DiGeorge syndrome presenting with palmoplantar pustules: Comparative analysis of serum IL-22, NETs and IL-8 with usual palmoplantar pustulosis.

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, shows cellular immunodeficiency due to by thymic hypoplasia and hypocalcemia caused by hypoparathyroidism. It was reported that erythrodermic psoriasis occurred in a patient with 22q11 deletion syndrome. Here, we report the first case of DiGeorge syndrome presenting with a severe palmoplantar pustulosis (PPP)-like eruption with extra-palmoplantar lesions on the distal limbs. Given that PPP is a subtype of pustular psoriasis, the pustular eruption may be associated with DiGeorge syndrome. We measured serum levels of citrullinated histone H3 (CitH3), a representative marker of neutrophil extracellular traps, interleukin (IL)-8, and IL-22 and compared them with nine cases of typical PPP. In the PPP patients, the three markers were higher than in healthy subjects with significant correlations between CitH3 and IL-8/IL-22. In our patient, CitH3, IL-8, and IL-22 were also high, and IL-22 was remarkably elevated compared with the PPP patients. Our case suggests that a certain T cell abnormality associated with DiGeorge syndrome induces IL-22 overproduction, leading to the PPP-like eruption with extra- palmoplantar lesions.

How Do Classical Subtypes Correspond to Endotypes in Atopic Dermatitis?

Since atopic dermatitis (AD) is a heterogeneous condition, the subtyping of AD is a crucial issue. The classical subtypes of AD are represented by extrinsic and intrinsic subtypes, European-American and Asian subtypes, and adult and pediatric subtypes. While the subtyping of AD was historically conducted based on the phenotype, recent findings on the mechanisms of AD have revealed the importance of the endotype, which can characterize individual patients more accurately. Considering the current development of AD therapies, AD endotyping is a prerequisite for a personalized therapeutic choice. Endotypes of AD can be stratified from different viewpoints, including cytokine expression patterns, allergen properties, epidermal barrier conditions, ceramide variation, the involvement of innate immunity, and serum biomarkers. Among them, the cytokine-based endotype seems to be the most useful one and is categorized into type 2 cytokine (IL-4, IL-13 and IL-31)-high, type 1 cytokine (IFN-γ)-high, and/or type 3 cytokine (IL-22 and IL-17)-high, or mixed subtypes. Recently proposed biomarker endotyping aims at individualized treatment options, although the daily clinical use of endotypes is a future issue. To better understand the endotypes for clinicians, attempts to adjust each of the classical subtypes to endotypes are required. This review will discuss the correspondence of the classical subtypes to the various endotypes that have recently been proposed.

Elevation of circulating neutrophil extracellular traps, interleukin (IL)-8, IL-22, and vascular endothelial growth factor in patients with venomous snake mamushi (Gloydius blomhoffii) bites.

Mamushi bites cause swelling and pain that extend from the bitten site. The coagulopathic, anti-coagulopathic, and vasculopathic actions of mamushi venom result in various laboratory abnormalities, occasionally with muscular, renal, and other organ damage. We investigated the serum biomarkers that were associated with the pathogenesis of mamushi bites, focusing on markers related to tissue-damage and neutrophil activation. Twenty patients (one case of grade 2, 13 cases of grade 3, and six cases of grade 4 of severity) seen by us in one summer season were enrolled. Peripheral blood samples were taken from the patients on day 0, day 2, and day 7 after mamushi bites. In addition to routine blood examination, serum samples were subjected to enzyme-linked immunosorbent assay for citrullinated histone H3 (CitH3), interleukin (IL)-8, IL-17A, IL-22, vascular endothelial growth factor (VEGF), high mobility group box protein 1 (HMGB1), tumor necrosis factor (TNF)-α, and IL-33. Creatinine kinase (CK) values significantly correlated with prothrombin time (PT) levels, suggesting that muscular damage is associated with exaggerated coagulation and fibrinolysis. In the vast majority of patients, HMGB1, TNF-α, and IL-33 were under detection levels. Neutrophil counts did not correlate with PT or CK, indicating that the coagulation disorder and muscular damage were virtually independent of the neutrophil activation. The neutrophil number significantly correlated with CitH3, a representative marker of neutrophil extracellular traps. Moreover, there were significant correlations between neutrophil number, CitH3, IL-8, IL-22, and VEGF. Our study suggests that there are two major cascades in mamushi bites. One is an already characterized venom effect on coagulation, vessels, and muscles. In the other novel cascade, we propose that neutrophil activation with IL-8 leads to the production of IL-22 and VEGF. This sequential event may contribute to both vascular damage and repair.

Questionnaire Survey of Possible Association of Allergic Diseases with Adverse Reactions to SARS-CoV-2 Vaccination.

To protect against COVID-19, SARS-CoV-2 vaccines have been widely used. Besides anaphylaxis, some less severe adverse effects may occur at higher frequencies. It remains unclear whether present or past histories of allergic diseases exert effects on local and systemic reactions. We conducted a questionnaire survey among workers in our hospital. We analyzed the adverse effects occurring after the first and second doses of the Pfizer-BioNTech vaccine in 955 subjects. The presence or absence of local injection reactions and systemic reactions (headache, fatigability, fever, muscle pain, and joint pain) was questioned. The intensities of these reactions were graded on a scale of 0-4 (except fever) or 0-2 (fever). The allergic diseases that we focused on were bronchial asthma, atopic dermatitis, food allergy, pollinosis, and hand eczema. For the systemic reactions, fatigability after the first dose tended to be more severe in the bronchial asthma than in the non-allergic group. Headache, joint pain, and fever tended to be more severe in the food allergy than in the non-allergic group after the second dose. For the local skin reactions, atopic dermatitis subjects tended to show rather less severe local skin reactions after the second dose. The results contribute to the guidelines for the care of individuals with different allergy histories, so that they may safely receive their vaccine.