Common Variable Immunodeficiency in Elderly Patients: A Long-Term Clinical Experience.

Background: Common variable immunodeficiency (CVID) is a complex, predominantly antibody deficiency usually diagnosed between 20−40 years. Few data about elderly patients are reported in the literature. Our aim was to evaluate the clinical phenotypes of elderly patients with CVID. Method: A retrospective analysis of adult patients with CVID was performed in our Referral Centre, focusing on the main differences between "older" patients (≥65 years at the diagnosis) and "younger" patients (<65 years). Results: The data from 65 younger and 13 older patients followed up for a median period of 8.5 years were available. At diagnosis, recurrent infections represented the only clinical manifestation in 61% and 69% of younger and older patients, respectively. The incidence of autoimmune diseases was higher in elderly patients compared with younger ones (30 vs. 18%, respectively). During the follow-up, the incidence of autoimmune disorders and enteropathy increased in the younger patients whereas neoplasia became the most prevalent complication in the elderly (38%). All patients received a replacement therapy with immunoglobulin, with good compliance. Conclusion: CVID occurrence in elderly patients is rarely described; therefore, the clinical characteristics are not completely known. In our series, neoplasia became the most prevalent complication in the elderly during the follow-up. In elderly patients, 20% SCIg was as safe as in the younger ones, with good compliance. A genetic analysis is important to confirm the diagnosis, identify specific presentations in the different ages, clarify the prognosis and guide the treatment. Future clinical research in this field may potentially help to guide their care.

Intravenous immunoglobulin as an important adjunct in the prevention and therapy of coronavirus 2019 disease.

The coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenged globally with its morbidity and mortality. A small percentage of affected patients (20%) progress into the second stage of the disease clinically presenting with severe or fatal involvement of lung, heart and vascular system, all contributing to multiple-organ failure. The so-called 'cytokines storm' is considered the pathogenic basis of severe disease and it is a target for treatment with corticosteroids, immunotherapies and intravenous immunoglobulin (IVIg). We provide an overview of the role of IVIg in the therapy of adult patients with COVID-19 disease. After discussing the possible underlying mechanisms of IVIg immunomodulation in COVID-19 disease, we review the studies in which IVIg was employed. Considering the latest evidence that show a link between new coronavirus and autoimmunity, we also discuss the use of IVIg in COVID-19 and anti-SARS-CoV-2 vaccination related autoimmune diseases and the post-COVID-19 syndrome. The benefit of high-dose IVIg is evident in almost all studies with a rapid response, a reduction in mortality and improved pulmonary function in critically ill COVID-19 patients. It seems that an early administration of IVIg is crucial for a successful outcome. Studies' limitations are represented by the small number of patients, the lack of control groups in some and the heterogeneity of included patients. IVIg treatment can reduce the stay in ICU and the demand for mechanical ventilation, thus contributing to attenuate the burden of the disease.

Replacement and Immunomodulatory Activities of 20% Subcutaneous Immunoglobulin Treatment: A Single-Center Retrospective Study in Autoimmune Myositis and CVID Patients.

Background: Immunoglobulin (Ig) replacement therapy represents a life-saving treatment in primary antibody deficiencies. The introduction of subcutaneous Ig (SCIg) administration brings a major improvement in quality of life for patients, compared to the traditional intravenous administration. In recent years, an additional role has been proposed for Ig therapy for various inflammatory and immune-mediated diseases. Consequently, the use of SCIg has expanded from immunodeficiencies to immune-mediated diseases, such as polymyositis (PM) and dermatomyositis (DM). Given the rarity of these conditions, it is still difficult to evaluate the real impact of SCIg treatment on PM and DM, and additional data are constantly required on this topic, particularly for long-term treatments in real-life settings. Aim: This study aimed to increase the knowledge about the anti-inflammatory and immunomodulatory effects of SCIg treatment for myositis. To this aim, a long-term evaluation of the effectiveness of 20% human SCIg treatment (20% SCIg, Hizentra®, CSL Behring) was carried out in patients with PM/DM in care at our Center. In addition, an evaluation of the 20% SCIg therapy in CVID patients was provided. This analysis, beside adding knowledge about the use of SCIg therapy in this real-life setting, was intended as a term of comparison, regarding the safety profile. Results: Results support the beneficial effect and tolerability of long-term 20% SCIg therapy in PM/DM patients, reporting a significant improvement in creatine kinase levels, muscle strength, skin conditions, dysphagia, disease activity (MITAX score) and disability (HAQ-DI score). None of the patients reported systemic reactions. The duration of the reported local reactions was a few hours in 80% of the patients, and all resolved spontaneously. CVID patients reported an improvement in all the considered effectiveness parameters at the end of 20% SCIg therapy. The frequency of the adverse events reported by PM/DM patients was not different from what reported in CVID patients, where the use of SCIg therapy is more consolidated. Conclusions: This study suggests that 20% SCIg treatment represents a viable and safe treatment for PM/DM patients and a valid therapeutic alternative to IVIg, with important advantages for patients' quality of life.

Incidence of malignancy in patients with common variable immunodeficiency according to therapeutic delay: an Italian retrospective, monocentric cohort study.

BACKGROUND: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency and has a broad spectrum of clinical manifestations. Among non-infectious complications, an increased incidence of malignancies may have a special relevance for survival, but little is known about treatment efficacy on malignant complications. METHODS: This was a monocenter retrospective study on CVID patients, designed to provide preliminary data for the investigation of the possible link between therapeutic delay and tumor incidence. RESULTS: A total of 67 CVID subjects were included. The median diagnostic delay was 7.5 years (range: 0-63 years), and the median therapeutic delay was 8.5 years (range: 0-67 years). Malignancies were diagnosed in 18 (27%) patients. Eight out of 18 (44%) patients with a malignancy had lymphoma. Patients who developed a malignancy showed a longer therapeutic delay in comparison to patients with no malignancy, although no statistical significance was achieved (11 years vs 8 years, respectively, p = 0.424). We observed a lower frequency of malignancy in CVID patients with reduced therapeutic delay compared with patients with therapeutic delay ≥ 10 years. With a therapeutic delay of > 1 year, 74% had no tumor, and 25% had a tumor; with a therapeutic delay of > 10 years, 65% had no tumor and 35% had a malignancy. Among patients who had no malignancy, 64% had a therapeutic delay of < 10 years, and 36% had a therapeutic delay of ≥ 10 years. Among patients with malignancy, 47% of subjects had a therapeutic delay < 10 years, and 53% a therapeutic delay ≥ 10 years. CONCLUSIONS: The observation of clinical characteristics of our patients with CVID may suggest that an early institution of IgG replacement therapy could be of benefit for the prevention of malignant complications.Name of the registry: Comitato Etico Regionale delle Marche. Trial registration number: 1505. Date of registration: 27/10/2016, Retrospectively registered URL of trial registry record: http://www.ospedaliriuniti.marche.it/portale/archivio13_cerm-ancona_0_446_1.html. The trial was not registered before the first participant was enrolled.