BACKGROUND: Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to ß-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.
Contact dermatitis is an inflammation of the epidermis and dermis at the site of exposure triggered by external agents. The two main forms are irritant and allergic contact dermatitis, which cause significant health and socioeconomic costs in addition to a marked reduction in quality of life. The anamnesis and the clinical picture are decisive for the necessary diagnostic measures. The most accurate possible diagnostic classification of contact dermatitis by means of allergological testing is important for disease management, since not only classical eczema therapy but also avoidance of the exogenous triggering factors are of great importance here. The choice of therapy should be based on the acuity, clinical severity, morphology of the lesions and localization of the contact dermatitis. A combination of basic therapy, topical, physical, and systemic therapy adapted to the patient's needs is required, whereby not all forms of therapy must be carried out simultaneously but can be used in a varying manner. Primary, secondary, and tertiary prevention strategies aim at the recognition of the triggering noxae or allergens with subsequent contact avoidance or minimization. The present S1-guideline on contact dermatitis is primarily intended to provide dermatologists, allergologists and physicians working in allergology and occupational dermatology with a decision-making aid for the selection and implementation of suitable and sufficient diagnostics, therapy, and prevention.
Dermatitis, Allergic Contact , Eczema , Allergens , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Dermatitis, Allergic Contact/therapy , Eczema/diagnosis , Humans , Patch Tests/adverse effects , Quality of Life
Most allergic reactions to antibiotics are caused by ß-lactam antibiotics; however non-ß-lactam antibiotics are also capable of causing both immediate allergic reactions as well as late-type reactions to these drugs. This is especially true for fluoroquinolones and sulfonamides. Of these, the combination of sulfamethoxazole with trimethoprim (Cotrimoxazol, e.g., Bactrim) is most important. However, there are certain types of reactions to non-ß-lactam antibiotics that are not associated with ß-lactam antibiotics. These include photosensitivity to sulfonamides, tetracyclines, and fluoroquinolones as well as different patterns of drug metabolism and associations with HLA alleles that may influence their prevalence. This review is focused on recent findings regarding the pathogenesis of allergic reactions to non-ß-lactam antibiotics.
BACKGROUND: Diagnosis of pollen allergies is mainly based on test allergens for skin prick testing. In the minimum battery of test inhalant allergens recommended by the Global Allergy and Asthma European Network 10 pollen allergens are included. Complementary other pollen allergens may need to be considered; however, respective awareness may not always be granted. Furthermore, at least in Germany, the situation may be even more complicated by the fact that test allergens need regulatory approval. A decline in commercially available test allergens may result in a diagnostic gap regarding patients with non-frequent allergies. How many patients with non-frequent pollen allergies would be affected by this gap? The data presented here partly answer this question. METHODS: The study consisted of a descriptive and an analytical part. In the descriptive part, sensitization to frequent pollen allergens (alder, hazel, birch, sweet grasses; according to the German Therapy Allergen Ordinance) and to respective non-frequent pollen allergens (cypress, Japanese cedar, ash, plane tree, olive, Bermuda grass, wall pellitory, plantain, goosefoot, mugwort, ragweed, and saltwort) was measured in adult patients with physician-diagnosed allergic rhinitis from two German federal states, namely North-Rhine Westphalia (n = 360) and Bavaria (n = 339), using skin prick testing and/or ISAC technology. Furthermore, respective regional pollen data were assessed. In the analytical part, sensitization data were correlated with each other and with anamnestic data on symptom periods. RESULTS: Sensitization to frequent pollen allergens ranged from 45% (sIgE to Aln g 1/Alder, NRW) to 72% (prick test reactivity to birch, NRW). Sensitization to non-frequent pollen allergens ranged from 0% (sIgE to Amb a 1/ragweed, NRW) to 41% (prick test reactivity to olive, Bavaria). Sensitization data partly correlated with each other and in connection with symptom periods showed a partly similar seasonal pattern as pollen data. CONCLUSIONS: Sensitization to non-frequent pollen allergens have to be considered when examining patients with respective seasonal symptoms, and test (and respective therapy) allergens for non-frequent pollen allergies need to be available. Further prerequisites for adequate patient management would be a nationwide pollen monitoring system giving continuous pollen data and a systematic sensitization monitoring at patient level.
Polychlorinated biphenyls (PCBs) are well known immunotoxic and carcinogenic compounds. Although cutaneous symptoms are the hallmark of exposure to these compounds, exact pathophysiologic mechanisms are not well understood. We took skin biopsies from moderately high PCB exposed workers (n = 25) after an informed consent and investigated the expression of immunological markers such as CCL-7, CCL-20, CXCL2, IL-1ß and IL-6, as well as the matrix metalloproteinase MMP-9, EPGN and NRF2 by RT-qPCR, and compared expression levels with plasma PCB levels. Statistical analyses showed a significant correlation between CCL-20, CXCL2, IL-6, IL-1ß, CCL-7 and MMP-9 and PCB serum levels. EPGN and NRF2 were not correlated to PCB levels in the blood. We found a significant correlation of genes involved in autoimmune, auto-inflammatory and carcinogenesis in skin samples of PCB exposed individuals with elevated plasma PCB levels. Confirmation of these findings needs to be performed in bigger study groups and larger gen-sets, including multiple housekeeping genes. Further study needs to be performed to see whether a chronical exposure to these and similar compounds can cause higher incidence of malignancies and inflammatory disease.
Polychlorinated Biphenyls , Carcinogens , Chemokine CCL20 , Chemokine CCL7 , Chemokine CXCL2 , Humans , Interleukin-6/genetics , Matrix Metalloproteinase 9/genetics , Polychlorinated Biphenyls/toxicity , Up-Regulation
Pregnancy Complications, Infectious , Syphilis , Anti-Bacterial Agents/therapeutic use , Female , Humans , Penicillins/therapeutic use , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Registries , Syphilis/diagnosis , Syphilis/drug therapy
Severe allergic reactions to vaccines are very rare. Single severe reactions have occurred worldwide after vaccination with the new mRNA-based COVID-19 vaccines. PEG2000 is discussed as a possible trigger. We provide guidance on risk assessment regarding COVID-19 vaccination in patients with allergic diseases and suggest a standardized, resource-oriented diagnostic and therapeutic procedure. Reports of severe allergic reactions in the context of COVID-19 vaccination can be made via www.anaphylaxie.net using an online questionnaire.
INTRODUCTION: Hyaluronan (HA) is a major component of the skin that exerts a variety of biological functions. Inter-α-trypsin inhibitor heavy chain (ITIH) proteins comprise a family of hyaladherins of which ITIH5 has recently been described in skin, where it plays a functional role in skin morphology and inflammatory skin diseases including allergic contact dermatitis (ACD). OBJECTIVE: The current study focused on the ITIH5-HA interaction and its potential clinical and functional impact in extracellular matrix (ECM) stabilization. METHODS: Studying the molecular effects of ITIH5 in skin, we established skin models comprising murine skin cells of Itih5 knockout mice and corresponding wild-type controls. In addition, human dermal fibroblasts with an ITIH5 knockdown as well as a murine recombinant Itih5 protein were established to examine the interaction between ITIH5 and HA using in vitro adhesion and HA degradation assays. To understand more precisely the role of ITIH5 in inflammatory skin diseases such as ACD, we generated ITIH5 knockout cells of the KeratinoSens® cell line. RESULTS: Using murine skin models, ITIH5 knockdown fibroblasts, and a reactive oxygen species (ROS)-mediated HA degradation assay, we proved that ITIH5 binds to HA, thereby acting as a stabilizer of HA. Moreover, microarray profiling revealed the impact of ITIH5 on biological processes such as skin development and ECM homeostasis. Performing the in vitro KeratinoSens skin sensitization assay, we detected that ITIH5 decreases the sensitizing potential of moderate and strong contact sensitizers. CONCLUSION: Taken together, our experiments revealed that ITIH5 forms complexes with HA, thereby on the one hand stabilizing HA and facilitating the formation of ECM structures and on the other hand modulating inflammatory responses.
Dermatitis, Allergic Contact/metabolism , Fibroblasts/metabolism , Hyaluronic Acid/metabolism , Proteinase Inhibitory Proteins, Secretory/metabolism , Skin/metabolism , Animals , Cell Adhesion , Cells, Cultured , Dermatitis, Allergic Contact/genetics , Dermatitis, Allergic Contact/pathology , Eugenol/pharmacology , Extracellular Matrix/metabolism , Fibroblasts/pathology , Humans , Mice, Inbred BALB C , Mice, Knockout , Protein Binding , Proteinase Inhibitory Proteins, Secretory/deficiency , Proteinase Inhibitory Proteins, Secretory/genetics , Skin/pathology , Thiazoles/pharmacology
This guideline on diagnostic procedures for suspected beta-lactam antibiotic (BLA) hypersensitivity was written by the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy in a consensus procedure according to the criteria of the German Association of Scientific Medical Societies. BLA such as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. However, the frequency of reports of suspected allergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected BLA allergies has a significant impact on, e.g., the quality of treatment received by the individual patient and the costs to society as a whole. Allergies to BLA are based on different immunological mechanisms and often manifest as maculopapular exanthema, as well as anaphylaxis; and there are also a number of less frequent special clinical manifestations of drug allergic reactions. All BLA have a beta-lactam ring. BLA are categorized into different classes: penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors with different chemical structures. Knowledge of possible cross-reactivity is of considerable clinical significance. Whereas allergy to the common beta-lactam ring occurs in only a small percentage of all BLA allergic patients, cross-reactivity due to side chain similarities, such as aminopenicillins and aminocephalosporins, and even methoxyimino cephalosporins, are more common. However, the overall picture is complex and its elucidation may require further research. Diagnostic procedures used in BLA allergy are usually made up of four components: patient history, laboratory diagnostics, skin testing (which is particularly important), and drug provocation testing. The diagnostic approach - even in cases where the need to administer a BLA is acute - is guided by patient history and risk - benefit ratio in the individual case. Here again, further studies are required to extend the present state of knowledge. Performing allergy testing for suspected BLA hypersensitivity is urgently recommended not only in the interests of providing the patient with good medical care, but also due to the immense impact of putative BLA allergies on society as a whole.
Specific IgE measurements obtained from patients suffering from respiratory allergy (n = 952) show that, despite similar climatic conditions, there are clear regional differences in pollen sensitization between North Rhine-Westphalia and Bavaria. The data on sensitization levels and pollen concentration was taken from the research and development project Ufoplan 3710 61 228 of the German Environment Agency for North Rhine-Westphalia and Bavaria (2011 - 2014). Most poly-sensitized patients have already shown sensitization, both in the form of cross-reactivity and species-specific sensitization, to "new" pollen allergens, such as Bermuda grass and olive tree. These plants are currently not common in Germany, but may become considerably more widespread due to the increase in average yearly temperatures caused by the global warming. The other "new" aeroallergens discussed here are plants that can be found throughout Germany, such as nettle, cypress, and pine. Their current sensitization levels are higher than 8%; however, their clinical impact appears to be underestimated. For clinical practice it is important to identify when patients' symptoms are typically severe and which regional plants might be responsible for the patients' complaints in this period of time, as this affects further diagnostic strategy. Allergens having an immune effect can then be targeted by specific immunotherapies. The information on complaints of the patients should be regularly recorded in symptom diaries. Recording this information for at least 1 year may allow to discover a correlation between specific types of pollen and allergy symptoms.
Coal tar therapy was used for centuries to treat skin disorders characterised by inflammation and skin barrier damage. It has been shown that the aryl hydrocarbon receptor (AhR) is the key target structure for these pharmacological effects of coal tar. Since coal tar has been used less and less because of the carcinogenicity of many ingredients of coal tar, other ligands of AhR were studied. Tapinarof is such a ligand and proved to be a promising new drug to treat psoriasis and atopic dermatitis. Since many endogenous and exogenous ligands of AhR are known, it may be that this "tar-smart" product is a first example of a new drug family with which dermatologists can treat skin disorders that are characterized by inflammation and skin barrier damage.
Dermatitis, Atopic , Eczema , Psoriasis , Receptors, Aryl Hydrocarbon , Coal Tar/pharmacology , Dermatitis, Atopic/drug therapy , Eczema/drug therapy , Humans , Psoriasis/drug therapy , Receptors, Aryl Hydrocarbon/drug effects
