Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for Pediatric Allergology (GPA), the German Contact Dermatitis Research Group (DKG), the German Society for Pneumology (DGP), the German Society of Otorhinolaryngology, Head and Neck Surgery, the Austrian Society of Allergology and Immunology (ÖGAI), the Austrian Society of Dermatology and Venereology (ÖGDV), the German Academy of Allergology and Environmental Medicine (DAAU), and the German Documentation Center for Severe Skin Reactions (dZh).

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A nontuberculous mycobacterium could solve the mystery of the lady from the Franciscan church in Basel, Switzerland.

BACKGROUND: In 1975, the mummified body of a female has been found in the Franciscan church in Basel, Switzerland. Molecular and genealogic analyses unveiled her identity as Anna Catharina Bischoff (ACB), a member of the upper class of post-reformed Basel, who died at the age of 68 years, in 1787. The reason behind her death is still a mystery, especially that toxicological analyses revealed high levels of mercury, a common treatment against infections at that time, in different body organs. The computed tomography (CT) and histological analysis showed bone lesions in the femurs, the rib cage, and the skull, which refers to a potential syphilis case. RESULTS: Although we could not detect any molecular signs of the syphilis-causing pathogen Treponema pallidum subsp. pallidum, we realized high prevalence of a nontuberculous mycobacterium (NTM) species in brain tissue sample. The genome analysis of this NTM displayed richness of virulence genes and toxins, and similarity to other infectious NTM, known to infect immunocompromised patients. In addition, it displayed potential resistance to mercury compounds, which might indicate a selective advantage against the applied treatment. This suggests that ACB might have suffered from an atypical mycobacteriosis during her life, which could explain the mummy's bone lesion and high mercury concentrations. CONCLUSIONS: The study of this mummy exemplifies the importance of employing differential diagnostic approaches in paleopathological analysis, by combining classical anthropological, radiological, histological, and toxicological observations with molecular analysis. It represents a proof-of-concept for the discovery of not-yet-described ancient pathogens in well-preserved specimens, using de novo metagenomic assembly.

[Cutaneous Vasculitides - Clinical Manifestations, Diagnosis, and Aetiology]. / Kutane Vaskulitiden.

Cutaneous Vasculitides - Clinical Manifestations, Diagnosis, and Aetiology Abstract. Vasculitides are a heterogeneous group of diseases that are classified differently, for example according to the size of the affected vessel or according to primary and secondary causes. The skin is most frequently affected; it can be involved both as single organ vasculitis and in the context of systemic forms. The combination of skin lesions, their anatomical location and information on the time course provide clues for a differential diagnosis. Purpura, blisters, necrosis, ulcerations and possibly a livedo are characteristic manifestations. Constitutional symptoms such as weight loss, exhaustion, fever, and arthralgias are indicative of a systemic form. It is important to differentiate vasculitides from vasculopathies, which can manifest similarly. The most common form in adults is cutaneous leukocytoclastic angiitis, in children IgA vasculitis (Schönlein-Henoch purpura). Various triggers are possible: infections, drugs, autoimmune diseases, and malignancies, whereby up to 50% remain etiologically unexplained. Skin biopsies and laboratory parameters, if necessary supplemented with imaging, are important steps in the clarification process. Treatment is primarily directed at the elimination of a possible triggering cause. Idiopathic cutaneous leukocytoclastic angiitis usually resolves spontaneously; treatment is symptomatic. In more severe cases, topical corticosteroids or calcineurin antagonists are primarily used. In case of therapeutic resistance, systemic immunosuppressants are recommended.

Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe.

PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Structured diagnostic assessment of hand eczema in cleaning workers.

Hand dermatitis is a widespread problem among cleaners. In most cases, it is caused by a combination of wet work and contact with irritants, which can result in irritant (toxic) contact dermatitis. In some cases, the irritant contact eczema then evolves into allergic contact dermatitis, although not all cases of allergic contact dermatitis are preceded by irritant contact dermatitis. This mini-review proposes a two-step diagnostic algorithm based on patch testing, which can be used if allergic contact dermatitis is suspected in cleaning workers. As a first step, we recommend performing the DKG standard series (German Contact allergy research group, DKG), the DKG rubber series, both DKG "further fragrances" series as well as the DKG preservative and disinfectant series. If there are clear hints of an occupational contact dermatitis, the first step can also involve testing patients' own products alongside the standardized tests. In a second step (at the latest), if standardized tests do not suffice to identify the culprit allergen and there is well-founded suspicion, we recommend testing the patients' own products. If necessary, the second step can also include testing the individual contact allergens contained in the screening mixes that are part of the standard series.

European Surveillance System on Contact Allergies (ESSCA): Characteristics of patients patch tested and diagnosed with irritant contact dermatitis.

BACKGROUND: Irritant contact dermatitis (ICD) is caused by the acute locally toxic effect of a strong irritant, or the cumulative exposure to various weaker physical and/or chemical irritants. OBJECTIVES: To describe the characteristics of patients with ICD in the population patch tested in the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) database. METHODS: Data collected by the ESSCA in consecutively patch-tested patients from January 2009 to December 2018 were analyzed. RESULTS: Of the 68 072 patients, 8702 were diagnosed with ICD (without concomitant allergic contact dermatitis [ACD]). Hand and face were the most reported anatomical sites, and 45.7% of the ICD was occupational ICD (OICD). The highest proportions of OICD were found in metal turners, bakers, pastry cooks, and confectionery makers. Among patients diagnosed with ICD, 45% were found sensitized with no relevance for the current disease. CONCLUSIONS: The hands were mainly involved in OICD also in the subgroup of patients with contact dermatitis, in whom relevant contact sensitization had been ruled out, emphasizing the need for limiting irritant exposures. However, in difficult-to-treat contact dermatitis, unrecognized contact allergy, or unrecognized clinical relevance of identified allergies owing to incomplete or wrong product ingredient information must always be considered.

Management of Hypersensitivity Reactions to Nondextran Iron Products: New Insights Into Predisposing Risk Factors.

BACKGROUND: Hypersensitivity reactions (HSRs) to nondextran iron products (NDIPs) are rare, but can manifest with severe signs and symptoms. Predisposing risk factors are not well understood. OBJECTIVE: To characterize patients with HSRs to NDIPs, with a special focus on possible risk factors. METHODS: We analyzed clinical characteristics of patients with HSRs to NDIPs referred to our allergy division between 2007 and 2019 compared with tolerant controls, including the type of the eliciting NDIP, severity and characteristics of the HSR, atopy status, history of allergies and urticaria, laboratory and skin test results, and outcome of reexposure with NDIPs. RESULTS: We evaluated the data of 59 patients and 21 controls. Sixteen patients and 4 controls received the NDIP iron sucrose and 41 patients and 15 controls received ferric carboxymaltose. In 2 patients and in 2 controls, the culprit NDIP was not known. Twenty-seven patients (46%) experienced an anaphylactic reaction grade I, 15 (25%) a grade II reaction, and 17 (29%) a grade III reaction according to Ring and Messmer. On analyzing the history, we found that 22 patients (37%) and 3 controls (14%) reported previous HSRs to other medications. Interestingly, more than half the patients (n = 35 [59%]) compared with only 7 controls (33%) reported an episode of any type of urticaria in their previous history. Most patients (n = 15 [79%]) tolerated reexposure of an NDIP using a low-reactogenic administration protocol. CONCLUSIONS: A history of drug hypersensitivity and urticaria represent potential risk factors for HSRs to NDIPs. On the basis of our findings, we propose an algorithm for practical management of patients receiving NDIPs aiming to prevent HSRs.

Patch test results with the European baseline series and additions thereof in the ESSCA network, 2015-2018.

BACKGROUND: Clinical surveillance of the prevalence of contact allergy in consecutively patch tested patients is a proven instrument to continually assess the importance of contact allergens (haptens) assembled in a baseline series. OBJECTIVES: To present current results from the European Surveillance System on Contact Allergies, including 13 countries represented by 1 to 11 departments. METHODS: Anonymized or pseudonymized patch test and clinical data from various data capture systems used locally or nationally as transferred to the Erlangen data centre were pooled and descriptively analysed after quality control. RESULTS: In the 4 years (2015-2018), data from 51 914 patients patch tested with the European baseline series (EBS) of contact allergens were analysed. Contact allergy to nickel was most frequent (17.6% positive), followed by contact allergy to fragrance mix I (6.9%), methylisothiazolinone (MI; 6.2%), and Myroxylon pereirae resin (balsam of Peru; 5.8%). CONCLUSIONS: While the prevalence of MI contact allergy decreased substantially following regulatory intervention, the persistently high levels of allergy to metals, fragrances, other preservatives, and rubber chemicals point to problems needing further research and, potentially, preventive efforts. Results with national additions to the baseline series provide important information on substances possibly to be considered for inclusion in the EBS.

Developing a cosmetic series: Results from the ESSCA network, 2009-2018.

BACKGROUND: There is considerable variability across European patch test centres as to which allergens are included in local and national cosmetics series. OBJECTIVES: To propose a standardized, evidence-based cosmetic series for Europe based on up-to-date analysis of relevant contact allergens. METHODS: We collated data from the European Surveillance System on Contact Allergies (ESSCA) from 2009 to 2018 to determine which cosmetic allergens produce a high yield of contact allergy. Contact allergens with a prevalence of >0.3% that were considered relevant were included. Rare contact allergens were excluded if deemed no longer relevant or added to a supplemental cosmetic series for further analysis. RESULTS: Sensitization prevalences of 39 cosmetic contact allergens were tabulated. Thirty of these allergens yielded >0.3% positive reactions and are therefore included in our proposed European cosmetic series. Six were considered no longer relevant and therefore excluded. Three were included in a supplementary European cosmetic series. An additional nine allergens were included in either the core or supplemental European cosmetic series following literature review. CONCLUSION: We have derived a potential European cosmetic series based upon the above methods. This will require ongoing investigation based upon the changing exposure profiles of cosmetic allergens as well as new and evolving substances.

Indium and iridium: Two rare metals with a high rate of contact sensitization.

BACKGROUND: Humans are exposed to a variety of metals on a daily basis, and nickel is the most frequent contact allergen. Little is known about the frequency of sensitization to indium and iridium. OBJECTIVES: Study the prevalence of indium and iridium sensitization and evaluate the optimal patch test conditions. METHODS: A total of 364 patients were patch tested at the allergy unit of the University Hospital of Basel. Pure metals, metal chlorides, and metal sulfates were applied in petrolatum or water in Inert Quadrate (IQ) test chambers for 2 days and read twice at day (D) 2, and between D4 and D7. RESULTS: Eleven patients reacted to indium salts (3.0%), 13 to iridium salts (3.6%), and one reacted to both salts. None of the patients reacted to pure metals. Nineteen of the 23 patients who reacted either to indium or iridium showed concomitant positive reactions to other metals, mainly nickel and palladium. CONCLUSION: This retrospective clinical study provides insight into the prevalence and test conditions of two rarely tested metal allergens in a large patient cohort. A considerable number of indium- or iridium-positive subjects had co-sensitization to other metals.