Adapting epicutaneous patch testing protocols to assess immediate-type skin reactions.

OBJECTIVE: During the development of cosmetic formulations, in vitro and in vivo methods are essential tools used to reliably assess the skin irritation potential of a product or ingredient. Epicutaneous patch testing (single and/or multiple application protocols) has long been used as an initial in vivo method to screen for possible skin irritation properties of a substance or formulation. To confirm the mildness and dermatological and/or consumer acceptance of a product, use tests are often subsequently conducted. A study was therefore initiated to see how well patch test results correlate with use tests with respect to irritation elicited by skincare (leave-on) products. METHODS/RESULTS: A number of different cosmetic formulations were assessed in both tests. Although the patch test results did not indicate substantial irritation potentials, immediate-type reactions (stinging and redness) were observed in some volunteers which disappeared within approx. 1 h. Although transient, these reactions suggested that consumer acceptance would probably be low and the studies were discontinued. Immediate-type reactions are rare but have been described for some substances used in cosmetics. These unexpected results were nevertheless intriguing and prompted the start of a journey to see if patch test protocols could be modified to assess these reactions. An occlusive short-term patch test protocol with an application period of 20 min was developed. Successful identification of the spontaneous reactions became possible. Furthermore, there was a correlation between the intensity of reactions observed in the short-term patch test and those observed in the controlled in-use studies. Short-term patch testing using the developed protocol can therefore reliably be used as a screening method, for example in the development and optimization of cosmetic formulations containing ingredients that could cause spontaneous reactions, for instance of non-immunological contact urticaria type. CONCLUSION: The lessons learned from this studies indicate that simple modifications of existing test protocols can lead to important insights into skin reactions. These modifications can then be used to create further building blocks in the development and optimization of test strategies for cosmetic formulations which offer reliable study designs for possible reactions product developers may encounter.

OBJECTIF: Lors du développement de formulations cosmétiques, les méthodes in vitro et in vivo sont des outils essentiels utilisés pour évaluer de manière fiable le potentiel d'irritation cutanée d'un produit ou d'un ingrédient. Le test épicutané (protocoles d'application uniques et / ou multiples) est utilisé depuis longtemps comme méthode initiale in vivo pour dépister les éventuelles propriétés d'irritation cutanée d'une substance ou d'une formulation. Afin de confirmer la douceur et l'acceptation dermatologique et / ou consommateur d'un produit, des tests d'usage sont souvent effectués ultérieurement. Une étude a donc été initiée pour voir dans quelle mesure les résultats des tests épicutanés correspondent aux tests d'usage en ce qui concerne l'irritation provoquée par les produits de soin (sans rinçage). MÉTHODES/RÉSULTATS: Un certain nombre de formulations cosmétiques différentes ont été évaluées dans les deux tests. Bien que les résultats du test épicutané n'indiquent pas de potentiels d'irritation substantiels, des réactions de type immédiat (picotements et rougeurs) ont été observées chez certains volontaires. Celles-ci ont disparu en à peu près 1 heure. Bien que transitoires, ces réactions de type 5 suggéraient que l'acceptation du consommateur serait probablement faible et les études ont été interrompues. Les réactions de type immédiat 6 sont rares mais ont été évoquées en relation avec certaines substances utilisées en cosmétique. Ces résultats inattendus étaient néanmoins intrigants et ont incité le lancement d'un processus pour voir si les protocoles de test épicutané pouvaient être modifiés pour évaluer ces réactions. Un protocole de test épicutané à court terme occlusif avec une période d'application de 20 min a été développé, permettant l'identification réussie des réactions spontanées. Il a été de plus constate une corrélation entre l'intensité des réactions observées dans le test épicutané à court terme et celles observées dans les test d'usage contrôlés. Le test épicutané à court terme utilisant le protocole développé peut donc être utilisé de manière fiable comme méthode de dépistage, par exemple dans le développement et l'optimisation de formulations cosmétiques contenant des ingrédients qui pourraient provoquer des réactions spontanées, par exemple de type urticaire de contact non immunologique. CONCLUSION: Les leçons tirées de ces études indiquent que de simples modifications des protocoles de test existants peuvent révéler des informations importantes sur les réactions cutanées. Ces modifications peuvent ensuite être utilisées pour créer d'autres blocs de construction dans le développement et l'optimisation de stratégies de test pour des formulations cosmétiques qui offrent des conceptions d'études fiables pour les réactions possibles que les développeurs de produits peuvent rencontrer.

[Toxicological risk assessment using the example of potential contact sensitization to resorcinol]. / Toxikologische Risikobewertung am Beispiel einer möglichen Kontaktsensibilisierung auf Resorcinol.

Resorcinol is a frequently used hair dye, whose quantitative risk assessment (QRA) for hair color products is presented in this review as an example to assess its skin sensitization risk after topical application. Its purpose is to determine the maximum concentration that can be used without expecting skin sensitization to occur. The focus is to prevent the de novo development of a contact allergy. Epidemiological data which are provided via dermatological surveillance, e.g., by the IVDK (Information Network of Departments of Dermatology) in Germany, are an important source of information that help to assess the quality and the effectivity of the QRA.

[Acute hypersensitivity reactions associated with monoclonal antibodies for targeted therapy]. / Akute Überempfindlichkeitsreaktionen auf monoklonale Antikörper zur zielgerichteten Therapie.

The application of biologics such as monoclonal antibodies for targeted therapy may lead to immediate adverse drug reactions with different pathophysiological mechanisms. Some of them are due to the immunogenicity of these drugs and are truly allergic, some of them are non-allergic, some are on-target, and some are off-target. The main example of non-allergic reactions are infusion reactions, mainly induced by cytokine release. They generally occur already at the first application and symptoms may decrease in subsequent applications. Allergic reactions need a preceding sensitization phase and therefore may not occur at first application. However, if the IgE-mediated reaction is due to cross-reactivity, they may occur at the first application of the monoclonal antibody. The management of these reactions depends on their severity and the ultimate need to treat the patient with these drugs.

[Lichenoid drug reactions]. / Lichenoide Arzneimittelreaktionen.

Lichenoid drug reactions are rare compared to typical morbilliform drug exanthema or urticaria. They are associated with specific drugs or drug families like gold, antimalarial drugs, ß­blockers and angiotensin-converting-enzyme inhibitors. Recent observations included associations with novel drugs such as biologics (e. g. tumour necrosis factor antagonists) and immune checkpoint inhibitors (anti-programme cell death protein 1 antibodies). Lichenoid drug reactions most often resemble lichen planus mainly in areas of ultraviolet-light exposed skin, but also mucosal lichen planus and even bullous lesions may occur.

Meat allergy associated with galactosyl-α-(1,3)-galactose (α-Gal)-Closing diagnostic gaps by anti-α-Gal IgE immune profiling.

BACKGROUND: Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab (CTX) and is associated with delayed anaphylaxis to red meat. In this study, different α-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal. METHODS: Three serum groups, α-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected MA, and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α-Gal-containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin (HSA)-conjugated α-Gal. RESULTS: Singleplex allergy diagnostics using the α-Gal analytes CTX and Bos d TG confirms the history of MA patients in 91% and 88% of the cases, respectively. A novel dot blot-based assay system for the detection of IgE against α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against CTX, Bos d TG, and HSA-α-Gal) was identified, which is associated with MA. CONCLUSIONS: Detection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal-sensitized patients. Higher amounts of α-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.

Regional differences of tibial and femoral cartilage in the chondrocyte gene expression, immunhistochemistry and composite in different stages of osteoarthritis.

The function of articular cartilage as an avascular tissue is mainly served by collagen type II and proteoglycan molecules. Within this matrix homeostasis between production and breakdown of the matrix is exceptionally sensitive. The current study was conducted to identify regional differences in specific alterations in cartilage composition during the osteoarthritic process of the human knee joint. Therefor the changes in the expression of the key molecules of the extracellular matrix were measured in dependence of the anatomical side (femoral vs tibial) and associated with immunohistochemistry and quantitative measurement. 60 serial osteochondral femoral condyle and the tibial plateau samples of patients undergoing implantation of total knee endoprosthesis of areas showing mild (Group A, macroscopically ICRS grade 1b) respectively advanced (Group B, macroscopically ICRS grade 3a/3b) (30 each) osteoarthritis according to the histological-histochemical grading system (HHGS) were compared with 20 healthy biopsies with immunohistochemistry and histology. We quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorometrically. In group A slightly increased colour intensity was found for collagen II in deeper layers, suggesting a persisting but initially still intact repair process. But especially on the medial tibia plateau the initial Col II increase in gene expression is followed by a decrease leading to the lowest over all Col II expression on the medial plateau, here especially in the central part. There in late stage diseases the collagen type I expression was also more pronounced. Markedly decreased safranin O staining intensity was observed in the radial zone and less reduced intensity in the transitional zone with loss of zonal anatomy in 40% of the specimens in group A and all specimens in group B. Correlation between colorometrically analysed proteoglycan GAG content and aggrecan Real Time PCR is mainly weak. Tibial and femoral cartilage in contrast to patellar cartilage both are preferential exposed to compressive stresses, but presence of menisci affects the load distribution at the tibial side, which creates varying conditions for the different cartilage surfaces in the knee. As directly measured Poissons ratio in tibial cartilage is higher but Younǵs modulus is lower than in femoral cartilage, different resulting feedback amplification loops interact with proceeding cartilage damage. The initial loss of aggrecan may support Matrix metalloproteinases (Mmps) in the access to the collagen network and the considerably differing mechanical properties at both joint surfaces result in varying increased synthesis and release of matrix degrading enzymes. The present study has identified a selection of events which reflect the response of cartilage structure and composite, chondrocytes itself and their productivity to changes in mechanical stress depending on the anatomical site.

High added value of a population-based participatory surveillance system for community acute gastrointestinal, respiratory and influenza-like illnesses in Sweden, 2013-2014 using the web.

In 2013-2014, the Public Health Agency of Sweden developed a web-based participatory surveillance system, Hӓlsorapport, based on a random sample of individuals reporting symptoms weekly online, to estimate the community incidence of self-reported acute gastrointestinal (AGI), acute respiratory (ARI) and influenza-like (ILI) illnesses and their severity. We evaluated Hӓlsorapport's acceptability, completeness, representativeness and its data correlation with other surveillance data. We calculated response proportions and Spearman correlation coefficients (r) between (i) incidence of illnesses in Hӓlsorapport and (ii) proportions of specific search terms to medical-advice website and reasons for calling a medical advice hotline. Of 34 748 invitees, 3245 (9·3%) joined the cohort. Participants answered 81% (139 013) of the weekly questionnaires and 90% (16 351) of follow-up questionnaires. AGI incidence correlated with searches on winter-vomiting disease [r = 0·81, 95% confidence interval (CI) 0·69-0·89], and ARI incidence correlated with searches on cough (r = 0·77, 95% CI 0·62-0·86). ILI incidence correlated with the web query-based estimated incidence of ILI patients consulting physicians (r = 0·63, 95% CI 0·42-0·77). The high response to different questionnaires and the correlation with other syndromic surveillance systems suggest that Hӓlsorapport offers a reasonable representation of AGI, ARI and ILI patterns in the community and can complement traditional and syndromic surveillance systems to estimate their burden in the community.

Food-induced anaphylaxis and cofactors - data from the anaphylaxis registry.

Food allergens are frequent causes of anaphylaxis. In particular in children and adolescents they are the most frequent elicitors of severe allergic reactions, and in adults food allergens rank third behind insect venom and drugs. Since July 2006 severe allergic reactions from Germany, Austria, and Switzerland are collected in the anaphylaxis registry. Currently 78 hospitals and private practises are connected. From July 2006 until February 2009 1,156 severe allergic reactions were registered. Among children and adolescents (n = 187, age range from 3 months to 17 years) food allergens were the most frequent triggers, comprising 58% of cases. In the adult group (n = 968, 18 - 85 years) food allergens were in the third position (16.3%) behind insect venom and drugs. In children legumes (31%) and in particular peanuts were frequently responsible food allergens, followed by tree nuts (25%) with hazelnut being the most frequent elicitor. In adults fruits (13.4%) most often induced severe food-dependent anaphylaxis, but also animal products (12.2%); among these most frequently crustaceans and molluscs. Cofactors were often suspected in food-dependent anaphylaxis, namely in 39% of the adult group and in 14% of the pediatric group. In adults drugs (22%) and physical activity (10%) were reported to be the most frequent cofactors, in children physical activity was suspected in 8.7% and drugs in 2.6%. Concomitant diseases like atopic dermatitis, allergic asthma, or allergic rhinoconjunctivitis were reported in 78% of children and adolescents and in 67% of the adults. In conclusion, food-induced anaphylaxis, its cofactors and concomitant diseases are age-dependent. The data offers to identify risk factors of anaphylaxis.

Good short- to medium-term results after osteochondral autograft transplantation (OAT) in middle-aged patients with focal, non-traumatic osteochondral lesions of the knee.

BACKGROUND: Osteochondral autograft transplantation (OAT) offers the opportunity to repair cartilaginous defects by restoring hyaline cartilage anatomy. Encouraging results have been reported in patients suffering from acute knee trauma or osteochondritis dissecans. Patients with focal chronic, non-traumatic osteochondral (FCNO) lesions of the knee, however, have rarely been the subject of investigation. Some authors even consider higher age as contraindications to OAT. OBJECTIVES: To assess the short- to medium-term outcomes of OAT in middle-aged patients with FCNO lesions of the knee and to identify predictors of clinical outcome. HYPOTHESIS: Filling FCNO defects with autologous osteochondral grafts should restore the congruency of the middle-aged knee joint and thereby reduce pain and loss of function on the one hand, and increase quality of life on the other hand. METHODS: One hundred and twelve patients (48.01±1.12yrs) with FCNO of the knee were assessed before OAT and 26.2±0.24 months after surgery. Clinical outcome was measured by WOMAC Index and the Visual Analogue Scale (VAS) for pain. RESULTS: Pain (pre-OAT VAS vs. post-OAT VAS: 7.14±0.19 vs. 3.74±0.26, P<0.001) was reduced and quality of life (pre-OAT WOMAC vs. post-OAT WOMAC: 134.88±5.84 vs. 65.92±5.34, P<0.001) improved. Retropatellar defects were associated with poor outcome, while overall surface and number of cylinders were not. DISCUSSION: Middle-aged patients with FCNO of the knee also profit from OAT at a short follow-up. LEVEL OF EVIDENCE: IV. Mono-centric, prospective clinical series.

Successful treatment of bullous pemphigoid with omalizumab as corticosteroid-sparing agent: report of two cases and review of literature.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease that is characterized by formation of subepidermal bullae due to functional disturbance of the hemidesmosomal proteins on the keratinocytes at the basal membrane zone. In recent years, several studies have emphasized the important role of IgE autoantibodies in the pathogenesis of BP. Consequently, a therapeutic approach using IgE depleting antibodies, such as a humanized monoclonal anti-IgE antibody (e.g. omalizumab) may represent a new option for treatment of this autoimmune disease. METHODS: In this paper, we report about the successful treatment of BP with omalizumab in two patients and provide a review of the current literature on the relationship between IgE antibodies and this autoimmune blistering disease. RESULTS: Two patients with therapy-resistant BP were treated with humanized monoclonal anti-IgE antibody omalizumab 300 mg subcutaneously every 3 weeks as corticosteroid-sparing agent. Under this therapy, both patients experienced a significant improvement of skin condition and almost complete resolution of pruritus. The treatment was well tolerated. CONCLUSION: Until recently IgG autoantibodies against the basal membrane proteins BP180 und BP230 were considered to be causative in the pathogenesis of BP. However, new in vitro studies as well as data from experimental mouse models have indicated that in addition to specific IgG, also IgE antibodies against BP180 and BP230 play a role in the development of this disease. Based on these new findings, new treatment modalities of BP became possible.

[Who Stays Loyal to Orthopaedics and Trauma Surgery? Results of a Nationwide Survey]. / Wer bleibt nach einer Famulatur in Orthopädie und Unfallchirurgie dem Fachbereich treu? Ergebnisse einer bundesweiten Umfrage.

INTRODUCTION: The general shortage of medical doctors in Germany can also be felt in the area of trauma and orthopaedics. Medical elective placements, in Germany known as "Famulatur", are sensitive interfaces between the theoretical university studies and the practical medical workplace. In this research project, the aim was to study how medical students perceive these types of placements and if it alters their decision making when planning their further career. METHODS: During the summer term of 2012, 9079 medical students answered an online questionnaire. Of these, the subgroup was evaluated that had had a placement of at least 4 weeks in the field of trauma and orthopaedics. Overall, 37 test items about this placement and further career steps were included in this study. Groups were evaluated separately by the item "I am considering a career in trauma and orthopaedics" (PJ-Ja) versus "I am not considering a career in trauma and orthopaedics" (PJ-Nein). RESULTS: Overall 397 students were included in this study; 55 % were female. 267 (67.3 %) stated: "I am considering a career in trauma and orthopaedics"; 130 (32.7 %) were not. There was no significant difference in age or sex between these groups (sex: χ²= 2.50, p = 0.114; age: F[1.93]< 1, p = 0.764). Specific and statistically significant differences between those groups were found in the items team integration, ward climate, qualification of teaching, training for specific knowledge in the field, practical aspects of the tasks performed, general planning and structure of the elective achievement of the teaching goals. DISCUSSION: Knowledge of satisfaction during medical elective placements is essential if one aims to inspire students for a specific medical profession. Instructors who can identify weaknesses and deficits in their training regime can therefore in the future increase the number of medical doctors who choose their speciality. The foundation of personal development has to be laid very early in the career of medical students.

[Important Aspects of Diagnosis and Minimally Invasive Treatment of Metastases in the Spine Through the Plasma Field Therapy (Cavity Coblation Method)]. / Besonderheiten der Diagnostik und der minimalinvasiven chirurgischen Behandlung von multiplen Metastasen an der Wirbelsäule durch Plasmafeldtherapie (Cavity-Coblation-Methode).

Background and objectives: Until recently, it was almost impossible to perform major surgery on metastases in the spine. This is especially the case for multiple spinal metastases and for older multi-morbid patients with higher OP risks. It is very important in such cases that the operation should be as minimally invasive as possible, and should aim to reduce pain, treat fractures and to improve the quality of life. The aim of this publication is to present and discuss the specific features of the methodology, problems, surgical techniques, as well as the effectiveness of the modernised cavity/coblation method and results of the treatment of 240 patients with spine metastases. Patients/Material and Method: Patients: Patients of every age with bone destruction were treated, with osteolysis and pathological fractures of vertebrae caused by metastases. The pre-operative diagnosis was evaluated by X-Ray, MRT, CT, whole-body F18-FDG-PET, whole-body bone scintigraphy, histology. Cavity/coblation method: Tumour resection was carried out by the plasma field (42 °C, cold energy) over the percutaneous trans-/extrapedicular access and was followed by balloon kyphoplasty. Tumour tissue was removed, deformation corrected and stability enhanced. The treatment clearly reduced the risks of recurrence, fracture and compression of the neural structures. Local radiotherapy and chemotherapy were performed post-operatively. Clinical and radiological follow-ups, included tumour staging, were performed regularly after the OP (after 2 and 14 days and 3, 6,12, 24, 36, 48 and 60 months), including data on pain and improvement in quality of life. Results: Within 6 years (03/08-04/14), we treated 240 patients with multiple spinal metastases (146 female, 94 male, age range 31-92 years, average age 65.5 years) or 784 vertebral bodies. 61 patients were also given dorsal percutaneous instrumentation and straightening. All patients experienced a significant reduction in pain, and improvements in satisfaction and quality of life. Treatment was combined with chemotherapy and local radiotherapy to reduce tumour cell growth or recurrence rate. Patients could be rapidly mobilised after surgery, blood loss was minimal, and the next oncology treatment could be initiated immediately. Discussion/Conclusions: Cavity/coblation is a safe and minimally invasive procedure, as confirmed by our own short- and long-term results, as well as by reports/publications of other workers. OP risks, blood loss, and surgical time are lower and shorter. This new method is very promising for the future. It is important that the indication is correct and the treatment strategy must be adapted individually. Prognosis must be assessed and the surgical technique must be precise.

[Psychiatric Nursing Internship and Promotion of Specialized Training Interest]. / Psychiatrisches Pflegepraktikum und die Förderung des fachspezifischen Ausbildungsinteresses.

Qualified personnel in the field of medical psychiatry are crucial to providing comprehensive care. The importance of a nursing internship as an access point to the psychiatric field is not considered by key players. A survey conducted across German medical schools in 2012 analyzed medical care internships as viewed by medical school students. From among students surveyed, those who participated in a nursing internship, and would consider taking part in further internships within the psychiatric department ("PFJ"), were separated from those who were not sure ("PFU") or who would not ("PFN") consider further study in the field of psychiatry. The survey's conclusion was that a comparably small number of students opted for a psychiatric nursing internship based upon practical aspects of content, satisfaction, and access to nursing internships. A potential solution to the low numbers of students selecting psychiatric internships is to restructure the initial contact program that psychiatric departments use to introduce prospective medical school students to the field of psychiatry.

Economic analysis of two-stage septic revision after total hip arthroplasty: What are the relevant costs for the hospital's orthopedic department?

BACKGROUND: The number of septic total hip arthroplasty (THA) revisions is increasing continuously, placing a growing financial burden on hospitals. Orthopedic departments performing septic THA revisions have no basis for decision making regarding resource allocation as the costs of this procedure for the departments are unknown. It is widely assumed that septic THA procedures can only be performed at a loss for the department. Therefore, the purpose of this study was to investigate whether this assumption is true by performing a detailed analysis of the costs and revenues for two-stage septic THA revision. METHODS: Patients who underwent revision THA for septic loosening in two sessions from January 2009 through March 2012 were included in this retrospective, consecutive cost study from the orthopedic department's point of view. We analyzed variable and case-fixed costs for septic revision THA with special regard to implantation and explantation stay. By using marginal costing approach we neglected hospital-fixed costs. Outcome measures include reimbursement and daily contribution margins. RESULTS: The average direct costs (reimbursement) incurred for septic two-stage revision THA was €10,828 (€24,201). The difference in cost and contribution margins per day was significant (p < .001 and p = 0.019) for ex- and implantation (€4147 vs. €6680 and €429 vs. €306) while length of stay and reimbursement were comparable. CONCLUSIONS: This is the first detailed analysis of the hospital department's cost for septic revision THA performed in two sessions. Disregarding hospital-fixed costs the included variable and case fixed-costs were covered by revenues. This study provides cost data, which will be guidance for health care decision makers.

Quantifying the incidence and cost of acute gastrointestinal illness in Sweden, 2013-2014.

In Sweden, acute gastrointestinal illness (AGI) incidence, severity, impact on productivity, related healthcare usage and associated costs are not ascertained. We measured these in 2013-2014 using a population-based cohort reporting weekly. We defined AGI as ⩾3 episodes of loose stools or vomiting/24 h; or loose stools or vomiting with ⩾2 other gastrointestinal symptoms. After each AGI episode, we collected information about perceived severity, healthcare use and absenteeism. We calculated incidence rates, AGI absenteeism and costs comprising direct healthcare costs and productivity loss due to work/school absenteeism. A total of 3241 participants reported 1696 AGI episodes [incidence 360/1000 person-years, 95% confidence interval (CI) 326-395; highest in the <5 years age group]. In the <5 years age group, 31% of episodes were perceived as mild, 61% as moderate and 8% as severe; 9·4% led to primary-care consultations, and 1·4% to hospital admissions. In the ⩾5 years age group, 18% of episodes were perceived as mild, 64% as moderate and 18% as severe; 6·4% led to primary-care consultations, and 1·9% to hospital admissions. AGI caused 8 891 000 days of absenteeism (95% CI 6 009 000-12 780 000). AGI cost €1 005 885 000 (95% CI 754 309 000-1 257 195 000) nationally for the year. In Sweden, a minority of cases perceive AGI as a mild illness. AGI is a burden on the healthcare system and causes productivity loss, with high costs. Countries may consider these estimates when prioritizing health interventions.

[Porphyria cutanea tara]. / Porphyria cutanea tarda.

Porphyria cutanea tara (PCT) has a prevelance of about 40 new diagnoses per 1 million people per year and is the most frequently occurring type of porphyria worldwide. Inhibition of the uroporphyrinogen decarboxylase (UROD) is the main cause of the disease, which can be the result of a heterozygous or homozygous mutation of the UROD gene; however, xenobiotics or other diseases may play an important role for the precipitation of the disease. Risk factors include alcohol, estrogen, iron overload, and hemochromatosis, hepatitis C or poisoning, e.g., with polyhalogenated aromatic compounds such as hexachlorobenzene. Signs and symptoms are blisters, skin fragility, erosions hyperpigmentation, sclerodermoid plaques. Therapy includes sun protection, prevention of risk factors, phlebotomy, and chloroquine.