SARS-CoV-2 and allergy - what have we learned after two and a half years?

BACKGROUND: Coronavirus disease-2019 (COVID-19) has significantly hampered the regular workflow for allergists and allergy departments. MATERIALS AND METHODS: The purpose of this review is to highlight our own experiences on SARS-CoV-2 and allergy as well as to discuss findings from the literature. RESULTS: Vaccination against SARS-CoV-2 is needed for protection against severe infection. Skin reactions may arise with SARS-CoV-2 infections. Short-term general immune reactions and skin reactions are also possible upon SARS-CoV-2 vaccination; however, they recur in only a proportion of patients during follow-up vaccinations. Initial reports of anaphylaxis after vaccination fueled public fear. On the other hand, more recent epidemiologic data do not show a substantially increased anaphylaxis risk compared with other vaccines. Fear-related reactions may be essential for many "anaphylaxis" reports. In Germany, the flow chart developed by Paul-Ehrlich-Institut (PEI) and Robert-Koch-Institut (RKI) together with the allergological societies helps to care for patients with suspected "allergy history" safely and effectively. Through this, patients with increased risk of anaphylaxis to SARS-CoV-2 vaccines and their ingredients (e.g., polyethylene glycol (PEG), polysorbate 80) are identified. However, since only small amounts of these excipients are contained in mRNA vaccines, even some PEG-allergic patients can tolerate the vaccination. In Germany, an allergy test-guided procedure is recommended for high-risk patients, including an allergy history, prick tests, intradermal and basophil activation tests, and, if necessary, provocation tests. This also appears effective for anxiety reduction in patients with vaccination skepticism. To date, all of our patients have been able to be vaccinated with SARS-CoV-2 vaccines without the occurrence of significant reactions. CONCLUSION: Many initial concerns about unexpected side effects of SARS-CoV-2 vaccination have not been confirmed. The flowchart and, in the case of suspicion of hypersensitivity, an allergy test-guided risk assessment helps to reduce patients' fear of vaccination and enables safe vaccination.

The neglected twin: Nummular eczema is a variant of atopic dermatitis with codominant TH2/TH17 immune response.

BACKGROUND: Nummular eczema (NE) is a common chronic inflammatory skin disease characterized by multiple, pruritic, discoid-shaped lesions. Since the underlying immune mechanisms are not fully understood, it is unclear whether NE should be regarded as variant of atopic dermatitis (AD) or a distinct disease. OBJECTIVE: We compared the clinical, histopathologic, and molecular signatures of NE with that of type 2 and type 3 skin diseases. METHODS: We performed bulk RNA sequencing as well as histologic and clinical studies in lesional and nonlesional skin biopsy specimens from NE (n = 50), AD (n = 47), and psoriasis (n = 90) patients. RESULTS: NE displayed typical hallmarks of AD, such as an impaired epidermal barrier, microbial colonization, spongiosis, and eosinophil infiltration, but also aspects of psoriasis, including increased epidermal thickness, number of Ki-67+ cells, and neutrophilic infiltration. At the gene expression level, neutrophil-attracting cytokines (IL19, CXCL8, CXCL5) were upregulated, whereas TH2-related cytokines (IL13, CCL17, CCL18, CCL26, CCL27) were similarly expressed in NE compared to AD. Principal component analysis of transcriptome data from lesional skin showed that AD and NE cluster together distinct of psoriasis. In line with this, an established molecular classifier identified NE as AD rather than psoriasis. Finally, we demonstrated clinical and molecular efficacy of dupilumab treatment in NE. CONCLUSION: NE shows overlapping type 2 and type 3 immune signatures, while type 2 immunity predominates and should be the primary target of specific therapeutic interventions. This supports the view of NE as a variant of AD.

Cutaneous reactions following COVID-19 vaccination assessed by dermatologists: a single-institutional study in Germany.

BACKGROUND AND OBJECTIVES: Cutaneous reactions following COVID-19 vaccination have been frequently described, whereas larger case series by dermatologists are lacking. This study assesses SARS-CoV-2 vaccination-associated skin reactions, severity, treatment, course, eliciting vaccines, allergy test results and tolerance to revaccination. PATIENTS AND METHODS: Single-institutional, non-interventional study of dermatologists assessing cutaneous manifestations in 83 patients in Germany. RESULTS: 93 reactions were presented. Manifestations clustered into immediate (n = 51, 54.8%) and delayed hypersensitivity reactions (n = 10, 10.8%), chronic inflammatory skin diseases (n = 13, 14.0%), reactivation of latent herpes virus infection (pityriasis rosea/herpes zoster; n = 9; 9.7%) and others (n = 10, 10.8%). Vaccination was associated with new (76.3%) - mostly hypersensitivity reactions - or exacerbation of known skin diseases (23.7%), in this case predominantly chronic inflammatory skin diseases. Reactions occurred primarily within the first week (72.8%) and after first vaccination (62.0%). Treatment was required in 83.9% and hospitalization in 19.4%. In 48.8% revaccination led to recurrence of the same reactions. Disease was ongoing at last consultation in 22.6%, primarily in chronic inflammatory skin diseases. Allergy tests were performed in 15 patients (18.1%) and resulted negative. CONCLUSIONS: It can be assumed that vaccination may trigger immune activation-related reactions especially in those patients predisposed to develop respective skin diseases.

The Impact and Consequences of SARS-CoV-2 Pandemic on a Single University Dermatology Outpatient Clinic in Germany.

The pandemic outbreak of coronavirus disease 2019 (COVID-19) affects health care systems globally and leads to other challenges besides infection and its direct medical consequences. The aim of this study was to investigate the impact of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic on the university dermatology outpatient clinic (UDOC) of the Technical University of Munich, Germany. We analyzed datasets from 2015 until 2020 extracted from the hospital information system database and our documented outpatient files regarding patient numbers, gender, age, and diagnoses. In 2020, case numbers of outpatient care declined significantly (p = 0.021) compared to previous years and was related to the timing of political announcements answering SARS-CoV-2 pandemic. Additionally, during calendar week 10 to 15-the peak time of the spread of COVID-19 in Germany-the proportion of patients missing their consultation was significantly higher in 2020 than in 2019 (22.4% vs. 12.4%; p < 0.001). Gender-associated differences regarding absences were not detected, but patients aged 85 years or older were significantly more likely to miss their consultation compared to all other age groups (p = 0.002). Regarding different disease clusters, patients with chronic inflammatory skin diseases and infectious and malignant diseases were more likely to miss their consultation (p = 0.006). Noticeably, less patients with malignant diseases, and particularly malignant melanoma, were registered during this pandemic. Our data support the hypothesis that medically constructive prioritization might not be implemented properly by patients themselves. Identifying missed patients and catching up on their medical care apart from COVID-19 will pose an enormous challenge for health care systems globally.