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.

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.

Subcutaneous immunoglobulin in inflammatory myopathies: efficacy in different organ systems.

MGD and CG were responsible for the study's conception and design. VP and DM contributed to data acquisition. VP and DB planned and performed the statistical analyses. All Authors contributed to data interpretation. MGD, CG, VP and DM drafted the manuscript. AG and DB revised the manuscript critically for intellectual content. All authors gave their final approval of the version of the manuscript to be published.

Subcutaneous IgG in the Myositis Spectrum Disorders.

The efficacy of subcutaneous immunoglobulin is reported in several neurological disorders and, more recently, its use has been extended to other inflammatory diseases, such as the idiopathic inflammatory myopathies, including polymyositis and dermatomyositis. Due to the rarity of these disorders, the role of immunoglobulin, administered intravenously or subcutaneously, remains unclear and poorly investigated. We report our experience about the use of subcutaneous immunoglobulin in myositis spectrum disorders, from idiopathic inflammatory myopathies to more complex conditions, such as overlap and cancer-associated myositis or pregnancy.

Facilitated Subcutaneous Immunoglobulin (fSCIg) in Autoimmune Cytopenias Associated with Common Variable Immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is the most common symptomatic primary immune deficiency of adulthood. Besides recurrent infections, autoimmune disorders-mainly cytopenias-affect 30% of patients with CVID. OBJECTIVES: To describe the efficacy and safety of facilitated subcutaneous immunoglobulin (fSCIg), which is a combination of 10% [human] SCIg with recombinant human hyaluronidase for the treatment of CVID-linked cytopenias. METHODS: We describe four women (mean age 54 years) with CVID associated with idiopathic thrombocytopenic purpura (ITP) (n=3) and autoimmune hemolytic anemia (AIHA) (n=1). Diagnosis of CVID was made according to the European Society of Immune Deficiencies / Pan-American Group for Immune Deficiency criteria. All were treated with fSCIg (bi-monthly, 20 g). RESULTS: After a median follow-up of 22 months, all patients achieved a stable remission from the cytopenias, characterized by increased platelet values in ITP (mean values 93000/mmc), and resolution of anemia. A reduction of the daily prednisone dose was documented in the patient with AIHA. No systemic adverse drug reactions were observed. CONCLUSIONS: Our preliminary data documented the efficacy and safety of fSCIg in the treatment of CVID associated with autoimmune cytopenias, with a good tolerability. We also noted the role of fSCIg as a steroid sparing agent. It is thus possible to suppose an immunomodulatory role for fSCIg, but linked to different mechanisms than IVIg, due to the peculiar pharmacokinetic and administration route of fSCIg.

Subcutaneous IgG in immune-mediate diseases: proposed mechanisms of action and literature review.

Intravenous immunoglobulin (IVIg) constitutes a relevant treatment option in various immune-mediated disorders, such as chronic inflammatory neuropathies and idiopathic inflammatory myopathies (IIM). Several advantages are linked to IVIg immunomodulatory and steroid sparing effects and to the possibility to withdraw the immunosuppressant therapy. However, the use of IVIg is not always easy to manage. It is associated with the need of an intravenous route of administration, high costs, and the risk of serious systemic adverse effects. More recently, the subcutaneous administration of immunoglobulin (SCIg) has been used in immunological practice as an alternative to IVIg, administered at lower dosages and more frequent intervals. This results in higher and more stable IgG serum levels and may prevent end-of-dose reduction and adverse effects caused by sudden IgG serum elevation. Moreover, the use of SCIg is more feasible, patient-friendly and cost-effective compared to the intravenous administration. In this context we compared IVIg and SCIg long term efficacy in the treatment of chronic inflammatory neuropathies and IIM, by reviewing the current literature and reporting the data obtained from our clinical experience about the use of SCIg in patients with myositis. We also described the most recent evidence on the immunomodulatory role of immunoglobulin, the pharmacokinetic properties of SCIg compared to the IVIg treatment, and the consequent clinical, laboratory and immunological implications.