Prophylaxis in hereditary angioedema: a United Kingdom Delphi consensus.

Hereditary angioedema (HAE) is a rare inherited disorder causing recurrent episodes of swelling that can be potentially life threatening. Treatment of HAE can be divided into on-demand treatment for swelling, and prophylaxis. The last UK consensus on HAE was in 2014 and since then, new medications for prophylaxis have been developed, with more drugs in the pipeline. International guidelines currently recommend the use of long-term prophylaxis (LTP) as the only way of achieving disease control and normalizing patient lives. Modern prophylactic medications are available in the UK, although access is restricted primarily by HAE attack frequency. To establish an updated view of UK clinicians and patients, a Delphi process was used to develop statements regarding LTP as well as other aspects of HAE management. There was consensus that UK access criteria for modern LTP agents based on numerical frequency of attacks alone are too simplistic and potentially disadvantage a cohort of patients who may benefit from LTP. Additionally, there was agreement that patients should be seen in expert centres, remote monitoring of patients is popular post-pandemic, and that the use of patient-reported outcome measures has the potential to improve patient care. Psychological health is an area in which patients may benefit, and recognition of this is important for future research and development.

Treatment of chronic or relapsing COVID-19 in immunodeficiency.

BACKGROUND: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. OBJECTIVE: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. METHODS: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting ≥21 days) or relapsing (≥2 episodes) of COVID-19. RESULTS: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of ≤20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. CONCLUSIONS: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise.

Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK.

In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.

Indolent Systemic Mastocytosis Manifesting as Protracted Anaphylactic Shock.

Systemic mastocytosis is a rare disease due to abnormal proliferation of mast cells (MCs). A case of indolent systemic mastocytosis is presented here. After anesthetic induction for elective thyroid swelling with propofol and atracurium followed by endotracheal intubation, a 57-year-old female patient developed acute hypotension, sinus tachycardia, red rashes, increased airway pressure along with difficult ventilation, and desaturation. She developed multiorgan failure subsequently. MC tryptase level was persistently high. Bone marrow study revealed mastocytosis. She required antihistaminic, steroid, and organ support. With treatment, organ functions recovered gradually. Atracurium precipitated anaphylactic shock causing severe morbidity in this patient.