at rest when the amount of gluten was upscaled. However, the eliciting amount and reaction threshold was lowered in the presence of exercise. Food allergy-related quality-of-life data can indicate psychological impairment due to the disease but may also serve as a patient-reported outcome tool which can support the diagnostic accuracy of wheat allergy.
The use of artificial intelligence (AI) in medicine requires a careful selection of suitable models, as there is no universal "one size fits all" method. While linear regression is convincing due to its simplicity and interpretability, it is limited due to the assumption of linearity and susceptibility to multicollinearity and outliers. More complex approaches such as neural networks show their strengths in the detection of non-linear patterns and automatic feature extraction but require large amounts of data, high computing capacity, and suffer from limited explainability. Principal component analysis (PCA) offers an efficient reduction of dimensionality. Ultimately, the choice of model depends on the balance between accuracy, interpretability, and data availability. A selection of machine learning models is presented in this article.