Clin Immunol Research Articles

Sensitization to trometamol in patients with delayed local reactions after administration of the Moderna mRNA-1273 vaccine against SARS-CoV-2

Sensitization to trometamol in patients with delayed local reactions after administration of the Moderna mRNA-1273 vaccine against SARS-CoV-2

Tyrosine kinase inhibitors for the treatment of indolent systemic mastocytosis: Are we there yet?

Indolent systemic mastocytosis (ISM) is the most prevalent form of systemic mastocytosis. Many patients with ISM suffer from mast cell (MC) mediator-related symptoms. In a small number of patients, hematologic progression is seen in the follow-up. In some patients with ISM, symptoms arising from MC-derived mediators including gastrointestinal symptoms, anaphylaxis, and neuropsychiatric symptoms are kept under control with conventional mediator-targeting drugs or MC-stabilizing agents. However, in a substantial number of patients, the symptoms are refractory to such conventional therapy. For these patients, novel drugs and targeted approaches are considered. One reasonable approach may be to apply tyrosine kinase inhibitors directed against KIT and other key kinase targets expressed in neoplastic MCs in ISM. Because MCs in more than 90% of all patients with typical ISM display the KIT D816V mutant receptor, clinically effective KIT-targeting drugs have to be active against this mutant form of KIT. The 2 such most effective and well-studied agents currently available are midostaurin and avapritinib. Other KIT-targeting drugs, such as imatinib or masitinib, are less effective or even noneffective against KIT D816V and are thus recommended for use only in patients with other KIT mutant forms (noncodon 816 mutations) or with wild-type KIT. In the present article, we review the current state in the treatment of ISM with tyrosine kinase inhibitors, with special emphasis on treatment responses and potential adverse effects. In fact, all of these agents also have unique and common adverse effects, and their use to treat patients with ISM should be balanced against their toxicity and short- and long-term safety.

Gender dimorphism in IgA subclasses in T2-high asthma

Immunoglobulin A (Chan in J Allergy Clin Immunol 134:1394–14014e4, 2014), the second most abundant immunoglobulin in serum, plays an important role in mucosal homeostasis. In human serum, there are two subclasses of IgA, IgA1 (≅ 90%) and IgA2 (≅ 10%), transcribed from two distinct heavy chain constant regions. This study evaluated the serum concentrations of total IgA, IgA1, and IgA2, and total IgG, IgG1, IgG2, IgG3, and IgG4 in T2-high asthmatics compared to healthy controls and the presence of gender-related variations of immunoglobulins. Total IgA levels were increased in asthmatics compared to controls. Even more marked was the increase in total IgA in male asthmatics compared to healthy male donors. IgA1 were increased only in male, but not in female asthmatics, compared to controls. Concentrations of IgG2, but not IgG1, IgG3, and IgG4, were reduced in asthmatics compared to controls. IgG4 levels were reduced in female compared to male asthmatics. In female asthmatics, IgA and IgA1 levels were increased in postmenopause compared to premenopause. IgA concentrations were augmented in mild, but not severe asthmatics. A positive correlation was found between IgA levels and the age of patients and an inverse correlation between serum concentrations of IgA2 and IgE in asthmatics. A positive correlation between total IgA or IgA2 and IgG2 was found in asthmatics. These results highlight a gender dimorphism in IgA subclasses in male and female T2-high asthmatics. More adequate consideration of immunological gender disparity in asthma may open new opportunities in personalized medicine by optimizing diagnosis and targeted therapy.

Fixed drug eruption after Pfizer-BioNTech COVID-19 vaccine: A case report

Fixed drug eruption after Pfizer-BioNTech COVID-19 vaccine: A case report

European tattoo ingredient ban: Implications for North America

Capsule Summary •Adverse reactions to tattoo ingredients are prompting stricter regulations in the European Union, while Canada and the United States are lacking similar oversight. •Dermatologists should be aware of tattoo related adverse reactions and educate patients on tattoo safety, while also petitioning North American policymakers to increase regulation. Despite increasing evidence regarding the carcinogenic properties and cutaneous complications of tattoo inks, there are limited regulations governing the permanent makeup and tattoo industries across North America. On January 4, 2022, in response to this growing evidence, the European Union restricted >4000 substances in tattoo inks and implemented stricter labeling and safety information (Table I). 1 European Parliament and Council concerning the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH)Commission Regulation (EU) 2020/2081 of 14 December 2020 amending Annex XVII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards substances in tattoo inks or permanent make-up (Text with EEA relevance). https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32020R2081&rid=7Date accessed: February 22, 2022 Google Scholar The United States and Canada do not have similar restrictions, despite higher estimated prevalence of adult tattoos (31%) than that reported in the European Union (12%). 1 European Parliament and Council concerning the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH)Commission Regulation (EU) 2020/2081 of 14 December 2020 amending Annex XVII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards substances in tattoo inks or permanent make-up (Text with EEA relevance). https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32020R2081&rid=7Date accessed: February 22, 2022 Google Scholar ,2 Kluger N. An update on cutaneous complications of permanent tattooing. Expert Rev Clin Immunol. 2019; 15: 1135-1143https://doi.org/10.1080/1744666X.2020.1676732 Crossref PubMed Scopus (19) Google Scholar Table IBrief summary of categories of chemicals limited and labeling requirements under the Registration, Evaluation, Authorisation, and Restriction of Chemicals restriction of hazardous substances in tattoo inks and permanent makeup Categories of chemicals limited under the EU-wide classification Labeling requirements Carcinogen and mutagen •Statement “Mixture for use in tattoos or permanent make-up” •Reference number to uniquely identify the batch •List of ingredients •The statement of the presence of any nickel and/or chromium (VI) and their potential to cause allergic reactions if under the specified concentration limit •The presence of any pH regulating substances •Relevant safety instructions Toxic to reproduction Skin sensitizer Skin corrosive, skin irritant, eye irritant, or eye damaging Adapted from European Parliament and Council concerning the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH). 1 European Parliament and Council concerning the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH)Commission Regulation (EU) 2020/2081 of 14 December 2020 amending Annex XVII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards substances in tattoo inks or permanent make-up (Text with EEA relevance). https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32020R2081&rid=7Date accessed: February 22, 2022 Google Scholar EU, European Union. Open table in a new tab Adapted from European Parliament and Council concerning the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH). 1 European Parliament and Council concerning the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH)Commission Regulation (EU) 2020/2081 of 14 December 2020 amending Annex XVII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards substances in tattoo inks or permanent make-up (Text with EEA relevance). https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32020R2081&rid=7Date accessed: February 22, 2022 Google Scholar EU, European Union.

Weight excess association with severity in children and adolescents with COVID-19: A systematic review.

Background & aimsConcomitantly to the coronavirus disease 2019 (COVID-19), in the child population there was already another pandemic wave in progress: childhood obesity. Numerous studies in adults have been carried out and describe obesity as an independent risk and prognostic factor for the severity of COVID-19. This study aims to systematically review the literature on the relation between weight excess and the severity of COVID-19 in children and adolescents.MethodsThis systematic review was developed following the PRISMA standards (Preferred Reporting Items for Systematic Review and Meta-Analysis). The literature search was performed in September 2020, in the following databases: MEDLINE (via PubMed), Embase, Scopus, The Cochrane Library (Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials (CENTRAL)), Web of Science, BVS/LILACS and SciELO. Registration on the PROSPERO platform (International Prospective Registry of Systematic Reviews) can be found under the registration number: CRD42021230686.ResultsOf the 667 selected articles, 11 were included according to all agreed criteria, most of them being unicentric and American. In assessing the risk of bias and quality, following the criteria of the Newcastle–Ottawa Scale, eight studies achieved scores higher than 7. Only 5 studies sought to assess obesity and its relation with worse outcomes (such as need for pediatric intensive care unit (PICU), mechanical ventilation (MV), tracheostomy, hospital readmission and mortality), and out of these, only one article demonstrated this comorbidity as a prognostic factor for worse evolution of the COVID picture.ConclusionsFew studies in the literature seek to assess excess weight and its relation with worse outcomes of COVID-19 in children and adolescents. Taking into account that there is already scientific evidence on this subject in adult patients, it is necessary to carry out more research in the pediatric age group.

Outbreak of Silicosis in Workers Producing Artificial Stone Skirting Boards: A Novel Application of Silica-Based Composites

Outbreak of Silicosis in Workers Producing Artificial Stone Skirting Boards: A Novel Application of Silica-Based Composites

Partnering to Improve Pediatric Asthma Quality.

Partnering to Improve Pediatric Asthma Quality.

The efficacy and safety of Janus kinase inhibitors in patients with atopic dermatitis: A systematic review and meta-analysis

To the Editor: Current treatments may not satisfactorily relieve symptoms of atopic dermatitis (AD), especially severe AD.1Leung D.Y. Guttman-Yassky E. Assessing the current treatment of atopic dermatitis: unmet needs.J Allergy Clin Immunol. 2017; 139: S47-S48Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Janus kinase inhibitors (JAKis) are increasingly being used in the treatment of AD, with both topical (ruxolitinib cream) and oral (upadacitinib and abrocitinib) versions recently receiving US Food and Drug Administration approval for this indication.2Kim B.S. Sun K. Papp K. Venturanza M. Nasir A. Kuligowski M.E. Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study.J Am Acad Dermatol. 2020; 82: 1305-1313Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar We systematically review the efficacy and safety of JAKis among existing randomized, double-blinded, and placebo-controlled clinical trials of JAKis for the treatment of AD. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in PROSPERO (CRD42020188514). We searched electronic databases (Embase, PubMed, and Cochrane Central Register of Controlled Trials) from their inception to September 16, 2021. We also searched unpublished clinical trials at ClinicTrials.gov. The search strategies and methods are provided in Supplementary Materials (available via Mendeley at https://data.mendeley.com/datasets/89x8s56p5z/2). We initially identified 1209 records from all 4 databases, as summarized in Supplementary Fig 1 (available via Mendeley at https://data.mendeley.com/datasets/89x8s56p5z/2). Of these, a total of 25 studies were finally included in the meta-analysis, including 8 studies on topical JAKis and 17 on oral JAKis. There were 9931 participants, consisting of 2383 involved in studies on topical JAKis and 7548 in studies on oral JAKis. Four kinds of topical JAKis (tofacitinib ointment, delgocitinib ointment, delgocitinib cream, and ruxolitinib cream) were applied, and 5 kinds of oral JAKis (baricitinib, abrocitinib, ASN002, SHR0302, and upadacitinib) were given at varying dosages. The detailed characteristics of the included studies are summarized in Supplementary Table I (available via Mendeley at https://data.mendeley.com/datasets/89x8s56p5z/2). We also assessed the risk of bias, as summarized in Supplementary Fig 2 (available via Mendeley at https://data.mendeley.com/datasets/89x8s56p5z/2) and Supplementary Table II (available via Mendeley at https://data.mendeley.com/datasets/89x8s56p5z/2). Overall, compared with placebos, the use of JAKis showed a significant improvement in the lesion score and pruritus: Eczema Area and Severity Index score (standard mean difference [95% CI], −0.79 [−0.97 to −0.61]; P < .00001); investigators’ global assessment score (odds ratio [OR] [95% CI], 5.08 [3.78-6.82]; P < .00001); and pruritus numerical rating scale (standard mean difference [95% CI], −0.49 [−0.67 to −0.32]; P < .00001) (Supplementary Table III [available via Mendeley at https://data.mendeley.com/datasets/89x8s56p5z/2] and Supplementary Figs 3 to 5 [available via Mendeley at https://data.mendeley.com/datasets/89x8s56p5z/2]). Although no significant adverse effects (AEs) were found for the topical JAKis, the oral JAKis showed an increased risk of at least 1 AE (OR [95% CI], 1.23 [1.11-1.36]; P < .0001) and the following most frequently reported AEs: gastrointestinal disorders (OR [95% CI], 2.49 [1.84-3.37]; P < .00001), nasopharyngitis (OR [95% CI], 1.23 [1.04-1.46]; P = .02), and headache (OR [95% CI], 1.57 [1.23-2.00]; P = .0003) (Supplementary Table IV, available via Mendeley at https://data.mendeley.com/datasets/89x8s56p5z/2). No malignancy or death was reported. Previous systematic reviews have reported that herpes zoster and serious infections are common in JAKi treatment.3Olivera P.A. Lasa J.S. Bonovas S. Danese S. Peyrin-Biroulet L. Safety of Janus kinase inhibitors in patients with inflammatory bowel diseases or other immune-mediated diseases: a systematic review and meta-analysis.Gastroenterology. 2020; 158: 1554-1573Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 4Bechman K. Subesinghe S. Norton S. et al.A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis.Rheumatology (Oxford). 2019; 58: 1755-1766Crossref PubMed Scopus (140) Google Scholar, 5Khoo J.K. Barnes H. Key S. Glaspole I.N. Östör A.J. Pulmonary adverse events of small molecule JAK inhibitors in autoimmune disease: systematic review and meta-analysis.Rheumatology (Oxford). 2020; 59: 2217-2225Crossref PubMed Scopus (17) Google Scholar However, these were infrequent in our systematic review. Creatine phosphokinase level elevations were mentioned in baricitinib and upadacitinib treatments: even though patients with creatine phosphokinase level elevation were asymptomatic, the incidence and relationship with JAKi therapy remain to be further investigated. Undoubtedly, long-term follow-up trials are needed for better assessing the safety profile. In conclusion, this systematic review and meta-analysis showed that JAKis are a promising treatment option for AD. Because of the higher risk of gastrointestinal disorders, nasopharyngitis, and headache during oral JAKi treatments, more attention should be paid to the AEs of patients treated with oral JAKis. Further studies with long follow-up in different conditions will be needed to fully elucidate the safety profile of the different JAKis. None disclosed.

Immunogenicity of a third COVID-19 messenger RNA vaccine dose in primary immunodeficiency disorder patients with functional B-cell defects

Immunogenicity of a third COVID-19 messenger RNA vaccine dose in primary immunodeficiency disorder patients with functional B-cell defects

Graded coronavirus disease 2019 vaccine administration: A safe alternative to vaccine avoidance

Graded coronavirus disease 2019 vaccine administration: A safe alternative to vaccine avoidance

COVID-19 infection in hypereosinophilic syndrome: A survey-based analysis

COVID-19 infection in hypereosinophilic syndrome: A survey-based analysis

Antibody responses to 2 doses of mRNA COVID-19 vaccine in pediatric patients with kidney diseases

Antibody responses to 2 doses of mRNA COVID-19 vaccine in pediatric patients with kidney diseases

Prophylaxis with anti-activated factor XII for hereditary angioedema

Hereditary angioedema is a rare autosomal dominant genetic disorder characterised by recurrent, localised swellings in various tissues including the skin, genitals, abdomen, face, and oropharyngeal region. These attacks can be painful, debilitating, and life-threatening, substantially affecting quality of life. 1 Banerji A The burden of illness in patients with hereditary angioedema. Ann Allergy Asthma Immunol. 2013; 111: 329-336 Google Scholar , 2 Bork K Hardt J Witzke G Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012; 130: 692-697 Google Scholar Inadequate control of the contact system, consisting of factor XII (FXII), plasma kallikrein, and high molecular weight kininogen, results in excessive bradykinin formation, which increases vascular permeability and thus causes angioedema attacks. 3 Fijen LM Bork K Cohn DM Current and prospective targets of pharmacologic treatment of hereditary angioedema types 1 and 2. Clin Rev Allergy Immunol. 2021; 61: 66-76 Google Scholar Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, phase 2 trialGaradacimab 200 mg and 600 mg every 4 weeks significantly reduced the number of monthly attacks versus placebo and was well tolerated during the study. Garadacimab is an efficacious, subcutaneous prophylaxis in patients with HAE-C1-INH and warrants phase 3 evaluation. Full-Text PDF

Timing of itch among children with atopic dermatitis

Itch is a subjective, defining symptom of atopic dermatitis (AD), which guides treatment decisions. 1 Fishbein AB Silverberg JI Wilson EJ Ong PY. Update on atopic dermatitis: diagnosis, severity assessment, and treatment selection. J Allergy Clin Immunol Pract. 2020; 8: 91-101 Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar In pediatric patients, clinic visits center on patient or parent-proxy report of itch. One study of 100 adult and adolescent patients found self-report of itch worsening generally in the evening and night. 2 Yosipovitch G Goon AT Wee J Chan YH Zucker I Goh CL. Itch characteristics in Chinese patients with atopic dermatitis using a new questionnaire for the assessment of pruritus. Int J Dermatol. 2002; 41: 212-216 Crossref PubMed Scopus (164) Google Scholar Timing of itch is one feature of AD to which treatment in children could be targeted. Nevertheless, there have been no pediatric studies evaluating itch timing. Given the frequency of sleep disturbance in AD and our clinical experience, 3 Fishbein AB Knutson KL Zee PC. Circadian disruption and human health. J Clin Invest. 2021; 131 Crossref PubMed Scopus (6) Google Scholar we hypothesized that pediatric patients experience greater nighttime itch in AD.

COVID-19 vaccination in the setting of mastocytosis—Pfizer-BioNTech mRNA vaccine is safe and well tolerated

COVID-19 vaccination in the setting of mastocytosis—Pfizer-BioNTech mRNA vaccine is safe and well tolerated

Safety of COVID-19 vaccination in patients with clonal mast cell disorders

Safety of COVID-19 vaccination in patients with clonal mast cell disorders

Disease characteristics, comorbidities, treatment patterns and quality of life impact in children

Disease characteristics, comorbidities, treatment patterns and quality of life impact in children <12 years old with atopic dermatitis: Interim results from the PEDISTAD Real-World Registry

A case of normal C1 esterase inhibitor hereditary angioedema successfully treated with berotralstat

A case of normal C1 esterase inhibitor hereditary angioedema successfully treated with berotralstat

Disseminated tense bullae on newborn

Disseminated tense bullae on newborn