A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency.

Background: Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management.

Objectives: To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK.

A Core Outcome Set for Efficacy of Acute Treatment of Hereditary Angioedema.

Background: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants.

Objective: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks.

Once-Daily Oral Berotralstat for Long-Term Prophylaxis of Hereditary Angioedema: The Open-Label Extension of the APeX-2 Randomized Trial.

Background: Berotralstat is a first-line, once-daily oral plasma kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients 12 years or older.

Objective: This analysis examined the safety and effectiveness of long-term prophylaxis with berotralstat.

Methods: APeX-2 was a phase 3, parallel-group, multicenter trial in patients with HAE caused by C1-inhibitor deficiency (NCT03485911).

An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial.

Background: Guidelines recommend effective on-demand therapy for all individuals with hereditary angioedema. We aimed to assess the novel oral plasma kallikrein inhibitor, sebetralstat, which is in development, for on-demand treatment of hereditary angioedema attacks.

Methods: In this two-part phase 2 trial, individuals with type 1 or 2 hereditary angioedema aged 18 years or older were recruited from 25 sites, consisting of specialty outpatient centres, across nine countries in Europe and the USA.

Gastrointestinal symptoms and nutritional issues in patients with hypermobility disorders: assessment, diagnosis and management.

Patients diagnosed with hypermobile Ehlers-Danlos syndrome and hypermobile spectrum disorders are increasingly presenting to secondary and tertiary care centres with gastrointestinal (GI) symptoms and nutritional issues. Due to the absence of specific guidance, these patients are investigated, diagnosed and managed heterogeneously, resulting in a growing concern that they are at increased risk of iatrogenic harm. This review aims to collate the evidence for the causes of GI symptoms, nutritional issues and associated conditions as well as the burden of polypharmacy in this group of patients.

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process.

Attenuated androgen discontinuation in patients with hereditary angioedema: a commented case series.

Background: Hereditary angioedema (HAE) is characterized by potentially severe and life-threatening attacks of localized swelling. Prophylactic therapies are available, including attenuated androgens. Efficacy of attenuated androgens has not been assessed in large, randomized, placebo-controlled trials and can be associated with frequent, and sometimes severe, side effects.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update.

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process.

Case report: Hereditary angioedema in pregnancy.

Hereditary angioedema (HAE) is a rare genetic condition associated with episodic swelling due to dysfunction of bradykinin regulation pathways. This is most frequently caused by low level and/or function of the C1-esterase inhibitor protein (C1INH) which is known as hereditary angioedema with C1 inhibitor deficiency (C1INH-HAE). Pregnancy and labour can precipitate an attack, but the majority of women have an uncomplicated, spontaneous vaginal delivery.

Measurement of C1-Inhibitor function alone is sufficient for diagnosis of hereditary angioedema.

The World Allergy Organisiation/European Academy of Allergy and Clinical Immunology (WAO/EAACI) 2017/2018 guidelines recommend measuring complement4 levels, followed by C1-inhibitor level and function for diagnosis of hereditary angioedema (HAE). We analysed 6 months' worth of data generated in our laboratory which is a specialist regional immunology service and also provides laboratory service for the Barts Health immunology department, which is a GA2LEN/HAEi-Angioedema Centre of Excellence and Reference (ACARE) and hence, investigates a large number of patients for HAE. We found that an efficient and sensitive approach for laboratory diagnosis of HAE is to only test the C1-inhibitor function.

Long-term safety and effectiveness of berotralstat for hereditary angioedema: The open-label APeX-S study.

Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long-term safety study of berotralstat in patients with HAE.

Methods: APeX-S is an ongoing, phase 2, open-label study conducted in 22 countries (ClinicalTrials.

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement.

Immunoglobulin abnormalities are frequent in patients with lupus nephritis.

Background: Hypogammaglobulinemia is a complication of B-cell targeting therapies (BCTT), used in vasculitis, rheumatoid arthritis and systemic lupus erythematosus (SLE). Since autoimmune diseases are associated with underlying and induced immune abnormalities, several societies recommend assessing immune function before and during rituximab treatment. In SLE, polyclonal hypergammaglobulinemia is the typical alteration of gammaglobulins, though hypogammaglobulinemia has also been reported.

Immunoglobulin replacement for secondary immunodeficiency after B-cell targeted therapies in autoimmune rheumatic disease: Systematic literature review.

Background: Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease.

Objectives: To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD).

Methods: Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor.

Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases.

Objectives: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases.

Methods: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative.

Measurement and interpretation of Salmonella typhi Vi IgG antibodies for the assessment of adaptive immunity.

Response to polysaccharide vaccination can be an invaluable tool for assessing functionality of the adaptive immune system. Measurement of antibodies raised in response to Pneumovax®23 is the current gold standard test, but there are significant challenges and constraints in both the measurement and interpretation of the response. An alternative polysaccharide vaccine approach (Salmonella typhi Vi capsule (ViCPS)) has been suggested.